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Age, low immunoglobulin G, and M serum levels predict infections in people with AQP4-IgG+ NMOSD treated with rituximab-A multicenter cohort study from the German Neuromyelitis Optica Study Group (NEMOS)
Get PDFINTRODUCTION: Rituximab is effective and widely used as long-term treatment in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD). However, infections remain a significant concern during rituximab treatment. METHODS: We conducted a retrospective multicenter cohort study within the NMO Study Group (NEMOS) in Germany, analyzing demographic and clinical data from people with AQP4-IgG+ NMOSD receiving rituximab or azathioprine by retrospective chart, and compared infection occurrence and severity. For rituximab-treated patients, we collected laboratory data (blood lymphocytes, B-cell counts, serum IgG, IgM, and IgA levels), assessed risk factors for infections, and determined the probability of infection within a 3-month window before and after the laboratory assessment. RESULTS: In 92/170 rituximab and in 12/33 azathioprine treatment episodes, one or more infections were documented. Rituximab and azathioprine showed comparable types and risk of infection (HR = 1.24, 95% CI: 0.68-2.25). Rituximab-treated individuals older than 60 years had a higher risk of infection (HR = 1.62, 95% CI: 1.02-2.57). Hypogammaglobulinemia (IgG 60 years and immunoglobulin serum levels during rituximab treatment may serve as predictors for infection and help to individualize treatment decisions in NMOSD
Improving machine-learning development in allergology: bridging the gap between open-access and cohort-based databases
Get PDFPURPOSE OF REVIEW: The advent of high-throughput data generation and artificial intelligence has transformed allergy research. Open-access database (OAD) and cohort-based database (CBD) provide essential resources for machine learning (ML)-driven algorithms for risk stratification and decision support. It is crucial for allergologists to understand their construction, strengths, and limitations. We review recently published databases with a focus on how these datasets can be combined to enhance research. RECENT FINDINGS: OAD, including environmental monitoring resources, omics repositories, and electronic health records, offer scale, diversity, and opportunities for new hypotheses, but are often limited by sparse clinical annotation, heterogeneous data generation, and incomplete linkage to patient-level outcomes. CBD provide wellphenotyped patients, longitudinal follow up, and high-quality clinical and immunological measurements, yet face constraints in sample size, population diversity, and data sharing. Studies integrating OAD breadth with CBD label fidelity report improved predictive performance when paired with disciplined evaluation. Federated learning and portable feature specifications are emerging to enable privacy-preserving collaborations. SUMMARY: Allergologists play a central role in building ML-ready resources. By ensuring rigorous clinical annotation, standardization of data, transparent methods, and independent validation, they can maximize the utility of OAD and CBD and their combination to accelerate progress toward precision allergy medicine
Meta-analysis of genome-wide association studies of food allergy and IgE-sensitization
No full textBACKGROUND: Food allergies (FA) arise from a complex interplay between an individual's genetic predisposition and environmental factors and their prevalence is increasing. Genome-wide association studies (GWAS) to date have been hindered by small sample sizes and varying FA definitions. OBJECTIVE: Identify novel food allergy risk loci by conducting a GWAS meta-analysis in children and adults using a multi-phenotype approach to ensure the trade-off between sufficient sample size and valid FA definitions. METHODS: Analyses were conducted separately in children and adults based on the following FA phenotypes: self-report, doctors-diagnosis, food-specific sensitization, and doctors-diagnosis plus food-specific sensitization. GWAS from up to 16 cohorts of European ancestry including 229,426 adults and 14,234 children were meta-analyzed. Models were adjusted for sex, age, principal components, and if applicable, further study-specific confounders. Sensitivity models were additionally adjusted for hay fever. Replication was conducted in additional external cohorts and a validation in oral food challenge-defined FA cases. RESULTS: 37 SNPs met suggestive significance (p-value < 1x10(-6)), with two reaching genome-wide significance: rs116936231 (FGL1) in adult doctors-diagnosed FA plus food-specific sensitization phenotype (stable after additional hay fever adjustment) and rs8022829 (AKAP6-NPAS3) which was significant only in the hay fever-adjusted model in adults. However, neither variant was validated. Further, we identified three SNPs previously reported for FA and atopic diseases. CONCLUSION:: This study identified 37 SNPs suggestively associated with FA and demonstrated genetic differences across phenotypes. It highlights the need for a unified FA definition and sheds light on its shared genetic architecture with allergies
Is neighborhood socioeconomic status associated with health behavior in Berlin? Cross-sectional data of the German National Cohort (NAKO)
Get PDFBACKGROUND: Neighborhood socioeconomic status (nSES) can complement individual SES to better assess health-behavior inequalities. The aim of this study was to investigate the relationship between the nSES of defined areas in Berlin with healthy lifestyle. METHODS: This cross-sectional analysis used baseline data from the three Berlin study centers of the German National Cohort (NAKO). We assessed body mass index (BMI), smoking, alcohol consumption, and objectively measured physical activity and combined them to a healthy lifestyle index (HLI; range:0–12 points; 12 = best score). To assess nSES, the Social Index from Berlin’s Social Structure Atlas (1 = best; 7 = worst) was assigned to the participants’ residential locations. We used multivariable regression analyses to examine the association between nSES and the HLI (mean difference with 95% confidence interval, CI) as well as the four individual lifestyle factors (odds ratios (OR) with 95% CI). In sensitivity analyses, nSES was modelled using all seven Social Index categories and as a dichotomy (categories 1–4 vs. 5–7). RESULTS: Of 204,801 NAKO participants, 31,075 were recruited in Berlin, of those 11,922 with complete accelerometry data were included (mean ± SD age 50.6 ± 12.9 years; 52.8% women). The mean HLI was 8.3 ± 2.0 points. Worsening of nSES by one point was associated with a 0.08-point lower HLI (-0.08 (95%-CI -0.10; -0.06)), with a reduced odds of normal weight (0.95; 0.93–0.97) and being a never-smoker (0.96; 0.94–0.98), while it was neither associated with alcohol consumption (1.01; 0.99–1.04)) nor physical activity (0.99; 0.97–1.02)). Sensitivity analyses suggested that differences were mainly driven by a contrast between categories 1–4 and the more disadvantaged categories 5–7. However, the overall pattern of results did not change. CONCLUSIONS: Our analyses suggest a rather small association between Berlin’s nSES and HLI, and slightly stronger associations with BMI and smoking. Future studies using longitudinal data and more neighbourhood measures are needed to better disentangle contextual influences from residential selection and to inform targeted prevention strategies
Sex-specific individual and joint associations of multiple environmental exposures with diabetes and obesity in the population-based German National Cohort (NAKO)
Get PDFRecent studies have suggested a potential association of particulate matter (PM) and noise with diabetes and obesity, but studies examining other environmental exposures and their sex-specific and joint associations remain limited. Therefore, we investigated sex-specific individual and joint associations of annual exposure to multiple environmental factors with diabetes and obesity-related measures using cross-sectional data from the population-based multi-center German National Cohort (NAKO). Outcomes included self-reported diabetes mellitus, body mass index (BMI), obesity (BMI ≥30 kg/m(2)), and waist circumference. Annual mean residential exposures included air pollutants, air temperature, day-evening-night road traffic noise (L(den)) and surrounding greenness (normalized difference vegetation index (NDVI)). We used sex-stratified linear and logistic regression models to assess individual associations and quantile g-computation to assess joint associations. Among 174,955 adult participants (50.4% women), 5.6% reported a diabetes diagnosis and 20.9% were obese. An interquartile range increase in PM(2.5) and L(den) was consistently associated with diabetes and obesity-related measures (e.g., PM(2.5)-diabetes for men: odds ratio (OR) [95% confidence interval] = 1.12 [1.02; 1.22]; L(den)-BMI for women: 0.22 kg/m(2) [0.16; 0.27]). Greenness showed non-linear (inverted U-shaped) with all outcomes. An interquartile range increase in multiple exposures simultaneously was associated with higher odds of diabetes, obesity and higher obesity-related measures (e.g., mixture (PM(2.5),L(den), lack of NDVI)-diabetes: OR = 1.20 [1.09; 1.33] for men; mixture (PM(2.5),L(den), lack of NDVI)-BMI: 0.33 kg/m(2) [0.21; 0.44] for women). While longitudinal studies need to confirm these findings, the study highlights that reducing multiple adverse environmental exposures could be potential targets for the prevention of diabetes and obesity
Convergent and lineage-specific genomic changes shape adaptations in sugar-consuming birds
No full textHigh-sugar diets cause human metabolic diseases, yet several bird lineages convergently adapted to feeding on sugar-rich nectar or fruits. We investigated the underlying molecular mechanisms in hummingbirds, parrots, honeyeaters, and sunbirds by generating nine new genomes and 90 tissue-specific transcriptomes. Comparative screens revealed an excess of repeated selection in both protein-coding and regulatory sequences in sugar-feeding birds, suggesting reuse of genetic elements. Sequence or expression changes in sugar-feeders affect genes involved in blood pressure regulation and lipid, amino acid, and carbohydrate metabolism, with experiments showing functional changes in honeyeater hexokinase 3. MLXIPL, a key regulator of sugar and lipid homeostasis, showed convergent sequence and regulatory changes across all sugar-feeding clades; experiments revealed enhanced sugar-induced transcriptional activity of hummingbird MLXIPL, highlighting its adaptive role in high-sugar diets
Systematic review of international population studies with cardiac magnetic resonance and genomics research data ("Imagenomics")
Get PDFEpidemiological population studies may include cardiac magnetic resonance (CMR)-derived phenotyping and large-scale genotyping, providing unprecedented level of detail to investigate novel gene-lifestyle-disease interactions. The systematic review presents high-level summaries and critically appraises contemporary challenges and biobank opportunities. The authors identified 17 relevant biobanks by searching "CMR," "genome" and "population study" on MEDLINE, EMBASE, and Web of Science 2025. Collectively, studies recruited ∼1 million participants with stored blood samples for extensive genomic analyses, of whom >180,000 have or will undergo CMR. Use of expansive personal data must safeguard participant confidentiality, encourage technological standardization, and champion inclusivity and sustainability. Application of genotypic and imaging-derived phenotypic information will be readily translatable to clinical practice through investigation of, among others, new therapeutic targets and highly sensitive and specific biomarkers. Imaging biobanks are accessible to researchers by application. This systematic review should inspire greater use and cross-collaboration and facilitate powerful discoveries in more heterogeneous population samples
Panchamahabhuta Genomics: Tridosha disease prediction model
No full textTrained Random Forest model for predicting disease category from protein Tridosha composition. Achieves 91.2% accuracy across 13 disease categories using 68,573 ClinVar pathogenic variants. Includes protein Prakriti database and feature encoders. Part of the Panchamahabhuta Genomics framework described in Pande et al. (2025)
Dataset for article "Somatosensory input drives membrane potential dynamics in motor cortex during voluntary limb movement"
No full textCorrespondence to be addressed to Luc Estebanez: [email protected] and James Poulet: [email protected] Whole cell recordings in mouse M1 during forelimb behaviors, with and without somatosensory feedback from the forelimb. The single 6.5 Go HDF5 file includes 44 recordings. Each recording is an HDF Group that contains several datasets: Data_ephys: the Vm samples (in mV, NaN when the recording failed or was interrupted), and the corresponding times in T_ephys. X_limb_tracking and Y_limb_tracking: the X and Y position of the IR reflector positioned on the right forelimb of the mouse. The corresponding time samples are in T_limb_tracking. The status (touched by the limb: 1, not touched: 0) of the capacitive sensors that form the rest ("rest_sensor") and target ("touch_sensor") surfaces, and corresponding times are in T_sensor. the opening of the valve that delivers a reward water droplet ("water_sensor"), and corresponding times are in T_sensor. In addition, each Group comes with 2 attributes: cortical_layer (either 23 or 5 for Layer 2/3 or Layer 5), and is_nerve_cut (0: feedback remains. 1: feedback removed)
Flow-induced Klf4-Akt signaling links EC cycling to mural cell defects in arterial-venous malformations
Get PDFFluid shear stress (FSS) safeguards vascular homeostasis, coordinating endothelial cell (EC) behavior and endothelial - mural cell communication. Disrupted flow sensing driving excessive proliferation contribute to arterial-venous malformations (AVMs) in Hereditary Hemorrhagic Telangiectasia (HHT) vascular disorder. Yet, how flow-dependent cell cycle regulation intersects with mural cell remodeling in HHT remains unclear. METHODS: We used a combination between in vitro shear stress assays and in vivo analyses of multiple murine HHT models, including endothelial-specific loss of Activin-like kinase 1 (Alk1) or Smad4 and bone morphogenic factor 9/10 (BMP9/10) ligand blockade. Retinal vasculature and human nasal mucosal biopsies from HHT2 patients were examined for pathway conservation. Endothelial - mural cell crosstalk was evaluated using transwell and three-dimensional flow-dependent co-culture assays. Loss and gain of function studies were employed to define disease mechanisms. RESULTS: Across all studied murine HHT models and in HHT2 telangiectasias, AVM endothelium exhibited excessive flow-induced Krüpper-like 4 (KLF4) - Akt pathway activation, sustained EC proliferation, and abolition of FSS-mediated cyclin-dependent kinases 2/6 (CDK2/6) inhibition. The hyperproliferative state suppressed the expression of endothelial platelet-derived growth factor B (PDGFB) leading to pericyte loss, and and mural cell remodeling in AVMs. Restoration of endothelial quiescence via inhibition of KLF4, Akt or CDK4/6 rescued FSS-induced PDGFB expression. Pharmacological PDGFB induction with thalidomide restored mural cell coverage, and significantly reduced AVM burden in vivo. CONCLUSION: Our study establishes EC cycle state as the upstream determinant of mural cell stability under pathological flow and provides the mechanistic reasoning for why distinct therapeutic strategies (e.g., CDK4/6 inhibition, Akt modulation, or thalidomide-induced PDGFB upregulation) converge on AVM stabilization