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Article ; Online: Perceived transition readiness among adolescents and young adults with neurofibromatosis type 1 and plexiform neurofibromas: a cross-sectional descriptive study.

Siegel, Atara / Lockridge, Robin / Struemph, Kari L / Toledo-Tamula, Mary Anne / Little, Paige / Wolters, Pamela L / Dufek, Anne / Tibery, Cecilia / Baker, Melissa / Wideman, Brigitte C / Martin, Staci

Journal of pediatric psychology

2024

Abstract: ... were still learning Self-Management skills (M = 3.37, SD = 1.08) and Self-Advocacy skills (M = 3.98, SD ...

Abstract	Objectives: Neurofibromatosis type 1 (NF1) is a genetic cancer predisposition syndrome that can impact multiple organ systems and is associated with plexiform neurofibroma tumors, requiring care from birth through adulthood. Adolescents and young adults (AYAs) with NF1 face several barriers to transition from pediatric to adult care. This cross-sectional study aimed to assess transition readiness in this population and to evaluate relationships between specific NF1 symptoms and transition readiness. Methods: AYAs (aged 16-24) enrolled in existing studies related to NF1 were eligible. AYAs and their parents completed measures of transition readiness (Transition Readiness Assessment Questionnaire version 4 [TRAQ-4]), and AYAs also completed a transition readiness interview (UNC TRxANSITION). Results: Thirty-eight AYAs (mean age = 19.95 ± 2.68 years) participated in the study. Average TRAQ scores indicated that AYAs were still learning Self-Management skills (M = 3.37, SD = 1.08) and Self-Advocacy skills (M = 3.98, SD = 0.67). Older AYAs had higher TRAQ scores for Self-Management (r = 0.70, p < .001) and Self-Advocacy (r = 0.41, p = .011) than younger AYAs. Parents and AYAs had similar TRAQ scores. About one third of AYAs (37.8%, n = 14) expressed uncertainty about how NF1 might affect them in the future. The remaining AYAs mostly expressed concerns regarding tumor growth, pain, or cancer. Conclusions: In this small study, preliminary findings suggest that AYAs with NF1 express confidence in many areas of transition readiness but continue to require support, particularly with Self-Management skills. Given the gaps in understanding of future health risks, AYAs with NF1 would benefit from early assessment, psychoeducation, and support for transition readiness to adult care.
Language	English
Publishing date	2024-02-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	625329-5
ISSN	1465-735X ; 0146-8693
ISSN (online)	1465-735X
ISSN	0146-8693
DOI	10.1093/jpepsy/jsae006
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Article ; Online: Aggregated spatial intensity as a method for estimating point-level exposures within area-level units: The case of tobacco retailer exposure in census tracts.

Brooks, Madeline M / Siegel, Scott D / Corrigan, Anne E / Curriero, Frank C

Spatial and spatio-temporal epidemiology

2022 Volume 41, Page(s) 100482

Abstract: Background: Aggregating point-level events to area-level units can produce misleading interpretations when displayed via choropleth maps. We developed the aggregated intensity method to share point-level location information across unit boundaries prior ...

Abstract	Background: Aggregating point-level events to area-level units can produce misleading interpretations when displayed via choropleth maps. We developed the aggregated intensity method to share point-level location information across unit boundaries prior to aggregation. This method was applied to tobacco retailers among census tracts in New Castle County, DE. Methods: Aggregated intensity uses kernel density estimation to generate spatially continuous expected counts of events per unit area, then aggregates these results to area-level units. We calculated a relative difference measure to compare aggregated intensity to observed counts. Results: Aggregated intensity produces estimates of event exposure unconstrained by boundaries. The relative difference between aggregated intensity and counts is greater for units with many events proximal to their borders. The appropriateness of aggregated intensity depends on events' spatial influence and proximity to unit boundaries, as well as computational inputs. Conclusions: Aggregated intensity may facilitate more spatially realistic estimates of exposure to point-level events.
MeSH term(s)	Census Tract ; Commerce ; Humans ; Spatial Analysis ; Nicotiana ; Tobacco Products
Language	English
Publishing date	2022-01-21
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2515896-X
ISSN	1877-5853 ; 1877-5845
ISSN (online)	1877-5853
ISSN	1877-5845
DOI	10.1016/j.sste.2022.100482
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Article ; Online: Regulus infers signed regulatory relations from few samples' information using discretization and likelihood constraints.

Louarn, Marine / Collet, Guillaume / Barré, Ève / Fest, Thierry / Dameron, Olivier / Siegel, Anne / Chatonnet, Fabrice

PLoS computational biology

2024 Volume 20, Issue 1, Page(s) e1011816

Abstract: Motivation: Transcriptional regulation is performed by transcription factors (TF) binding to DNA in context-dependent regulatory regions and determines the activation or inhibition of gene expression. Current methods of transcriptional regulatory ... ...

Abstract	Motivation: Transcriptional regulation is performed by transcription factors (TF) binding to DNA in context-dependent regulatory regions and determines the activation or inhibition of gene expression. Current methods of transcriptional regulatory circuits inference, based on one or all of TF, regions and genes activity measurements require a large number of samples for ranking the candidate TF-gene regulation relations and rarely predict whether they are activations or inhibitions. We hypothesize that transcriptional regulatory circuits can be inferred from fewer samples by (1) fully integrating information on TF binding, gene expression and regulatory regions accessibility, (2) reducing data complexity and (3) using biology-based likelihood constraints to determine the global consistency between a candidate TF-gene relation and patterns of genes expressions and region activations, as well as qualify regulations as activations or inhibitions. Results: We introduce Regulus, a method which computes TF-gene relations from gene expressions, regulatory region activities and TF binding sites data, together with the genomic locations of all entities. After aggregating gene expressions and region activities into patterns, data are integrated into a RDF (Resource Description Framework) endpoint. A dedicated SPARQL (SPARQL Protocol and RDF Query Language) query retrieves all potential relations between expressed TF and genes involving active regulatory regions. These TF-region-gene relations are then filtered using biological likelihood constraints allowing to qualify them as activation or inhibition. Regulus provides signed relations consistent with public databases and, when applied to biological data, identifies both known and potential new regulators. Regulus is devoted to context-specific transcriptional circuits inference in human settings where samples are scarce and cell populations are closely related, using discretization into patterns and likelihood reasoning to decipher the most robust regulatory relations.
MeSH term(s)	Humans ; Gene Expression Regulation/genetics ; Transcription Factors/metabolism ; Genomics/methods ; Databases, Factual ; Protein Binding ; Gene Regulatory Networks/genetics
Chemical Substances	Transcription Factors
Language	English
Publishing date	2024-01-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2193340-6
ISSN	1553-7358 ; 1553-734X
ISSN (online)	1553-7358
ISSN	1553-734X
DOI	10.1371/journal.pcbi.1011816
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Article ; Online: Using automated reasoning to explore the metabolism of unconventional organisms: a first step to explore host-microbial interactions.

Frioux, Clémence / Dittami, Simon M / Siegel, Anne

Biochemical Society transactions

2020 Volume 48, Issue 3, Page(s) 901–913

Abstract: Systems modelled in the context of molecular and cellular biology are difficult to represent with a single calibrated numerical model. Flux optimisation hypotheses have shown tremendous promise to accurately predict bacterial metabolism but they require ... ...

Abstract	Systems modelled in the context of molecular and cellular biology are difficult to represent with a single calibrated numerical model. Flux optimisation hypotheses have shown tremendous promise to accurately predict bacterial metabolism but they require a precise understanding of metabolic reactions occurring in the considered species. Unfortunately, this information may not be available for more complex organisms or non-cultured microorganisms such as those evidenced in microbiomes with metagenomic techniques. In both cases, flux optimisation techniques may not be applicable to elucidate systems functioning. In this context, we describe how automatic reasoning allows relevant features of an unconventional biological system to be identified despite a lack of data. A particular focus is put on the use of Answer Set Programming, a logic programming paradigm with combinatorial optimisation functionalities. We describe its usage to over-approximate metabolic responses of biological systems and solve gap-filling problems. In this review, we compare steady-states and Boolean abstractions of metabolic models and illustrate their complementarity via applications to the metabolic analysis of macro-algae. Ongoing applications of this formalism explore the emerging field of systems ecology, notably elucidating interactions between a consortium of microbes and a host organism. As the first step in this field, we will illustrate how the reduction in microbiotas according to expected metabolic phenotypes can be addressed with gap-filling problems.
MeSH term(s)	Algorithms ; Arabidopsis ; Bacteria/metabolism ; Computational Biology ; Escherichia coli ; Haemophilus influenzae ; Metabolic Networks and Pathways ; Microbial Interactions ; Models, Biological ; Models, Theoretical ; Pattern Recognition, Automated ; Phenotype ; Seaweed/microbiology ; Software ; Systems Biology
Language	English
Publishing date	2020-05-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	184237-7
ISSN	1470-8752 ; 0300-5127
ISSN (online)	1470-8752
ISSN	0300-5127
DOI	10.1042/BST20190667
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Article: Editorial: Applications of biological networks in biomedicine.

Maracaja-Coutinho, Vinicius / Di Genova, Alex / Siegel, Anne / Latorre, Mauricio

Frontiers in molecular biosciences

2023 Volume 9, Page(s) 1005183

Language	English
Publishing date	2023-01-10
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2022.1005183
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Article: The Effect of Non-penicillin Antibiotic Regimens on Neonatal Outcomes in Preterm Premature Rupture of Membranes.

Siegel, Anne M / Heine, Robert Phillips / Dotters-Katz, Sarah K

AJP reports

2019 Volume 9, Issue 1, Page(s) e67–e71

Abstract: ... ...

Abstract	Objective
Language	English
Publishing date	2019-03-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2628074-7
ISSN	2157-7005 ; 2157-6998
ISSN (online)	2157-7005
ISSN	2157-6998
DOI	10.1055/s-0039-1683378
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Zs.A 6934: Show issues

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Article ; Online: An activation specific anti-Mac-1 designed ankyrin repeat protein improves survival in a mouse model of acute lung injury.

Siegel, Patrick M / Przewosnik, Anne-Sophie / Wrobel, Jan / Heidt, Timo / Moser, Martin / Peter, Karlheinz / Bode, Christoph / Diehl, Philipp / Bojti, István

Scientific reports

2022 Volume 12, Issue 1, Page(s) 6296

Abstract: The acute respiratory distress syndrome (ARDS) is a life-threatening clinical condition. The number of ARDS cases has risen dramatically recently but specific treatment options are limited. ARDS is associated with an overshooting inflammatory response ... ...

Abstract	The acute respiratory distress syndrome (ARDS) is a life-threatening clinical condition. The number of ARDS cases has risen dramatically recently but specific treatment options are limited. ARDS is associated with an overshooting inflammatory response and neutrophils play a central role in its pathogenesis. Neutrophils express the integrin Mac-1 on their surface which adopts a resting and activated conformation depending on leukocyte activation. The aim of this study was to investigate the anti-inflammatory effects of the unique activation-specific anti-Mac-1 DARPin 'F7' in a mouse model of ARDS. ARDS was induced by intratracheal lipopolysaccharide (LPS) instillation and the acute (day 1-4) and chronic phase (day 5-10) were studied. After expression and purification, F7, a control DARPin and PBS, were applied daily via the intraperitoneal route. Survival and weight loss were recorded. Histological analysis of lung sections, flow cytometric leukocyte analysis of blood and bronchioalveolar lavage (BALF) were performed. Moreover, protein concentration and cytokine levels were determined in the BALF. Treatment with F7 improved survival and reduced weight loss significantly compared to treatment with the control DARPin or PBS. Neutrophil count in the BALF and peripheral blood were significantly reduced in mice treated with F7. Histology revealed significantly reduced pulmonary inflammation in the F7 treated group. Treatment with DARPin F7 inhibited neutrophil accumulation, reduced signs of local and systemic inflammation and improved survival in a mouse model of ARDS. F7 may be a novel anti-inflammatory drug candidate for the treatment of severe ARDS.
MeSH term(s)	Acute Lung Injury/metabolism ; Animals ; Ankyrin Repeat ; Anti-Inflammatory Agents/pharmacology ; Bronchoalveolar Lavage Fluid ; Disease Models, Animal ; Lipopolysaccharides/metabolism ; Lung/pathology ; Macrophage-1 Antigen/metabolism ; Mice ; Respiratory Distress Syndrome/drug therapy ; Weight Loss
Chemical Substances	Anti-Inflammatory Agents ; Lipopolysaccharides ; Macrophage-1 Antigen
Language	English
Publishing date	2022-04-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-10090-6
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Article ; Online: Constructing xenobiotic maps of metabolism to predict enzymes catalyzing metabolites capable of binding to DNA.

Conan, Mael / Théret, Nathalie / Langouet, Sophie / Siegel, Anne

BMC bioinformatics

2021 Volume 22, Issue 1, Page(s) 450

Abstract: Background: The liver plays a major role in the metabolic activation of xenobiotics (drugs, chemicals such as pollutants, pesticides, food additives ... ). Among environmental contaminants of concern, heterocyclic aromatic amines (HAA) are xenobiotics ... ...

Abstract	Background: The liver plays a major role in the metabolic activation of xenobiotics (drugs, chemicals such as pollutants, pesticides, food additives...). Among environmental contaminants of concern, heterocyclic aromatic amines (HAA) are xenobiotics classified by IARC as possible or probable carcinogens (2A or 2B). There exist little information about the effect of these HAA in humans. While HAA is a family of more than thirty identified chemicals, the metabolic activation and possible DNA adduct formation have been fully characterized in human liver for only a few of them (MeIQx, PhIP, A[Formula: see text]C). Results: We have developed a modeling approach in order to predict all the possible metabolites of a xenobiotic and enzymatic profiles that are linked to the production of metabolites able to bind DNA. Our prediction of metabolites approach relies on the construction of an enriched and annotated map of metabolites from an input metabolite.The pipeline assembles reaction prediction tools (SyGMa), sites of metabolism prediction tools (Way2Drug, SOMP and Fame 3), a tool to estimate the ability of a xenobotics to form DNA adducts (XenoSite Reactivity V1), and a filtering procedure based on Bayesian framework. This prediction pipeline was evaluated using caffeine and then applied to HAA. The method was applied to determine enzymes profiles associated with the maximization of metabolites derived from each HAA which are able to bind to DNA. The classification of HAA according to enzymatic profiles was consistent with their chemical structures. Conclusions: Overall, a predictive toxicological model based on an in silico systems biology approach opens perspectives to estimate the genotoxicity of various chemical classes of environmental contaminants. Moreover, our approach based on enzymes profile determination opens the possibility of predicting various xenobiotics metabolites susceptible to bind to DNA in both normal and physiopathological situations.
MeSH term(s)	Amines ; Bayes Theorem ; Carcinogens ; DNA Adducts ; Humans ; Xenobiotics
Chemical Substances	Amines ; Carcinogens ; DNA Adducts ; Xenobiotics
Language	English
Publishing date	2021-09-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2041484-5
ISSN	1471-2105 ; 1471-2105
ISSN (online)	1471-2105
ISSN	1471-2105
DOI	10.1186/s12859-021-04363-6
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Article ; Online: Voraussetzungen für eine gute medizinische Gewaltopferversorgung und eine qualitätsgesicherte „vertrauliche Spurensicherung“. Eine qualitative Studie mit Ärztinnen und Ärzten aus NRW.

Siegel, Melanie / Ritz-Timme, Stefanie / Tank, Anne / Gahr, Britta

Zeitschrift fur Evidenz, Fortbildung und Qualitat im Gesundheitswesen

2022 Volume 169, Page(s) 12–18

Abstract: Background: Sexual and domestic violence against women and young girls are widespread and can lead to significant psychological, psychosocial and health consequences for the victims. "Confidential Securing of Evidence" ("vertrauliche Spurensicherung", ... ...

Title translation	Requirements of good medical care for victims of violence and quality-assured "confidential securing of evidence". A qualitative study among physicians in Northrhine-Westphalia.
Abstract	Background: Sexual and domestic violence against women and young girls are widespread and can lead to significant psychological, psychosocial and health consequences for the victims. "Confidential Securing of Evidence" ("vertrauliche Spurensicherung", VSS) offers victims the opportunity to have the consequences of the violent acts they have suffered documented without primary police involvement, thus gaining time for decision-making. However, VSS and, in general, the care for victims of violence pose special challenges to physicians. In North Rhine-Westphalia, the documentation app iGOBSIS was developed in a project to support physicians in the care for victims of violence, especially in the VSS. Objectives: The aim of the work was to clarify how physicians in North Rhine-Westphalia evaluate the functionality of violence victim care and VSS. Specifically, main deficits were to be identified, and suggestions and recommendations for optimizing care and VSS be explored. Materials and methods: Interviews with 39 physicians were conducted in focus groups and analyzed using qualitative content analysis. Results: Medical care for victims of violence and VSS are mainly complicated by stress and time constraints and lack of professional qualification. There is a need for more public relations and educational work, better professional qualification, consistent documentation and secure funding. Conclusions: Readily available forensic medical support for documentation that will hold up in court, secure funding, networking and public relations are important elements to ensure good medical care for victims of violence and a functional VSS.
MeSH term(s)	Documentation ; Domestic Violence ; Female ; Germany ; Humans ; Physicians ; Qualitative Research
Language	German
Publishing date	2022-02-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2412512-X
ISSN	2212-0289 ; 1865-9217
ISSN (online)	2212-0289
ISSN	1865-9217
DOI	10.1016/j.zefq.2021.12.007
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Article: Empirical evidence for metabolic drift in plant and algal lipid biosynthesis pathways.

Zonnequin, Maëlle / Belcour, Arnaud / Delage, Ludovic / Siegel, Anne / Blanquart, Samuel / Leblanc, Catherine / Markov, Gabriel V

Frontiers in plant science

2024 Volume 15, Page(s) 1339132

Abstract: Metabolic pathway drift has been formulated as a general principle to help in the interpretation of comparative analyses between biosynthesis pathways. Indeed, such analyses often indicate substantial differences, even in widespread pathways that are ... ...

Abstract	Metabolic pathway drift has been formulated as a general principle to help in the interpretation of comparative analyses between biosynthesis pathways. Indeed, such analyses often indicate substantial differences, even in widespread pathways that are sometimes believed to be conserved. Here, our purpose is to check how much this interpretation fits to empirical data gathered in the field of plant and algal biosynthesis pathways. After examining several examples representative of the diversity of lipid biosynthesis pathways, we explain why it is important to compare closely related species to gain a better understanding of this phenomenon. Furthermore, this comparative approach brings us to the question of how much biotic interactions are responsible for shaping this metabolic plasticity. We end up introducing some model systems that may be promising for further exploration of this question.
Language	English
Publishing date	2024-01-31
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2613694-6
ISSN	1664-462X
ISSN	1664-462X
DOI	10.3389/fpls.2024.1339132
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