Miracle-dz/UniFAR-FTUs huggingface dataset:
MicroRNAs Associated With Reverse Left Ventricular Remodeling in Humans Identify Pathways of Heart Failure Progression

Background: Plasma extracellular RNAs have recently garnered interest as biomarkers in heart failure (HF). Most studies in HF focus on single extracellular RNAs related to phenotypes and outcomes, and few describe their functional roles. We hypothesized that clusters of plasma microRNAs (miRNAs) associated with left ventricular (LV) remodeling in human HF would identify novel subsets of genes involved in HF in animal models. Methods and Results: We prospectively measured circulating miRNAs in 64 patients with systolic HF (mean age, 64.8 years; 91% men; median LV ejection fraction, 26%) with serial echocardiography (10 months apart) during medical therapy. We defined LV reverse remodeling as a 15% reduction in LV end-systolic volume index. Using principal components analysis, we identified a component associated with LV reverse remodeling (odds ratio=3.99; P=0.01) that provided risk discrimination for LV reverse remodeling superior to a clinical model (C statistic, 0.58 for a clinical model versus 0.71 for RNA-based model). Using network bioinformatics, we uncovered genes not previously widely described in HF regulated simultaneously by >2 miRNAs. We observed increased myocardial expression of these miRNAs during HF development in animals, with downregulation of target gene expression, suggesting coordinate miRNA–mRNA regulation. Target mRNAs were involved in autophagy, metabolism, and inflammation. Conclusions: Plasma miRNAs associated with LV reverse remodeling in humans are dysregulated in animal HF and target clusters of genes involved in mechanisms implicated in HF. A translational approach integrating human HF, bioinformatics, and model systems may uncover novel pathways involved in HF. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials. gov. Unique identifier: NCT00351390
MicroRNA-150 inhibitors enhance cell apoptosis of melanoma by targeting PDCD4

Malignant melanoma is a tumor with a high mortality rate. Previous studies have demonstrated that the oncogenesis of melanoma is associated with microRNA (miR)-150. However, the role of miR-150 in melanoma and its regulatory mechanisms are still unclear. In the present study, melanoma cancer tissues and adjacent normal tissues were obtained from 20 melanoma patients. The expression level of miR-150 in melanoma tissue and cell lines was detected by reverse transcription-quantitative polymerase chain reaction. miR-150 inhibitors/negative control were transfected into melanoma A375 cells in order to investigate the effects of miR-150 on cell proliferation, apoptosis, cell cycle migration and invasion using a Cell Counting Kit-8, colony formation, Hoechst 33528, flow cytometry, and Transwell assays. The association between miR-150 and programmed cell death protein-4 (PDCD4) was detected by a dual luciferase reporter assay. The functional role of PDCD4 in miR-150-affected melanoma cells was confirmed by small interfering (si)RNA knockdown. Results demonstrated that miR-150 was significantly upregulated and mRNA and protein expressions of PDCD4 were decreased in melanoma cancer tissues as compared with adjacent normal tissues. The level of PDCD4 was inversely associated with the level of miR-150. Transfection of miR-150 inhibitors suppressed cell proliferation, migration, and invasion, while the apoptosis of cells was promoted and G2/M cell arrest was induced. MiR-150 inhibitors enhanced the expression of caspase-8 and p21. The PDCD4 was identified as a direct target gene of miR-150. The effects of miR-150 inhibitors on apoptosis and apoptosis-associated proteins, including caspase-8 and p21, of A375 cells, were reversed following transfection of siRNA-PDCD4. Therefore, miR-150 inhibitors enhance cell apoptosis via upregulation of PDCD4-mediated activation of caspase-8 and p21. These findings demonstrate the potential for a promising therapeutic strategy in the management of melanoma.
Comparison of Automated Antimicrobial Susceptibility Testing Systems To Detect mecC-Positive Methicillin-Resistant Staphylococcus aureus

Methicillin resistance in Staphylococcus aureus is classically mediated by the mecA gene carried on a mobile genetic element, called staphylococcal cassette chromosome mec (SCC mec ). mecA encodes an additional penicillin binding protein, named PBP2a, with low affinity for all beta-lactams except
Respiratory Function as a Marker of Bone Health and Fracture Risk in an Older Population

Identification of those at high risk of osteoporosis and fractures using clinically available tests beyond BMD measures is a major clinical challenge. We examined forced expiratory volume in 1 s (FEV1), an easily obtainable measure of respiratory function, as a clinical measure for fracture prediction. In the context of the European Prospective Investigation into Cancer‐Norfolk Study, 8304 women and 6496 men 42–81 yr of age underwent a health check including spirometry and heel quantitative ultrasonography between 1997 and 2000 and were followed up for incident hip fractures until 2007. The main outcome measures were broadband ultrasound attenuation (BUA) of the heel (cross‐sectional analysis) and hip fracture risk (prospective analysis). In multivariate regression models, a 1‐liter increase in FEV1 was associated with a statistically significant 2.2‐dB/MHz increase in BUA, independent of age, smoking, height, body mass index, history of fracture, and use of corticosteroids. Mean FEV1 was significantly lower among 84 women and 36 men with hip fracture compared with other participants. In multivariate proportional‐hazard regression models, the relative risk (RR) of hip fracture associated with a 1‐liter increase in FEV1 was 0.5 (95% CI, 0.3–0.9; p < 0.001) for both men and women. RR of hip fracture for a 1 SD increase in FEV1 was approximately equivalent to a 0.5 SD increase in BUA among women (1 SD among men) and an ∼5‐yr decrease in age among both men and women. Middle‐aged and older people with low respiratory function are at increased risk of osteoporosis and hip fracture. FEV1, an easy, low‐cost, and feasible clinical measure, may help improve the identification of high‐risk groups.
Timed high‐fat diet resets circadian metabolism and prevents obesity

Disruption of circadian rhythms leads to obesity and metabolic disorders. Timed restricted feeding (RF) provides a time cue and resets the circadian clock, leading to better health. In contrast, a high‐fat (HF) diet leads to disrupted circadian expression of metabolic factors and obesity. We tested whether long‐term (18 wk) clock resetting by RF can attenuate the disruptive effects of diet‐induced obesity. Analyses included liver clock gene expression, locomotor activity, blood glucose, metabolic markers, lipids, and hormones around the circadian cycle for a more accurate assessment. Compared with mice fed the HF diet ad libitum, the timed HF diet restored the expression phase of the clock genes Clock and Cry1 and phase‐advanced Per1, Per2, Cry2, Bmal1, Rorα, and Rev‐erbα. Although timed HF‐diet‐fed mice consumed the same amount of calories as ad libitum low‐fat diet‐fed mice, they showed 12% reduced body weight, 21% reduced cholesterol levels, and 1.4‐fold increased insulin sensitivity. Compared with the HF diet ad libitum, the timed HF diet led to 18% lower body weight, 30% decreased cholesterol levels, 10% reduced TNF‐α levels, and 3.7‐fold improved insulin sensitivity. Timed HF‐diet‐fed mice exhibited a better satiated and less stressed phenotype of 25% lower ghrelin and 53% lower corticosterone levels compared with mice fed the timed low‐fat diet. Taken together, our findings suggest that timing can prevent obesity and rectify the harmful effects of a HF diet. —Sherman, H. , Genzer, Y. , Cohen, R. , Chapnik, N. , Madar, Z. , Froy, O. Timed high‐fat diet resets circadian metabolism and prevents obesity. FASEB J. 26, 3493–3502 (2012). www.fasebj. org
Core area and centre of activity of maned wolves, Chrysocyon brachyurus (Illiger) (Mammalia, Canidae), submitted to supplemental feeding

Based on the finding of remains (tracks, scats, and hairs), an analysis was made of the core area and centre of activity of maned wolves, Chrysocyon brachyurus (Illiger, 1815), living in a private natural reserve in which ecotourism activities are developed and these animals are daily fed bovine meat. A total of 465 samples of remains were recorded. Using the fixed kernel method, the area encompassing all samples recorded was estimated at 25.7 km2, yet 50% of all samples were found in an area of only 1.5 km2, representing 5.8% of the total area covered. For estimating the core area of the animals, the frequency of occurrence of the samples was determined by superimposing a 50 x 50 m cell grid over a map of the area encompassing all recorded occurrences. Based on the cells containing more than six occurrences, the animals' core area was 0.99 km2, which included the place where the animals are fed. The centre of activity was located only 0.50 km from this place. The high negative correlation (r = -0.93, p < 0.05) between the densities of the recorded occurrences and the distances from these to the sanctuary indicates that the core area and centre of activity are conditioned by artificial feeding.
The KIT and PDGFRA switch-control inhibitor DCC-2618 blocks growth and survival of multiple neoplastic cell types in advanced mastocytosis

Systemic mastocytosis is a complex disease defined by abnormal growth and accumulation of neoplastic mast cells in various organs. Most patients exhibit a D816V-mutated variant of KIT, which confers resistance against imatinib. Clinical problems in systemic mastocytosis arise from mediator-related symptoms and/or organ destruction caused by malignant expansion of neoplastic mast cells and/or other myeloid cells in various organ systems. DCC-2618 is a spectrum-selective pan KIT and PDGFRA inhibitor which blocks KIT D816V and multiple other kinase targets relevant to systemic mastocytosis. We found that DCC-2618 inhibits the proliferation and survival of various human mast cell lines (HMC-1, ROSA, MCPV-1) as well as primary neoplastic mast cells obtained from patients with advanced systemic mastocytosis (IC50 <1 μM). Moreover, DCC-2618 decreased growth and survival of primary neoplastic eosinophils obtained from patients with systemic mastocytosis or eosinophilic leukemia, leukemic monocytes obtained from patients with chronic myelomonocytic leukemia with or without concomitant systemic mastocytosis, and blast cells obtained from patients with acute myeloid leukemia. Furthermore, DCC-2618 was found to suppress the proliferation of endothelial cells, suggesting additional drug effects on systemic mastocytosis-related angiogenesis. Finally, DCC-2618 was found to downregulate IgE-mediated histamine release from basophils and tryptase release from mast cells. Together, DCC-2618 inhibits growth, survival and activation of multiple cell types relevant to advanced systemic mastocytosis. Whether DCC-2618 is effective in vivo in patients with advanced systemic mastocytosis is currently under investigation in clinical trials.
Comparing the effects of atrazine and an environmentally relevant mixture on estrogen‐responsive gene expression in the northern leopard frog and the fathead minnow

In Nebraska, fish are exposed to herbicides in agricultural runoff. The study objectives were to determine 1) if fathead minnows and northern leopard frogs exposed to atrazine experience alterations in gene expression, and 2) whether these changes are elicited by a simulated herbicide mixture. Following a 7‐d exposure to atrazine, female minnows were defeminized, whereas male frogs were feminized. The mixture did not elicit statistically significant effects in either species. Environ Toxicol Chem 2018;37:1182–1188. © 2018 SETAC
The challenges of achieving postprandial glucose control using closed‐loop systems in patients with type 1 diabetes

For patients with type 1 diabetes, closed‐loop delivery systems (CLS) combining an insulin pump, a glucose sensor and a dosing algorithm allowing a dynamic hormonal infusion have been shown to improve glucose control when compared with conventional therapy. Yet, reducing glucose excursion and simplification of prandial insulin doses remain a challenge. The objective of this literature review is to examine current meal‐time strategies in the context of automated delivery systems in adults and children with type 1 diabetes. Current challenges and considerations for post‐meal glucose control will also be discussed. Despite promising results with meal detection, the fully automated CLS has yet failed to provide comparable glucose control to CLS with carbohydrate‐matched bolus in the post‐meal period. The latter strategy has been efficient in controlling post‐meal glucose using different algorithms and in various settings, but at the cost of a meal carbohydrate counting burden for patients. Further improvements in meal detection algorithms or simplified meal‐priming boluses may represent interesting avenues. The greatest challenges remain in regards to the pharmacokinetic and dynamic profiles of available rapid insulins as well as sensor accuracy and lag‐time. New and upcoming faster acting insulins could provide important benefits. Multi‐hormone CLS (eg, dual‐hormone combining insulin with glucagon or pramlintide) and adjunctive therapy (eg, GLP‐1 and SGLT2 inhibitors) also represent promising options. Meal glucose control with the artificial pancreas remains an important challenge for which the optimal strategy is still to be determined.
Big Data Classification using Fuzzy K-Nearest Neighbor

becomes troublesome to perform effective analysis using the current traditional techniques. Big data put forward a lot of challenges due to its several characteristics like volume, velocity, variety, variability, value and complexity. Today there is not only a necessity for efficient data mining techniques to process large volume of data but in addition a need for a means to meet the computational requirements to process such huge volume of data. The objective of this paper is to classify big data using Fuzzy K-Nearest Neighbor classifier, and to provide a comparative study between the results of the proposed systems and the method reviewed in the literature. In this paper we implemented the Fuzzy KNearest Neighbor method using the MapReduce paradigm to process on big data. Results on different data sets show that the proposed Fuzzy K-Nearest Neighbor method outperforms a better performance than the method reviewed in the literature.
Identification of katG Mutations Associated with High-Level Isoniazid Resistance in Mycobacterium tuberculosis

ABSTRACT Isoniazid (INH) is an effective first-line antituberculosis drug. KatG, a catalase-peroxidase, converts INH to an active form in Mycobacterium tuberculosis, and katG mutations are major causes of INH resistance. In the present study, we sequenced katG of 108 INH-resistant M. tuberculosis clinical isolates. Consequently, 9 novel KatG mutants with a single-amino-acid substitution were found. All of these mutants had significantly lower INH oxidase activities than the wild type, and each mutant showed various levels of activity. Isolates having mutations with relatively low activities showed high-level INH resistance. On the basis of our results and known mutations associated with INH resistance, we developed a new hybridization-based line probe assay for rapid detection of INH-resistant M. tuberculosis isolates.
Single-shot high dynamic range imaging via deep convolutional neural network

We propose a single-shot high dynamic range (HDR) imaging algorithm with row-wise varying exposures in a single image using a deep convolutional neural network (CNN). We first convert an input raw Bayer image into irradiance values by calibrating rows with different exposures. Then, we develop a new CNN model to restore missing information resulting from under- or over-exposed pixels and reconstruct the raw radiance map. Finally, we obtain the HDR image by applying a demosaicing algorithm to the raw radiance map. Experimental results on simulated images demonstrate that the proposed algorithm provides higher quality HDR images, with more details and less artifacts, than conventional algorithms.
The Conceptualization and Measurement of Perceived Wellness: Integrating Balance across and within Dimensions

Purpose. The impact of individual perceptions on health is well-established. However, no valid and reliable measure of individual wellness perceptions exists. Therefore, the purpose was to introduce a measure called the Perceived Wellness Survey (PWS). Design. Convenience sampling facilitated recruitment of a sample large enough to perform factor analysis with adequate power (.85). The appropriateness of factor analysis is supported by Bartlett's test (χ2 = 7110, p ≤ .01) and the Kaiser-Meyer-Olkin measure of sampling adequacy (.91). Setting. The sample (n = 558) was composed of 3M Inc. employees from multiple sites in Austin, Texas (n = 393); employees from MuRata Electronics, Inc., College Station, Pennsylvania (n = 53); and students enrolled at the University of Texas at Austin (n = 112). Subjects. Racial, gender, and age distribution was, respectively, 6.3% African-American (n = 35), 8.2% Asian (n = 46), 73.3% Caucasian (n = 409), 9.5% Hispanic (n = 53), and 2.7% other (n = 15); 47.8% male (n = 267), and 52.2% female (n = 291); and 36.8 years. Measures. Measures included the Perceived Wellness Survey, and two additional versions of the Perceived Wellness Survey designed to measure both discriminant and face validity. Perceived Wellness Survey subscales include physical, spiritual, intellectual, psychological, social, and emotional dimensions. Results. All subscales were correlated (p ≤ .05) with the Perceived Wellness Survey composite and with each other. Evidence of internal consistency (α = .88 to .93), and discriminant, face, and factorial validity was provided. Finally, the Perceived Wellness Survey appears to be a unidimensional scale. Conclusion. The unidimensional nature of the Perceived Wellness Survey suggests that perceptions of wellness in various dimensions are intertwined by their affective nature. The Perceived Wellness Survey appears to be reasonably valid and reliable; however, further research is needed.
Mixed Precision Training

Deep neural networks have enabled progress in a wide variety of applications. Growing the size of the neural network typically results in improved accuracy. As model sizes grow, the memory and compute requirements for training these models also increases. We introduce a technique to train deep neural networks using half precision floating point numbers. In our technique, weights, activations and gradients are stored in IEEE half-precision format. Half-precision floating numbers have limited numerical range compared to single-precision numbers. We propose two techniques to handle this loss of information. Firstly, we recommend maintaining a single-precision copy of the weights that accumulates the gradients after each optimizer step. This single-precision copy is rounded to half-precision format during training. Secondly, we propose scaling the loss appropriately to handle the loss of information with half-precision gradients. We demonstrate that this approach works for a wide variety of models including convolution neural networks, recurrent neural networks and generative adversarial networks. This technique works for large scale models with more than 100 million parameters trained on large datasets. Using this approach, we can reduce the memory consumption of deep learning models by nearly 2x. In future processors, we can also expect a significant computation speedup using half-precision hardware units.
Heme Oxygenase 1 Polymorphisms and Plasma Concentrations in Critically Ill Patients

Heme oxygenase 1 (HO-1) is a cytoprotective enzyme upregulated by various critical illness-related stress stimuli. We investigated the association of HO-1 gene polymorphisms and plasma concentrations with the outcome of critically ill patients in a prospective cohort study of 231 critically ill patients admitted to tertiary care medical and medical-surgical intensive care units. Blood samples were collected on days 1, 2, and 3 to 4 in the intensive care unit. The HO-1 plasma concentration was measured in serial samples, and HO-1 single nucleotide polymorphisms, −413A/T and +99G/C, and HO-1 promoter GTn repeat length polymorphism were determined. The +99C and long GTn alleles were in perfect linkage disequilibrium, and the −413T/GT(L)/+99C haplotype had significant independent effect on first-day HO-1 plasma concentrations in linear regression analysis (P = 0.03) and associated with lower HO-1 plasma levels. Furthermore, −413T/GT(L)/+99C haplotype associated with a lower frequency of multiple-organ dysfunction compared with other haplotypes (P = 0.017). The HO-1 plasma concentrations of study patients were significantly higher than the values of healthy controls at all time points (P < 0.001), and the first-day plasma HO-1 levels were independently associated with the Sequential Organ Failure Assessment score (P = 0.001). In conclusion, the HO-1 −413T/GT(L)/+99C haplotype is associated with HO-1 plasma levels and the frequency of multiple-organ dysfunction in critically ill patients. The HO-1 plasma concentrations are significantly increased among critically ill patients and associated with the degree of organ dysfunction.
Graduated compression stockings for runners: friend, foe, or fake?

OBJECTIVE To assess the effect of graduated compression stockings (GCS) on lower leg volume and leg complaints in runners during and after exercise. DESIGN Cross-sectional study. SETTING Radboud University Nijmegen Medical Centre and an outdoor running track in Nijmegen, The Netherlands. PATIENTS OR OTHER PARTICIPANTS Thirteen Dutch trained recreational runners. INTERVENTION(S) Participants used a GCS on 1 leg during running. MAIN OUTCOME MEASURES (1) Lower leg volume of both legs was measured at baseline, directly after running, and at 5 minutes and 30 minutes after running using a validated perometer. (2) Leg complaints were reported on questionnaires at set intervals. RESULTS (1) In both experiments, the legs with GCS showed a reduction in mean (± SEM) leg volume directly after running, as compared with the leg without GCS: -14.1 ± 7.6 mL (P = .04) for the 10-km running track and -53.5 ± 17.8 mL (P = .03) for the maximum exercise test. This effect was not observed at 5 and 30 minutes after running. (2) No differences in leg complaints were reported in either experiment. CONCLUSIONS The GCS prevented an increase in leg volume just after the running exercise. However, this result was not accompanied by a reduction in subjective questionnaire-reported leg complaints. The practical consequences of the present findings need further study.