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Showing papers by "Universidade Federal de Minas Gerais published in 2016"


Journal ArticleDOI
Daniel J. Klionsky1, Kotb Abdelmohsen2, Akihisa Abe3, Joynal Abedin4  +2519 moreInstitutions (695)
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

5,187 citations


Journal ArticleDOI
Theo Vos1, Christine Allen1, Megha Arora1, Ryan M Barber1  +696 moreInstitutions (260)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) as discussed by the authors was used to estimate the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.

5,050 citations


Journal ArticleDOI
Haidong Wang1, Mohsen Naghavi1, Christine Allen1, Ryan M Barber1  +841 moreInstitutions (293)
TL;DR: The Global Burden of Disease 2015 Study provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015, finding several countries in sub-Saharan Africa had very large gains in life expectancy, rebounding from an era of exceedingly high loss of life due to HIV/AIDS.

4,804 citations


Journal ArticleDOI
Bin Zhou1, Yuan Lu2, Kaveh Hajifathalian2, James Bentham1  +494 moreInstitutions (170)
TL;DR: In this article, the authors used a Bayesian hierarchical model to estimate trends in diabetes prevalence, defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs in 200 countries and territories in 21 regions, by sex and from 1980 to 2014.

2,782 citations


Journal ArticleDOI
Nicholas J Kassebaum1, Megha Arora1, Ryan M Barber1, Zulfiqar A Bhutta2  +679 moreInstitutions (268)
TL;DR: In this paper, the authors used the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015.

1,533 citations


Journal ArticleDOI
26 Jul 2016-eLife
TL;DR: The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
Abstract: Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.

1,348 citations


Journal ArticleDOI
Eric Schuettpelz1, Harald Schneider2, Alan R. Smith3, Peter Hovenkamp4, Jefferson Prado, Germinal Rouhan5, Alexandre Salino6, Michael A. Sundue7, Thaís Elias Almeida8, Barbara S. Parris, Emily B. Sessa9, Ashley R. Field10, André Luís de Gasper, Carl J. Rothfels3, Michael D. Windham11, Marcus Lehnert12, Benjamin Dauphin13, Atsushi Ebihara, Samuli Lehtonen14, Pedro Bond Schwartsburd, Jordan S. Metzgar15, Li-Bing Zhang16, Li-Yaung Kuo17, Patrick J. Brownsey18, Masahiro Kato, Marcelo D. Arana19, Francine Costa Assis6, Michael S. Barker20, David S. Barrington7, Ho-Ming Chang21, Yi-Han Chang, Yi-Shan Chao22, Cheng-Wei Chen, De-Kui Chen23, Wen-Liang Chiou, Vinícius Antonio de Oliveira Dittrich24, Yi-Fan Duan25, Jean-Yves Dubuisson5, Donald R. Farrar26, Susan Fawcett7, Jose María Gabriel y Galán27, Luiz Armando de Araújo Góes-Neto6, Jason R. Grant13, Amanda L. Grusz, Christopher H. Haufler28, Warren D. Hauk29, Hai He23, Sabine Hennequin5, Regina Y. Hirai, Layne Huiet11, Michael Kessler30, Petra Korall, Paulo H. Labiak, Anders Larsson, Blanca León, Chun-Xiang Li, Fay-Wei Li, Melanie A. Link-Pérez, Hong-Mei Liu, Ngan Thi Lu, Esteban I. Meza-Torres, Xin-Yuan Miao, Robbin C. Moran, Claudine M. Mynssen, Nathalie S. Nagalingum, Benjamin Øllgaard, Alison M. Paul, Jovani B. S. Pereira, Leon R. Perrie, M. Mónica Ponce, Tom A. Ranker, Christian Schulz, Wataru Shinohara, Alexander Shmakov, Erin M. Sigel, Filipe Soares de Souza, Lana da Silva Sylvestre, Weston Testo, Luz Amparo Triana-Moreno, Chie Tsutsumi, Hanna Tuomisto, Ivan A. Valdespino, Alejandra Vasco, Raquel Stauffer Viveros, Alan S. Weakley, Ran Wei, Stina Weststrand, Paul G. Wolf, George Yatskievych, Xiao-Gang Xu, Yue-Hong Yan, Liang Zhang16, Xian-Chun Zhang, Xin-Mao Zhou 
TL;DR: A modern, comprehensive classification for lycophytes and ferns, down to the genus level, utilizing a community‐based approach, that uses monophyly as the primary criterion for the recognition of taxa, but also aims to preserve existing taxa and circumscriptions that are both widely accepted and consistent with the understanding of pteridophyte phylogeny.
Abstract: Phylogeny has long informed pteridophyte classification. As our ability to infer evolutionary trees has improved, classifications aimed at recognizing natural groups have become increasingly predic ...

971 citations


Journal ArticleDOI
TL;DR: Synthesis of cholinergic neurons located in the basal forebrain, including the neurons that form the nucleus basalis of Meynert, are severely lost in Alzheimer’s disease, and drugs that act on the choline system represent a promising option to treat AD patients.
Abstract: Acetylcholine (ACh) has a crucial role in the peripheral and central nervous systems. The enzyme choline acetyltransferase (ChAT) is responsible for synthesizing ACh from acetyl-CoA and choline in the cytoplasm and the vesicular acetylcholine transporter (VAChT) uptakes the neurotransmitter into synaptic vesicles. Following depolarization, ACh undergoes exocytosis reaching the synaptic cleft, where it can bind its receptors, including muscarinic and nicotinic receptors. ACh present at the synaptic cleft is promptly hydrolyzed by the enzyme acetylcholinesterase (AChE), forming acetate and choline, which is recycled into the presynaptic nerve terminal by the high-affinity choline transporter (CHT1). Cholinergic neurons located in the basal forebrain, including the neurons that form the nucleus basalis of Meynert, are severely lost in Alzheimer's disease (AD). AD is the most ordinary cause of dementia affecting 25 million people worldwide. The hallmarks of the disease are the accumulation of neurofibrillary tangles and amyloid plaques. However, there is no real correlation between levels of cortical plaques and AD-related cognitive impairment. Nevertheless, synaptic loss is the principal correlate of disease progression and loss of cholinergic neurons contributes to memory and attention deficits. Thus, drugs that act on the cholinergic system represent a promising option to treat AD patients.

865 citations


Journal ArticleDOI
13 Apr 2016
TL;DR: In this article, structural defects in two-dimensional transition metal dichalcogenides (TMDs) have been studied and the authors provide a comprehensive understanding of structural defects and the pathways to generating structural defects during and after synthesis.
Abstract: Two-dimensional transition metal dichalcogenides (TMDs), an emerging family of layered materials, have provided researchers a fertile ground for harvesting fundamental science and emergent applications. TMDs can contain a number of different structural defects in their crystal lattices which significantly alter their physico-chemical properties. Having structural defects can be either detrimental or beneficial, depending on the targeted application. Therefore, a comprehensive understanding of structural defects is required. Here we review different defects in semiconducting TMDs by summarizing: (i) the dimensionalities and atomic structures of defects; (ii) the pathways to generating structural defects during and after synthesis and, (iii) the effects of having defects on the physico-chemical properties and applications of TMDs. Thus far, significant progress has been made, although we are probably still witnessing the tip of the iceberg. A better understanding and control of defects is important in order to move forward the field of Defect Engineering in TMDs. Finally, we also provide our perspective on the challenges and opportunities in this emerging field.

789 citations


Journal ArticleDOI
TL;DR: It is shown that the use of culturomics allows the culture of organisms corresponding to sequences previously not assigned, which doubles the number of species isolated at least once from the human gut.
Abstract: Metagenomics revolutionized the understanding of the relations among the human microbiome, health and diseases, but generated a countless number of sequences that have not been assigned to a known microorganism1. The pure culture of prokaryotes, neglected in recent decades, remains essential to elucidating the role of these organisms2. We recently introduced microbial culturomics, a culturing approach that uses multiple culture conditions and matrix-assisted laser desorption/ionization–time of flight and 16S rRNA for identification2. Here, we have selected the best culture conditions to increase the number of studied samples and have applied new protocols (fresh-sample inoculation; detection of microcolonies and specific cultures of Proteobacteria and microaerophilic and halophilic prokaryotes) to address the weaknesses of the previous studies3–5. We identified 1,057 prokaryotic species, thereby adding 531 species to the human gut repertoire: 146 bacteria known in humans but not in the gut, 187 bacteria and 1 archaea not previously isolated in humans, and 197 potentially new species. Genome sequencing was performed on the new species. By comparing the results of the metagenomic and culturomic analyses, we show that the use of culturomics allows the culture of organisms corresponding to sequences previously not assigned. Altogether, culturomics doubles the number of species isolated at least once from the human gut. Optimization of culturing techniques has allowed the identification of 1,057 prokaryotic species within the human gut microbiome repertoire, doubling the previous number of isolated species from the human gut.

697 citations


Journal ArticleDOI
TL;DR: In this article, the authors quantified maternal mortality throughout the world by underlying cause and age from 1990 to 2015 for ages 10-54 years by systematically compiling and processing all available data sources from 186 of 195 countries and territories.

Journal ArticleDOI
TL;DR: This work surveys the current state-of-the-art methods of ECG-based automated abnormalities heartbeat classification by presenting the ECG signal preprocessing, the heartbeat segmentation techniques, the feature description methods and the learning algorithms used.

Journal ArticleDOI
TL;DR: An exhaustive review and reanalysis of geological, paleontological, and molecular records converge upon a cohesive narrative of gradually emerging land and constricting seaways, with formation of the Isthmus of Panama sensu stricto around 2.8 Ma.
Abstract: The formation of the Isthmus of Panama stands as one of the greatest natural events of the Cenozoic, driving profound biotic transformations on land and in the oceans. Some recent studies suggest that the Isthmus formed many millions of years earlier than the widely recognized age of approximately 3 million years ago (Ma), a result that if true would revolutionize our understanding of environmental, ecological, and evolutionary change across the Americas. To bring clarity to the question of when the Isthmus of Panama formed, we provide an exhaustive review and reanalysis of geological, paleontological, and molecular records. These independent lines of evidence converge upon a cohesive narrative of gradually emerging land and constricting seaways, with formation of the Isthmus of Panama sensu stricto around 2.8 Ma. The evidence used to support an older isthmus is inconclusive, and we caution against the uncritical acceptance of an isthmus before the Pliocene.

Journal ArticleDOI
Haidong Wang1, Zulfiqar A Bhutta2, Zulfiqar A Bhutta3, Matthew M Coates1  +610 moreInstitutions (263)
TL;DR: The Global Burden of Disease 2015 Study provides an analytical framework to comprehensively assess trends for under-5 mortality, age-specific and cause-specific mortality among children under 5 years, and stillbirths by geography over time and decomposed the changes in under- 5 mortality to changes in SDI at the global level.

Journal ArticleDOI
Haidong Wang1, Timothy M. Wolock1, Austin Carter1, Grant Nguyen1  +497 moreInstitutions (214)
TL;DR: This report provides national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.

Journal ArticleDOI
TL;DR: In this article, the authors synthesize reservoir CH4, CO2, and N2O emission data with three main objectives: (1) to generate a global estimate of GHG emissions from reservoirs, (2) to identify the best predictors of these emissions, and (3) to consider the effect of methodology on emission estimates.
Abstract: Collectively, reservoirs created by dams are thought to be an important source of greenhouse gases (GHGs) to the atmosphere. So far, efforts to quantify, model, and manage these emissions have been limited by data availability and inconsistencies in methodological approach. Here, we synthesize reservoir CH4, CO2, and N2O emission data with three main objectives: (1) to generate a global estimate of GHG emissions from reservoirs, (2) to identify the best predictors of these emissions, and (3) to consider the effect of methodology on emission estimates. We estimate that GHG emissions from reservoir water surfaces account for 0.8 (0.5-1.2) Pg CO2 equivalents per year, with the majority of this forcing due to CH4. We then discuss the potential for several alternative pathways such as dam degassing and downstream emissions to contribute significantly to overall emissions. Although prior studies have linked reservoir GHG emissions to reservoir age and latitude, we find that factors related to reservoir productivity are better predictors of emission.

Journal ArticleDOI
TL;DR: Isavuconazole showed activity against mucormycosis with efficacy similar to amphotericin B, and can be used for treatment of mucormYcosis and is well tolerated.
Abstract: Summary Background Mucormycosis is an uncommon invasive fungal disease with high mortality and few treatment options. Isavuconazole is a triazole active in vitro and in animal models against moulds of the order Mucorales. We assessed the efficacy and safety of isavuconazole for treatment of mucormycosis and compared its efficacy with amphotericin B in a matched case-control analysis. Methods In a single-arm open-label trial (VITAL study), adult patients (≥18 years) with invasive fungal disease caused by rare fungi, including mucormycosis, were recruited from 34 centres worldwide. Patients were given isavuconazole 200 mg (as its intravenous or oral water-soluble prodrug, isavuconazonium sulfate) three times daily for six doses, followed by 200 mg/day until invasive fungal disease resolution, failure, or for 180 days or more. The primary endpoint was independent data review committee-determined overall response—ie, complete or partial response (treatment success) or stable or progressive disease (treatment failure)—according to prespecified criteria. Mucormycosis cases treated with isavuconazole as primary treatment were matched with controls from the FungiScope Registry, recruited from 17 centres worldwide, who received primary amphotericin B-based treatment, and were analysed for day-42 all-cause mortality. VITAL is registered with ClinicalTrials.gov, number NCT00634049. FungiScope is registered with ClinicalTrials.gov, number NCT01731353. Findings Within the VITAL study, from April 22, 2008, to June 21, 2013, 37 patients with mucormycosis received isavuconazole for a median of 84 days (IQR 19–179, range 2–882). By day 42, four patients (11%) had a partial response, 16 (43%) had stable invasive fungal disease, one (3%) had invasive fungal disease progression, three (8%) had missing assessments, and 13 (35%) had died. 35 patients (95%) had adverse events (28 [76%] serious). Day-42 crude all-cause mortality in seven (33%) of 21 primary-treatment isavuconazole cases was similar to 13 (39%) of 33 amphotericin B-treated matched controls (weighted all-cause mortality: 33% vs 41%; p=0·595). Interpretation Isavuconazole showed activity against mucormycosis with efficacy similar to amphotericin B. Isavuconazole can be used for treatment of mucormycosis and is well tolerated. Funding Astellas Pharma Global Development, Basilea Pharmaceutica International.

Journal ArticleDOI
23 Sep 2016-Science
TL;DR: Using 835 inventories covering 4660 species of woody plants, marked floristic turnover among inventories and regions indicates that numerous conservation areas across many countries will be needed to protect the full diversity of tropical dry forests.
Abstract: Seasonally dry tropical forests are distributed across Latin America and the Caribbean and are highly threatened, with less than 10% of their original extent remaining in many countries. Using 835 inventories covering 4660 species of woody plants, we show marked floristic turnover among inventories and regions, which may be higher than in other neotropical biomes, such as savanna. Such high floristic turnover indicates that numerous conservation areas across many countries will be needed to protect the full diversity of tropical dry forests. Our results provide a scientific framework within which national decision-makers can contextualize the floristic significance of their dry forest at a regional and continental scale.

Journal ArticleDOI
TL;DR: The aim of this conceptual paper was to propose a complex system model for sports injuries and to demonstrate how the implementation of complex system thinking may allow us to better address the complex nature of the sports injuries aetiology.
Abstract: Injury prediction is one of the most challenging issues in sports and a key component for injury prevention. Sports injuries aetiology investigations have assumed a reductionist view in which a phenomenon has been simplified into units and analysed as the sum of its basic parts and causality has been seen in a linear and unidirectional way. This reductionist approach relies on correlation and regression analyses and, despite the vast effort to predict sports injuries, it has been limited in its ability to successfully identify predictive factors. The majority of human health conditions are complex. In this sense, the multifactorial complex nature of sports injuries arises not from the linear interaction between isolated and predictive factors, but from the complex interaction among a web of determinants. Thus, the aim of this conceptual paper was to propose a complex system model for sports injuries and to demonstrate how the implementation of complex system thinking may allow us to better address the complex nature of the sports injuries aetiology. According to this model, we should identify features that are hallmarks of complex systems, such as the pattern of relationships (interactions) among determinants, the regularities (profiles) that simultaneously characterise and constrain the phenomenon and the emerging pattern that arises from the complex web of determinants. In sports practice, this emerging pattern may be related to injury occurrence or adaptation. This novel view of preventive intervention relies on the identification of regularities or risk profile, moving from risk factors to risk pattern recognition.

Journal ArticleDOI
TL;DR: It is promising the clinical and laboratory use of endothelial, inflammatory and pro-coagulant biomarkers for predicting the risk of cardiovascular and renal complications in diabetic patients and for monitoring these patients.
Abstract: Background Vascular complications are the leading cause of morbidity and mortality among patients with type 1 and type 2 diabetes mellitus. These vascular abnormalities result of a chronic hyperglycemic state, which leads to an increase in oxidative stress and inflammatory responses. Aim This review addresses the relationships among endothelial dysfunction, hypercoagulability and inflammation and their biomarkers in the development of vascular complications in type 1 and type 2 diabetes. Results Inflammation, endothelial dysfunction, and hypercoagulability are correlated to each other, playing an important role in the development of vascular complications in diabetic patients. Moreover, it has been observed that several endothelial, inflammatory and pro-coagulant biomarkers, such as VWF, IL-6, TNF-α, D-dimer and PAI-1, are increased in diabetic patients who have microvascular and macrovascular complications, including nephropathy or cardiovascular disease. Conclusion It is promising the clinical and laboratory use of endothelial, inflammatory and pro-coagulant biomarkers for predicting the risk of cardiovascular and renal complications in diabetic patients and for monitoring these patients.

Journal ArticleDOI
TL;DR: It is suggested that several mediators that promote the inflammatory phase of inflammation can simultaneously initiate a program for active resolution and several events enact a decrease in the local chemokine concentration, essential to inhibit further infiltration of neutrophils into the tissue.
Abstract: An effective resolution program may be able to prevent the progression from non-resolving acute inflammation to persistent chronic inflammation. It has now become evident that coordinated resolution programs initiate shortly after inflammatory responses begin. In this context, several mechanisms provide the fine-tuning of inflammation and create a favorable environment for the resolution phase to take place and for homeostasis to return. In this review, we focus on the events required for an effective transition from the proinflammatory phase to the onset and establishment of resolution. We suggest that several mediators that promote the inflammatory phase of inflammation can simultaneously initiate a program for active resolution. Indeed, several events enact a decrease in the local chemokine concentration, a reduction which is essential to inhibit further infiltration of neutrophils into the tissue. Interestingly, although neutrophils are cells that characteristically participate in the active phase of inflammation, they also contribute to the onset of resolution. Further understanding of the molecular mechanisms that initiate resolution may be instrumental to develop pro-resolution strategies to treat complex chronic inflammatory diseases in humans. The efforts to develop strategies based on resolution of inflammation have shaped a new area of pharmacology referred to as ‘resolution pharmacology’.

Journal ArticleDOI
TL;DR: It is shown that campo rupestre is fully comparable to and remarkably convergent with both fynbos and kwongkan, and fulfills the criteria for a classic OCBIL.
Abstract: Botanists, ecologists and evolutionary biologists are familiar with the astonishing species richness and endemism of the fynbos of the Cape Floristic Region and the ancient and unique flora of the kwongkan of south-western Australia. These regions represent old climatically-buffered infertile landscapes (OCBILs) that are the basis of a general hypothesis to explain their richness and endemism. However, few ecologists are familiar with the campo rupestre of central and eastern Brazil, an extremely old mountaintop ecosystem that is both a museum of ancient lineages and a cradle of continuing diversification of endemic lineages. Diversification of some lineages of campo rupestre pre-dates diversification of lowland cerrado, suggesting it may be the most ancient open vegetation in eastern South America. This vegetation comprises more than 5000 plant species, nearly 15 % of Brazil’s plant diversity, in an area corresponding to 0.78 % of its surface. Reviewing empirical data, we scrutinise five predictions of the OCBIL theory, and show that campo rupestre is fully comparable to and remarkably convergent with both fynbos and kwongkan, and fulfills the criteria for a classic OCBIL. The increasing threats to campo rupestre are compromising ecosystem services and we argue for the implementation of more effective conservation and restoration strategies.


Journal ArticleDOI
TL;DR: The results reveal the immense potential for translating the dispersed expertise in biological assays involving human pathogens into drug discovery starting points, by providing open access to new families of molecules, and emphasize how a small additional investment made to help acquire and distribute compounds, and sharing the data, can catalyze drug discovery for dozens of different indications.
Abstract: A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemistry programs. The data for all of these assays are presented and analyzed to show how outstanding leads for many indications can be selected. These results reveal the immense potential for translating the dispersed expertise in biological assays involving human pathogens into drug discovery starting points, by providing open access to new families of molecules, and emphasize how a small additional investment made to help acquire and distribute compounds, and sharing the data, can catalyze drug discovery for dozens of different indications. Another lesson is that when multiple screens from different groups are run on the same library, results can be integrated quickly to select the most valuable starting points for subsequent medicinal chemistry efforts.

Journal ArticleDOI
01 Jul 2016
TL;DR: This work surveys VANETs focusing on their communication and application challenges, and discusses the protocol stack of this type of network, and provides a qualitative comparison between most common protocols in the literature.
Abstract: VANETs have emerged as an exciting research and application area. Increasingly vehicles are being equipped with embedded sensors, processing and wireless communication capabilities. This has opened a myriad of possibilities for powerful and potential life-changing applications on safety, efficiency, comfort, public collaboration and participation, while they are on the road. Although, considered as a special case of a Mobile Ad Hoc Network, the high but constrained mobility of vehicles bring new challenges to data communication and application design in VANETs. This is due to their highly dynamic and intermittent connected topology and different application's QoS requirements. In this work, we survey VANETs focusing on their communication and application challenges. In particular, we discuss the protocol stack of this type of network, and provide a qualitative comparison between most common protocols in the literature. We then present a detailed discussion of different categories of VANET applications. Finally, we discuss open research problems to encourage the design of new VANET solutions.

Journal ArticleDOI
TL;DR: The authors present a method based on a physical model of light propagation that takes into account the most significant effects to image degradation: absorption, scattering, and backscattering to restore the visual quality of the images acquired in typical underwater scenarios.
Abstract: In underwater environments, the scattering and absorption phenomena affect the propagation of light, degrading the quality of captured images. In this work, the authors present a method based on a physical model of light propagation that takes into account the most significant effects to image degradation: absorption, scattering, and backscattering. The proposed method uses statistical priors to restore the visual quality of the images acquired in typical underwater scenarios.

Journal ArticleDOI
15 Mar 2016-Brain
TL;DR: Microglial activation appears at the prodromal and possibly at the preclinical stage of Alzheimer's disease, and seems to play a protective role in the clinical progression of the disease at these early stages, according to a second-generation 18-kDa translocator protein positron emission tomography radiotracer.
Abstract: While emerging evidence suggests that neuroinflammation plays a crucial role in Alzheimer's disease, the impact of the microglia response in Alzheimer's disease remains a matter of debate. We aimed to study microglial activation in early Alzheimer's disease and its impact on clinical progression using a second-generation 18-kDa translocator protein positron emission tomography radiotracer together with amyloid imaging using Pittsburgh compound B positron emission tomography. We enrolled 96 subjects, 64 patients with Alzheimer's disease and 32 controls, from the IMABio3 study, who had both (11)C-Pittsburgh compound B and (18)F-DPA-714 positron emission tomography imaging. Patients with Alzheimer's disease were classified as prodromal Alzheimer's disease (n = 38) and Alzheimer's disease dementia (n = 26). Translocator protein-binding was measured using a simple ratio method with cerebellar grey matter as reference tissue, taking into account regional atrophy. Images were analysed at the regional (volume of interest) and at the voxel level. Translocator protein genotyping allowed the classification of all subjects in high, mixed and low affinity binders. Thirty high+mixed affinity binders patients with Alzheimer's disease were dichotomized into slow decliners (n = 10) or fast decliners (n = 20) after 2 years of follow-up. All patients with Alzheimer's disease had an amyloid positive Pittsburgh compound B positron emission tomography. Among controls, eight had positive amyloid scans (n = 6 high+mixed affinity binders), defined as amyloidosis controls, and were analysed separately. By both volumes of interest and voxel-wise comparison, 18-kDa translocator protein-binding was higher in high affinity binders, mixed affinity binders and high+mixed affinity binders Alzheimer's disease groups compared to controls, especially at the prodromal stage, involving the temporo-parietal cortex. Translocator protein-binding was positively correlated with Mini-Mental State Examination scores and grey matter volume, as well as with Pittsburgh compound B binding. Amyloidosis controls displayed higher translocator protein-binding than controls, especially in the frontal cortex. We found higher translocator protein-binding in slow decliners than fast decliners, with no difference in Pittsburgh compound B binding. Microglial activation appears at the prodromal and possibly at the preclinical stage of Alzheimer's disease, and seems to play a protective role in the clinical progression of the disease at these early stages. The extent of microglial activation appears to differ between patients, and could explain the overlap in translocator protein binding values between patients with Alzheimer's disease and amyloidosis controls.

Journal ArticleDOI
TL;DR: The current evidence suggests that exercise alone or in combination with education is effective for preventing low back pain, and other interventions, including education alone, back belts, and shoe insoles do not appear to prevent LBP.
Abstract: Importance Existing guidelines and systematic reviews lack clear recommendations for prevention of low back pain (LBP). Objective To investigate the effectiveness of interventions for prevention of LBP. Data Sources MEDLINE, EMBASE, Physiotherapy Evidence Database Scale, and Cochrane Central Register of Controlled Trials from inception to November 22, 2014. Study Selection Randomized clinical trials of prevention strategies for nonspecific LBP. Data Extraction and Synthesis Two independent reviewers extracted data and assessed the risk of bias. The Physiotherapy Evidence Database Scale was used to evaluate the risk-of-bias. The Grading of Recommendations Assessment, Development, and Evaluation system was used to describe the quality of evidence. Main Outcomes and Measures The primary outcome measure was an episode of LBP, and the secondary outcome measure was an episode of sick leave associated with LBP. We calculated relative risks (RRs) and 95% CIs using random-effects models. Results The literature search identified 6133 potentially eligible studies; of these, 23 published reports (on 21 different randomized clinical trials including 30 850 unique participants) met the inclusion criteria. With results presented as RRs (95% CIs), there was moderate-quality evidence that exercise combined with education reduces the risk of an episode of LBP (0.55 [0.41-0.74]) and low-quality evidence of no effect on sick leave (0.74 [0.44-1.26]). Low- to very low–quality evidence suggested that exercise alone may reduce the risk of both an LBP episode (0.65 [0.50-0.86]) and use of sick leave (0.22 [0.06-0.76]). For education alone, there was moderate- to very low–quality evidence of no effect on LBP (1.03 [0.83-1.27]) or sick leave (0.87 [0.47-1.60]). There was low- to very low–quality evidence that back belts do not reduce the risk of LBP episodes (1.01 [0.71-1.44]) or sick leave (0.87 [0.47-1.60]). There was low-quality evidence of no protective effect of shoe insoles on LBP (1.01 [0.74-1.40]). Conclusion and Relevance The current evidence suggests that exercise alone or in combination with education is effective for preventing LBP. Other interventions, including education alone, back belts, and shoe insoles, do not appear to prevent LBP. Whether education, training, or ergonomic adjustments prevent sick leave is uncertain because the quality of evidence is low.

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TL;DR: A benchmark comparison of twenty-four popular sentiment analysis methods, covering messages posted on social networks, movie and product reviews, as well as opinions and comments in news articles is presented, highlighting the extent to which the prediction performance of these methods varies considerably across datasets.
Abstract: In the last few years thousands of scientific papers have investigated sentiment analysis, several startups that measure opinions on real data have emerged and a number of innovative products related to this theme have been developed. There are multiple methods for measuring sentiments, including lexical-based and supervised machine learning methods. Despite the vast interest on the theme and wide popularity of some methods, it is unclear which one is better for identifying the polarity (i.e., positive or negative) of a message. Accordingly, there is a strong need to conduct a thorough apple-to-apple comparison of sentiment analysis methods, as they are used in practice, across multiple datasets originated from different data sources. Such a comparison is key for understanding the potential limitations, advantages, and disadvantages of popular methods. This article aims at filling this gap by presenting a benchmark comparison of twenty-four popular sentiment analysis methods (which we call the state-of-the-practice methods). Our evaluation is based on a benchmark of eighteen labeled datasets, covering messages posted on social networks, movie and product reviews, as well as opinions and comments in news articles. Our results highlight the extent to which the prediction performance of these methods varies considerably across datasets. Aiming at boosting the development of this research area, we open the methods’ codes and datasets used in this article, deploying them in a benchmark system, which provides an open API for accessing and comparing sentence-level sentiment analysis methods.

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TL;DR: A positive association between UPF consumption and hypertension risk was observed in this large prospective cohort of Spanish middle‐aged adult university graduates, and additional longitudinal studies are needed to confirm the results.