Miracle-dz/UniFAR-FTUs huggingface dataset:
Should the IDEFICS outcomes have been expected?

The Identification and prevention of Dietary‐ and lifestyle‐induced health EFfects In Children and infantS (IDEFICS) study evaluated with a large sample a comprehensive carefully planned obesity prevention intervention targeting multiple levels of influence that were culturally adapted to the situations in eight European countries. Despite the great effort and attention to detail, the IDEFICS study did not achieve its targeted adiposity or behaviour change objectives. Should we be surprised that the IDEFICS trial did not have its intended effects? We think not, and would have been surprised if it did. Recent research has revealed the lack of consistent meaningful relationships between several apparently obesogenic behaviours and adiposity, weak or no relationships among behavioural change procedures, mediating variables and targeted behaviours and inadequate attention to moderating effects. Future obesity prevention interventions would benefit from a more thorough understanding of the complex relationships that have been hypothesized and the interrelationships with biological factors. While systems modelling has been proposed as providing the solution, important less complex identification of new constructs, new relationships and community interventions are still needed, both to find innovative solutions and to provide input into the systems models. We should question results from cross‐sectional studies and be satisfied only with longitudinal or experimental tests of relationships.
Interrogating the relationship between rat in vivo tissue distribution and drug property data for >200 structurally unrelated molecules

The ability to explain distribution patterns from drug physicochemical properties and binding characteristics has been explored for more than 200 compounds by interrogating data from quantitative whole body autoradiography studies (QWBA). These in vivo outcomes have been compared to in silico and in vitro drug property data to determine the most influential properties governing drug distribution. Consistent with current knowledge, in vivo distribution was most influenced by ionization state and lipophilicity which in turn affected phospholipid and plasma protein binding. Basic and neutral molecules were generally better distributed than acidic counterparts demonstrating weaker plasma protein and stronger phospholipid binding. The influence of phospholipid binding was particularly evident in tissues with high phospholipid content like spleen and lung. Conversely, poorer distribution of acidic drugs was associated with stronger plasma protein and weaker phospholipid binding. The distribution of a proportion of acidic drugs was enhanced, however, in tissues known to express anionic uptake transporters such as the liver and kidney. Greatest distribution was observed into melanin containing tissues of the eye, most likely due to melanin binding. Basic molecules were consistently better distributed into parts of the eye and skin containing melanin than those without. The data, therefore, suggest that drug binding to macromolecules strongly influences the distribution of total drug for a large proportion of molecules in most tissues. Reducing lipophilicity, a strategy often used in discovery to optimize pharmacokinetic properties such as absorption and clearance, also decreased the influence of nonspecific binding on drug distribution.
Ecosystem Services and Biodiversity in a Rapidly Transforming Landscape in Northern Borneo

Because industrial agriculture keeps expanding in Southeast Asia at the expense of natural forests and traditional swidden systems, comparing biodiversity and ecosystem services in the traditional forest–swidden agriculture system vs. monocultures is needed to guide decision making on land-use planning. Focusing on tree diversity, soil erosion control, and climate change mitigation through carbon storage, we surveyed vegetation and monitored soil loss in various land-use areas in a northern Bornean agricultural landscape shaped by swidden agriculture, rubber tapping, and logging, where various levels and types of disturbance have created a fine mosaic of vegetation from food crop fields to natural forest. Tree species diversity and ecosystem service production were highest in natural forests. Logged-over forests produced services similar to those of natural forests. Land uses related to the swidden agriculture system largely outperformed oil palm or rubber monocultures in terms of tree species diversity and service production. Natural and logged-over forests should be maintained or managed as integral parts of the swidden system, and landscape multifunctionality should be sustained. Because natural forests host a unique diversity of trees and produce high levels of ecosystem services, targeting carbon stock protection, e.g. through financial mechanisms such as Reducing Emissions from Deforestation and Forest Degradation (REDD+), will synergistically provide benefits for biodiversity and a wide range of other services. However, the way such mechanisms could benefit communities must be carefully evaluated to counter the high opportunity cost of conversion to monocultures that might generate greater income, but would be detrimental to the production of multiple ecosystem services.
Optical and Scintillation Properties of Polydimethyl-Diphenylsiloxane Based Organic Scintillators

Polysiloxane based scintillators with high light yield have been synthesized. The polymer consists in cross-linked polydimethyl-co-diphenylsiloxane with different molar percentages of phenyl units. 2,5-diphenyl oxazole (PPO) and 2,5-bis(5-ter-butyl-2-benzoxazolyl)thiophene (BBOT) have been dispersed in the polymer as dopants. The energy transfer and scintillation capabilities have been investigated, for two different amounts of phenyl groups in the polymer network and for different concentrations of dye molecules, by means of fluorescence spectroscopy, ion beam induced luminescence (IBIL) and scintillation yield measurements with ¿ particles from an 241Am source. The luminescence features and the scintillation yields have been correlated to the composition of the scintillators.
MINT: the Molecular INTeraction database

The Molecular INTeraction database (MINT, ) aims at storing, in a structured format, information about molecular interactions (MIs) by extracting experimental details from work published in peer-reviewed journals. At present the MINT team focuses the curation work on physical interactions between proteins. Genetic or computationally inferred interactions are not included in the database. Over the past four years MINT has undergone extensive revision. The new version of MINT is based on a completely remodeled database structure, which offers more efficient data exploration and analysis, and is characterized by entries with a richer annotation. Over the past few years the number of curated physical interactions has soared to over 95 000. The whole dataset can be freely accessed online in both interactive and batch modes through web-based interfaces and an FTP server. MINT now includes, as an integrated addition, HomoMINT, a database of interactions between human proteins inferred from experiments with ortholog proteins in model organisms ().
Recognition of HLA-Cw4 but Not HLA-Cw6 by the NK Cell Receptor Killer Cell Ig-Like Receptor Two-Domain Short Tail Number 41

NK cells are cytotoxic to virus-infected and tumor cells that have lost surface expression of class I MHC proteins. Target cell expression of class I MHC proteins inhibits NK cytotoxicity through binding to inhibitory NK receptors. In contrast, a similar family of activating NK receptors, characterized by the presence of a charged residue in their transmembrane portion and a truncated cytoplasmic tail, augment lysis by NK cells when ligated by an appropriate class I MHC protein. However, the class I MHC specificity of many of these activating NK receptors is still unknown. Here, we show enhanced lysis of HLA-Cw4 but not HLA-Cw6-expressing cells, by a subset of NK clones. This subset may express killer cell Ig-like receptor two-domain short tail number 4 (KIR2DS4), as suggested by staining with various mAb. It is still possible, however, that these clones may express receptors other than KIR2DS4 that might recognize HLA-Cw4. Binding of KIR2DS4-Ig fusion protein to cells expressing HLA-Cw4 but not to those expressing HLA-Cw6 was also observed. The binding of KIR2DS4-Ig to HLA-Cw4 is weaker than that of killer cell Ig-like receptor two-domain long tail number 1 (KIR2DL1)-Ig fusion protein; however, such weak recognition is capable of inhibiting lysis by an NK transfectant expressing a chimeric molecule of KIR2DS4 fused to the transmembrane and cytoplasmic portion of KIR2DL1. Residue α14 is shown to be important in the KIR2DS4 binding to HLA-Cw4. Implications of the role of the activating NK receptors in immunosurveillance are discussed.
The effect of hormone therapy on mean blood pressure and visit-to-visit blood pressure variability in postmenopausal women: results from the Women's Health Initiative randomized controlled trials

Objectives: Mean and visit-to-visit variability (VVV) of blood pressure (BP) are associated with an increased cardiovascular disease risk. We examined the effect of hormone therapy on mean and VVV of BP in postmenopausal women from the Women's Health Initiative (WHI) randomized controlled trials. Methods: BP was measured at baseline and annually in the two WHI hormone therapy trials, in which 10 739 and 16 608 postmenopausal women were randomized to conjugated equine estrogens (CEEs, 0.625 mg/day) or placebo, and CEEs and medroxyprogesterone acetate (MPA, 2.5 mg/day) or placebo, respectively. Results: At the first annual visit (year 1), mean SBP was 1.04 mmHg [95% confidence interval (CI) 0.58, 1.50] and 1.35 mmHg (95% CI 0.99, 1.72) higher in the CEEs and CEEs and MPA arms, respectively, compared with the corresponding placebos. These effects remained stable after year 1. CEEs also increased the VVV of SBP (ratio of VVV in CEEs vs. placebo, 1.03; P < 0.001), whereas CEEs and MPA did not (ratio of VVV in CEEs and MPA vs. placebo, 1.01; P = 0.20). After accounting for study drug adherence, the effects of CEEs and CEEs and MPA on mean SBP increased at year 1, and the differences in the CEEs and CEEs and MPA arms vs. placebos also continued to increase after year 1. Further, both CEEs and CEEs and MPA significantly increased the VVV of SBP (ratio of VVV in CEEs vs. placebo, 1.04; P < 0.001; ratio of VVV in CEEs and MPA vs. placebo, 1.05; P < 0.001). Conclusion: Among postmenopausal women, CEEs and CEEs and MPA at conventional doses increased mean and VVV of SBP.
Feature Selection using PSO-SVM

The feature selection process can be considered a problem of global combinatorial optimization in machine learning, which reduces the number of features, removes irrelevant, noisy and redundant data, and results in an acceptable classification accuracy. Feature selection is of great importance in pattern classification, medical data processing, machine learning, and data mining applications. Therefore, a good feature selection method based on the number of features investigated for sample classification is needed in order to speed up the processing rate, predictive accuracy, and to avoid incomprehensibility. In this paper, particle swarm optimization (PSO) is used to implement a feature selection, and support vector machines (SVMs) with the one-versus-rest method serve as a fitness function of PSO for the classification problem. The proposed method is applied to five classification problems from the literature. Experimental results show that our method simplifies features effectively and obtains a higher classification accuracy compared to the other feature selection methods.
New therapeutic approaches for treatment of tularaemia: a review

Antibiotic treatment of tularaemia is based on a few drugs, including the fluoroquinolones (e.g., ciprofloxacin), the tetracyclines (e.g., doxycycline), and the aminoglycosides (streptomycin and gentamicin). Because no effective and safe vaccine is currently available, tularaemia prophylaxis following proven exposure to F. tularensis also relies on administration of antibiotics. A number of reasons make it necessary to search for new therapeutic alternatives: the potential toxicity of first-line drugs, especially in children and pregnant women; a high rate of treatment relapses and failures, especially for severe and/or suppurated forms of the disease; and the possible use of antibiotic-resistant strains in the context of a biological threat. This review presents novel therapeutic approaches that have been explored in recent years to improve tularaemia patients' management and prognosis. These new strategies have been evaluated in vitro, in axenic media and cell culture systems and/or in animal models. First, the activities of newly available antibiotic compounds were evaluated against F. tularensis, including tigecycline (a glycylcycline), ketolides (telithromycin and cethromycin), and fluoroquinolones (moxifloxacin, gatifloxacin, trovafloxacin and grepafloxacin). The liposome delivery of some antibiotics was evaluated. The effect of antimicrobial peptides against F. tularensis was also considered. Other drugs were evaluated for their ability to suppress the intracellular multiplication of F. tularensis. The effects of the modulation of the innate immune response (especially via TLR receptors) on the course of F. tularensis infection was characterized. Another approach was the administration of specific antibodies to induce passive resistance to F. tularensis infection. All of these studies highlight the need to develop new therapeutic strategies to improve the management of patients with tularaemia. Many possibilities exist, some unexplored. Moreover, it is likely that new therapeutic alternatives that are effective against this intracellular pathogen could be, at least partially, extrapolated to other human pathogens.
Leveraging stereo matching with learning-based confidence measures

We propose a new approach to associate supervised learning-based confidence prediction with the stereo matching problem. First of all, we analyze the characteristics of various confidence measures in the regression forest framework to select effective confidence measures using training data. We then train regression forests again to predict the correctness (confidence) of a match by using selected confidence measures. In addition, we present a confidence-based matching cost modulation scheme based on the predicted correctness for improving the robustness and accuracy of various stereo matching algorithms. We apply the proposed scheme to the semi-global matching algorithm to make it robust under unexpected difficulties that can occur in outdoor environments. We verify the proposed confidence measure selection and cost modulation methods through extensive experimentation with various aspects using KITTI and challenging outdoor datasets.
Design of a Thermoacoustic Sensor for Low Intensity Ultrasound Measurements Based on an Artificial Neural Network

In therapeutic ultrasound applications, accurate ultrasound output intensities are crucial because the physiological effects of therapeutic ultrasound are very sensitive to the intensity and duration of these applications. Although radiation force balance is a benchmark technique for measuring ultrasound intensity and power, it is costly, difficult to operate, and compromised by noise vibration. To overcome these limitations, the development of a low-cost, easy to operate, and vibration-resistant alternative device is necessary for rapid ultrasound intensity measurement. Therefore, we proposed and validated a novel two-layer thermoacoustic sensor using an artificial neural network technique to accurately measure low ultrasound intensities between 30 and 120 mW/cm2. The first layer of the sensor design is a cylindrical absorber made of plexiglass, followed by a second layer composed of polyurethane rubber with a high attenuation coefficient to absorb extra ultrasound energy. The sensor determined ultrasound intensities according to a temperature elevation induced by heat converted from incident acoustic energy. Compared with our previous one-layer sensor design, the new two-layer sensor enhanced the ultrasound absorption efficiency to provide more rapid and reliable measurements. Using a three-dimensional model in the K-wave toolbox, our simulation of the ultrasound propagation process demonstrated that the two-layer design is more efficient than the single layer design. We also integrated an artificial neural network algorithm to compensate for the large measurement offset. After obtaining multiple parameters of the sensor characteristics through calibration, the artificial neural network is built to correct temperature drifts and increase the reliability of our thermoacoustic measurements through iterative training about ten seconds. The performance of the artificial neural network method was validated through a series of experiments. Compared to our previous design, the new design reduced sensing time from 20 s to 12 s, and the sensor’s average error from 3.97 mW/cm2 to 1.31 mW/cm2 respectively.
The Biological Activity of the Prototypic Cyclotide Kalata B1 Is Modulated by the Formation of Multimeric Pores*

The cyclotides are a large family of circular mini-proteins containing a cystine knot motif. They are expressed in plants as defense-related proteins, with insecticidal activity. Here we investigate their role in membrane interaction and disruption. Kalata B1, a prototypic cyclotide, was found to induce leakage of the self-quenching fluorophore, carboxyfluorescein, from phospholipid vesicles. Alanine-scanning mutagenesis of kalata B1 showed that residues essential for lytic activity are clustered, forming a bioactive face. Kalata B1 was sequestered at the membrane surface and showed slow dissociation from vesicles. Electrophysiological experiments showed that conductive pores were induced in liposome patches on incubation with kalata B1. The conductance calculated from the current-voltage relationship indicated that the diameter of the pores formed in the bilayer patches is 41–47 Å. Collectively, the findings provide a mechanistic explanation for the diversity of biological functions ascribed to this fascinating family of ultrastable macrocyclic peptides.
Phase II evaluation of oral estramustine and oral etoposide in hormone-refractory adenocarcinoma of the prostate.

PURPOSE Estramustine and etoposide (VP-16) have been demonstrated to inhibit the growth of prostate cancer cells in experimental models. This led us to evaluate the effectiveness of this combination in the treatment of patients with metastatic prostate carcinoma refractory to hormone therapy. PATIENTS AND METHODS Estramustine 15 mg/kg/d and VP-16 50 mg/m2/d, were administered orally in divided doses for 21 days. Patients were then taken off therapy for 7 days and the cycle then repeated. Therapy continued until evidence of disease progression. RESULTS Forty-two patients have been enrolled onto this trial with a minimum of 40 weeks follow-up. Of 18 patients with measurable soft tissue disease, three demonstrated a complete response (CR) and six a partial response (PR) for longer than 2 months. Of these 18 patients, pretreatment prostate-specific antigen (PSA) levels decreased by at least 75% in five men (28%) and by at least 50% in nine (50%). The median survival duration has not been reached in those patients who demonstrated a response either by soft tissue or PSA criteria. Of 24 patients with disease limited to bone, six (25%) demonstrated improvement and nine (38%) demonstrated stability in their bone scans. Five men (21%) demonstrated a decrease of at least 75% in pretreatment PSA levels and 14 (58%) demonstrated at least a 50% decrease; the median survival duration has not been reached in these patients. Pretreatment performance status is an important predictor of survival. CONCLUSION We conclude that the combination of estramustine and VP-16 is an active oral regimen in hormone-refractory prostate cancer.
Normalisation of physical function by infliximab in patients with RA: factors associated with normal physical function.

OBJECTIVES We conducted a two-year prospective study to identify possible factors associated with normalisation of physical function by infliximab treatment in 125 patients with rheumatoid arthritis (RA). METHODS RA patients who had been scheduled to receive infliximab at 3 mg/kg were registered and prospectively examined for disease activity, joint damage, and physical function for 102 weeks using the Disease Activity Score of 28 Joints (DAS-28) using C-reactive protein, van der Heijde-modified Sharp score (vdH-Sharp score) of hand and foot x-ray, and Health Assessment Questionnaire Disability Index (HAQ-DI). Normal physical function and clinical remission were defined as a HAQ-DI of 0.5 or less, and DAS28 (CRP) <2.6, respectively. RESULTS Forty-two of 125 patients (42%) achieved normal physical function at 102 weeks. The percentage of normal physical function at 102 weeks was significantly higher in the patients achieving clinical remission at 102 weeks (60%) than in those without (16%). In the patients with clinical remission at 102 weeks, less structural damage at baseline was correlated with a higher rate of normal physical function, suggesting the critical importance of joint destruction prior to infliximab therapy, in addition to clinical response. Logistic regression analysis further identified HAQ-DI, serum MMP-3 level, vdH-Sharp score, and methotrexate (MTX) dose as baseline factors contributing to normal physical function with 2-year infliximab treatment. CONCLUSIONS Treatment with anti-TNF biologics in combination with MTX may achieve the normalisation of physical function in patients with established RA. Critical factors contributing to the normalisation of function were tight control of disease activity and less joint damage.
Association of TCF7L2 gene polymorphisms with reduced acute insulin response in Hispanic Americans.

CONTEXT Genetic variation at the transcription factor 7-like 2 locus has been linked to type 2 diabetes in predominantly European-derived populations. The biological basis of these associations remains to be determined. OBJECTIVE The objective of this study was to evaluate previously associated variants for association with measures of glucose homeostasis in Hispanic-Americans and African-Americans and determine the biological mechanism(s) through which these variants exert their effect. DESIGN This study was the Insulin Resistance Atherosclerosis Family Study (IRAS-FS). SETTING The IRAS-FS is a community-based study of Hispanic-Americans (San Antonio, TX, and San Luis Valley, CO) and African-Americans (Los Angeles, CA). PARTICIPANTS A total of 1040 Hispanic-American and 500 African-American individuals from the IRAS-FS formed the basis of this study. MAIN OUTCOMES MEASURES(S): The primary glucose homeostasis phenotypes of interest in this study were derived from the frequently sampled iv glucose tolerance test and include insulin sensitivity, acute insulin response, and disposition index. RESULTS In Hispanic-Americans, significant evidence of association was observed between single-nucleotide polymorphisms rs7903146 and rs112255372 with reduced insulin secretion as measured by acute insulin response and adjusted for the degree of insulin sensitivity (P = 0.032 and 0.036, respectively). Other quantitative measures, e.g. insulin sensitivity or disposition index, were not associated with the single nucleotide polymorphisms examined. In African-Americans there was no evidence of association observed. CONCLUSIONS These results suggest that transcription factor 7-like 2 variants could play a role in the pathogenesis of type 2 diabetes in the Hispanic-American population through a mechanism involving insulin secretion.