Synthesis, characterization, molecular docking studies and biological activity of coumarin linked 2-pyridone heterocycles

231-237In the present paper, the synthesis, characterization, antimicrobial activity and in silico molecular docking study of 6-((arylidene)amino)-4-(4-chlorophenyl)-2-oxo-1-((1-(2-oxo-2H-chromen-3-yl)ethylidene)amino)-1,2-dihydropyridine-3,5-dicarbonitriles 4a-o have been reported. Compounds 4d, 4g, 4j, 4k, 4m and 4o show significant activity. Structure determination of the synthesized compounds has been done by the standard spectroscopic techniques. It is observed that biological activity is influenced by electronic environment of the molecules. Electron withdrawing group at para position plays a major role for enhancing the biological activity for antibacterial activity and the electron donating group at para position for antifungal activity. Compounds 4a-o have been further evaluated for cytotoxicity on HeLa cells. From the cytotoxicity results, compounds have been found to possess low cytotoxicity with potent antimicrobial activity

Variability in soil properties influencing pigeonpea (Cajanus cajana L.) yield: a multivariate statistical analysis [version 3; peer review: 2 approved]

Aims: The aim of the study was to reveal the variability in soil properties influencing pigeonpea (Cajanus cajana L.) seed yield under semi-arid rainfed condition. Methods: Soils were initially classified into series level and further these series were divided into soil-phase units. For two site years viz., 2018-19 and 2019-20, surface soil samples from each soil-phase unit were collected before sowing of pigeonpea and subsequently crop growth parameters at critical stages were recorded. Results: The principal component analysis with varimax rotation resulted in seven components for both the site years, having eigenvalues greater than one, explained more than 80% of the variability. The step wise linear regression analysis showed that the pigeonpea seed yield was linearly correlated with PC3 (p<0.01), PC4 (p<0.01) and PC7 (p<0.05) of soil properties with R2 = 0.679, during 2018-19. Whereas, during 2019-20, the seed yield was linearly correlated with PC1 (p<0.01), PC3 (p<0.01) and PC6 (p<0.05) with R2 = 0.677. In site year 1, the available P2O5, Fe, Zn, S, Cu, number of pods, surface soil moisture determined the yield. In site year 2, the available K2O, P2O5, Fe, Zn, S, clay, CEC and available water content determined the yield. All these variables together explain variability in yield

Relative Biological Effectiveness Studies Using 3 MeV Proton Beam from Folded Tandem Ion Accelerator: An Experimental and Theoretical Approach

Proton being the easiest light ion to accelerate and achieve desired beam profile, has been pursued as a popular particulate radiation for therapy applications. In the present study, Saccharomyces cerevisiae D7 strain was used to estimate the RBE values of the 3 MeV proton beam, and an attempt was made to derive mathematical formula for calculating RBE value with respect to the dose. Dosimetry studies were carried out using Fricke dosimetry and Semiconductor Surface Barrier detector to calibrate the absorbed doses of Gamma chamber-1200 and Folded Tandem Ion Accelerator respectively. Gold standard cell survival assay and gene conversion assay were used to compare gamma and proton radiation induced cell death and genetic endpoint. Multi target single hit model was used to derive mathematical formula for RBE estimation. The results show a linear survival-dose response after proton radiation and sigmoid survival-dose response after gamma radiation treatment. The calculated RBE value from the survival and gene conversion studies was 1.60 and 3.93, respectively. The derived mathematical formula is very useful in calculating RBE value, which varies from 3.61 to 1.80 with increasing dose. The estimated RBE value from the mathematical formula is comparable with the experimental values. With the help of the present mathematical formulation, RBE value at any dose can be calculated in the exponential and sigmoidal regions of the survival curve without actually extending the experiment in that dose region, which is not possible using conventional methods

mRNA Coronavirus Disease 2019 Vaccine-Associated Myopericarditis in Adolescents: A Survey Study

In this survey study of institutions across the US, marked variability in evaluation, treatment, and follow-up of adolescents 12 through 18 years of age with mRNA coronavirus disease 2019 (COVID-19) vaccine-associated myopericarditis was noted. Only one adolescent with life-threatening complications was reported, with no deaths at any of the participating institutions

Under-Five Mortality in High Focus States in India: A District Level Geospatial Analysis

<div><h3>Background</h3><p>This paper examines if, when controlling for biophysical and geographical variables (including rainfall, productivity of agricultural lands, topography/temperature, and market access through road networks), socioeconomic and health care indicators help to explain variations in the under-five mortality rate across districts from nine high focus states in India. The literature on this subject is inconclusive because the survey data, upon which most studies of child mortality rely, rarely include variables that measure these factors. This paper introduces these variables into an analysis of 284 districts from nine high focus states in India.</p> <h3>Methodology/Principal Findings</h3><p>Information on the mortality indicator was accessed from the recently conducted Annual Health Survey of 2011 and other socioeconomic and geographic variables from Census 2011, District Level Household and Facility Survey (2007–08), Department of Economics and Statistics Divisions of the concerned states. Displaying high spatial dependence (spatial autocorrelation) in the mortality indicator (outcome variable) and its possible predictors used in the analysis, the paper uses the Spatial-Error Model in an effort to negate or reduce the spatial dependence in model parameters. The results evince that the coverage gap index (a mixed indicator of district wise coverage of reproductive and child health services), female literacy, urbanization, economic status, the number of newborn care provided in Primary Health Centers in the district transpired as significant correlates of under-five mortality in the nine high focus states in India. The study identifies three clusters with high under-five mortality rate including 30 districts, and advocates urgent attention.</p> <h3>Conclusion</h3><p>Even after controlling the possible biophysical and geographical variables, the study reveals that the health program initiatives have a major role to play in reducing under-five mortality rate in the high focus states in India.</p> </div

The global burden of adolescent and young adult cancer in 2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15–39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods: Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15–39 years to define adolescents and young adults. Findings: There were 1·19 million (95% UI 1·11–1·28) incident cancer cases and 396 000 (370 000–425 000) deaths due to cancer among people aged 15–39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59·6 [54·5–65·7] per 100 000 person-years) and high-middle SDI countries (53·2 [48·8–57·9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14·2 [12·9–15·6] per 100 000 person-years) and middle SDI (13·6 [12·6–14·8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23·5 million (21·9–25·2) DALYs to the global burden of disease, of which 2·7% (1·9–3·6) came from YLDs and 97·3% (96·4–98·1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation: Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Funding: Bill &amp; Melinda Gates Foundation, American Lebanese Syrian Associated Charities, St Baldrick's Foundation, and the National Cancer Institute

Measuring routine childhood vaccination coverage in 204 countries and territories, 1980-2019: a systematic analysis for the Global Burden of Disease Study 2020, Release 1

Background: Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time. // Methods: For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dose-specific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in country-reported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development. // Findings: By 2019, global coverage of third-dose DTP (DTP3; 81·6% [95% uncertainty interval 80·4–82·7]) more than doubled from levels estimated in 1980 (39·9% [37·5–42·1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38·5% [35·4–41·3] in 1980 to 83·6% [82·3–84·8] in 2019). Third-dose polio vaccine (Pol3) coverage also increased, from 42·6% (41·4–44·1) in 1980 to 79·8% (78·4–81·1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56·8 million (52·6–60·9) to 14·5 million (13·4–15·9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019. // Interpretation: After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations

Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Funding: F Carvalho and E Fernandes acknowledge support from Fundação para a Ciência e a Tecnologia, I.P. (FCT), in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy i4HB; FCT/MCTES through the project UIDB/50006/2020. J Conde acknowledges the European Research Council Starting Grant (ERC-StG-2019-848325). V M Costa acknowledges the grant SFRH/BHD/110001/2015, received by Portuguese national funds through Fundação para a Ciência e Tecnologia (FCT), IP, under the Norma Transitória DL57/2016/CP1334/CT0006.proofepub_ahead_of_prin