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Article: Radiation-Induced Brain Injury: Age Dependency of Neurocognitive Dysfunction Following Radiotherapy.

Rübe, Claudia E / Raid, Silvia / Palm, Jan / Rübe, Christian

2023 Volume 15, Issue 11

Abstract: Cranial radiotherapy is a known risk factor for neurocognitive impairment in cancer survivors. Although radiation-induced cognitive dysfunction is observed in patients of all ages, children seem to be more vulnerable than adults to suffering age-related ... ...

Abstract	Cranial radiotherapy is a known risk factor for neurocognitive impairment in cancer survivors. Although radiation-induced cognitive dysfunction is observed in patients of all ages, children seem to be more vulnerable than adults to suffering age-related deficits in neurocognitive skills. So far, the underlying mechanisms by which IR negatively influences brain functions as well as the reasons for the profound age dependency are still insufficiently known. We performed a comprehensive Pubmed-based literature search to identify original research articles that reported on age dependency of neurocognitive dysfunction following cranial IR exposure. Numerous clinical trials in childhood cancer survivors indicate that the severity of radiation-induced cognitive dysfunction is clearly dependent on age at IR exposure. These clinical findings were related to the current state of experimental research providing important insights into the age dependency of radiation-induced brain injury and the development of neurocognitive impairment. Research in pre-clinical rodent models demonstrates age-dependent effects of IR exposure on hippocampal neurogenesis, radiation-induced neurovascular damage and neuroinflammation.
Language	English
Publishing date	2023-05-31
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15112999
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Article ; Online: Imaging doses for different CBCT protocols on the Halcyon 3.0 linear accelerator - TLD measurements in an anthropomorphic phantom.

Altergot, Angelika / Schürmann, Michaela / Jungert, Tanja / Auerbach, Hendrik / Nüsken, Frank / Palm, Jan / Rübe, Christian / Rübe, Claudia E / Dzierma, Yvonne

Zeitschrift fur medizinische Physik

2023

Abstract: Introduction: Image guided radiotherapy allows for particularly conformal tumour irradiation through precise patient positioning. Becoming the standard for radiotherapy, this increases imaging doses to the patient. The Halcyon 3.0 linear accelerator ( ... ...

Abstract	Introduction: Image guided radiotherapy allows for particularly conformal tumour irradiation through precise patient positioning. Becoming the standard for radiotherapy, this increases imaging doses to the patient. The Halcyon 3.0 linear accelerator (Varian Medical Systems, Palo Alto, CA) requires daily imaging due to its geometry. For this reason, the accelerator is equipped with on-line kV and MV imaging. However, daily CBCT images required for irradiation apply additional radiation, which increases the dose to normal tissue and therefore can affect the patient's secondary cancer risk. In this study, actual organ doses were measured for the kV system, and a comparison of normal tissue doses for all available kV CBCT protocols was presented to demonstrate differences in imaging doses across entities and protocols. In addition, effective dose and secondary cancer risk from imaging are evaluated. Material and methods: Measurements were performed with thermoluminescent dosimeters in an anthropomorphic phantom positioned according to each entity (brain, head and neck, breast, lung, pelvis). CBCT images were obtained, using all available pre-set protocols without further adjustment of the parameters. Measured doses for each position and each protocol were then compared and secondary cancer risk of relevant and specifically radiosensitive organs was calculated. Results: It was found that imaging doses for protocols such as Pelvis and Head could be reduced by up to half using the corresponding Fast and Low Dose modes, respectively. On the other hand, larger field sizes or the Large mode yielded higher doses than their initial protocols. Image Gently was found to spare normal tissue best, however it is not suitable for certain entities due to low image quality or insufficient projection data. Discussion: By using appropriate kV-CBCT protocols, it is possible to reduce imaging doses to a significant extent and therefore spare healthy tissue. Combined with studies of image quality, the results of this study could lead to adjustments in workflow regarding the choice of protocols used in daily routine. This could prevent unnecessary radiation exposure and reduce secondary cancer risk.
Language	English
Publishing date	2023-04-22
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1104517-6
ISSN	1876-4436 ; 0939-3889 ; 0040-5973
ISSN (online)	1876-4436
ISSN	0939-3889 ; 0040-5973
DOI	10.1016/j.zemedi.2023.03.002
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Article ; Online: AN INTERACTIVE ONLINE LEARNING PROGRAM ON CHILD ABUSE AND ITS REPORTING.

Levi, Benjamin H / Mundy, Mandy / Palm, Cathleen / Verdiglione, Nicole / Fiene, Richard / Mincemoyer, Claudia

The journal of educators online

2021 Volume 18, Issue 2

Abstract: This article describes the content and pedagogical foundations of iLookOut for Child Abuse, an interactive, online learning program that was designed for early childhood professionals and others who provide childcare to young children. It also describes ... ...

Abstract	This article describes the content and pedagogical foundations of iLookOut for Child Abuse, an interactive, online learning program that was designed for early childhood professionals and others who provide childcare to young children. It also describes how an online intervention can address a complex social and behavioral issue--viz., how to identify and appropriately respond to concerns of possible child abuse.
Language	English
Publishing date	2021-10-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2413626-8
ISSN	1547-500X ; 1547-500X
ISSN (online)	1547-500X
ISSN	1547-500X
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Article ; Online: Cultured Human Foreskin as a Model System for Evaluating Ionizing Radiation-Induced Skin Injury.

Hippchen, Yanick / Tewary, Gargi / Jung, Daniela / Schmal, Zoé / Meessen, Stephan / Palm, Jan / Rübe, Claudia E

International journal of molecular sciences

2022 Volume 23, Issue 17

Abstract: Purpose: Precise molecular and cellular mechanisms of radiation-induced dermatitis are incompletely understood. Histone variant H2A.J is associated with cellular senescence and modulates senescence-associated secretory phenotype (SASP) after DNA- ... ...

Abstract	Purpose: Precise molecular and cellular mechanisms of radiation-induced dermatitis are incompletely understood. Histone variant H2A.J is associated with cellular senescence and modulates senescence-associated secretory phenotype (SASP) after DNA-damaging insults, such as ionizing radiation (IR). Using ex vivo irradiated cultured foreskin, H2A.J was analyzed as a biomarker of radiation-induced senescence, potentially initiating the inflammatory cascade of radiation-induced skin injury. Methods: Human foreskin explants were collected from young donors, irradiated ex vivo with 10 Gy, and cultured in air-liquid interphase for up to 72 h. At different time-points after ex vivo IR exposure, the foreskin epidermis was analyzed for proliferation and senescence markers by immunofluorescence and immunohistochemical staining of sectioned tissue. Secretion of cytokines was measured in supernatants by ELISA. Using our mouse model with fractionated in vivo irradiation, H2A.J expression was analyzed in epidermal stem/progenitor cell populations localized in different regions of murine hair follicles (HF). Results: Non-vascularized foreskin explants preserved their tissue homeostasis up to 72 h (even after IR exposure), but already non-irradiated foreskin epithelium expressed high levels of H2A.J in all epidermal layers and secreted high amounts of cytokines. Unexpectedly, no further increase in H2A.J expression and no obvious upregulation of cytokine secretion was observed in the foreskin epidermis after ex vivo IR. Undifferentiated keratinocytes in murine HF regions, by contrast, revealed low H2A.J expression in non-irradiated skin and significant radiation-induced H2A.J upregulations at different time-points after IR exposure. Based on its staining characteristics, we presume that H2A.J may have previously underestimated the importance of the epigenetic regulation of keratinocyte maturation. Conclusions: Cultured foreskin characterized by highly keratinized epithelium and specific immunological features is not an appropriate model for studying H2A.J-associated tissue reactions during radiation-induced dermatitis.
MeSH term(s)	Animals ; Cells, Cultured ; Cellular Senescence/radiation effects ; Cytokines ; Epigenesis, Genetic ; Foreskin ; Histones ; Humans ; Male ; Mice ; Radiation, Ionizing ; Radiodermatitis
Chemical Substances	Cytokines ; Histones
Language	English
Publishing date	2022-08-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23179830
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Article ; Online: Deep learning-based differentiation of peripheral high-flow and low-flow vascular malformations in T2-weighted short tau inversion recovery MRI.

Hammer, Simone / Nunes, Danilo Weber / Hammer, Michael / Zeman, Florian / Akers, Michael / Götz, Andrea / Balla, Annika / Doppler, Michael Christian / Fellner, Claudia / Platz Batista da Silva, Natascha / Thurn, Sylvia / Verloh, Niklas / Stroszczynski, Christian / Wohlgemuth, Walter Alexander / Palm, Christoph / Uller, Wibke

Clinical hemorheology and microcirculation

2024

Abstract: Background: Differentiation of high-flow from low-flow vascular malformations (VMs) is crucial for therapeutic management of this orphan disease.: Objective: A convolutional neural network (CNN) was evaluated for differentiation of peripheral ... ...

Abstract	Background: Differentiation of high-flow from low-flow vascular malformations (VMs) is crucial for therapeutic management of this orphan disease. Objective: A convolutional neural network (CNN) was evaluated for differentiation of peripheral vascular malformations (VMs) on T2-weighted short tau inversion recovery (STIR) MRI. Methods: 527 MRIs (386 low-flow and 141 high-flow VMs) were randomly divided into training, validation and test set for this single-center study. 1) Results of the CNN's diagnostic performance were compared with that of two expert and four junior radiologists. 2) The influence of CNN's prediction on the radiologists' performance and diagnostic certainty was evaluated. 3) Junior radiologists' performance after self-training was compared with that of the CNN. Results: Compared with the expert radiologists the CNN achieved similar accuracy (92% vs. 97%, p = 0.11), sensitivity (80% vs. 93%, p = 0.16) and specificity (97% vs. 100%, p = 0.50). In comparison to the junior radiologists, the CNN had a higher specificity and accuracy (97% vs. 80%, p < 0.001; 92% vs. 77%, p < 0.001). CNN assistance had no significant influence on their diagnostic performance and certainty. After self-training, the junior radiologists' specificity and accuracy improved and were comparable to that of the CNN. Conclusions: Diagnostic performance of the CNN for differentiating high-flow from low-flow VM was comparable to that of expert radiologists. CNN did not significantly improve the simulated daily practice of junior radiologists, self-training was more effective.
Language	English
Publishing date	2024-02-01
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1381750-4
ISSN	1875-8622 ; 1386-0291
ISSN (online)	1875-8622
ISSN	1386-0291
DOI	10.3233/CH-232071
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bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
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Article ; Online: Cultured Human Foreskin as a Model System for Evaluating Ionizing Radiation-Induced Skin Injury

Yanick Hippchen / Gargi Tewary / Daniela Jung / Zoé Schmal / Stephan Meessen / Jan Palm / Claudia E. Rübe

International Journal of Molecular Sciences, Vol 23, Iss 9830, p

2022 Volume 9830

Abstract	Purpose: Precise molecular and cellular mechanisms of radiation-induced dermatitis are incompletely understood. Histone variant H2A.J is associated with cellular senescence and modulates senescence-associated secretory phenotype (SASP) after DNA-damaging insults, such as ionizing radiation (IR). Using ex vivo irradiated cultured foreskin, H2A.J was analyzed as a biomarker of radiation-induced senescence, potentially initiating the inflammatory cascade of radiation-induced skin injury. Methods: Human foreskin explants were collected from young donors, irradiated ex vivo with 10 Gy, and cultured in air-liquid interphase for up to 72 h. At different time-points after ex vivo IR exposure, the foreskin epidermis was analyzed for proliferation and senescence markers by immunofluorescence and immunohistochemical staining of sectioned tissue. Secretion of cytokines was measured in supernatants by ELISA. Using our mouse model with fractionated in vivo irradiation, H2A.J expression was analyzed in epidermal stem/progenitor cell populations localized in different regions of murine hair follicles (HF). Results: Non-vascularized foreskin explants preserved their tissue homeostasis up to 72 h (even after IR exposure), but already non-irradiated foreskin epithelium expressed high levels of H2A.J in all epidermal layers and secreted high amounts of cytokines. Unexpectedly, no further increase in H2A.J expression and no obvious upregulation of cytokine secretion was observed in the foreskin epidermis after ex vivo IR. Undifferentiated keratinocytes in murine HF regions, by contrast, revealed low H2A.J expression in non-irradiated skin and significant radiation-induced H2A.J upregulations at different time-points after IR exposure. Based on its staining characteristics, we presume that H2A.J may have previously underestimated the importance of the epigenetic regulation of keratinocyte maturation. Conclusions: Cultured foreskin characterized by highly keratinized epithelium and specific immunological features is not an appropriate ...
Keywords	cultured foreskin ; ionizing radiation ; radiation-induced dermatitis ; histone variant H2A.J ; cellular senescence ; senescence-associated secretory phenotype (SASP) ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: The Effect of Brachionus calyciflorus (Rotifera) on Larviculture and Fatty Acid Composition of Pikeperch ( Sander lucioperca (L.)) Cultured under Pseudo-Green Water Conditions

Adrian A. Bischoff / Melanie Kubitz / Claudia M. Wranik / Laura Ballesteros-Redondo / Patrick Fink / Harry W. Palm

Sustainability, Vol 14, Iss 6607, p

2022 Volume 6607

Abstract: A new cultivation system with the chlorophyte Monoraphidium contortum combined with a self-sustaining culture of the freshwater rotifer Brachionus calyciflorus was applied for Sander lucioperca (L.) larviculture. Survival, morphometrics, as well as fatty ...

Abstract	A new cultivation system with the chlorophyte Monoraphidium contortum combined with a self-sustaining culture of the freshwater rotifer Brachionus calyciflorus was applied for Sander lucioperca (L.) larviculture. Survival, morphometrics, as well as fatty acid composition of pikeperch larvae were analyzed after a ten-day feeding period. By using the pseudo-green water technique with improved aeration and water movement at the surface, survival rates reached up to 94%, with a total larval length of 8.1 ± 0.3 mm and a specific length growth rate of up to 4.1% day −1 for S. lucioperca . The biochemical composition of B. calyciflorus and especially its contents in C18 PUFAs and suitable n-3/n-6 ratios met the nutritional requirements of pikeperch larvae. The high abundance of highly unsaturated fatty acids (HUFAs) in the diet appeared to be less important in the first feeding due to a possible retention of essential fatty acids, which originate from the yolk sac reserves, at adequate levels. Exponential growth of microalgae and zooplankton under the applied conditions was most effective when stocking M. contortum five days and B. calyciflorus three days before adding the fish larvae. Appropriate timing and sufficient live feed density allowed a successful integration of B. calyciflorus into pikeperch larviculture. We hypothesize that feeding pikeperch larvae with a self-sustaining Brachionus -culture under pseudo-green water conditions with minor disruptions during larviculture will improve survival and growth. This system is a first step towards pikeperch larviculture inside recirculated aquaculture systems (RAS) under continuous feed supply with live feed within the same aquaculture unit.
Keywords	pikeperch Sander lucioperca ; pseudo-green water technique ; Brachionus calyciflorus ; survival ; growth ; fatty acid composition ; Environmental effects of industries and plants ; TD194-195 ; Renewable energy sources ; TJ807-830 ; Environmental sciences ; GE1-350
Subject code	333
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Neurological outcome in long-chain hydroxy fatty acid oxidation disorders.

Mütze, Ulrike / Ottenberger, Alina / Gleich, Florian / Maier, Esther M / Lindner, Martin / Husain, Ralf A / Palm, Katja / Beblo, Skadi / Freisinger, Peter / Santer, René / Thimm, Eva / Vom Dahl, Stephan / Weinhold, Natalie / Grohmann-Held, Karina / Haase, Claudia / Hennermann, Julia B / Hörbe-Blindt, Alexandra / Kamrath, Clemens / Marquardt, Iris /

Marquardt, Thorsten / Behne, Robert / Haas, Dorothea / Spiekerkoetter, Ute / Hoffmann, Georg F / Garbade, Sven F / Grünert, Sarah C / Kölker, Stefan

Annals of clinical and translational neurology

2024 Volume 11, Issue 4, Page(s) 883–898

Abstract: Objective: This study aims to elucidate the long-term benefit of newborn screening (NBS) for individuals with long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (MTP) deficiency, inherited metabolic diseases ... ...

Abstract	Objective: This study aims to elucidate the long-term benefit of newborn screening (NBS) for individuals with long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (MTP) deficiency, inherited metabolic diseases included in NBS programs worldwide. Methods: German national multicenter study of individuals with confirmed LCHAD/MTP deficiency identified by NBS between 1999 and 2020 or selective metabolic screening. Analyses focused on NBS results, confirmatory diagnostics, and long-term clinical outcomes. Results: Sixty-seven individuals with LCHAD/MTP deficiency were included in the study, thereof 54 identified by NBS. All screened individuals with LCHAD deficiency survived, but four with MTP deficiency (14.8%) died during the study period. Despite NBS and early treatment neonatal decompensations (28%), symptomatic disease course (94%), later metabolic decompensations (80%), cardiomyopathy (28%), myopathy (82%), hepatopathy (32%), retinopathy (17%), and/or neuropathy (22%) occurred. Hospitalization rates were high (up to a mean of 2.4 times/year). Disease courses in screened individuals with LCHAD and MTP deficiency were similar except for neuropathy, occurring earlier in individuals with MTP deficiency (median 3.9 vs. 11.4 years; p = 0.0447). Achievement of dietary goals decreased with age, from 75% in the first year of life to 12% at age 10, and consensus group recommendations on dietary management were often not achieved. Interpretation: While NBS and early treatment result in improved (neonatal) survival, they cannot reliably prevent long-term morbidity in screened individuals with LCHAD/MTP deficiency, highlighting the urgent need of better therapeutic strategies and the development of disease course-altering treatment.
MeSH term(s)	Infant, Newborn ; Humans ; Child ; Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase/metabolism ; Lipid Metabolism, Inborn Errors/diagnosis ; Lipid Metabolism, Inborn Errors/therapy ; Lipid Metabolism, Inborn Errors/metabolism ; Mitochondrial Trifunctional Protein/metabolism ; Mitochondrial Trifunctional Protein/deficiency ; Fatty Acids/metabolism ; Cardiomyopathies ; Nervous System Diseases ; Rhabdomyolysis ; Mitochondrial Myopathies
Chemical Substances	Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase (EC 1.1.1.211) ; Mitochondrial Trifunctional Protein (EC 2.3.1.16) ; Fatty Acids
Language	English
Publishing date	2024-01-23
Publishing country	United States
Document type	Multicenter Study ; Journal Article
ZDB-ID	2740696-9
ISSN	2328-9503 ; 2328-9503
ISSN (online)	2328-9503
ISSN	2328-9503
DOI	10.1002/acn3.52002
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Article ; Online: Increasing genomic instability during cancer therapy in a patient with Li-Fraumeni syndrome.

Schuler, Nadine / Palm, Jan / Schmitz, Sabine / Lorat, Yvonne / Rübe, Claudia E

Clinical and translational radiation oncology

2017 Volume 7, Page(s) 71–78

Abstract: Background: Li-Fraumeni syndrome (LFS) is a cancer predisposition disorder characterized by germline mutations of the p53 tumor-suppressor gene. In response to DNA damage, p53 stimulates protective cellular processes including cell-cycle arrest and ... ...

Abstract	Background: Li-Fraumeni syndrome (LFS) is a cancer predisposition disorder characterized by germline mutations of the p53 tumor-suppressor gene. In response to DNA damage, p53 stimulates protective cellular processes including cell-cycle arrest and apoptosis to prevent aberrant cell proliferation. Current cancer therapies involve agents that damage DNA, which also affect non-cancerous hematopoietic stem/progenitor cells. Here, we report on a child with LFS who developed genomic instability during craniospinal irradiation for metastatic choroid plexus carcinoma (CPC). Case presentation: This previously healthy 4-year-old boy presented with parieto-temporal brain tumor, diagnosed as CPC grade-3. Screening for cancer-predisposing syndrome revealed heterozygous p53 germline mutation, leading to LFS diagnosis. After tumour resection and systemic chemotherapy, entire craniospinal axis was irradiated due to leptomeningeal seeding, resulting in disease stabilization for nearly 12 months. Blood lymphocytes of LFS patient (p53-deficient) and age-matched tumor-children (p53-proficient) were collected before, during and after craniospinal irradiation and compared with asymptomatic carriers for identical p53 mutation, not exposed to DNA-damaging treatment. In p53-deficient lymphocytes of LFS patient radiation-induced DNA damage failed to induce cell-cycle arrest or apoptosis. Although DNA repair capacity was not impaired, p53-deficient blood lymphocytes of LFS patient showed significant accumulation of 53BP1-foci during and even several months after irradiation, reflecting persistent DNA damage. Electron microscopy revealed DNA abnormalities ranging from simple unrepaired lesions to chromosomal abnormalities. Metaphase spreads of p53-deficient lymphocytes explored by mFISH revealed high amounts of complex chromosomal aberrations after craniospinal irradiation. Conclusions: Tumor suppressor p53 plays a central role in maintaining genomic stability by promoting cell-cycle checkpoints and apoptosis. Here, we demonstrate that a patient with LFS receiving craniospinal irradiation including large volumes of bone marrow developed progressive genomic instability of the hematopoietic system. During DNA-damaging radiotherapy, genome-stabilizing mechanisms in proliferating stem/progenitor cells are perturbed by p53 deficiency, increasing the risk of cancer initiation and progression.
Language	English
Publishing date	2017-11-02
Publishing country	Ireland
Document type	Case Reports
ISSN	2405-6308
ISSN (online)	2405-6308
DOI	10.1016/j.ctro.2017.10.004
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Article ; Online: Concordance of SNP- and allele-based typing workflows in the context of a large-scale international

Coipan, Claudia E / Dallman, Timothy J / Brown, Derek / Hartman, Hassan / van der Voort, Menno / van den Berg, Redmar R / Palm, Daniel / Kotila, Saara / van Wijk, Tom / Franz, Eelco

Microbial genomics

2020 Volume 6, Issue 3

Abstract: A large European multi- ... ...

Abstract	A large European multi-country
MeSH term(s)	Alleles ; Disease Outbreaks ; Humans ; Polymorphism, Single Nucleotide ; Salmonella Infections/epidemiology ; Salmonella Infections/microbiology ; Salmonella enteritidis/genetics ; Whole Genome Sequencing ; Workflow
Language	English
Publishing date	2020-02-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2835258-0
ISSN	2057-5858 ; 2057-5858
ISSN (online)	2057-5858
ISSN	2057-5858
DOI	10.1099/mgen.0.000318
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