Miracle-dz/UniFAR-FTUs huggingface dataset:
Learning Opportunities for Drug Repositioning via GWAS and PheWAS Findings

Drug repositioning for available medications can be preferred over traditional drug development, which requires substantially more effort to uncover new insights into medications and diseases. Genome-Wide Association Studies (GWAS) and Phenome-Wide Association Studies (PheWAS) are two complimentary methods for finding novel associations between genes and diseases. We hypothesize that discoveries from these studies could be leveraged to find new targets for existing drugs. Thus, we propose a framework to learn opportunities for inferring such relationships via overlapped genes between disease-associated genes (e.g. GWAS and PheWAS findings) and drugtargeted genes. We use drug indications found in Medication Indication Resource (MEDI) as a gold standard to evaluate if drug indications learned from GWAS and PheWAS findings have clinical indications. We examined 151,011 pairs from 987 drugs across 153 diseases and 763 pairs were statistically significant. Out of these 763 pairs, 16 of them were found to have clinical indications.
Has the athlete trained enough to return to play safely? The acute:chronic workload ratio permits clinicians to quantify a player's risk of subsequent injury

The return to sport from injury is a difficult multifactorial decision, and risk of reinjury is an important component. Most protocols for ascertaining the return to play status involve assessment of the healing status of the original injury and functional tests which have little proven predictive ability. Little attention has been paid to ascertaining whether an athlete has completed sufficient training to be prepared for competition. Recently, we have completed a series of studies in cricket, rugby league and Australian rules football that have shown that when an athlete's training and playing load for a given week (acute load) spikes above what they have been doing on average over the past 4 weeks (chronic load), they are more likely to be injured. This spike in the acute:chronic workload ratio may be from an unusual week or an ebbing of the athlete's training load over a period of time as in recuperation from injury. Our findings demonstrate a strong predictive (R2=0.53) polynomial relationship between acute:chronic workload ratio and injury likelihood. In the elite team setting, it is possible to quantify the loads we are expecting athletes to endure when returning to sport, so assessment of the acute:chronic workload ratio should be included in the return to play decision-making process.
A Parametric Comparison of Diagnostic Accuracy with Three Ordinal Diagnostic Groups

Many medical diagnostic studies involve three ordinal diagnostic groups in which the diagnostic accuracy can be summarized by the volume or partial volume under a Receiver Operating Characteristic (ROC) surface. We study in this paper the statistical comparison of diagnostic accuracy from multiple diagnostic tests when three ordinal diagnostic groups are involved. Under the assumption that the multiple diagnostic tests follow a multivariate normal distribution within each diagnostic group, we provide the asymptotic variance and covariance for the maximum likelihood estimates of the volumes under the ROC surfaces from multiple diagnostic tests and propose statistical tests to test whether the diagnostic accuracy as measured by the volume under the ROC surface is the same for multiple diagnostic tests. We also propose a confidence interval estimate to the difference of two volumes under two ROC surfaces. Our approach depends crucially on the assumptions of normal distributions on diagnostic tests, which might not be robust when such assumptions are violated. Finally, we apply our proposed methodology to a real data set of 118 subjects to compare the diagnostic accuracy of early stage Alzheimer's disease (AD) from multiple neuropsychological tests. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Localization of Epidermal Growth Factor-stimulated Ras/Raf-1 Interaction to Caveolae Membrane (*)

An essential step in the epidermal growth factor (EGF)-dependent activation of MAP kinase is the recruitment of Raf-1 to the plasma membrane. Here we present evidence that caveolae are the membrane site where Raf-1 is recruited. Caveolae fractions prepared from normal Rat-1 cells grown in the absence of serum were highly enriched in both EGF receptors and Ras. Thirty seconds after EGF was added to these cells Raf-1 began to appear in caveolae but not in non-caveolae membrane fractions. The maximum concentration was reached at 3 min followed by a decline over the next 60 min. During this time EGF receptors disappeared from the caveolae fraction while the concentration of Ras remained constant. The Raf-1 in this fraction was able to phosphorylate MAP kinase kinase, whereas cytoplasmic Raf-1 in the same cell was inactive. Elevation of cellular cAMP blocked the recruitment of Raf-1 to caveolae. Overexpression of Ha-Ras caused the recruitment of Raf-1 to caveolae independently of EGF stimulation, and this was blocked by the farnesyltransferase inhibitor BZA-5B. Finally, prenylation appeared to be required for localization of Ras to caveolae.
Appariement de descripteurs évoluant en temps

Dans le domaine du web, et plus particulierement de la comparaison d'assurance en ligne, les donnees evoluent constamment ce qui rend leur exploitation difficile. Par exemple, la plupart des methodes d'apprentissage standards necessitent des descripteurs de donnees identiques pour les echantillons d'apprentissage et test. Cependant, afin de repondre aux attentes metier, les formulaires en ligne d'ou proviennent les donnees sont regulierement modifies. Cela implique une modification reguliere des variables et des descripteurs de donnees qui complexifie les analyses. Dans ce travail, nous proposons une methode permettant d'estimer et de comprendre les liens qui se forment lors de la modification des descripteurs de donnees afin de les apparier. Cette etape est preliminaire a l'application de nombreuses methodes d'apprentissage ulterieures.
The androgen/androgen receptor axis in prostate cancer

Purpose of review The review highlights recently discovered mechanisms that sustain castration-resistant prostate cancer (CRPC) growth and describes advances in CRPC therapeutics. Recent findings Recent reports have shed new light on the molecular processes underlying CRPC survival during androgen deprivation therapy (ADT). This study summarizes recent findings and comments on their clinical relevance. Included in this review is a discussion on molecular mechanisms that regulate androgen receptor (AR) signaling in normal prostate epithelium and CRPC, biologically significant differences in the androgen-regulated transcriptional programs of androgen-dependent prostate cancer and CRPC, and recent discoveries involving de-novo androgen production and transport. We review the status and results of current clinical trials and finally, discuss the implications of evidence suggesting a declining importance of AR signaling in prostate cancers with PTEN loss. Summary Advances in the understanding of AR signaling in CRPC have identified novel drug targets and improved the rational design of targeted therapy, while illuminating a subset of prostate cancers that may progress to become completely independent of the AR signaling program.
Processing of Snack of Goat Chub Chili (Capsicum annuum L.) with Formulations of Tomato and Tomato-Marjoram

The cultivation of goat chili has potentially increased in Chile, due to different varieties of gourmet products made with it; for this reason, new industrial projects are sought to the growing volume to adapt them to the new trends in consumption habits, mainly focused on achieving an attractive meal, a fast preparation and consumption, while nutrients are provided to offer some benefits for human health. The “snacks” products that include the use of fruit satisfactorily respond to these requirements, in addition to providing marketing alternatives to the surplus of fruit exports. For this reason, the present test, consisting of the processing of snacks based on goat chub chili with the addition of tomato and marjoram, was carried out to increase the palatability and the sensorial quality of the final product. The following formulations were used: only chili (T1); chili and tomato (T2); chili, tomato and marjoram (T3). The latter one was characterized by a good flavor and aroma. A large amount of the fruit water content had been removed by drying it with forced hot air. A product without chemical preserves was obtained, with physical and chemical parameters similar to those required by similar foods existing on the market today. In sensorial terms, the formulation to which marjoram was added showed good sensorial and acceptability attributes, highlighting them from the rest of the treatments. The snack color was maintained after the dehydration process, according to panelists.
Lycopene, Tomatoes, and the Prevention of Coronary Heart Disease

Coronary heart disease (CHD) is one of the primary causes of death in the Western world. The emphasis so far has been on the relationship between serum cholesterol levels and the risk of CHD. More recently, oxidative stress induced by reactive oxygen species (ROS) is also considered to play an important part in the etiology of this disease. Oxidation of the circulating low-density lipoprotein (LDLox) is thought to play a key role in the pathogenesis of atherosclerosis and CHD. According to this hypothesis, macrophages inside the arterial wall take up the LDLox and initiate the process of plaque formation. Dietary antioxidants such as vitamin E and ß-carotene have been shown in In vitro studies to prevent the formation of LDLox and their uptake by microphages. In a recent study, healthy human subjects ingesting lycopene, a carotenoid antioxidant, in the form of tomato juice, tomato sauce, and oleoresin soft gel capsules for 1 week had significantly lower levels of LDLox compared with controls. The antioxidant effects of lycopene have also been shown in four other human trials, including one where lycopene consumption reduced the levels of breath pentane. However, in one recent study, dietary supplementation with ß-carotene but not with lycopene was shown to inhibit LDL oxidation. The sources of lycopene used in most of these studies were either tomato products or lycopene extracted from tomatoes containing other carotenoids in various proportions. Therefore, it is not possible to attribute the effects solely to lycopene. Mechanisms other than the antioxidant properties of lycopene have also been shown to reduce the risk of CHD. Lycopene was shown to inhibit the activity of an essential enzyme involved in cholesterol synthesis in an in vitro and a small clinical study suggesting a hypocholesterolemic effect. Other possible mechanisms include enhanced LDL degradation, LDL particle size and composition, plaque rupture, and altered endothelial functions. Recent epidemiological studies have also shown an inverse relationship between tissue and serum levels of lycopene and mortality from CHD, cerebrovascular disease, and myocardial infraction. However, the most impressive population-based evidence comes from a multicenter case-control study where subjects from 10 European countries were evaluated for relationship between antioxidant status and acute myocardial infarctions. After adjusting for a range of dietary variables, only lycopene levels but not ß-carotene were found to be protective. At present, the role of lycopene in the prevention of CHD is strongly suggestive. Although the antioxidant property of lycopene may be one of the principal mechanism for its effect, other mechanisms may also be responsible. Controlled clinical and dietary intervention studies using well-defined subject populations and disease end points must be undertaken in the future to provide definitive evidence for the role of lycopene in the prevention of CHD. Mechanistic studies must also be initiated to understand the mode of lycopene action.
Encapsulating sulfur into hierarchically ordered porous carbon as a high-performance cathode for lithium-sulfur batteries.

A three-dimensional (3D) hierarchical carbon-sulfur nanocomposite that is useful as a high-performance cathode for rechargeable lithium-sulfur batteries is reported. The 3D hierarchically ordered porous carbon (HOPC) with mesoporous walls and interconnected macropores was prepared by in situ self-assembly of colloidal polymer and silica spheres with sucrose as the carbon source. The obtained porous carbon possesses a large specific surface area and pore volume with narrow mesopore size distribution, and acts as a host and conducting framework to contain highly dispersed elemental sulfur. Electrochemical tests reveal that the HOPC/S nanocomposite with well-defined nanostructure delivers a high initial specific capacity up to 1193 mAh g(-1) and a stable capacity of 884 mAh g(-1) after 50 cycles at 0.1 C. In addition, the HOPC/S nanocomposite exhibits high reversible capacity at high rates. The excellent electrochemical performance is attributed exclusively to the beneficial integration of the mesopores for the electrochemical reaction and macropores for ion transport. The mesoporous walls of the HOPC act as solvent-restricted reactors for the redox reaction of sulfur and aid in suppressing the diffusion of polysulfide species into the electrolyte. The "open" ordered interconnected macropores and windows facilitate transportation of electrolyte and solvated lithium ions during the charge/discharge process. These results show that nanostructured carbon with hierarchical pore distribution could be a promising scaffold for encapsulating sulfur to approach high specific capacity and energy density with long cycling performance.
A 0.7 V Relative Temperature Sensor With a Non-Calibrated $\pm 1~^{\circ}{\rm C}$ 3$\sigma$ Relative Inaccuracy

This paper presents a new low-voltage relative temperature sensor for multi-core digital processor on-chip thermal management in a 180 nm CMOS process. Three types of sensing diodes including Schottky barrier diode (SBD), subthreshold MOSFET diode and dynamic threshold MOSFET (DTMOS) diode have been investigated for low-voltage operation, while traditional parasitic PNP-bipolar junction transistor (BJT) diodes are implemented to provide a performance reference. A matrix of 7 × 7 small remote sensor nodes is implemented on the chip with a deployment density of 49/0.81 mm2 and sharing the same bias current generator, control logic, and data converter. The measured minimum supply voltage (not including the clock control block) of the sensor is 0.7 V over -55 °C to 125 °C. The relative sensing inaccuracies (3σ) without calibration are less than ±1.5 °C, ±1.2 °C and ±1 °C for the designs based on SBD, subthreshold MOSFET, and DTMOS, respectively. To the best of the authors' knowledge, this is the first time that non-calibrated relative sensing accuracy is reported for SBD-based and DTMOS-based temperature sensors, and the best reported result for the design based on subthreshold MOSFET. The absolute inaccuracies with calibration-per-chip are also presented. Furthermore, the multi-location thermal monitoring function has been experimentally demonstrated and a 1.8 °C/mm on-chip temperature gradient was detected.
Abstract. Primary central nervous system lymphoma (PcnSl) is a non-Hodgkin's lymphoma arising in the central nervous system. combined methotrexate-based chemoradiotherapy is the standard treatment for PcnSl, resulting in a median overall survival of 25-51 months. Failure of first-line treatment has 

Primary central nervous system lymphoma (PcnSl) is a non-Hodgkin's lymphoma arising in the central nervous system. combined methotrexate-based chemoradiotherapy is the standard treatment for PcnSl, resulting in a median overall survival of 25-51 months. Failure of first-line treatment has been reported in most patients with PcnSl. Salvage therapy improves outcome; however, since many different treatments have been applied, conclusions cannot be drawn regarding an optimal treatment schedule. This review analyzes the efficacy of different salvage therapies that have been reported in the literature. These well-designed, randomized trials may help elucidate issues such as the best chemotherapy regimen for second-line treatment.
Under the influence of crowding effects: Stability, bifurcation and chaos control for a discrete-time predator–prey model

The interaction between predators and preys exhibits more complicated behavior under the influence of crowding effects. By taking into account the crowding effects, the qualitative behavior of a prey–predator model is investigated. Particularly, we examine the boundedness as well as existence and uniqueness of positive steady-state and stability analysis of the unique positive steady-state. Moreover, it is also proved that the system undergoes Hopf bifurcation and flip bifurcation with the help of bifurcation theory. Moreover, a chaos control technique is proposed for controlling chaos under the influence of bifurcations. Finally, numerical simulations are provided to illustrate the theoretical results. These results of numerical simulations demonstrate chaotic long-term behavior over a broad range of parameters. The presence of chaotic behavior in the model is confirmed by computing maximum Lyapunov exponents.
A 6.78-MHz Single-Stage Wireless Power Receiver Using a 3-Mode Reconfigurable Resonant Regulating Rectifier

A 6.78-MHz wireless power receiver using a 3-mode reconfigurable resonant regulating rectifier for resonant wireless power transfer is presented. The proposed receiver improves power conversion efficiency and reduces die area and off-chip components by achieving power conversion plus voltage regulation in one stage, using only four on-chip power transistors and one off-chip capacitor. Moreover, the proposed 3-mode operation reduces the output voltage ripples and accomplishes switching synchronization easily during mode switching. The proposed pulsewidth modulation controller using ramp-stacking technique and type-II compensation achieves tight voltage regulation in the full loading range with fast transient responses. An adaptive sizing method is also employed to further improve the light-load efficiency of the receiver. Fabricated in a standard 0.35-<inline-formula> <tex-math notation="LaTeX">$\mu \text{m}$ </tex-math></inline-formula> CMOS process using 5-V devices, the receiver regulates the output voltage at 5 V and delivers a maximum power of 6 W. The measured peak efficiency reaches 92.2% when delivering an output power of 3.5 W. For a load step between 0.5 and 5 W, the overshoot and undershoot are less than 300 mV and the settling times are less than 16 <inline-formula> <tex-math notation="LaTeX">$\mu \text{s}$ </tex-math></inline-formula>.
The Health Care Experiments at Many Farms: The Navajo, Tuberculosis, and the Limits of Modern Medicine, 1952-1962

In January 1952 a team of medical researchers from Cornell Medical College learned that tuberculosis raged untreated on the Navajo Reservation in Arizona. These researchers, led by Walsh McDermott, recognized a valuable opportunity for medical research, and they began a ten-year project to evaluate the efficacy of new antibiotics and test the power of modern medicine to improve the health conditions of an impoverished rural society. The history of this endeavor exposes a series of tensions at the heart of medical research and practice. Researchers exploited the opportunities made possible by the ill-health of a marginalized population, but did so with the cooperation and gratitude of the Navajo. They introduced new antibiotics that liberated patients from hospitals, but erected an intrusive system of outpatient surveillance. They provided innovative health-care services, but failed to reduce the dominant causes of morbidity and mortality. As every act of treatment became an experiment, they risked undermining the trust on which research and clinical care depended.
AP-2 c promotes proliferation in breast tumour cells by direct repression of the CDKN 1 A gene

Overexpression of the activator protein (AP)-2c transcription factor in breast tumours has been identified as an independent predictor of poor outcome and failure of hormone therapy. To understand further the function of AP-2c in breast carcinoma, we have used an RNA interference and gene expression profiling strategy with the MCF-7 cell line as a model. Gene expression changes between control and silenced cells implicate AP-2c in the control of cell cycle progression and developmental signalling. A function for AP-2c in cell cycle control was verified using flow cytometry: AP-2c silencing led to a partial G1/S arrest and induction of the cyclin-dependent kinase inhibitor, p21cip/CDKN1A. Reporter and chromatin immunoprecipitation assays demonstrated a direct, functional interaction by AP-2c at the CDKN1A proximal promoter. AP-2c silencing coincided with acquisition of an active chromatin conformation at the CDKN1A locus and increased gene expression. These data provide a mechanism whereby AP-2c overexpression can promote breast epithelial proliferation and, coupled with previously published data, suggest how loss of oestrogen regulation of AP-2c may contribute to the failure of hormone therapy in patients. The EMBO Journal (2009) 28, 3591–3601. doi:10.1038/ emboj.2009. 290; Published online 1 October 2009 Subject Categories: molecular biology of disease
Screening for stratification in two-phase ('two- stage') epidemiological surveys

Screening is undertaken not only for the purpose of giving therapeutic treatment to those among screen positive subjects found to be diagnosis positive, but it is also used in epidemiology as the first phase of multi-phase sampling designs. We review the use of such designs in epidemiology, and in psychiatric epidemiology in particular, focusing on two-phase or double sampling. We then compare a variety of approaches to the statistical analysis of data from such designs including the use of sampling weights, Gibbs sampling, full maximum likelihood for random effects logistic regression and a simple E-M algorithm for incomplete data. The methods are illustrated using data from a recent multi-phase study of psychiatric morbidity in northern Spain.
Major polymer damage of drug-eluting stents.

A 67-year-old man presented with stable angina pectoris on exertion. He had a history of type 2 diabetes, severe peripheral vascular disease with bilateral above-knee amputations, renal insufficiency requiring dialysis, and arterial hypertension for more than 20 years. Coronary angiography revealed a long, calcified 90% bifurcation lesion of the left anterior …