Watersgregory1316

To determine risk factors and outcomes of necrotizing enterocolitis (NEC)-associated sepsis in infants with NEC.

A retrospective review comparing demographic and clinical information in infants with and without NEC-associated sepsis (defined as positive blood culture at the time of NEC onset).

A total of 209 infants with medical (n = 98) and surgical NEC (n = 111) had a median gestational age of 27 weeks (IQR 25; 30.5) and a median birth weight of 910 g [IQR 655; 1138]. Fifty of 209 (23.9%) infants had NEC-associated sepsis. Infants with NEC-associated sepsis had lower median GA (26.4 vs. 27.4 weeks; p = 0.01), lower birth weight (745 vs. 930 g; p = 0.009), were more likely mechanically ventilated [p < 0.001], received dopamine [p < 0.001], had more evidence of acute kidney injury [60% vs. 38.4%, p = 0.01], longer postoperative ileus (16 [13.0; 22.0] vs. 12 [8; 16] days; p = 0.006), higher levels of C-reactive protein, lower platelet counts, longer hospitalization compared to infants without NEC-aer NEC onset than those with Gram-positive sepsis.

NEC-associated sepsis was present in 24% of infants with NEC. Gram-positive bacteria, Gram-negative bacteria, and Candida were found in 15.3%, 10.5%, and 2.8% of cases, respectively. Infants with NEC-associated sepsis had a greater inflammatory response (CRP levels), received more blood transfusion before NEC onset, frequently needed assisted ventilation ionotropic support, and had acute kidney injury after NEC onset. NEC infants with Gram-negative sepsis had higher portal venous gas, received more platelet transfusions before NEC onset, and had higher CRP levels and lower median lymphocyte counts at 24 h after NEC onset than those with Gram-positive sepsis.Cancer is one of the most difficult diseases in human society. Therefore, it is urgent for us to understand its pathogenesis and improve the cure rate. Exosomes are nanoscale membrane vesicles formed by a variety of cells through endocytosis. As a new means of intercellular information exchange, exosomes have attracted much attention. Noncoding RNAs exist in various cell compartments and participate in a variety of cellular reactions; in particular, they can be detected in exosomes bound to lipoproteins and free circulating molecules. Increasing evidence has suggested the potential roles of exosomal noncoding RNAs in the progression of tumors. Herein, we present a comprehensive update on the biological functions of exosomal noncoding RNAs in the development of cancer. Specifically, we mainly focus on the effects of exosomal noncoding RNAs, including microRNAs, circular RNAs, long noncoding RNAs, small nuclear RNAs, and small nucleolar RNAs, on tumor growth, metastasis, angiogenesis, and chemoresistance. Moreover, we outline the current clinical implications concerning exosomal noncoding RNAs in cancer treatment.Retinal fundus photographs can be used to detect a range of retinal conditions. Here we show that deep-learning models trained instead on external photographs of the eyes can be used to detect diabetic retinopathy (DR), diabetic macular oedema and poor blood glucose control. We developed the models using eye photographs from 145,832 patients with diabetes from 301 DR screening sites and evaluated the models on four tasks and four validation datasets with a total of 48,644 patients from 198 additional screening sites. For all four tasks, the predictive performance of the deep-learning models was significantly higher than the performance of logistic regression models using self-reported demographic and medical history data, and the predictions generalized to patients with dilated pupils, to patients from a different DR screening programme and to a general eye care programme that included diabetics and non-diabetics. We also explored the use of the deep-learning models for the detection of elevated lipid levels. The utility of external eye photographs for the diagnosis and management of diseases should be further validated with images from different cameras and patient populations.We demonstrate a repeatable all-electric magnetic switching behaviour in a PMN-PT/FeRh thin film artificial multiferroic. The magnitude of the effect is significantly smaller than expected from conventional thermomagnetic switching of FeRh thin films and we explore properties of the PMN-PT/FeRh system in order to understand the origin of this reduction. The data demonstrate the importance of the crystallographic phase of PMN-PT and show how a phase transition at ~ 100 °C modifies the magneto-electric coupling. We demonstrate a large strain remanence effect in the PMN-PT substrate, which limits the magnetoelectric coupling on successive cycling of the applied electric field.Proteins are the main targets of most drugs; however, system-wide methods to monitor protein activity and function are still underused in drug discovery. Calpeptin supplier Novel biochemical approaches, in combination with recent developments in mass spectrometry-based proteomics instrumentation and data analysis pipelines, have now enabled the dissection of disease phenotypes and their modulation by bioactive molecules at unprecedented resolution and dimensionality. In this Review, we describe proteomics and chemoproteomics approaches for target identification and validation, as well as for identification of safety hazards. We discuss innovative strategies in early-stage drug discovery in which proteomics approaches generate unique insights, such as targeted protein degradation and the use of reactive fragments, and provide guidance for experimental strategies crucial for success.The role of glucose-6-phosphate dehydrogenase (G6PD) in human cancer is incompletely understood. In a metabolite screening, we observed that inhibition of H3K9 methylation suppressed aerobic glycolysis and enhances the PPP in human mesothelioma cells. Genome-wide screening identified G6PD as an H3K9me3 target gene whose expression is correlated with increased tumor cell apoptosis. Inhibition of aerobic glycolysis enzyme LDHA and G6PD had no significant effects on tumor cell survival. Ablation of G6PD had no significant effect on human mesothelioma and colon carcinoma xenograft growth in athymic mice. However, activation of G6PD with the G6PD-selective activator AG1 induced tumor cell death. AG1 increased tumor cell ROS production and the resultant extrinsic and intrinsic death pathways, mitochondrial processes, and unfolded protein response in tumor cells. Consistent with increased tumor cell death in vitro, AG1 suppressed human mesothelioma xenograft growth in a dose-dependent manner in vivo. Furthermore, AG1 treatment significantly increased tumor-bearing mouse survival in an intra-peritoneum xenograft athymic mouse model. Therefore, in human mesothelioma and colon carcinoma, G6PD is not essential for tumor growth. G6PD acts as a metabolic checkpoint to control metabolic flux towards the PPP to promote tumor cell apoptosis, and its expression is repressed by its promotor H3K9me3 deposition.Tumor therapeutics often target the primary tumor bulk but fail to eradicate therapy-resistant cancer stem cells (CSCs) in quiescent state. These can then become activated to initiate recurrence and/or metastasis beyond therapy. Here, we identified and isolated chemoradiotherapy-resistant CSCs in quiescent state with high capacity of tumor-initiation and tumorsphere formation from three types of breast tumors in mice. Experiments of knockdown and rescue revealed DEK, a nuclear protein, as essential for CSC activation. Exogenous DEK was then used to trigger quiescence exit of CSCs. ChIP-seq and ATAC-seq showed that DEK directly binds to chromatin, facilitating its genome-wide accessibility. The resulting epigenetic events upregulate the expression of cellular activation-related genes including MYC targets, whereas cellular quiescence-related genes including the p53 signaling pathway are silenced. However, twinned with DEK-induced activation, formerly resistant CSCs were then destroyed by chemotherapy in vitro. In mice, traditional chemoradiotherapy concurrent with the injection of DEK-containing exosomes resulted in eradication of primary tumors together with formerly resistant CSCs without recurrence or metastasis. Our findings advance knowledge of the mechanism of quiescent CSC activation and may provide novel clinical opportunities for removal of quiescence-linked therapy resistance.Genome-wide association studies (GWAS) have reported substantial genomic loci significantly associated with clinical risk of bipolar disorder (BD), and studies combining techniques of genetics, neuroscience, neuroimaging, and pharmacology are believed to help tackle clinical problems (e.g., identifying novel therapeutic targets). However, translating findings of psychiatric genetics into biological mechanisms underlying BD pathogenesis remains less successful. Biological impacts of majority of BD GWAS risk loci are obscure, and the involvement of many GWAS risk genes in this illness is yet to be investigated. It is thus necessary to review the progress of applying BD GWAS risk genes in the research and intervention of the disorder. A comprehensive literature search found that a number of such risk genes had been investigated in cellular or animal models, even before they were highlighted in BD GWAS. Intriguingly, manipulation of many BD risk genes (e.g., ANK3, CACNA1C, CACNA1B, HOMER1, KCNB1, MCHR1, NCAN, SHA and intervention of BD.We propose an approach for the identification of mutant genes for rare diseases in single cases of unknown etiology. All genes with rare biologically significant variants sorted from individual exome data are tested further for profiling of their spatial-temporal and cell/tissue specific expression compared to that of their paralogs. We developed a simple bioinformatics tool ("Essential Paralogue by Expression" (EPbE)) for such analysis. Here, we present rare clinical forms of early ataxia with cerebellar hypoplasia. Using whole-exome sequencing and the EPbE tool, we identified two novel mutant genes previously not associated with congenital human diseases. In Family I, the unique missense mutation (p.Lys258Glu) was found in the LRCH2 gene inherited in an X-linked manner. p.Lys258Glu occurs in the evolutionarily invariant site of the leucine-rich repeat domain of LRCH2. In Family II and Family III, the identical genetic variant was found in the CSMD1 gene inherited as an autosomal-recessive trait. The variant leads to amino acid substitution p.Gly2979Ser in a highly conserved region of the complement-interacting domain of CSMD1. The LRCH2 gene for Family I patients (in which congenital cerebellar hypoplasia was associated with demyelinating polyneuropathy) is expressed in Schwann and precursor Schwann cells and predominantly over its paralogous genes in the developing cerebellar cortex. The CSMD1 gene is predominantly expressed over its paralogous genes in the cerebellum, specifically in the period of late childhood. Thus, the comparative spatial-temporal expression of the selected genes corresponds to the neurological manifestations of the disease.The SARS-CoV-2 virus is responsible for the COVID-19 global public health emergency, and the disease it causes is highly variable in its clinical presentation. Clinical phenotypes are heterogeneous both in terms of presentation of symptoms in the host and response to therapy. Several studies and initiatives have been established to analyse and review host genetic epidemiology associated with COVID-19. Our research group curated these articles into a web-based database using the python application-server framework Django. The database provides a searchable research tool describing current literature surrounding COVID-19 host genetic factors associated with disease outcome. This paper describes the COHG-SA database and provides an overview of the analyses that can be derived from these data.