Miracle-dz/UniFAR-FTUs huggingface dataset:
Off-label drug prescriptions in French general practice: a cross-sectional study

Objectives Off-label drug prescribing is a public health and economic issue. The aim of this study was to describe off-label prescription in general practice in France, in terms of frequency and nature, and to identify its main determining factors. Design Multicentre cross-sectional study Setting Twenty-three training general practice offices Participants All the voluntary patients coming for a medical consultation or visited at home over a cumulative period of 5 days per office between November 2015 and January 2016. Methods Eleven interns, acting as observers, collected data. Two reviewers analysed the drugs prescribed by the trainers, in order to identify those prescribed off-label in terms of their indication or the age of the patient. We used a univariate, then a multivariate model, based on hierarchical mixed-effects logistic regression. Results Among the 4932 drug prescriptions registered, 911 (18.5%[95% CI17.4% to 19.6%]) were off-label, of which 865 (17.6%) due to the indication of the drug and 58 (1.2%) due to the age of the patient. The prescription never mentioned the off-label use, neither was the patient informed of it, as required by the French law. With the multivariate analysis, variables contributing to off-label prescription were the number of drugs (OR=1.05 for each additional drug), the initiation of new drug therapy (OR=1.26) and the non-specific goal of the prescription (OR=1.43); the age of the patient ≤14 years (OR=1.42); the rural location of the physician’s practice (OR=1.38) and the low frequency of the visits of national health insurance representatives (OR=0.93). Conclusion Almost one out of five drugs prescribed in French general practice was off-label. It seems necessary to better train physicians in clinical pharmacology, to provide them with more effective drug prescription software, to reinforce postmarketing surveillance and to clearly define off-label use by consensus.
Repeatability of regional pulmonary functional metrics of Hyperpolarized 129Xe dissolved‐phase MRI

MRI of hyperpolarized 129Xenon (HP 129Xe) is increasingly utilized for investigating pulmonary function. The solubility of HP 129Xe in lung tissue, blood plasma (Barrier), and red blood cells (RBC), with unique chemical shifts, enables spectroscopic imaging of potential imaging biomarkers of gas exchange and microstructural pulmonary physiology.
Less Binge Eating and Loss of Control over Eating Are Associated with Greater Levels of Mindfulness: Identifying Patterns in Postmenopausal Women with Obesity

Obesity is a public health concern resulting in widespread personal, social, and economic burden. Many individuals with obesity report feeling unable to stop eating or to control their food intake (i.e., a loss of control over eating) despite their best efforts. Experiencing loss of control over eating predicts further eating pathology and is a key feature of binge eating. Mindfulness (i.e., awareness and acceptance of current thoughts, feelings, sensations, and surrounding events) has emerged as a potential strategy to treat such eating disorder behaviors, but it is not known whether there is merit in investigating this strategy to address binge eating in postmenopausal women with obesity. Thus, this study aimed to examine the relationships between binge eating and mindfulness in postmenopausal women with obesity seeking weight loss treatment. Participants (n = 101) were assessed with the Eating Disorder Examination Questionnaire, the Loss of Control over Eating Scale, the Five-Facet Mindfulness Questionnaire, and the Langer Mindfulness Scale. Participants´ overall scores on both mindfulness scales were significantly and negatively correlated with binge eating frequency or the severity of loss of control over eating. Moreover, participants who reported fewer binge eating episodes were significantly more mindful than those who reported greater frequencies of binge eating episodes within the past 28 days. These findings suggest a merit in investigating the use of mindfulness-based therapies to treat binge eating in postmenopausal women with obesity.
Rapid screening mutations of first-line-drug-resistant genes in Mycobacterium tuberculosis strains by allele-specific real-time quantitative PCR

Tuberculosis (TB) is a worldwide health, economic, and social burden, especially in developing countries. Drug-resistant TB is the most serious type of this burden. Thus, it is necessary to screen drug-resistant mutations by using a simple and rapid detection method. A total of 32 pairs of allele-specific PCR (AS-PCR) primers were designed to screen mutation and/or wild-type alleles of 16 variations in four first-line drug-resistant genes (katG, rpoB, rpsL, and embB) of TB strains. A pair of primers was designed to amplify 16S rRNA gene and to verify successful amplification. Subsequently, we tested the specificity and sensitivity of these AS-PCR primers. The optimized condition of these AS-PCR primers was first confirmed. All mutations could be screened in general AS-PCR, but only 13 of 16 variations were intuitively investigated by using real-time quantitative PCR (qPCR) and AS-PCR primers. The results of specificity assay suggested that the AS-PCR primers with mutation and/or wildtype alleles could successfully amplify the corresponding allele under optimized PCR conditions. The sensitivity of nine pairs of primers was 500 copy numbers, and the other seven pairs of primers could successfully amplify correct fragments with a template comprising 103 or 104 copy numbers template. An optimized AS-qPCR was established to screen drug-resistant mutations in TB strains with high specificity and sensitivity.
Isolation of Antimicrobial Compounds From Cnestis ferruginea Vahl ex. DC (Connaraceae) Leaves Through Bioassay-Guided Fractionation

Different parts of Cnestis ferruginea are used in traditional African medicine for treating infectious diseases such as dysentery, bronchitis, eye troubles, conjunctivitis, sinusitis, gonorrhea, and syphilis. Despite its long traditional use in the treatment of infections, this plant is not well studied for its in vitro antimicrobial properties. Therefore, the present study aims to establish the antimicrobial activity profile of extracts from this plant, as well as to isolate and evaluate the antimicrobial activity of the most abundant bioactive compound in C. ferruginea leaves through bioassay-guided purification, using Staphylococcus aureus as a target organism. Although both methanol and water extracts of the plant leaves proved active against S. aureus, a water extract was pursued, and subjected further to liquid-liquid partitioning (ethyl acetate, butanol, and water). The ethyl acetate fraction was found to be the most potent and was subjected to silica gel chromatography. In total, 250 fractions were obtained, and those with similar TLC profiles were clustered into 22 major groups, of which pooled fraction-F6 (83 mg) was the most potent. Additional purification by HPLC resulted in two active peaks, which were identified, using a combination of NMR and mass spectrometry, as hydroquinone and caffeic acid methyl ester. Their antimicrobial activity was confirmed using a microdilution protocol on S. aureus, where hydroquinone had a stronger activity (MIC50 = 63 μg/mL) compared to caffeic acid methyl ester (>200 μg/mL). Traditionally this plant is used as an aqueous preparation to treat many infections, and the present study also demonstrated antimicrobial activity in the aqueous extract, which appears due mainly to two major water-soluble compounds isolated through bioassay-guided purification. This supports the clinical use of the aqueous extract of C. ferruginea leaves as a phytotherapeutic for bacterial infections.
Osteolytic Lesions in Primary Myelofibrosis and Effect of Ruxolitinib Therapy: Report of a Case and Literature Review

Here, we report the case of a young female affected by primary myelofibrosis (PMF) who developed an osteolytic lesion of the humerus during the follow-up, and the possible efficacy of ruxolitinib in controlling this rare event. After 26 years of follow-up, the patient reported onset of acute pain at the proximal region of the left upper limb. An X-ray revealed an osteolytic bone lesion in the proximal third of the humeral shaft, which was then confirmed by magnetic resonance imaging. A biopsy of the lytic lesion was done, revealing hypercellular bone marrow with hyperplastic granulopoiesis associated with megakaryocytic proliferation and atypia, accompanied by a diffuse and dense increase in reticulin fibrosis with extensive intersections and coarse bundles of thick fibers, consistent with a grade 3 collagen fibrosis. No new therapeutic intervention was initially required; however, 2 years later, the patient reported symptomatic splenomegaly and drenching night sweats, so ruxolitinib therapy was started. By week 8, the patient had near resolution of constitutional symptoms and a reduction of > 50% of the spleen size that normalized by 6 months; in addition, a repeat bone marrow biopsy showed a decrease in reticulin fibrosis grade. Interestingly, after 9 months of ruxolitinib therapy, further magnetic resonance imaging of the left upper limb showed the absence of bone lytic lesions and a substantial normalization of the bone tissue. In conclusion, with the present case report, we confirm ruxolitinib efficacy in reducing bone marrow fibrosis grade and assume its possible role in the resolution of osteolytic lesions in PMF. Obviously, further studies with a greater number of patients are needed to document the exact frequency of these unusual findings and the possible role of ruxolitinib in their treatment.
Thinking an ethics of gender exploration: Against delaying transition for transgender and gender creative youth

Youth explore their genders – both theirs and those of others. Exploration is not only a vessel of discovery and understanding but also of creation. Centring the notion of gender exploration, this article inquires into the ethical issues surrounding care for transgender youth. Arguing that exploration is best seen not as a precondition to transition-related care but as a process that can operate through transitioning, the article concludes that the gender-affirmative approach to trans youth care best fosters youth’s capacity for healthy exploration. Unbounded social transition and ready access to puberty blockers ought to be treated as the default option, and support should be offered to parents who may have difficulty accepting their youth.
In silico construction of a flexibility-based DNA Brownian ratchet for directional nanoparticle delivery

A Brownian ratchet device based on DNA with periodic flexibility variation is proposed for directional nanoparticle delivery. Brownian particles confined in a system with periodic and asymmetric potential can be transported in a specific direction along the potential by repetitively switching the potential on and off. Here, we propose a DNA-based Brownian ratchet for directional transport of positively charged nanoparticles in which nanoparticle delivery follows the path dictated by a single, long, double-stranded DNA. We performed Brownian dynamics simulations to prove its realization using coarse-grained models. A periodic and asymmetric potential for nanoparticle binding is constructed along a single, long, double-stranded DNA molecule by a novel strategy that uses variation in sequence-dependent DNA flexibility. Directional and processive motion of nanoparticles is achieved by changing salt concentration repetitively over several cycles to switch the asymmetric potential on and off. This work suggests that double-stranded DNA molecules with elaborately designed flexibility variation can be used as a molecule-scale guide for spatial and dynamic control of nanoparticles for future applications.
BRCA1 and EZH2 cooperate in regulation of prostate cancer stem cell phenotype

Prostate cancer (PCa) is the second most common malignancy and the sixth leading cause of cancer‐related death among men worldwide. Prostate carcinogenesis is driven by the accumulation of genetic and epigenetic aberrations, which regulate cancer cell transition between a stem‐ and nonstem‐cell state and accelerate tumor evolution. Elevated expression of enhancer of zeste homolog 2 (EZH2) histone methyltransferase, a core member of the polycomb repressive complex 2 (PRC2), results in cancer progression through histone methylation‐driven tumor cells dedifferentiation. Previous studies demonstrated that tumor suppressor breast cancer 1 (BRCA1) is a negative regulator of PRC2‐dependent H3K27 methylation. Our recent studies revealed that inhibition of EZH2‐mediated histone methylation radiosensitizes prostate cancer stem cells (CSCs) population. However, the link between BRCA1 and EZH2 in regulation of prostate CSCs remains elusive. Present study demonstrated that BRCA1 and EZH2 are coregulated in patients’ tumors and PCa cell lines, and cooperate in regulation of CSC phenotype and properties. Knockdown of BRCA1 expression significantly increases the number and the size of tumor spheres. Inhibition of BRCA1 and EZH2 expression leads to an increase of aldehyde dehydrogenase (ALDH)‐positive cell population that is, at least partially, attributed to the upregulation of ALDH1A3 protein. Treatment with a global histone methylation inhibitor 3‐Deazaneplanocin A abrogates this regulation, downregulates BRCA1 and EZH2 expression and has an inhibitory effect on the tumorigenic properties of radioresistant PCa cells in vivo. We found that EZH2/BRCA1 signaling mechanisms play an important role in the maintenance of prostate CSC properties and may be a promising target for tumor treatment.
Heterogeneous emergency department management of published recommendation defined hypotension in patients with acute traumatic spinal cord injury: A multi‐centre overview

Evidence‐based management for patients with acute traumatic spinal cord injury (TSCI) in the ED has a critical impact on long‐term outcomes. Acute hypotension post‐injury may compromise spinal cord perfusion and extend neurological damage. Published guidelines recommend mean arterial blood pressure (BP) maintenance between 85 and 90 mmHg for 7 days post‐injury; the extent to which this is followed in Australia is unknown.
Wideband and Low Direct-Coupling Tapered Slot Antenna Using Electromagnetic Bandgap Structures

This paper proposes a wideband and low direct-coupling tapered slot antenna (TSA) using electromagnetic bandgap (EBG) structure. We name this antenna the EBG-TSA. In some near field imaging systems including ground penetrating radars, a number of TSAs are arranged into an array with very small spacing in order to realize high-resolution imaging without synthetic aperture processing. Then, the direct coupling among TSA elements is nonnegligible and harmful. In this paper, we show that the EBG structure is effective in reducing the direct coupling with its stopband, which prevents an electromagnetic wave from propagating in a specific frequency band. Our EBG-TSA reduces its direct coupling by 3 dB or more in a wide band. We also find that the tapered EBG structure area assists the radiation by guiding the fin current flow two-dimensionally along the tapered slot so that the boresight gain increases. The EBG structure contributes to both the direct coupling reduction and the boresight gain enhancement.
Multi-Scale Convolutional Neural Networks Aggregation For Hyperspectral Images Classification

Hyperspectral image feature extraction and classification is an important part in remote sensing field, and convolutional neural networks (CNNs) show their advantages in it. However, it is still affected by the lack of training samples, which may lead to the occurrence of overfitting. This issue gets more serious when dealing with high-dimensional data such as HSI. And the single scale of the input data ignores the abundance of multi-scale spatial information. In response to the above problems, we propose a multi-scale convolutional neural network method. And the method can extract multiple scale areas centered on the pixel to be classified. Then it adjusts the areas to the same size and inputs the adjusted data into the standard convolutional neural network for training and testing. Experimental results indicate that proposed method boost the performances in terms of classification accuracies.
An Internal Validity Index Based on Density-Involved Distance

It is crucial to evaluate the quality of clustering results in cluster analysis. Although many cluster validity indices (CVIs) have been proposed in the literature, they have some limitations when dealing with non-spherical datasets. One reason is that the measure of cluster separation does not consider the impact of outliers and neighborhood clusters. In this paper, a new robust distance measure, one into which density is incorporated, is designed to solve the problem, and an internal validity index based on this separation measure is then proposed. This index can cope with both the spherical and non-spherical structure of clusters. The experimental results indicate that the proposed index outperforms some classical CVIs.
Design and Development of High-Gain SIW H-Plane Horn Antenna Loaded With Waveguide, Dipole Array, and Reflector Nails Using Thin Substrate

In this communication, a new probe-fed substrate integrated waveguide (SIW) H-plane horn antenna including three linear dipole arrays is proposed. To feed the dipole arrays, a portion of a rectangular waveguide is placed at the front of the radiating aperture of the SIW horn in conjunction with two slots, which are etched at the top and bottom of the substrate. A row of reflector nails is also added to reduce the backward radiation and to improve the antenna gain. A prototype of the proposed antenna is fabricated using the printed circuit board process. The proposed antenna is numerically investigated by a software package. The simulated and measured results are reported for verification. The measured results show that the proposed antenna provides 13.97 dBi gain at 20.5 GHz with a low backward radiation.
Toward Ultimate Control of Terahertz Wave Absorption in Graphene

It is commonly believed that weak light–matter interactions in low-mobility graphene dramatically limits tunability of graphene-based optoelectronic devices, such as tunable absorbers or switches. In this paper, we use a simple circuit model to understand absorption in graphene sheets. In particular, we show that light interacts weakly also with very high-mobility graphene sheets and propose systematic design means to overcome these problems. The results have allowed us to demonstrate in the terahertz band that perfect absorption with excellent electrical tunability can be achieved within a wide span of mobility values (from 200 to 20000 cm2V−1s−1) which almost covers the whole range of ever reported room-temperature mobilities. Remarkably, concentrating on the most practical low-mobility graphene devices, we exemplify our theory with two cases: frequency-tunable and switchable absorbers with near 100% modulation efficiencies. Our work provides systematic and instructive insights into the design of highly tunable absorbers, without restrictions on graphene mobility. The design strategy and the developed analytical model can, in principle, be generalized to other wavelength regions from microwave to mid-infrared range, and other 2-D materials such as transition metal dichalcogenides and black phosphorus.
Conserved motifs in nuclear genes encoding predicted mitochondrial proteins in Trypanosoma cruzi

Trypanosoma cruzi, the protozoan parasite that causes Chagas’ disease, exhibits peculiar biological features. Among them, the presence of a unique mitochondrion is remarkable. Even though the mitochondrial DNA constitutes up to 25% of total cellular DNA, the structure and functionality of the mitochondrion are dependent on the expression of the nuclear genome. As in other eukaryotes, specific peptide signals have been proposed to drive the mitochondrial localization of a subset of trypanosomatid proteins. However, there are mitochondrial proteins encoded in the nuclear genome that lack of a peptide signal. In other eukaryotes, alternative protein targeting to subcellular organelles via mRNA localization has also been recognized and specific mRNA localization towards the mitochondria has been described. With the aim of seeking for mitochondrial localization signals in T. cruzi, we developed a strategy to build a comprehensive database of nuclear genes encoding predicted mitochondrial proteins (MiNT) in the TriTryps (T. cruzi, T. brucei and L. major). We found that approximately 15% of their nuclear genome encodes mitochondrial products. In T. cruzi the MiNT database reaches 1438 genes and a conserved peptide signal, M(L/F) R (R/S) SS, named TryM-TaPe is found in 60% of these genes, suggesting that the canonical mRNA guidance mechanism is present. In addition, the search for compositional signals in the transcripts of T. cruzi MiNT genes produce a list, being worth to note a conserved non-translated element represented by the consensus sequence DARRVSG. Taking into account its reported interaction with the T. brucei TRRM3 protein which is enriched in the mitochondrial membrane fraction, we here suggest a putative zip code role for this element. Globally, here we provide an inventory of the mitochondrial proteins in T. cruzi and give evidence for the existence of both peptide and mRNA signals specific to nuclear encoded mitochondrial proteins.
Spatially Filtered Multilevel Analysis on Spatial Determinants for Malaria Occurrence in Korea

Since its re-emergence in 1993, the spatial patterns of malaria outbreaks in South Korea have drastically changed. It is well known that complicated interactions between humans, nature, and socio-economic factors lead to a spatial dependency of vivax malaria occurrences. This study investigates the spatial factors determining malaria occurrences in order to understand and control malaria risks in Korea. A multilevel model is applied to simultaneously analyze the variables in different spatial scales, and eigenvector spatial filtering is used to explain the spatial autocorrelation in the malaria occurrence data. The results show that housing costs, average age, rice paddy field ratio, and distance from the demilitarized zone (DMZ) are significant on the level-1 spatial scale; health budget per capita and military base area ratio are significant on the level-2 spatial scale. The results show that the spatially filtered multilevel model provides better analysis results in handling spatial issues.