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  • Mishra, A, et al. (författare)
  • Diminishing benefits of urban living for children and adolescents' growth and development
  • 2023
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
  • 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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  • Ruilope, LM, et al. (författare)
  • Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
  • 2019
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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  • He, YQ, et al. (författare)
  • A polygenic risk score for nasopharyngeal carcinoma shows potential for risk stratification and personalized screening
  • 2022
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 1966-
  • Tidskriftsartikel (refereegranskat)abstract
    • Polygenic risk scores (PRS) have the potential to identify individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we construct and validate a genome-wide association study (GWAS) derived PRS for nasopharyngeal carcinoma (NPC), using a multi-center study of six populations (6 059 NPC cases and 7 582 controls), and evaluate its utility in a nested case-control study. We show that the PRS enables effective identification of NPC high-risk individuals (AUC = 0.65) and improves the risk prediction with the PRS incremental deciles in each population (Ptrend ranging from 2.79 × 10−7 to 4.79 × 10−44). By incorporating the PRS into EBV-serology-based NPC screening, the test’s positive predictive value (PPV) is increased from an average of 4.84% to 8.38% and 11.91% in the top 10% and 5% PRS, respectively. In summary, the GWAS-derived PRS, together with the EBV test, significantly improves NPC risk stratification and informs personalized screening.
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  • Gao, SN, et al. (författare)
  • Identification of a prognostic risk-scoring model and risk signatures based on glycosylation-associated cluster in breast cancer
  • 2022
  • Ingår i: Frontiers in genetics. - : Frontiers Media SA. - 1664-8021. ; 13, s. 960567-
  • Tidskriftsartikel (refereegranskat)abstract
    • Breast cancer is a heterogeneous disease whose subtypes represent different histological origins, prognoses, and therapeutic sensitivity. But there remains a strong need for more specific biomarkers and broader alternatives for personalized treatment. Our study classified breast cancer samples from The Cancer Genome Atlas (TCGA) into three groups based on glycosylation-associated genes and then identified differentially expressed genes under different glycosylation patterns to construct a prognostic model. The final prognostic model containing 23 key molecules achieved exciting performance both in the TCGA training set and testing set GSE42568 and GSE58812. The risk score also showed a significant difference in predicting overall clinical survival and immune infiltration analysis. This work helped us to understand the heterogeneity of breast cancer from another perspective and indicated that the identification of risk scores based on glycosylation patterns has potential clinical implications and immune-related value for breast cancer.
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  • Guo, JP, et al. (författare)
  • Sequencing of the MHC region defines HLA-DQA1 as the major genetic risk for seropositive rheumatoid arthritis in Han Chinese population
  • 2019
  • Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:6, s. 773-780
  • Tidskriftsartikel (refereegranskat)abstract
    • The strong genetic contribution of the major histocompatibility complex (MHC) region to rheumatoid arthritis (RA) has been generally attributed to human leukocyte antigen (HLA)-DRB1. However, due to the high polymorphisms and linkage disequilibrium within MHC, it is difficult to define novel and/or independent genetic risks using conventional HLA genotyping or chip-based microarray technology. This study aimed to identify novel RA risk variants by performing deep sequencing for MHC.MethodsWe first conducted target sequencing for the entire MHC region in 357 anticitrullinated protein antibodies (ACPA)-positive patients with RA and 1001 healthy controls, and then performed HLA typing in an independent case–control cohort consisting of 1415 samples for validation. All study subjects were Han Chinese. Genetic associations for RA susceptibility and severity were analysed. Comparative modelling was constructed to predict potential functions for the newly discovered RA association variants.ResultsHLA-DQα1:160D conferred the strongest and independent susceptibility to ACPA-positive RA (p=6.16×10−36, OR=2.29). DRβ1:37N had an independent protective effect (p=5.81×10−16, OR=0.49). As predicted by comparative modelling, the negatively charged DQα1:160D stabilises the dimer of dimers, thus may lead to an increased T cell activation. The negatively charged DRβ1:37N encoding alleles preferentially bind with epitope P9 arginine, thus may result in a decreased RA susceptibility.ConclusionsWe provide the first evidence that HLA-DQα1:160D, instead of HLA-DRB1*0405, is the strongest and independent genetic risk for ACPA-positive RA in Han Chinese. Our study also illustrates the value of deep sequencing for fine-mapping disease risk variants in the MHC region.
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  • Hu, XJ, et al. (författare)
  • Development and External Validation of a Radiomics Model Derived from Preoperative Gadoxetic Acid-Enhanced MRI for Predicting Histopathologic Grade of Hepatocellular Carcinoma
  • 2023
  • Ingår i: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 13:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Histopathologic grade of hepatocellular carcinoma (HCC) is an important predictor of early recurrence and poor prognosis after curative treatments. This study aims to develop a radiomics model based on preoperative gadoxetic acid-enhanced MRI for predicting HCC histopathologic grade and to validate its predictive performance in an independent external cohort. Clinical and imaging data of 403 consecutive HCC patients were retrospectively collected from two hospitals (265 and 138, respectively). Patients were categorized into poorly differentiated HCC and non-poorly differentiated HCC groups. A total of 851 radiomics features were extracted from the segmented tumor at the hepatobiliary phase images. Three classifiers, logistic regression (LR), support vector machine, and Adaboost were adopted for modeling. The areas under the curve of the three models were 0.70, 0.67, and 0.61, respectively, in the external test cohort. Alpha-fetoprotein (AFP) was the only significant clinicopathological variable associated with HCC grading (odds ratio: 2.75). When combining AFP, the LR+AFP model showed the best performance, with an AUC of 0.71 (95%CI: 0.59–0.82) in the external test cohort. A radiomics model based on gadoxetic acid-enhanced MRI was constructed in this study to discriminate HCC with different histopathologic grades. Its good performance indicates a promise in the preoperative prediction of HCC differentiation levels.
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  • Ji, MF, et al. (författare)
  • Mass screening for liver cancer: results from a demonstration screening project in Zhongshan City, China
  • 2018
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 12787-
  • Tidskriftsartikel (refereegranskat)abstract
    • Current Chinese national guidelines recommend routine screening for liver cancer in patients positive for HBsAg, irrespective of fibrosis status, age, or family history of liver cancer. We aim to evaluate whether the recommended screening strategy could reduce liver-cancer-specific mortality. We conducted a liver cancer mass screening trial in Xiaolan Town, Zhongshan City, China, among residents aged 35–64 years in 2012. All volunteers were offered serological testing for hepatitis B virus surface antigen (HBsAg). We proposed biannual screening using serum alpha-fetoprotein (AFP) and ultrasonography examination for subjects positive for HBsAg. Among 17,966 participants (26.2% of 68,510 eligible residents) who were free of liver cancer at baseline in 2012, we identified 57 incident cases of liver cancer within the first 4 years of follow-up (i.e., 43 among 2,848 HBsAg-positive participants and 14 among 15,118 HBsAg-negative participants), compared with 104 cases identified in non-participants (N = 50,544). A total of 207 participants had the recommended number of ultrasonography examinations (every 6 months) during the screening period. Compared with cases identified from non-participants, the cases arising among participants were more likely to be at early stage and had better survival than those among non-participants. However, we did not observe a reduction in liver cancer-specific mortality rate among participants (relative risk = 1.04, 95% confidence interval = 0.68, 1.58, P = 0.856). Our demonstration screening study does not show a reduction in liver cancer mortality within the first 4 years of follow-up according to current guidance in China, although long-term efficacy remains to be evaluated. Targeted surveillance among high-risk individuals as recommended by international guidelines, along with measures to improve compliance, should be evaluated in the Chinese population.
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  • Kinyoki, DK, et al. (författare)
  • Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017
  • 2020
  • Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 26:5, s. 750-759
  • Tidskriftsartikel (refereegranskat)abstract
    • A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic.
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  • Liu, N, et al. (författare)
  • Predictors of outcome of myasthenic crisis
  • 2015
  • Ingår i: Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. - : Springer Science and Business Media LLC. - 1590-3478. ; 36:5, s. 801-802
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • Pelaz, B, et al. (författare)
  • Diverse Applications of Nanomedicine
  • 2017
  • Ingår i: ACS nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 11:3, s. 2313-2381
  • Tidskriftsartikel (refereegranskat)
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