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result(s) for
"Schulze Freya"
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Synthetic bone marrow images augment real samples in developing acute myeloid leukemia microscopy classification models
by
Eckardt, Jan-Niklas
,
Schulze, Freya
,
Winter, Susann
in
631/67/1990/283/1897
,
692/699/1541/1990/283/1897
,
Biomedicine
2025
High-quality image data is essential for training deep learning (DL) classifiers, yet data sharing is often limited by privacy concerns. We hypothesized that generative adversarial networks (GANs) could synthesize bone marrow smear (BMS) images suitable for classifier training. BMS from 1251 patients with acute myeloid leukemia (AML), 51 patients with acute promyelocytic leukemia (APL), and 236 stem cell donors were digitized, and synthetic images were generated using StyleGAN2-Ada. In a blinded visual Turing test, eight hematologists achieved 63% accuracy in identifying synthetic images, confirming high image quality. DL classifiers trained on real data achieved AUROCs of 0.99 across AML, APL, and donor classifications, with performance remaining above 0.95 even when incrementally substituting real data for synthetic samples. Adding synthetic data to real training data offered performance gains for an exceptionally rare disease (APL). Our study demonstrates the usability of synthetic BMS data for training highly accurate image classifiers in microscopy.
Journal Article
Image-based explainable artificial intelligence accurately identifies myelodysplastic neoplasms beyond conventional signs of dysplasia
2025
Cytomorphological assessment of bone marrow smears (BMS) is essential in the diagnosis of myelodysplastic neoplasms (MDS), yet manual evaluation is prone to inter-observer variability. We trained end-to-end deep learning models to distinguish between MDS, acute myeloid leukemia, and bone marrow donor BMS with high accuracy in internal tests and external validation. Occlusion sensitivity mapping revealed the high importance of nuclear structures beyond canonical dysplasia, demonstrating accurate, interpretable MDS detection without labor-intensive cell-level annotation.
Journal Article
Specific CD4+ T Cell Responses to Ancestral SARS-CoV-2 in Children Increase With Age and Show Cross-Reactivity to Beta Variant
by
Tolosa, Eva
,
Woidy, Mathias
,
Weiskopf, Daniela
in
activation induced marker (AIM)
,
Age groups
,
ancestral
2022
SARS-CoV-2 is still a major burden for global health despite effective vaccines. With the reduction of social distancing measures, infection rates are increasing in children, while data on the pediatric immune response to SARS-CoV-2 infection is still lacking. Although the typical disease course in children has been mild, emerging variants may present new challenges in this age group. Peripheral blood mononuclear cells (PBMC) from 51 convalescent children, 24 seronegative siblings from early 2020, and 51 unexposed controls were stimulated with SARS-CoV-2-derived peptide MegaPools from the ancestral and beta variants. Flow cytometric determination of activation-induced markers and secreted cytokines were used to quantify the CD4+ T cell response. The average time after infection was over 80 days. CD4+ T cell responses were detected in 61% of convalescent children and were markedly reduced in preschool children. Cross-reactive T cells for the SARS-CoV-2 beta variant were identified in 45% of cases after infection with an ancestral SARS-CoV-2 variant. The CD4+ T cell response was accompanied most predominantly by IFN-γ and Granzyme B secretion. An antiviral CD4+ T cell response was present in children after ancestral SARS-CoV-2 infection, which was reduced in the youngest age group. We detected significant cross-reactivity of CD4+ T cell responses to the more recently evolved immune-escaping beta variant. Our findings have epidemiologic relevance for children regarding novel viral variants of concern and vaccination efforts.
Journal Article
Reduced Humoral and Cellular Immune Response to Primary COVID-19 mRNA Vaccination in Kidney Transplanted Children Aged 5–11 Years
2023
The situation of limited data concerning the response to COVID-19 mRNA vaccinations in immunocom-promised children hinders evidence-based recommendations. This prospective observational study investigated humoral and T cell responses after primary BNT162b2 vaccination in secondary immunocompromised and healthy children aged 5–11 years. Participants were categorized as: children after kidney transplantation (KTx, n = 9), proteinuric glomerulonephritis (GN, n = 4) and healthy children (controls, n = 8). Expression of activation-induced markers and cytokine secretion were determined to quantify the T cell response from PBMCs stimulated with peptide pools covering the spike glycoprotein of SARS-CoV-2 Wuhan Hu-1 and Omicron BA.5. Antibodies against SARS-CoV-2 spike receptor-binding domain were quantified in serum. Seroconversion was detected in 56% of KTx patients and in 100% of the GN patients and controls. Titer levels were significantly higher in GN patients and controls than in KTx patients. In Ktx patients, the humoral response increased after a third immunization. No differences in the frequency of antigen-specific CD4+ and CD8+ T cells between all groups were observed. T cells showed a predominant anti-viral capacity in their secreted cytokines; however, this capacity was reduced in KTx patients. This study provides missing evidence concerning the humoral and T cell response in immunocompromised children after COVID-19 vaccination.
Journal Article
Occupational UV-Exposure is a Major Risk Factor for Basal Cell Carcinoma: Results of the Population-Based Case-Control Study FB-181
by
Allam, Jean Pierre
,
Trautmann, Freya
,
Letzel, Stephan
in
Basal cell carcinoma
,
Cancer
,
Case studies
2018
OBJECTIVE:The aim of this study was to investigate the role of occupational and nonoccupational ultraviolet (UV)-exposure concerning the development of basal cell carcinoma (BCC).
METHODS:We undertook a population-based multicenter case–control study. Patients with first incident BCC (n = 836) were propensity score matched by age and sex to controls without skin cancer (n = 836). Sociodemographic characteristics, clinical characteristics, and lifetime UV-exposure were assessed by trained investigators. The differential estimation of occupational and nonoccupational UV-exposure dosages was based on validated instruments and established reference values. Associations were assessed using multivariable-adjusted conditional logistic regression models.
RESULTS:Individuals with high levels of occupational UV-exposure were at significantly increased BCC-risk compared with individuals with low [odds ratio (OR) 1.84; 95% confidence interval (95% CI) 1.19 to 2.83 and moderate (OR 1.97; 95% CI 1.20 to 3.22) occupational UV-exposure. Nonoccupational UV-exposure was not independently associated with BCC.
CONCLUSION:Skin cancer prevention strategies should be expanded to the occupational setting.
Journal Article
Long-Term Antibody Response to SARS-CoV-2 in Children
2023
Almost 2 years into the pandemic and with vaccination of children significantly lagging behind adults, long-term pediatric humoral immune responses to SARS-CoV-2 are understudied. The C19.CHILD Hamburg (COVID-19 Child Health Investigation of Latent Disease) Study is a prospective cohort study designed to identify and follow up children and their household contacts infected in the early 2020 first wave of SARS-CoV-2. We screened 6113 children < 18 years by nasopharyngeal swab-PCR in a low-incidence setting after general lockdown, from May 11 to June 30, 2020. A total of 4657 participants underwent antibody testing. Positive tests were followed up by repeated PCR and serological testing of all household contacts over 6 months. In total, the study identified 67 seropositive children (1.44%); the median time after infection at first presentation was 83 days post-symptom onset (PSO). Follow-up of household contacts showed less than 100% seroprevalence in most families, with higher seroprevalence in families with adult index cases compared to pediatric index cases (OR 1.79,
P
= 0.047). Most importantly, children showed sustained seroconversion up to 9 months PSO, and serum antibody concentrations persistently surpassed adult levels (ratio serum IgG spike children vs. adults 90 days PSO 1.75,
P
< 0.001; 180 days 1.38,
P
= 0.01; 270 days 1.54,
P
= 0.001). In a low-incidence setting, SARS-CoV-2 infection and humoral immune response present distinct patterns in children including higher antibody levels, and lower seroprevalence in families with pediatric index cases. Children show long-term SARS-CoV-2 antibody responses. These findings are relevant to novel variants with increased disease burden in children, as well as for the planning of age-appropriate vaccination strategies.
Journal Article