Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrated Informatics Analysis of Cancer-Related Variants

PURPOSE The modern researcher is confronted with hundreds of published methods to interpret genetic variants. There are databases of genes and variants, phenotype-genotype relationships, algorithms that score and rank genes, and in silico variant effect prediction tools. Because variant prioritization is a multifactorial problem, a welcome development in the field has been the emergence of decision support frameworks, which make it easier to integrate multiple resources in an interactive environment. Current decision support frameworks are typically limited by closed proprietary architectures, access to a restricted set of tools, lack of customizability, Web dependencies that expose protected data, or limited scalability. METHODS We present the Open Custom Ranked Analysis of Variants Toolkit1 (OpenCRAVAT) a new open-source, scalable decision support system for variant and gene prioritization. We have designed the resource catalog to be open and modular to maximize community and developer involvement, and as a result, the catalog is being actively developed and growing every month. Resources made available via the store are well suited for analysis of cancer, as well as Mendelian and complex diseases. RESULTS OpenCRAVAT offers both command-line utility and dynamic graphical user interface, allowing users to install with a single command, easily download tools from an extensive resource catalog, create customized pipelines, and explore results in a richly detailed viewing environment. We present several case studies to illustrate the design of custom workflows to prioritize genes and variants. CONCLUSION OpenCRAVAT is distinguished from similar tools by its capabilities to access and integrate an unprecedented amount of diverse data resources and computational prediction methods, which span germline, somatic, common, rare, coding, and noncoding variants.
NOD1 and NOD2 Activation by Diverse Stimuli: a Possible Role for Sensing Pathogen-Induced Endoplasmic Reticulum Stress

Prompt recognition of microbes by cells is critical to eliminate invading pathogens. Some cell-associated pattern recognition receptors (PRRs) recognize and respond to microbial ligands. However, others can respond to cellular perturbations, such as damage-associated molecular patterns (DAMPs). Nucleotide oligomerization domains 1 and 2 (NOD1/2) are PRRs that recognize and respond to multiple stimuli of microbial and cellular origin, such as bacterial peptidoglycan, viral infections, parasitic infections, activated Rho GTPases, and endoplasmic reticulum (ER) stress. ABSTRACT Prompt recognition of microbes by cells is critical to eliminate invading pathogens. Some cell-associated pattern recognition receptors (PRRs) recognize and respond to microbial ligands. However, others can respond to cellular perturbations, such as damage-associated molecular patterns (DAMPs). Nucleotide oligomerization domains 1 and 2 (NOD1/2) are PRRs that recognize and respond to multiple stimuli of microbial and cellular origin, such as bacterial peptidoglycan, viral infections, parasitic infections, activated Rho GTPases, and endoplasmic reticulum (ER) stress. How NOD1/2 are stimulated by such diverse stimuli is not fully understood but may partly rely on cellular changes during infection that result in ER stress. NOD1/2 are ER stress sensors that facilitate proinflammatory responses for pathogen clearance; thus, NOD1/2 may help mount broad antimicrobial responses through detection of ER stress, which is often induced during a variety of infections. Some pathogens may subvert this response to promote infection through manipulation of NOD1/2 responses to ER stress that lead to apoptosis. Here, we review NOD1/2 stimuli and cellular responses. Furthermore, we discuss pathogen-induced ER stress and how it might potentiate NOD1/2 signaling.
School-Based Multicomponent Intervention to Promote Physical Activity and Reduce Sedentary Time of Disadvantaged Children Aged 6-10 Years: Protocol for a Randomized Controlled Trial

Background In our modern society, physical activity (PA) is decreasing and sedentary time (ST) is increasing, especially for children from disadvantaged neighborhoods. School-based interventions to promote PA and decrease ST are therefore required among this population in order to change children’s lifestyle habits. Moreover, attentional capacities and academic achievement can be enhanced by chronic PA during childhood. The relationships between these variables have been poorly studied with this population. Objective The objective of this study is to present the rationale and methods for a randomized controlled trial among 6-10-year-old children with low socioeconomic status that will (1) evaluate the effectiveness of a school-based intervention designed to promote PA and reduce ST and (2) study the relationships between PA, ST, motor skills, attentional capacities, and academic achievement. Methods A randomized controlled trial was conducted in 2 eligible primary schools. During academic year 2016-2017, 1 school was randomly assigned as the experiment one and the other was assigned as the control one. Five assessments times were used: baseline (T1 [November 2016] to T2 [June 2017]), follow-up (T3 [November 2017] to T4 [June 2018]), and final assessment (T5 [June 2019]). The school-based intervention included various components on different levels of the socioecological model: (1) curriculum-based program for children; (2) sensitization workshops and newsletters for parents; (3) training workshops for teachers; (4) environmental adaptation of playgrounds and reorganization of recess time; (5) time adaptation of lunch breaks; and (6) collaboration with political groups. PA, ST, motor skills, and attentional capacities were evaluated and academic achievement was recorded. Results The presented intervention and its different assessments have been successfully implemented. In order to achieve the 2 objectives of this randomized controlled trial, data analyses are about to be completed. Conclusions The implementation of this randomized controlled trial can help to determine effective strategies to promote PA in the context of increasing prevalence of physical inactivity among children with sedentary lifestyle which will be useful for researchers, stakeholders, and public policy makers. Trial Registration ClinicalTrials.gov NCT03983447; https://clinicaltrials.gov/ct2/show/NCT03983447 International Registered Report Identifier (IRRID) RR1-10.2196/17815
Antiestrogenic Activity and Possible Mode of Action of Certain New Nonsteroidal Coumarin-4-acetamides

The preparation of certain 2-(2-oxo-2H-chromen-4-yl)-N-substituted acetamides IIIa–h was planned as a step in the development of new modified nonsteroidal antiestrogens. The purity of target compounds IIIa–h was checked by thin-layer chromatography (TLC), and their structures were confirmed using various spectroscopic tools including IR, 1H-NMR, 13C-NMR, and MS spectroscopy. Viability tests were applied using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cytotoxic effect of the synthesized compounds against two breast cancer cell lines, MCF-7 and MDA-MB-231. Compound IIIb proved the most active against MCF-7 cells, with an IC50 value of 0.32 μM. The results of an analysis of in vitro antiestrogenic activity indicated that only compound IIIb exhibited antiestrogenic activity; its IC50 value of 29.49 μM was about twice as potent as that of the reference compound, MIBP. The aromatase activity was evaluated for the synthesized target compounds IIIa–g and the intermediates Ib and IIa. A significant aromatase inhibition was observed for the intermediate Ib and compound IIIe, with IC50 values of 14.5 and 17.4 μM, respectively. Compound IIIb, namely 7-methoxy-4-(2-oxo-2-(piperidin-1-yl)ethyl)-2H-chromen-2-one, could be used as an antiestrogen and/or cytotoxic agent with selective activity against tumor cells.
In-Vitro and In-Vivo Evaluation of Velpatasvir- Loaded Mesoporous Silica Scaffolds. A Prospective Carrier for Drug Bioavailability Enhancement

The limited aqueous solubility of many active pharmaceutical ingredients (APIs) is responsible for their poor performance and low drug levels in blood and at target sites. Various approaches have been adopted to tackle this issue. Most recently, mesoporous silica nanoparticles (MSN) have gained attention of pharmaceutical scientists for bio-imaging, bio-sensing, gene delivery, drug solubility enhancement, and controlled and targeted drug release. Here, we have successfully incorporated the poorly water soluble antiviral drug velpatasvir (VLP) in MSN. These spherical particles were 186 nm in diameter with polydispersity index of 0.244. Blank MSN have specific surface area and pore diameter of 602.5 ± 0.7 m2/g and 5.9 nm, respectively, which reduced after successful incorporation of drug. Drug was in amorphous form in synthesized VLP-loaded silica particles (VLP-MSN) with no significant interaction with carrier. Pure VLP showed poor dissolution with progressive increment in pH of dissolution media which could limit its availability in systemic circulation after oral administration. After VLP loading in silica carriers, drug released rapidly over a wide range of pH values, i.e., 1.2 to 6.8, thus indicating an improvement in the solubility profile of VLP. These particles were biocompatible, with an LD50 of 448 µg/mL, and in-vivo pharmacokinetic results demonstrated that VLP-MSN significantly enhanced the bioavailability as compared to pure drug. The above results clearly demonstrate satisfactory in-vitro performance, biocompatibility, non-toxicity and in-vivo bioavailability enhancement with VLP-MSN.
Effect of chamomile oil on cesarean section pain in primiparous women: a randomized clinical trial.

BACKGROUND Pain after cesarean section can turn the pleasant event of childbirth into an unpleasant experience for the mother. Pain relief through non-pharmaceutical methods, such as aromatherapy, could potentially be a useful intervention. In this study, the analgesic effect of chamomile oil was studied. PURPOSE The current research was conducted to study the effect of chamomile oil on cesarean section pain in primiparous women. MATERIALS AND METHODS This was a randomized double blind clinical trial wherein 128 primiparous pregnant women (who willingly selected cesarean section) took part. In the aromatherapy group, the subjects inhaled one drop of 5% chamomile oil, and in the control group the subjects inhaled one placebo drop. In both groups the subjects inhaled for 15-20 minutes at a distance of 5 cm from the nose at 4, 8, and 12 hours after surgery, and pain intensity was measured before and after half an hour after inhalation using the visual analog scale (VAS). For data analysis, the software SPSS (version 25) and descriptive statistics (frequency, frequency percentage, mean, and standard deviation) were used. In order to determine the significance, inferential statistics (Mann-Whitney, Wilcoxon, independent t-test, and Chi-square) were used. FINDINGS Data indicated that the intervention and placebo groups were homogeneous in terms of demographic variables. The average weights and heights of women in the intervention group were 86/5± 5/9 and 163/7 ±5/1, respectively. Corresponding values women in the control group were 84/5± 5/7 kg and 163/4± 5/8 cm. The finding of the current research indicates that the intervention and placebo groups showed no significant statistical difference in terms of baseline pain before intervention (p=0.08), while the difference between the two groups was significant in terms of pain 4, 8, and 12 hours after intervention (p<0.01). Therefore, inhalation of chamomile oil reduced pain intensity significantly compared to post-intervention. CONCLUSION According to the results of the present study, inhalation of chamomile oil following caesarean section in primiparous women reduced pain and also the need for analgesics. Therefore, the use of aromatherapy with chamomile oil as a simple way without any side effects for the reduction of pain in mothers after cesarean section is recommended.
Ischaemic skin lesions with multi-organ failure due to cocaine intake

The prevalence of cocaine abuse in Europe was reported to be 1.1% in 2018 and is rising annually. In the United States, there are concerns about the serious adverse effects due to levamisole, a cutting agent, in cocaine users, such as skin necrosis, and dermatologists should be aware of their existence. We report the case of a patient with acute toxicity due to cocaine, cut with levamisole, who presented with skin necrosis and fulminant hepatic and renal failure. A 33-year-old man without any medical history or treatments was admitted to the emergency unit due to unconsciousness. Glasgow coma scale was 14 with drowsiness. He did not have a fever and blood pressure was normal. He had painless retiform purpura with central necrosis and blistering on the anterior faces of the thighs and on the left shoulder (figure 1A, B). Two days before, he had snorted cocaine, smoked cannabis and drunk alcohol bought in France during a festival. He did not inject himself with any of the products and was not a user of injected drugs. Serological tests for HIV and hepatitis viruses A, B, C and E were negative. C-reactive protein level, protein electrophoresis, blood cell count, and platelets were normal. He had an acute kidney injury (creatinine: 180 mol/L, urea: 5 mmol/L), rhabdomyolysis (CPK: 2,255 U/L), severe hepatic cytolysis (ASAT: 3,400 U/L, ALAT: 2,877 U/L) and hepatocellular dysfunction (prothrombin level: 64%, factor V level: 28%) without cholestasis. Investigation for toxins in the blood and urine was positive for levamisole, cocaine and its metabolites, and tetrahydrocannabinol. Cryoglobulinaemia, lupus anticoagulant, and anti-cardiolipid, anti-Beta2GP1, anti-neutrophil cytoplasmic, and anti-nuclear antibodies (ANAs) were absent. Skin biopsy showed fibrinoid necrosis of the small vessel walls and intra-capillary thrombosis, but no vasculitis (figure 1C). In the hours after admission, he had renal tubular necrosis with rhabdomyosis and fulminant hepatic failure (prothrombin level: 33%, factor V level: 15%, and creatinine: 424 mol/L). Hepatic and renal ultrasound were normal. Hepatic function normalized within five days after volume expansion and N-acetylcysteine administration. Creatinine returned to normal within three weeks. In contrast, skin necrosis worsened in spite of daily antiseptic care with silver sulfadiazine ointments. Three surgical excisions with one-week intervals, followed by skin grafts, achieved complete skin recovery within six weeks. This observation illustrates the acute toxicity of cocaine cut with levamisole. Few cases have been reported in France [1, 2] among users of cocaine. The cocaine metabolites are toxic for hepatocytes [3] and can induce renal failA B
Spatio-temporal Index Based on Time Series of Leaf Area Index for Identifying Heavy Metal Stress in Rice under Complex Stressors

Crops under various types of stresses, such as stress caused by heavy metals, drought and pest/disease exhibit similar changes in physiological-biochemical parameters (e.g., leaf area index [LAI] and chlorophyll). Thus, differentiating between heavy metal stress and nonheavy metal stress presents a great challenge. However, different stressors in crops do cause variations in spatiotemporal characteristics. This study aims to develop a spatiotemporal index based on LAI time series to identify heavy metal stress under complex stressors on a regional scale. The experimental area is located in Zhuzhou City, Hunan Province. The situ measured data and Sentinel-2A images from 2017 and 2018 were collected. First, a series of LAI in rice growth stages was simulated based on the WOrld FOod STudies (WOFOST) model incorporated with Sentinel 2 images. Second, the local Moran’s I and dynamic time warping (DTW) of LAI were calculated. Third, a stress index based on spatial and temporal features (SIST) was established to assess heavy metal stress levels according to the spatial autocorrelation and temporal dissimilarity of LAI. Results revealed the following: (1) The DTW of LAI is a good indicator for distinguishing stress levels. Specifically, rice subjected to high stress levels exhibits high DTW values. (2) Rice under heavy metal stress is well correlated with high-high SIST clusters. (3) Rice plants subjected to high pollution are observed in the northwest of the study regions and rice under low heavy metal stress is found in the south. The results suggest that SIST based on a sensitive indicator of rice biochemical impairment can be used to accurately detect regional heavy metal stress in rice. Combining spatial-temporal features and spectral information appears to be a highly promising method for discriminating heavy metal stress from complex stressors.
Data Mining Implementation Using Naïve Bayes Method for Prediction of Customers in Customer's Credit Payment in CS Finance

: Credit collectibility is a way to find out the quality of credit so that Central Santosa Finance can anticipate credit risk early because credit risk can affect the continuity of business enterprises. The quality is based on 3 main standards, one of which is the ability of customers to pay the principal and interest at the time agreed upon together. Whereas, to accurately predict the ability of prospective customers to repay loans based on the characteristics of manually owned data sets is very difficult. Data Mining with the Naïve Bayes method was chosen to find patterns in analyzing and predicting the ability to repay prospective borrowers. The test will be carried out by comparing the initial dataset and dataset characteristics using the attribute selector Gain Ratio Attribute algorithm with the help of WEKA tools. The results showed that there was a difference in the results of accuracy, and that the ROC or AUC (Area Under Cover) curve was greater in the dataset characteristics using the selector attribute by using the Gain Ratio attribute, although not too significant. And the results of this study produced an accuracy rate of 78.56% with a precision of 93.46% and a recall of 72.78%. The method used is included in Good Classification and will later become a reference for the management of Central Santosa Finance, to address the problems that may arise in decreasing the quality of credit (eg decreasing the company's ratio with customers).
Characterization of Emotional Speech for Gender Classification

Researchers have argued that, recognition systems trained with gender specific speech signals outperform than corresponding systems not taking gender information into account. In this context, detection of speech signals colored with emotion remains a challenge as the emotional contents in speech signal is little understood. Recognition of gender information in speech signal is crucial in speaker annotation, speaker diarization, speaker clustering, social robots, interactive TV programming, multi-media retrieval, bio-metrics and host of other such application. One such attempt is taken here to characterize and classify speech emotions based on gender specific information using frequency informative features. Fundamental frequency, formants, magnitude and amplitude of spectrum are extracted from angry, fear and happy speech emotions for characterizing the emotions to distinguish different gender. The information is used as features for classification of speech emotions using K-means classifier. The results are promising and have provided an improved accuracy above 5% for gender specific emotion recognition as compared to corresponding gender independent speech emotion recognition.
Offering Secure Information in the Cloud for the Dynamic Group

-Cloud computing is a developing processing ideal model in which assets of the registering framework are given as administrations over the Web. Offering gathering asset among cloud clients is a real issue, so Cloud computing gives an efficient and effective compact. Mona, secure information imparting in a multi-manager way for element gatherings preserve information, identity protection from an untrusted cloud and permits successive change of the participation. In this paper, we propose a confined multi manager information offering scheme, for element amasses in the cloud. By leveraging group signature and dynamic show encryption systems, any cloud client can secretly impart information to others. Proposing another model for offering Secure Information in the Cloud for the dynamic group.
Macroeconomic problems and approach of the parametric control theory

The paper presents the results of the approach to the solution of some macroeconomic problems of the regions (economic growth, reduction of regional disproportions, reduction of trade deficits and growth of the agricultural, forestry and fishery sector outputs) based on the developed Model and the approach of the parametric control theory. The developed Model is a global multi-country dynamic computable general equilibrium model (CGE model) which was built based on the known static CGE model Globe 1. The assessment of the fulfillment of the conditions for transferring the results of computational experiments based on the Model was carried out both by the approach of the parametric control theory and by other known methods. The problems of dynamic optimization that allow solving these macroeconomic problems at the level of individual countries, the economic union and the world economy were solved based on the Model, with methods of the parametric control theory. The greater benefit from joint concerted actions to solve the problems under consideration in comparison with the corresponding solutions of such problems at the level of individual regions (countries) is corroborated. Keywords— Macroeconomic problem, Parametric control theory, CGE Model, testing of the Model
How Special Are They?

Specialty hospitals, owned and operated by physicians with an expertise in a particular medical condition, offer the opportunity to design a utopian care environment for optimal delivery of care. In fact, the concept of specialty heart hospitals dates back to the mid-19th century in England, with the opening in 1857 of London’s National Hospital for Diseases of the Heart and Paralysis. The institution of specialty hospitals in the United States underwent acceleration by the mid-1990’s.1 Many confluent factors explain the development of specialty cardiac hospitals in the United States, including significant advances in cardiovascular technology, dramatic increases in the cost (and profitability) of cardiovascular care, and, most important, the perceived financial constraints on both hospitals and practicing physicians from health plans and payers, which results in a perception of reduced practice autonomy by physicians and hospitals.2,3 Presently, 100 specialty hospitals exist in the United States, with many focusing on cardiac care. Although specialty hospitals have the potential to improve care by focusing considerable clinical expertise and resources for the care of a limited spectrum of disease, empirical evidence that demonstrates improved outcomes is minimal or potentially biased because of challenges of adequate risk adjustment for the somewhat debated presence of lower-risk patients treated by specialty hospitals compared with their general hospital counterparts.4–6