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1.
Res Pract Thromb Haemost ; 8(2): 102382, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38601061

ABSTRACT

Background: Despite systematic thromboprophylaxis, 30% of the COVID-19 patients in intensive care units develop thrombosis. This occurrence is associated with a hypofibrinolytic state measured by thromboelastometry when adding tissue plasminogen activator (tPA) to citrated whole blood for a further run for EXTEM (ROTEM). Objectives: Because hydroxyethyl starches (HESs) affect fibrin polymerization, we have assessed its potential effect on in vitro tPA-induced fibrinolysis. Methods: Fifteen successive COVID-19 patients from the local intensive care units were selected for tPA resistance occurrence. HES was added to whole blood samples with proportion similar to the pharmacologic recommendations. Samples were run for EXTEM on a ROTEM delta device after further addition of tPA. Paired controls were whole blood samples with the same volume of saline added. To assess the impact of HES on coagulation, thrombin generation was measured in 10 COVID-19 patients in the presence of either HES or saline; then, the clots obtained were used to generate electron microscope images. Results: Clot firmness at 5 minutes and the lysis index at 30 minutes were decreased in presence of HES compared with saline (Wilcoxon test, P < .01 for HES vs saline and HES vs untreated). However, no statistically significant difference was observed for all thrombin generation assay parameters studied (endogenous thrombin potential, peak thrombin, and time to peak). With HES, fibrin fibers of either COVID-19 patients or control subjects were thicker than those of saline-treated samples. Conclusion: These results highlight that HES increased apparent in vitro tPA-induced fibrinolysis in case of severe COVID-19 disease. Use of this plasma volume expander may translate as a potential help against COVID-19-induced thrombosis occurrence.

2.
J Affect Disord ; 352: 296-305, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38360365

ABSTRACT

BACKGROUND: Depression and fatigue are commonly observed sequelae following viral diseases such as COVID-19. Identifying symptom constellations that differentially classify post-COVID depression and fatigue may be helpful to individualize treatment strategies. Here, we investigated whether self-reported post-COVID depression and post-COVID fatigue are associated with the same or different symptom constellations. METHODS: To address this question, we used data from COVIDOM, a population-based cohort study conducted as part of the NAPKON-POP platform. Data were collected in three different German regions (Kiel, Berlin, Würzburg). We analyzed data from >2000 individuals at least six months past a PCR-confirmed COVID-19 disease, using elastic net regression and cluster analysis. The regression model was developed in the Kiel data set, and externally validated using data sets from Berlin and Würzburg. RESULTS: Our results revealed that post-COVID depression and fatigue are associated with overlapping symptom constellations consisting of difficulties with daily activities, perceived health-related quality of life, chronic exhaustion, unrestful sleep, and impaired concentration. Confirming the overlap in symptom constellations, a follow-up cluster analysis could categorize individuals as scoring high or low on depression and fatigue but could not differentiate between both dimensions. LIMITATIONS: The data presented are cross-sectional, consisting primarily of self-reported questionnaire or medical records rather than biometric data. CONCLUSIONS: In summary, our results suggest a strong link between post-COVID depression and fatigue, highlighting the need for integrative treatment approaches.


Subject(s)
COVID-19 , Sleep Wake Disorders , Humans , Quality of Life , Depression/epidemiology , Depression/therapy , Cross-Sectional Studies , Prospective Studies , Cohort Studies , COVID-19/complications , COVID-19/epidemiology , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/etiology , Sleep Wake Disorders/therapy , Fatigue/epidemiology , Fatigue/etiology
3.
Infection ; 52(1): 93-104, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37434025

ABSTRACT

BACKGROUND: The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) pandemic causes a high burden of acute and long-term morbidity and mortality worldwide despite global efforts in containment, prophylaxis, and therapy. With unprecedented speed, the global scientific community has generated pivotal insights into the pathogen and the host response evoked by the infection. However, deeper characterization of the pathophysiology and pathology remains a high priority to reduce morbidity and mortality of coronavirus disease 2019 (COVID-19). METHODS: NAPKON-HAP is a multi-centered prospective observational study with a long-term follow-up phase of up to 36 months post-SARS-CoV-2 infection. It constitutes a central platform for harmonized data and biospecimen for interdisciplinary characterization of acute SARS-CoV-2 infection and long-term outcomes of diverging disease severities of hospitalized patients. RESULTS: Primary outcome measures include clinical scores and quality of life assessment captured during hospitalization and at outpatient follow-up visits to assess acute and chronic morbidity. Secondary measures include results of biomolecular and immunological investigations and assessment of organ-specific involvement during and post-COVID-19 infection. NAPKON-HAP constitutes a national platform to provide accessibility and usability of the comprehensive data and biospecimen collection to global research. CONCLUSION: NAPKON-HAP establishes a platform with standardized high-resolution data and biospecimen collection of hospitalized COVID-19 patients of different disease severities in Germany. With this study, we will add significant scientific insights and provide high-quality data to aid researchers to investigate COVID-19 pathophysiology, pathology, and chronic morbidity.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , SARS-CoV-2 , Pandemics/prevention & control , Quality of Life , Germany/epidemiology , Observational Studies as Topic
4.
Int J Mol Sci ; 24(23)2023 Nov 21.
Article in English | MEDLINE | ID: mdl-38068874

ABSTRACT

Variant identification underlying inherited dysfibrinogenemia quite exceptionally fails. We report on two dysfibrinogenemia cases whose underlying DNA variant could not be identified by Sanger analysis. These failures result from two distinct mechanisms. The first case involved raw signal overcorrection by a built-in software, and the second constituted the first description of mosaicism for one of the fibrinogen genes. This mosaicism was subsequently identified by next-generation sequencing reanalysis of the sample.


Subject(s)
Afibrinogenemia , Mosaicism , Humans , Afibrinogenemia/diagnosis , Afibrinogenemia/genetics , Mutation, Missense , Algorithms , Mutation
5.
Sensors (Basel) ; 23(20)2023 Oct 16.
Article in English | MEDLINE | ID: mdl-37896585

ABSTRACT

This study proposes a new hybrid multi-modal sensory feedback system for prosthetic hands that can provide not only haptic and proprioceptive feedback but also facilitate object recognition without the aid of vision. Modality-matched haptic perception was provided using a mechanotactile feedback system that can proportionally apply the gripping force through the use of a force controller. A vibrotactile feedback system was also employed to distinguish four discrete grip positions of the prosthetic hand. The system performance was evaluated with a total of 32 participants in three different experiments (i) haptic feedback, (ii) proprioceptive feedback and (iii) object recognition with hybrid haptic-proprioceptive feedback. The results from the haptic feedback experiment showed that the participants' ability to accurately perceive applied force depended on the amount of force applied. As the feedback force was increased, the participants tended to underestimate the force levels, with a decrease in the percentage of force estimation. Of the three arm locations (forearm volar, forearm ventral and bicep), and two muscle states (relaxed and tensed) tested, the highest accuracy was obtained for the bicep location in the relaxed state. The results from the proprioceptive feedback experiment showed that participants could very accurately identify four different grip positions of the hand prosthesis (i.e., open hand, wide grip, narrow grip, and closed hand) without a single case of misidentification. In experiment 3, participants could identify objects with different shapes and stiffness with an overall high success rate of 90.5% across all combinations of location and muscle state. The feedback location and muscle state did not have a significant effect on object recognition accuracy. Overall, our study results indicate that the hybrid feedback system may be a very effective way to enrich a prosthetic hand user's experience of the stiffness and shape of commonly manipulated objects.


Subject(s)
Feedback, Sensory , Haptic Technology , Humans , Feedback, Sensory/physiology , Feedback , Prostheses and Implants , Hand/physiology , Muscle, Skeletal , Visual Perception , Hand Strength/physiology
6.
Stud Health Technol Inform ; 307: 31-38, 2023 Sep 12.
Article in English | MEDLINE | ID: mdl-37697835

ABSTRACT

INTRODUCTION: With increasing availability of reusable biomedical data - from cohort studies to clinical routine data, data re-users face the problem to manage transferred data according to the heterogeneous data use agreements. While structured metadata is addressed in many contexts including informed consent, contracts are to date still unstructured text documents. In particular within collaborative and active working groups the actual usage agreement's regulations are highly relevant for the daily practice - can I share the data with colleagues from the same university or the same research network, can they be stored on a PHD student's laptop, can I store the data for further approved data usage requests? METHODS: In this article, we inspect and review seven different data usage agreements. We focus on digital data that is copied and transferred to the requester's environment. RESULTS: We identified 24 metadata items in the four main categories data usage, storage, and sharing, as well as publication of results. DISCUSSION: While the topics are largely overlap in the data use agreements, the actual regulations of the topics are diverse. Although we do not explicitly investigate trusted research environments, where data is offered within an analytics platform, we consider them a as subgroup, where most of the practical questions from the data scientist's perspective also arise. CONCLUSION: With a limited set of structured metadata items, data scientists could have information about the data use agreement at hand along with the transferred data in an easily accessible way.


Subject(s)
Metadata , Physicians , Humans , Informed Consent , Microcomputers , Trust
7.
Stud Health Technol Inform ; 307: 39-48, 2023 Sep 12.
Article in English | MEDLINE | ID: mdl-37697836

ABSTRACT

INTRODUCTION: The increasing need for secondary use of clinical study data requires FAIR infrastructures, i.e. provide findable, accessible, interoperable and reusable data. It is crucial for data scientists to assess the number and distribution of cohorts that meet complex combinations of criteria defined by the research question. This so-called feasibility test is increasingly offered as a self-service, where scientists can filter the available data according to specific parameters. Early feasibility tools have been developed for biosamples or image collections. They are of high interest for clinical study platforms that federate multiple studies and data types, but they pose specific requirements on the integration of data sources and data protection. METHODS: Mandatory and desired requirements for such tools were acquired from two user groups - primary users and staff managing a platform's transfer office. Open Source feasibility tools were sought by different literature search strategies and evaluated on their adaptability to the requirements. RESULTS: We identified seven feasibility tools that we evaluated based on six mandatory properties. DISCUSSION: We determined five feasibility tools to be most promising candidates for adaption to a clinical study research data platform, the Clinical Communication Platform, the German Portal for Medical Research Data, the Feasibility Explorer, Medical Controlling, and the Sample Locator.


Subject(s)
Biomedical Research , Physicians , Humans , Feasibility Studies
8.
Stud Health Technol Inform ; 307: 152-158, 2023 Sep 12.
Article in English | MEDLINE | ID: mdl-37697849

ABSTRACT

INTRODUCTION: Contradiction is a relevant data quality indicator to evaluate the plausibility of interdependent health data items. However, while contradiction assessment is achieved using domain-established contradictory dependencies, recent studies have shown the necessity for additional requirements to reach conclusive contradiction findings. For example, the oral or rectal methods used in measuring the body temperature will influence the thresholds of fever definition. The availability of this required information as explicit data items must be guaranteed during study design. In this work, we investigate the impact of activities related to study database implementation on contradiction assessment from two perspectives including: 1) additionally required metadata and 2) implementation of checks within electronic case report forms to prevent contradictory data entries. METHODS: Relevant information (timestamps, measurement methods, units, and interdependency rules) required for contradiction checks are identified. Scores are assigned to these parameters and two different studies are evaluated based on the fulfillment of the requirements by two selected interdependent data item sets. RESULTS: None of the studies have fulfilled all requirements. While timestamps and measurement units are found, missing information about measurement methods may impede conclusive contradiction assessment. Implemented checks are only found if data are directly entered. DISCUSSION: Conclusive contradiction assessment typically requires metadata in the context of captured data items. Consideration during study design and implementation of data capture systems may support better data quality in studies and could be further adopted in primary health information systems to enhance clinical anamnestic documentation.


Subject(s)
Data Accuracy , Health Information Systems , Body Temperature , Databases, Factual , Documentation
10.
Stud Health Technol Inform ; 302: 93-97, 2023 May 18.
Article in English | MEDLINE | ID: mdl-37203616

ABSTRACT

The COVID-19 pandemic has urged the need to set up, conduct and analyze high-quality epidemiological studies within a very short time-scale to provide timely evidence on influential factors on the pandemic, e.g. COVID-19 severity and disease course. The comprehensive research infrastructure developed to run the German National Pandemic Cohort Network within the Network University Medicine is now maintained within a generic clinical epidemiology and study platform NUKLEUS. It is operated and subsequently extended to allow efficient joint planning, execution and evaluation of clinical and clinical-epidemiological studies. We aim to provide high-quality biomedical data and biospecimens and make its results widely available to the scientific community by implementing findability, accessibility, interoperability and reusability - i.e. following the FAIR guiding principles. Thus, NUKLEUS might serve as role model for FAIR and fast implementation of clinical epidemiological studies within the setting of University Medical Centers and beyond.


Subject(s)
Epidemiologic Studies , Pandemic Preparedness , Schools, Medical , Germany/epidemiology , COVID-19/epidemiology , Time Factors , Pandemic Preparedness/organization & administration , Public Health Infrastructure/organization & administration , Humans
11.
Stud Health Technol Inform ; 302: 302-306, 2023 May 18.
Article in English | MEDLINE | ID: mdl-37203667

ABSTRACT

Contradictions as a data quality indicator are typically understood as impossible combinations of values in interdependent data items. While the handling of a single dependency between two data items is well established, for more complex interdependencies, there is not yet a common notation or structured evaluation method established to our knowledge. For the definition of such contradictions, specific biomedical domain knowledge is required, while informatics domain knowledge is responsible for the efficient implementation in assessment tools. We propose a notation of contradiction patterns that reflects the provided and required information by the different domains. We consider three parameters (α, ß, θ): the number of interdependent items as α, the number of contradictory dependencies defined by domain experts as ß, and the minimal number of required Boolean rules to assess these contradictions as θ. Inspection of the contradiction patterns in existing R packages for data quality assessments shows that all six examined packages implement the (2,1,1) class. We investigate more complex contradiction patterns in the biobank and COVID-19 domains showing that the minimum number of Boolean rules might be significantly lower than the number of described contradictions. While there might be a different number of contradictions formulated by the domain experts, we are confident that such a notation and structured analysis of the contradiction patterns helps to handle the complexity of multidimensional interdependencies within health data sets. A structured classification of contradiction checks will allow scoping of different contradiction patterns across multiple domains and effectively support the implementation of a generalized contradiction assessment framework.


Subject(s)
COVID-19 , Data Accuracy , Humans
12.
Small Methods ; 7(6): e2300098, 2023 06.
Article in English | MEDLINE | ID: mdl-37035956

ABSTRACT

Advances in cryo-electron microscopy (EM) enable imaging of protein assemblies within mammalian cells in a near native state when samples are preserved by cryogenic vitrification. To accompany this progress, specialized EM labelling protocols must be developed. Gold nanoparticles (AuNPs) of 2 nm are synthesized and functionalized to bind selected intracellular targets inside living human cells and to be detected in vitreous sections. As a proof of concept, thioaminobenzoate-, thionitrobenzoate-coordinated gold nanoparticles are functionalized on their surface with SV40 Nuclear Localization Signal (NLS)-containing peptides and 2 kDa polyethyleneglycols (PEG) by thiolate exchange to target the importin-mediated nuclear machinery and facilitate cytosolic diffusion by shielding the AuNP surface from non-specific binding to cell components, respectively. After delivery by electroporation into the cytoplasm of living human cells, the PEG-coated AuNPs diffuse freely in the cytoplasm but do not enter the nucleus. Incorporation of NLS within the PEG coverage promotes a quick nuclear import of the nanoparticles in relation to the density of NLS onto the AuNPs. Cryo-EM of vitreous cell sections demonstrate the presence of 2 nm AuNPs as single entities in the nucleus. Biofunctionalized AuNPs combined with live-cell electroporation procedures are thus potent labeling tools for the identification of macromolecules in cellular cryo-EM.


Subject(s)
Gold , Metal Nanoparticles , Animals , Humans , Gold/chemistry , Cryoelectron Microscopy , Metal Nanoparticles/chemistry , Cell Nucleus/metabolism , Mammals/metabolism
13.
Clin Res Cardiol ; 112(7): 923-941, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36884078

ABSTRACT

The German Centre for Cardiovascular Research (DZHK) is one of the German Centres for Health Research and aims to conduct early and guideline-relevant studies to develop new therapies and diagnostics that impact the lives of people with cardiovascular disease. Therefore, DZHK members designed a collaboratively organised and integrated research platform connecting all sites and partners. The overarching objectives of the research platform are the standardisation of prospective data and biological sample collections among all studies and the development of a sustainable centrally standardised storage in compliance with general legal regulations and the FAIR principles. The main elements of the DZHK infrastructure are web-based and central units for data management, LIMS, IDMS, and transfer office, embedded in a framework consisting of the DZHK Use and Access Policy, and the Ethics and Data Protection Concept. This framework is characterised by a modular design allowing a high standardisation across all studies. For studies that require even tighter criteria additional quality levels are defined. In addition, the Public Open Data strategy is an important focus of DZHK. The DZHK operates as one legal entity holding all rights of data and biological sample usage, according to the DZHK Use and Access Policy. All DZHK studies collect a basic set of data and biosamples, accompanied by specific clinical and imaging data and biobanking. The DZHK infrastructure was constructed by scientists with the focus on the needs of scientists conducting clinical studies. Through this, the DZHK enables the interdisciplinary and multiple use of data and biological samples by scientists inside and outside the DZHK. So far, 27 DZHK studies recruited well over 11,200 participants suffering from major cardiovascular disorders such as myocardial infarction or heart failure. Currently, data and samples of five DZHK studies of the DZHK Heart Bank can be applied for.


Subject(s)
Biological Specimen Banks , Humans , Prospective Studies
14.
Methods Inf Med ; 62(S 01): e47-e56, 2023 06.
Article in English | MEDLINE | ID: mdl-36596462

ABSTRACT

BACKGROUND: As a national effort to better understand the current pandemic, three cohorts collect sociodemographic and clinical data from coronavirus disease 2019 (COVID-19) patients from different target populations within the German National Pandemic Cohort Network (NAPKON). Furthermore, the German Corona Consensus Dataset (GECCO) was introduced as a harmonized basic information model for COVID-19 patients in clinical routine. To compare the cohort data with other GECCO-based studies, data items are mapped to GECCO. As mapping from one information model to another is complex, an additional consistency evaluation of the mapped items is recommended to detect possible mapping issues or source data inconsistencies. OBJECTIVES: The goal of this work is to assure high consistency of research data mapped to the GECCO data model. In particular, it aims at identifying contradictions within interdependent GECCO data items of the German national COVID-19 cohorts to allow investigation of possible reasons for identified contradictions. We furthermore aim at enabling other researchers to easily perform data quality evaluation on GECCO-based datasets and adapt to similar data models. METHODS: All suitable data items from each of the three NAPKON cohorts are mapped to the GECCO items. A consistency assessment tool (dqGecco) is implemented, following the design of an existing quality assessment framework, retaining their-defined consistency taxonomies, including logical and empirical contradictions. Results of the assessment are verified independently on the primary data source. RESULTS: Our consistency assessment tool helped in correcting the mapping procedure and reveals remaining contradictory value combinations within COVID-19 symptoms, vital signs, and COVID-19 severity. Consistency rates differ between the different indicators and cohorts ranging from 95.84% up to 100%. CONCLUSION: An efficient and portable tool capable of discovering inconsistencies in the COVID-19 domain has been developed and applied to three different cohorts. As the GECCO dataset is employed in different platforms and studies, the tool can be directly applied there or adapted to similar information models.


Subject(s)
COVID-19 , Data Accuracy , Humans , Consensus , Pandemics , Quality Indicators, Health Care , COVID-19/epidemiology , Data Collection
15.
J Am Acad Child Adolesc Psychiatry ; 62(9): 953-956, 2023 09.
Article in English | MEDLINE | ID: mdl-36333214

ABSTRACT

The COVID-19 pandemic has been identified as a mental health crisis for children and adolescents in America.1 Social isolation and loneliness during the pandemic present a significant challenge. A rapid systematic review published in this journal found that social isolation correlates with depression and anxiety and may heighten the risk of disorder onset.2 Specifically in an infectious disease context, research on the H1N1 influenza pandemic showed that children in North America required to quarantine were 5 to 30 times more likely to meet criteria for posttraumatic stress disorder than children not under these restrictions.2.


Subject(s)
COVID-19 , Influenza A Virus, H1N1 Subtype , Psychiatry , Child , Humans , Adolescent , Inpatients , Pandemics/prevention & control , Technology
16.
JAMA Netw Open ; 5(12): e2244661, 2022 12 01.
Article in English | MEDLINE | ID: mdl-36459140

ABSTRACT

Importance: Unprofessional behaviors and mistreatment directed at trainees continue to challenge the learning environment. Academic medical institutions should encourage reports of inappropriate behavior and address such reports directly to create a safe learning environment. Objective: To determine the feasibility of creating and implementing an online reporting system for receiving and reviewing complaints of unprofessional behavior directed toward or experienced by students, postdoctoral trainees, and residents. Design, Setting, and Participants: This cohort study assessed implementation of an online reporting system (feedback form) with a method for triaging reports, providing both positive and negative feedback, as well as adjudication and transparent public disclosure of aggregate data. The system was launched at a large urban academic medical center with numerous trainees that is fully integrated with a health system of 8 hospitals. Participants included faculty who interact with trainees, medical students, graduate students and postdoctoral fellows, and residents and clinical fellows. Follow-up began in October 2019 (at the time of tool launch) and lasted through December 2021. Data were analyzed from January to March 2022. Main Outcomes and Measures: The primary outcomes were the numbers and types of reports according to the reporter and the person reported about. Results: Participants included 2900 faculty who interact with trainees, 600 medical students, more than 1000 graduate students and postdoctoral fellows, and 2600 residents and clinical fellows. Trainees submitted 196 reports, 173 (88.3%) of which described unprofessional interactions. Among the reports describing unprofessional behavior, 60 (34.7%) were from medical students, 96 (55.5%) were from residents and fellows, 17 (9.8%) were from graduate students or postdoctoral trainees, and 78 (45.1%) were from men. The majority of negative reports described behaviors by faculty (106 [61.3%]), followed by residents and fellows (24 [13.9%]). Twenty faculty (<1.0%) accounted for 52 (50.0%) of the 104 reports describing unprofessional behaviors. Since implementation, most trainees are aware of this process. An increasing number have reported instances of mistreatment, and those who shared concerns through the online system report satisfaction with the outcome of the response to the report. Conclusions and Relevance: In this cohort study, the new reporting mechanism facilitated identification of the small number of individuals associated with unprofessional behaviors toward trainees and increased awareness of the school's commitment to creating a safe learning environment.


Subject(s)
Professional Misconduct , Students, Medical , Male , Humans , Cohort Studies , Academic Medical Centers , Online Systems
17.
Front Psychol ; 13: 854093, 2022.
Article in English | MEDLINE | ID: mdl-36211849

ABSTRACT

A sample of tourists (N = 780) responded to a survey addressing purchasing intentions and consumption motives in relation to buying sustainable groceries at a local food market. These intentions and motives were contrasted for two consumption contexts: on vacation vs. at home. An initial analysis of the data indicated that self-reported purchasing intentions were weaker for a vacation scenario than for a home scenario. Further analyses suggested that motives associated with purchasing intentions were not universal between contexts. At home, normative motives (i.e., good conscience) were positively associated with intentions, whereas other motives failed to explain significant variance (i.e., value for money, calm and safe, avoid boredom, pleasure, and good impression). On vacation, associations with intentions followed a similar pattern, except for the finding that hedonic motives (i.e., pleasure) added explanatory variance. Despite the increased importance of hedonic motives on vacation compared to at home, normative motives showed the strongest association with purchasing intentions in both consumption contexts. The findings are discussed with reference to the literature on contextual discrepancies in environmental behavior, while noting possible implications for promoting sustainable consumption among tourists.

18.
Pharmaceutics ; 14(8)2022 Aug 09.
Article in English | MEDLINE | ID: mdl-36015281

ABSTRACT

Theragnostic pairs of isotopes are used to infer radiation dosimetry for a therapeutic radiopharmaceutical from a diagnostic imaging study with the same tracer molecule labelled with an isotope better suited for the imaging task. We describe the transfer of radiation dosimetry from the diagnostic radioiodine isotope 123I, labelled for the hypoxia tracer molecule iodoazomycin arabinoside ([123I]IAZA), to isotopes 131I (therapeutic) and 124I (PET imaging). Uncertainties introduced by the dissimilar isotope half-lives are discussed in detail. Radioisotope dosimetries for [123I]IAZA were obtained previously. These data are used here to calculate residence times for 131I and 124I and their uncertainties. We distinguish two cases when extrapolating to infinity: purely physical decay (case A) and physical decay plus biological washout (case B). Organ doses were calculated using the MIRD schema with the OLIDNA/EXM code. Significant increases in some organ doses (in mSv per injected activity) were found for 131I and 124I. The most affected organs were the intestinal walls, thyroid, and urinary bladder wall. Uncertainty remained similar to 123I for case A but considerably greater for case B, especially for long biological half-lives (GI tract). Normal tissue dosimetries for IAZA must be considered carefully when substituting isotope species. A long biological half-life can significantly increase dosimetric uncertainties. These findings are relevant when considering PET imaging studies with [124I]IAZA or therapeutic administration of [131I]IAZA.

19.
Eur J Epidemiol ; 37(8): 849-870, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35904671

ABSTRACT

The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON's goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36-62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON's design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities.Trial registration https://clinicaltrials.gov/ct2/show/NCT04768998 . https://clinicaltrials.gov/ct2/show/NCT04747366 . https://clinicaltrials.gov/ct2/show/NCT04679584.


Subject(s)
COVID-19 , Pandemics , Adult , COVID-19/epidemiology , Child , Clinical Trials as Topic , Female , Humans , Intensive Care Units , Male , Middle Aged , Research Design , SARS-CoV-2
20.
Stem Cell Res ; 62: 102815, 2022 07.
Article in English | MEDLINE | ID: mdl-35617842

ABSTRACT

We describe the generation of an isogenic control cell line DJ-1-delP GC13 from an induced pluripotent stem cell (iPSC) line DJ-1-delP LCSBi008-A that was derived from fibroblasts obtained from a Parkinson's disease (PD) patient. Using CRISPR/Cas9 technology, we corrected the disease causing c.471_473delGCC homozygous mutation in the PARK7 gene leading to p.158P deletion in the encoded protein DJ-1. The generated isogenic pair will be used for phenotypic analysis of PD-patient derived neurons and astrocytes.


Subject(s)
Induced Pluripotent Stem Cells , Parkinson Disease , Astrocytes/metabolism , Cell Line , Humans , Induced Pluripotent Stem Cells/metabolism , Mutation/genetics , Neurons/metabolism , Parkinson Disease/genetics , Parkinson Disease/metabolism
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