Showing papers by "Mahidol University published in 2019"
TL;DR: Overall survival was significantly longer in the pembrolizumab group than in the chemotherapy group in all three TPS populations, and the benefit-to-risk profile suggests that first-line pembrology monotherapy can be extended as first line therapy for locally advanced or metastatic non-small-cell lung cancer patients with sensitising EGFR or ALK translocation.
1,999 citations
TL;DR: To better understand the epidemiology of preterm birth, the quality and volume of data needs to be improved, including standardisation of definitions, measurement, and reporting.
1,579 citations
Barbara Burtness1, Kevin J. Harrington2, Richard Greil, Denis Soulières3 +202 more•Institutions (18)
TL;DR: A randomised, phase 3 study of participants with untreated locally incurable recurrent or metastatic HNSCC done at 200 sites in 37 countries finds that pembrolizumab alone improved overall survival and progression-free survival and cetuximab with chemotherapy improved Overall survival in the total population.
1,490 citations
Carlos III Health Institute1, University of Cologne2, University of Sydney3, Paris Descartes University4, Universidade Federal de Ciências da Saúde de Porto Alegre5, Pontifícia Universidade Católica do Rio Grande do Sul6, Medical University of Graz7, University of California, San Diego8, University of Copenhagen9, Katholieke Universiteit Leuven10, University of Bologna11, University of the Witwatersrand12, RMIT University13, McGill University14, Hacettepe University15, University of Paris16, Utrecht University17, Mazandaran University of Medical Sciences18, Tel Aviv University19, Hospital General de México20, Istituto Giannina Gaslini21, Mahidol University22, Federal University of São Paulo23, King's College, Aberdeen24, Comenius University in Bratislava25, Boston Children's Hospital26, Hospital General Universitario Gregorio Marañón27, Complutense University of Madrid28, University Hospital Heidelberg29, University of California, Los Angeles30, American University of Beirut31, Innsbruck Medical University32, University of Lausanne33, Catholic University of Korea34, Goethe University Frankfurt35, National and Kapodistrian University of Athens36, Erasmus University Rotterdam37, Monash University38, Federal University of Rio de Janeiro39, Catholic University of the Sacred Heart40, University of Health Sciences Antigua41, National Institutes of Health42, Amrita Institute of Medical Sciences and Research Centre43, University of Pittsburgh44, Peter MacCallum Cancer Centre45, University of Melbourne46, P. D. Hinduja Hospital and Medical Research Centre47, University of Southern California48, Duke University49, Singapore General Hospital50, NewYork–Presbyterian Hospital51, Cardiff University52, University of Texas Health Science Center at San Antonio53, Children's Hospital of Philadelphia54, Post Graduate Institute of Medical Education and Research55
TL;DR: Management of mucormycosis depends on recognising disease patterns and on early diagnosis, and limited availability of contemporary treatments burdens patients in low and middle income settings.
Abstract: Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence on mucormycosis management and provided consensus recommendations addressing differences between the regions of the world as part of the "One World One Guideline" initiative of the European Confederation of Medical Mycology (ECMM). Diagnostic management does not differ greatly between world regions. Upon suspicion of mucormycosis appropriate imaging is strongly recommended to document extent of disease and is followed by strongly recommended surgical intervention. First-line treatment with high-dose liposomal amphotericin B is strongly recommended, while intravenous isavuconazole and intravenous or delayed release tablet posaconazole are recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty were identified and future research directions specified.
842 citations
TL;DR: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community providing the theory and key practical aspects offlow cytometry enabling immunologists to avoid the common errors that often undermine immunological data.
Abstract: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
698 citations
State University of New York System1, Detroit Medical Center2, Universidade Federal do Rio Grande do Sul3, Rappaport Faculty of Medicine4, Rambam Health Care Campus5, National and Kapodistrian University of Athens6, University of North Carolina at Chapel Hill7, University of Genoa8, Drexel University9, Erasmus University Rotterdam10, University of Houston11, Mahidol University12, Northwestern University13, Monash University, Clayton campus14, Monash University15, University of Michigan16
TL;DR: In this paper, the authors report consensus therapeutic guidelines for agent selection and dosing of colistin and polymyxin antibiotics for optimal use in adult patients, as endorsed by the American College of Clinical Pharmacy (ACCP), Infectious Diseases Society of America (IDSA), International Society of Anti-Infective Pharmacology (ISAP), Society for Critical Care Medicine (SCCM), and Society of Infectious diseases Pharmacists (SIDP).
Abstract: The polymyxin antibiotics colistin (polymyxin E) and polymyxin B became available in the 1950s and thus did not undergo contemporary drug development procedures. Their clinical use has recently resurged, assuming an important role as salvage therapy for otherwise untreatable gram-negative infections. Since their reintroduction into the clinic, significant confusion remains due to the existence of several different conventions used to describe doses of the polymyxins, differences in their formulations, outdated product information, and uncertainties about susceptibility testing that has led to lack of clarity on how to optimally utilize and dose colistin and polymyxin B. We report consensus therapeutic guidelines for agent selection and dosing of the polymyxin antibiotics for optimal use in adult patients, as endorsed by the American College of Clinical Pharmacy (ACCP), Infectious Diseases Society of America (IDSA), International Society of Anti-Infective Pharmacology (ISAP), Society for Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). The European Society for Clinical Microbiology and Infectious Diseases (ESCMID) endorses this document as a consensus statement. The overall conclusions in the document are endorsed by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). We established a diverse international expert panel to make therapeutic recommendations regarding the pharmacokinetic and pharmacodynamic properties of the drugs and pharmacokinetic targets, polymyxin agent selection, dosing, dosage adjustment and monitoring of colistin and polymyxin B, use of polymyxin-based combination therapy, intrathecal therapy, inhalation therapy, toxicity, and prevention of renal failure. The treatment guidelines provide the first ever consensus recommendations for colistin and polymyxin B therapy that are intended to guide optimal clinical use.
446 citations
University of Leicester1, University of Melbourne2, Walter and Eliza Hall Institute of Medical Research3, Brigham and Women's Hospital4, GlaxoSmithKline5, Mahidol University6, University of Arizona7, University of Oxford8, University of British Columbia9, University of Cambridge10, Imperial College London11, Greifswald University Hospital12, University of Edinburgh13, University of Liverpool14, Sir Charles Gairdner Hospital15, Swiss Tropical and Public Health Institute16, Science for Life Laboratory17, University of Helsinki18, University of Tampere19, University of Bergen20, Johns Hopkins University21, Laval University22, University Medical Center Groningen23, Icahn School of Medicine at Mount Sinai24, Anschutz Medical Campus25, Peking University26, Uppsala University27, Wellcome Trust Centre for Human Genetics28, Merck & Co.29, University of Aberdeen30, University of Münster31, University of Nottingham32, University of Dundee33, Autonomous University of Barcelona34, VA Boston Healthcare System35, University of California, San Francisco36, Princeton University37, Turku University Hospital38, University of Split39, University of Basel40, University of Western Australia41, Wellcome Trust Sanger Institute42, St George's, University of London43, National Institute for Health Research44
TL;DR: In this paper, a genome-wide association study in 400,102 individuals of European ancestry was conducted to define 279 lung function signals, 139 of which are new and the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups.
Abstract: Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.
295 citations
TL;DR: In this article, a modularized neural network for low-dose CT (LDCT) was proposed and compared with commercial iterative reconstruction methods from three leading CT vendors, and the learned workflow allows radiologists-in-the-loop to optimize the denoising depth in a task-specific fashion.
Abstract: Commercial iterative reconstruction techniques help to reduce CT radiation dose but altered image appearance and artifacts limit their adoptability and potential use. Deep learning has been investigated for low-dose CT (LDCT). Here we design a modularized neural network for LDCT and compared it with commercial iterative reconstruction methods from three leading CT vendors. While popular networks are trained for an end-to-end mapping, our network performs an end-to-process mapping so that intermediate denoised images are obtained with associated noise reduction directions towards a final denoised image. The learned workflow allows radiologists-in-the-loop to optimize the denoising depth in a task-specific fashion. Our network was trained with the Mayo LDCT Dataset, and tested on separate chest and abdominal CT exams from Massachusetts General Hospital. The best deep learning reconstructions were systematically compared to the best iterative reconstructions in a double-blinded reader study. This study confirms that our deep learning approach performed either favorably or comparably in terms of noise suppression and structural fidelity, and is much faster than the commercial iterative reconstruction algorithms.
265 citations
TL;DR: Dihydroartemisinin-piperaquine is not treating malaria effectively across the eastern Greater Mekong subregion, and a highly drug-resistant P falciparum co-lineage is evolving, acquiring new resistance mechanisms, and spreading.
Abstract: Summary Background The emergence and spread of resistance in Plasmodium falciparum malaria to artemisinin combination therapies in the Greater Mekong subregion poses a major threat to malaria control and elimination. The current study is part of a multi-country, open-label, randomised clinical trial (TRACII, 2015–18) evaluating the efficacy, safety, and tolerability of triple artemisinin combination therapies. A very high rate of treatment failure after treatment with dihydroartemisinin-piperaquine was observed in Thailand, Cambodia, and Vietnam. The immediate public health importance of our findings prompted us to report the efficacy data on dihydroartemisinin-piperaquine and its determinants ahead of the results of the overall trial, which will be published later this year. Methods Patients aged between 2 and 65 years presenting with uncomplicated P falciparum or mixed species malaria at seven sites in Thailand, Cambodia, and Vietnam were randomly assigned to receive dihydroartemisinin-piperaquine with or without mefloquine, as part of the TRACII trial. The primary outcome was the PCR-corrected efficacy at day 42. Next-generation sequencing was used to assess the prevalence of molecular markers associated with artemisinin resistance ( kelch13 mutations, in particular Cys580Tyr) and piperaquine resistance ( plasmepsin-2 and plasmepsin-3 amplifications and crt mutations). This study is registered with ClinicalTrials.gov , number NCT02453308 . Findings Between Sept 28, 2015, and Jan 18, 2018, 539 patients with acute P falciparum malaria were screened for eligibility, 292 were enrolled, and 140 received dihydroartemisinin-piperaquine. The overall Kaplan-Meier estimate of PCR-corrected efficacy of dihydroartemisinin-piperaquine at day 42 was 50·0% (95% CI 41·1–58·3). PCR-corrected efficacies for individual sites were 12·7% (2·2–33·0) in northeastern Thailand, 38·2% (15·9–60·5) in western Cambodia, 73·4% (57·0–84·3) in Ratanakiri (northeastern Cambodia), and 47·1% (33·5–59·6) in Binh Phuoc (southwestern Vietnam). Treatment failure was associated independently with plasmepsin2/3 amplification status and four mutations in the crt gene (Thr93Ser, His97Tyr, Phe145Ile, and Ile218Phe). Compared with the results of our previous TRACI trial in 2011–13, the prevalence of molecular markers of artemisinin resistance ( kelch13 Cys580Tyr mutations) and piperaquine resistance ( plasmepsin2/3 amplifications and crt mutations) has increased substantially in the Greater Mekong subregion in the past decade. Interpretation Dihydroartemisinin-piperaquine is not treating malaria effectively across the eastern Greater Mekong subregion. A highly drug-resistant P falciparum co-lineage is evolving, acquiring new resistance mechanisms, and spreading. Accelerated elimination of P falciparum malaria in this region is needed urgently, to prevent further spread and avoid a potential global health emergency. Funding UK Department for International Development, Wellcome Trust, Bill & Melinda Gates Foundation, Medical Research Council, and National Institutes of Health.
227 citations
Brigham and Women's Hospital1, Mahidol University2, Harvard University3, University of Leicester4, University of Washington5, New Generation University College6, National Institutes of Health7, Boston University8, University of Arizona9, University of British Columbia10, University of Bergen11, Columbia University12, Johns Hopkins University13, Lovelace Respiratory Research Institute14, Erasmus University Rotterdam15, Ghent University Hospital16, University Medical Center Groningen17, University of Colorado Denver18, University of Nottingham19, National Institute for Health Research20, Anschutz Medical Campus21, Kangwon National University22, University College London23, University of Nebraska Medical Center24, AstraZeneca25, St George's, University of London26, GlaxoSmithKline27, University of Manchester28, Laval University29, University of Virginia30, Ghent University31
TL;DR: This paper performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium and identified 82 loci associated with P < 5'×'10'8; 47 of these were previously described in association with either COPD or population-based measures of lung function.
Abstract: Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 × 10-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.
226 citations
University of California, San Francisco1, University of California, San Diego2, University of Oxford3, University of Health and Allied Sciences4, Pennsylvania State University5, Harvard University6, University of Washington7, Mahidol University8, National Institute of Malaria Research9, The Global Fund to Fight AIDS, Tuberculosis and Malaria10, University College London11, Bill & Melinda Gates Foundation12, Chinese Center for Disease Control and Prevention13, Duke University14, National University of Colombia15, Universiti Malaysia Sarawak16
TL;DR: Authors: Richard G. A. Feachem, Ingrid Chen*, Omar Akbari‡, Amelia Bertozzi-Villa, Samir Bhatt, Fred Binka, Maciej Boni, Caroline Buckee, Joseph Dieleman, Arjen Dondorp, Neelam Sekhri FeAChem, Scott Filler, Peter Gething, Roly Gosling, Annie Haakenstad.
TL;DR: After emerging and circulating for several years within Cambodia, the P falciparum KEL1/PLA1 co-lineage diversified into multiple subgroups and acquired new genetic features, including novel crt mutations.
Abstract: Summary Background A multidrug-resistant co-lineage of Plasmodium falciparum malaria, named KEL1/PLA1, spread across Cambodia in 2008–13, causing high rates of treatment failure with the frontline combination therapy dihydroartemisinin-piperaquine. Here, we report on the evolution and spread of KEL1/PLA1 in subsequent years. Methods For this genomic epidemiology study, we analysed whole genome sequencing data from P falciparum clinical samples collected from patients with malaria between 2007 and 2018 from Cambodia, Laos, northeastern Thailand, and Vietnam, through the MalariaGEN P falciparum Community Project. Previously unpublished samples were provided by two large-scale multisite projects: the Tracking Artemisinin Resistance Collaboration II (TRAC2) and the Genetic Reconnaissance in the Greater Mekong Subregion (GenRe-Mekong) project. By investigating genome-wide relatedness between parasites, we inferred patterns of shared ancestry in the KEL1/PLA1 population. Findings We analysed 1673 whole genome sequences that passed quality filters, and determined KEL1/PLA1 status in 1615. Before 2009, KEL1/PLA1 was only found in western Cambodia; by 2016–17 its prevalence had risen to higher than 50% in all of the surveyed countries except for Laos. In northeastern Thailand and Vietnam, KEL1/PLA1 exceeded 80% of the most recent P falciparum parasites. KEL1/PLA1 parasites maintained high genetic relatedness and low diversity, reflecting a recent common origin. Several subgroups of highly related parasites have recently emerged within this co-lineage, with diverse geographical distributions. The three largest of these subgroups (n=84, n=79, and n=47) mostly emerged since 2016 and were all present in Cambodia, Laos, and Vietnam. These expanding subgroups carried new mutations in the crt gene, which arose on a specific genetic background comprising multiple genomic regions. Four newly emerging crt mutations were rare in the early period and became more prevalent by 2016–17 (Thr93Ser, rising to 19·8%; His97Tyr to 11·2%; Phe145Ile to 5·5%; and Ile218Phe to 11·1%). Interpretation After emerging and circulating for several years within Cambodia, the P falciparum KEL1/PLA1 co-lineage diversified into multiple subgroups and acquired new genetic features, including novel crt mutations. These subgroups have rapidly spread into neighbouring countries, suggesting enhanced fitness. These findings highlight the urgent need for elimination of this increasingly drug-resistant parasite co-lineage, and the importance of genetic surveillance in accelerating malaria elimination efforts. Funding Wellcome Trust, Bill & Melinda Gates Foundation, UK Medical Research Council, and UK Department for International Development.
TL;DR: Early norepinephrine was significantly associated with increased shock control by 6 hours in adults diagnosed with sepsis with hypotension and further studies are needed before this approach is introduced in clinical resuscitation practice.
Abstract: Rationale: Recent retrospective evidence suggests the efficacy of early norepinephrine administration during resuscitation; however, prospective data to support this assertion are scarce.Objectives...
TL;DR: In this article, the authors presented the second catalog of LAT-detected GRBs, covering the first 10 yr of operations, from 2008 to 2018 August 4, and found a total of 186 GRBs are found; of these, 91 showed emission in the range 30-100 MeV (17 of which were seen only in this band) and 169 are detected above 100 MeV.
Abstract: The Large Area Telescope (LAT) aboard the Fermi spacecraft routinely observes high-energy emission from gamma-ray bursts (GRBs). Here we present the second catalog of LAT-detected GRBs, covering the first 10 yr of operations, from 2008 to 2018 August 4. A total of 186 GRBs are found; of these, 91 show emission in the range 30–100 MeV (17 of which are seen only in this band) and 169 are detected above 100 MeV. Most of these sources were discovered by other instruments (Fermi/GBM, Swift/BAT, AGILE, INTEGRAL) or reported by the Interplanetary Network (IPN); the LAT has independently triggered on four GRBs. This catalog presents the results for all 186 GRBs. We study onset, duration, and temporal properties of each GRB, as well as spectral characteristics in the 100 MeV–100 GeV energy range. Particular attention is given to the photons with the highest energy. Compared with the first LAT GRB catalog, our rate of detection is significantly improved. The results generally confirm the main findings of the first catalog: the LAT primarily detects the brightest GBM bursts, and the high-energy emission shows delayed onset as well as longer duration. However, in this work we find delays exceeding 1 ks and several GRBs with durations over 10 ks. Furthermore, the larger number of LAT detections shows that these GRBs not only cover the high-fluence range of GBM-detected GRBs but also sample lower fluences. In addition, the greater number of detected GRBs with redshift estimates allows us to study their properties in both the observer and rest frames. Comparison of the observational results with theoretical predictions reveals that no model is currently able to explain all results, highlighting the role of LAT observations in driving theoretical models.
TL;DR: In this paper, a systematic review used "science mapping" as a means of understanding the evolution of research in educational administration (EA), and the review sought to document the size, growth trajectory, and an...
Abstract: This systematic review used “science mapping” as a means of understanding the evolution of research in educational administration (EA). The review sought to document the size, growth trajectory, an...
TL;DR: This article aims to review and update current information on the pharmacology, mechanism of action, clinical efficacy, and adverse events of topical minoxidil.
Abstract: Minoxidil was first introduced as an antihypertensive medication and the discovery of its common adverse event, hypertrichosis, led to the development of a topical formulation for promoting hair growth. To date, topical minoxidil is the mainstay treatment for androgenetic alopecia and is used as an off-label treatment for other hair loss conditions. Despite its widespread application, the exact mechanism of action of minoxidil is still not fully understood. In this article, we aim to review and update current information on the pharmacology, mechanism of action, clinical efficacy, and adverse events of topical minoxidil.
TL;DR: This first phase 3 randomised trial recruiting only Asian patients to compare alectinib with crizotinib as a first-line treatment for ALK-positive non-small-cell lung cancer with 600 mg of alect inib twice per day confirmed consistency of the progression-free survival benefit with the global phase 3 ALEX study.
TL;DR: Single‐dose tafenoquine resulted in a significantly lower risk of P. vivax recurrence than placebo in patients with phenotypically normal G6PD activity, which resolved without intervention.
Abstract: Background Treatment of Plasmodium vivax malaria requires the clearing of asexual parasites, but relapse can be prevented only if dormant hypnozoites are cleared from the liver (a treatmen...
Indian Veterinary Research Institute1, Razi Vaccine and Serum Research Institute2, Barkatullah University3, Tamil Nadu Veterinary and Animal Sciences University4, Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir5, G. B. Pant University of Agriculture and Technology6, Monterrey Institute of Technology and Higher Education7, Mahidol University8, University of Miami9
TL;DR: The present review describes the current progress of identifying biomarkers, their prognostic, and therapeutic values in stress-related diseases and disorders, and therapy guidance.
Abstract: Various internal and external factors negatively affect the homeostatic equilibrium of organisms at the molecular to the whole-body level, inducing the so-called state of stress. Stress affects an organism's welfare status and induces energy-consuming mechanisms to combat the subsequent ill effects; thus, the individual may be immunocompromised, making them vulnerable to pathogens. The information presented here has been extensively reviewed, compiled, and analyzed from authenticated published resources available on Medline, PubMed, PubMed Central, Science Direct, and other scientific databases. Stress levels can be monitored by the quantitative and qualitative measurement of biomarkers. Potential markers of stress include thermal stress markers, such as heat shock proteins (HSPs), innate immune markers, such as Acute Phase Proteins (APPs), oxidative stress markers, and chemical secretions in the saliva and urine. In addition, stress biomarkers also play critical roles in the prognosis of stress-related diseases and disorders, and therapy guidance. Moreover, different components have been identified as potent mediators of cardiovascular, central nervous system, hepatic, and nephrological disorders, which can also be employed to evaluate these conditions precisely, but with stringent validation and specificity. Considerable scientific advances have been made in the detection, quantitation, and application of these biomarkers. The present review describes the current progress of identifying biomarkers, their prognostic, and therapeutic values.
TL;DR: Screening of vitamin D deficiency by measuring serum 25(OH)D is recommended in individuals at risk such as patients with diseases affecting vitamin D metabolism and absorption, osteoporosis, and older adults with a history of falls or nontraumatic fracture.
Abstract: Vitamin D plays an essential role in regulating calcium and phosphate metabolism and maintaining a healthy mineralized skeleton. Humans obtain vitamin D from sunlight exposure, dietary foods and supplements. There are two forms of vitamin D: vitamin D3 and vitamin D2. Vitamin D3 is synthesized endogenously in the skin and found naturally in oily fish and cod liver oil. Vitamin D2 is synthesized from ergosterol and found in yeast and mushrooms. Once vitamin D enters the circulation it is converted by 25-hydroxylase in the liver to 25-hydroxyvitamin D [25(OH)D], which is further converted by the 25-hydroxyvitamin D-1α-hydroxylase in the kidneys to the active form, 1,25-dihydroxyvitamin D [1,25(OH)2D]. 1,25(OH)2D binds to its nuclear vitamin D receptor to exert its physiologic functions. These functions include: promotion of intestinal calcium and phosphate absorption, renal tubular calcium reabsorption, and calcium mobilization from bone. The Endocrine Society's Clinical Practice Guideline defines vitamin D deficiency, insufficiency, and sufficiency as serum concentrations of 25(OH)D of
Stanford University1, Taipei Veterans General Hospital2, Academia Sinica3, National Taiwan University4, Seoul National University Hospital5, University of Hong Kong6, Carlos III Health Institute7, Chulalongkorn University8, Mahidol University9, Sun Yat-sen University10, Palo Alto Medical Foundation11, University of California, San Francisco12, Kaohsiung Medical University13, Tri-Service General Hospital14, University of Michigan15, China Medical University (Taiwan)16
TL;DR: A systematic review and meta-analysis of cohort studies found a low rate of HBsAg seroclearance in untreated and treated patients (pooled annual rate, approximately 1%), which occurred mainly in patients with less active disease.
TL;DR: The electrochemical upgrading of bio-oil is a potential renewable approach toward generating liquid biofuels or industrial chemicals under mild reaction conditions (≤80 °C and ambient pressure) as mentioned in this paper.
Abstract: The electrochemical upgrading of bio-oil is a potential renewable approach toward generating liquid biofuels or industrial chemicals under mild reaction conditions (≤80 °C and ambient pressure). Th...
Barkatullah University1, Razi Vaccine and Serum Research Institute2, Indian Veterinary Research Institute3, Tamil Nadu Veterinary and Animal Sciences University4, Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir5, Monterrey Institute of Technology and Higher Education6, University of Miami7, Mahidol University8
TL;DR: Various activators and suppressors of autophagy are described, which could be used to design novel intervention strategies against numerous diseases and develop therapeutic drugs to protect human and animal health.
Abstract: Autophagy (self-eating) is a conserved cellular degradation process that plays important roles in maintaining homeostasis and preventing nutritional, metabolic, and infection-mediated stresses. Autophagy dysfunction can have various pathological consequences, including tumor progression, pathogen hyper-virulence, and neurodegeneration. This review describes the mechanisms of autophagy and its associations with other cell death mechanisms, including apoptosis, necrosis, necroptosis, and autosis. Autophagy has both positive and negative roles in infection, cancer, neural development, metabolism, cardiovascular health, immunity, and iron homeostasis. Genetic defects in autophagy can have pathological consequences, such as static childhood encephalopathy with neurodegeneration in adulthood, Crohn’s disease, hereditary spastic paraparesis, Danon disease, X-linked myopathy with excessive autophagy, and sporadic inclusion body myositis. Further studies on the process of autophagy in different microbial infections could help to design and develop novel therapeutic strategies against important pathogenic microbes. This review on the progress and prospects of autophagy research describes various activators and suppressors, which could be used to design novel intervention strategies against numerous diseases and develop therapeutic drugs to protect human and animal health.
TL;DR: In this article, the effects of synthesis methods on optoelectronic properties of 2D titanium carbonitride, Ti3CNTx, were systematic studied and the impact of the C and N site composition on electronic transport has not been explored.
Abstract: MXenes, a relatively new class of two-dimensional (2D) transition-metal carbides, carbonitrides, and nitrides, exhibit unique properties such as high electronic conductivity, a wide range of optical characteristics, hydrophilicity, and mechanical stability. Because of the high electronic conductivity, MXenes have shown promise in many applications, such as energy storage, electromagnetic interference shielding, antennas, and transparent coatings. 2D titanium carbide (Ti3C2Tx, where Tx represents surface terminations), the first discovered and most studied MXene, has the highest electronic conductivity exceeding 10 000 S cm–1. There have been several efforts to alter the conductivity of MXenes, such as manipulation of the transition-metal layer and control of surface terminations. However, the impact of the C and N site composition on electronic transport has not been explored. In this study, the effects of synthesis methods on optoelectronic properties of 2D titanium carbonitride, Ti3CNTx, were systematic...
TL;DR: The focus of this review is current knowledge about the epidemiology, clinical manifestations, diagnosis, and treatment of both pulmonary sarcoidosis and extrapulmonary sarCOidosis, with a focus on glucocorticoids.
TL;DR: Among patients with normal G6PD enzyme activity, the decline in hemoglobin level with tafenoquine did not differ significantly from that with primaquine, and tafinoquine showed efficacy for the radical cure of P. vivax malaria, although tafanoquine was not shown to be noninferior to Primaquine.
Abstract: Background Tafenoquine, a single-dose therapy for Plasmodium vivax malaria, has been associated with relapse prevention through the clearance of P. vivax parasitemia and hypnozoites, terme...
TL;DR: At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared withprednisone alone, and the primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day Prednisone dose from month 0 to month 60.
Abstract: Summary Background The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. Methods We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate. MGTX patients were aged 18 to 65 years at enrolment, had generalised non-thymomatous myasthenia gravis of less than 5 years' duration, had acetylcholine receptor antibody titres of 1·00 nmol/L or higher (or concentrations of 0·50–0·99 nmol/L if diagnosis was confirmed by positive edrophonium or abnormal repetitive nerve stimulation, or abnormal single fibre electromyography), had Myasthenia Gravis Foundation of America Clinical Classification Class II–IV disease, and were on optimal anticholinesterase therapy with or without oral corticosteroids. In MGTX, patients were randomly assigned (1:1) to either thymectomy plus prednisone or prednisone alone. All patients in both groups received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00294658. It is closed to new participants, with follow-up completed. Findings Of the 111 patients who completed the 3-year MGTX, 68 (61%) entered the extension study between Sept 1, 2009, and Aug 26, 2015 (33 in the prednisone alone group and 35 in the prednisone plus thymectomy group). 50 (74%) patients completed the 60-month assessment, 24 in the prednisone alone group and 26 in the prednisone plus thymectomy group. At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted mean QMG scores (5·47 [SD 3·87] vs 9·34 [5·08]; p=0·0007) and mean alternate-day prednisone doses (24 mg [SD 21] vs 48 mg [29]; p=0·0002) than did those in the prednisone alone group. 14 (42%) of 33 patients in the prednisone group, and 12 (34%) of 35 in the thymectomy plus prednisone group, had at least one adverse event by month 60. No treatment-related deaths were reported during the extension phase. Interpretation At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared with prednisone alone. Although caution is appropriate when generalising our findings because of the small sample size of our study, they nevertheless provide further support for the benefits of thymectomy in patients with generalised non-thymomatous myasthenia gravis. Funding National Institutes of Health, National Institute of Neurological Disorders and Stroke.
Imperial College London1, University of Basel2, Swiss Tropical and Public Health Institute3, University of London4, Karolinska Institutet5, Walter and Eliza Hall Institute of Medical Research6, University of Notre Dame7, University of Melbourne8, Pasteur Institute9, Addis Ababa University10, Radboud University Nijmegen11, PATH12, University of Oxford13, Wellcome Trust Centre for Human Genetics14, University of Health and Allied Sciences15, University of Paris16, University of the Sciences17, University of Ghana18, Centers for Disease Control and Prevention19, National Institute for Medical Research20, University of California, San Francisco21, Dar es Salaam University College of Education22, University of Edinburgh23, Mahidol University24
TL;DR: Results indicate that subpatent infections contribute to the infectious reservoir, may be long lasting, and require more sensitive diagnostics to detect them in lower transmission settings.
Abstract: Malaria infections occurring below the limit of detection of standard diagnostics are common in all endemic settings. However, key questions remain surrounding their contribution to sustaining transmission and whether they need to be detected and targeted to achieve malaria elimination. In this study we analyse a range of malaria datasets to quantify the density, detectability, course of infection and infectiousness of subpatent infections. Asymptomatically infected individuals have lower parasite densities on average in low transmission settings compared to individuals in higher transmission settings. In cohort studies, subpatent infections are found to be predictive of future periods of patent infection and in membrane feeding studies, individuals infected with subpatent asexual parasite densities are found to be approximately a third as infectious to mosquitoes as individuals with patent (asexual parasite) infection. These results indicate that subpatent infections contribute to the infectious reservoir, may be long lasting, and require more sensitive diagnostics to detect them in lower transmission settings.
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Nanjing University1, University of Turin2, University of Geneva3, Purple Mountain Observatory4, University of Arizona5, Southwest Jiaotong University6, University of Calgary7, Peking University8, Guangxi University9, Istituto Nazionale di Fisica Nucleare10, Shandong University11, Centre national de la recherche scientifique12, Mahidol University13, National Research Nuclear University MEPhI14, Russian Academy of Sciences15, Sun Yat-sen University16, Nanchang University17, Chinese Academy of Sciences18, Xinjiang Astronomical Observatory19, Max Planck Society20, University of Nevada, Las Vegas21, Yunnan University22
TL;DR: The Large High Altitude Air Shower Observatory (LHAASO) project is a new generation multi-component instrument, to be built at 4410 meters of altitude in the Sichuan province of China, with the aim to study with unprecedented sensitivity the spec trum, the composition and the anisotropy of cosmic rays in the energy range between 10$^{12}$ and 10$€18}$ eV, as well as to act simultaneously as a wide aperture (one stereoradiant), continuously operated gamma ray telescope in the EH range between
Abstract: The Large High Altitude Air Shower Observatory (LHAASO) project is a new generation multi-component instrument, to be built at 4410 meters of altitude in the Sichuan province of China, with the aim to study with unprecedented sensitivity the spec trum, the composition and the anisotropy of cosmic rays in the energy range between 10$^{12}$ and 10$^{18}$ eV, as well as to act simultaneously as a wide aperture (one stereoradiant), continuously-operated gamma ray telescope in the energy range between 10$^{11}$ and $10^{15}$ eV. The experiment will be able of continuously surveying the TeV sky for steady and transient sources from 100 GeV to 1 PeV, t hus opening for the first time the 100-1000 TeV range to the direct observations of the high energy cosmic ray sources. In addition, the different observables (electronic, muonic and Cherenkov/fluorescence components) that will be measured in LHAASO will allow to investigate origin, acceleration and propagation of the radiation through a measurement of energy spec trum, elemental composition and anisotropy with unprecedented resolution. The remarkable sensitivity of LHAASO in cosmic rays physics and gamma astronomy would play a key-role in the comprehensive general program to explore the High Energy Universe. LHAASO will allow important studies of fundamental physics (such as indirect dark matter search, Lorentz invariance violation, quantum gravity) and solar and heliospheric physics. In this document we introduce the concept of LHAASO and the main science goals, providing an overview of the project.
Peter MacCallum Cancer Centre1, The Royal Marsden NHS Foundation Trust2, Paracelsus Private Medical University of Salzburg3, Université de Montréal4, National and Kapodistrian University of Athens5, Hebron University6, University of Kansas7, Oslo University Hospital8, Medical University of Vienna9, Royal Brisbane and Women's Hospital10, Mahidol University11, University of Zurich12, University of Malaya13, Merck & Co.14, Yale University15
TL;DR: At the second interim analysis (IA2), P significantly improved OS in the phase 3 study of P or P + chemo (C) vs EXTREME (E) as 1L therapy for R/M HNSCC (NCT02358031).
Abstract: 6000Background: KEYNOTE-048 is a phase 3 study of P or P + chemo (C) vs EXTREME (E) as 1L therapy for R/M HNSCC (NCT02358031). At the second interim analysis (IA2), P significantly improved OS in t...