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Childhood obesity poses a significant public health challenge, yet the molecular intricacies underlying its pathobiology remain elusive. Leveraging extensive multi-omics profiling (methylome, miRNome, transcriptome, proteins and metabolites) and a rich phenotypic characterization across two parts of Europe within the population-based Human Early Life Exposome project, we unravel the molecular landscape of childhood obesity and associated metabolic dysfunction. Our integrative analysis uncovers three clusters of children defined by specific multi-omics profiles, one of which characterized not only by higher adiposity but also by a high degree of metabolic complications. This high-risk cluster exhibits a complex interplay across many biological pathways, predominantly underscored by inflammation-related cascades. Further, by incorporating comprehensive information from the environmental risk-scape of the critical pregnancy period, we identify pre-pregnancy body mass index and environmental pollutants like perfluorooctanoate and mercury as important determinants of the high-risk cluster. Overall, our work helps to identify potential risk factors for prevention and intervention strategies early in the life course aimed at mitigating obesity and its long-term health consequences., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Urinary metabolic profiling is a promising powerful tool to reflect dietary intake and can help understand metabolic alterations in response to diet quality. Here, we used 1 H NMR spectroscopy in a multicountry study in European children (1147 children from 6 different cohorts) and identified a common panel of 4 urinary metabolites (hippurate, N -methylnicotinic acid, urea, and sucrose) that was predictive of Mediterranean diet adherence (KIDMED) and ultra-processed food consumption and also had higher capacity in discriminating children's diet quality than that of established sociodemographic determinants. Further, we showed that the identified metabolite panel also reflected the associations of these diet quality indicators with C-peptide, a stable and accurate marker of insulin resistance and future risk of metabolic disease. This methodology enables objective assessment of dietary patterns in European child populations, complementary to traditional questionary methods, and can be used in future studies to evaluate diet quality. Moreover, this knowledge can provide mechanistic evidence of common biological pathways that characterize healthy and unhealthy dietary patterns, and diet-related molecular alterations that could associate to metabolic disease., Competing Interests: NS, AS, EP, AN, YZ, KM, CL, LM, SF, LA, SA, XB, AB, MC, SF, RG, BH, RM, HM, CM, FR, OR, TR, EB, ES, JU, MV, PV, TV, JW, DC, MV, HK, LC No competing interests declared, MC Is an employee of AstraZeneca. The author declares that no other competing interests exist, (© 2022, Stratakis et al.)

Rates of migration to Europe, and within Europe, have increased in recent years, with considerable implications for health systems. Migrants in Europe face a disproportionate burden of tuberculosis, HIV, and hepatitis B and C, yet experience a large number of barriers to accessing statutory health care on arrival. A better understanding of how to deliver effective and cost-effective screening, vaccination, and health services to this group is now crucial. We did a systematic review to document and assess the effectiveness and cost-effectiveness of approaches used for infectious diseases screening, and to explore facilitators and barriers experienced by migrants to accessing screening programmes. Following PRISMA guidelines, we searched Embase, PubMed, PsychINFO, the Cochrane Library, and Web of Science (1989 to July 1, 2015, updated on Jan 1, 2018), with no language restrictions, and systematically approached experts across the European Union (EU) for grey literature. Inclusion criteria were primary research studies assessing screening interventions for any infectious disease in the migrant (foreign-born) population residing in EU or European Economic Area (EEA) countries. Primary outcomes were the following effectiveness indicators: uptake of screening, coverage, infections detected, and treatment outcomes. Of 4112 unique records, 47 studies met our inclusion criteria, from ten European countries (Belgium, Denmark, France, Italy, the Netherlands, Norway, Spain, Sweden, Switzerland, and the UK) encompassing 248 402 migrants. We found that most European countries screening migrants focus on single diseases only-predominantly active or latent tuberculosis infection-and specifically target asylum seekers and refugees, with 22 studies reporting on other infections (including HIV and hepatitis B and C). An infection was detected in 3·74% (range 0·00-95·16) of migrants. Latent tuberculosis had the highest prevalence across all infections (median 15·02% [0·35-31·81]). Uptake of screening by migrants was high (median 79·50% [18·62-100·00]), particularly in primary health-care settings (uptake 96·77% [76·00-100·00]). However, in 24·62% (0·12-78·99) of migrants screening was not completed and a final diagnosis was not made. Pooled data highlight high treatment completion in migrants (83·79%, range 0·00-100·00), yet data were highly heterogeneous for this outcome, masking important disparities between studies and infections, with only 54·45% (35·71-72·27) of migrants with latent tuberculosis ultimately completing treatment after screening. Coverage of the migrant population in Europe is low (39·29% [14·53-92·50]). Data on cost-effectiveness were scarce, but suggest moderate to high cost-effectiveness of migrant screening programmes depending on migrant group and disease targeted. European countries have adopted a variety of approaches to screening migrants for infections; however, these are limited in scope to single diseases and a narrow subset of migrants, with low coverage. More emphasis must be placed on developing innovative and sustainable strategies to facilitate screening and treatment completion and improve health outcomes, encompassing multiple key infections with consideration given to a wider group of high-risk migrants. Policy makers and researchers involved with global migration need to ensure a longer-term view on improving health outcomes in migrant populations as they integrate into health systems in host countries., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Neurodegenerative diseases of the central nervous system are characterized by pathogenetic cellular and molecular changes in specific areas of the brain that lead to the dysfunction and/or loss of explicit neuronal populations. Despite exhibiting different clinical profiles and selective neuronal loss, common features such as abnormal protein deposition, dysfunctional cellular transport, mitochondrial deficits, glutamate excitotoxicity, iron accumulation and inflammation are observed in many neurodegenerative disorders, suggesting converging pathways of neurodegeneration. We have generated comparative genome-wide gene expression data, using the Illumina HumanRef 8 Beadchip, for Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis, Parkinson's disease, and schizophrenia using an extensive cohort (n = 113) of well-characterized post-mortem brain tissues. The analysis of whole-genome expression patterns across these major disorders offers an outstanding opportunity not only to look into exclusive disease-specific changes, but more importantly to look for potential common molecular pathogenic mechanisms. Surprisingly, no dysregulated gene that passed our selection criteria was found in common across all six diseases. However, 61 dysregulated genes were shared when comparing five and four diseases. The few genes highlighted by our direct gene comparison analysis hint toward common neuronal homeostatic, survival and synaptic plasticity pathways. In addition, we report changes to several inflammation-related genes in all diseases. This work is supportive of a general role of the innate immune system in the pathogenesis and/or response to neurodegeneration.

The use of an appropriate reference gene to ensure accurate normalisation is crucial for the correct quantification of gene expression using qPCR assays and RNA arrays. The main criterion for a gene to qualify as a reference gene is a stable expression across various cell types and experimental settings. Several reference genes are commonly in use but more and more evidence reveals variations in their expression due to the presence of on-going neuropathological disease processes, raising doubts concerning their use. We conducted an analysis of genome-wide changes of gene expression in the human central nervous system (CNS) covering several neurological disorders and regions, including the spinal cord, and were able to identify a number of novel stable reference genes. We tested the stability of expression of eight novel (ATP5E, AARS, GAPVD1, CSNK2B, XPNPEP1, OSBP, NAT5 and DCTN2) and four more commonly used (BECN1, GAPDH, QARS and TUBB) reference genes in a smaller cohort using RT-qPCR. The most stable genes out of the 12 reference genes were tested as normaliser to validate increased levels of a target gene in CNS disease. We found that in human post-mortem tissue the novel reference genes, XPNPEP1 and AARS, were efficient in replicating microarray target gene expression levels and that XPNPEP1 was more efficient as a normaliser than BECN1, which has been shown to change in expression as a consequence of neuronal cell loss. We provide herein one more suitable novel reference gene, XPNPEP1, with no current neuroinflammatory or neurodegenerative associations that can be used for gene quantitative gene expression studies with human CNS post-mortem tissue and also suggest a list of potential other candidates. These data also emphasise the importance of organ/tissue-specific stably expressed genes as reference genes for RNA studies.