Floresmccarty1110

Long non-coding RNAs (lncRNAs) are involved in breast cancer pathogenesis through chromatin remodeling, transcriptional and post-transcriptional gene regulation. We report robust associations between lncRNA expression and breast cancer clinicopathological features in two population-based cohorts SCAN-B and TCGA. Using co-expression analysis of lncRNAs with protein coding genes, we discovered three distinct clusters of lncRNAs. In silico cell type deconvolution coupled with single-cell RNA-seq analyses revealed that these three clusters were driven by cell type specific expression of lncRNAs. In one cluster lncRNAs were expressed by cancer cells and were mostly associated with the estrogen signaling pathways. In the two other clusters, lncRNAs were expressed either by immune cells or fibroblasts of the tumor microenvironment. Selleckchem AZD9291 To further investigate the cis-regulatory regions driving lncRNA expression in breast cancer, we identified subtype-specific transcription factor (TF) occupancy at lncRNA promoters. We also integrated lncRNA expression with DNA methylation data to identify long-range regulatory regions for lncRNA which were validated using ChiA-Pet-Pol2 loops. lncRNAs play an important role in shaping the gene regulatory landscape in breast cancer. We provide a detailed subtype and cell type-specific expression of lncRNA, which improves the understanding of underlying transcriptional regulation in breast cancer.The scale of cumulative cultural evolution (CCE) is a defining characteristic of humans. Despite marked scientific interest in CCE, the cognitive underpinnings supporting its development remain understudied. We examined the role cognitive flexibility plays in CCE by studying U.S. children's (N = 167, 3-5-year-olds) propensity to relinquish an inefficient solution to a problem in favor of a more efficient alternative, and whether they would resist reverting to earlier versions. In contrast to previous work with chimpanzees, most children who first learned to solve a puzzlebox in an inefficient way switched to an observed, more efficient alternative. However, over multiple task interactions, 85% of children who switched reverted to the inefficient method. Moreover, almost all children in a control condition (who first learned the efficient method) switched to the inefficient method. Thus, children were keen to explore an alternative solution but, like chimpanzees, are overall conservative in reverting to their first-learned one.Adequate endodontic diagnostic is essential when making a therapy decision. Radiographic imagining acquisition methods (IAMs) are fundamental apical lesions of endodontic (ALE) origin diagnose tool. Thus, the aim of this research was to compare the simulated apical lesions (SALs) diagnose potential of digital intraoral radiography (DIR) and cone-beam computed tomography (CBCT), if there is a relationship between the IAMs, SALs-depth and their correct diagnose likelihood in human mandibular specimens' datasets. 1024 SALs were prepared in cancellous and cortical bone with different penetration depths. The SALs-stages were radiographed with CBCT and DIR. The IAMs were randomly evaluated by 16 observers in two trials. Possible SAL findings were analyzed according to a five-point scale. The null hypothesis established that SALs detection accuracy does not differ between CBCT and DIR. Significantly differences (first 0.935 and second trial 0.960) were found for the CBCT area under the curve when compared with the DIR (first 0.859 and second trial 0.862) findings. SALs of smaller size were earlier detected by CBCT. In SALs without cortical involvement the probability of detection increased from 90 to 100%. The SALs-depth had the highest detectability influence on cancellous bone lesions and CBCT SALs detectability was 84.9% higher than with DIR images. The CBCT diagnose reproducibility was higher than the one of DIR (Kappa CBCT 75.7-81.4%; DIR 53.4-57.1%). Our results showed that CBCT has a higher SALs IAM diagnosing accuracy and that SALs detection accuracy incremented as the SALs-size increased.Fever in neutropenia (FN) remains an unavoidable, potentially lethal complication of chemotherapy. Timely administration of empirical broad-spectrum intravenous antibiotics has become standard of care. But the impact of time to antibiotics (TTA), the lag period between recognition of fever or arrival at the hospital to start of antibiotics, remains unclear. Here we aimed to analyze the association between TTA and safety relevant events (SRE) in data from a prospective multicenter study. We analyzed the association between time from recognition of fever to start of antibiotics (TTA) and SRE (death, admission to intensive care unit, severe sepsis and bacteremia) with three-level mixed logistic regression. We adjusted for possible triage bias using a propensity score and stratified the analysis by severity of disease at presentation with FN. We analyzed 266 FN episodes, including 53 (20%) with SRE, reported in 140 of 269 patients recruited from April 2016 to August 2018. TTA (median, 120 min; interquartile range, 49-180 min) was not associated with SRE, with a trend for less SREs in episodes with longer TTA. Analyses applying the propensity score suggested a relevant triage bias. Only in patients with severe disease at presentation there was a trend for an association of longer TTA with more SRE. In conclusion, TTA was unrelated to poor clinical outcome in pediatric patients with FN presenting without severe disease. We saw strong evidence for triage bias which could only be partially adjusted.

A fixed 6 mg dexamethasone dose for 10 days is the standard treatment for all hospitalised COVID-19 patients who require supplemental oxygen. Yet, the pharmacokinetic properties of dexamethasone can lead to diminishing systemic dexamethasone exposure with increasing body mass index (BMI). The present study examines whether this translates to overweight and obesity being associated with worse clinical outcomes, defined as ICU admission or in hospital death, in COVID-19 patients treated with fixed-dose dexamethasone.

We conducted a single centre retrospective cohort study in COVID-19 patients who were admitted to a non-ICU ward and were treated with dexamethasone (6 mg once daily for a maximum of ten days) between June 2020 and January 2021. Univariable and multivariable logistic regression analyses were conducted to assess the association between BMI-categories and an unfavourable clinical course (ICU admission and/or in hospital death). Analyses were adjusted for age, comorbidities, inflammatory status, abesity are not associated with an unfavourable clinical course in COVID-19 patients admitted to a non-ICU ward and treated with 6 mg dexamethasone once daily.

Overweight and obesity are not associated with an unfavourable clinical course in COVID-19 patients admitted to a non-ICU ward and treated with 6 mg dexamethasone once daily.We investigated the effect of pharmacologically induced weight loss on markers of glucagon resistance in individuals with overweight during treatment with the glucagon-like peptide-1 receptor agonist liraglutide. We performed an open-label study in 14 men with overweight (age 38 ± 11 years, BMI 32 ± 4 kg/m2) without simultaneously diabetes. Subjects were treated with liraglutide, initiated and titrated with 0.6 mg/day/week to reach the final dose of 3.0 mg/day. Subjects were examined at baseline, during titration (Week 4), after 2 weeks of steady state (Week 6) of final dosing of liraglutide and 3 weeks after discontinuation of liraglutide (follow-up). Study participants lost 3.3 ± 1.9 kg (3%) total body weight during the first 4 weeks of treatment with liraglutide. Simultaneously, liver fat content decreased from 12.4 ± 11.6% to 10.2 ± 11.1%, p = 0.025, whereas fat content in the spleen and subcutaneous tissue was unaltered. Markers of glucagon resistance, including plasma glucagon and the glucagon-alanine-index, also decreased significantly during treatment, but total and individual plasma amino acid concentrations did not. Insulin resistance (HOMA-IR) was unchanged during treatment, whereas insulin clearance increased. Treatment with the GLP-1 receptor analogue liraglutide decreased liver fat content, and simultaneously attenuated glucagon concentrations and the glucagon-alanine index in individuals with overweight without diabetes.Cetylpyridinium chloride (CPC), a quaternary ammonium compound, which is present in mouthwash, is effective against bacteria, fungi, and enveloped viruses. This study was conducted to explore the antiviral effect of CPC on SARS-CoV-2. There are few reports on the effect of CPC against wild-type SARS-CoV-2 at low concentrations such as 0.001%-0.005% (10-50 µg/mL). Interestingly, we found that low concentrations of CPC suppressed the infectivity of human isolated SARS-CoV-2 strains (Wuhan, Alpha, Beta, and Gamma) even in saliva. Furthermore, we demonstrated that CPC shows anti-SARS-CoV-2 effects without disrupting the virus envelope, using sucrose density analysis and electron microscopic examination. In conclusion, this study provided experimental evidence that CPC may inhibit SARS-CoV-2 infection even at lower concentrations.We compared the aqueous profiles, baseline characteristics, and clinical outcomes of 54 eyes with macular edema secondary to major branch retinal vein occlusion (BRVO) and macular BRVO. We also identified the characteristics of poor responders to anti-vascular endothelial growth factor (VEGF) injections. Aqueous inflammatory cytokine and VEGF concentrations were significantly higher in major BRVO. In optical coherence tomography, major BRVO had a higher proportion with subretinal fluid, disorganization of retinal inner layers, and ellipsoid zone disruption. Comparing the clinical outcomes, major BRVO required more intravitreal anti-VEGF injections and had a poorer visual prognosis in the first 12 months. A significantly higher proportion of patients with major BRVO required additional treatments after 6 months compared to macular BRVO. Patients who responded poorly to anti-VEGF had higher aqueous VEGF levels and central subfield thickness (CST) at baseline. In conclusion, major BRVO patients required more and longer treatments, and had worse visual prognoses. BRVO that responds poorly to anti-VEGF had greater CST and higher aqueous VEGF levels at baseline.Walkability is an important measure with strong ties to our health. However, there are existing gaps in the literature. Our previous work proposed new approaches to address existing limitations. This paper explores new ways of applying transferability using transfer-learning. Road networks, POIs, and road-related characteristics grow/change over time. Moreover, calculating walkability for all locations in all cities is very time-consuming. Transferability enables reuse of already-learned knowledge for continued learning, reduce training time, resource consumption, training labels and improve prediction accuracy. We propose ALF-Score++, that reuses trained models to generate transferable models capable of predicting walkability score for cities not seen in the process. We trained transfer-learned models for St. John's NL and Montréal QC and used them to predict walkability scores for Kingston ON and Vancouver BC. MAE error of 13.87 units (ranging 0-100) was achieved for transfer-learning using MLP and 4.56 units for direct-training (random forest) on personalized clusters.