| 1. |
- Tobias, Deirdre K, et al.
(författare)
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
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Ingår i: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
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Forskningsöversikt (refereegranskat)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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| 2. |
- Middeldorp, Christel M., et al.
(författare)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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| 3. |
- Liu, Xueping, et al.
(författare)
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Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P=3.96×10-14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.
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| 4. |
- Cagnoli, Patricia, et al.
(författare)
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Reduced Insular Glutamine and N-Acetylaspartate in Systemic Lupus Erythematosus: A Single-Voxel H-1-MR Spectroscopy Study
- 2013
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Ingår i: Academic Radiology. - : Elsevier BV. - 1878-4046 .- 1076-6332. ; 20:10, s. 1286-1296
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Tidskriftsartikel (refereegranskat)abstract
- Rationale and Objectives: To investigate for differences in metabolic concentrations and ratios between patients with systemic lupus erythematosus (SLE) without (group SLE) and those with neurological symptoms (group NPSLE) compared to a healthy control (group HC) in three normal-appearing brain regions: the frontal white matter, right insula (RI), and occipital gray matter and whether changes in any of the metabolites or metabolic ratios are correlated to disease activity and other clinical parameters. Materials and Methods: Twenty patients with SLE (18 women and 2 men, age range 23.4-64.6 years, mean age 43.9 years), 23 NPSLE patients (23 women, age range 23.7-69.8 years, mean age 42.4 years), and 21 HC (19 women and 2 men, age range 21.0-65.7 years, mean age 43.4 years) were included. All subjects had conventional brain magnetic resonance imaging and H-1 single-voxel spectroscopy, clinical assessment, and laboratory testing. Results: NPSLE patients had significantly reduced N-acetylaspartate (NAA)/creatine compared to HC (P = .02) and SLE patients (P = .01) in the RI. Lower glutamine/creatine levels were also detected in RI in both patient groups and in frontal white matter in NPSLE patients compared to HC (P = .01, P = .02). NAA/Cr ratio in the RI was significantly negatively correlated with the Systemic Lupus Erythematosus Disease Activity Index (r = -0.41; P = .008), and patients with active SLE symptoms also had a trend toward lower NAA/creatine ratios (1.02 vs 1.12; P = .07). Conclusions: The present data support previous findings of abnormal metabolic changes in normal-appearing regions in the brain of both SLE and NPSLE patients and raise the possibility that especially NAA, glutamine, and glutamate may be additional biomarkers for cerebral disease activity in SLE patients as these early metabolic changes occur in the brain of SLE patients before neurologic and imaging manifestations become apparent.
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| 5. |
- Wang, Page I., et al.
(författare)
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Perfusion-weighted MR Imaging in Cerebral Lupus Erythematosus
- 2012
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Ingår i: Academic Radiology. - : Elsevier BV. - 1878-4046 .- 1076-6332. ; 19:8, s. 965-970
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Tidskriftsartikel (refereegranskat)abstract
- Rationale and Objective: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a diagnostically challenging, severe, and life-threatening condition, which is currently lacking a "gold standard." Our aim with this study is to look for magnetic resonance (MR) perfusion differences in NPSLE, SLE, and healthy control (HC) patients and correlate our findings with clinical parameters. Materials and Methods: Twenty-four NPSLE patients, 21 SLE patients, and 21 HC underwent dynamic susceptibility contrast enhanced MR perfusion using a 3-T scanner. Nine prospectively selected intracranial regions of interest were placed in white and gray matter and the cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MU) values were calculated. Subjects underwent clinical evaluation with SLEDAI and serum antibodies. Results: The SLE patients had higher CBF and CBV compared to the HC overall (P =.01) and in specific areas (P =.03-.048). SLE patients with signs of active disease (elevated SLEDAI and anti-double-stranded DNA) had significantly elevated CBV, CBF, and MU in the posterior cingulate gyrus (P =.01-.02). No significant difference was seen in the magnetic resonance perfusion measurements of NPSLE patients compared to SLE and HC, although the NPSLE patients also showed higher CBV variability compared to the SLE (P =.0004) and HC cohort (P <.0001). Conclusion: SLE patients have increased CBV and CBF compared to healthy controls. The SLE patients with clinical markers for active disease have elevated CBV, CBF, and MU in the posterior cingulate gyrus. NPSLE patients show increased variability in perfusion measurements, which may explain why susceptibility contrast enhanced MRI has not yet provided a specific target for NPSLE.
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