Miracle-dz/UniFAR-FTUs huggingface dataset:
Antileishmanial Activity of 2-Methoxy-4H-spiro-[naphthalene-1,2′-oxiran]-4-one (Epoxymethoxy-lawsone): A Promising New Drug Candidate for Leishmaniasis Treatment

Epoxymethoxy-lawsone is a naphthoquinone derivative promising as drug candidate for the treatment of leishmaniases. In the present work the effectiveness of epoxymethoxylawsone, and meglumine antimoniate on Leishmania (Leishmania) amazonensis parasites and on mice paw lesions of infected BALB/c mice was assessed. In an intracellular amastigotes assay, the half-maximal inhibitory concentration (IC50) value for epoxymethoxylawsone was slightly higher (1.7-fold) than that found for meglumine antimoniate. The efficacy of both drugs became more evident after 48 h of exposure when either the oxirane compound and reference drug reached 18-fold and 7.4-fold lower IC50 values (0.40 ± 0.001 µM and 0.60 ± 0.02 µM), respectively. Promastigotes were also affected by epoxymethoxylawsone after 24 h of incubation (IC50 = 45.45 ± 5.0 µM), but with IC50 6-fold higher than those found for intracellular amastigotes. Cytotoxicity analysis revealed that epoxymethoxylawsone (CC50 = 40.05 ± µM) has 1.7-fold higher effects than meglumine antimoniate (CC50 = 24.14 ± 2.6 µM). Treatment of the paw lesion in infected BALB/c mice with epoxymethoxy-lawsone led to a significant 27% reduction (p < 0.05) of the lesion size, for all administrated doses, compared to the control group. Lesion reduction was also detected after mice treatment with meglumine antimoniate, reaching 31.0% (0.23 mg of Sb(V)/Kg/day and 2.27 mg of Sb(V)/Kg/day) and 64.0% (22.7 mg of Sb(V)/Kg/day). In addition, mice lesion ultrastructural changes were evidenced in amastigotes. The set of data gathered here indicate that epoxymethoxylawsone has pronounced effects on parasites and merits furthering to the preclinical stage.
Effects of curcumin on performance, antioxidation, intestinal barrier and mitochondrial function in ducks fed corn contaminated with ochratoxin A.

Curcumin has been attributed with antioxidant, anti-inflammatory, antibacterial activities, and has shown highly protective effects against enteropathogenic bacteria and mycotoxins. Ochratoxin A (OTA) is one of the major intestinal pathogenic mycotoxins. The possible effect of curcumin on the alleviation of enterotoxicity induced by OTA is unknown. The effects of dietary curcumin supplementation on OTA-induced oxidative stress, intestinal barrier and mitochondrial dysfunctions were examined in young ducks. A total of 540 mixed-sex 1-day-old White Pekin ducklings with initial BW (43.4±0.1 g) were randomly assigned into controls (fed only the basal diet), a group fed an OTA-contaminated diet (2 mg/kg feed), and a group fed the same OTA-contaminated feed plus 400 mg/kg of curcumin. Each treatment consisted of six replicates, each containing 30 ducklings and treatment lasted for 21 days. There was a significant decrease in average daily gain (ADG) and increased feed : gain caused by OTA (P<0.05); curcumin co-treatment prevented the decrease in BW and ADG compared with the OTA group (P<0.05). Histopathological and ultrastructural examination showed clear signs of enterotoxicity caused by OTA, but these changes were largely prevented by curcumin supplementation. Curcumin decreased the concentrations of interleukin-1β, tumor necrosis factor-α and malondialdehyde, and increased the activity of glutathione peroxidase induced by OTA in the jejunal mucosa of ducks (P<0.05). Additionally, curcumin increased jejunal mucosa occludin and tight junction protein 1 mRNA and protein levels, and decreased those of ρ-associated protein kinase 1 (P<0.05). Notably, curcumin inhibited the increased expression of apoptosis-related genes, and downregulated mitochondrial transcription factors A, B1 and B2 caused by OTA without any effects on RNA polymerase mitochondrial (P<0.05). These results indicated that curcumin could protect ducks from OTA-induced impairment of intestinal barrier function and mitochondrial integrity.
Formation of Earth-like Planets During and After Giant Planet Migration

Close-in giant planets are thought to have formed in the cold outer regions of planetary systems and migrated inward, passing through the orbital parameter space occupied by the terrestrial planets in our own solar system. We present dynamical simulations of the effects of a migrating giant planet on a disk of protoplanetary material and the subsequent evolution of the planetary system. We numerically investigate the dynamics of postmigration planetary systems over 200 million years using models with a single migrating giant planet, one migrating and one nonmigrating giant planet, and excluding the effects of a gas disk. Material that is shepherded in front of the migrating giant planet by moving mean motion resonances accretes into "hot Earths," but survival of these bodies is strongly dependent on dynamical damping. Furthermore, a significant amount of material scattered outward by the giant planet survives in highly excited orbits; the orbits of these scattered bodies are then damped by gas drag and dynamical friction over the remaining accretion time. In all simulations Earth-mass planets accrete on approximately 100 Myr timescales, often with orbits in the habitable zone. These planets range in mass and water content, with both quantities increasing with the presence of a gas disk and decreasing with the presence of an outer giant planet. We use scaling arguments and previous results to derive a simple recipe that constrains which giant planet systems are able to form and harbor Earth-like planets in the habitable zone, demonstrating that roughly one-third of the known planetary systems are potentially habitable.
Vitamin D supply in shift working nurses

ABSTRACT We studied determinants of Vitamin D in serum of 67 female health care workers (aged 25–60 years), including age, body mass index, physical activity, and shift work. Overall, vitamin D levels were low, ranging from 6 to 51 ng/mL (median: 20 ng/mL). Lower serum levels were found in samples drawn in winter and spring and in obese subjects. Shift work had only small effects on vitamin D levels. The high prevalence of vitamin D undersupply is in line with observations from the German general population. Vitamin D supply particularly in winter and spring should be ensured to avoid health problems.
A narrow, edge-on disk resolved around HD 106906 with SPHERE

Context. HD 106906AB is the only young binary system so far around which a planet has been imaged and a debris disk has been shown to exist, thanks to a strong IR excess. As such, it represents a unique opportunity for studying the dynamics of young planetary systems. Aims. We aim at further investigating the close (tens of au scales) environment of the HD 106906AB system. Methods. We used the extreme adaptive-optics-fed, high-contrast imager SPHERE that has recently been installed on the VLT to observe HD 106906. Both the IRDIS imager and the Integral Field Spectrometer were used. Results. We discovered a highly inclined, ring-like disk at a distance of 65 au from the star. The disk shows a strong brightness asymmetry with respect to its semi-major axis. It shows a smooth outer edge, compatible with ejection of small grains by the stellar radiation pressure. We show furthermore that the planet's projected position is significantly above the PA of the disk. Given the determined disk inclination, it is not excluded, however, that the planet could still orbit within the disk plane if at a large separation (2000 3000 au). We identified several additional point sources in the SPHERE /IRDIS field of view that appear to be background objects. We compare this system with other debris disks sharing similarities, and we briefly discuss the present results in the framework of dynamical evolution.
A 250 mV 8 kb 40 nm Ultra-Low Power 9T Supply Feedback SRAM (SF-SRAM)

Low voltage operation of digital circuits continues to be an attractive option for aggressive power reduction. As standard SRAM bitcells are limited to operation in the strong-inversion regimes due to process variations and local mismatch, the development of specially designed SRAMs for low voltage operation has become popular in recent years. In this paper, we present a novel 9T bitcell, implementing a Supply Feedback concept to internally weaken the pull-up current during write cycles and thus enable low-voltage write operations. As opposed to the majority of existing solutions, this is achieved without the need for additional peripheral circuits and techniques. The proposed bitcell is fully functional under global and local variations at voltages from 250 mV to 1.1 V. In addition, the proposed cell presents a low-leakage state reducing power up to 60%, as compared to an identically supplied 8T bitcell. An 8 kbit SF-SRAM array was implemented and fabricated in a low-power 40 nm process, showing full functionality and ultra-low power.
Rheumatoid Arthritis and Lung Disease: From Mechanisms to a Practical Approach

Abstract Rheumatoid arthritis (RA) is a common chronic systemic autoimmune disease characterized by joint inflammation and, in a proportion of patients, extra-articular manifestations (EAM). Lung disease, either as an EAM of the disease, related to the drug therapy for RA, or related to comorbid conditions, is the second commonest cause of mortality. All areas of the lung including the pleura, airways, parenchyma, and vasculature may be involved, with interstitial and pleural disease and infection being the most common problems. High-resolution computed tomography of the chest forms the basis of investigation and when combined with clinical information and measures of physiology, a multidisciplinary team can frequently establish the diagnosis without the need for an invasive biopsy procedure. The most frequent patterns of interstitial lung disease (ILD) are usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP), with some evidence for the prognosis being better than for the idiopathic equivalents. Risk factors depend on the type of disease but for ILD (mainly UIP and NSIP) include smoking, male gender, human leukocyte antigen haplotype, rheumatoid factor, and anticitrullinated protein antibodies (ACPAs). Citrullination of proteins in the lung, frequently thought to be incited by smoking, and the subsequent development of ACPA appear to play an important role in the development of lung and possibly joint disease. The biologic and nonbiological disease modifying antirheumatic drugs (DMARDs) have had a substantial impact on morbidity and mortality from RA, and although there multiple reports of drug-related lung toxicity and possible exacerbation of underlying ILD, overall these reactions are rare and should only preclude the use of DMARDs in a minority of patients. Common scenarios facing pulmonologists and rheumatologists are addressed using the current best evidence; these include screening the new patient; monitoring and choosing RA treatment in the presence of subclinical disease; treating deteriorating ILD; and establishing a diagnosis in a patient with an acute respiratory presentation.
The Role, Involvement and Function(s) of Interleukin-35 and Interleukin-37 in Disease Pathogenesis

The recently identified cytokines—interleukin (IL)-35 and interleukin (IL)-37—have been described for their anti-inflammatory and immune-modulating actions in numerous inflammatory diseases, auto-immune disorders, malignancies, infectious diseases and sepsis. Either cytokine has been reported to be reduced and in some cases elevated and consequently contributed towards disease pathogenesis. In view of the recent advances in utilizing cytokine profiles for the development of biological macromolecules, beneficial in the management of certain intractable immune-mediated disorders, these recently characterized cytokines (IL-35 and IL-37) offer potential as reasonable targets for the discovery of novel immune-modulating anti-inflammatory therapies. A detailed comprehension of their sophisticated regulatory mechanisms and patterns of expression may provide unique opportunities for clinical application as highly selective and target specific therapeutic agents. This review seeks to summarize the recent advancements in discerning the dynamics, mechanisms, immunoregulatory and anti-inflammatory actions of IL-35 and IL-37 as they relate to disease pathogenesis.
Medical hyperspectral imaging: a review

Abstract. Hyperspectral imaging (HSI) is an emerging imaging modality for medical applications, especially in disease diagnosis and image-guided surgery. HSI acquires a three-dimensional dataset called hypercube, with two spatial dimensions and one spectral dimension. Spatially resolved spectral imaging obtained by HSI provides diagnostic information about the tissue physiology, morphology, and composition. This review paper presents an overview of the literature on medical hyperspectral imaging technology and its applications. The aim of the survey is threefold: an introduction for those new to the field, an overview for those working in the field, and a reference for those searching for literature on a specific application.
Multi-Component Analysis of Ilex Kudingcha C. J. Tseng by a Single Marker Quantification Method and Chemometric Discrimination of HPLC Fingerprints

The quantitative analysis of multiple components with a single marker (QAMS) method was firstly established for simultaneous determination of 18 active components in Ilex kudingcha C. J. Tseng by HPLC. Using rutin, isochlorogenic acid A and kudinoside A as internal refererence substances (IRS), compatibility results showed that the relative correction factors (RCFs) of all compounds showed good reproducibility under different chromatographic conditions. On the basis of previous studies, the accuracy of the QAMS method was systematically evaluated by investigating the influences of curve intercept, analytes and IRS concentration. The results showed that the concentration (especially at low level) of analytes and curve intercept were the major influencing parameters for the LRG-QAMS method (LRG = linear regression), whereas the influence of IRS concentration seemed more apparent in terms of the AVG-QAMS method (AVG = average). The two approaches were complementary with each other. In addition, hierarchical clustering analysis (HCA), principal components analysis (PCA) and similarity analysis (SA) were performed to differentiate and classify the samples based on the contents of 18 marker compounds. The results of the different chemometric analyses were completely consistent with each other, and could be supported by the quantification results.
A Comparative Study of Wireless Protocols: Bluetooth, UWB, ZigBee, and Wi-Fi

Bluetooth (over IEEE 802.15.1), ultra-wideband (UWB, over IEEE 802.15.3), ZigBee (over IEEE 802.15.4), and Wi-Fi (over IEEE 802.11) are four protocol standards for short- range wireless communications with low power consumption. From an application point of view, bluetooth is intended for a cordless mouse, keyboard, and hands-free headset, UWB is oriented to high-bandwidth multimedia links, ZigBee is designed for reliable wirelessly networked monitoring and control networks, while Wi-Fi is directed at computer-to-computer connections as an extension or substitution of cabled networks. In this paper, we provide a study of these popular wireless communication standards, evaluating their main features and behaviors in terms of various metrics, including the transmission time, data coding efficiency, complexity, and power consumption. It is believed that the comparison presented in this paper would benefit application engineers in selecting an appropriate protocol.
Roles of PAD4 and NETosis in Experimental Atherosclerosis and Arterial Injury: Implications for Superficial Erosion

Rationale: Neutrophils likely contribute to the thrombotic complications of human atheromata. In particular, neutrophil extracellular traps (NETs) could exacerbate local inflammation and amplify and propagate arterial intimal injury and thrombosis. PAD4 (peptidyl arginine deiminase 4) participates in NET formation, but an understanding of this enzyme’s role in atherothrombosis remains scant. Objective: This study tested the hypothesis that PAD4 and NETs influence experimental atherogenesis and in processes implicated in superficial erosion, a form of plaque complication we previously associated with NETs. Methods and Results: Bone marrow chimeric Ldlr deficient mice reconstituted with either wild-type or PAD4-deficient cells underwent studies that assessed atheroma formation or procedures designed to probe mechanisms related to superficial erosion. PAD4 deficiency neither retarded fatty streak formation nor reduced plaque size or inflammation in bone marrow chimeric mice that consumed an atherogenic diet. In contrast, either a PAD4 deficiency in bone marrow-derived cells or administration of DNaseI to disrupt NETs decreased the extent of arterial intimal injury in mice with arterial lesions tailored to recapitulate characteristics of human atheroma complicated by erosion. Conclusions: These results indicate that PAD4 from bone marrow-derived cells and NETs do not influence chronic experimental atherogenesis, but participate causally in acute thrombotic complications of intimal lesions that recapitulate features of superficial erosion.
Identification of Small and Non-Small Cell Lung Cancer Markers in Peripheral Blood Using Cytokinesis-Blocked Micronucleus and Spectral Karyotyping Assays

Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer. There is an urgent need to develop tools to identify individuals at high risk of developing SCLC. We have previously reported that the cytokinesis-blocked micronucleus (CBMN) assay is a strong predictor of non-small cell lung cancer (NSCLC). Here, we investigate the sensitivity of the CBMN endpoints as predictors of SCLC risk. We conducted the CBMN assay on SCLC patients (n = 216), NSCLC patients (n = 173), and healthy controls (n = 204). Per sample, 1,000 binucleated cells (BN) were scored, and 3 endpoints, micronuclei (BN-MN), nucleoplasmic bridges (BN-NPB), and nuclear buds(BN-BUD), were recorded. Spectral karyotyping was also conducted on SCLC patients (n = 116) and NSCLC patients (n = 137) to identify genomic regions unique to each disease. Significantly higher levels of CBMN endpoints were observed in both cancer groups compared to controls. BN-NPBs were significantly higher among SCLC patients compared to NSCLC patients (p < 0.001). Chromosomes 5 and 17 were associated with BN-MN, and chromosomes 5, 18, 20, and 22 were associated with BN-NPBs in SCLC patients. Given the high frequency of chromosome aberrations observed in SCLC, events such as reinsertion of the micronucleus and chromothripsis may be potential mechanisms for the genetic instability in these patients.
Dramatic decline in the HIV-1 RNA level over calendar time in a large urban HIV practice.

BACKGROUND We have previously showed that as antiretroviral therapy has improved over time since 1995-1996, the likelihood of achieving virologic suppression has also improved. Antiretroviral therapy and antiretroviral therapy guidelines have continued to evolve, and we wished to determine the trend in human immunodeficiency virus (HIV-1) RNA levels over time in HIV-infected persons receiving care in our large urban HIV clinical practice in Baltimore, Maryland. METHODS The HIV-1 RNA level was assessed each year from 1996 through 2010 at the date closest to 1 July for all patients in care and followed up in the Johns Hopkins HIV Clinical Cohort. The clinic population's median HIV-1 RNA level and stratified threshold levels were plotted. The demographic characteristics of the population were also assessed over time. RESULTS From 1996 (shortly after highly active antiretroviral therapy [HAART] was introduced) to 2010, the median HIV-1 RNA level decreased from 10,400 to <200 copies/mL. The proportion of patients with an HIV-1 RNA level >500 copies/mL decreased from 75% to only 16% during this same period. The population itself became older, had a higher proportion of women, and a lower proportion of patients with injection drug use as a transmission risk, but it was geographically stable. There was an increase in HAART use over time. DISCUSSION Our results demonstrate the remarkable impact of increased use of and improved management with HAART in this urban HIV-infected population.
Lower gene expression for KCNS3 potassium channel subunit in parvalbumin-containing neurons in the prefrontal cortex in schizophrenia.

OBJECTIVE In schizophrenia, alterations in markers of cortical GABA neurotransmission are prominent in parvalbumin-containing neurons. Parvalbumin neurons selectively express KCNS3, the gene encoding the Kv9.3 potassium channel α-subunit. Kv9.3 subunits are present in voltage-gated potassium channels that contribute to the precise detection of coincident excitatory synaptic inputs to parvalbumin neurons. This distinctive feature of parvalbumin neurons appears important for the synchronization of cortical neural networks in γ-oscillations. Because impaired prefrontal cortical γ-oscillations are thought to underlie the cognitive impairments in schizophrenia, the authors investigated whether KCNS3 mRNA levels are altered in the prefrontal cortex of schizophrenia subjects. METHOD KCNS3 mRNA expression was evaluated by in situ hybridization in 22 matched pairs of schizophrenia and comparison subjects and by microarray analyses of pooled samples of individually dissected neurons that were labeled with Vicia villosa agglutinin (VVA), a parvalbumin neuron-selective marker, in a separate cohort of 14 pairs. Effects of chronic antipsychotic treatments on KCNS3 expression were tested in the prefrontal cortex of antipsychotic-exposed monkeys. RESULTS By in situ hybridization, KCNS3 mRNA levels were 23% lower in schizophrenia subjects. At the cellular level, both KCNS3 mRNA-expressing neuron density and KCNS3 mRNA level per neuron were significantly lower. By microarray, KCNS3 mRNA levels were lower by 40% in VVA-labeled neurons from schizophrenia subjects. KCNS3 mRNA levels were not altered in antipsychotic-exposed monkeys. CONCLUSIONS These findings reveal lower KCNS3 expression in prefrontal cortical parvalbumin neurons in schizophrenia, providing a molecular basis for compromised detection of coincident synaptic inputs to parvalbumin neurons that could contribute to altered γ-oscillations and impaired cognition in schizophrenia.