Showing papers by "Mahidol University published in 2017"
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TL;DR: The number of adults with raised blood pressure increased from 594 million in 1975 to 1·13 billion in 2015, with the increase largely in low-income and middle-income countries, and the contributions of changes in prevalence versus population growth and ageing to the increase.
1,573 citations
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University of Edinburgh1, University of Glasgow2, Johns Hopkins University3, University of Colorado Boulder4, University of the Witwatersrand5, International Military Sports Council6, Aga Khan University7, Medical Research Council8, King George's Medical University9, Kenya Medical Research Institute10, International Centre for Diarrhoeal Disease Research, Bangladesh11, Centers for Disease Control and Prevention12, Tribhuvan University13, University of Bergen14, University of Barcelona15, Utrecht University16, Emory University17, All India Institute of Medical Sciences18, University of Liverpool19, Boston Children's Hospital20, National Institute of Virology21, University of Zambia22, University of Health Sciences Antigua23, National Health Laboratory Service24, Chinese Center for Disease Control and Prevention25, Austral University26, University of Michigan27, Vanderbilt University28, University of New South Wales29, University of Otago30, University of Auckland31, Universidad del Valle de Guatemala32, University of Jordan33, University of Maryland, Baltimore34, National Scientific and Technical Research Council35, Research Institute for Tropical Medicine36, Pwani University College37, University of Cape Town38, University of Warwick39, Academy of Medical Sciences, United Kingdom40, Tohoku University41, École normale supérieure de Lyon42, John E. Fogarty International Center43, Charité44, Universidad Nacional de Asunción45, Tehran University of Medical Sciences46, Robert Koch Institute47, University of London48, University of New Mexico49, Capital Medical University50, Alaska Native Tribal Health Consortium51, Innlandet Hospital Trust52, Columbia University53, Mahidol University54, University of Pretoria55, Thailand Ministry of Public Health56, Peking Union Medical College57, Nagasaki University58, Public Health Foundation of India59
TL;DR: In this paper, the authors estimated the incidence and hospital admission rate of RSV-associated acute lower respiratory infection (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions.
1,470 citations
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TL;DR: The subcommittee reviewed the prevalence, incidence, risk factors, natural history, morbidity and questionnaires reported in epidemiological studies of dry eye disease and confirmed that prevalence increases with age, however signs showed a greater increase per decade than symptoms.
Abstract: The subcommittee reviewed the prevalence, incidence, risk factors, natural history, morbidity and questionnaires reported in epidemiological studies of dry eye disease (DED). A meta-analysis of published prevalence data estimated the impact of age and sex. Global mapping of prevalence was undertaken. The prevalence of DED ranged from 5 to 50%. The prevalence of signs was higher and more variable than symptoms. There were limited prevalence studies in youth and in populations south of the equator. The meta-analysis confirmed that prevalence increases with age, however signs showed a greater increase per decade than symptoms. Women have a higher prevalence of DED than men, although differences become significant only with age. Risk factors were categorized as modifiable/non-modifiable, and as consistent, probable or inconclusive. Asian ethnicity was a mostly consistent risk factor. The economic burden and impact of DED on vision, quality of life, work productivity, psychological and physical impact of pain, are considerable, particularly costs due to reduced work productivity. Questionnaires used to evaluate DED vary in their utility. Future research should establish the prevalence of disease of varying severity, the incidence in different populations and potential risk factors such as youth and digital device usage. Geospatial mapping might elucidate the impact of climate, environment and socioeconomic factors. Given the limited study of the natural history of treated and untreated DED, this remains an important area for future research.
1,322 citations
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University of Texas Health Science Center at Houston1, Memorial Sloan Kettering Cancer Center2, Heidelberg University3, Mayo Clinic4, Harvard University5, University of California, Los Angeles6, Autonomous University of Barcelona7, University of Southern California8, University of California, San Francisco9, Université catholique de Louvain10, Seoul National University11, Wayne State University12, National Cheng Kung University13, Mahidol University14, Katholieke Universiteit Leuven15, National Taiwan University16, Ohio State University17, Novartis18
TL;DR: BGJ398 is a first-in-class FGFR kinase inhibitor with manageable toxicities that shows meaningful clinical activity against chemotherapy-refractory cholangiocarcinoma containing FGFR2 fusions.
Abstract: PurposeNo standard treatment exists for patients with cholangiocarcinoma for whom first-line gemcitabine-based therapy fails. Fibroblast growth factor receptor 2 (FGFR2) fusions/translocations are present in 13% to 17% of intrahepatic cholangiocarcinomas. BGJ398, an orally bioavailable, selective pan-FGFR kinase inhibitor, has shown preliminary clinical activity against tumors with FGFR alterations.MethodsA multicenter, open-label, phase II study (ClinicalTrials.gov identifier: NCT02150967) evaluated BGJ398 antitumor activity in patients age ≥ 18 years with advanced or metastatic cholangiocarcinoma containing FGFR2 fusions or other FGFR alterations whose disease had progressed while receiving prior therapy. Patients received BGJ398 125 mg once daily for 21 days, then 7 days off (28-day cycles). The primary end point was investigator-assessed overall response rate.ResultsSixty-one patients (35 women; median age, 57 years) with FGFR2 fusion (n = 48), mutation (n = 8), or amplification (n = 3) participated. ...
473 citations
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International Agency for Research on Cancer1, Université Paris-Saclay2, Lund University3, American University of Beirut4, University of North Carolina at Chapel Hill5, University of Regensburg6, Southampton General Hospital7, World Health Organization8, University of Amsterdam9, State University of New York System10, Maastricht University11, Mahidol University12, Harvard University13
TL;DR: Energy intake that exceeds energy expenditure is the main driver of weight gain and the quality of the diet may exert its effect on energy balance through complex hormonal and neurological pathways that influence satiety and possibly through other mechanisms.
Abstract: The aim of this paper is to review the evidence of the association between energy balance and obesity. In December 2015, the International Agency for Research on Cancer (IARC), Lyon, France convened a Working Group of international experts to review the evidence regarding energy balance and obesity, with a focus on Low and Middle Income Countries (LMIC). The global epidemic of obesity and the double burden, in LMICs, of malnutrition (coexistence of undernutrition and overnutrition) are both related to poor quality diet and unbalanced energy intake. Dietary patterns consistent with a traditional Mediterranean diet and other measures of diet quality can contribute to long-term weight control. Limiting consumption of sugar-sweetened beverages has a particularly important role in weight control. Genetic factors alone cannot explain the global epidemic of obesity. However, genetic, epigenetic factors and the microbiota could influence individual responses to diet and physical activity. Energy intake that exceeds energy expenditure is the main driver of weight gain. The quality of the diet may exert its effect on energy balance through complex hormonal and neurological pathways that influence satiety and possibly through other mechanisms. The food environment, marketing of unhealthy foods and urbanization, and reduction in sedentary behaviors and physical activity play important roles. Most of the evidence comes from High Income Countries and more research is needed in LMICs.
418 citations
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TL;DR: In this paper, the uncertainty of the Galactic Center (GC) excess spectrum and morphology due to uncertainties in cosmic-ray source distributions and propagation, uncertainties in the distribution of interstellar gas in the Milky Way, and uncertainties due to a potential contribution from the Fermi bubbles.
Abstract: The region around the Galactic Center (GC) is now well established to be brighter at energies of a few GeV than what is expected from conventional models of diffuse gamma-ray emission and catalogs of known gamma-ray sources. We study the GeV excess using 6.5 yr of data from the Fermi Large Area Telescope. We characterize the uncertainty of the GC excess spectrum and morphology due to uncertainties in cosmic-ray source distributions and propagation, uncertainties in the distribution of interstellar gas in the Milky Way, and uncertainties due to a potential contribution from the Fermi bubbles. We also evaluate uncertainties in the excess properties due to resolved point sources of gamma rays. The GC is of particular interest, as it would be expected to have the brightest signal from annihilation of weakly interacting massive dark matter (DM) particles. However, control regions along the Galactic plane, where a DM signal is not expected, show excesses of similar amplitude relative to the local background. Based on the magnitude of the systematic uncertainties, we conservatively report upper limits for the annihilation cross-section as a function of particle mass and annihilation channel.
355 citations
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TL;DR: The results suggest that the dominant artemisinin-resistant P falciparum C580Y lineage probably arose in western Cambodia and then spread to Thailand and Laos, outcompeting other parasites and acquiring piperaquine resistance.
Abstract: Summary Background Evidence suggests that the PfKelch13 mutations that confer artemisinin resistance in falciparum malaria have multiple independent origins across the Greater Mekong subregion, which has motivated a regional malaria elimination agenda. We aimed to use molecular genotyping to assess antimalarial drug resistance selection and spread in the Greater Mekong subregion. Methods In this observational study, we tested Plasmodium falciparum isolates from Myanmar, northeastern Thailand, southern Laos, and western Cambodia for PfKelch13 mutations and for Pfplasmepsin2 gene amplification (indicating piperaquine resistance). We collected blood spots from patients with microscopy or rapid test confirmed uncomplicated falciparum malaria. We used microsatellite genotyping to assess genetic relatedness. Findings As part of studies on the epidemiology of artemisinin-resistant malaria between Jan 1, 2008, and Dec 31, 2015, we collected 434 isolates. In 2014–15, a single long PfKelch13 C580Y haplotype (−50 to +31·5 kb) lineage, which emerged in western Cambodia in 2008, was detected in 65 of 88 isolates from northeastern Thailand, 86 of 111 isolates from southern Laos, and 14 of 14 isolates from western Cambodia, signifying a hard transnational selective sweep. Pfplasmepsin2 amplification occurred only within this lineage, and by 2015 these closely related parasites were found in ten of the 14 isolates from Cambodia and 15 of 15 isolates from northeastern Thailand. C580Y mutated parasites from Myanmar had a different genetic origin. Interpretation Our results suggest that the dominant artemisinin-resistant P falciparum C580Y lineage probably arose in western Cambodia and then spread to Thailand and Laos, outcompeting other parasites and acquiring piperaquine resistance. The emergence and spread of fit artemisinin-resistant P falciparum parasite lineages, which then acquire partner drug resistance across the Greater Mekong subregion, threatens regional malaria control and elimination goals. Elimination of falciparum malaria from this region should be accelerated while available antimalarial drugs still remain effective. Funding The Wellcome Trust and the Bill and Melinda Gates Foundation.
352 citations
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TL;DR: Accumulating data suggest an association between OSA and type 1 diabetes as well as gestational diabetes, and the impact of OSA treatment on glucose metabolism.
345 citations
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TL;DR: The mechanisms of actions of COS have been found to involve the modulation of several important pathways including the suppression of nuclear factor kappa B and mitogen‐activated protein kinases (MAPK and the activation of AMP‐activatedprotein kinase (AMPK).
341 citations
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National Institutes of Health1, University of Texas Health Science Center at San Antonio2, University of Sydney3, Broad Institute4, St George's, University of London5, Second Military Medical University6, University of Milan7, Pasteur Institute8, University of Adelaide9, Los Angeles Biomedical Research Institute10, Imperial College London11, Nagasaki University12, University of British Columbia13, Oswaldo Cruz Foundation14, University of Massachusetts Medical School15, University of Birmingham16, Mahidol University17, University of Alabama at Birmingham18, Duke University19, Robert Koch Institute20, Cornell University21, McMaster University22, Johns Hopkins University School of Medicine23
TL;DR: In the absence of biological differences between clades and no consensus about how DNA sequence alone can delineate a species, it is recommended to use “Cryptococcus neoformans species complex” and “C. gattii speciescomplex” as a practical intermediate step, rather than creating more species.
Abstract: Cryptococcosis is a potentially lethal disease of humans/animals caused by Cryptococcus neoformans and Cryptococcus gattii. Distinction between the two species is based on phenotypic and genotypic characteristics. Recently, it was proposed that C. neoformans be divided into two species and C. gattii into five species based on a phylogenetic analysis of 115 isolates. While this proposal adds to the knowledge about the genetic diversity and population structure of cryptococcosis agents, the published genotypes of 2,606 strains have already revealed more genetic diversity than is encompassed by seven species. Naming every clade as a separate species at this juncture will lead to continuing nomenclatural instability. In the absence of biological differences between clades and no consensus about how DNA sequence alone can delineate a species, we recommend using "Cryptococcus neoformans species complex" and "C. gattii species complex" as a practical intermediate step, rather than creating more species. This strategy recognizes genetic diversity without creating confusion.
331 citations
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TL;DR: The Third catalog of Hard Fermi-LAT Sources (3FHL) as mentioned in this paper contains 1556 objects characterized in the 10 GeV-2 TeV energy range.
Abstract: We present a catalog of sources detected above 10 GeV by the Fermi Large Area Telescope (LAT) in the first 7 years of data using the Pass 8 event-level analysis. This is the Third Catalog of Hard Fermi-LAT Sources (3FHL), containing 1556 objects characterized in the 10 GeV–2 TeV energy range. The sensitivity and angular resolution are improved by factors of 3 and 2 relative to the previous LAT catalog at the same energies (1FHL). The vast majority of detected sources (79%) are associated with extragalactic counterparts at other wavelengths, including 16 sources located at very high redshift (z > 2). Eight percent of the sources have Galactic counterparts and 13% are unassociated (or associated with a source of unknown nature). The high-latitude sky and the Galactic plane are observed with a flux sensitivity of 4.4 to 9.5 ×10 −11 ph cm −2 s −1 , respectively (this is approximately 0.5 % and 1 % of the Crab Nebula flux above 10 GeV). The catalog includes 214 new γ-ray sources. The substantial increase in the number of photons (more than 4 times relative to 1FHL and 10 times to 2FHL) also allows us to measure significant spectral curvature for 32 sources and find flux variability for 163 of them. Furthermore, we estimate that for the same flux limit of 10 −12 erg cm −2 s −1 , the energy range above 10 GeV has twice as many sources as above 50 GeV, highlighting the importance, for future Cherenkov telescopes, of lowering the energy threshold as much as possible.
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TL;DR: The exo-E415G SNP and plasmepsin 2-3 amplification are markers of piperquine resistance and dihydroartemisinin-piperaquine failures in Cambodia, and can help monitor the spread of these phenotypes into other countries of the Greater Mekong subregion, and elucidate the mechanism of p Piperaquine resistance.
Abstract: Summary Background As the prevalence of artemisinin-resistant Plasmodium falciparum malaria increases in the Greater Mekong subregion, emerging resistance to partner drugs in artemisinin combination therapies seriously threatens global efforts to treat and eliminate this disease. Molecular markers that predict failure of artemisinin combination therapy are urgently needed to monitor the spread of partner drug resistance, and to recommend alternative treatments in southeast Asia and beyond. Methods We did a genome-wide association study of 297 P falciparum isolates from Cambodia to investigate the relationship of 11 630 exonic single-nucleotide polymorphisms (SNPs) and 43 copy number variations (CNVs) with in-vitro piperaquine 50% inhibitory concentrations (IC 50 s), and tested whether these genetic variants are markers of treatment failure with dihydroartemisinin–piperaquine. We then did a survival analysis of 133 patients to determine whether candidate molecular markers predicted parasite recrudescence following dihydroartemisinin–piperaquine treatment. Findings Piperaquine IC 50 s increased significantly from 2011 to 2013 in three Cambodian provinces (2011 vs 2013 median IC 50 s: 20·0 nmol/L [IQR 13·7–29·0] vs 39·2 nmol/L [32·8–48·1] for Ratanakiri, 19·3 nmol/L [15·1–26·2] vs 66·2 nmol/L [49·9–83·0] for Preah Vihear, and 19·6 nmol/L [11·9–33·9] vs 81·1 nmol/L [61·3–113·1] for Pursat; all p≤10 −3 ; Kruskal-Wallis test). Genome-wide analysis of SNPs identified a chromosome 13 region that associates with raised piperaquine IC 50 s. A non-synonymous SNP (encoding a Glu415Gly substitution) in this region, within a gene encoding an exonuclease, associates with parasite recrudescence following dihydroartemisinin–piperaquine treatment. Genome-wide analysis of CNVs revealed that a single copy of the mdr1 gene on chromosome 5 and a novel amplification of the plasmepsin 2 and plasmepsin 3 genes on chromosome 14 also associate with raised piperaquine IC 50 s. After adjusting for covariates, both exo-E415G and plasmepsin 2–3 markers significantly associate (p=3·0 × 10 −8 and p=1·7 × 10 −7 , respectively) with decreased treatment efficacy (survival rates 0·38 [95% CI 0·25–0·51] and 0·41 [0·28–0·53], respectively). Interpretation The exo-E415G SNP and plasmepsin 2–3 amplification are markers of piperaquine resistance and dihydroartemisinin–piperaquine failures in Cambodia, and can help monitor the spread of these phenotypes into other countries of the Greater Mekong subregion, and elucidate the mechanism of piperaquine resistance. Since plasmepsins are involved in the parasite's haemoglobin-to-haemozoin conversion pathway, targeted by related antimalarials, plasmepsin 2–3 amplification probably mediates piperaquine resistance. Funding Intramural Research Program of the US National Institute of Allergy and Infectious Diseases, National Institutes of Health, Wellcome Trust, Bill & Melinda Gates Foundation, Medical Research Council, and UK Department for International Development.
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TL;DR: Elimination of artemisinin resistance will imply elimination of all falciparum malaria from the same areas, and novel regimens and strategies using existing antimalarial drugs will be needed until novel compounds can be deployed.
Abstract: Increasing antimalarial drug resistance once again threatens effective antimalarial drug treatment, malaria control, and elimination. Artemisinin combination therapies (ACTs) are first-line treatment for uncomplicated falciparum malaria in all endemic countries, yet partial resistance to artemisinins has emerged in the Greater Mekong Subregion. Concomitant emergence of partner drug resistance is now causing high ACT treatment failure rates in several areas. Genetic markers for artemisinin resistance and several of the partner drugs have been established, greatly facilitating surveillance. Single point mutations in the gene coding for the Kelch propeller domain of the K13 protein strongly correlate with artemisinin resistance. Novel regimens and strategies using existing antimalarial drugs will be needed until novel compounds can be deployed. Elimination of artemisinin resistance will imply elimination of all falciparum malaria from the same areas. In vivax malaria, chloroquine resistance is an increasing problem.
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TL;DR: It is discovered that DHF/DSS patients respond to infection by producing IgGs with enhanced affinity for the activating Fc receptor FcγRIIIA due to afucosylated Fc glycans and IgG1 subclass, which is implicated in severe dengue disease during secondary infections.
Abstract: Dengue virus (DENV) infection in the presence of reactive, non-neutralizing immunoglobulin G (IgG) (RNNIg) is the greatest risk factor for dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Progression to DHF/DSS is attributed to antibody-dependent enhancement (ADE); however, because only a fraction of infections occurring in the presence of RNNIg advance to DHF/DSS, the presence of RNNIg alone cannot account for disease severity. We discovered that DHF/DSS patients respond to infection by producing IgGs with enhanced affinity for the activating Fc receptor FcγRIIIA due to afucosylated Fc glycans and IgG1 subclass. RNNIg enriched for afucosylated IgG1 triggered platelet reduction in vivo and was a significant risk factor for thrombocytopenia. Thus, therapeutics and vaccines restricting production of afucosylated, IgG1 RNNIg during infection may prevent ADE of DENV disease.
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TL;DR: The density of the retinal capillary microvasculature is reduced and the area of flow deficit in the CC is increased in eyes with greater myopia, and the relevance of microvascular alterations in the setting of myopia warrants further study.
Abstract: Purpose To study the retinal capillary microvasculature and the choriocapillaris (CC) in myopic eyes using quantitative optical coherence tomography angiography (OCTA) analysis. Methods Macular OCTA images of 3 × 3 mm were obtained using the RTVue-XR Avanti with AngioVue. Quantitative measurements of the retinal capillary microvascular layers and the CC were analyzed using en face projection images. Vessel density and fractal dimension of the superficial and deep retinal capillary plexus, and area and density of flow reduction in the CC were analyzed, quantified, and compared with an age-matched control group. Results Fifty eyes with myopia and 34 age-matched healthy eyes were included in this study. The vessel density and the vessel branching complexity using fractal dimension of the retinal capillary microvasculature were significantly lower in myopic eyes (P < 0.001 and P = 0.001). The total number of flow voids in the CC was lower (108.93 vs. 138.63, P = 0.001) but the total and average flow void area was significantly higher (total area 3.715 ± 0.257 vs. 3.596 ± 0.194 mm2, P = 0.026; average area 0.044 ± 0.029 vs. 0.028 ± 0.010 mm2, P = 0.002) compared with the healthy control group. Average choroidal thickness was lower in the myopic group versus the normal control cohort (123.538 ± 73.477 vs. 246.97 ± 41.745 μm, P < 0.05) and significantly reduced in eyes with lacquer cracks (LC) compared with myopic eyes without LC formation (P = 0.003). There was no correlation between choroidal thickness and quantitative parameters of the CC in the myopic eyes. Conclusions The density of the retinal capillary microvasculature is reduced and the area of flow deficit in the CC is increased in eyes with greater myopia. The relevance of microvascular alterations in the setting of myopia warrants further study.
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Brigham and Women's Hospital1, Harvard University2, Johns Hopkins University3, International Rescue Committee4, University of London5, World Health Organization6, Universidade Federal de Pelotas7, Columbia University8, University of Copenhagen9, University of North Carolina at Chapel Hill10, Universidade Católica de Pelotas11, Aga Khan University12, Bill & Melinda Gates Foundation13, Pontifical Catholic University of Chile14, Ghent University15, International Food Policy Research Institute16, Kenya Medical Research Institute17, Centers for Disease Control and Prevention18, National Institute for Medical Research19, Kathmandu20, Mahidol University21, University of Los Andes22, University College London23, Liverpool School of Tropical Medicine24, Malawi-Liverpool-Wellcome Trust Clinical Research Programme25, George Washington University26, University of the Witwatersrand27, Imperial College London28
TL;DR: In low and middle income countries, about one in five infants are born small for gestational age, and one in four neonatal deaths are among such infants, so increased efforts are required to improve the quality of care for and survival of these high risk infants.
Abstract: Objectives To estimate small for gestational age birth prevalence and attributable neonatal mortality in low and middle income countries with the INTERGROWTH-21 st birth weight standard. Design Secondary analysis of data from the Child Health Epidemiology Reference Group (CHERG), including 14 birth cohorts with gestational age, birth weight, and neonatal follow-up. Small for gestational age was defined as infants weighing less than the 10th centile birth weight for gestational age and sex with the multiethnic, INTERGROWTH-21 st birth weight standard. Prevalence of small for gestational age and neonatal mortality risk ratios were calculated and pooled among these datasets at the regional level. With available national level data, prevalence of small for gestational age and population attributable fractions of neonatal mortality attributable to small for gestational age were estimated. Setting CHERG birth cohorts from 14 population based sites in low and middle income countries. Main outcome measures In low and middle income countries in the year 2012, the number and proportion of infants born small for gestational age; number and proportion of neonatal deaths attributable to small for gestational age; the number and proportion of neonatal deaths that could be prevented by reducing the prevalence of small for gestational age to 10%. Results In 2012, an estimated 23.3 million infants (uncertainty range 17.6 to 31.9; 19.3% of live births) were born small for gestational age in low and middle income countries. Among these, 11.2 million (0.8 to 15.8) were term and not low birth weight (≥2500 g), 10.7 million (7.6 to 15.0) were term and low birth weight ( Conclusions In low and middle income countries, about one in five infants are born small for gestational age, and one in four neonatal deaths are among such infants. Increased efforts are required to improve the quality of care for and survival of these high risk infants in low and middle income countries
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TL;DR: Resistance to artemisinin resistance in Plasmodium falciparum is observed in a patient who was working in Equatorial Guinea.
Abstract: The emergence of artemisinin resistance in Plasmodium falciparum has threatened the effectiveness of malaria treatment in Southeast Asia. In this report, such resistance has been observed in a patient who was working in Equatorial Guinea.
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TL;DR: It is found that the ability of the EC to bind targets genome-wide depends on temperature, and co-occurrence of phytochrome B at multiple sites where the EC is bound provides a mechanism for integrating environmental information.
Abstract: Plants maximize their fitness by adjusting their growth and development in response to signals such as light and temperature. The circadian clock provides a mechanism for plants to anticipate events such as sunrise and adjust their transcriptional programmes. However, the underlying mechanisms by which plants coordinate environmental signals with endogenous pathways are not fully understood. Using RNA-sequencing and chromatin immunoprecipitation sequencing experiments, we show that the evening complex (EC) of the circadian clock plays a major role in directly coordinating the expression of hundreds of key regulators of photosynthesis, the circadian clock, phytohormone signalling, growth and response to the environment. We find that the ability of the EC to bind targets genome-wide depends on temperature. In addition, co-occurrence of phytochrome B (phyB) at multiple sites where the EC is bound provides a mechanism for integrating environmental information. Hence, our results show that the EC plays a central role in coordinating endogenous and environmental signals in Arabidopsis.
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Washington University in St. Louis1, Smithsonian Conservation Biology Institute2, United States Geological Survey3, Thailand National Science and Technology Development Agency4, Mahidol University5, Department of National Parks, Wildlife and Plant Conservation6, Tunghai University7, University of Buea8, Indiana University9, Smithsonian Tropical Research Institute10, United States Department of Agriculture11, National Museum of Natural History12, Utah State University13, University of Peradeniya14, University of Alberta15, Sun Yat-sen University16, University of Wisconsin–Green Bay17, University of California, Los Angeles18, National Taiwan University19, Los Alamos National Laboratory20, University of Montana21, Smithsonian Environmental Research Center22, Centre national de la recherche scientifique23, Academy of Sciences of the Czech Republic24, Sewanee: The University of the South25, University of the Philippines Diliman26, Harvard University27, University of Hawaii at Hilo28, National Dong Hwa University29, Missouri Botanical Garden30, Washington State University Vancouver31, University of Minnesota32, Far Eastern University33
TL;DR: Global patterns in tree species diversity reflect not only stronger CNDD at tropical versus temperate latitudes but also a latitudinal shift in the relationship between CNDd and species abundance.
Abstract: Theory predicts that higher biodiversity in the tropics is maintained by specialized interactions among plants and their natural enemies that result in conspecific negative density dependence (CNDD). By using more than 3000 species and nearly 2.4 million trees across 24 forest plots worldwide, we show that global patterns in tree species diversity reflect not only stronger CNDD at tropical versus temperate latitudes but also a latitudinal shift in the relationship between CNDD and species abundance. CNDD was stronger for rare species at tropical versus temperate latitudes, potentially causing the persistence of greater numbers of rare species in the tropics. Our study reveals fundamental differences in the nature of local-scale biotic interactions that contribute to the maintenance of species diversity across temperate and tropical communities.
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TL;DR: It is shown that Gli1+ mesenchymal stromal cells are recruited from the endosteal and perivascular niche to become fibrosis-driving myofibroblasts in the bone marrow, and Gli1 expression in BMF significantly correlates with the severity of the disease.
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TL;DR: Scrub typhus appears to be a truly neglected tropical disease mainly affecting rural populations, but increasingly also metropolitan areas, and rising minimum incidence rates have been reported over the past 8–10 years from countries with an established surveillance system.
Abstract: Background
Scrub typhus is a vector-borne zoonotic disease that can be life-threatening. There are no licensed vaccines, or vector control efforts in place. Despite increasing awareness in endemic regions, the public health burden and global distribution of scrub typhus remains poorly known.
Methods
We systematically reviewed all literature from public health records, fever studies and reports available on the Ovid MEDLINE, Embase Classic + Embase and EconLit databases, to estimate the burden of scrub typhus since the year 2000.
Findings
In prospective fever studies from Asia, scrub typhus is a leading cause of treatable non-malarial febrile illness. Sero-epidemiological data also suggest that Orientia tsutsugamushi infection is common across Asia, with seroprevalence ranging from 9.3%–27.9% (median 22.2% IQR 18.6–25.7). A substantial apparent rise in minimum disease incidence (median 4.6/100,000/10 years, highest in China with 11.2/100,000/10 years) was reported through passive national surveillance systems in South Korea, Japan, China, and Thailand. Case fatality risks from areas of reduced drug-susceptibility are reported at 12.2% and 13.6% for South India and northern Thailand, respectively. Mortality reports vary widely around a median mortality of 6.0% for untreated and 1.4% for treated scrub typhus. Limited evidence suggests high mortality in complicated scrub typhus with CNS involvement (13.6% mortality), multi-organ dysfunction (24.1%) and high pregnancy miscarriage rates with poor neonatal outcomes.
Interpretation
Scrub typhus appears to be a truly neglected tropical disease mainly affecting rural populations, but increasingly also metropolitan areas. Rising minimum incidence rates have been reported over the past 8–10 years from countries with an established surveillance system. A wider distribution of scrub typhus beyond Asia is likely, based on reports from South America and Africa. Unfortunately, the quality and quantity of the available data on scrub typhus epidemiology is currently too limited for any economical, mathematical modeling or mapping approaches.
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TL;DR: The authors (GDS, KS) acknowledge funding administered by the British Council under the Newton Fund Researcher Links Programme, for a UK-Thailand bilateral workshop entitled "Scientific, technological and social solutions for sustainable aquaculture in Thailand: a key player in global aquatic food supply," Bangkok, March 2016.
Abstract: The authors (GDS, KS) acknowledge funding administered by the British Council under the Newton Fund Researcher Links Programme, for a UK-Thailand bilateral workshop entitled "Scientific, technological and social solutions for sustainable aquaculture in Thailand: a key player in global aquatic food supply," Bangkok, March 2016. Further funding support is acknowledged from the European Commission (EC) and the UK Department for Environment, Food and Rural Affairs (Defra) under contracts C6928 and FB002 (to GDS and DB); from the Royal Society under a University Research Fellowship (to BAPW); and to the Agricultural Research Development Agency (ARDA) and National Research Council of Thailand (NRCT) (to KS, TWF, and OI). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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TL;DR: Extant evidence supports the association between obesity and adverse health outcomes among individuals with depressive disorders and the treatment of one condition appears to improve the course of the other condition.
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TL;DR: Fair to poor OH increases the risk of periodontitis by two‐ to five‐fold, and this risk can be reduced by regular toothbrushing and dental visits.
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Hiroshima University1, Clemson University2, Santa Cruz Institute for Particle Physics3, Istituto Nazionale di Fisica Nucleare4, Stanford University5, Goddard Space Flight Center6, University of St Andrews7, Agenzia Spaziale Italiana8, George Mason University9, Fermilab10, University of Iceland11, Tokyo University of Science12, Mahidol University13, Max Planck Society14, University of Padua15, University of Innsbruck16, Nagoya University17, Institut de Ciències de l'Espai18, University of Denver19, University of Geneva20
TL;DR: In this paper, a measurement of the cosmic-ray electron+positron spectrum between 7 GeV and 2 TeV was performed with almost seven years of data collected with the Fermi Large Area Telescope.
Abstract: We present a measurement of the cosmic-ray electron+positron spectrum between 7 GeV and 2 TeV performed with almost seven years of data collected with the Fermi Large Area Telescope. We find that the spectrum is well fit by a broken power law with a break energy at about 50 GeV. Above 50 GeV, the spectrum is well described by a single power law with a spectral index of 3.07 ± 0.02 (stat+syst) ± 0.04 (energy measurement). An exponential cutoff lower than 1.8 TeV is excluded at 95% CL. PACS numbers: 98.70.Sa, 96.50.sb, 95.85.Ry, 95.55.Vj
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TL;DR: Clinical efficacy data from the region is reviewed that provides strong evidence that the loss of first‐line ACTs in western Cambodia, first artesunate‐mefloquine and then DHA‐piperaquine, can be attributed primarily to K13 mutated parasites.
Abstract: Artemisinins are the most rapidly acting of currently available antimalarial drugs. Artesunate has become the treatment of choice for severe malaria, and artemisinin-based combination therapies (ACTs) are the foundation of modern falciparum malaria treatment globally. Their safety and tolerability profile is excellent. Unfortunately, Plasmodium falciparum infections with mutations in the 'K13' gene, with reduced ring-stage susceptibility to artemisinins, and slow parasite clearance in patients treated with ACTs, are now widespread in Southeast Asia. We review clinical efficacy data from the region (2000-2015) that provides strong evidence that the loss of first-line ACTs in western Cambodia, first artesunate-mefloquine and then DHA-piperaquine, can be attributed primarily to K13 mutated parasites. The ring-stage activity of artemisinins is therefore critical for the sustained efficacy of ACTs; once it is lost, rapid selection of partner drug resistance and ACT failure are inevitable consequences. Consensus methods for monitoring artemisinin resistance are now available. Despite increased investment in regional control activities, ACTs are failing across an expanding area of the Greater Mekong subregion. Although multiple K13 mutations have arisen independently, successful multidrug-resistant parasite genotypes are taking over and threaten to spread to India and Africa. Stronger containment efforts and new approaches to sustaining long-term efficacy of antimalarial regimens are needed to prevent a global malaria emergency.
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TL;DR: This work demonstrates a synergistic strategy to prepare efficient metal-free B-g-C3N4 nanosheets as a promising photocatalyst for H2 evolution under visible light with good stability.
Abstract: A new type of boron-doped graphitic carbon nitride (B-g-C3N4) nanosheets was prepared by a benign one-pot thermal polycondensation process. Systematic studies revealed that a B-doping amount of 1 at% into g-C3N4 (1at%B-g-C3N4) showed the best photocatalytic H2 evolution activity of 1880 μmol h−1 g−1 under visible light irradiation (>400 nm), which is more than 12 times that of the pristine g-C3N4 bulk. Detailed characterizations revealed that the high photocatalytic performance could be attributed to the combination of band structure engineering and morphological control. B-doping not only reduces the band gap to absorb more visible light but also exhibits a higher surface area of B-g-C3N4 (49.47 m2 g−1) as compared to that of g-C3N4 bulk (8.24 m2 g−1), which subsequently improve the photocatalytic performance drastically. This work demonstrates a synergistic strategy to prepare efficient metal-free B-g-C3N4 nanosheets as a promising photocatalyst for H2 evolution under visible light with good stability.
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TL;DR: In this article, the authors examined the influences of socioeconomic factors and climate adaptation communication processes on farmers' decision to apply adaptation strategies against drought and flood, and found that farmers' intention to adapt was mostly affected by perceived behavioral control factors, followed by attitude and subjective norms.
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TL;DR: Two isolates of non-A.
Abstract: Diseases caused by motile aeromonads in freshwater fish have been generally assumed to be linked with mainly Aeromonas hydrophila while other species were probably overlooked. Here, we identified two isolates of non-A. hydrophila recovered from Nile tilapia exhibiting disease and mortality after exposed to transport-induced stress and subsequently confirmed their virulence in artificial infection. The bacterial isolates were identified as Aeromonas jandaei and Aeromonas veronii based on phenotypic features and homology of 16S rDNA. Experimental infection revealed that the high dose of A. jandaei (3.7 × 106 CFU fish−1) and A. veronii (8.9 × 106 CFU fish−1) killed 100% of experimental fish within 24 h, while a 10-fold reduction dose killed 70% and 50% of fish, respectively. When the challenge dose was reduced 100-fold, mortality of the fish exposed to A. jandaei and A. veronii decreased to 20% and 10%, respectively. The survivors from the latter dose administration were rechallenged with respective bacterial species. Lower mortality of rechallenged fish (0%–12.5%) compared to the control groups receiving a primary infection (37.5%) suggested that the survivors after primary infection were able to resist secondary infection. Fish exposed to either A. jandaei or A. veronii exhibited similar clinical signs and histological manifestation.
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Harvard University1, Paris Descartes University2, French Institute of Health and Medical Research3, Université Paris-Saclay4, University of Paris5, Autonomous University of Barcelona6, McGill University7, Massachusetts Institute of Technology8, Ghent University9, University of Freiburg10, Yonsei University11, University of Erlangen-Nuremberg12, University of Münster13, Max Planck Society14, National Institutes of Health15, Iran University of Medical Sciences16, King Edward Memorial Hospital17, GeneDx18, Hospital Kuala Lumpur19, Mackay Memorial Hospital20, Boston Children's Hospital21, Oklahoma Medical Research Foundation22, University of Michigan23, King Abdulaziz University24, Université de Montréal25, Baylor College of Medicine26, University of Jordan27, University of Tehran28, Yamagata University29, Hacettepe University30, University of Western Ontario31, University of Groningen32, Guy's and St Thomas' NHS Foundation Trust33, Cairo University34, Taipei Medical University35, University of Duisburg-Essen36, University of Utah37, Mahidol University38, University of Oklahoma39, University of Texas Southwestern Medical Center40, Tuen Mun Hospital41, Singapore–MIT alliance42, Yale University43, Rockefeller University44, University of Toronto45, Rambam Health Care Campus46
TL;DR: Four new monogenic causes of GAMOS are identified, a link between KEOPS function and human disease is described, and potential pathogenic mechanisms are delineated.
Abstract: Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms.