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Objectives: The relationship between adiposity and sepsis has received increasing attention. This study aims to explore the causal relationship between life course adiposity and the sepsis incidence. Methods: Mendelian randomization (MR) method was employed in this study. Instrumental variants were obtained from genome-wide association studies for life course adiposity, including birth weight, childhood body mass index (BMI), childhood obesity, adult BMI, waist circumference, visceral adiposity, and body fat percentage. A meta-analysis of genome-wide association studies for sepsis including 10,154 cases and 454,764 controls was used in this study. MR analyses were performed using inverse variance weighted, MR Egger regression, weighted median, weighted mode, and simple mode. Instrumental variables were identified as significant single nucleotide polymorphisms at the genome-wide significance level (P < 5×10-8). The sensitivity analysis was conducted to assess the reliability of the MR estimates. Results: Analysis using the MR analysis of inverse variance weighted method revealed that genetic predisposition to increased childhood BMI (OR = 1.29, P = 0.003), childhood obesity (OR = 1.07, P = 0.034), adult BMI (OR = 1.38, P < 0.001), adult waist circumference (OR = 1.01, P = 0.028), and adult visceral adiposity (OR = 1.53, P < 0.001) predicted a higher risk of sepsis. Sensitivity analysis did not identify any bias in the MR results. Conclusion: The results demonstrated that adiposity in childhood and adults had causal effects on sepsis incidence. However, more well-designed studies are still needed to validate their association.
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Adiposidade , Índice de Massa Corporal , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Sepse , Humanos , Adiposidade/genética , Sepse/genética , Sepse/epidemiologia , Predisposição Genética para Doença , Obesidade Infantil/genética , Obesidade Infantil/epidemiologia , Obesidade Infantil/complicações , Adulto , Circunferência da Cintura , Criança , Masculino , FemininoRESUMO
INTRODUCTION: Paxlovid (nirmatrelvir/ritonavir) has received endorsement from several guidelines for treating COVID-19 in adults, but its use in children is still uncertain. OBJECTIVES: This study aimed to evaluate the safety and effectiveness of paxlovid in pediatric patients in the pediatric intensive care unit (PICU). METHODS: A retrospective analysis was performed on children with COVID-19. The children who received paxlovid comprised the paxlovid group; otherwise, they were referred to as the control group. RESULTS: A total of 31 children were enrolled, with 12 and 19 participants assigned to the paxlovid and control groups, respectively. Approximately 35% had received vaccination against the novel coronavirus. The control group exhibited a significantly lower mean age in comparison to the paxlovid group (p < 0.001). However, no significant differences were observed between the groups in terms of other baseline data and biochemical indexes at admission. However, on the fifth day of drug administration, the paxlovid group exhibited a statistically significant decrease in temperature compared to the control group (p < 0.05). Additionally, the paxlovid group exhibited a significantly shorter conversion time to negativity for novel coronary genes in the respiratory tract (9.5 days) compared to the control group (16 days, p < 0.05). The administration of paxlovid did not result in any observed adverse reactions. Merely two patients exhibited a transient elevation in liver enzyme levels. CONCLUSION: The application of paxlovid in critically ill pediatric patients with COVID-19 can effectively control symptoms and promote virus clearance, demonstrating efficacy and a relatively low-risk profile.
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BACKGROUND: Metagenomic next-generation sequencing (mNGS) excels in diagnosis of infection pathogens. We aimed to evaluate the performance of mNGS for the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-HIV infected children. METHODS: Totally 36 PJP children and 61 non-PJP children admitted to the pediatric intensive care unit from March 2018 to December 2021 were retrospectively enrolled. Clinical features of PJP children were summarized. 1,3-ß-D glucan (BDG) test and bronchoalveolar lavage fluid (BALF) mNGS were used for evaluation of PJP diagnostic performance. Antimicrobial management modifications for PJP children after the mNGS results were also reviewed. RESULTS: Pneumocystis jirovecii was detected in all PJP children by mNGS (36/36), and the sensitivity of mNGS was 100% (95% confidence interval [CI]: 90.26-100%). The sensitivity of BDG was 57.58% (95% CI: 39.22-74.52%). Of the 26 (72.2%) PJP patients with mixed infection, twenty-four (66.7%) were detected by BALF-mNGS. Thirteen patients (36.1%) had their antimicrobial management adjusted according to the mNGS results. Thirty-six PJP children included 17 (47.2%) primary immunodeficiency and 19 (52.8%) secondary immunodeficiency, of whom 19 (52.8%) survived and 17 (47.2%) died. Compared to survival subgroup, non-survival subgroup had a higher rate of primary immunodeficiency (64.7% vs. 31.6%, P = 0.047), younger age (7 months vs. 39 months, P = 0.011), lower body weight (8.0 kg vs. 12.0 kg, P = 0.022), and lower T lymphocyte counts. CONCLUSIONS: The mortality rate of PJP in immunosuppressed children without HIV infection is high and early diagnosis is challenging. BALF-mNGS could help identify PJP and guide clinical management.
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Líquido da Lavagem Broncoalveolar , Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/mortalidade , Estudos Retrospectivos , Masculino , Feminino , Pré-Escolar , Pneumocystis carinii/isolamento & purificação , Pneumocystis carinii/genética , Líquido da Lavagem Broncoalveolar/microbiologia , Lactente , Criança , Metagenômica/métodos , beta-Glucanas , Unidades de Terapia Intensiva PediátricaRESUMO
Objective: To evaluate the incidence, outcome, and prognostic factors of prolonged mechanical ventilation (PMV) in children in Mainland China. Methods: A prospective study was conducted in 11 pediatric intensive care units (PICUs) from May 1, 2021, to April 30, 2022. All pediatric patients on mechanical ventilation meeting the criteria for PMV were included in the study. Results: Out of 5,292 patients receiving mechanical ventilation, 278 children met the criteria for PMV (5.3%). After excluding case with incomplete data or lost to follow-up, the study included 250 patients. Among them, 115 were successfully weaned from mechanical ventilation, 90 died, and 45 were still on mechanical ventilation. The 6-month survival rate was 64%. The primary associated conditions of PMV were lower airway diseases (36%), central nervous system diseases (32%), and neuromuscular diseases (14%). The stepwise multiple logistic regression analysis indicated that the utilization of vasoactive agents and an elevated pediatric logistic organ dysfunction-2 (PELOD-2) score on the day of PMV diagnosis were significantly associated with an increased of PMV death. Specifically, the odds ratio (OR) for vasoactive agent use was 2.86; (95% CI: 0.15-0.84; P = 0.018), and for the PELOD-2 score, it was 1.37; 95% CI: 1.17-1.61; P < .001). Conversely, early rehabilitation intervention was negatively associated with the risk of PMV death (OR = 0.45; 95% CI: 0.22-0.93; P = .032). Furthermore, the tracheotomy timing emerged as an independent predictor of failure to wean from PMV, with an OR of 1.08, (95% CI: 1.01-1.16; P = .030). Conclusions: The study revealed a 5.3% incidence of PMV in children requiring mechanical ventilation in China. The use of vasoactive agents and a higher PELOD-2 score at PMV diagnosis were significantly associated with an increased risk of PMV death, whereas early rehabilitation intervention was identified as crucial for improving patient outcomes. The timing of tracheostomy was identified as a high-risk factor for failure to wean from mechanical ventilation.
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The selective hydrodeoxygenation (HDO) of lignin-derived methoxyphenols to cyclohexanol is one of the most significant transformation in biomass conversion since cyclohexanol is an important industrial raw material. This study has disclosed a series of tungstated zirconia with different Zr/W ratio supported Ru catalysts (Ru/xZrW, x means the molar ration of Zr/W) for the hydrodeoxygenation (HDO) of guaiacol to cyclohexanol. Among these catalysts, Ru/16ZrW has the best catalytic activity, which can achieve 92 % yield of cyclohexanol under the conditions of 180 °C and 1â MPa H2 pressure for 2â h (TOF 231â h-1). Compared with Ru/ZrO2, Ru/16ZrW has smaller particles, more dispersed and electron-rich Ru species, significant hydrogen spillover and more acid sites, which are the main reason for its excellent performance on this reaction. Apart from guaiacol, other methoxy substitution phenols and organosolv lignin can also be converted into cyclohexanol via hydrodeoxygenation reactions over this catalyst.
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Tigecycline-non-susceptible Klebsiella pneumoniae (TNSKP) is increasing and has emerged as a global public health issue. However, the mechanism of tigecycline resistance remains unclear. The objective of this study was to investigate the potential role of efflux pump system in tigecycline resistance. 29 tigecycline-non-susceptible Klebsiella pneumoniae (TNSKP) strains were collected and their minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. The ramR, acrR, rpsJ, tet(A), and tet(X) were amplified by polymerase chain reaction (PCR). The mRNA expression of different efflux pump genes and regulator genes were analyzed by real-time PCR. Additionally, KP14 was selected for genome sequencing. KP14 genes without acrB, oqxB, and TetA were modified using suicide plasmids and MIC of tigecycline of KP14 with target genes knocked out was investigated. It was found that MIC of tigecycline of 20 out of the 29 TNSKP strains decreased by over four folds once combined with phenyl-arginine-ß-naphthylamide dihydrochloride (PaßN). Most strains exhibited upregulation of AcrAB and oqxAB efflux pumps. The strains with acrB, oqxB, and tetA genes knocked out were constructed, wherein the MIC of tigecycline of KP14∆acrB and KP14∆tetA was observed to be 2 µg/mL (decreased by 16 folds), the MIC of tigecycline of KP14ΔacrBΔTetA was 0.25 µg/mL (decreased by 128 folds), but the MIC of tigecycline of KP14∆oqxB remained unchanged at 32 µg/mL. The majority of TNSKP strains demonstrated increased expression of AcrAB-TolC and oqxAB, while certain strains showed mutations in other genes associated with tigecycline resistance. In KP14, both overexpression of AcrAB-TolC and tet(A) gene mutation contributed to the mechanism of tigecycline resistance.
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Antibacterianos , Proteínas de Bactérias , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Mutação , Tigeciclina , Tigeciclina/farmacologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Farmacorresistência Bacteriana/genética , Humanos , AntiportersRESUMO
With the application of engineered nanomaterials and antibiotics in the fields of medicine, aerospace, new energy and agriculture, the associated contamination is detected widely in soil-groundwater systems. It is of great scientific and practical significance to deeply explore the environmental interface process between nanoparticles and antibiotics for the scientific assessment of environmental fate and ecological environmental risks, as well as the development of new composite pollution control technologies. In this study, the co-transport behaviors of positively charged titanium dioxide nanoparticles (TiO2-NPs) and negatively charged levofloxacin (LEV) in quartz sand (QS) are investigated in this study. The results show that TiO2-NPs hardly flow out when transported alone in the column because of its positive charge, which creates a strong attraction with the negatively charged quartz sand on the surface. When TiO2-NPs co-migrate with LEV in porous media, the presence of LEV promotes the transport of TiO2-NPs, while the presence of TiO2-NPs inhibits LEV transport. Non-XDLVO interactions based on molecular dynamics (MD) simulations can help explain the observed promotion and inhibition phenomena as well as the correlation between TiO2-NPs and LEV. The results indicate that TiO2-LEV complexes or aggregates can be formed during the co-transportation process of TiO2-NPs and LEV in porous media. As flow velocity increases from 0.204 cm min-1 to 1.630 cm min-1, both the transport capacities of TiO2-NPs and LEV are enhanced significantly. Under the condition of high citric acid (CA) concentration (15 mmol L-1), the transport capacity of TiO2-NPs is slightly inhibited, while the transport capacity of LEV is enhanced. This study provides new insights into the transport of nanometallic oxides and antibiotics in porous media, which suggests that non-XDLVO interactions should be considered together when assessing the environmental risks and fate of nanometallic oxides and antibiotics in soil-groundwater systems.
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Levofloxacino , Titânio , Titânio/química , Levofloxacino/química , Porosidade , Nanopartículas/química , Antibacterianos/química , Poluentes Químicos da Água/química , Poluentes do Solo/química , Nanopartículas Metálicas/química , Água Subterrânea/química , Simulação de Dinâmica MolecularRESUMO
Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses immense threats to the health of infected patients worldwide, especially children. This study reports the infection caused by CRKP in a paediatric intensive care unit (PICU) child and its drug-resistant mutation during the treatment. Twelve Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains were isolated from the child. Broth microdilution method, plasmid transformation assay, and whole genome sequencing (WGS) were performed to investigate the antimicrobial susceptibility, resistance mechanisms, and genetic structural features of CRKPs. The results showed that 12 strains were highly resistant to most available antimicrobial agents. Among them, K. pneumoniae FD11 and K. pneumoniae FD12 were resistant to ceftazidime-avibactam (CZA, MIC >64 mg/L) and restored the carbapenem susceptibility (Imipenem, MIC =0.25 mg/L; Meropenem, MIC =2 mg/L). The patient improved after treatment with CZA in combination with aztreonam. Plasmid transformation assay demonstrated that the blaKPC-33-positive transformant increased MICs of CZA by at least 33-fold and 8-fold compared with the recipient Escherichia coli DH5α and blaKPC-2-positive transformants. WGS analysis revealed that all strains belonged to the ST11-KL64 type and showed highly homologous (3-26 single nucleotide polymorphisms [SNPs]). A single base mutation (G532T) of blaKPC-2 resulted in a tyrosine to aspartic acid substitution at Ambler amino acid position 179 (D179Y), which conferred CZA resistance in K. pneumoniae. This is the first report of a drug-resistant mutation evolving into blaKPC-33 during the treatment of blaKPC-2-positive CRKP in paediatric-infected patients. It advises clinicians that routine sequential antimicrobial susceptibility testing and KPC genotyping are critical during CZA therapy in children infected with CRKP.
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Antibacterianos , Compostos Azabicíclicos , Proteínas de Bactérias , Ceftazidima , Combinação de Medicamentos , Infecções por Klebsiella , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , beta-Lactamases , Humanos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/isolamento & purificação , Compostos Azabicíclicos/farmacologia , Ceftazidima/farmacologia , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/tratamento farmacológico , beta-Lactamases/genética , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Sequenciamento Completo do Genoma , Farmacorresistência Bacteriana Múltipla/genética , Criança , Plasmídeos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Masculino , Aztreonam/farmacologiaRESUMO
BACKGROUND: Antimicrobial resistance (AMR) is a major threat to children's health, particularly in respiratory infections. Accurate identification of pathogens and AMR is crucial for targeted antibiotic treatment. Metagenomic next-generation sequencing (mNGS) shows promise in directly detecting microorganisms and resistance genes in clinical samples. However, the accuracy of AMR prediction through mNGS testing needs further investigation for practical clinical decision-making. METHODS: We aimed to evaluate the performance of mNGS in predicting AMR for severe pneumonia in pediatric patients. We conducted a retrospective analysis at a tertiary hospital from May 2022 to May 2023. Simultaneous mNGS and culture were performed on bronchoalveolar lavage fluid samples obtained from pediatric patients with severe pneumonia. By comparing the results of mNGS detection of microorganisms and antibiotic resistance genes with those of culture, sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: mNGS detected bacterial in 71.7% cases (86/120), significantly higher than culture (58/120, 48.3%). Compared to culture, mNGS demonstrated a sensitivity of 96.6% and a specificity of 51.6% in detecting pathogenic microorganisms. Phenotypic susceptibility testing (PST) of 19 antibiotics revealed significant variations in antibiotics resistance rates among different bacteria. Sensitivity prediction of mNGS for carbapenem resistance was higher than penicillins and cephalosporin (67.74% vs. 28.57%, 46.15%), while specificity showed no significant difference (85.71%, 75.00%, 75.00%). mNGS also showed a high sensitivity of 94.74% in predicting carbapenem resistance in Acinetobacter baumannii. CONCLUSIONS: mNGS exhibits variable predictive performance among different pathogens and antibiotics, indicating its potential as a supplementary tool to conventional PST. However, mNGS currently cannot replace conventional PST.
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Antibacterianos , Pneumonia , Humanos , Criança , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Estudos Retrospectivos , Farmacorresistência Bacteriana/genética , Sequenciamento de Nucleotídeos em Larga Escala , Carbapenêmicos , Sensibilidade e Especificidade , Líquido da Lavagem BroncoalveolarRESUMO
Azido-tetrazolo tautomerizations between azido N-heteroaromatic compounds and tetrazole-fused energetic materials can produce a new generation of high-energy density compounds. Density functional theory (DFT) computations are performed to explore the relationship between reaction barriers and electron densities of bonding N atoms, i.e., the terminal N1 and heterocyclic N2 atoms, for six reported tautomerizations. The results reveal four linear correlations between reverse reaction barriers (Gr) and the electron densities of N1 and N2 atoms in the product. N1 electron density (ρN1) and N-N bond polarity, as measured by the difference between the electron densities on the two N atoms (ΔρN = ρN1 - ρN2) in products, are inversely proportional to the reverse reaction barriers. They are also proportional to the energy barrier differences between the forward and reverse reactions (ΔG = Gf - Gr). Polar solvents, including DMSO, water, and acetone, can effectively increase the reverse reaction barriers (Gr) by improving the stability of products. This regularity is further confirmed by its application to four additional tautomerizations and can be used to screen out unfavorable azido-tetrazolo tautomerization reactions and increase the success rate of such synthesis.
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Developing methods for the accurate identification and analysis of sulfur-containing compounds (SCCs) is of great significance because of their essential roles in living organisms and the diagnosis of diseases. Herein, Se-doping improved oxidase-like activity of iron-based carbon material (Fe-Se/NC) was prepared and applied to construct a four-channel colorimetric sensor array for the detection and identification of SCCs (including biothiols and sulfur-containing metal salts). Fe-Se/NC can realize the chromogenic oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by activating O2 without relying on H2O2, which can be inhibited by different SCCs to diverse degrees to produce different colorimetric response changes as "fingerprints" on the sensor array. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) revealed that nine kinds of SCCs could be well discriminated. The sensor array was also applied for the detection of SCCs with a linear range of 1-50 µM and a limit of detection of 0.07-0.2 µM. Moreover, colorimetric sensor array inspired by the different levels of SCCs in real samples were used to discriminate cancer cells and food samples, demonstrating its potential application in the field of disease diagnosis and food monitoring. ENVIRONMENTAL IMPLICATIONS: In this work, a four-channel colorimetric sensor array for accurate SCCs identification and detection was successfully constructed. The colorimetric sensor array inspired by the different levels of SCCs in real samples were also used to discriminate cancer cells and food samples. Therefore, this Fe-Se/NC based sensor array is expected to be applied in the field of environmental monitoring and environment related disease diagnosis.
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Benzidinas , Carbono , Colorimetria , Ferro , Carbono/química , Ferro/química , Ferro/análise , Colorimetria/métodos , Benzidinas/química , Humanos , Compostos de Enxofre/análise , Compostos de Enxofre/química , Análise de Componente Principal , Linhagem Celular Tumoral , Limite de Detecção , Oxirredução , Oxirredutases , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/análiseRESUMO
Designing biomimetic nanomaterials with peroxidase (POD)-like activity at neutral pH remains a significant challenge. An S-doping strategy is developed to afford an iron single-atom nanomaterial (Fe1@CN-S) with high POD-like activity under neutral conditions. To the best of knowledge, there is the first example on the achievement of excellent POD-like activity under neutral conditions by regulating the active site structure. S-doping not only promotes the dissociation of the NâH bond in 3,3â³,5,5â³-tetramethylbenzidine (TMB), but also facilitates the desorption of OH* by the transformation of iron species' spin states from middle-spin (MS FeII) to low-spin (LS FeII). Meanwhile, LS FeII sites typically have more unfilled d orbitals, thereby exhibiting stronger interactions with H2O2 than MS FeII, which can enhance POD-like activity. Finally, a one-pot visual detection of glucose at pH 7 is performed, demonstrating the best selectivity and sensitivity than previous reports.
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Myeloid-derived suppressor cells (MDSCs) expand during sepsis and contribute to the development of persistent inflammation-immunosuppression-catabolism syndrome. However, the underlying mechanism remains unclear. Exploring the mechanisms of MDSCs generation may provide therapeutic targets for improving immune status in sepsis. Here, a sepsis mouse model is established by cecal ligation and perforation. Bone marrow cells at different sepsis time points are harvested to detect the proportion of MDSCs and search for differentially expressed genes by RNA-sequence. In lethal models of sepsis, polymorphonuclear-MDSCs (PMN-MDSCs) decrease in early but increase and become activated in late sepsis, which is contrary to the expression of metastasis-associated lung adenocarcinoma transcript 1 (Malat1). In vivo, Malat1 inhibitor significantly increases the mortality in mice with late sepsis. And in vitro, Malat1 down-regulation increases the proportion of PMN-MDSCs and enhanced its immunosuppressive ability. Mechanistically, Malat1 limits the differentiation of PMN-MDSCs by accelerating the degradation of phosphorylated STAT3. Furthermore, Stattic, an inhibitor of STAT3 phosphorylation, improves the survival of septic mice by inhibiting PMN-MDSCs. Overall, the study identifies a novel insight into the mechanism of sepsis-induced MDSCs and provides more evidence for targeting MDSCs in the treatment of sepsis.
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Células Supressoras Mieloides , Sepse , Animais , Camundongos , Modelos Animais de Doenças , Terapia de Imunossupressão , Células Supressoras Mieloides/metabolismo , Sepse/metabolismoRESUMO
In this study, we devised a diagnostic platform harnessing a combination of recombinase polymerase amplification (RPA) and the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a system. Notably, this platform obviates the need for intricate equipment and finds utility in diverse settings. Two result display methods were incorporated in this investigation: the RPA-Cas12a-fluorescence method and the RPA-Cas12a-LFS (lateral flow strip). Upon validation, both display platforms exhibited no instances of cross-reactivity, with seven additional types of fungal pathogens responsible for respiratory infections. The established detection limit was ascertained to be as low as 102 copies/µL. In comparison to fluorescence quantitative PCR, the platform demonstrated a sensitivity of 96.7%, a specificity of 100%, and a consistency rate of 98.0%.This platform provides expeditious, precise, and on-site detection capabilities, thereby rendering it a pivotal diagnostic instrument amenable for deployment in primary healthcare facilities and point-of-care settings.
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Pneumonia , Recombinases , Aspergillus fumigatus/genética , Sistemas CRISPR-Cas , Coloração e RotulagemRESUMO
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) not only significantly improves survival rates in severely ill neonates but also is associated with long-term neurodevelopmental issues. To systematically review the available literature on the neurodevelopmental outcomes of neonates and infants who have undergone ECMO treatment, with a focus on motor deficits, cognitive impairments, sensory impairments, and developmental delays. This review aims to understand the incidence, prevalence, and risk factors for these problems and to explore current nursing care and management strategies. DATA SOURCES: A comprehensive literature search was performed across PubMed, EMBASE, and Web of Science using a wide array of keywords and phrases pertaining to ECMO, neonates, infants, and various facets of neurodevelopment. The initial screening involved reviewing titles and abstracts to exclude irrelevant articles, followed by a full-text assessment of potentially relevant literature. The quality of each study was evaluated based on its research methodology and statistical analysis. Moreover, citation searches were conducted to identify potentially overlooked studies. Although the focus was primarily on neonatal ECMO, studies involving children and adults were also included due to the limited availability of neonate-specific literature. RESULTS: About 50% of neonates post-ECMO treatment exhibit varying degrees of brain injury, particularly in the frontal and temporoparietal white matter regions, often accompanied by neurological complications. Seizures occur in 18%-23% of neonates within the first 24 hours, and bleeding events occur in 27%-60% of ECMO procedures, with up to 33% potentially experiencing ischemic strokes. Although some studies suggest that ECMO may negatively impact hearing and visual development, other studies have found no significant differences; hence, the influence of ECMO remains unclear. In terms of cognitive, language, and intellectual development, ECMO treatment may be associated with potential developmental delays, including lower composite scores in cognitive and motor functions, as well as potential language and learning difficulties. These studies emphasize the importance of early detection and intervention of potential developmental issues in ECMO survivors, possibly necessitating the implementation of a multidisciplinary follow-up plan that includes regular neuromotor and psychological evaluations. Overall, further multicenter, large-sample, long-term follow-up studies are needed to determine the impact of ECMO on these developmental aspects. CONCLUSIONS: The impact of ECMO on an infant's nervous system still requires further investigation with larger sample sizes for validation. Fine-tuned management, comprehensive nursing care, appropriate patient selection, proactive monitoring, nutritional support, and early rehabilitation may potentially contribute to improving the long-term outcomes for these infants.
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Oxigenação por Membrana Extracorpórea , Humanos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Recém-Nascido , Lactente , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/epidemiologia , Feminino , Masculino , Encéfalo/crescimento & desenvolvimento , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/epidemiologiaRESUMO
Background: Acute kidney injury (AKI) is a common and serious organ dysfunction in critically ill children. Early identification and prediction of AKI are of great significance. However, current AKI criteria are insufficiently sensitive and specific, and AKI heterogeneity limits the clinical value of AKI biomarkers. This study aimed to establish and validate an explainable prediction model based on the machine learning (ML) approach for AKI, and assess its prognostic implications in children admitted to the pediatric intensive care unit (PICU). Methods: This multicenter prospective study in China was conducted on critically ill children for the derivation and validation of the prediction model. The derivation cohort, consisting of 957 children admitted to four independent PICUs from September 2020 to January 2021, was separated for training and internal validation, and an external data set of 866 children admitted from February 2021 to February 2022 was employed for external validation. AKI was defined based on serum creatinine and urine output using the Kidney Disease: Improving Global Outcome (KDIGO) criteria. With 33 medical characteristics easily obtained or evaluated during the first 24 h after PICU admission, 11 ML algorithms were used to construct prediction models. Several evaluation indexes, including the area under the receiver-operating-characteristic curve (AUC), were used to compare the predictive performance. The SHapley Additive exPlanation method was used to rank the feature importance and explain the final model. A probability threshold for the final model was identified for AKI prediction and subgrouping. Clinical outcomes were evaluated in various subgroups determined by a combination of the final model and KDIGO criteria. Findings: The random forest (RF) model performed best in discriminative ability among the 11 ML models. After reducing features according to feature importance rank, an explainable final RF model was established with 8 features. The final model could accurately predict AKI in both internal (AUC = 0.929) and external (AUC = 0.910) validations, and has been translated into a convenient tool to facilitate its utility in clinical settings. Critically ill children with a probability exceeding or equal to the threshold in the final model had a higher risk of death and multiple organ dysfunctions, regardless of whether they met the KDIGO criteria for AKI. Interpretation: Our explainable ML model was not only successfully developed to accurately predict AKI but was also highly relevant to adverse outcomes in individual children at an early stage of PICU admission, and it mitigated the concern of the "black-box" issue with an undirect interpretation of the ML technique. Funding: The National Natural Science Foundation of China, Jiangsu Province Science and Technology Support Program, Key talent of women's and children's health of Jiangsu Province, and Postgraduate Research & Practice Innovation Program of Jiangsu Province.
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This technical paper investigates the cluster synchronization of finite-field networks (FFNs) based on the algebraic state space representation. By resorting to the semi-tensor product of matrices, the cluster synchronization of an FFN can be completely converted into the set stability of state trajectory. Then, a necessary and sufficient condition for the cluster synchronization of FFNs is obtained based on the invariant subset and one-step transition matrix. In particular, the obtained results are applicable to check the leader-follower synchronization and group consensus of FFNs. Finally, a numerical example is given to illustrate the feasibility of the obtained results.
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Because of the intricate topological structure and connection of the human brain, extracting deep spatial features from electroencephalograph (EEG) signals is a challenging and time-consuming task. The extraction of topological spatial information plays a crucial role in EEG classification, and the architecture of the spatial convolution greatly affects the performance and complexity of convolutional neural network (CNN) based EEG classification models. In this study, a progressive convolution CNN architecture named EEGProgress is proposed, aiming to efficiently extract the topological spatial information of EEG signals from multi-scale levels (electrode, brain region, hemisphere, global) with superior speed. To achieve this, the raw EEG data is permuted using the empirical topological permutation rule, integrating the EEG data with numerous topological properties. Subsequently, the spatial features are extracted by a progressive feature extractor including prior, electrode, region, and hemisphere convolution blocks, progressively extracting the deep spatial features with reduced parameters and speed. Finally, the comparison and ablation experiments under both cross-subject and within-subject scenarios are conducted on a public dataset to verify the performance of the proposed EEGProgress and the effectiveness of the topological permutation. The results demonstrate the superior feature extraction ability of the proposed EEGProgress, with an average increase of 4.02% compared to other CNN-based EEG classification models under both cross-subject and within-subject scenarios. Furthermore, with the obtained average testing time, FLOPs, and parameters, the proposed EEGProgress outperforms other comparison models in terms of model complexity.
Assuntos
Encéfalo , Redes Neurais de Computação , Humanos , Eletrodos , EletroencefalografiaRESUMO
Resurgence and spread of macrolide-resistant Bordetella pertussis (MRBP) threaten global public health. We collected 283 B. pertussis isolates during 2016-2022 in Shanghai, China, and conducted 23S rRNA gene A2047G mutation detection, multilocus variable-number tandem-repeat analysis, and virulence genotyping analysis. We performed whole-genome sequencing on representative strains. We detected pertussis primarily in infants (0-1 years of age) before 2020 and older children (>5-10 years of age) after 2020. The major genotypes were ptxP1/prn1/fhaB3/ptxA1/ptxC1/fim2-1/fim3-1 (48.7%) and ptxP3/prn2/fhaB1/ptxA1/ptxC2/fim2-1/fim3-1 (47.7%). MRBP increased remarkably from 2016 (36.4%) to 2022 (97.2%). All MRBPs before 2020 harbored ptxP1, and 51.4% belonged to multilocus variable-number tandem-repeat analysis type (MT) 195, whereas ptxP3-MRBP increased from 0% before 2020 to 66.7% after 2020, and all belonged to MT28. MT28 ptxP3-MRBP emerged only after 2020 and replaced the resident MT195 ptxP1-MRBP, revealing that 2020 was a watershed in the transformation of MRBP.
Assuntos
Bordetella pertussis , Coqueluche , Criança , Lactente , Humanos , Adolescente , Pré-Escolar , Bordetella pertussis/genética , Coqueluche/epidemiologia , China/epidemiologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Macrolídeos/farmacologia , Evolução MolecularRESUMO
Cytokine storms are crucial in the development of various inflammatory diseases, including sepsis and autoimmune disorders. The immunosuppressive cytokine INTERLEUKIN (IL)-37 consists of five isoforms (IL-37a-e). We identified IL-37a as a nuclear cytokine for the first time. Compared to IL-37b, IL-37a demonstrated greater efficacy in protecting against Toll-like receptor-induced cytokine hypersecretion and lethal endotoxic shock. The full-length (FL) form of IL-37a and the N-terminal fragment, which is processed by elastase, could translocate into cell nuclei through a distinctive nuclear localization sequence (NLS)/importin nuclear transport pathway. These forms exerted their regulatory effects independent of the IL-1R8 receptor by transcriptionally upregulating the nuclear receptor peroxisome proliferator-activated receptor (PPARγ). This process involved the recruitment of the H3K4 methyltransferase complex WDR5/MLL4/C/EBPß and H3K4me1/2 to the enhancer/promoter of Pparg. The receptor-independent regulatory pathway of the nuclear IL-37a-PPARγ axis and receptor-dependent signaling by secreted IL-37a maintain homeostasis and are potential therapeutic targets for various inflammatory diseases, including sepsis.