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Traditional recommender systems (RS) assume users' taste to be static (taste remains same over time) and reactive (a change in taste cannot be predicted and is observed only after it occurs). Further, traditional RS restricts the recommendation process to candidate items generation. This work aims to explore two phases of RS, i.e., Candidate Generation as well as Candidate Ranking. We propose a RS from a multi-objective (short-term prediction, long-term prediction, diversity, and popularity bias) perspective which was previously overlooked. The sequential and non-sequential behavior of users is exploited to predict future behavioral trajectories with the consideration of short-term and long-term prediction using recurrent neural networks and nearest neighbors approach. Further, a novel candidate ranking method is introduced to prevent users from being entangled in recommended items. On multiple datasets, largest being MovieLens (ML) 1M, our model shows excellent results achieving a hit rate and short-term prediction success of 58% and 71% respectively on ML 1M. Further, it implicitly handles two important parameters, i.e., diversity and item popularity with a success rate of 59.22% and 34.28% respectively.
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BACKGROUND: Discontinuation of inappropriate antimicrobial therapy is an important target for stewardship intervention. The drug and duration-dependent effects of antibiotics on the developing neonatal gut microbiota needs to be precisely quantified. METHODS: In this retrospective, cross-sectional study, we performed 16S rRNA sequencing on stool swab samples collected from neonatal intensive care unit patients within 7 days of discontinuation of therapy who received ampicillin and tobramycin (AT), ampicillin and cefotaxime (AC), or ampicillin, tobramycin, and metronidazole (ATM). We compared taxonomic composition within term and preterm infant groups between treatment regimens. We calculated adjusted effect estimates for antibiotic type and duration of therapy on the richness of obligate anaerobes and known butyrate-producers in all infants. RESULTS: A total of 72 infants were included in the study. Term infants received AT (20/28; 71%) or AC (8/28; 29%) with median durations of 3 and 3.5 days, respectively. Preterm infants received AT (32/44; 73%) or ATM (12/44; 27%) with median durations of 4 and 7 days, respectively. Compositional analyses of 67 stool swab samples demonstrated low diversity and dominance by potential pathogens. Within 1 week of discontinuation of therapy, each additional day of antibiotics was associated with lower richness of obligate anaerobes (adjusted risk ratio [aRR], 0.84; 95% confidence interval [CI], .73-.95) and butyrate-producers (aRR, 0.82; 95% CI, .67-.97). CONCLUSIONS: Each additional day of antibiotics was associated with lower richness of anaerobes and butyrate-producers within 1 week after therapy. A longitudinally sampled cohort with preexposure sampling is needed to validate our results.
Assuntos
Microbioma Gastrointestinal , Antibacterianos/uso terapêutico , Estudos Transversais , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , RNA Ribossômico 16S , Estudos RetrospectivosRESUMO
Commensal microbiota are immunomodulatory, and their pathological perturbation can affect the risk and outcomes of infectious and inflammatory diseases. Consequently, the human microbiota is an emerging diagnostic and therapeutic target in critical illness. In this study, we compared four sample types-rectal, naris, and antecubital swabs and stool samples-for 16S rRNA gene microbiota sequencing in intensive care unit (ICU) patients. Stool samples were obtained in only 31% of daily attempts, while swabs were reliably obtained (≥97% of attempts). Swabs were compositionally distinct by anatomical site, and rectal swabs identified within-patient temporal trends in microbiota composition. Rectal swabs from ICU patients demonstrated differences from healthy stool similar to those observed in comparing stool samples from ICU patients to those from the same healthy controls. Rectal swabs are a useful complement to other sample types for analysis of the intestinal microbiota in critical illness, particularly when obtaining stool may not be feasible or practical.IMPORTANCE Perturbation of the microbiome has been correlated with various infectious and inflammatory diseases and is common in critically ill patients. Stool is typically used to sample the microbiota in human observational studies; however, it is often unavailable for collection from critically ill patients, reducing its utility as a sample type to study this population. Our research identified alternatives to stool for sampling the microbiota during critical illness. Rectal and naris swabs were practical alternatives for use in these patients, as they were observed to be more reliably obtained than stool, were suitable for culture-independent analysis, and successfully captured within- and between-patient microbiota differences.
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Estado Terminal , Microbiota , Nariz/microbiologia , Reto/microbiologia , Análise por Conglomerados , DNA Ribossômico/química , DNA Ribossômico/genética , Fezes/microbiologia , Humanos , Unidades de Terapia Intensiva , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Pele/microbiologiaRESUMO
[This corrects the article DOI: 10.1128/mSphere.00219-18.].
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The red-eared slider turtle, Trachemys scripta elegans, is a model organism commonly used to study the environmental stress of anoxia. It exhibits multiple biochemical adaptations to ensure its survival during the winter months where quantities of oxygen are largely depleted. We proposed that JAK-STAT signaling would display stress responsive regulation to mediate the survival of the red-eared slider turtle, Trachemys scripta elegans, during anoxic stress. Importantly, the JAK-STAT signaling pathway is involved in transmitting extracellular signals to the nucleus resulting in the expression of select genes that aid cell survival and growth. Immunoblotting was used to compare the relative phosphorylation levels of JAK proteins, STAT proteins, and two of its inhibitors, SOCS and PIAS, in response to anoxia. A clear activation of the JAK-STAT pathway was observed in the liver tissue while no significant changes were found in the skeletal muscle. To further support our findings we also found an increase in mRNA transcripts of downstream targets of STATs, namely bcl-xL and bcl-2, using PCR analysis in the liver tissues. These findings suggest an important role for the JAK-STAT pathway in exhibiting natural anoxia tolerance by the red-eared slider turtle.
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Hipóxia/metabolismo , Janus Quinases/metabolismo , Oxigênio/metabolismo , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais , Tartarugas/metabolismo , Animais , Núcleo Celular/genética , Núcleo Celular/metabolismo , Hipóxia/genética , Janus Quinases/genética , Fosforilação , Fatores de Transcrição STAT/genética , Tartarugas/genéticaRESUMO
The North American wood frog, Rana sylvatica, is one of just a few anuran species that tolerates whole body freezing during the winter and has been intensely studied to identify the biochemical adaptations that support freeze tolerance. Among these adaptations is the altered expression of many genes, making freeze-responsive changes to gene regulatory mechanisms a topic of interest. The present study focuses on the potential involvement of microRNAs as one such regulatory mechanism and aims to better understand freeze/thaw stress-induced microRNA responses in the freeze-tolerant wood frog. Using quantitative PCR, relative levels of 53 microRNAs were measured in heart and skeletal muscle of control, 24 h frozen, and 8 h thawed frogs. MicroRNAs showed tissue specific expression patterns: 21 microRNAs decreased in the heart during thawing, whereas 16 microRNAs increased during freezing stress in skeletal muscle. These findings suggest that select genes may be activated and suppressed in heart and skeletal muscle, respectively, in response to freezing. Bioinformatics analysis using the DIANA miRPath program (v.2.0) predicted that the differentially expressed microRNAs may collectively regulate tissue-specific cellular pathways to promote survival of wood frogs undergoing freezing and thawing.