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Atrial fibrillation (AF) is a continually growing health-care burden that often presents together with metabolic disorders, including diabetes mellitus and obesity. Current treatments often fall short of preventing AF and its adverse outcomes. Accumulating evidence suggests that metabolic disturbances can promote the development of AF through structural and electrophysiological remodelling, but the underlying mechanisms that predispose an individual to AF are aetiology-dependent, thus emphasizing the need for tailored therapeutic strategies to treat AF that target an individual’s metabolic profile. AF itself can induce changes in glucose, lipid and ketone metabolism, mitochondrial function and myofibrillar energetics (as part of a process referred to as ‘metabolic remodelling’), which can all contribute to atrial dysfunction. In this Review, we discuss our current understanding of AF in the setting of metabolic disorders, as well as changes in atrial metabolism that are relevant to the development of AF. We also describe the potential of available and emerging treatment strategies to target metabolic remodelling in the setting of AF and highlight key questions and challenges that need to be addressed to improve outcomes in these patients.

Percutaneous active mechanical circulatory support (MCS) devices are being increasingly used in the treatment of acute myocardial infarction-related cardiogenic shock (AMICS) despite conflicting evidence regarding their effect on mortality. We aimed to ascertain the effect of early routine active percutaneous MCS versus control treatment on 6-month all-cause mortality in patients with AMICS.

Open-cell ceramic foams are widely used as filters for the purification of molten metals due to their high permeability and high efficiency for capturing non-metallic inclusions. With the consideration of manufacture and filtration behaviour, most filters are produced by replica methods. The intrinsic multiscale porous structure requires the ceramic foams to have sufficient strength. As a consequence, different processing approaches, material compositions and characterizations are investigated. Meanwhile, to further enhance the filtration performance, the functionalization of ceramic foam filters is often conducted with surface coating. This review summarizes the processing and characteristics of ceramic foam filters (CFFs), the nature and formation of non-metallic inclusions (NMIs), the filtration mechanism and applications of CFFs. The characterization of mechanical and filtration performance, as well as the corresponding strengthening and functionalization methods are also presented.

We revisit a service provider’s problem to match supply and demand via an online appointment system such as a doctor in the health care sector. We identify in a survey that an extensive set of available appointments leads to significantly less demand because customers infer a lower quality of the service, as part of an observational learning process. We capture the quality inference effect in a multinomial logit framework and present a Markov decision process for solving the problem of releasing available slots of the appointment system to optimality aiming at maximizing the expected profits. We further evaluate several simple decision rules and provide management insights on which rule to apply under different generic scenarios. Different from current literature, offering all available appointments may lead to suboptimal results when accounting for the quality inference effect. The profit-maximizing strategy then is to offer a subset of the available appointments.

SummaryAre you having trouble getting married? These days, there are lots of products on the market for dating, from apps to websites and matchmakers, but we know a simpler way! That’s right—your path to coupled life isn’t through Tinder; it’s through Sudoku! Read our fabulous paper, where we explore the Stable Marriage Problem to help you find happiness and stability in marriage through math. As a bonus, you get two Sudoku puzzles with a new flavor.

Location information is often used as a proxy to guarantee the performance of a wireless communication link. However, localization errors can result in a significant mismatch with the guarantees, particularly detrimental to users operating the ultra-reliable low-latency communication (URLLC) regime. This paper unveils the fundamental statistical relations between location estimation uncertainty and wireless link reliability, specifically in the context of rate selection for ultra-reliable communication. We start with a simple one-dimensional narrowband Rayleigh fading scenario and build towards a two-dimensional scenario in a rich scattering environment. The wireless link reliability is characterized by the meta-probability, the probability with respect to localization error of exceeding the outage capacity, and by removing other sources of errors in the system, we show that reliability is sensitive to localization errors. The $\epsilon $ -outage coherence radius is defined and shown to provide valuable insight into the problem of location-based rate selection. However, it is generally challenging to guarantee reliability without accurate knowledge of the propagation environment. Finally, several rate-selection schemes are proposed, showcasing the problem’s dynamics and revealing that properly accounting for the localization error is critical to ensure good performance in terms of reliability and achievable throughput.

Hintergrund: Digitale Gesundheitsanwendungen (DiGA) können seit 2020 verordnet werden. Fragestellung: Wie ist die Nutzung von DiGA für die Psychoonkologie einzuschätzen? Methode: Die im DiGA-Verzeichnis gelisteten Anwendungen wurden gesichtet sowie deren Nutzung und Wirksamkeit und die Perspektiven verschiedener Akteur*innen (Firmen, Krankenversicherung, Solidargemeinschaft, Patient*innen, Leistungserbringende) in einem Literaturreview (einschließlich grauer Literatur) eruiert. Zusätzlich wurden qualitative Interviews mit Ärzt*innen, medizinischen Fachangestellten und Psychotherapeut*innen zu ihren Erfahrungen mit DiGA geführt. Ergebnisse: Der DiGA-Markt ist dynamisch. Gegenwärtig sind für psychische Erkrankungen 26 DiGA zugelassen, drei für Brustkrebserkrankungen. Sechs DiGA wurden zunächst zugelassen und danach wieder aus dem Verzeichnis gestrichen. Bis September 2023 wurden 451.056 DiGA-Codes genehmigt, 11 % davon direkt durch die Krankenkasse, also ohne dass Behandelnde involviert waren. Unabhängige Reviews kommen zu dem Schluss, dass die Evidenz für positive Versorgungseffekte bislang ungenügend sei und ein hohes Biasrisiko bestehe (Hauptprobleme: keine aktive Kontrollgruppe, unizentrische Studien, direkte Mitwirkung der Hersteller, keine Verblindung, hohes Drop-out, fehlende Erfassung unerwünschter Wirkungen). Die Perspektiven der Akteur*innen auf DiGA sind unterschiedlich. Es wurden insgesamt 13 Interviews mit Leistungserbringenden geführt. Sie erwarten eine zügige Unterstützung, vor allem als Überbrückung bis ein Psychotherapieplatz zur Verfügung steht, Psychoedukation und Empowerment. Bemängelt wurden fehlende Wirksamkeitsnachweise sowie schwache Zulassungskriterien im Vergleich zu Medikamenten. Sorgen richten sich auf eine Enthumanisierung des für psychotherapeutische Prozesse wichtigen menschlichen Kontakts sowie auf Datenschutz und Datensicherheit, die als nicht ausreichend vermutet werden. Schlussfolgerung: Die bisherigen Erfahrungen mit DiGA ergeben ein gemischtes Bild. Es gibt noch zu wenig gute Belege für die Verbesserung patientenrelevanter Endpunkte. Ärzt*innen und Psychotherapeut*innen sollten sich im Vorfeld einer Verordnung über die jeweilige DiGA gut informieren. Die Informationen zu Wirksamkeit und Datensicherheit von DiGA müssen von unabhängigen Einrichtungen zusammengestellt, kritisch geprüft und gut zugänglich sein.

Thermoresponsive microgels experience a volume phase transition triggered by temperature changes, a phenomenon often analyzed using dynamic light scattering to observe overall size alterations via the diffusion coefficient. However, local structural changes are typically assessed using more intricate and expensive techniques like small-angle neutron or X-ray scattering. In our research, we investigate the volume phase transition of poly-N-isopropylacrylamide (PNIPAM)-based microgels by employing a combination of temperature-dependent dynamic light scattering and simpler, faster, and more efficient attenuation measurements. We utilize attenuation at a fixed wavelength as a direct measure of dispersion turbidity, linking the absolute changes in hydrodynamic radius to the absolute changes in turbidity. This approach allows us to compare “classical” PNIPAM microgels from precipitation polymerization, charged copolymer microgels from precipitation copolymerization, and core–shell microgels from seeded precipitation polymerization. Our study includes a systematic analysis and comparison of 30 different microgels. By directly comparing data from dynamic light scattering and attenuation spectroscopy, we gain insights into structural heterogeneity and deviations from the established fuzzy sphere morphology. Furthermore, we demonstrate how turbidity data can be converted to swelling curves.

AbstractBackgroundLeft atrial (LA) strain, comprising LA reservoir, conduit and contractile function could add mechanistic information of patients after arterial switch operation (ASO) for transposition of the great arteries (TGA). ASO patients might have abnormal ventriculoarterial coupling, which makes them vulnerable to left ventricle (LV) dysfunction and results in reduced exercise capacity. This explorative study aimed to evaluate the relation between LA strain, atrial size, ventricular function, and exercise data obtained by cardiopulmonary exercise testing (CPET).MethodsIn a cohort of 44 patients (71% male, mean age 25 ± 4 years) LA strain was measured using transthoracic speckle-tracking echocardiography. Further assessment involved standard echocardiography, CPET evaluation, and blood sampling. LA strain values were compared to normal values. Correlations were calculated. Regression analysis with all strain variables to the CPET data was performed.ResultsLA reservoir, conduit and contractile strain were normal in 30%, 89% and 50% of the patients, respectively. LA reservoir/contractile straincorrelated to LV ejection fraction (ρ0.310/−0.159, respectively) and LA reservoir/conduit straincorrelated to the LA volume index (ρ0.336/−0.357, respectively). None of the individual LA strain parameterswere associated with the CPET variables. In multivariate regression analysis, LA contractile strainwas significantly associated with the percentage of predicted maximal heart rate (β − 2.555).ConclusionsThese data suggest that in TGA patients after ASO repair LA strain is impaired and correlates with LA size and LV function. However, impaired LA strain wasn’t associated with the standard CPET parameters. As such, clinical significance needs to be further unravelled.

Arctic and alpine tundra ecosystems are large reservoirs of organic carbon1,2. Climate warming may stimulate ecosystem respiration and release carbon into the atmosphere3,4. The magnitude and persistency of this stimulation and the environmental mechanisms that drive its variation remain uncertain5–7. This hampers the accuracy of global land carbon–climate feedback projections7,8. Here we synthesize 136 datasets from 56 open-top chamber in situ warming experiments located at 28 arctic and alpine tundra sites which have been running for less than 1 year up to 25 years. We show that a mean rise of 1.4 °C [confidence interval (CI) 0.9–2.0 °C] in air and 0.4 °C [CI 0.2–0.7 °C] in soil temperature results in an increase in growing season ecosystem respiration by 30% [CI 22–38%] (n= 136). Our findings indicate that the stimulation of ecosystem respiration was due to increases in both plant-related and microbial respiration (n= 9) and continued for at least 25 years (n= 136). The magnitude of the warming effects on respiration was driven by variation in warming-induced changes in local soil conditions, that is, changes in total nitrogen concentration and pH and by context-dependent spatial variation in these conditions, in particular total nitrogen concentration and the carbon:nitrogen ratio. Tundra sites with stronger nitrogen limitations and sites in which warming had stimulated plant and microbial nutrient turnover seemed particularly sensitive in their respiration response to warming. The results highlight the importance of local soil conditions and warming-induced changes therein for future climatic impacts on respiration.

Graphic abstract:

Artificial intelligence electrocardiogram can be used to screen for an abnormal heart function after anthracycline chemotherapy, opening the door to new ways of cost-effective screening of cancer survivors at risk of cardiotoxicity over long periods of time.Graphical abstract

Hintergrund und Fragestellung: Die Laienreanimationsrate in Deutschland hinkt trotz messbarem Anstieg in den letzten Jahren dem europäischen Vergleich hinterher. In der klinischen Versorgung der Postreanimationsphase haben sich spezielle Kliniken zur Versorgung von Patienten nach Herz-Kreislauf-Stillstand, die sog. Cardiac Arrest Center (CAC), etabliert. Ziel dieser Arbeit ist zu evaluieren, welche Rolle die CAC, neben der innerklinischen Patientenversorgung, in der Verbesserung der Laienreanimationsrate in Deutschland einnehmen und welche Hindernisse in der Durchführung von Wiederbelebungsschulungen bestehen. Material und Methoden: Onlineumfrage der Arbeitsgruppe Kardiopulmonale Reanimation (AG42) der Deutschen Gesellschaft für Kardiologie (DGK) und des Deutschen Rats für Wiederbelebung (German Resuscitation Council, GRC). Ergebnisse: Von den 74 teilnehmenden Kliniken (78,4 % zertifizierte CAC) führen 23 (31,1 %) Laienreanimationsschulungen (Basic Life Support, BLS) durch. Vornehmlich finden diese im Rahmen von Aktionstagen zur Wiederbelebung (82,6 %) oder in Schulen (39,1 %) statt. Eine feste Kooperation mit mindestens einer Schule bestand in 52,2 %. Reanimationspuppen werden in 63,5 %, ein automatisierter externer Defibrillator ([AED-]Demogerät) in 43,2 % dieser Kliniken vorgehalten. Die größten Hindernisse für eine konsequente Implementierung von Wiederbelebungskursen im Schulunterricht bestehen, nach Angaben der Befragten, neben dem Mangel an qualifizierten Instruktoren in der fehlenden Refinanzierung sowie der Schwierigkeit im Hinblick auf koordinierende Tätigkeiten zwischen den Schulen und anbietenden Erbringern. Schlussfolgerungen: Die direkte Ausbildung von Laienhelfern*innen durch Krankenhäuser hat mit mehreren Hindernissen zu kämpfen. Zur Erhöhung der Laienreanimationsrate kann die Fokussierung auf gezielte Schulungen von Lehrkräften als Multiplikatoren (Train the Trainer) ein guter Ansatz für Cardiac Arrest Center sein.

Monitoring environmental DNA can track the presence of organisms, from viruses to animals, but requires continuous sampling of transient sequences from a complex milieu. Here we designed living sentinels using Bacillus subtilisto report the uptake of a DNA sequence after matching it to a preencoded target. Overexpression of ComK increased DNA uptake 3,000-fold, allowing for femtomolar detection in samples dominated by background DNA. This capability was demonstrated using human sequences containing single-nucleotide polymorphisms (SNPs) associated with facial features. Sequences were recorded with high efficiency and were protected from nucleases for weeks. The SNP could be determined by sequencing or in vivo using CRISPR interference to turn on reporter expression in response to a specific base. Multiple SNPs were recorded by one cell or through a consortium in which each member recorded a different sequence. Sentinel cells could surveil for specific sequences over long periods of time for applications spanning forensics, ecology and epidemiology.

Background: When shunt dysfunction is suspected, radiation exposure due to X-rays or a CT-scan is inevitable. Less-invasive and more reliable methods are warranted. In this study, we aimed to assess the usability of smartphone-based thermography to detect shunt patency in patients with hydrocephalus. Methods: This prospective observational pilot study evaluated the use of smartphone-based video thermography to detect flow of cerebrospinal fluid in the shunt of 51 patients from the Department of Neurosurgery at a tertiary referral institute. Patients with a shunt for hydrocephalus without the suspect of dysfunction were included in the study from December 2021 to May 2022. Results: We included 51 patients with a mean age of 53.3 years. Of these patients 14 were male (27.5%) and 37 were female (72.5%). The most frequent cause of the hydrocephalus was the normal pressure hydrocephalus followed by the congenital hydrocephalus. Most patients (96%) had a ventriculoperitoneal shunt, whereas two had a ventriculo-atrial shunt. In total, 43 patient (84%) had a shunt on the right side and 8 patient (16%) had the shunt located on the left side. In 45 patients (88.2%), we observed a clear flow of cerebrospinal fluid in the cooled shunt trajectory. Conclusions: The findings of this study indicate that in patients with a shunt to treat hydrocephalus, the smartphone-based video thermography may be a safe and simple alternative to show shunt patency without the exposure to radiation.

AbstractAs a response to the increased need for humanization and representation in STEM, a set of open-source, customizable icons was developed using stackable vector graphics to allow participants to design their own research icons. These icons have the potential to both grant research participant’s greater agency in their representation and attempt to minimize bias introduced by the researcher. Additionally, the representation provided by the developed icons help to illuminate those that are participating in geoscience. The visual representation of research participants provides an opportunity for these individuals to see themselves represented in geoscience spaces and aids in visualizing the geoscience community. Examples of implementation in both quantitative and qualitative research are provided and the authors encourage their use by the broader research community.

Powerful distributed computing can be achieved by communicating cells that individually perform simple operations. Here, we report design software to divide a large genetic circuit across cells as well as the genetic parts to implement the subcircuits in their genomes. These tools were demonstrated using a 2-bit version of the MD5 hashing algorithm, which is an early predecessor to the cryptographic functions underlying cryptocurrency. One iteration requires 110 logic gates, which were partitioned across 66 Escherichia colistrains, requiring the introduction of a total of 1.1 Mb of recombinant DNA into their genomes. The strains were individually experimentally verified to integrate their assigned input signals, process this information correctly and propagate the result to the cell in the next layer. This work demonstrates the potential to obtain programable control of multicellular biological processes.

The PIWI-interacting RNA (piRNA) pathway guides the DNA methylation of young, active transposons during germline development in male mice1. piRNAs tether the PIWI protein MIWI2 (PIWIL4) to the nascent transposon transcript, resulting in DNA methylation through SPOCD1 (refs. 2–5). Transposon methylation requires great precision: every copy needs to be methylated but off-target methylation must be avoided. However, the underlying mechanisms that ensure this precision remain unknown. Here, we show that SPOCD1 interacts directly with SPIN1 (SPINDLIN1), a chromatin reader that primarily binds to H3K4me3-K9me3 (ref. 6). The prevailing assumption is that all the molecular events required for piRNA-directed DNA methylation occur after the engagement of MIWI2. We find that SPIN1 expression precedes that of both SPOCD1 and MIWI2. Furthermore, we demonstrate that young LINE1 copies, but not old ones, are marked by H3K4me3, H3K9me3 and SPIN1 before the initiation of piRNA-directed DNA methylation. We generated a Spocd1separation-of-function allele in the mouse that encodes a SPOCD1 variant that no longer interacts with SPIN1. We found that the interaction between SPOCD1 and SPIN1 is essential for spermatogenesis and piRNA-directed DNA methylation of young LINE1 elements. We propose that piRNA-directed LINE1 DNA methylation requires a developmentally timed two-factor authentication process. The first authentication is the recruitment of SPIN1–SPOCD1 to the young LINE1 promoter, and the second is MIWI2 engagement with the nascent transcript. In summary, independent authentication events underpin the precision of piRNA-directed LINE1 DNA methylation.

As interest in the implementation of active learning practices grows, so too does the body of literature illustrating negative experiences of these practices among some populations of students. These trends necessitate a critical inquiry into how students with identities that are traditionally marginalized in mathematical spaces differentially experience active learning practices. We leverage critical quantitative theories to analyze how shifts in precalculus and calculus students’ math affect are mediated by intersectional race-gender identities and the active learning instructional practices of math engagement, peer collaboration, instructor inquiry, and participation. Drawing on a dataset of over 30,000 U.S. student survey responses, we found that experiencing high levels of all four practices increased math affect for all student identity groups in our dataset. Considering each individual practice revealed variation of students’ affective changes based on race-gender identities, such that not every individual practice benefited every student identity group. These findings emphasize the value in promoting the collective high use of multiple active learning practices, coupled with more in-depth understandings and attention to how these individual practices can differentially impact students.

Algorithmic materials discovery is a multidisciplinary domain that integrates insights from specialists in alloy design, synthesis, characterization, experimental methodologies, computational modeling, and optimization. Central to this effort is a robust data management system paired with an interactive work platform. This platform should empower users to not only access others’ data but also integrate their analyses, paving the way for sophisticated data pipelines. To realize this vision, there is a need for an integrative collaboration platform, streamlined data sharing and analysis tools, and efficient communication channels. Such a collaborative mechanism should transcend geographical barriers, facilitating remote interaction and fostering a challenge-response dynamic. To further enhance precision and interoperability in this multifaceted research landscape, we must explore innovative ways to refine these processes and improve the integration of expertise and data across diverse domains. In this paper, we present our ongoing efforts in addressing the critical challenges related to an accelerated materials discovery framework as a part of the High-Throughput Materials Discovery for Extreme Conditions (HTMDEC) Initiative. Our BIRDSHOT(Batch-wise Improvement in Reduced Materials Design Space using a Holistic Optimization Technique) Center has successfully harnessed various tools and strategies, including the utilization of cloud-based storage, a standardized sample naming convention, a structured file system, the implementation of sample travelers, a robust sample tracking method, and the incorporation of knowledge graphs for efficient data management. Additionally, we present the development of a data collection platform, reinforcing seamless collaboration among our team members. In summary, this paper provides an illustration and insight into the various elements of an efficient and effective workflow within an accelerated materials discovery framework while highlighting the dynamic and adaptable nature of the data management tools and sharing platforms.

Recreational use of bathing waters is very popular in Germany and the European Union (EU). Therefore, the spread of antibiotic-resistant facultative-pathogenic bacteria (ARB) presents a possible public health issue. During the 2018 summer bathing season, a prevalence study involving 16 selected EU bathing waters in North Rhine-Westphalia was conducted. The aim was to identify the presence of ARB, antibiotic residues or resistance genes, and to develop a tool that assists advisers on prevention measures for individuals and the health authorities. The study included (i) hygienic-microbiological analyses according to the EU Bathing Water Directive, (ii) antibiotic residue measurements, (iii) cultural and molecular analyses to identify ARB and resistance genes and (iv) development of a risk assessment tool based on the burden of the bathing water and the vulnerability of bathing persons. All bathing waters were complied with the EU Bathing Water Directive. Three samples were found to contain very small amounts of ARB. Small quantities of antibiotic residues were detected in three bathing waters. Only one sample contained a resistance gene. In total, only 2 bathing waters were assumed to be systemically burdened with ARB and antibiotic residues or resistance genes. 4 bathing waters indicated single contamination events, 10 bathing waters were unburdened. In conclusion, bathing waters fulfilling criteria of the EU bathing water directive did not show high contaminations with ARB, antibiotic residues or resistance genes. However, we propose that people with risk factors should avoid swimming in burdened waters; people with immune deficiency should avoid swimming at all.

The 3D sand printing (3DSP) process is a binder jetting class of additive manufacturing process that can incorporate complex 3D mold designs and consolidate cores with intricate features that were previously inaccessible. Prior studies in 3DSP mold design have been shown to improve pouring and filling conditions for sand casting. However, the opportunity to improve casting quality by exploring 3D riser designs during the solidification stage has not yet been explored. In this research, three novel 3D riser geometries—ellipsoid, spherical, and a fusion riser (combination of cylindrical and ellipsoid riser) were investigated. The results were compared to the benchmark cylindrical risers to assess casting performance (e.g., reduction in shrinkage porosity, increase in solidification time). Computational solidification simulations have been presented to evaluate the characteristics of the novel risers for three different metal alloys- nickel aluminum bronze (NAB), low-carbon steel A216 (WCB), and aluminum alloy (A319) alloy. From the results of this research, spherical risers were found to provide 45% yield improvement of for the three alloys studied. In addition, the riser neck diameter using a spherical riser experienced up to 77% reduction when compared to the recommended dimensions from previous literature. Finally, one of the spherical riser designs provided 18% improvement in terms of riser-pipe safety height over the benchmark design. Findings from this research will help metalcasting industries to optimize their riser designs for complex casting geometries by implementing 3D riser geometries (via 3DSP) into traditional mold making for yield improvement and defect-free castings.

When implementing business model innovation (BMI), managers of incumbent firms can choose between two options. They can either separate BMI from the existing business, such as in a spin-off, or integrate it into existing structures, or business units. However, extant literature offers limited evidence on the nature of both options and their specific benefits. To address this research gap, in this article, we draw insights from eight cases of BMI in five large incumbent firms. This study makes several contributions to existing literature. First, it provides an in-depth account of the implementation factors employed during BMI in large incumbent organizations. Consequently, we show that factors, such as organizational climate, management support, patience, and implementation policies and practices, serve multiple purposes, ranging from providing expertise to the core implementation team to reducing widespread skepticism among the nonengaged workforce. Second, we illustrate how the cases account for the organizational assimilation of innovation (i.e., integration) or insulation from organizational influences (i.e., separation). Specifically, we illustrate the nature and benefits of integrating and separating BMI among the incumbent firms. Third, we shed light on strategies for BMI implementation, balancing separation and integration during BMI implementation, from an ambidexterity perspective.

Errors in pharmacy medication directions, such as incorrect instructions for dosage or frequency, can increase patient safety risk substantially by raising the chances of adverse drug events. This study explores how integrating domain knowledge with large language models (LLMs)—capable of sophisticated text interpretation and generation—can reduce these errors. We introduce MEDIC (medication direction copilot), a system that emulates the reasoning of pharmacists by prioritizing precise communication of core clinical components of a prescription, such as dosage and frequency. It fine-tunes a first-generation LLM using 1,000 expert-annotated and augmented directions from Amazon Pharmacy to extract the core components and assembles them into complete directions using pharmacy logic and safety guardrails. We compared MEDIC against two LLM-based benchmarks: one leveraging 1.5 million medication directions and the other using state-of-the-art LLMs. On 1,200 expert-reviewed prescriptions, the two benchmarks respectively recorded 1.51 (confidence interval (CI) 1.03, 2.31) and 4.38 (CI 3.13, 6.64) times more near-miss events—errors caught and corrected before reaching the patient—than MEDIC. Additionally, we tested MEDIC by deploying within the production system of an online pharmacy, and during this experimental period, it reduced near-miss events by 33% (CI 26%, 40%). This study shows that LLMs, with domain expertise and safeguards, improve the accuracy and efficiency of pharmacy operations.

Zusammenfassung: Ausgewählte Markergene sowie deren Kombinationen wurden an verschiedenen minimalen Prostatagewebeproben hinsichtlich ihres diagnostischen Potenzials analysiert. Als Modellsystem zur Evaluierung und Optimierung dienten zunächst artifizielle Prostatabiopsien aus Präparaten von radikalen Prostatektomien (RPE). Anschließend erfolgte die Übertragung der Methoden auf Feinnadelbiopsien, welche routinemäßig zum histopathologischen Prostatakarzinomnachweis entnommen werden. Die Prostatabiopsien wurden nach standardisierten Methoden kryokonserviert und aufgearbeitet. Die RNA-Mengen, die aus je einer Biopsiehälfte gewonnen werden konnten, waren ausreichend, um 11 Markergene und ein Referenzgen (TBP) mittels quantitativer PCR bestimmen zu können. Zur Berechnung der Überexpression der Markergene in tumorhaltigen verglichen mit tumorfreien Prostatabiopsien dienten die relativen Transkriptmengen. Neben der Auswertung als Einzelmarker wurden die relativen Transkriptmengen auch in Markerkombinationen analysiert. Zwei optimierte mathematische Genmodelle auf der Basis der relativen Transkriptmengen von EZH2, Hepsin, PCA3, Prostein und TRPM8 wurden auf ihre Eignung zur Prostatakarzinomvorhersage an minimalen Gewebeproben evaluiert. Im Gegensatz zur Einzelmarkeranalyse zeigten diese Modelle eine deutlich höhere Sensitivität und Spezifität für die Prostatakarzinomvorhersage. Die hier etablierte Methodik erlaubt die Analyse prostatakarzinomassoziierter Markergene an minimalen Gewebemengen und könnte eine Ergänzung zur herkömmlichen Diagnostik von Prostatabiopsien darstellen. Die Untersuchung weiterer Markergenmodelle, auch in Hinblick auf eine Prognosevorhersage, sowie die Übertragung auf Urinproben sind Gegenstand weiterer Untersuchungen.