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The length of waiting time has become an important indicator of the efficiency of medical services and the quality of medical care. Lengthy waiting times for patients will inevitably affect their mood and reduce satisfaction. For patients who are in urgent need of hospitalization, delayed admission often leads to exacerbation of the patient's condition and may threaten the patient's life. We gathered patients' information about outpatient visits and hospital admissions in the Nephrology Department of a large tertiary hospital in western China from January 1st, 2014, to December 31st, 2016, and we used big data-enabled analysis methods, including univariate analysis and multivariate linear regression models, to explore the factors affecting waiting time. We found that gender (P=0.048), the day of issuing the admission card (Saturday, P=0.028), the applied period for admission (P less then 0.001), and the registration interval (P less then 0.001) were positive influencing factors of patients' waiting time. Disease type (after kidney transplantation, P less then 0.001), number of diagnoses (P=0.037), and the day of issuing the admission card (Sunday, P=0.001) were negative factors. A linear regression model built using these data performed well in the identification of factors affecting the waiting time of patients in the Nephrology Department. These results can be extended to other departments and could be valuable for improving patient satisfaction and hospital service quality by identifying the factors affecting waiting time.Extracellular vesicles (EVs) derived from the secretome of human mesenchymal stromal cells (MSC) contain numerous factors that are known to exert anti-inflammatory effects. MSC-EVs may serve as promising cell-based therapeutics for the inner ear to attenuate inflammation-based side effects from cochlear implantation which represents an unmet clinical need. In an individual treatment performed on a 'named patient basis', we intraoperatively applied allogeneic umbilical cord-derived MSC-EVs (UC-MSC-EVs) produced according to good manufacturing practice. A 55-year-old patient suffering from Menière's disease was treated with intracochlear delivery of EVs prior to the insertion of a cochlear implant. This first-in-human use of UC-MSC-EVs demonstrates the feasibility of this novel adjuvant therapeutic approach. The safety and efficacy of intracochlear EV-application to attenuate side effects of cochlea implants have to be determined in controlled clinical trials.Oncogenic RAS impacts communication between cancer cells and their microenvironment, but it is unclear how this process influences cellular interactions with extracellular vesicles (EVs). Bromelain manufacturer This is important as intercellular EV trafficking plays a key role in cancer invasion and metastasis. Here we report that overexpression of mutant RAS drives the EV internalization switch from endocytosis (in non-transformed cells) to macropinocytosis (in cancer cells) resulting in enhanced EV uptake. This process depends on the surface proteoglycan, fibronectin and EV engulfment mechanism regulated by CRAF. Both mutant RAS and activated CRAF expression is associated with formation of membrane ruffles to which they colocalize along with actin, sodium-hydrogen exchangers (NHEs) and phosphorylated myosin phosphatase (pMYPT). RAS-transformed cells internalize EVs in the vicinity of ruffled structures followed by apparent trafficking to lysosome and degradation. NHE inhibitor (EIPA) suppresses RAS-driven EV uptake, along with adhesion-independent clonal growth and experimental metastasis in mice. Thus, EV uptake may represent a targetable step in progression of RAS-driven cancers.The secreting function of pituitary adenomas (PAs) plays a critical role in making the treatment strategies. However, Magnetic Resonance Imaging (MRI) analysis for pituitary adenomas is labor intensive and highly variable among radiologists. In this work, by applying convolutional neural network (CNN), we built a segmentation and classification model to help distinguish functioning pituitary adenomas from non-functioning subtypes with 3D MRI images from 185 patients with PAs (two centers). Specifically, the classification model adopts the concept of transfer learning and uses the pre-trained segmentation model to extract deep features from conventional MRI images. As a result, both segmentation and classification models obtained high performance in two internal validation datasets and an external testing dataset (for segmentation model Dice score = 0.8188, 0.8091 and 0.8093 respectively; for classification model AUROC = 0.8063, 0.7881 and 0.8478, respectively). In addition, the classification model considers the attention mechanism for better model interpretation. Taken together, this work provides the first deep learning-based tumor region segmentation and classification models of PAs, which enables early diagnosis and subtyping PAs from MRI images.Codon degeneracy of amino acid sequences permits an additional "mRNP code" layer underlying the genetic code that is related to RNA processing. In pre-mRNA splicing, splice site usage is determined by both intrinsic strength and sequence context providing RNA binding sites for splicing regulatory proteins. In this study, we systematically examined modification of splicing regulatory properties in the neighborhood of a GT site, i.e. potential splice site, without altering the encoded amino acids. We quantified the splicing regulatory properties of the neighborhood around a potential splice site by its Splice Site HEXplorer Weight (SSHW) based on the HEXplorer score algorithm. To systematically modify GT site neighborhoods, either minimizing or maximizing their SSHW, we designed the novel stochastic optimization algorithm ModCon that applies a genetic algorithm with stochastic crossover, insertion and random mutation elements supplemented by a heuristic sliding window approach. To assess the achievable range in SSHW in human splice donors without altering the encoded amino acids, we applied ModCon to a set of 1000 randomly selected Ensembl annotated human splice donor sites, achieving substantial and accurate changes in SSHW. Using ModCon optimization, we successfully switched splice donor usage in a splice site competition reporter containing coding sequences from FANCA, FANCB or BRCA2, while retaining their amino acid coding information. The ModCon algorithm and its R package implementation can assist in reporter design by either introducing novel splice sites, silencing accidental, undesired splice sites, and by generally modifying the entire mRNP code while maintaining the genetic code.

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