PREDICT: a method for inferring novel drug indications with application to personalized medicine

The authors present a new method, PREDICT, for the large-scale prediction of drug indications, and demonstrate its use on both approved drugs and novel molecules. They also provide a proof-of-concept for its potential utility in predicting patient-specific medications

Burden of anemia in patients with osteoarthritis and rheumatoid arthritis in French secondary care

<p>Abstract</p> <p>Background</p> <p>Arthritic disorders can be the cause of hospitalizations, especially among individuals 60 years and older. The objective of this study is to investigate associations between health care resource utilization in arthritis patients with and without concomitant anemia in a secondary care setting in France.</p> <p>Methods</p> <p>This retrospective cohort study utilized data on secondary care activity in 2001 from the Programme de Médicalisation des Systèmes d'Information database. Two cohorts were defined using ICD-10 codes: patients with an arthritis diagnosis with a concomitant diagnosis of anemia; and arthritis patients without anemia. Health care resource utilization for both populations was analyzed separately in public and private hospitals. Study outcomes were compared between the cohorts using standard bivariate and multivariable methods.</p> <p>Results</p> <p>There were 300,865 hospitalizations for patients with arthritis only, and 2,744 for those with concomitant anemia. Over 70% of patients with concomitant anemia were in public hospitals, compared with 53.5% of arthritis-only patients. Arthritis patients without anemia were younger than those with concomitant anemia (mean age 66.7 vs 74.6, public hospitals; 67.1 vs 72.2, private hospitals). Patients with concomitant anemia/arthritis only had a mean length of stay of 11.91 (SD 14.07)/8.04 (SD 9.93) days in public hospitals, and 10.68 (SD 10.16)/9.83 (SD 7.76) days in private hospitals. After adjusting for confounders, the mean (95% CI) additional length of stay for arthritis patients with concomitant anemia, compared with those with arthritis only, was 1.56 (1.14-1.98) days in public and 0.69 (0.22-1.16) days in private hospitals. Costs per hospitalization were €;480 (227-734) greater for arthritis patients with anemia in public hospitals, and €;30 (-113-52) less in private hospitals, than for arthritis-only patients.</p> <p>Conclusions</p> <p>Arthritis patients with concomitant anemia have a longer length of stay, undergo more procedures, and have higher hospitalization costs than nonanemic arthritis patients in public hospitals in France. In private hospitals, concomitant anemia was associated with modest increases in length of stay and number of procedures; however, this did not translate into higher costs. Such evidence of anemia-related health care utilization and costs can be considered as a proxy for the clinical significance of anemia.</p

The Pap smear screening as an occasion for smoking cessation and physical activity counselling: baseline characteristics of women involved in the SPRINT randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Gender-specific smoking cessation strategies have rarely been developed. Evidence of effectiveness of physical activity (PA) promotion and intervention in adjunct to smoking cessation programs is not strong. SPRINT study is a randomized controlled trial (RCT) designed to evaluate a counselling intervention on smoking cessation and PA delivered to women attending the Italian National Health System Cervical Cancer Screening Program. This paper presents study design and baseline characteristics of the study population.</p> <p>Methods/Design</p> <p>Among women undergoing the Pap examination in three study centres (Florence, Turin, Mantua), participants were randomized to the smoking cessation counselling [S], the smoking cessation + PA counselling [S + PA], or the control [C] groups. The program under evaluation is a standard brief counselling on smoking cessation combined with a brief counselling on increasing PA, and was delivered in 2010. A questionnaire, administered before, after 6 months and 1 year from the intervention, was used to track behavioural changes in tobacco use and PA, and to record cessation rates in participants.</p> <p>Discussion</p> <p>Out of the 5,657 women undergoing the Pap examination, 1,100 participants (55% of smokers) were randomized in 1 of the 3 study groups (363 in the S, 366 in the S + PA and 371 in the C groups). The three arms did not differ on any demographic, PA, or tobacco-use characteristics. Recruited smokers were older, less educated than non-participant women, more motivated to quit (33% vs.9% in the Preparation stage, <it>p </it>< 0.001), smoked more cigarettes per day (12 vs.9, <it>p </it>< 0.001), and were more likely to have already done 1 or more quit attempts (64% vs.50%, <it>p </it>< 0.001). The approach of SPRINT study appeared suitable to enrol less educated women who usually smoke more and have more difficulties to quit.</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN52660565">ISRCTN52660565</a></p

An open-access database and analysis tool for perovskite solar cells based on the FAIR data principles

Large datasets are now ubiquitous as technology enables higher-throughput experiments, but rarely can a research field truly benefit from the research data generated due to inconsistent formatting, undocumented storage or improper dissemination. Here we extract all the meaningful device data from peer-reviewed papers on metal-halide perovskite solar cells published so far and make them available in a database. We collect data from over 42,400 photovoltaic devices with up to 100 parameters per device. We then develop open-source and accessible procedures to analyse the data, providing examples of insights that can be gleaned from the analysis of a large dataset. The database, graphics and analysis tools are made available to the community and will continue to evolve as an open-source initiative. This approach of extensively capturing the progress of an entire field, including sorting, interactive exploration and graphical representation of the data, will be applicable to many fields in materials science, engineering and biosciences

A philosophical analysis of the evidence-based medicine debate

BACKGROUND: The term "evidence-based medicine" (or EBM) was introduced about ten years ago, and there has been considerable debate about the value of EBM. However, this debate has sometimes been obscured by a lack of conceptual clarity concerning the nature and status of EBM. DISCUSSION: First, we note that EBM proponents have obscured the current debate by defining EBM in an overly broad, indeed almost vacuous, manner; we offer a clearer account of EBM and its relation to the alternative approaches to medicine. Second, while EBM proponents commonly cite the philosophical work of Thomas Kuhn and claim that EBM is a Kuhnian 'paradigm shift,' we argue that such claims are seriously mistaken and unduly polarize the EBM debate. Third, we suggest that it is much more fruitful to understand the relationship between EBM and its alternatives in light of a different philosophical metaphor: W.V. Quine's metaphor of the web of belief. Seen in this way, we argue that EBM is an approach to medical practice that is indeed importantly different from the alternatives. SUMMARY: We can have a more productive debate about the value of EBM by being clearer about the nature of EBM and its relationship to alternative approaches to medicine

Crowding Alone Cannot Account for Cosolute Effect on Amyloid Aggregation

Amyloid fiber formation is a specific form of protein aggregation, often resulting from the misfolding of native proteins. Aimed at modeling the crowded environment of the cell, recent experiments showed a reduction in fibrillation halftimes for amyloid-forming peptides in the presence of cosolutes that are preferentially excluded from proteins and peptides. The effect of excluded cosolutes has previously been attributed to the large volume excluded by such inert cellular solutes, sometimes termed “macromolecular crowding”. Here, we studied a model peptide that can fold to a stable monomeric β-hairpin conformation, but under certain solution conditions aggregates in the form of amyloid fibrils. Using Circular Dichroism spectroscopy (CD), we found that, in the presence of polyols and polyethylene glycols acting as excluded cosolutes, the monomeric β-hairpin conformation was stabilized with respect to the unfolded state. Stabilization free energy was linear with cosolute concentration, and grew with molecular volume, as would also be predicted by crowding models. After initiating the aggregation process with a pH jump, fibrillation in the presence and absence of cosolutes was followed by ThT fluorescence, transmission electron microscopy, and CD spectroscopy. Polyols (glycerol and sorbitol) increased the lag time for fibril formation and elevated the amount of aggregated peptide at equilibrium, in a cosolute size and concentration dependent manner. However, fibrillation rates remained almost unaffected by a wide range of molecular weights of soluble polyethylene glycols. Our results highlight the importance of other forces beyond the excluded volume interactions responsible for crowding that may contribute to the cosolute effects acting on amyloid formation

Functional MRI and Diffusion Tensor Imaging of Brain Reorganization After Experimental Stroke

The potential of the adult brain to reorganize after ischemic injury is critical for functional recovery and provides a significant target for therapeutic strategies to promote brain repair. Despite the accumulating evidence of brain plasticity, the interaction and significance of morphological and physiological modifications in post-stroke brain tissue remain mostly unclear. Neuroimaging techniques such as functional MRI (fMRI) and diffusion tensor imaging (DTI) enable in vivo assessment of the spatial and temporal pattern of functional and structural changes inside and outside ischemic lesion areas. This can contribute to the elucidation of critical aspects in post-stroke brain remodeling. Task/stimulus-related fMRI, resting-state fMRI, or pharmacological MRI enables direct or indirect measurement of neuronal activation, functional connectivity, or neurotransmitter system responses, respectively. DTI allows estimation of the structural integrity and connectivity of white matter tracts. Together, these MRI methods provide an unprecedented means to (a) measure longitudinal changes in tissue structure and function close by and remote from ischemic lesion areas, (b) evaluate the organizational profile of neural networks after stroke, and (c) identify degenerative and restorative processes that affect post-stroke functional outcome. Besides, the availability of MRI in clinical institutions as well as research laboratories provides an optimal basis for translational research on stroke recovery. This review gives an overview of the current status and perspectives of fMRI and DTI applications to study brain reorganization in experimental stroke models

Measuring macroscopic brain connections in vivo

Decades of detailed anatomical tracer studies in non-human animals point to a rich and complex organization of long-range white matter connections in the brain. State-of-the art in vivo imaging techniques are striving to achieve a similar level of detail in humans, but multiple technical factors can limit their sensitivity and fidelity. In this review, we mostly focus on magnetic resonance imaging of the brain. We highlight some of the key challenges in analyzing and interpreting in vivo connectomics data, particularly in relation to what is known from classical neuroanatomy in laboratory animals. We further illustrate that, despite the challenges, in vivo imaging methods can be very powerful and provide information on connections that is not available by any other means

Prion protein facilitates uptake of zinc into neuronal cells

Zinc is released into the synaptic cleft upon exocytotic stimuli, although the mechanism for its reuptake into neurons is unresolved. Here we show that the cellular prion protein enhances the uptake of zinc into neuronal cells. This prion-protein-mediated zinc influx requires the octapeptide repeats and amino-terminal polybasic region in the prion protein, but not its endocytosis. Selective antagonists of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors block the prion protein-mediated zinc uptake, and the prion protein co-immunoprecipitates with both GluA1 and GluA2 AMPA receptor subunits. Zinc-sensitive intracellular tyrosine phosphatase activity is decreased in cells expressing prion protein and increased in the brains of prion-protein-null mice, providing evidence of a physiological consequence of this process. Prion protein-mediated zinc uptake is ablated in cells expressing familial associated mutants of the protein and in prion-infected cells. These data suggest that alterations in the cellular prion protein-mediated zinc uptake may contribute to neurodegeneration in prion and other neurodegenerative diseases