Miracle-dz/UniFAR-FTUs huggingface dataset:
Microbubbles: A Novel Strategy for Chemotherapy.

BACKGROUND Ultrasound microbubbles have conventionally been used for diagnostic purposes. In recent years, however, new types of microbubbles have emerged as important carriers for drug delivery. Moreover, studies have shown that ultrasound microbubbles can serve as valuable and noninvasive tools in cancer therapy; thus the use of ultrasound microbubbles to deliver chemotherapeutic drugs to malignant tissues is a promising possibility. METHODS In this review, we briefly describe the status of ultrasound microbubbles in clinical practice and then discuss the development of targeted microbubbles. Finally, we consider novel strategies for the use of microbubbles in cancer therapy. RESULTS Many different kinds of microbubbles are emerged. Novel strategies of ultrasound microbubble have been shown to be effective in cancer therapy. CONCLUSION Although many problems need to be solved in the future, the ultrasound drugs loaded microbubbles still have strong potential for the use in clinical cancer therapy.
Class-Wide Access to a Commercial Step 1 Question Bank During Preclinical Organ-Based Modules: A Pilot Project

Purpose The authors examined the usefulness of a commercially available Step 1 question bank as a formative academic support tool throughout organ-based modules in an integrated preclinical medical curriculum. The authors also determined the extent to which correlation between question bank utilization and academic metrics varied with Medical College Admission Test (MCAT) scores. Method In 2015, a cohort of 185 first-year medical students at University of Alabama School of Medicine were provided with 18-month full access to a commercially available Step 1 question bank of over 2,100 items throughout organ-based modules, although there were no requirements for use. Data on student use of the question bank were collected via an online administrative portal. Relationships between question bank utilization and academic outcomes including exams, module grades, and United States Medical Licensing Examination (USMLE) Step 1 were determined using multiple linear regression. Results MCAT scores and number of items attempted in the question bank significantly predicted all academic measures, with question bank utilization as the stronger predictor. The association between question bank utilization and academic outcome was stronger for individuals with lower MCAT scores. Conclusions The findings elucidate a novel academic support mechanism that, for some programs, may help bridge the gap between holistic and mission-based admissions practices and a residency match process that places a premium on USMLE exam scores. Distributed formative use of USMLE Step 1 practice questions may be of value as an academic support tool that benefits all students, but particularly those entering with lower MCAT scores.
Homophobia, hypermasculinity and the US black church

Black churches in the USA constitute a significant source of the homophobia that pervades black communities. This theologically‐driven homophobia is reinforced by the anti‐homosexual rhetoric of black nationalism. Drawing on a variety of sources, this paper discusses the sources of homophobia within black communities, and its impact upon self‐esteem, social relationships and physical health. Religion‐based homophobia and black nationalism point to wider structures which have influenced their emergence, including racism, patriarchy and capitalism. It is vital for US black churches and communities to understand and transcend their longstanding resistance to openly addressing complex, painful issues of sexuality and embrace healthier definitions of black manhood.
Bone metastasis pattern in initial metastatic breast cancer: a population-based study

Purpose Bone is one of the most common sites of breast cancer metastasis, and population-based studies of patients with bone metastasis in initial metastatic breast cancer (MBC) are lacking. Materials and methods From 2010 to 2013, 245,707 breast cancer patients and 8901 patients diagnosed with initial bone metastasis were identified by Surveillance, Epidemiology, and End Results database of the National Cancer Institute. Multivariate logistic and Cox regression were used to identify predictive factors for the presence of bone metastasis and prognosis factors. Kaplan–Meier method and log-rank test were used for survival analysis. Results Eight thousand nine hundred one patients with initial MBC had bone involvement, accounting for 3.6% of the entire cohort and 62.5% of the patients with initial MBC. Also, 70.5% of patients with bone metastasis were hormone receptor (HR) positive (HR+/human epidermal growth factor receptor 2 [HER2]−: 57.6%; HR+/HER2+: 12.9%). Patients with initial bone metastasis had a better 5-year survival rate compared to those with initial brain, liver, or lung metastasis. HR+/HER2− and HR+/HER2+ breast cancer had a propensity of bone metastasis in the entire cohort and were correlated with better prognosis in patients with initial bone metastasis. Local surgery had significantly improved overall survival in initial MBC patients with bone metastasis. Conclusion Our study has provided population-based estimates of epidemiologic characteristics and prognosis in patients with bone metastasis at the time of breast cancer diagnosis. These findings would lend support to optimal surveillance and treatment of bone metastasis in breast cancer.
Nitrogen dynamics in flooded soil systems: an overview on concepts and performance of models

Abstract Extensive modelling studies on nitrogen (N) dynamics in flooded soil systems have been published. Consequently, many N dynamics models are available for users to select from. With the current research trend, inclined towards multidisciplinary research, and with substantial progress in understanding of N dynamics in flooded soil systems, the objective of this paper is to provide an overview of the modelling concepts and performance of 14 models developed to simulate N dynamics in flooded soil systems. This overview provides breadth of knowledge on the models, and, therefore, is valuable as a first step in the selection of an appropriate model for a specific application. © 2017 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
A Comparison of Single Molecule and Amplification Based Sequencing of Cancer Transcriptomes

The second wave of next generation sequencing technologies, referred to as single-molecule sequencing (SMS), carries the promise of profiling samples directly without employing polymerase chain reaction steps used by amplification-based sequencing (AS) methods. To examine the merits of both technologies, we examine mRNA sequencing results from single-molecule and amplification-based sequencing in a set of human cancer cell lines and tissues. We observe a characteristic coverage bias towards high abundance transcripts in amplification-based sequencing. A larger fraction of AS reads cover highly expressed genes, such as those associated with translational processes and housekeeping genes, resulting in relatively lower coverage of genes at low and mid-level abundance. In contrast, the coverage of high abundance transcripts plateaus off using SMS. Consequently, SMS is able to sequence lower- abundance transcripts more thoroughly, including some that are undetected by AS methods; however, these include many more mapping artifacts. A better understanding of the technical and analytical factors introducing platform specific biases in high throughput transcriptome sequencing applications will be critical in cross platform meta-analytic studies.
Improving efficiency of parameter estimation in case‐cohort studies with multivariate failure time data

The case‐cohort study design is an effective way to reduce cost of assembling and measuring expensive covariates in large cohort studies. Recently, several weighted estimators were proposed for the case‐cohort design when multiple diseases are of interest. However, these existing weighted estimators do not make effective use of the covariate information available in the whole cohort. Furthermore, the auxiliary information for the expensive covariates, which may be available in the studies, cannot be incorporated directly. In this article, we propose a class of updated‐estimators. We show that, by making effective use of the whole cohort information, the proposed updated‐estimators are guaranteed to be more efficient than the existing weighted estimators asymptotically. Furthermore, they are flexible to incorporate the auxiliary information whenever available. The advantages of the proposed updated‐estimators are demonstrated in simulation studies and a real data analysis.
Automatic Parameter Learning for Multiple Local Network Alignment

We developed Graemlin 2.0, a new multiple network aligner with (1) a new multi-stage approach to local network alignment; (2) a novel scoring function that can use arbitrary features of a multiple network alignment, such as protein deletions, protein duplications, protein mutations, and interaction losses; (3) a parameter learning algorithm that uses a training set of known network alignments to learn parameters for our scoring function and thereby adapt it to any set of networks; and (4) an algorithm that uses our scoring function to find approximate multiple network alignments in linear time. We tested Graemlin 2.0's accuracy on protein interaction networks from IntAct, DIP, and the Stanford Network Database. We show that, on each of these datasets, Graemlin 2.0 has higher sensitivity and specificity than existing network aligners. Graemlin 2.0 is available under the GNU public license at http://graemlin.stanford. edu .
c-AMP Dependent Protein Kinase a Inhibitory Activity of Six Algal Extracts from South Eastern Australia and Their Fatty Acid Composition

c-AMP Dependent protein kinase (protein kinase A, PKA) is an important enzyme involved in the regulation of an increasing number of physiological processes including immune function, cardiovascular disease, memory disorders and cancer. The objective of this study was to evaluate the PKA inhibitory activity of a range of algal extracts, along with their fatty acid composition. Six algal species were investigated including two Chlorophyta (Codium dimorphum and Ulva lactuca), two Phaeophyta (Phyllospora comosa and Sargassum sp.) and two Rhodophyta (Prionitis linearis and Corallina vancouveriensis), with the order of PKA inhibitory activity of their extracts identified as follows: brown seaweeds > red seaweeds > green seaweeds with the brown alga Sargassum sp. exhibiting the highest PKA inhibitory activity (84% at 100 μg/mL). GC/MS analysis identified a total of 18 fatty acids in the six algal extracts accounting for 72-87% of each extract, with hexadecanoic acid and 9,12-octadecadienoic acid as the dominant components. The most active extract (Sargassum sp.) also contained the highest percentage of the saturated C14:0 fatty acid (12.8% of the total extract), which is a known to inhibit PKA. These results provide the first description of the PKA inhibitory activity of marine algae along with the first description of the fatty acid composition of these six algal species from South Eastern Australian waters. Importantly, this study reveals that abundant and readily available marine algae are a new and relatively unexplored source of PKA inhibitory compounds.
The small molecule AU14022 promotes colorectal cancer cell death via p53‐mediated G2/M‐phase arrest and mitochondria‐mediated apoptosis

The p53 tumor suppressor plays critical roles in cell cycle regulation and apoptotic cell death, with its activation capable of sensitizing cancer cells to radiotherapy or chemotherapy. To identify small molecules that induce apoptosis via increased p53 transcriptional activity, we used a novel in‐house library containing 96 small‐molecule compounds. Using a cell‐based screening method with a p53‐responsive luciferase‐reporter assay system involving benzoxazole derivatives, we found that AU14022 administration significantly increased p53 transcriptional activity in a concentration‐dependent manner. Treatment with AU14022 increased p53 protein expression, p53 Ser15 phosphorylation, p53‐mediated expression of downstream target genes, and apoptosis in p53‐wild‐type HCT116 human colon cancer cells, but not in p53‐knockout HCT116 cells. Additionally, p53‐wild‐type HCT116 cells treated with AU14022 exhibited mitochondrial dysfunction, including modulated expression of B‐cell lymphoma‐2 family proteins and cytochrome c release. Combination treatment with AU14022 and ionizing radiation (IR) synergistically induced apoptosis as compared with IR or AU14022 treatment alone, with further investigation demonstrating that cell cycle progression was significantly arrested at the G2/M phase following AU14022 treatment. Furthermore, in a mouse p53‐wild‐type HCT116 colon cancer xenograft model, combined treatment with AU14022 and IR inhibited tumor growth more effectively than radiation alone. Therefore, AU14022 treatment induced apoptosis through p53‐mediated cell cycle arrest involving mitochondrial dysfunction, leading to enhanced radiosensitivity in colon cancer cells. These results provide a basis for further assessments of AU14022 as a promising anticancer agent.
Biomarkers for In Vivo Assessment of Transporter Function

Drug–drug interactions are a major concern not only during clinical practice, but also in drug development. Due to limitations of in vitro–in vivo predictions of transporter-mediated drug–drug interactions, multiple clinical Phase I drug–drug interaction studies may become necessary for a new molecular entity to assess potential drug interaction liabilities. This is a resource-intensive process and exposes study participants, who frequently are healthy volunteers without benefit from study treatment, to the potential risks of a new drug in development. Therefore, there is currently a major interest in new approaches for better prediction of transporter-mediated drug–drug interactions. In particular, researchers in the field attempt to identify endogenous compounds as biomarkers for transporter function, such as hexadecanedioate, tetradecanedioate, coproporphyrins I and III, or glycochenodeoxycholate sulfate for hepatic uptake via organic anion transporting polypeptide 1B or N1-methylnicotinamide for multidrug and toxin extrusion protein–mediated renal secretion. We summarize in this review the currently proposed biomarkers and potential limitations of the substances identified to date. Moreover, we suggest criteria based on current experiences, which may be used to assess the suitability of a biomarker for transporter function. Finally, further alternatives and supplemental approaches to classic drug–drug interaction studies are discussed.
The investigation of antistatic effects of 1-ethyl-2,3-dimethylimidazolium ethyl sulphate for acrylic-based polymer film

This study aims to produce a long-term antistatic acrylic-based film by incorporating ionic liquid (IL), 1-ethyl-2,3-dimethylimidazolium ethyl sulphate (EIL) into acrylic resin. After loading, characterisations of samples were conducted by mechanically, thermally and morphologically. In order to determine antistatic properties, surface resistivity of samples was measured by using at different time intervals. The results indicated that IL loaded polymers showed a good antistatic property for a long time. The effect of incorporation on tensile strength, tensile modulus, flexural strength and flexural modulus of polymer were also obtained. After loading process, tensile strength, tensile modulus, flexural strength and flexural modulus values decreased considerably. The decrement in tensile strength of polymer is much less than that in flexural strength. The effect of EIL incorporation into acrylic resin on thermal conductivity and surface wettability was also investigated. From scanning electron microscopy images, EIL particles in nano-size range were observed in polymer structure.
Detection and analysis of change in remotely sensed imagery with application to wide area surveillance

A new approach to wide area surveillance is described that is based on the detection and analysis of changes across two or more images over time. Methods for modeling and detecting general patterns of change associated with construction and other kinds of activities that can be observed in remotely sensed imagery are presented. They include a new nonlinear prediction technique for measuring changes between images and temporal segmentation and filtering techniques for analyzing patterns of change over time. These methods are applied to the problem of detecting facility construction using Landsat Thematic Mapper imagery. Full scene results show the methods to be capable of detecting specific patterns of change with very few false alarms. Under all conditions explored, as the number of images used increases, the number of false alarms decreases dramatically without affecting the detection performance. It is argued that the processing gain that results in using more than two images justifies the increased computational complexity and storage requirements of our approach over single image object detection and conventional change detection techniques.
PEAR: PEriodic And fixed Rank separation for fast fMRI

Purpose: In functional MRI (fMRI), faster acquisition via undersampling of data can improve the spatial‐temporal resolution trade‐off and increase statistical robustness through increased degrees‐of‐freedom. High‐quality reconstruction of fMRI data from undersampled measurements requires proper modeling of the data. We present an fMRI reconstruction approach based on modeling the fMRI signal as a sum of periodic and fixed rank components, for improved reconstruction from undersampled measurements. Methods: The proposed approach decomposes the fMRI signal into a component which has a fixed rank and a component consisting of a sum of periodic signals which is sparse in the temporal Fourier domain. Data reconstruction is performed by solving a constrained problem that enforces a fixed, moderate rank on one of the components, and a limited number of temporal frequencies on the other. Our approach is coined PEAR ‐ PEriodic And fixed Rank separation for fast fMRI. Results: Experimental results include purely synthetic simulation, a simulation with real timecourses and retrospective undersampling of a real fMRI dataset. Evaluation was performed both quantitatively and visually versus ground truth, comparing PEAR to two additional recent methods for fMRI reconstruction from undersampled measurements. Results demonstrate PEAR's improvement in estimating the timecourses and activation maps versus the methods compared against at acceleration ratios of R = 8,10.66 (for simulated data) and R = 6.66,10 (for real data). Conclusions: This paper presents PEAR, an undersampled fMRI reconstruction approach based on decomposing the fMRI signal to periodic and fixed rank components. PEAR results in reconstruction with higher fidelity than when using a fixed‐rank based model or a conventional Low‐rank + Sparse algorithm. We have shown that splitting the functional information between the components leads to better modeling of fMRI, over state‐of‐the‐art methods.
Changes in the incidence and surgical treatment of ankyloglossia in Canada.

Background Recent reports show increases in rates of ankyloglossia and frenotomy in British Columbia. We carried out a study to determine temporal trends and regional variations in ankyloglossia and frenotomy in Canada. Methods The study included all hospital-based live births in Canada (excluding Quebec) between April 2002 and March 2015, with information obtained from the Canadian Institute for Health Information. Information on ankyloglossia and frenotomy was obtained from records of hospital admission for childbirth. Temporal trends and provincial/territorial variations were quantified using rate ratios (RR) and 95% confidence intervals (CI). Results Ankyloglossia rates increased from 6.86 in 2002 to 22.6 per 1000 live births in 2014 (P for trend < 0.001), while frenotomy rates increased from 3.76 in 2002 to 14.7 per 1000 live births in 2014 (P for trend < 0.001). Frenotomy rates among infants with ankyloglossia increased from 54.7% in 2002 to 63.9% in 2014 (RR: 1.18, 95% CI: 1.13-1.24). Compared with British Columbia, rates of ankyloglossia were over three-fold higher in Saskatchewan (RR: 3.40, 95% CI: 3.16-3.67), Alberta (RR: 3.50, 95% CI: 3.29-3.72) and the Yukon (RR: 3.62, 95% CI: 2.67-4.92), while rates of frenotomy were three- to four-fold higher in the Yukon (RR: 3.41, 95% CI: 2.28-5.10), Alberta (RR: 4.01, 95% CI: 3.71-4.33) and Saskatchewan (RR: 4.12, 95% CI: 3.76-4.52). Conclusion A desire to increase rates of breast feeding initiation and absence of standardized criteria for the diagnosis of ankyloglossia have resulted in runaway rates of frenotomy for newborn infants in some parts of Canada.
Inflammation, remodeling, and other factors affecting HDL cholesterol efflux

Purpose of review The ability of HDL to promote cholesterol efflux from macrophages is a predictor of cardiovascular risk independent of HDL cholesterol levels. However, the molecular determinants of HDL cholesterol efflux capacity (CEC) are largely unknown. Recent findings The term HDL defines a heterogeneous population of particles with distinct size, shape, protein, and lipid composition. Cholesterol efflux is mediated by multiple pathways that may be differentially modulated by HDL composition. Furthermore, different subpopulations of HDL particles mediate CEC via specific pathways, but the molecular determinants of CEC, either proteins or lipids, are unclear. Inflammation promotes a profound remodeling of HDL and impairs overall HDL CEC while improving ATP-binding cassette transporter G1-mediated efflux. This review discusses recent findings that connect HDL composition and CEC. Summary Data from recent animal and human studies clearly show that multiple factors associate with CEC including individual proteins, lipid composition, as well as specific particle subpopulations. Although acute inflammation remodels HDL and impairs CEC, chronic inflammation has more subtle effects. Standardization of assays measuring HDL composition and CEC is a necessary prerequisite for understanding the factors controlling HDL CEC. Unraveling these factors may help the development of new therapeutic interventions improving HDL function.