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This study aims to investigate the roles of gut microbiota and plasma metabolites in salt sensitivity (SS) of blood pressure (SSBP) and hypertension. A 23-day, multicenter, dietary salt intervention trial (the MetaSalt study) recruited 528 participants who underwent a baseline observation, low-salt, and high-salt interventions. SSBP was assessed and used as the primary outcome, and fecal shotgun metagenome and plasma targeted metabolome were measured. We found that high salt significantly altered 85 gut-microbial species ( p  < 9.42 × 10 −5 ) and 70 metabolites ( p  < 2.26 × 10 −4 ). Among them, the changes in 22 species and 8 metabolites were associated with SSBP ( p  < 0.05), and a gut microbiota-acylcarnitine network implicated in SSBP was identified, with a gut microbiota-derived metabolite, isovalerylcarnitine, as the core metabolite. Isovalerylcarnitine was also inversely associated with SSBP in the GenSalt study ( p  = 0.0102). Importantly, increased isovalerylcarnitine attenuated SS hypertension and improved endothelial function in rats, and was associated with reduced risk (ranging from 13% to 19%) of BP progression and incident hypertension in a prospective cohort (n = 3907, median follow-up = 5.5 years). This study demonstrated that the gut-acylcarnitine axis may play roles in the development of SS hypertension. Trial number: ChiCTR1900025171. Here, combining data from a clinical trial and animal models, the authors show a role for a gut-acylcarnitine axis in the development of salt-sensitive hypertension, and identify isovalerylcarnitine as a key microbiota-derived modulator and potential target for the precision prevention of hypertension.

Multimedia data are usually associated with multiple modalities represented by heterogeneous features. Recently, many information retrieval tasks are not only restricted to the case of a single modal and the contend-based cross modal retrieval has become one of the popular research fields. The premise of cross modal retrieval is discovering the relationships between different modalities efficiently. Though some approaches have been proposed to address this challenging problem, they either ignores the precious labels, or heavily depends on the completely labeled training data. In addition, for features with relatively high dimensionality, it is of great importance to select the most informative ones. In this paper, we propose a semi-supervised algorithm for cross modal learning. Our algorithm can make full use of both a small number of labeled and an abundant unlabeled data to establish connections between modalities via a shared semantic space discovering. On the other hand, our algorithm automatically filter out the noisy and redundant features to further improve our model. Finally, we give an efficient solution to the objective function. The experiments on two publicly available datasets demonstrate that the proposed method is competitive with or even superior to the state-of-art counterparts.

Background Risk factors related to mortality due to Acinetobacter baumannii (AB) bacteremia have been unveiled previously, but early clinical manifestations of AB bacteremia based on prognosis remain uncovered. Methods The demographic characteristics, clinical features, antibiotic susceptibility, and outcomes of 37 hospitalized children with laboratory-confirmed AB bacteremia from Suzhou, China, were collected and analyzed retrospectively. Results Of the 37 children with AB bacteremia included in this study, 23 were males and 14 were females, with a median age of 4.83 (0.60 to 10.15) years. Among the children, 18 died (48.65%, 18/37) and 19 survived (51.35%, 19/37). The dead group had a significantly higher incidence of respiratory failure (p = 0.008), shock (P = 0.000), MODS (p = 0.000), neutropenia (< 1.5 × 10 9 /L) (p = 0.000) and serious neutropenia (< 0.5 × 10 9 /L) (p = 0.000) than those in the survival group. The death group had significantly more invasive procedures (2 or more) than that in the survival group at 2 weeks before onset (p = 0.005). The proportion of MDR-AB in the death group was significantly higher than that in the survival group (p = 0.000), while the PICS score was significantly lower in the survival group than that in the death group (p = 0.000). There was no significant difference in effective antibiotic use within 24 h between these two groups (p = 0.295). Among the 37 children with bloodstream infection of AB, 56.76% (21/37) of the underlying diseases were hematological diseases and oncology. Among them, 17 (81.00%) were died in the hospital. The proportion of white blood cells (p = 0.000), neutrophils (p = 0.042), eosinophils (p = 0.029), the ANC (p = 0.000) and lymphocyte (p = 0.000), the NLR(p = 0.011), hemoglobin (p = 0.001), platelets (p = 0.000), prealbumin (P = 0.000), LDH (p = 0.017), blood gas pH (p = 0.000), and serum potassium (p = 0.002) in the death group were significantly lower than those in the survival group. However, CRP (p = 0.000) and blood glucose(p = 0.036) were significantly higher in the death group than those in the survival group. By further multivariate analysis, CRP [OR (95% CI): 1.022(1.003, 1.041), p = 0.021] and neutropenia [OR (95% CI): 21.634 (2.05, 228.313, p = 0.011] within 24 h of infection were independent risk factors for death in children with AB bacteremia. When CRP was higher than 59.02 mg/L, the sensitivity of predicting mortality was 88.9%, and the specificity was 78.9%. And the sensitivity and specificity of neutropenia for predicting mortality were 83.3% and 84.2%. Conclusions AB bacteremia has a high mortality in children, especially in patients with hematological diseases and oncology. Many early indicators were associated with poor prognosis, while elevated CRP and neutropenia were the independent predictors for the 30-day mortality of children with laboratory-confirmed AB bacteremia.

The prognostic impact of immunosuppressant therapies for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), along with the outcomes and prognosis of children with relapsed/refractory B cell acute lymphoblastic leukaemia (B-ALL) undergoing chimeric antigen receptor (CAR) T-cell therapy, varies across populations. However, studies specifically focusing on these factors in the pediatric B-ALL population remain limited. We investigated the effects of immunosuppressants on outcome efficacy and prognosis in a retrospective cohort of 120 patients treated with CAR T-cell infusion at a single institution from March 2017 to August 2023. The 30-day complete response rate, progression-free survival (PFS), overall survival (OS), and event-free survival (EFS) were evaluated. The median age of the patients was 8.0 years (range, 2.2-18.0 years). Following CAR T-cell therapy, 91.67% of patients developed CRS and 25.83% developed ICANS. At 1 month after CAR T-cell infusion, 70.83% of patients received tocilizumab (TCZ), 24.17% received ruxolitinib (RUX), and 50.83% received glucocorticoids (GC) for CRS or ICANS management. By day 30, 92.08% of patients achieved a complete response. The complete-response rates did not differ between the GC and non-GC, TCZ and non-TCZ, or RUX and non-RUX groups. The median follow-up time was 20.6 months (range, 4.26-38.82 months). OS, EFS, and PFS did not significantly differ between the RUX and non-RUX or TCZ and non-TCZ groups. However, patients receiving low-dose GC (≤ 8 mg kg ¹) exhibited better PFS than the non-GC group, with multivariable analysis demonstrating low-dose GC as an independent protective factor for PFS (hazard ratio, 0.45; 95% confidence interval, 0.21-0.96). In the context of CRS/ICANS management, low-dose GC independently confers long-term PFS benefits to pediatric B-ALL patients without compromising CAR T-cell activity when using appropriate GC, TCZ, or RUX regimens.

Background POLR3-related leukodystrophy is an autosomal recessive neurodegenerative disorder characterized by onset time ranging from the neonatal period to late childhood, progressive motor decline that manifests as spasticity, ataxia, tremor, and cerebellar symptoms, as well as mild cognitive regression and hypodontia. POLR3-related leukodystrophy belongs to the family of RNA polymerase III-related leukodystrophy, which are caused by biallelic mutations in the POLR3A, POLR3B, POLRC1 , or POLR3K genes. Case presentation In this study, we report a female child with POLR3-related leukodystrophy manifesting as cognitive decline, moderate dysarthria, motor decline, cerebellar syndrome, short stature, dysphagia, hypodontia, and mild delayed myelination by brain imaging. Interestingly, polytrichia and bronchodysplasia were first observed in a POLR3-related leukodystrophy patient. Medical exome sequencing with high coverage depth was employed to identify potential genetic variants in the patient. Novel compound heterozygous mutations of the POLR3A gene, c.1771-6C > G and c.2611del (p.M871Cfs*8), were detected. One of them is an uncommon splice site mutation, and this is the first report of this mutation in a Chinese family. The father was determined to be a heterozygous carrier of the c.2611del (p.M871Cfs*8) mutation and the mother a heterozygous carrier of the c.1771-6C > G mutation. Conclusion The patient’s newly emerged clinical features and mutations provide useful information for further exploration of genotype-phenotype correlations of POLR3-related leukodystrophy.

Background Human-induced pluripotent stem cell (hiPSC)-derived functional hepatic endoderm (HE) is supposed to be an alternative option for replacement therapy for end-stage liver disease. However, the high heterogeneity of HE cell populations is still challenging. Hepatic specification of definitive endoderm (DE) is an essential stage for HE induction in vitro. Recent studies have suggested that circular RNAs (circRNAs) determine the fate of stem cells by acting as competing endogenous RNAs (ceRNAs). To date, the relationships between endogenous circRNAs and hepatic specification remain elusive. Methods The identities of DE and HE derived from hiPSCs were determined by qPCR, cell immunofluorescence, and ELISA. Differentially expressed circRNAs (DEcircRNAs) were analysed using the Arraystar Human circRNA Array . qPCR was performed to validate the candidate DEcircRNAs. Intersecting differentially expressed genes (DEGs) of the GSE128060 and GSE66282 data sets and the DEcircRNA-predicted mRNAs were imported into Cytoscape for ceRNA networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were involved in the enrichment analysis. Hepatic markers and Wnt/β-catenin were detected in hsa_circ_004658-overexpressing cells by western blotting. Dual-luciferase reporter assays were used to evaluate the direct binding among hsa_circ_004658, miRNA-1200 and CDX2. DE cells were transfected with miR-1200 mimics, adenovirus containing CDX2, and Wnt/β-catenin was detected by western blotting. Results hiPSC-derived DE and HE were obtained at 4 and 9 days after differentiation, as determined by hepatic markers. During hepatic specification, 626 upregulated and 208 downregulated DEcircRNAs were identified. Nine candidate DEcircRNAs were validated by qPCR. In the ceRNA networks, 111 circRNA–miRNA–mRNA pairs were involved, including 90 pairs associated with hsa_circ_004658. In addition, 53 DEGs were identified among the intersecting mRNAs of the GSE128060 and GSE66282 data sets and the hsa_circ_004658-targeted mRNAs. KEGG and GO analyses showed that the DEGs associated with hsa_circ_004658 were mainly enriched in the WNT signalling pathway. Furthermore, hsa_circ_004658 was preliminarily verified to promote hepatic specification, as determined by hepatic markers (AFP, ALB, HNF4A, and CK19) ( p  < 0.05 ) . This promotive effect may be related to the inhibition of the Wnt/β-catenin signalling pathway (detected by β-catenin, p-β-catenin, and TCF4) when hsa_circ_004658 was overexpressed ( p  < 0.05). Dual-luciferase reporter assays showed that there were binding sites for miR-1200 in the hsa_circ_004658 sequence, and confirmed the candidate DEG (CDX2) as a miR-1200 target. The level of miR-1200 decreased and the level of CDX2 protein expression increased when hsa_circ_004658 was overexpressed ( p  < 0.05). In addition, the results showed that CDX2 may suppress the Wnt/β-catenin signalling during hepatic specification ( p  < 0.05). Conclusions This study analysed the profiles of circRNAs during hepatic specification. We identified the hsa_circ_004658/miR-1200/CDX2 axis and preliminarily verified its effect on the Wnt/β-catenin signalling pathway during hepatic specification. These results provide novel insight into the molecular mechanisms involved in hepatic specification and could improve liver development in the future. Graphical Abstract

Background Published data and practice recommendations on end-of-life care generally reflect Western practice frameworks; there are limited data on withdrawal of treatment for children in China. Methods Withdrawal of treatment for children in the pediatric intensive care unit (PICU) of a regional children’s hospital in eastern China from 2006 to 2017 was studied retrospectively. Withdrawal of treatment was categorized as medical withdrawal or premature withdrawal. The guardian’s self-reported reasons for abandoning the child’s treatment were recorded from 2011. Results The incidence of withdrawal of treatment for children in the PICU decreased significantly; for premature withdrawal the 3-year average of 15.1% in 2006–2008 decreased to 1.9% in 2015–2017 (87.4% reduction). The overall incidence of withdrawal of care reduced over the time period, and withdrawal of therapy by guardians was the main contributor to the overall reduction. The median age of children for whom treatment was withdrawn increased from 14.5 months (interquartile range: 4.0–72.0) in 2006 to 40.5 months (interquartile range: 8.0–99.0) in 2017. Among the reasons given by guardians of children whose treatment was withdrawn in 2011–2017, “illness is too severe” ranked first, accounting for 66.3%, followed by “condition has been improved” (20.9%). Only a few guardians ascribed treatment withdrawal to economic reasons. Conclusions The frequency of withdrawal of medical therapy has changed over time in this children’s hospital PICU, and parental decision-making has been a large part of the change.

Self-supervised stereo matching holds great promise by eliminating the reliance on expensive ground-truth data. Its dominant paradigm, based on photometric consistency, is however fundamentally hindered by the occlusion challenge -- an issue that persists regardless of network architecture. The essential insight is that for any occluders, valid feedback signals can only be derived from the unoccluded areas on one side of the occluder. Existing methods attempt to address this by focusing on the erroneous feedback from the other side, either by identifying and removing it, or by introducing additional regularities for correction on that basis. Nevertheless, these approaches have failed to provide a complete solution. This work proposes a more fundamental solution. The core idea is to transform the fixed state of one-sided valid and one-sided erroneous signals into a probabilistic acquisition of valid feedback from both sides of an occluder. This is achieved through a complete framework, centered on a pseudo-stereo inputs strategy that decouples the input and feedback, without introducing any additional constraints. Qualitative results visually demonstrate that the occlusion problem is resolved, manifested by fully symmetrical and identical performance on both flanks of occluding objects. Quantitative experiments thoroughly validate the significant performance improvements resulting from solving the occlusion challenge.

Self-supervised stereo matching holds great promise for application and research due to its independence from expensive labeled data. However, direct self-supervised stereo matching paradigms based on photometric loss functions have consistently struggled with performance issues due to the occlusion challenge. The crux of the occlusion challenge lies in the fact that the positions of occluded pixels consistently align with the epipolar search direction defined by the input stereo images, leading to persistent information loss and erroneous feedback at fixed locations during self-supervised training. In this work, we propose a simple yet highly effective pseudo-stereo inputs strategy to address the core occlusion challenge. This strategy decouples the input and feedback images, compelling the network to probabilistically sample information from both sides of the occluding objects. As a result, the persistent lack of information in the aforementioned fixed occlusion areas is mitigated. Building upon this, we further address feedback conflicts and overfitting issues arising from the strategy. By integrating these components, our method achieves stable and significant performance improvements compared to existing methods. Quantitative experiments are conducted to evaluate the performance. Qualitative experiments further demonstrate accurate disparity inference even at occluded regions. These results demonstrate a significant advancement over previous methods in the field of direct self-supervised stereo matching based on photometric loss. The proposed pseudo-stereo inputs strategy, due to its simplicity and effectiveness, has the potential to serve as a new paradigm for direct self-supervised stereo matching. Code is available at https://github.com/qrzyang/Pseudo-Stereo.

Background: Published data and practice recommendations on end-of-life care generally reflect Western practice frameworks; there are limited data on withdrawal of treatment for children in China. Methods: Withdrawal of treatment for children in the pediatric intensive care unit (PICU) of a regional children’s hospital in eastern China from 2006 to 2017 was studied retrospectively. Withdrawal of treatment was categorized as medical withdrawal or premature withdrawal. The guardian’s self-reported reasons for abandoning the child’s treatment were recorded from 2011. Results: The incidence of withdrawal of treatment for children in the PICU decreased significantly; for premature withdrawal the 3-year average of 15.1% in 2006–2008 decreased to 1.9% in 2015–2017 (87.4% reduction). The overall incidence of withdrawal of care reduced over the time period, and withdrawal of therapy by guardians was the main contributor to the overall reduction. The median age of children for whom treatment was withdrawn increased from 14.5 months (interquartile range: 4.0–72.0) in 2006 to 40.5 months (interquartile range: 8.0–99.0) in 2017. Among the reasons given by guardians of children whose treatment was withdrawn in 2011–2017, “illness is too severe” ranked first, accounting for 66.3%, followed by “condition has been improved” (20.9%). Only a few guardians ascribed treatment withdrawal to economic reasons. Conclusions: The frequency of withdrawal of medical therapy has changed over time in this children’s hospital PICU, and parental decision-making has been a large part of the change.