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Concentration gradients of soluble signaling molecules-morphogens-determine the cellular organization in tissue development. Morphogen-releasing microgels have shown potential to recapitulate this principle in engineered tissue constructs, however, with limited control over the molecular cues in space and time. Inspired by the functionality of sulfated glycosaminoglycans (sGAGs) in morphogen signaling in vivo, a library of sGAG-based microgels is developed and designated as µGel Units to Instruct Development (µGUIDEs). Adjustment of the microgel's sGAG sulfation patterns and concentration enabled the programming of electrostatic affinities that control the release of morphogens. Based on computational analyses of molecular transport processes, µGUIDEs provided unprecedented precision in the spatiotemporal modulation of vascular endothelial growth factor (VEGF) gradients in a microgel-in-gel vasculogenesis model and kidney organoid cultures. The versatile approach offers new options for creating morphogen signaling centers to advance the understanding of tissue and organ development., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Introduction: High email load has been associated with impaired well-being because emails impose specific demands, disturb the workflow, and thereby overtax individuals' action regulation toward prioritized goals. However, the causes and well-being-related consequences of email load are not yet well understood, as previous studies have neglected the interaction type and function of emails as well as co-occurring stressors as antecedents of high email load and have relied predominantly on cross-sectional designs., Methods: In two studies, we aimed to clarify the nature of email load through the lens of action regulation theory. The first study, a two-wave investigation with a fortnightly interval, examined the lagged relationships among email load, work stressors, strain, and affective well-being. The sample included 444 individuals across various occupations and organizations, with 196 of them working from home or remotely at least part of the time. In the second cross-sectional study, we surveyed 257 individuals using a convenience sampling approach, 108 of whom worked from home or remotely at least partially. This study focused on evaluating how different email classes-distinguished by email interaction type (received vs. processed) and email function (communication vs. task)-serve as predictors of high email load., Results: In Study 1, we found a positive lagged effect of high email load on strain, even when controlling for the co-occurring stressors time pressure and work interruptions. In addition, lagged effects of email load on time pressure and interruptions were identified, while no evidence was found for the reverse direction. The results of Study 2 suggest that only the number of communication-related emails received, but not the number of task-related emails received, or the number of all emails processed contribute to high email load., Conclusion: Findings suggest that email load can be considered a unique stressor and that different classes of email need to be distinguished to understand its nature. Clarifying the sources of email load can help develop effective strategies to address it., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kern, Ohly, Ďuranová and Friedrichs.)

Importance: The prognosis of patients with adenocarcinoma of the esophagus and esophagogastric junction (AEG) is poor. From current evidence, it remains unclear to what extent preoperative chemoradiotherapy (CRT) or preoperative and/or perioperative chemotherapy achieve better outcomes than surgery alone., Objective: To assess the association of preoperative CRT and preoperative and/or perioperative chemotherapy in patients with AEG with overall survival and other outcomes., Data Sources: Literature search in PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and International Clinical Trials Registry Platform was performed from inception to April 21, 2023., Study Selection: Two blinded reviewers screened for randomized clinical trials comparing preoperative CRT plus surgery with preoperative and/or perioperative chemotherapy plus surgery, 1 intervention with surgery alone, or all 3 treatments. Only data from participants with AEG were included from trials that encompassed mixed histology or gastric cancer. Among 2768 initially identified studies, 17 (0.6%) met the selection criteria., Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed for extracting data and assessing data quality by 2 independent extractors. A bayesian network meta-analysis was conducted using the 2-stage approach., Main Outcomes and Measures: Overall and disease-free survival, postoperative morbidity, and mortality., Results: The analyses included 2549 patients (2206 [86.5%] male; mean [SD] age, 61.0 [9.4] years) from 17 trials (conducted from 1989-2016). Both preoperative CRT plus surgery (hazard ratio [HR], 0.75 [95% credible interval (CrI), 0.62-0.90]; 3-year difference, 105 deaths per 1000 patients) and preoperative and/or perioperative chemotherapy plus surgery (HR, 0.78 [95% CrI, 0.64-0.91]; 3-year difference, 90 deaths per 1000 patients) showed longer overall survival than surgery alone. Comparing the 2 modalities yielded similar overall survival (HR, 1.04 [95% CrI], 0.83-1.28]; 3-year difference, 15 deaths per 1000 patients fewer for CRT). Similarly, disease-free survival was longer for both modalities compared with surgery alone. Postoperative morbidity was more frequent after CRT plus surgery (odds ratio [OR], 2.94 [95% CrI, 1.01-8.59]) than surgery alone. Postoperative mortality was not significantly more frequent after CRT plus surgery than surgery alone (OR, 2.50 [95% CrI, 0.66-10.56]) or after chemotherapy plus surgery than CRT plus surgery (OR, 0.44 [95% CrI, 0.08-2.00])., Conclusions and Relevance: In this meta-analysis of patients with AEG, both preoperative CRT and preoperative and/or perioperative chemotherapy were associated with longer survival without relevant differences between the 2 modalities. Thus, either of the 2 treatments may be recommended to patients.

Hydrogel-based 3D cell cultures can recapitulate (patho)physiological phenomena ex vivo. However, due to their complex multifactorial regulation, adapting these tissue and disease models for high-throughput screening workflows remains challenging. In this study, a new precision culture scaling (PCS-X) methodology combines statistical techniques (design of experiment and multiple linear regression) with automated, parallelized experiments and analyses to customize hydrogel-based vasculogenesis cultures using human umbilical vein endothelial cells and retinal microvascular endothelial cells. Variations of cell density, growth factor supplementation, and media composition are systematically explored to induce vasculogenesis in endothelial mono- and cocultures with mesenchymal stromal cells or retinal microvascular pericytes in 384-well plate formats. The developed cultures are shown to respond to vasculogenesis inhibitors in a compound- and dose-dependent manner, demonstrating the scope and power of PCS-X in creating parallelized tissue and disease models for drug discovery and individualized therapies., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Background: With the continuous advancement of cancer treatments, a comprehensive analysis of the impact of multivisceral oncological pancreatic resections on morbidity, mortality, and long-term survival is currently lacking., Objective: This manuscript presents the protocol for a systematic review and meta-analysis designed to summarize the existing evidence concerning the outcomes of multivisceral oncological pancreatic resections across diverse tumor entities., Methods: We will conduct a systematic search of the PubMed or MEDLINE, Embase, Cochrane Library, CINAHL, and ClinicalTrials.gov databases in strict accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The predefined outcomes encompass postoperative mortality, postoperative morbidity, overall and disease-free survival (1- to 5-year survival rates), the proportion of macroscopically complete (R0) resections (according to the Royal College of Pathologists definition), duration of hospital stay (in days), reoperation rate (%), postoperative complications (covering all complications according to the Clavien-Dindo classification), as well as pancreatic fistula, postpancreatectomy hemorrhage, and delayed gastric emptying (all according to the definitions of the International Study Group of Pancreas Surgery)., Results: Systematic database searches will begin in July 2024. The completion of the meta-analysis is anticipated by December 2024. Before completion, the literature search will be checked for new publications that must be considered in the context of the work., Conclusions: The forthcoming findings will provide an up-to-date overview of the feasibility, safety, and oncological efficacy of multivisceral pancreatic resections across diverse tumor entities. This data will serve as a valuable resource for health care professionals and patients to make well-informed clinical decisions., Trial Registration: PROSPERO CRD42023437858; https://tinyurl.com/bde5xmfw., International Registered Report Identifier (irrid): PRR1-10.2196/54089., (©Melina Neuhaus, Juliane Friedrichs, Maurizio Grilli, Jörg Ukkat, Johannes Klose, Ulrich Ronellenfitsch, Jörg Kleeff, Artur Rebelo. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 11.06.2024.)

Gregarines are usually classified as parasites, but recent studies suggest that they should be viewed on a parasitism-mutualism spectrum and may even be seen as part of the gut microbiota of host insects. As such, they may also impact the consumption of their hosts and/or be involved in the digestion or detoxification of the host's diet. To study such effects of a gregarine species on those traits in its host, the mustard leaf beetle ( Phaedon cochleariae ) was used. This beetle species feeds on Brassicaceae plants that contain glucosinolates, which form toxic compounds when hydrolyzed by myrosinases. We cleaned host eggs from gametocysts and spores and reinfected half of the larvae with gregarines, to obtain gregarine-free (G-) and gregarine-infected (G+) larvae. Growth and food consumption parameters of these larvae were assessed by rearing individuals on watercress ( Nasturtium officinale , Brassicaceae). A potential involvement of gregarines in the glucosinolate metabolism of P. cochleariae larvae was investigated by offering G- and G+ larvae leaf discs of watercress (containing mainly the benzenic 2-phenylethyl glucosinolate and myrosinases) or pea ( Pisum sativum , Fabaceae, lacking glucosinolates and myrosinases) treated with the aliphatic 4-pentenyl glucosinolate or the indole 1-methoxy-3-indolylmethyl glucosinolate. Larval and fecal samples were analyzed via UHPLC-QTOF-MS/MS to search for breakdown metabolites. Larval development, body mass, growth rate and efficiency to convert food into body mass were negatively affected by gregarine infection while the pupal mass remained unaffected. The breakdown metabolites of benzenic and aliphatic glucosinolates were conjugated with aspartic acid, while those of the indole glucosinolate were conjugated with glutamic acid. Gregarine infection did not alter the larvae's ability to metabolize glucosinolates and was independent of plant myrosinases. In summary, some negative effects of gregarines on host performance could be shown, indicating parasitism. Future studies may further disentangle this gregarine-host relationship and investigate the microbiome potentially involved in the glucosinolate metabolism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Barber, Friedrichs and Müller.)

Introduction: Perforated peptic ulcers are a life-threatening complication associated with high morbidity and mortality. Several treatment approaches are available. The aim of this network meta-analysis (NMA) is to compare surgical and alternative approaches for the treatment of perforated peptic ulcers regarding mortality and other patient-relevant outcomes., Methods and Analysis: A systematic literature search of PubMed/MEDLINE, Cochrane Library, Embase, CINAHL, ClinicalTrials.gov trial registry and ICTRP will be conducted with predefined search terms.To address the question of the most effective treatment approach, an NMA will be performed for each of the outcomes mentioned above. A closed network of interventions is expected. The standardised mean difference with its 95% CI will be used as the effect measure for the continuous outcomes, and the ORs with 95% CI will be calculated for the binary outcomes., Ethics and Dissemination: In accordance with the nature of the data used in this meta-analysis, which involves aggregate information from previously published studies ethical approval is deemed unnecessary. Results will be disseminated directly to decision-makers (eg, surgeons, gastroenterologists) through publication in peer-reviewed journals and presentation at conferences., Prospero Registration Number: CRD42023482932., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The discovery of novel structural classes of antibiotics is urgently needed to address the ongoing antibiotic resistance crisis 1-9 . Deep learning approaches have aided in exploring chemical spaces 1,10-15 ; these typically use black box models and do not provide chemical insights. Here we reasoned that the chemical substructures associated with antibiotic activity learned by neural network models can be identified and used to predict structural classes of antibiotics. We tested this hypothesis by developing an explainable, substructure-based approach for the efficient, deep learning-guided exploration of chemical spaces. We determined the antibiotic activities and human cell cytotoxicity profiles of 39,312 compounds and applied ensembles of graph neural networks to predict antibiotic activity and cytotoxicity for 12,076,365 compounds. Using explainable graph algorithms, we identified substructure-based rationales for compounds with high predicted antibiotic activity and low predicted cytotoxicity. We empirically tested 283 compounds and found that compounds exhibiting antibiotic activity against Staphylococcus aureus were enriched in putative structural classes arising from rationales. Of these structural classes of compounds, one is selective against methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci, evades substantial resistance, and reduces bacterial titres in mouse models of MRSA skin and systemic thigh infection. Our approach enables the deep learning-guided discovery of structural classes of antibiotics and demonstrates that machine learning models in drug discovery can be explainable, providing insights into the chemical substructures that underlie selective antibiotic activity., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Proton exchange membrane fuel cells (PEMFCs) are seen as one possible future means of driving the change towards a zero-emission society. In a civil aircraft, fuel cell systems can have multiple potential benefits, such as reduced noise, lowered emissions and higher fuel economy compared to jet aircraft. For controlling the fuel cell temperature, thermal management systems are required which can be optimized for aircraft applications regarding their weight and reliability. In this work, a simplified and light-weight thermal management system relying on hydrogen cooling is presented and analysed. To investigate the feasibility, a test rig and a three-dimensional, singular channel model in ANSYS Fluent were designed. Fuel cell temperature could be maintained within the set threshold in the model and the test rig, thus showing that controlling the fuel cell temperature via the hydrogen reactant flow is a viable alternative thermal management system. Results from the model indicate that both the hydrogen mass flow and hydrogen inlet temperature should be used to control the fuel cell temperature. Furthermore, operating the fuel cell at medium to low current densities is favourable for hydrogen cooling. Future studies will explore alternate flow field designs to facilitate thermal management system relying on hydrogen., (© 2024. The Author(s).)

Control of adhesion is a striking feature of living matter that is of particular interest regarding technological translation 1-3 . We discovered that entropic repulsion caused by interfacial orientational fluctuations of cholesterol layers restricts protein adsorption and bacterial adhesion. Moreover, we found that intrinsically adhesive wax ester layers become similarly antibioadhesive when containing small quantities (under 10 wt%) of cholesterol. Wetting, adsorption and adhesion experiments, as well as atomistic simulations, showed that repulsive characteristics depend on the specific molecular structure of cholesterol that encodes a finely balanced fluctuating reorientation at the interface of unconstrained supramolecular assemblies: layers of cholesterol analogues differing only in minute molecular variations showed markedly different interfacial mobility and no antiadhesive effects. Also, orientationally fixed cholesterol layers did not resist bioadhesion. Our insights provide a conceptually new physicochemical perspective on biointerfaces and may guide future material design in regulation of adhesion., (© 2023. The Author(s).)

Background: In 13 European countries, laws have been passed that allow nurses to prescribe medicines, but mostly within a limited framework and with a doctor involved. Germany is not among these countries. Only the prescription of medical aids has already been included into the development of extended nursing competencies. We investigated the views of the health care professions involved (doctors, pharmacists and nurses) regarding the role of nurses in pharmaceutical care., Method: We conducted 22 semi-structured interviews with 23 members of the three professional groups involved in the European research project DeMoPhaC. These data collected in Germany were analysed using qualitative content analysis. Five main categories were developed., Results: Pharmaceutical care by nurses can be described within the following main categories: 1. Knowledge and competences, 2. Patient care, 3. Communication, 4. Multi-professional team and 5. System. The communication between the professional groups involved and with patients and caregivers is of particular importance. Interaction in the multi-professional team is just as crucial. Pharmaceutical care takes place within the health system which sets the framework and often boundaries as well. The current and ideally conceived roles of nurses are seen differently in the respondents' respective contexts. Between the professional groups there is both agreement and dissent on the topics addressed. However, the development of nursing roles requires collaborative and transparent processes in teams and organisations. Particularly in the hospital setting, the participants saw a great need for change in order to achieve cooperation at eye level., Discussion: The results show that nurses play their role in the complex field of pharmaceutical care under very heterogeneous circumstances. The empowerment of nurses, which was called for by some participants, cannot be achieved from within the professional group alone. Cooperation from all the players involved is needed. The development of nursing roles in the medication process with simultaneous expansion of qualifications and competences can contribute to making the nursing role more attractive. Clear role models promote the transparency of processes for all involved. If all players know what they can expect of nurses, tasks can be redistributed in the multiprofessional team., Conclusion: The above-mentioned diversity of perspectives can be a resource for development and individual solutions. However, it can also be interpreted negatively as a sign of uncertainty and less standardised ways of working. In view of the data evaluated here, the prescription of medicines by non-medical professionals remains a distant goal for developments in the German health care system. First of all, structures and processes are required that permanently guarantee safe pharmaceutical care with equal participation of all relevant stakeholders., (Copyright © 2022. Published by Elsevier GmbH.)

Background: With the advances in multimodality treatment, an analysis of the outcome of arterial resections (AR) in surgery of cholangiocarcinoma is lacking. The aim of this meta-analysis was to summarize the currently available evidence onof AR for the treatment of cholangiocarcinoma., Methods: A systematic literature search was carried out according to PRISMA guidelines., Results: 10 retrospective cohort studies published from 2007 to 2020 with 2530 patients (408 AR group and 2122 control group) were identified. Higher in-hospital mortality rates (6.8% vs 3.3%, OR 2.65, 95% CI [1.27; 5.32], p = 0.009), higher morbidity rates (Clavien-Dindo classification ≥3 ) (52% vs 47%, OR 1.44, 95% CI [1.02; 1.75], p = 0.04) and lower 1-year, 3-year and 5-year survival rates (54% vs 69%, OR 0.55, 95% CI [0.34; 0.91 p = 0.02), (34% vs 38%, OR 0.74, 95% CI [0.55; 0.98, p = 0.03), (18% vs 29%, OR 0.54, 95% CI [0.39; 0.75, p = 0.0002) were observed in the AR group when compared to the control group., Conclusion: Evidence from non-randomized studies shows a higher morbidity and mortality and shorter long-term survival in patients undergoing AR. However, the results are prone to selection bias, and only randomized trials comparing AR and palliative treatments AR might reveal a possible benefit of AR., Systematic Review Registration: PROSPERO ID 223396., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Myelodysplastic syndromes (MDS) comprise a heterogeneous group of hematologic malignancies characterized by clonal hematopoiesis, one or more cytopenias such as anemia, neutropenia, or thrombocytopenia, abnormal cellular maturation, and a high risk of progression to acute myeloid leukemia. The bone marrow microenvironment (BMME) in general and mesenchymal stromal cells (MSCs) in particular contribute to both the initiation and progression of MDS. However, little is known about the role of MSC-derived extracellular matrix (ECM) in this context. Therefore, we performed a comparative analysis of in vitro deposited MSC-derived ECM of different MDS subtypes and healthy controls. Atomic force microscopy analyses demonstrated that MDS ECM was significantly thicker and more compliant than those from healthy MSCs. Scanning electron microscopy showed a dense meshwork of fibrillar bundles connected by numerous smaller structures that span the distance between fibers in MDS ECM. Glycosaminoglycan (GAG) structures were detectable at high abundance in MDS ECM as white, sponge-like arrays on top of the fibrillar network. Quantification by Blyscan assay confirmed these observations, with higher concentrations of sulfated GAGs in MDS ECM. Fluorescent lectin staining with wheat germ agglutinin and peanut agglutinin demonstrated increased deposition of N -acetyl-glucosamine GAGs (hyaluronan (HA) and heparan sulfate) in low risk (LR) MDS ECM. Differential expression of N -acetyl-galactosamine GAGs (chondroitin sulfate, dermatan sulfate) was observed between LR- and high risk (HR)-MDS. Moreover, increased amounts of HA in the matrix of MSCs from LR-MDS patients were found to correlate with enhanced HA synthase 1 mRNA expression in these cells. Stimulation of mononuclear cells from healthy donors with low molecular weight HA resulted in an increased expression of various pro-inflammatory cytokines suggesting a contribution of the ECM to the inflammatory BMME typical of LR-MDS. CD34 + hematopoietic stem and progenitor cells (HSPCs) displayed an impaired differentiation potential after cultivation on MDS ECM and modified morphology accompanied by decreased integrin expression which mediate cell-matrix interaction. In summary, we provide evidence for structural alterations of the MSC-derived ECM in both LR- and HR-MDS. GAGs may play an important role in this remodeling processes during the malignant transformation which leads to the observed disturbance in the support of normal hematopoiesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bains, Behrens Wu, Rivière, Rother, Magno, Friedrichs, Werner, Bornhäuser, Götze, Cross, Platzbecker and Wobus.)

Brassicaceae plants contain glucosinolates, which are hydrolysed by myrosinases to toxic products such as isothiocyanates and nitriles, acting as defences. Herbivores have evolved various detoxification strategies, which are reviewed here. Larvae of Phaedon cochleariae (Coleoptera: Chrysomelidae) metabolise hydrolysis products of benzenic glucosinolates by conjugation with aspartic acid. In this study, we investigated whether P. cochleariae uses the same metabolic pathway for structurally different glucosinolates, whether the metabolism differs between adults and larvae and which hydrolysis products are formed as intermediates. Feeding experiments were performed with leaves of watercress (Nasturtium officinale, Brassicaceae) and pea (Pisum sativum, non-Brassicaceae), to which glucosinolates with structurally different side chains (benzenic, indole or aliphatic) or their hydrolysis products were applied. Samples were analysed by UHPLC-QTOF-MS/MS or TD-GC-MS. The same aspartic acid conjugates as previously identified in larvae were also detected as major metabolites of benzenic glucosinolates in adults. Indol-3-ylmethyl glucosinolate was mainly metabolised to N-(1H-indol-3-ylcarbonyl) glutamic acid in adults and larvae, while the metabolism of 2-propenyl glucosinolate remains unclear. The metabolism may thus proceed primarily via isothiocyanates rather than via nitriles, while the hydrolysis occurs independently of plant myrosinases. A detoxification by conjugation with these amino acids is not yet known from other Brassicaceae-feeders., (© 2022. The Author(s).)

Background: Lymph node yield is the number of lymph nodes retrieved during oncological resection and histopathologically identified in the resection specimen. It is an important surrogate parameter for assessing the oncological radicality of the resection of gastrointestinal carcinomas, as well as a prognostic factor in these diseases. It remains unclear if and to what extent neoadjuvant chemotherapy, radiotherapy, or chemoradiotherapy, which have become established treatments for carcinoma of the esophagus, stomach, and rectum and are increasingly used in pancreatic carcinoma, affect the lymph node yield., Objective: This systematic review with meta-analysis is conducted with the aim of summarizing the available evidence regarding the lymph node yield, an oncological surrogate marker, in patients with gastrointestinal carcinomas undergoing surgery after neoadjuvant therapy compared to those undergoing surgery without neoadjuvant therapy., Methods: Randomized and nonrandomized studies comparing oncological resection of esophageal, stomach, pancreatic, and rectal carcinoma with and without prior neoadjuvant therapy are eligible for inclusion regardless of study design. Publications will be identified with a defined search strategy in 2 electronic databases: PubMed and Cochrane Library. The primary endpoint of the analysis is the number of lymph nodes identified in the resected specimen. Secondary endpoints include the number of harvested metastatic lymph nodes, operation time, postoperative complications, pathological TNM staging, and overall and recurrence-free survival time. Using suitable statistical methods, the endpoints between patients with and without neoadjuvant therapy, as well as in defined subgroups (neoadjuvant chemotherapy, radiotherapy, or chemoradiotherapy; and patients with esophageal, gastric, pancreatic, or rectal cancer), will be compared., Results: The literature search and data collection started in October 2021. Results are expected to be published in mid-2022., Conclusions: This meta-analysis will provide the most up-to-date and complete summary of the evidence on an association between neoadjuvant therapy and lymph node yield in gastrointestinal cancer surgery. The underlying hypothesis is that neoadjuvant therapy decreases the number and size of lymph nodes through lymphocyte depletion and radiation-induced fibrosis, thus leading to a lower possible lymph node yield. The findings of the meta-analysis will show if this hypothesis is supported by evidence., Trial Registration: PROSPERO CRD218459; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021218459., International Registered Report Identifier (irrid): DERR1-10.2196/35243., (©Ulrich Ronellenfitsch, Nika Mathis, Juliane Friedrichs, Jörg Kleeff. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 28.04.2022.)