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Objective: Elevated intra-abdominal pressure (IAP) is associated with organ dysfunction in critically ill children. Thus far, the predictive value of IAP for mortality remains unknown. Moreover, only few studies determined normal IAP values in pediatric intensive care unit (PICU) children. This study aimed to determine the predictive value of IAP for mortality and calculate normal IAP values in PICU patients. Methods: This prospective observational study was conducted in two PICUs of two tertiary care university teaching hospitals. Patients admitted to the PICU between December 2013 and November 2015 were included. IAP was determined by bladder pressure measurements performed every 8 h until 48 h or until PICU discharge. All patients (except neonatal patients) aged ≤ 14 years who were admitted to the PICUs and had no history of chemical neuromuscular blockade use, neurogenic bladder, or bladder surgery were enrolled. Binary logistic regression was used to analyze the predictive value of IAP for 28-day mortality. Receiver operating characteristic curves were generated to evaluate the prediction effect of IAP. Results: Overall, 229 patients were enrolled. IAP (hazard ratio 1.09, 95% confidence interval [CI] 1.029-1.161, P = 0.004) and lactic acid (hazard ratio 3.04, 95% CI 1.769-5.21, P < 0.001) were independent predictors of 28-day mortality. Additionally, IAP had good predictive power for 28-day mortality, with an area under the curve of 0.74. The optimal cutoff point was 12.13 mmHg (sensitivity 0.58, specificity 0.80). The Youden index was 0.38.Furthermore, 111 (48.47%) patients without high-risk factors or clinical manifestations of IAH were analyzed to determine normal IAP values, which were 7.57 ± 2.85 mmHg (range, 1.98-13.16 mmHg). There were no significant differences in normal IAP values according to different diseases, sex, age, weight, or body mass index (BMI). Conclusions: IAP has good predictive power for 28-day mortality. The optimal IAP cutoff point is 12.13 mmHg. The IAP reference range is 2.0-13.2 mmHg, which was not associated with factors such as sex, age, weight, and BMI in PICU children. We recommend that IAP be included in critical illness scoring systems in the future. IAP >12.13 mmHg may be more suitable for IAH definition in PICU patients.
The sedative effects of dexmedetomidine (Dex) are similar to natural sleep, with easy wakening following Dex administration, and Dex has minor effects on breathing, reducing emergence agitation in children. The aim of this study was to systematically evaluate the effects of Dex on recovery quality in children following general anaesthesia with sevoflurane, to aid clinical decision making.
It is currently assumed that 3D chromosomal organization plays a central role in transcriptional control. However, depletion of cohesin and CTCF affects the steady-state levels of only a minority of transcripts. Here, we use high-resolution Capture Hi-C to interrogate the dynamics of chromosomal contacts of all annotated human gene promoters upon degradation of cohesin and CTCF. We show that a majority of promoter-anchored contacts are lost in these conditions, but many contacts with distinct properties are maintained, and some new ones are gained. The rewiring of contacts between promoters and active enhancers upon cohesin degradation associates with rapid changes in target gene transcription as detected by SLAM sequencing (SLAM-seq). These results provide a mechanistic explanation for the limited, but consistent, effects of cohesin and CTCF depletion on steady-state transcription and suggest the existence of both cohesin-dependent and -independent mechanisms of enhancer-promoter pairing.
Non-mass enhancement (NME) is a diagnostic dilemma and highly reliant on the experience of the radiologists. Texture analysis (TA) could serve as an objective method to quantify lesion characteristics. However, it remains unclear what role TA plays in a predictive model based on routine MRI characteristics. The purpose of this study was to explore the value of TA in distinguishing between benign and malignant NME in premenopausal women.
Fusarium wilt of banana caused by Fusarium oxysporum f. sp. cubense (Foc) is a disastrous soil-borne fungal disease. Foc tropical race 4 (Foc TR4) can infect almost all banana cultivars. Until now, there is a shortage of safety and effective control methods and commercial banana cultivars with a resistance against Foc TR4. Biocontrol using environmentally friendly microbes is a promising strategy for the management of Foc TR4. Here, a strain 5-10, newly isolated from a medicinal plant (Curculigo capitulata), exhibited a high antifungal activity against Foc TR4. Combing the morphological characteristics and molecular identification, strain 5-10 was classified as a Streptomyces genus. The sequenced genome revealed that more than 39 gene clusters were involved in the biosynthesis of secondary metabolites. Some multidrug resistance gene clusters were also identified such as mdtD, vatB, and vgaE. To improve the anti-Foc TR4 activity of the strain 5-10 extracts, an optimization method of fermentation broth was established. Antifungal activity increased by 72.13% under the fermentation system containing 2.86 g/L of NaCl and 11.57% of inoculation amount. After being treated with the strain 5-10 extracts, the Foc TR4 hyphae shrinked, deformed, and ruptured. The membrane integrity and cell ultrastructure incurred irreversible damage. Streptomyces sp. 5-10 extracts play a fungicidal role in Foc TR4. Hence, Streptomyces sp. 5-10 will be a potential biocontrol agent to manage fungal diseases by exploring the microbial fertilizer.
The germ line produces gametes that transmit genetic and epigenetic information to the next generation. Maintenance of germ cells and development of gametes require germ granules-well-conserved membraneless and RNA-rich organelles. The composition of germ granules is elusive owing to their dynamic nature and their exclusive expression in the germ line. Using Caenorhabditis elegans germ granule, called P granule, as a model system, we employed a proximity-based labeling method in combination with mass spectrometry to comprehensively define its protein components. This set of experiments identified over 200 proteins, many of which contain intrinsically disordered regions (IDRs). An RNA interference-based screen identified factors that are essential for P granule assembly, notably EGGD-1 and EGGD-2, two putative LOTUS-domain proteins. Loss of eggd-1 and eggd-2 results in separation of P granules from the nuclear envelope, germline atrophy, and reduced fertility. We show that IDRs of EGGD-1 are required to anchor EGGD-1 to the nuclear periphery while its LOTUS domains are required to promote the perinuclear localization of P granules. Taken together, our work expands the repertoire of P granule constituents and provides new insights into the role of LOTUS-domain proteins in germ granule organization.
Frail patients with chronic obstructive pulmonary disease (COPD) face a higher risk of adverse outcomes, but there is no clear consensus on which frailty measures are most suitable for COPD patients. Herein we evaluated the ability of frailty measurements in predicting 1-year acute exacerbation, hospitalization, and mortality in older patients with COPD.
Sepsis is an inflammatory disease with high mortality and morbidity. Inflammation plays an essential role in sepsis, and suppressing inflammation has been shown to ameliorate sepsis. Rnf144b is an ubiquitin E3 ligation with anti-inflammation activities. Its precise roles in sepsis remain unknown. Here, we explored the function of Rnf144b in sepsis.
Genetic information is stored in linear DNA molecules, which are highly folded inside cells. DNA replication along the folded template path yields two sister chromatids that initially occupy the same nuclear region in an intertwined arrangement. Dividing cells must disentangle and condense the sister chromatids into separate bodies such that a microtubule-based spindle can move them to opposite poles. While the spindle-mediated transport of sister chromatids has been studied in detail, the chromosome-intrinsic mechanics presegregating sister chromatids have remained elusive. Here, we show that human sister chromatids resolve extensively already during interphase, in a process dependent on the loop-extruding activity of cohesin, but not that of condensins. Increasing cohesin's looping capability increases sister DNA resolution in interphase nuclei to an extent normally seen only during mitosis, despite the presence of abundant arm cohesion. That cohesin can resolve sister chromatids so extensively in the absence of mitosis-specific activities indicates that DNA loop extrusion is a generic mechanism for segregating replicated genomes, shared across different Structural Maintenance of Chromosomes (SMC) protein complexes in all kingdoms of life.
Accounting for cell type compositions has been very successful at analyzing high-throughput data from heterogeneous tissues. Differential gene expression analysis at cell type level is becoming increasingly popular, yielding biomarker discovery in a finer granularity within a particular cell type. Although several computational methods have been developed to identify cell type-specific differentially expressed genes (csDEG) from RNA-seq data, a systematic evaluation is yet to be performed. Here, we thoroughly benchmark six recently published methods: CellDMC, CARseq, TOAST, LRCDE, CeDAR and TCA, together with two classical methods, csSAM and DESeq2, for a comprehensive comparison. We aim to systematically evaluate the performance of popular csDEG detection methods and provide guidance to researchers. In simulation studies, we benchmark available methods under various scenarios of baseline expression levels, sample sizes, cell type compositions, expression level alterations, technical noises and biological dispersions. Real data analyses of three large datasets on inflammatory bowel disease, lung cancer and autism provide evaluation in both the gene level and the pathway level. We find that csDEG calling is strongly affected by effect size, baseline expression level and cell type compositions. Results imply that csDEG discovery is a challenging task itself, with room to improvements on handling low signal-to-noise ratio and low expression genes.
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