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| 2. |
- Andersson, Björn, 1977, et al.
(författare)
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Proteins related to lipoprotein profile were identified using a pharmaco-proteomic approach as markers for growth response to growth hormone (GH) treatment in short prepubertal children
- 2009
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Ingår i: Proteome Science. - : Springer Science and Business Media LLC. - 1477-5956. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The broad range in growth observed in response to growth hormone (GH) treatment is mainly caused by individual variations in both GH secretion and GH sensitivity. Individual GH responsiveness can be estimated using evidence-based models that predict the response to GH treatment; however, these models can be improved. High-throughput proteomics techniques can be used to identify proteins that may potentially be used as variables in such models in order to improve their predictive ability. Previously we have reported that proteomic analyses can identify biomarkers that discriminate between short prepubertal children with idiopathic short stature (ISS) who show good or poor growth in response to GH treatment. In this study we used a pharmaco-proteomic approach to identify novel factors that correlate with the growth response to GH treatment in prepubertal children who are short due to GH deficiency or ISS. The study included 128 short prepubertal children receiving GH treatment, of whom 39 were GH-deficient and 89 had ISS. Serum protein expression profiles at study start and after 1 year of GH treatment were analyzed using SELDI-TOF. Cross-validated regression and random permutation analyses were performed to identify significant correlations between protein expression patterns and the 2-year growth response to GH treatment. RESULTS: At start of treatment we identified a combination of seven protein peaks that correlated with the 2-year growth response in the GH-deficient group (R2 = 0.73). After 1 year of treatment, a combination of four peaks in the GH-deficient group (R2 = 0.64), eight peaks in the ISS group R2 = 0.47) and eight peaks in the total study group correlated with the 2-year growth response R2 = 0.38).The peaks identified corresponded to apolipoproteins A-I, A-II, C-I, C-III, transthyretin and serum amyloid A 4, which are all part of the high-density lipoprotein. CONCLUSION: Using a proteomic approach we identified biomarkers related to the lipoprotein profile that could be used to predict growth response to GH treatment in prepubertal children who are short as a result of GH-deficiency or who have ISS.These results support our previous findings that apolipoproteins and transthyretin may have a role in GH sensitivity.
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| 4. |
- Even, L., et al.
(författare)
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Role of growth hormone in enchondroplasia and chondral osteogenesis: evaluation by X-ray of the hand
- 2014
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Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 76:1, s. 109-114
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The process of growth and maturation of long (radius and ulna) and short (metacarpals and phalanges) bones of the hand (enchondroplasia) differs from that of the carpal cuboid bones (chondral osteogenesis). This study aimed to assess the impact of growth hormone (GH) on these two processes of bone maturation. METHODS: Subjects of the study were 95 prepubertal children: 30 children with GH deficiency and 65 children with idiopathic short stature, aged 7.4 +/- 1.9 y (mean +/- SD) (trial registration number 98-0198-033). Bone maturation was assessed by the Greulich and Pyle method from X-rays obtained at the start and at 1 and 2 y of GH treatment, separately for carpals, long bones, and short bones, and was expressed as years of delay relative to chronological age. RESULTS: At GH start, the delay in bone maturation in the GH-deficient group was significantly greater for carpals (3.6 +/- 1.3 y) than for long (3.0 +/- 1.3 y) and short (1.7 +/- 1.1 y) bones. The delay was nonsignificantly greater for carpal bones in GH-deficient subjects than in subjects with idiopathic short stature (3.6 +/- 1.3 vs. 3.1 +/- 1.1 y, respectively) and was normalized after 2 y of GH treatment. CONCLUSION: The dominant effect of GH was on chondral osteogenesis, with milder effect on enchondroplasia. A distinct delay in carpal and long-bone maturation, which normalizes during 2 y of GH treatment, was typical in GH-deficient children. Therefore, separate carpal bone assessment in bone age reading is needed.
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- Hochberg, Z., et al.
(författare)
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Child health, developmental plasticity, and epigenetic programming
- 2011
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Ingår i: Endocrine reviews. - : The Endocrine Society. - 0163-769X .- 1945-7189. ; 32:2, s. 159-224
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Forskningsöversikt (refereegranskat)abstract
- Plasticity in developmental programming has evolved in order to provide the best chances of survival and reproductive success to the organism under changing environments. Environmental conditions that are experienced in early life can profoundly influence human biology and long-term health. Developmental origins of health and disease and life-history transitions are purported to use placental, nutritional, and endocrine cues for setting long-term biological, mental, and behavioral strategies in response to local ecological and/or social conditions. The window of developmental plasticity extends from preconception to early childhood and involves epigenetic responses to environmental changes, which exert their effects during life-history phase transitions. These epigenetic responses influence development, cell- and tissue-specific gene expression, and sexual dimorphism, and, in exceptional cases, could be transmitted transgenerationally. Translational epigenetic research in child health is a reiterative process that ranges from research in the basic sciences, preclinical research, and pediatric clinical research. Identifying the epigenetic consequences of fetal programming creates potential applications in clinical practice: the development of epigenetic biomarkers for early diagnosis of disease, the ability to identify susceptible individuals at risk for adult diseases, and the development of novel preventive and curative measures that are based on diet and/or novel epigenetic drugs.
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| 6. |
- Hochberg, Z., et al.
(författare)
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Evo-devo of infantile and childhood growth
- 2008
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Ingår i: Pediatric Research. - 0031-3998. ; 64:1, s. 2-7
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Tidskriftsartikel (refereegranskat)abstract
- Human size is a tradeoff between the evolutionary advantages and disadvantages of being small or big. We now propose that adult size is determined to an important extent during transition from infancy to childhood. This transition is marked by a growth spurt. A delay in the transition has a lifelong impact on stature and is responsible for 44% of children with short stature in developed countries and many more in developing countries. Here, we present the data and theory of an evolutionary adaptive strategy of plasticity in the timing of transition from infancy into childhood to match the prevailing energy supply. We propose that humans have evolved to withstand energy crises by decreasing their body size, and that evolutionary short-term adaptations to energy crises trigger a predictive adaptive response that modify the transition into childhood, culminating in short stature.
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| 7. |
- Jaworek, T., et al.
(författare)
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Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke
- 2022
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 99:16
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives Current genome-wide association studies of ischemic stroke have focused primarily on late-onset disease. As a complement to these studies, we sought to identify the contribution of common genetic variants to risk of early-onset ischemic stroke. Methods We performed a meta-analysis of genome-wide association studies of early-onset stroke (EOS), ages 18-59 years, using individual-level data or summary statistics in 16,730 cases and 599,237 nonstroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late-onset stroke (LOS) and compared polygenic risk scores (PRS) for venous thromboembolism (VTE) between EOS and LOS. Results We observed genome-wide significant associations of EOS with 2 variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared with LOS. The odds ratio (OR) for rs529565, tagging O1, was 0.88 (95% confidence interval [CI]: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using PRSs, we observed that greater genetic risk for VTE, another prothrombotic condition, was more strongly associated with EOS compared with LOS (p = 0.008). Discussion The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.
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| 9. |
- Martin, D. D., et al.
(författare)
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The Use of Bone Age in Clinical Practice - Part 1
- 2011
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Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 76:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- This review examines the role of skeletal maturity ('bone age', BA) assessment in clinical practice. BA is mainly used in children with the following conditions: short stature (addressed in part 1 of this review), tall stature, early or late puberty, and congenital adrenal hyperplasia (all addressed in part 2). Various manual and automatic methods of BA assessment have been developed. Healthy tall children tend to have advanced BA and healthy short children tend to have delayed BA in comparison to chronological age. Growth hormone (GH) treatment of children with GH deficiency leads to a catch-up in BA that is usually appropriate for the height of the child. Response to GH is dependent on BA delay in young children with idiopathic short stature, and GH dosage appears to affect BA acceleration. In chronic renal failure, BA is delayed until puberty but then increases due to increased sensitivity of the growth plate to sex steroids, thus further impairing adult height. The assessment of BA provides an important contribution to the diagnostic workup and management of children with short stature.
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| 10. |
- Shmoish, M., et al.
(författare)
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Prediction of Adult Height by Machine Learning Technique
- 2021
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 106:7
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Tidskriftsartikel (refereegranskat)abstract
- Context: Prediction of AH is frequently undertaken in the clinical setting. The commonly used methods are based on the assessment of skeletal maturation. Predictive algorithms generated by machine learning, which can already automatically drive cars and recognize spoken language, are the keys to unlocking data that can precisely inform the pediatrician for real-time decision making. Objective: To use machine learning (ML) to predict adult height (AH) based on growth measurements until age 6 years. Methods: Growth data from 1596 subjects (798 boys) aged 0-20 years from the longitudinal GrowUp 1974 Gothenburg cohort were utilized to train multiple ML regressors. Of these, 100 were used for model comparison, the rest was used for 5-fold cross-validation. The winning model, random forest (RF), was first validated on 684 additional subjects from the 1974 cohort. It was additionally validated using 1890 subjects from the GrowUp 1990 Gothenburg cohort and 145 subjects from the Edinburgh Longitudinal Growth Study cohort. Results: RF with 51 regression trees produced the most accurate predictions. The best predicting features were sex and height at age 3.4-6.0 years. Observed and predicted AHs were 173.98.9 cm and 173.9 +/- 7.7 cm, respectively, with prediction average error of -0.4 +/- 4.0 cm. Validation of prediction for 684 GrowUp 1974 children showed prediction accuracy r=0.87 between predicted and observed AH (R-2 = 0.75). When validated on the 1990 Gothenburg and Edinburgh cohorts (completely unseen by the learned RF model), the prediction accuracy was r = 0.88 in both cases (R-2 = 0.77). AH in short children was overpredicted and AH in tall children was underpredicted. Prediction absolute error correlated negatively with AH (P < .0001). Conclusion: We show successful, validated ML of AH using growth measurements before age 6 years. The most important features for prediction were sex, and height at age 3.4-6.0. Prediction errors result in over- or underestimates of AH for short and tall subjects, respectively. Prediction by ML can be generalized to other cohorts.
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