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- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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- Wu, K, et al.
(författare)
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Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas
- 2015
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6, s. 10131-
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Tidskriftsartikel (refereegranskat)abstract
- The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13 significantly mutated genes are identified, including the most commonly mutated gene TP53 and novel mutation targets such as RHPN2, GLI3 and MRC2. TP53 mutations are furthermore significantly enriched in tumours from patients harbouring metastases. Genes regulating cytoskeleton remodelling processes are also frequently altered, especially in metastatic samples, of which the high expression level of IQGAP3 is identified as a marker for poor prognosis. Our study represents the first large-scale sequencing effort on lung adenocarcinoma in Asian patients and provides a comprehensive mutational landscape for both primary and metastatic tumours. This may thus form a basis for personalized medical care and shed light on the molecular pathogenesis of metastatic lung adenocarcinoma.
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- Menden, MP, et al.
(författare)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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- He, ZC, et al.
(författare)
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Composition of Urine Collected from Non-Stone-Forming Chinese Persons during Different Short-Term Periods of the Day
- 2022
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Ingår i: Urologia internationalis. - : S. Karger AG. - 1423-0399 .- 0042-1138. ; 106:3, s. 227-234
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study in a small group of non-stone-forming Chinese persons was to measure the levels of supersaturation with calcium oxalate and calcium phosphate and pH with the aim of confirming if any of the different short-term urine samples were better for risk evaluation than a 24-h sample. Nine normal men and 1 woman collected urine during 4 periods of the day. <i>Period 1</i> between 08 and 12 h, <i>Period 2</i> between 12 and 18 h, <i>Period 3</i> between 18 and 22 h, and <i>Period 4</i> between 22 and 08 h. Each sample was analysed for calcium, oxalate, citrate, magnesium and phosphate, and estimates of supersaturation with calcium oxalate (CaOx) and calcium phosphate (CaP) were expressed in terms of AP(CaOx) and AP(CaP) index. An estimate of the solute load of CaOx was also calculated. Urine composition for 24-h urine (<i>Period 24</i>) was obtained mathematically from the analysed variables. Urine composition corresponding to 14-h urine portions 22–12 h (<i>Period 14</i>N) and 08–22 h (<i>Period 14 D</i>) were calculated. The lowest pH levels were recorded in <i>Period 1</i> urine. The highest level of AP(CaOx) index was recorded during <i>Period 1</i>, and the product AP(CaOx) index × 10<sup>7</sup> × hydrogen ion concentration was significantly higher in Period 1 urine than in 24-h urine (<i>p</i> = 0.02). Also, the product SL(CaOx) × 10<sup>7</sup> × hydrogen ion concentration was significantly higher in <i>Period 1</i> urine (<i>p</i> = 0.02). Low AP (CaP) index levels were recorded in <i>Period 4</i>, but also in all periods following dietary loads of calcium and phosphate. With the important reservation that the analytical results were obtained from non-stone-forming persons, the conclusion is that analysis of urine samples collected between 08 and 12 h might be an alternative to 24-h urine. The risk evaluation might advantageously be expressed either in terms of the product AP(CaOx) index × 10<sup>7</sup> × hydrogen ion concentration or the product SL(CaOx) × 10<sup>7</sup> × hydrogen ion concentration.
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