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Optical coherence elastography (OCE) is a powerful imaging modality for assessing the mechanical properties of biological tissues. We employed an OCE system based on an Optores OMES 3.2 MHz OCT platform combined with an in-house developed air-jet excitation source to characterize healthy and tumorous (meningioma) human brain tissue. This paper presents a comprehensive software framework for processing large OCE datasets, enabling robust extraction of characteristic features from phase-derived displacement data and calculation of mechanical proxy parameters for detailed tissue characterization. Feature detection is achieved using a modified triangle threshold algorithm applied to the displacement curves from the OCE phase data. Extensive pre- and post-processing steps, including percentile-based filtering and adaptive histogram equalization, are applied to mitigate phase unwrapping errors and enhance visualization of the high dynamic range of OCE data. Exemplary measurements on human brain tumor samples demonstrate the framework's ability to differentiate between tissue types, highlighting its potential for future clinical and research applications.
Evaluation of electronic nursing process documentation in the acute inpatient setting: A mixed methods convergent parallel design Abstract: Background: To identify potential improvements in the quality of nursing process documentation, it is essential to record the baseline situation, considering the perspectives of the nursing staff. Aims: The study aimed to evaluate electronic nursing process documentation in an acute inpatient setting, taking into account the views of nursing staff. Methods: A mixed-methods convergent parallel design was applied. In the quantitative part of the study, an extended Q-DIO (Quality of Nursing Diagnoses, Interventions and Outcomes) document analysis (n = 30) was conducted and analyzed descriptively. In the qualitative part, semi-structured expert interviews (n = 6) were conducted and analyzed using structured content analysis. Quantitative and qualitative results were then combined based on the phases of the nursing process and compared for convergence and divergence. Results: The results for the aspects of nursing assessment, nursing diagnoses and nursing goals revealed divergence. For instance, the quantitative data indicated good quality in nursing diagnoses, whereas nurses expressed differing views on the necessity of documenting these diagnoses. Convergences were observed in the planning and implementation of nursing interventions, as well as in nursing evaluation. Conclusions: The evaluation revealed potential for optimization. When implementing the recommendations, human, technical and organizational factors must be considered, as they are interdependent. Zusammenfassung: Hintergrund: Um Verbesserungspotenziale in der Qualität der Pflegeprozessdokumentation (PPDOK) zu identifizieren, ist es wichtig, die Ausgangssituation unter Berücksichtigung der Perspektiven des Pflegepersonals zu erfassen. Ziel: Ziel war die Evaluation der elektronischen PPDOK in einem Tertiärkrankenhaus unter Einbezug der Perspektiven der Pflegefachpersonen. Methode: Die Mixed-Methods-Studie folgte einem Convergent Parallel Design. Im quantitativen Studienteil wurde eine Dokumentenanalyse (n = 30) mithilfe des erweiterten Q-DIO (Quality of Nursing Diagnoses, Interventions and Outcomes) durchgeführt. Der qualitative Studienteil umfasste semistrukturierte Experteninterviews (n = 6), die mittels strukturierender Inhaltsanalyse analysiert wurden. Die quantitativen und qualitativen Ergebnisse wurden anhand der Phasen des Pflegeprozesses zusammengeführt und hinsichtlich Konvergenzen und Divergenzen verglichen. Ergebnisse: Die Ergebnisse zu den Aspekten Pflegeassessment, Pflegediagnosen und Pflegeziele wiesen Divergenzen auf. So ließ sich zum Aspekt Pflegediagnosen quantitativ eine „gute“ Qualität feststellen, unter Pflegefachpersonen zeigten sich jedoch Unstimmigkeiten hinsichtlich der Notwendigkeit von Pflegediagnosen. Konvergenzen ergaben sich in den Aspekten Planung der Pflegeinterventionen, Durchführung der Pflegeinterventionen und Pflegeevaluation. Schlussfolgerung: Die Evaluation hat Optimierungspotenziale aufgezeigt. Bei der Umsetzung der Empfehlungen müssen menschliche, technische und organisatorische Faktoren berücksichtigt werden, da diese miteinander in Wechselwirkung stehen.
The mycotic aortic aneurysm (MAA) is a rare life-threatening condition. Treatment options include open surgical resection (OR) with prosthesis implantation and endovascular aortic repair (EVAR). Presentation of the therapeutic decisions illustrated by clinical case examples and discussion of current references from the medical scientific literature. 1. An emergency resection of a covered ruptured abdominal aortic aneurysm (AAA) in a 74-year-old female patient revealed a MAA. A xenograft was implanted. Ultimately, the comorbidities led to death. 2. A 79-year-old male patient with a MAA as the focus of a Salmonella sepsis underwent EVAR using implantation of a stent graft. Correct graft placement and adequate perfusion were confirmed. On postoperative day 7, the patient was discharged with long-term antibiotic therapy. 3. A 63-year-old male patient with a covered ruptured AAA and psoas muscle abscess underwent emergency surgery with OR and implantation of a xenograft prosthesis. On postoperative day 12 the patient was discharged with long-term antibiotic therapy. An analysis of 21 studies (2433 patients) showed a better short-term survival using EVAR (3-month survival, 96% vs. 74% for OR) but a higher reinfection rate (42 % vs. 18 %). The 5‑year survival rates are similar (EVAR: 57-79.7%, OR: 60%). The most common pathogens were Salmonella (26.3%) and Staphylococcus aureus (13.9%). Blood cultures remained negative in 37.4%. Risk factors are advanced age, male gender and comorbidities. A long-term antibiotic therapy of > 6 months improves the outcome. The treatment of MAA requires an individualized approach as both OR and EVAR exhibit similar long-term outcomes but different early complication rates. Long-term antibiotic therapy is essential for an optimal outcome. HINTERGRUND: Das mykotische Aortenaneurysma (MAA) ist eine seltene lebensbedrohliche Erkrankung. Therapeutisch steht die offen-chirurgische Resektion (OR) mit Prothesenimplantation dem endovaskulären Aortenrepair (EVAR) gegenüber. ZIEL: Darstellung der Therapieentscheidung anhand von Fallbeispielen mit Diskussion der aktuellen Studienlage. FäLLE: 1. Bei der notfallmäßigen Resektion eines gedeckt rupturierten Bauchaortenaneurysmas (BAA) einer 74-jährigen Patientin zeigt sich ein MAA. Es wird ein Xenograft implantiert. Im Verlauf kommt es durch Komorbiditäten zum Exitus letalis. 2. Bei einem 79-jährigen Patienten mit MAA als Fokus einer Salmonellensepsis erfolgt ein EVAR mit Stentgraft. Eine gute Prothesenlage und Perfusion werden festgestellt. Am 7. postoperativen Tag wird der Patient mit Langzeitantibiotikatherapie entlassen. 3. Ein 63-jähriger Patient mit gedeckt rupturiertem MAA und Psoasabszess wird notfallmäßig mittels OR und Implantation einer Xenograft-Prothese versorgt. Am 12. postoperativen Tag wird der Patient mit Langzeitantibiotikatherapie entlassen. Die Analyse von 21 Studien (2433 Patienten) zeigte bessere Kurzzeitergebnisse bei EVAR (3-Monats-Überleben 96 % vs. 74 % bei OR), aber höhere Reinfektionsraten (42 % vs. 18 %). Das 5‑Jahres-Überleben ist ähnlich (EVAR: 57–79,7 %; OR: 60 %). Häufigste Erreger waren Salmonellen (26,3 %) sowie Staphylococcus aureus (13,9 %). Blutkulturen blieben bei 37,4 % negativ. Risikofaktoren sind ein fortgeschrittenes Alter, männliches Geschlecht und Komorbiditäten. Die Antibiotikatherapie von 6 Monaten verbessert das Outcome. Die Wahl der Therapie erfolgt individuell. Beide Verfahren zeigen ähnliche Langzeitergebnisse bei unterschiedlichen Frühkomplikationen. Die langfristige Antibiotikatherapie ist essenziell für ein optimales Outcome.
Osmotic stress represents a major challenge to cells, particularly in the kidney, where tonicity gradients are both physiologically relevant and pathologically altered. The transcription factor nuclear factor of activated T cells 5 (NFAT5) is a key regulator of the osmoadaptive response, yet its downstream metabolic effectors remain incompletely understood. In this study, we identify the glycolytic side-branch enzyme 2,3-bisphosphoglycerate mutase (BPGM) as a transcriptional NFAT5 target that is induced under hypertonic conditions. RNA-seq analysis revealed that Bpgm knockdown significantly alters gene expression under osmotic stress (450 mOsmol/kg), with substantial overlap between BPGM- and NFAT5-responsive transcriptional programs. Bpgm depletion impairs the induction of canonical NFAT5 target genes, suggesting a functional interplay between metabolic and transcriptional adaptation. Promoter enrichment analysis showed that genes regulated by both NFAT5 and BPGM under hypertonic conditions are associated with CpG islands and GC-rich elements, supporting a link to chromatin structure and transcriptional accessibility. Consistently, we show that HIF-1α expression is regulated downstream of NFAT5 and BPGM, indicating a hierarchical organization of osmotic and hypoxic stress responses. We propose that BPGM facilitates NFAT5 function through metabolic-epigenetic coupling, acting as an amplifier of protective gene expression. Notably, this axis is active in BPGM-expressing cells such as those of the distal convoluted tubule. Thus, our findings establish BPGM as a critical node in the osmoadaptive gene regulatory network and highlight how cell type-specific metabolic profiles influence the transcriptional response to hypertonic stress.
When illuminated with green light, tissue shows negligible autofluorescence in comparison to urinary stones. In automatically controlled lithotripsy, this property is utilized to prevent the laser from being triggered if the fiber is mispositioned: the fluorescence signal is compared to a set threshold before each pulse. However, previous studies have shown that tissue damage cannot be completely ruled out. We are investigating this phenomenon and its impact on fluorescence guidance. An experiment with porcine calyx (with the automatic control switched off) shows that single Ho:YAG laser pulses are sufficient to coagulate tissue, resulting in an increase in autofluorescence. During lithotripsy of fluorescent artificial stones embedded in renal cortex, thermal damage occurs despite automatic laser control. Maximum fluorescence values measured on those tissue places were above the control's set threshold for laser emission. Therefore, an increase in autofluorescence in the event of denaturation must be considered when using automatically controlled lithotripsy.
Staging of prostate carcinoma (PCa) still largely relies on histopathologic examination of prostate tissue. In the last few years, PET/CT with radiotracers that target the prostate-specific membrane antigen (PSMA) has emerged as a noninvasive and sensitive method for staging of PCa. Compared with [68Ga]PSMA-11, [18F]PSMA-1007 is a relatively new radiotracer for PSMA PET/CT with favorable characteristics such as a longer physical half-life, reduced bladder background uptake, and improved availability due to production off-site. The objective of this systematic review and metaanalysis is to summarize the efficacy of [18F]PSMA-1007 in primary T, N, and M staging of PCa in comparison to histopathology. Methods: Clinical trials on primary staging of PCa with [18F]PSMA-1007 (both prospective and retrospective studies) were identified by a systematic search in PubMed. Relevant literature used histopathology as a comparator and reported discrete values for sensitivity and specificity. A metaanalysis assessed differences in diagnostic parameters. Results: Nineteen studies were included in this review: 10 studies reported on T staging (739 patients), 8 studies reported on N staging (865 patients), and 1 study reported on M staging (79 patients). For T staging, our metaanalyses of extraprostatic extension on a patient level based on 3 studies revealed a pooled sensitivity of 54% (95% CI, 46%-63%) and a pooled specificity of 92% (95% CI, 76%-98%). For N staging, our metaanalyses on detection of lymph node metastases on a patient level based on 5 studies revealed a pooled sensitivity of 42% (95% CI, 28%-57%) and a pooled specificity of 94% (95% CI, 90%-97%). In terms of sensitivity for M staging on a patient level, [18F]PSMA-1007 PET/CT outperformed all other tested conventional imaging modalities. Conclusion: PET/CT imaging with [18F]PSMA-1007 provides high sensitivity and specificity in T, N, and M staging of PCa when compared with histopathology. It offers the possibility to perform noninvasive primary T, N, and M staging before treatment in a single procedure.
The indications for treatment with a cochlear implant (CI) have steadily expanded over the years. While the CI was originally designed for deaf adults, the range of indications now also includes patients with profound uni- or bilateral sensorineural hearing loss, unilateral deafness, or residual hearing. Infants and toddlers are also fitted, preferably before the age of 1 year, in order to create optimal conditions for language development. New developments such as gene therapy for otoferlin mutations or CI treatment for vestibular schwannomas further expand the treatment options. The indication is determined individually for each ear, taking audiological, imaging, psychosocial, and cognitive factors into account. The current S2k guideline of the Association of the Scientific Medical Societies in Germany (AWMF) aims to promote high-quality care and emphasizes the importance of interprofessional collaboration in the diagnostic and care process. Die Indikationen für die Cochlea-Implantat (CI) Versorgung haben sich über die Jahre stetig erweitert. War das CI ursprünglich für beidseitig taube Erwachsene konzipiert, umfasst das Indikationsspektrum heute Patienten mit beid- oder einseitiger innenohrbedingter hochgradiger bzw. an Taubheit grenzender Schwerhörigkeit inklusive Taubheit. Die Versorgung von Säuglingen und Kleinkindern erfolgt, vorzugsweise im ersten Lebensjahr, um optimale Bedingungen für die Sprachentwicklung zu gewährleisten. Neue Entwicklungen wie die Gentherapie bei Otoferlin-Mutationen oder die CI-Versorgung bei Vestibularisschwannomen erweitern die Therapieoptionen. Die Indikationsstellung erfolgt individuell je Ohr, unter Berücksichtigung audiologischer, bildgebender, psychosozialer und kognitiver Faktoren. Die aktuelle S2k-Leitlinie der AWMF hat zum Ziel, eine qualitativ hochwertige Versorgung zu fördern und betont die Bedeutung einer interprofessionellen Zusammenarbeit im Diagnostik- und Versorgungsprozess.
In April 2024, the Adult Immunization Board convened a technical meeting to explore the latest strategies and identify exemplary approaches regarding the implementation of vaccines for adults into Europe's National Immunization Programs (NIPs). The meeting was built around three pillars: decision making for introducing a new vaccine, implementation, monitoring, and evaluation. The increasing number of new vaccines available in a context of competing health priorities warrants transparent and evidence-based decision-making processes for vaccine introduction. In Europe, burden of disease, vaccine efficacy or effectiveness, and safety are universally used decision-making criteria. While economic evaluations and the quality of evidence are being increasingly considered, public acceptance, equity, and operational criteria remain underutilized. Vaccine implementation requires planning and coordination. Implementation activities discussed during the meeting were vaccine program goals, target population identification, communication, training of healthcare professionals, and involvement of pharmacists. Once operational, NIPs are to be monitored in terms of safety, effectiveness, and impact. Implementation science as well as behavioral and cultural insights can be used to identify tangible interventions to improve uptake. Meeting discussions allowed to identify adult vaccine implementation barriers and possible strategies to overcome them. Enhanced cooperation and coordination throughout the Europe region were recognized as critical components of progress.
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The increasing bureaucratic burden in everyday clinical practice impairs doctor-patient communication (DPC). Effective use of digital technologies, such as automated semantic speech recognition (ASR) with automated extraction of diagnostically relevant information can provide a solution. The aim was to determine the extent to which ASR in conjunction with semantic information extraction for automated documentation of the doctor-patient dialogue (ADAPI) can be integrated into everyday clinical practice using the IVI routine as an example and whether patient care can be improved through process optimization. In a prospective monocentric study at the Sulzbach Eye Clinic, 50 patients were included in the period from 2020 to 2022. As part of a project funded by the "Zentrale Initiative des Mittelstandes" (ZIM), a demonstrator was developed with the consortium partners and integrated into the hospital information system (HIS). For qualitative and quantitative evaluation, a survey of patients was carried out using a questionnaire before and after implementation of the ADAPI module, supplemented by a determination of acceptance and possible time saving for users. The ADAPI module was successfully integrated into the HIS. The documentation of the findings and connection of the subsequent processes could be automated. An improvement in the DPC was reported for 13/50 patients (26%). The majority 35/50 (70%) did not notice any subjective change. The average duration of the conversation in the area of conventional documentation was 4.46 min (1-10 min) and 3.9 min with ADAPI (1-10 min). With respect to the quality of the conversation within the DPC, no relevant differences could be shown with both types of documentation; however, larger case numbers and other areas of application still need to be evaluated. In the long term, the use of automated documentation solutions will sustainably improve the efficiency, completeness and consistency of clinical documentation. HINTERGRUND: Der zunehmende bürokratische Aufwand im klinischen Alltag beeinträchtigt die Arzt-Patienten-Kommunikation (APK). Eine effektive Nutzung von digitalen Technologien, wie z. B. eine automatisierte semantische Spracherkennung (ASR) mit automatisierter Informationsextraktion diagnostisch relevanter Informationen, kann Abhilfe schaffen. Ziel war es zu ermitteln, inwieweit sich eine automatisierte Spracherkennung in Verbindung mit einer semantischen Informationsextraktion zur automatisierten Dokumentation des Arzt-Patienten-Dialoges (ADAPI) am Beispiel der IVOM-Routine in den klinischen Alltag integrieren lässt und ob sich die Patientenversorgung durch eine Prozessoptimierung verbessern lässt. In einer prospektiven, monozentrischen Untersuchung an der Augenklinik Sulzbach wurden 50 Patienten im Zeitraum von 2020 bis 2022 eingeschlossen. Im Rahmen eines durch die „Zentrale Initiative des Mittelstandes“ (ZIM) geförderten Projektes wurde mit den Partnern des Konsortiums ein Demonstrator entwickelt und in das Klinikinformationssystem (KIS) integriert. Zur qualitativen und quantitativen Evaluierung erfolgte eine Umfrage bei Patienten mittels Fragenkatalog vor sowie nach Implementierung des ADAPI-Moduls, ergänzt durch eine Ermittlung der Akzeptanz und möglicher Zeitersparnisse für die Anwender. Es konnte eine erfolgreiche Integration des ADAPI-Moduls in das KIS erreicht werden. Die Dokumentation des Befundes und Anbindung der nachfolgenden Prozessabläufe konnten automatisiert werden. Bei 13/50 Patienten wurde eine Verbesserung der APK angegeben (26 %). Die Mehrheit 35/50 (70 %) konnte keine subjektive Veränderung feststellen. Die Gesprächsdauer im Bereich der konventionellen Dokumentation lag bei durchschnittlich 4,46 min (1–10 min), sowie bei 3,9 min mit ADAPI (1–10 min). Im Hinblick auf die Gesprächsqualität innerhalb der APK ließen sich keine relevanten Unterschiede mit beiden Dokumentationsarten darstellen. Größere Fallzahlen sowie weitere Anwendungsgebiete sind jedoch noch zu evaluieren. Perspektivisch wird der Einsatz automatisierter Dokumentationslösungen die Effizienz, Vollständigkeit und Konsistenz der klinischen Dokumentation nachhaltig verbessern.
In April 2017, a rat was observed on an airplane during a flight from Miami (USA) to Berlin (Germany). After landing in Berlin, significant efforts were made to trap the rat and disinfect the airplane. As rats are known reservoir hosts for a variety of zoonotic pathogens, this event necessitated the establishment of a standard workflow for the detection of rodent-borne pathogens. Tissue and blood samples were collected to screen for zoonotic pathogens and other known and novel infectious agents using an array of open-view methods (cultivation and characterization of bacteria, high-throughput sequencing) and pathogen-specific methods (e.g. PCR, RT-PCR and multiplex serology). The black rat (Rattus rattus), as confirmed by mtDNA sequences, carried several infectious agents. Cultivation experiments revealed the presence of seven bacterial and two fungal genera. In addition, a methicillin-susceptible Staphylococcus aureus strain of MLST-CC45 was detected by culture-based approaches, and its full genome was sequenced. High-throughput sequencing identified novel picobirnaviruses and various bacterial genera, the majority of which represent commensals rather than pathogens. Despite the diversity of bacterial, viral, and fungal species that can be expected in wild rats, only a few zoonotic and non-zoonotic pathogens were detected in the stowaway rat. Nonetheless, this incident highlights the potential of international (and cross-continental) dissemination of pathogens and the need for a standardized workflow to provide comprehensive coverage of the diversity of microorganisms in such animals.
 Prethrombin-1 is a Gla-domain lacking enzymatically inactive split product that results from the cleavage of fragment 1 from prothrombin by thrombin in a feedback reaction.  A prethrombin-1 preparation derived from human plasma was tested for its hemostatic and thrombogenic properties. Animal models of nail clipping (for rabbits) and tail clipping (for mice) were developed to measure blood loss in FVIII-inhibitor or rivaroxaban anticoagulated rabbits and mice, respectively. A modified Wessler test was used in rabbits to assess the thrombogenic potential by Wessler score and clot weight. Studies were performed in groups of three to six for prethrombin-1 dose escalation and comparison with prothrombin, Beriplex®, FEIBA®, and saline as a control. Data were analyzed using t-statistics or the Mann Whitney U test as applicable.  Prethrombin-1 has excellent hemostatic properties in anticoagulated mouse and rabbit bleeding models. Wessler tests suggest that in contrast to activated and nonactivated prothrombin complexes, prethrombin-1 has negligible thrombogenic potential.  The thrombin zymogen prethrombin-1 promotes hemostasis with reduced risk of thrombosis. Prethrombin-1 may have potential to become a life-saving treatment for patients who bleed or are at risk of bleeding.
We present the first preparation of novel 6-O-(fluoroalkyl)-6-O-desmethyl-diprenorphine analogs and 6-O-(tosyloxyalkyl)-6-O-desmethyl-3-O-trityl-diprenorphine-type precursors for the radiosynthesis of 6-O-([18F]fluoroalkyl)-6-O-desmethyl-diprenorphine radiotracers for molecular imaging by positron emission tomography (PET). The synthesis sequence to the new opioid receptor ligands consists of eleven steps starting from the poppy alkaloid thebaine. The precursor molecules were prepared in a three-step synthesis process from the «Luthra precursor» (TDDPN). We report the complete 1H- and 13C-NMR assignment of the new 6-O-(substituted)-6-O-desmethyl-diprenorphine derivatives, as well as the results of docking studies in silico for diverse novel opioid receptor ligands, including a new series of 6-O-(fluoroalkyl)- and 6-O-(hydroxyalkyl)-6-O-desmethyl-diprenorphine derivatives.
The development of novel treatments has improved cancer outcomes but may result in cardiovascular toxicities. Traditional approaches to clinical trial safety evaluation have limitations in their ability to detect signals of cardiovascular risk. Mechanisms to increase power and specificity to clarify cardiovascular safety are required. However, implications include increased costs and slower development. The Cardiovascular Safety Research Consortium facilitated stakeholder discussions with representation from academia, industry, and regulators. A think tank was assembled with the aim of providing recommendations for improved collection and reporting of cardiovascular safety signals in oncology trials. Two working groups were formed. The first focuses on incorporation of consensus definitions of cardiovascular disease into the Common Terminology Criteria for Adverse Events used in oncology trial reporting. The second group considers methods for ascertainment and adjudication of cardiovascular events in cancer trials. The overarching aim of this primer is to improve understanding of the potential cardiovascular toxicities of cancer therapies.
The evaluation of real-world data (RWD) enables insights to be gained from a wide range of patient data collected in routine clinical practice. In addition, multicenter analyses represent a broad and representative patient population and have the potential to capture the actual treatment situation. As a basis for this, the definition of datasets and an infrastructure for data exchange is necessary. Data integration centers (DIC) have already been established at (university) hospitals throughout Germany in order to extract RWD for scientific analyses from the various source systems and integrate them into research-compatible data infrastructures. The project described here aims to demonstrate the added value of this data integration using a case of application in ophthalmology, defining a core dataset as an ophthalmology extension module and establishing a cross-site data exchange infrastructure. As a first step, the treatment success of eye diseases treated with intravitreal injection (IVI) should be improved. To achieve this goal a dashboard for clinical data is provided that clearly visualizes the merged data. Furthermore, algorithms will be developed to identify new imaging biomarkers that can be used for treatment monitoring and predict treatment outcomes. Die Auswertung von Real-World-Daten (RWD) ermöglicht Erkenntnisse aus einer Vielzahl von Patientendaten, die in der klinischen Routine erhoben werden. Multizentrische Analysen bilden darüber hinaus eine breite und repräsentative Patientenpopulation ab und bergen das Potenzial, die reale Versorgungssituation zu erfassen. Als Basis dafür sind die Definition von Datensätzen und eine Infrastruktur zum Datenaustausch notwendig. Datenintegrationszentren (DIZ) sind bereits bundesweit an (universitären) Standorten etabliert worden, um RWD für wissenschaftliche Analysen aus den verschiedenen Quellsystemen zu extrahieren und in forschungskompatiblen Dateninfrastrukturen zu integrieren. Das hier beschriebene Projekt soll den Mehrwert dieser Datenzusammenführung anhand eines Ophthalmologie-Anwendungsfalls demonstrieren und dazu einen Kerndatensatz als Augenheilkunde-Erweiterungsmodul definieren sowie eine standortübergreifende Datenaustauschinfrastruktur etablieren. In einem ersten Schritt soll der Behandlungserfolg bei Augenkrankheiten verbessert werden, die mit intravitrealer operativer Medikamentenapplikation (IVOM) behandelt werden. Zur Erreichung dieses Ziels soll ein Dashboard für klinische Daten bereitgestellt werden, das die zusammengeführten Daten übersichtlich visualisiert. Darüber hinaus sollen Algorithmen zur Identifikation neuer bildgebender Biomarker entwickelt werden, die der Therapieüberwachung dienen und Behandlungsergebnisse prognostizieren können.
Urm1 from yeast is a unique ubiquitin-like protein with dual functionality. It has been shown to operate in tRNA thiolation and protein urmylation, combining features typical of bacterial sulfur carriers and classical ubiquitin-like modifiers. Hence, in evolutionary terms, Urm1 may be placed at the crossroad of prokaryotic sulfur transfer and eukaryotic protein conjugation pathways. Prompted by Urm1-like proteins identified in Archaea, we examined Urm1 functional conservation using URM1 gene shuffle from Sulfolobus acidocaldarius to Saccharomyces cerevisiae. We find that archaeal Urm1 conjugates to peroxiredoxin Ahp1, a bona fide urmylation target in yeast, but cannot support tRNA thiolation. Ahp1 conjugation requires sulfur transfer onto the archaeal Urm1 modifier from Uba4, the E1-like urmylation activator in yeast. Thus, thioactivation of archaeal Urm1 and urmylation-like conjugation are conserved and exchangeable processes between Sulfolobus and Saccharomyces. Our survey underlines that Urm1 likely occupies a key role in the evolution of the ubiquitin-like protein family.
Nuclear factor of activated T-cells 5 (NFAT5) is a transcription factor known for its role in osmotic stress adaptation in the renal inner medulla, due to the osmotic gradient that is generated between the renal cortex and renal inner medulla. However, its broader implications in kidney injury and chronic kidney disease (CKD) are less understood. Here we used two different Cre deleter mice (Ksp1.3-Cre and Aqp2-Cre) to generate tubule segment and even cell type-specific NFAT5-deficient mice and performed extensive gene expression profiling. In both Nfat5 knockout models, we observed massive changes in gene expression pattern, with heightened inflammatory responses and renal injury, culminating in renal fibrosis. Interestingly, inflammatory responses were much more prominent in the Aqp2Cre+/-Nfat5fl/fl mice that lack NFAT5 only in the collecting duct. By analyzing gene expression in the medullary and cortical regions of the kidney separately, we confirmed that the loss of NFAT5 results in kidney injury that extends beyond hypertonic areas. Renal injury correlates with the expression level of genes involved in inflammatory response, injury severity, and cytokine signaling. Thus, NFAT5 is essential not only for adapting to osmotic stress but also for its loss of function, which induces activation of inflammatory response and cytokine signaling that might affect regions with functional NFAT5 expression.
Timely and accurate detection of tumor recurrence in pancreatic ductal adenocarcinoma (PDAC) patients is an urgent and unmet medical need. This study aimed to develop a noninvasive molecular diagnostic procedure for the detection of recurrence after PDAC resection based on quantification of circulating mRNA and miRNA biomarkers in serum samples. In a multicentric study, serum samples from a total of 146 patients were prospectively collected after resection. Samples were classified into a "No Evidence of Disease" and a "Recurrence" group based on clinical follow-up data. A multianalyte biomarker panel was composed of mRNAs and miRNA markers and simultaneously analyzed in serum samples using custom microfluidic qPCR arrays (TaqMan array cards). A diagnostic algorithm was developed combining a 7-gene marker signature with CA19-9 data. The best-performing marker combination achieved 90% diagnostic accuracy in predicting the presence of tumor recurrence (98% sensitivity; 84% specificity), clearly outperforming the singular CA 19-9 analysis. Moreover, time series data obtained by analyzing successively collected samples from 5 patients during extended follow-up suggested that molecular diagnosis has the potential to detect recurrence earlier than routine clinical procedures. TaqMan array card measurements were found to be biologically valid and technically reproducible. The BioPac multianalyte marker panel is capable of sensitive and accurate detection of recurrence in patients resected for PDAC using a simple blood test. This could allow a closer follow-up using shorter time intervals than currently used for imaging, thus potentially prompting an earlier work-up with additional modalities to allow for earlier therapeutic intervention. This study provides a promising approach for improved postoperative monitoring of resected PDAC patients, which is an urgent and unmet clinical need.
The increasing integration of artificial intelligence (AI) in healthcare not only holds the potential for efficiency gains, personalized medicine, and evidence-based decisions but also raises ethical and social challenges, such as bias, lack of transparency, and acceptance. Participatory approaches that actively involve patients, physicians, caregivers, and other stakeholders in the development process make it possible to align technological innovations with actual needs and to design them in a socially just way.The analysis distinguishes between participation as active co-design and partaking as access to social resources. Theoretical models such as the "ladder of participation" (Arnstein) illustrate the different levels of participation. In addition, methodological approaches such as action research, community-based participatory research, ethics by design, and value-sensitive design are discussed, which promote early ethical reflection and continuous user feedback.Practical examples such as KIPA (AI-supported patient information), KIDELIR (delirium prevention in care), and PRIVETDIS (neurotechnologies and mental privacy) show how participatory research can contribute to the optimization of care concepts. In addition to opportunities such as increased acceptance and user-centered technology design, challenges are identified, including limited resources, lack of representativeness, and invisible additional burdens for those involved. Finally, it is emphasized that in addition to technical and regulatory measures, continuous ethical reflection and transparent communication are essential to implement trustworthy and effective AI systems in healthcare. Die zunehmende Integration von künstlicher Intelligenz (KI) im Gesundheitswesen birgt neben Potenzialen für Effizienzsteigerungen, personalisierte Medizin und evidenzbasierte Entscheidungen auch ethische und soziale Herausforderungen, etwa in Bezug auf Bias, mangelnde Transparenz und Akzeptanz. Partizipative Ansätze, die Patient:innen, Ärzt:innen, Pflegefachkräfte und weitere Stakeholder:innen aktiv in den Entwicklungsprozess einbeziehen, ermöglichen es, technologische Innovationen an den tatsächlichen Bedürfnissen auszurichten und sozial gerecht zu gestalten.In der Analyse werden Partizipation als aktive Mitgestaltung und Teilhabe als Zugang zu gesellschaftlichen Ressourcen voneinander abgegrenzt. Theoretische Modelle wie die „Ladder of Participation“ (Arnstein) veranschaulichen die unterschiedlichen Grade der Einbindung. Zudem werden methodische Ansätze wie Aktionsforschung, Community-based Participatory Research, Ethics-by-Design und Value-Sensitive-Design diskutiert, die eine frühzeitige ethische Reflexion und kontinuierliches Nutzerfeedback fördern.Anhand von Praxisbeispielen wie KIPA (KI-gestützte Patientenaufklärung), KIDELIR (Delirprävention in der Pflege) und PRIVETDIS (Neurotechnologien und mentale Privatheit) wird gezeigt, dass partizipative Forschung zur Optimierung von Versorgungskonzepten beitragen kann. Neben Chancen wie erhöhter Akzeptanz und bedarfsgerechter Technologiegestaltung werden Herausforderungen identifiziert, darunter begrenzte Ressourcen, mangelnde Repräsentativität und unsichtbare Mehrbelastungen. Abschließend wird betont, dass neben technischen und regulatorischen Maßnahmen eine kontinuierliche ethische Reflexion sowie transparente Kommunikation unerlässlich sind, um vertrauenswürdige und effektive KI-Systeme im Gesundheitswesen zu realisieren.