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    CALIFRAME: a proposed method of calibrating reporting guidelines with FAIR principles to foster reproducibility of AI research in medicine

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    Background Procedural and reporting guidelines are crucial in framing scientific practices and communications among researchers and the broader community. These guidelines aim to ensure transparency, reproducibility, and reliability in scientific research. Despite several methodological frameworks proposed by various initiatives to foster reproducibility, challenges such as data leakage and reproducibility remain prevalent. Recent studies have highlighted the transformative potential of incorporating the FAIR (Findable, Accessible, Interoperable, and Reusable) principles into workflows, particularly in contexts like software and machine learning model development, to promote open science. Objective This study aims to introduce a comprehensive framework, designed to calibrate existing reporting guidelines against the FAIR principles. The goal is to enhance reproducibility and promote open science by integrating these principles into the scientific reporting process. Methods We employed the “Best fit” framework synthesis approach which involves systematically reviewing and synthesizing existing frameworks and guidelines to identify best practices and gaps. We then proposed a series of defined workflows to align reporting guidelines with FAIR principles. A use case was developed to demonstrate the practical application of the framework. Results The integration of FAIR principles with established reporting guidelines through the framework effectively bridges the gap between FAIR metrics and traditional reporting standards. The framework provides a structured approach to enhance the findability, accessibility, interoperability, and reusability of scientific data and outputs. The use case demonstrated the practical benefits of the framework, showing improved data management and reporting practices. Discussion The framework addresses critical challenges in scientific research, such as data leakage and reproducibility issues. By embedding FAIR principles into reporting guidelines, the framework ensures that scientific outputs are more transparent, reliable, and reusable. This integration not only benefits researchers by improving data management practices but also enhances the overall scientific process by promoting open science and collaboration. Conclusion The proposed framework successfully combines FAIR principles with reporting guidelines, offering a robust solution to enhance reproducibility and open science. This framework can be applied across various contexts, including software and machine learning model development stages, to foster a more transparent and collaborative scientific environment

    Charakterisierung der interindividuellen Variabilität der Expression von Transportproteinen und Metabolisierungsenzymen im menschlichen Darm und mögliche Implikationen für die Pharmakotherapie

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    Obwohl die Aufnahme von Wirkstoffen aus dem Darm ein hochvariabler Prozess mit vielen Einflussfaktoren ist, ist die orale Arzneimittelgabe die bevorzugte Applikationsroute für Medikamente. Intestinale Metabolisierungsenzyme und Transportproteine stellen Faktoren dar, die die Absorption deutlich beeinflussen können. Obwohl bereits viel über ihre Funktion, Regulation und Lage im Darm bekannt ist, fehlen Daten über die interindividuelle Expression. Ziel dieser Arbeit war, diese im Hinblick auf die demographischen Faktoren biologisches Geschlecht, Alter und das Vorliegen der Volkskrankheit Diabetes mellitus Typ 2 hin zu charakterisieren und gegebenenfalls Schlüsse auf Implikationen für die Arzneimitteltherapie zu ziehen. Dafür wurde intraoperativ gewonnenes kryokonserviertes Jejunumgewebe verwendet und Vergleichsgruppen (Geschlecht, Alter, Typ-2-Diabetiker) anhand der zugehörigen Datenbank gebildet. Die Expression relevanter Arzneimitteltransporter und Metabolisierungsenzyme wurde auf mRNA-Ebene bestimmt, die Expression ausgewählter Arzneimitteltransporter auch auf Protein-Ebene. Der relative mRNA-Gehalt wurde mittels reverser Transkription und quantitativer PCR bestimmt. Für die Protein-Messung wurde das gesamte Gewebeprotein filterbasiert extrahiert, mittels Trypsin gespalten und anschließend die erhaltenen transporterspezifischen Peptide mittels Flüssigchromatographie und Massenspektrometrie nach etablierter Methode quantifiziert (targeted proteomics). Die Ergebnisse bewegen sich in der Größenordnung anderer Arbeiten ähnlicher Methodik. mRNA und Protein korrelierten, wie in der Literatur beschrieben, kaum. Obwohl die Untersuchung bei relativ kleiner Probenzahl der Vergleichsgruppen underpowered ist, fanden sich einige signifikante Ergebnisse zwischen den Geschlechtern sowie den Typ-2-Diabetikern und der Kontrollgruppe. Hervorzuheben ist die deutlich niedrigere mRNA-Expression des Metformin-Transporters SLC29A4 bei Diabetikern. Auf Proteinebene zeigten Typ-2-Diabetiker eine ca. 20% niedrigere Expression von PEPT1 als Nicht-Diabetiker. Frauen exprimierten P-gp ca. 20% höher. In der im Rahmen dieser Arbeit durchgeführten Untersuchung zeigte sich kein signifikanter Einfluss des Alters und lediglich ein limitierter Einfluss der Faktoren Geschlecht und Typ-2-Diabetes auf das Expressionsprofil der untersuchten Arzneimitteltransporter und -enzyme, vor allem auf Protein-Ebene. Eine pharmakokinetische Relevanz dieser Faktoren durch Beeinflussung der Expression von Transportproteinen und Metabolisierungsenzymen für die orale Arzneimitteltherapie bleibt somit fraglich

    Absolute Proteinquantifizierung erlaubt Einblicke in den Proteintransport

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    With the help of methodological adaptations and suitable protein standards, mass spectrometry can determine the number of protein molecules per cell. This article describes recent developments in absolute protein quantification extending the method to analytically challenging proteins from the cell membrane or the extracellular medium. Finally, the integration of such data leads to information on the speed of protein transport and thus provides new insights into bacterial cell physiology

    General hospital patients’ attitude towards systematic health risk behavior screening and intervention

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    Background Systematic counseling on behavioral health risk factors (HRFs) may be suitable to promote health among general hospital patients. This study aimed to investigate the openness of patients towards systematic screening and intervention of HRFs, its relation to actual participation in a multi-behavioral intervention, and whether socio-economic characteristics, HRFs and health indicators are related to approval. Methods All 18- to 64-year-old patients hospitalized in five medical departments at the University Medicine Hospital Greifswald in Germany were asked between May and July 2022 to participate in a survey and in a subsequent pre-post intervention study. Among all eligible patients, 225 (78.9%) participated in the survey. Patients’ approval of systematic screening and intervention of HRFs was assessed using five statements with a total sum score of 0–20 (i.e., scores of 0–6, 7–13, 14–20 referring to low, medium and high approval). Associations with intervention participation, socio-economic, behavioral and health-related patient characteristics were analyzed using logistic and multivariable linear regression analyses. Results The mean total approval of screening and intervention was 13.8 (SD = 4.8). Of the 125/ 73/ 16 patients with high/ medium/ low approval, 88.0%/ 78.1%/ 50.0% participated in the subsequent intervention, respectively. Approval was independent of socio-demographic and -economic characteristics and self-rated general health. Current tobacco smoking was the only HRF negatively ( p  = 0.02) and diabetes mellitus was the only disease positively ( p  = 0.01) associated with approval. Conclusion High approval of HRF screening, which was rather independent of socio-economic characteristics and worse self-rated general health, speaks in favor of proactively approaching and motivating all general hospital patients to participate in health behavior change intervention. Tobacco smokers might need higher efforts to motivate participation than non-smokers. Trial registration ClinicalTrials.gov Identifier NCT05365269 on May 9, 2022

    A Scale-space Approach for Surface Normal Vector Estimation from Depth Maps

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    Surface normal vectors provide cues about the local geometric features of the scene which are utilized in many computer vision and computer graphics applications. Thus, the estimation of surface normals by utilizing structured range sensor data is an important research field. Thereupon, we propose a learning-free algorithm to estimate the surface normal vectors from depth maps. Our simple yet effective method relies on computations carried out in scale-space. Our main idea is to estimate the surface normals which cannot be properly computed in the finest scale from the coarser scales. Our method can estimate the surface normals even for images included in datasets that have challenging characteristics such as noisy real-world data or significantly large planar regions that either have a small or no gradient change. We analyze our algorithm’s performance by utilizing five benchmarks, namely, the MIT-Berkeley Intrinsic Images dataset, the New Tsukuba Dataset, the SceneNet RGB-D dataset, the IID-NORD dataset, and the NYU Depth Dataset V2, and by using two different evaluation strategies. According to the experimental results, our method can estimate surface normals efficiently without requiring neither complex computations nor huge amounts of data

    Infectious complications following transperineal prostate biopsy with or without periprocedural antibiotic prophylaxis—a systematic review including meta-analysis of all comparative studies

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    Background Despite the relatively low infection rate following transperineal prostate biopsy (TPB), it remains unresolved whether periprocedural antibiotic prophylaxis (PAP) can be omitted. Our aim was to compare infectious complications (genitourinary infections/GUI, fever, sepsis, readmission rate, 30-day-mortality) following TPB, considering all studies of varying levels of evidence that enable a direct comparison between patients with and without PAP. Methods We performed a comprehensive search in PubMed/Medline, Embase, Web of Science, and Cochrane databases, as well as grey literature sources, to identify reports published until January 2024. All studies comparing the incidence of infectious endpoints following TPB with vs. without PAP were included in the analyses. The GRADE approach was employed to assess the certainty of evidence for each comparison. Results Twenty-three studies met the inclusion criteria involving 6520 and 5804 patients who underwent TPB with vs. without PAP, respectively. Two of the 23 studies were randomized-controlled trials, not all studies investigated all endpoints. Pooled incidences between patients with vs. without PAP for the endpoints GUI (0.50% vs. 0.37%), fever (0.44% vs. 0.26%), sepsis (0.16% vs. 0.13%), and readmission rate (0.35% vs. 0.29%) showed no significant differences (all p  0.250). The corresponding odds ratios (including 95% confidence interval) also revealed no statistically significant differences: 1.37 (0.74–2.54) [GUI], 0.87 (0.28–2.66) [fever], 1.30 (0.46–3.67) [sepsis], and 1.45 (0.70–3.03) [readmission rate]. No study reported events regarding 30-day-mortality. In subgroup analyses and sensitivity analyses, TPB without PAP showed no significantly higher complication rates regarding all analyzed endpoints. Conclusions Infectious complications after TPB occur very rarely and cannot be further reduced by PAP. Considering the results of this systematic review and adhering to the principles of effective antibiotic stewardship, omitting PAP in the context of TPB is advisable

    Clinical and radiological outcome of surgical hallux valgus correction: open versus minimally invasive

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    Introduction Hallux valgus (HV) is the most common forefoot deformity. Surgical correction of HV aims to reduce pain, preserve joints, and re-establish foot function while restoring the hallux valgus angle (HVA) and intermetatarsal angle (IMA). Many surgical procedures have been proposed, including open and minimally invasive (MI) techniques. This study aimed to compare the midterm outcomes of open vs. MI procedures and their impact on the duration of surgery, hospital stay, HVA, and IMA post-operatively. Materials and methods One hundred and twenty HV patients operated by open or MI surgery between October 2019 and October 2022 were included. One hundred three patients met the inclusion criteria and consented to the study. Patients were prospectively surveyed for foot functionality, post-operative pain, and complications using the AOFAS score. Radiographic measurements of HV angles, length of hospital stay, and surgery duration were analysed. Results MI surgery patients had significantly better AOFAS scores ( p  < 0.001) 12 months post-operatively compared to open surgery. Complication rates were lower in the MI group (3.8% vs. 33.3%, p  < 0.001). MI surgery patients also had shorter hospital stays (0.9 ± 0.3 days vs. 2.0 ± 0.0 days) and surgery duration (19.7 ± 2.3 min vs. 80.7 ± 6.8 min). MI surgery was more effective in correcting the IMA but equally effective as open surgery for HVA correction. Conclusion MI surgery resulted in better patient satisfaction, fewer complications, and more precise correction of IMA values. Moreover, the duration of surgery and hospital stay were significantly lower in patients undergoing MI surgery. Further research is needed to validate these findings in controlled, prospective randomised trials

    Cold Atmospheric Plasma Is a Promising Alternative Treatment Option in Case of Split Skin Graft Failure

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    Cold atmospheric plasma (CAP) has shown promising potential in promoting wound healing. This case report presents the successful application of CAP in a 42-year-old female patient with extensive wound healing disorders and superinfections following the excision of an abscess in the left thoracic region. After several failed split skin graft attempts, the implementation of CAP led to significant improvements in wound healing. This report highlights the wound healing-promoting effects of CAP and discusses its potential mechanisms of action

    Untersuchungen zum 3D-Druck für die individualisierte Herstellung von nicht-oralen Arzneiformen am Beispiel von Sinus-Implantaten und Suppositorien

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    Innerhalb der individualisierten Medizin steht zunehmend der einzelne Patient mit seinen spezifischen Voraussetzungen und Bedürfnissen im Fokus der Arzneimitteltherapie. Die Verwendung von 3D-Drucktechnologien bietet ein hohes Potenzial für die individualisierte Herstellung von Arzneiformen, die spezifisch auf die Bedürfnisse des jeweiligen Patienten zugeschnitten sind. Aufgrund der hohen Flexibilität hinsichtlich der Anpassung von Form und Größe der gedruckten Arzneiformen sowie der damit verbundenen Dosis oder des Freisetzungsverhaltens eröffnet der 3D-Druck neue vielversprechende Möglichkeiten diesen individuellen Anforderungen zu begegnen. Das Ziel dieser Arbeit war die Eignung des 3D-Drucks für die Herstellung von individualisierten wirkstoffbeladenen Arzneiformen im nicht-oralen Applikationsbereich zu untersuchen und relevante Einflussfaktoren zu identifizieren. Hierzu wurden reproduzierbare Herstellungsprozesse unter der Verwendung von zwei extrusionsbasierten 3D-Drucktechnologien (FDM, Fused Deposition Modeling und SSE, Semi-Solid Extrusion) für die Herstellung von Sinus-Implantaten und Suppositorien entwickelt und optimiert. Während bei der Herstellung von Suppositorien primär die Form und Größe mittels des 3D-Drucks angepasst werden können, erfordert die Entwicklung von Sinus-Implantaten aufgrund der hohen anatomischen Variabilität eine exakte Anpassung der Implantatform an die komplexe patientenindividuelle Anatomie. Ein Schwerpunkt dieser Arbeit stellt die Untersuchung des Einflusses der individualisierten Form auf das Freisetzungsverhalten im Zusammenhang mit den entwickelten Sinus-Implantaten dar. Anhand von Modell-Implantaten mit vereinfachter Geometrie wurden die zugrundeliegenden mathematischen Zusammenhänge ermittelt und die Möglichkeit zur Vorhersage des Freisetzungsverhaltens von patientenindividuell geformten Implantaten untersucht. Die hierbei erlangten Erkenntnisse könnten aus regulatorischer Sicht vielversprechend sein, um zukünftig umfangreiche und zerstörerische In vitro-Untersuchungen an der spezifischen Implantatform zu umgehen und somit den Aspekt der Einzelanfertigung im Rahmen der individuellen Herstellung zu stärken. Des Weiteren wurden wesentliche Einflussfaktoren auf die Wirkstoffstabilität während des Prozesses der Schmelzextrusion zur Herstellung wirkstoffbeladener Polymerfilamente als Ausgangsmaterial für den 3D-Druck sowie während des 3D-Druckprozesses selbst am Beispiel des antiinflammatorischen Wirkstoffs Dexamethason untersucht. Hierbei konnte neben dem maßgeblichen Einfluss der verwendeten Prozesstemperaturen ebenfalls der Einfluss der Polymerauswahl auf die Wirkstoffstabilität demonstriert werden, was die Relevanz von Stabilitätsuntersuchungen für den spezifischen Prozess unabhängig von den Ergebnissen thermogravimetrischer Analysen unterstreicht. Insgesamt verdeutlicht die vorliegende Arbeit die Eignung des 3D-Druckverfahrens insbesondere für die fokussierten Applikationsformen der Sinus-Implantate sowie der Suppositorien, wobei sich die erlangten Erkenntnisse hinsichtlich der Herstellung, Individualisierung und erzielbarer Eigenschaften zusätzlich auf weitere Applikationsorte übertragen lassen. Insgesamt stellt der 3D-Druck ein gut geeignetes Verfahren für die reproduzierbare Herstellung von Arzneiformen dar, das insbesondere aufgrund des hohen Freiheitsgrades an realisierbaren Formen entscheidende Vorteile für verschiedene Darreichungsformen bietet, die einen ausgeprägten Individualisierungsgrad benötigen.In the context of individualized medicine, the focus of drug therapy is increasingly on the individual patient with their specific requirements and needs. The use of 3D printing technologies offers great potential for the individualized manufacturing of dosage forms that are specifically tailored to the needs of each patient. Due to the high degree of flexibility in terms of adapting the shape and size of the printed dosage forms and subsequent the dose or behavior in drug release, 3D printing provides promising new possibilities to meet these individual requirements. The aim of this work was to investigate the suitability of 3D printing for the manufacturing of individualized drug-loaded dosage forms in the non-oral application area and to identify relevant influencing factors. For this purpose, reproducible manufacturing processes were developed and optimized using two extrusion-based 3D printing technologies (FDM, Fused Deposition Modeling and SSE, Semi-Solid Extrusion) for the manufacturing of sinus implants and suppositories. Whereas the shape and size of suppositories can be primarily adapted using 3D printing, the development of sinus implants requires precise adaptation of the implant shape to the complex patient-specific anatomy due to the high anatomical variability. One main aspect of this work is the investigation of the influence of the individualized shape on the release behavior in context of the developed sinus implants. Using model implants with simplified geometry, the corresponding mathematical relationships were determined and the possibility of prediction for the release behavior of patient-specific shaped implants was studied. From a regulatory perspective, the findings could be promising to avoid extensive and destructive in vitro tests on the specific shaped implants in the future and thus strengthen the aspect of single-unit fabrication in the context of individual manufacturing. Furthermore, the main factors influencing drug stability during the melt extrusion process for the manufacturing of drug-loaded polymer filaments as a feedstock for 3D printing and during the 3D printing process itself were investigated on the example of the anti-inflammatory drug dexamethasone. Besides the substantial influence of the applied process temperatures, the influence of the polymer selection on the drug stability could be demonstrated, which highlights the relevance of stability studies for the specific process independent of the results of thermogravimetric analyses. This work demonstrates the suitability of the 3D printing process in particular for the focused application forms of sinus implants and suppositories, whereby the findings with regard to manufacturing, individualization and feasible characteristics can also be transferred to further application sites. Overall, 3D printing is a well suited process for the reproducible manufacturing of dosage forms, which offers substantial advantages for various dosage forms that require a high degree of individualization, in particular due to the high degree in freedom of realizable shapes

    Spatial distribution of bioeconomy R&D funding: opportunities for rural and lagging regions?

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    The promotion of R&D carries the risk that economically strong regions will benefit to a greater extent and that regional disparities will increase by focusing the economy on high technology. However, this is expected to depend on the specific sectoral and technological composition of R&D funding. R&D funding for a bio-based economy in Germany is particularly illustrative for a shift in funding focus from a narrow concept of biotechnology to a broader concept of bioeconomy. Along with this shift, an impact on the spatial distribution of R&D funding is assumed. Against the background of inclusive innovation policy, this study examines the potential of the bioeconomy for a reduction of regional disparities in public R&D funding. Based on a database containing publicly-funded R&D projects in Germany and further regional data, comparative regressions are conducted in order to identify spatial patterns. The results demonstrate distinct funding mechanisms in the different areas of the bioeconomy. The broadening of R&D funding for bio-based activities from the biotechnology vision towards bioresources and bioecology leads to a greater participation of rural and lagging regions which is expected to be the result of the inclusion of more traditional industries as recipients of R&D funding

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