Bronchopulmonary malinosculation: a case report

Pulmonary malinosculation, which include a broad spectrum of disorders that involve abnormalities in one or more of the three main components of the lung, namely, the airways and lung parenchyma, arteries and veins. A case of bronchopulmonary malinosculation was presented due to its rarity

Risk predictors for the development of retinopathy of prematurity in very low birth weight neonates

Background: Retinopathy of prematurity (ROP) is an important cause of visual and neurological impairment in premature infants.Identification of risk factors and effective management of the same will help in better outcomes. Information on ROP and its riskfactors are limited especially from South India and interventions directed at prevention and treatments have produced only modestresults. Methods: The study was of a prospective, unmatched case–control design and was conducted in premature, very low birthweight infants (<34 weeks; <1500 g) admitted to Neonatal Intensive Care Unit in a tertiary care center in South India during an18-month period. The neonates were screened for ROP and subjects who developed ROP were classified as cases and those whodid not were categorized as controls. The maternal risk factors studied were the type of delivery, maternal fever, pregnancy-inducedhypertension (PIH), gestational diabetes mellitus, cardiac disease, premature rupture of membrane, antepartum hemorrhage,chorioamnionitis, multiple pregnancy, infertility treatment, urinary tract infections, polyhydramnios, and oligohydramnios. Theneonatal factors studied were gestational age, birth weight, septicemia, apnea, anemia, hypotension, need for inotropic support, typeand duration of oxygen therapy, patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage, and phototherapy.Both univariate and multivariate analyses were carried out. Results: A total of 54 cases and 54 controls (1:1) were enrolled intothe study. Males dominated the study (63% of cases). Univariate analysis showed gestational age, PIH, birth weight, sepsis, oxygenadministration, hypotension and packed cell transfusion as important risk factors for ROP. On binary logistic regression analysis,birth weight (odds ratio: 6.00; p: 0.014), oxygen exposure (odds ratio: 11.05; p: 0.003), and hypotension (odds ratio: 6.85; p: 0.009)were identified as important risk predictors of ROP. Conclusions: The study adds important information to the understanding ofrisk factors of ROP

Developing a model of pedagogical content knowledge for secondary and post-secondary mathematics instruction

The accepted framing of mathematics pedagogical content knowledge (PCK) as part of mathematical knowledge for teaching has centered on the question: What mathematical reasoning, insight, understanding, and skills are required for a person to teach elementary mathematics? Many have worked to address this question in K-8 teaching. Yet, there remains a call for examples and theory in the context of teachers with greater mathematical preparation and older students with varied and complex experiences in learning mathematics. In this theory development report we offer background and examples for an extended model of PCK – as the interplay among conceptually-rich mathematical understandings, experience in and of teaching, and multiple culturally-mediated classroom interactions

Co-inhibition of TGF-β and PD-L1 pathways in a metastatic colorectal cancer mouse model triggers interferon responses, innate cells and T cells, alongside metabolic changes and tumor resistance

Colorectal cancer (CRC) is the third most prevalent cancer worldwide with a high mortality rate (20–30%), especially due to metastasis to adjacent organs. Clinical responses to chemotherapy, radiation, targeted and immunotherapies are limited to a subset of patients making metastatic CRC (mCRC) difficult to treat. To understand the therapeutic modulation of immune response in mCRC, we have used a genetically engineered mouse model (GEMM), “KPN”, which resembles the human ‘CMS4’-like subtype. We show here that transforming growth factor (TGF-β1), secreted by KPN organoids, increases cancer cell proliferation, and inhibits splenocyte activation in vitro. TGF-β1 also inhibits activation of naive but not pre-activated T cells, suggesting differential effects on specific immune cells. In vivo, the inhibition of TGF-β inflames the KPN tumors, causing infiltration of T cells, monocytes and monocytic intermediates, while reducing neutrophils and epithelial cells. Co-inhibition of TGF-β and PD-L1 signaling further enhances cytotoxic CD8+T cells and upregulates innate immune response and interferon gene signatures. However, simultaneous upregulation of cancer-related metabolic genes correlated with limited control of tumor burden and/or progression despite combination treatment. Our study illustrates the importance of using GEMMs to predict better immunotherapies for mCRC

MTar: a computational microRNA target prediction architecture for human transcriptome

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) play an essential task in gene regulatory networks by inhibiting the expression of target mRNAs. As their mRNA targets are genes involved in important cell functions, there is a growing interest in identifying the relationship between miRNAs and their target mRNAs. So, there is now a imperative need to develop a computational method by which we can identify the target mRNAs of existing miRNAs. Here, we proposed an efficient machine learning model to unravel the relationship between miRNAs and their target mRNAs.</p> <p>Results</p> <p>We present a novel computational architecture MTar for miRNA target prediction which reports 94.5% sensitivity and 90.5% specificity. We identified 16 positional, thermodynamic and structural parameters from the wet lab proven miRNA:mRNA pairs and MTar makes use of these parameters for miRNA target identification. It incorporates an Artificial Neural Network (ANN) verifier which is trained by wet lab proven microRNA targets. A number of hitherto unknown targets of many miRNA families were located using MTar. The method identifies all three potential miRNA targets (5' seed-only, 5' dominant, and 3' canonical) whereas the existing solutions focus on 5' complementarities alone.</p> <p>Conclusion</p> <p>MTar, an ANN based architecture for identifying functional regulatory miRNA-mRNA interaction using predicted miRNA targets. The area of target prediction has received a new momentum with the function of a thermodynamic model incorporating target accessibility. This model incorporates sixteen structural, thermodynamic and positional features of residues in miRNA: mRNA pairs were employed to select target candidates. So our novel machine learning architecture, MTar is found to be more comprehensive than the existing methods in predicting miRNA targets, especially human transcritome.</p

Mapping development and health effects of cooking with solid fuels in low-income and middle-income countries, 2000–18: a geospatial modelling study

Background: More than 3 billion people do not have access to clean energy and primarily use solid fuels to cook. Use of solid fuels generates household air pollution, which was associated with more than 2 million deaths in 2019. Although local patterns in cooking vary systematically, subnational trends in use of solid fuels have yet to be comprehensively analysed. We estimated the prevalence of solid-fuel use with high spatial resolution to explore subnational inequalities, assess local progress, and assess the effects on health in low-income and middle-income countries (LMICs) without universal access to clean fuels. Methods: We did a geospatial modelling study to map the prevalence of solid-fuel use for cooking at a 5 km × 5 km resolution in 98 LMICs based on 2·1 million household observations of the primary cooking fuel used from 663 population-based household surveys over the years 2000 to 2018. We use observed temporal patterns to forecast household air pollution in 2030 and to assess the probability of attaining the Sustainable Development Goal (SDG) target indicator for clean cooking. We aligned our estimates of household air pollution to geospatial estimates of ambient air pollution to establish the risk transition occurring in LMICs. Finally, we quantified the effect of residual primary solid-fuel use for cooking on child health by doing a counterfactual risk assessment to estimate the proportion of deaths from lower respiratory tract infections in children younger than 5 years that could be associated with household air pollution. Findings: Although primary reliance on solid-fuel use for cooking has declined globally, it remains widespread. 593 million people live in districts where the prevalence of solid-fuel use for cooking exceeds 95%. 66% of people in LMICs live in districts that are not on track to meet the SDG target for universal access to clean energy by 2030. Household air pollution continues to be a major contributor to particulate exposure in LMICs, and rising ambient air pollution is undermining potential gains from reductions in the prevalence of solid-fuel use for cooking in many countries. We estimated that, in 2018, 205 000 (95% uncertainty interval 147 000–257 000) children younger than 5 years died from lower respiratory tract infections that could be attributed to household air pollution. Interpretation: Efforts to accelerate the adoption of clean cooking fuels need to be substantially increased and recalibrated to account for subnational inequalities, because there are substantial opportunities to improve air quality and avert child mortality associated with household air pollution. Funding: Bill &amp; Melinda Gates Foundation

Mapping development and health effects of cooking with solid fuels in low-income and middle-income countries, 2000-18 : a geospatial modelling study

Background More than 3 billion people do not have access to clean energy and primarily use solid fuels to cook. Use of solid fuels generates household air pollution, which was associated with more than 2 million deaths in 2019. Although local patterns in cooking vary systematically, subnational trends in use of solid fuels have yet to be comprehensively analysed. We estimated the prevalence of solid-fuel use with high spatial resolution to explore subnational inequalities, assess local progress, and assess the effects on health in low-income and middle-income countries (LMICs) without universal access to clean fuels.Methods We did a geospatial modelling study to map the prevalence of solid-fuel use for cooking at a 5 km x 5 km resolution in 98 LMICs based on 2.1 million household observations of the primary cooking fuel used from 663 population-based household surveys over the years 2000 to 2018. We use observed temporal patterns to forecast household air pollution in 2030 and to assess the probability of attaining the Sustainable Development Goal (SDG) target indicator for clean cooking. We aligned our estimates of household air pollution to geospatial estimates of ambient air pollution to establish the risk transition occurring in LMICs. Finally, we quantified the effect of residual primary solid-fuel use for cooking on child health by doing a counterfactual risk assessment to estimate the proportion of deaths from lower respiratory tract infections in children younger than 5 years that could be associated with household air pollution.Findings Although primary reliance on solid-fuel use for cooking has declined globally, it remains widespread. 593 million people live in districts where the prevalence of solid-fuel use for cooking exceeds 95%. 66% of people in LMICs live in districts that are not on track to meet the SDG target for universal access to clean energy by 2030. Household air pollution continues to be a major contributor to particulate exposure in LMICs, and rising ambient air pollution is undermining potential gains from reductions in the prevalence of solid-fuel use for cooking in many countries. We estimated that, in 2018, 205000 (95% uncertainty interval 147000-257000) children younger than 5 years died from lower respiratory tract infections that could be attributed to household air pollution.Interpretation Efforts to accelerate the adoption of clean cooking fuels need to be substantially increased and recalibrated to account for subnational inequalities, because there are substantial opportunities to improve air quality and avert child mortality associated with household air pollution. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.Peer reviewe

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens