Search

Freerk Prenzel1,2 *, Regina Treudler1,3 *, Tobias Lipek,1,2 Maike vom Hove,1,2 Paula Kage,1,3 Simone Kuhs,1,4 Thorsten Kaiser,1,4 Maximilian Bastl,5 Jan Bumberger,6– 8 Jon Genuneit,9,10 Thomas Hornick,8,11 Stefan Klotz,8,12 Julia Zarnowski,1,3 Maren Boege,1,13 Veit Zebralla,1,13 Jan-Christoph Simon,1,3 Susanne Dunker8,11 1Leipziger Interdisciplinary Center for Allergy (LICA), Comprehensive Allergy Center, Leipzig, Germany; 2University of Leipzig, Medical Center, Department of Pediatrics, Leipzig, Germany; 3University of Leipzig, Medical Center, Department of Dermatology, Venerology and Allergy, Leipzig, Germany; 4University of Leipzig, Medical Center, Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig, Germany; 5Medical University of Vienna, Department of Otorhinolaryngology, Vienna, Austria; 6Helmholtz-Centre for Environmental Research (UFZ), Department Monitoring and Exploration Technologies, Leipzig, Germany; 7Helmholtz-Centre for Environmental Research (UFZ), Research Data Management, Leipzig, Germany; 8German Centre for Integrative Biodiversity Research (iDiv) Halle, Jena, Leipzig, Germany; 9Pediatric Epidemiology, Department of Pediatrics, Medical Faculty, Leipzig University, Leipzig, Germany; 10German Center for Child and Youth Health, Leipzig/ Dresden, Dresden, Germany; 11Helmholtz-Centre for Environmental Research (UFZ), Department Physiological Diversity, Leipzig, Germany; 12Helmholtz-Centre for Environmental Research (UFZ), Department Community Ecology, Halle, Germany; 13University of Leipzig, Medical Center, Department of Otorhinolaryngology, Head and Neck Surgery, Leipzig, Germany*These authors contributed equally to this workCorrespondence: Susanne Dunker, Helmholtz Centre for Environmental Research – UFZ, Leipzig, Germany, Tel +49 341 9733170, Email susanne.dunker@ufz.dePurpose: Ailanthus altissima is one of the world’s most invasive species with a globally problematic spread. Pollen is dispersed locally and partially airborne. We aimed at investigating if (i) A. altissima pollen can be detected in relevant quantity in the air and if (ii) sensitization to A. altissima can be detected in patients with seasonal exacerbation of atopic diseases.Patients and Methods: We recorded distribution of A. altissima in Leipzig, Germany. In 2019 and 2020, pollen was collected with a Hirst-type pollen trap placed on the roof of the University Hospital. Specific IgE investigations were performed in children and adults with history of atopic diseases with deterioration between May and July. We analysed specific IgE for A. altissima, Alternaria sp., birch, grasses, profilins, polcalcins and crossreacting carbohydrates.Results: We found abundant growth of A. altissima and pollen was detected from early June to mid-July with a maximum pollen concentration of 31 pollen/m3. Out of 138 patients (63 female, 69 children/adolescents), 95 (69%) had seasonal allergic rhinitis, 84 (61%) asthma, and 43 (31%) atopic dermatitis. Sensitization to A. altissima was shown in 59 (42%). There were no significant differences between age groups. In 59% of patients sensitized (35/59), there was no sensitization to possibly cross-reacting structures.Conclusion: Sensitization to A. altissima pollen could be detected in 42% of our patients with atopic diseases, suggesting allergenic potential of this neophyte. In the context of further spread with climate change, eradication strategies and population-based sensitization studies are needed.Keywords: allergy, invasive species, neophyte, pollinosis, pollen count

The possibility of establishing a novel technique for reliably accessing glycemic information in a non-invasive, easy to implement method at THz frequencies via the fingernail bed is investigated. The nail bed’s major content is blood at its various glucose levels and is also partially protected from environmental conditions by the nail plate, making it a desirable platform for non-invasive glucose sensing. The study is based on a 2D computational electromagnetics (EM) model of the layered fingernail in COMSOL Multiphysics, where the required dielectric function (i.e. permittivity and conductivity) of the fingernail plate is measured using THz-Time-Domain- Spectroscopy (THz-TDS), and the glucose-dependend dielectric functions of the fingernail bed are taken from available experimental data in the literature. From this data a material model using a multipole Cole-Cole model is established for both, the nail plate and the nail bed, where the glucose content in the latter is varied from 3.0-19.0 mmol/l. A numerical analysis of the THz reflectometry at the fingernail in the frequency range of 0.1-2.0 THz revealed that the reflectance spectra are sensitive to the glucose content in the nail bed proving that accurate glucose sensing via the fingernail bed may become feasible around 0.2-0.4 THz.

The shortage of grafts for liver transplantation requires risk stratification and adequate allocation rules. This study aims to improve the model of end-stage liver disease (MELD) score for 90-day mortality prediction with the help of different machine-learning algorithms.

Psychotherapy outcome research mainly focuses on scale-level changes and constructs that were developed using cross-sectional statistical analysis, possibly concealing important findings on the level of single items, and limiting the clinical utility of outcome scales. Our goal was to explore changes in symptoms, interpersonal problems, and level of functioning in everyday life and to establish groups of items with similar rates of change that could be used to form more coherent targets for measuring different therapeutic outcomes. Triangulated maximally filtered graphs were used to model the network structure of the Outcome Questionnaire-45 in a data set of N = 12,075 university counseling center patients. Dynamic exploratory graph analysis was used to establish communities of items with similar rates of change. Five item communities (anxiety, hopelessness, interpersonal problems, well-being, and work impairment) were found. Compared to the original Outcome Questionnaire-45 subscales, they showed better fit to the data. The "hopelessness" community, which describes the extent of a patient's demoralization before the start of therapy, had a significantly higher rate of change compared to other communities. The discerned item communities provide clinicians with theoretically grounded, precise targets for outcome tracking, thereby enhancing the responsiveness and adaptability of treatment interventions to individual client trajectories. Such granularity enriches our understanding of therapeutic change, with direct implications for tailoring intervention strategies to maximize early therapeutic gains and sustain long-term recovery. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Flow cytometry is a key technology for the analysis and sorting of cells or particles at high throughput. Conventional and current flow cytometry is primarily based on fluorescent stains to detect the cells of interest. However, such stains also have disadvantages, as their effect on cells must be carefully tested to avoid effects on the results of the experiments. Alternative approaches using imaging or other label-free techniques often require highly sophisticated setups, are commonly limited in resolution, and produce challenging amounts of data. Our technology exploits scattered light instead. The custom-built flow cytometry setup comprises a fiber array in forward scatter detection for angular resolution and captures the whole pulse shape with advanced signal processing. Thereby this setup enables cell analysis and sorting purely based on scattered light signals without the need for fluorescent labels. We demonstrate the feasibility of this cell sorting technology by sorting cell lines for their cell cycle stages based on scattered light. Furthermore, we demonstrate the ability to classify human peripheral blood T- and B-cell subsets., (© 2024. The Author(s).)

Abstract: This is the first study to empirically determine the potential for data-driven personalization in the context of chronic primary pain (CPP). Effect sizes of psychological treatments for individuals with CPP are small to moderate on average. Aiming for better treatment outcomes for the individual patient, the call to personalize CPP treatment increased over time. However, empirical evidence that personalization of psychological treatments can optimize treatment outcomes in CPP is needed. This study seeks to estimate heterogeneity of treatment effect for cognitive behavioral therapy (CBT) as the psychological treatment approach for CPP with the greatest evidence base. For this purpose, a Bayesian variance ratio meta-regression is conducted using updated data from 2 recently published meta-analyses with randomized controlled trials comparing CBT delivered face-to-face to treatment-as-usual or waiting list controls. Heterogeneity in patients with CPP would be reflected by a larger overall variance in the post-treatment score compared with the control group. We found first evidence for an individual treatment effect in CBT compared with the control group. The estimate for the intercept was 0.06, indicating a 6% higher variance of end point values in the intervention groups. However, this result warrants careful consideration. Further research is needed to shed light on the heterogeneity of psychological treatment studies and thus to uncover the full potential of data-driven personalized psychotherapy for patients with CPP.A Bayesian variance ratio meta-regression indicates empirical evidence that data-driven personalized psychotherapy for patients with chronic primary pain could increase effects of cognitive behavioral therapy., (Copyright © 2024 International Association for the Study of Pain.)

Microglia carry out important functions as the resident macrophages of the brain. To study their role in health and disease, the research community needs tools to genetically modify them with maximum completeness in a manner that distinguishes them from closely related cell types, such as monocytes. While currently available tamoxifen-inducible CreERT2 lines can achieve the differentiation from other cells, the field needs improved and publicly available constitutively active Cre lines, especially ones with favorable efficiency and specificity profiles for studies where high recombination efficiency is imperative and where tamoxifen administration is contraindicated. Here, we leverage the microglia-specific Fcrls gene to generate mice expressing Cre. Using genomic methods, we show correct positioning of the transgene and intact microglia homeostasis in Fcrls-2A-Cre mice. Crossing Fcrls-2A-Cre mice to four different reporters, we demonstrate highly efficient recombination in microglia across differentially sensitive loxP alleles in different genomic contexts, indicating robust applicability of the line. Further, we show that microglia recombine a loxP reporter during early embryonic development, supporting the use of the line for developmental studies. Finally, using immunofluorescence and flow cytometry, we reveal that most border-associated macrophages are also targeted whereas only few liver and spleen macrophages and virtually no white blood cell subsets exhibit Cre activity, distinguishing this line from another publicly available Cre line, Cx3cr1-Cre M Fcrls-2A-Cre mice are immediately available (JAX #036591) and serve as a valuable addition to the community's microglia toolbox by providing highly efficient constitutive Cre activity with excellent specificity, particularly for studies where tamoxifen administration is undesirable., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Kaiser et al.)

Objectives: Soluble transferrin receptor (sTfR) is a marker of both erythropoiesis and iron status and is considered useful for detecting iron deficiency, especially in inflammatory conditions, but reference intervals covering the entire pediatric age spectrum are lacking., Methods: We studied 1,064 (48.5 % female) healthy children of the entire pediatric age spectrum to determine reference values and percentiles for sTfR and the ratio of sTfR to log-ferritin (sTfR-F index) using a standard immunoturbidimetric assay., Results: Soluble TfR levels were highly age-specific, with a peak in infancy and a decline in adulthood, whereas the sTfR-F index was a rather constant parameter. There were positive linear relationships for sTfR with hemoglobin (Hb) (p=0.008) and transferrin (females p<0.001; males p=0.003). A negative association was observed between sTfR and ferritin in females (p<0.0001) and for transferrin saturation and mean corpuscular volume (MCV) in both sexes (both p<0.0001). We found a positive relationship between sTfR and body height, body mass index (BMI) and inflammatory markers (CrP p<0.0001; WBC p=0.0172), while sTfR-F index was not affected by inflammation., Conclusions: Soluble TfR values appear to reflect the activity of infant erythropoiesis and to be modulated by inflammation and iron deficiency even in a healthy cohort., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Biofiltration processes are often part of advanced wastewater treatment (aWWT) technologies for the removal of organic micropollutants (OMP) from conventional wastewater treatment plant (WWTP) effluents. Although biological effects are not always the main focus of these technologies (e.g. filtration through granular activated carbon), they have been shown to contribute significantly to total OMP removal. While OMP biodegradation kinetics in conventional biological wastewater treatment are well researched, no systematic comparison to biomass from aWWT is available. This biomass faces different growth conditions and higher OMP concentrations relative to the background organic matter. Adaptation to these conditions could be possible and could lead to faster OMP biodegradation kinetics, which would show in a larger pseudo first-order biodegradation kinetic constant k biol . In this work, k biol values for biomass obtained from aWWT biofilters were determined by evaluating OMP removals measured in lab-scale biofilters using a mechanistic model of the experimental setup. A comparison to k biol values from literature for conventional wastewater treatment (with nutrient removal) revealed similar OMP biodegradation kinetics without any advantages of biomass from aWWT. A conceptual evaluation of influencing factors on OMP removal in biofilters showed that operational parameters (such as the biomass concentration or the empty bed contact time) and the affinity of OMPs to adsorb on biomass have a significant additional effect on biological OMP removal. Therefore, k biol values alone are not sufficient to estimate biological OMP removal in biofilters and further information about the system is required., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Importance: While the effects of internet- and mobile-based interventions (IMIs) for depression have been extensively studied, no systematic evidence is available regarding the heterogeneity of treatment effects (HTEs), indicating to what extent patient-by-treatment interactions exist and personalized treatment models might be necessary., Objective: To investigate the HTEs in IMIs for depression as well as their efficacy and effectiveness., Data Sources: A systematic search in Embase, MEDLINE, Central, and PsycINFO for randomized clinical trials and supplementary reference searches was conducted on October 13, 2019, and updated March 25, 2022. The search string included various terms related to digital psychotherapy, depression, and randomized clinical trials., Study Selection: Titles, abstracts, and full texts were reviewed by 2 independent researchers. Studies of all populations with at least 1 intervention group receiving an IMI for depression and at least 1 control group were eligible, if they assessed depression severity as a primary outcome and followed a randomized clinical trial (RCT) design., Data Extraction and Synthesis: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. Risk of bias was evaluated using the Cochrane Risk of Bias Tool. HTE was investigated using logarithmic variance ratios (lnVR) and effect sizes using Hedges g. Three-level bayesian meta-regressions were conducted., Main Outcomes and Measures: Heterogeneity of treatment effects was the primary outcome of this study; magnitudes of treatment effect sizes were the secondary outcome. Depression severity was measured by different self-report and clinician-rated scales in the included RCTs., Results: The systematic review of 102 trials included 19 758 participants (mean [SD] age, 39.9 [10.58] years) with moderate depression severity (mean [SD] in Patient Health Questionnaire-9 score, 12.81 [2.93]). No evidence for HTE in IMIs was found (lnVR = -0.02; 95% credible interval [CrI], -0.07 to 0.03). However, HTE was higher in more severe depression levels (β̂ = 0.04; 95% CrI, 0.01 to 0.07). The effect size of IMI was medium (g = -0.56; 95% CrI, -0.46 to -0.66). An interaction effect between guidance and baseline severity was found (β̂ = -0.24, 95% CrI, -0.03 to -0.46)., Conclusions and Relevance: In this systematic review and meta-analysis of RCTs, no evidence for increased patient-by-treatment interaction in IMIs among patients with subthreshold to mild depression was found. Guidance did not increase effect sizes in this subgroup. However, the association of baseline severity with HTE and its interaction with guidance indicates a more sensitive, guided, digital precision approach would benefit individuals with more severe symptoms. Future research in this population is needed to explore personalization strategies and fully exploit the potential of IMI.

This paper details the design and implementation of a harmonic frequency-modulated continuous-wave (FMCW) radar system, specialized in detecting harmonic tags and achieving precise range estimation. Operating within the 2.4-2.5 GHz frequency range for the forward channel and 4.8-5.0 GHz for the backward channel, this study delves into the various challenges faced during the system's realization. These challenges include selecting appropriate components, calibrating the system, processing signals, and integrating the system components. In addition, we introduce a single-layer passive harmonic tag, developed specifically for assessing the system, and provide an in-depth theoretical analysis and simulation results. Notably, the system is characterized by its low power consumption, making it particularly suitable for short-range applications. The system's efficacy is further validated through experimental evaluations in a real-world indoor environment across multiple tag positions. Our measurements underscore the system's robust ranging accuracy and its ability to mitigate self-interference, showcasing its significant potential for applications in harmonic tag detection and ranging.

Background: Timely diagnosis is crucial for sepsis treatment. Current machine learning (ML) models suffer from high complexity and limited applicability. We therefore created an ML model using only complete blood count (CBC) diagnostics., Methods: We collected non-intensive care unit (non-ICU) data from a German tertiary care centre (January 2014 to December 2021). Using patient age, sex, and CBC parameters (haemoglobin, platelets, mean corpuscular volume, white and red blood cells), we trained a boosted random forest, which predicts sepsis with ICU admission. Two external validations were conducted using data from another German tertiary care centre and the Medical Information Mart for Intensive Care IV database (MIMIC-IV). Using the subset of laboratory orders also including procalcitonin (PCT), an analogous model was trained with PCT as an additional feature., Results: After exclusion, 1 381 358 laboratory requests (2016 from sepsis cases) were available. The CBC model shows an area under the receiver operating characteristic (AUROC) of 0.872 (95% CI, 0.857-0.887). External validations show AUROCs of 0.805 (95% CI, 0.787-0.824) for University Medicine Greifswald and 0.845 (95% CI, 0.837-0.852) for MIMIC-IV. The model including PCT revealed a significantly higher AUROC (0.857; 95% CI, 0.836-0.877) than PCT alone (0.790; 95% CI, 0.759-0.821; P < 0.001)., Conclusions: Our results demonstrate that routine CBC results could significantly improve diagnosis of sepsis when combined with ML. The CBC model can facilitate early sepsis prediction in non-ICU patients with high robustness in external validations. Its implementation in clinical decision support systems has strong potential to provide an essential time advantage and increase patient safety., (© Association for Diagnostics & Laboratory Medicine 2024.)

Objective: To describe the use of a synthetic hemostatic dressing, QuikClot Combat Gauze (QCG), in dogs with bleeding wounds., Case Series Summary: Two dogs presented with bleeding traumatic wounds, and QCG was used to achieve hemostasis during stabilization of these dogs. In the other 2 dogs, QCG was used to help attenuate bleeding associated with a surgical procedure., New or Unique Information Provided: While hemostatic dressings have been widely studied and used in human medicine, there is minimal information on the use and efficacy of these hemostatic dressings in veterinary medicine. This case series describes the use of QCG in dogs with hemorrhaging wounds. QCG could be a valuable resource in veterinary emergency and critical care settings., (© Veterinary Emergency and Critical Care Society 2024.)

Objectives: Severe hypo- and hypercalcemia are common and urgent treatment is recommended. Free calcium (fCa) is the gold standard but needs blood gas tests with challenging preanalytics. Total calcium (tCa) and calculated adjusted calcium (aCa) are readily available, but their interpretation is hampered by identical tCa and aCa cutoffs, laborious local aCa calculation and difficult comparability of calcium biomarkers., Methods: Laboratory results from University Medicine Leipzig were evaluated over a five-year period (236,274 patients). A local aCa equation was derived by linear least squares regression, the agreement between fCa, tCa and aCa assessed with Cohen's κ and decision thresholds derived by this indirect method., Results: The local aCa equation was created from data of 9,756 patients, each with one paired measurement of tCa, fCa and albumin. Derived aCa cutoffs (1.95/3.15 mmol/L) differ markedly from derived tCa cutoffs (1.6/2.9 mmol/L) and severe hypo- and hypercalcemia can be more accurately assessed by aCa (κ=0.489, 0.812) than by tCa (κ=0.445, 0.744). Comparing our approach to standard care (tCa, literature cutoff), a total 3,250 of 3,680 (88.3 %) misclassified measurements were correctly classified when using aCa with evidence-based cutoffs., Conclusions: Optimized cutoffs for aCa and tCa hold great potential for improved patient care. Locally derived aCa equations differ mostly in the chosen mean normal calcium and provide minimal overall improvement, but entail a close examination of the used cutoffs before application., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Host diet and gut microbiota interact to contribute to perioperative complications, including anastomotic leak (AL). Using a murine surgical model of colonic anastomosis, we investigated how diet and fecal microbial transplantation (FMT) impacted the intestinal microbiota and if a predictive signature for AL could be determined. We hypothesized that a Western diet (WD) would impact gut microbial composition and that the resulting dysbiosis would correlate with increased rates of AL, while FMT from healthy, lean diet (LD) donors would reduce the risk of AL. Furthermore, we predicted that surgical outcomes would allow for the development of a microbial preclinical translational tool to identify AL. Here, we show that AL is associated with a dysbiotic microbial community characterized by increased levels of Bacteroides and Akkermansia . We identified several key taxa that were associated with leak formation, and developed an index based on the ratio of bacteria associated with the absence and presence of leak. We also highlight a modifiable connection between diet, microbiota, and anastomotic healing, potentially paving the way for perioperative modulation by microbiota-targeted therapeutics to reduce AL.

Objective: Due to the lack of randomization, pre-post routine outcome data precludes causal conclusions. We propose the "synthetic waiting list" (SWL) control group to overcome this limitation., Method: First, a step-by-step introduction illustrates this novel approach. Then, this approach is demonstrated using an empirical example with data from an outpatient cognitive-behavioral therapy (CBT) clinic (N = 139). We trained an ensemble machine learning model ("Super Learner") on a data set of patients waiting for treatment (N = 311) to make counterfactual predictions of symptom change during this hypothetical period., Results: The between-group treatment effect was estimated to be d = 0.42. Of the patients who received CBT, 43.88% achieved reliable and clinically significant change, while this probability was estimated to be 14.54% in the SWL group. Counterfactual estimates suggest a clear net benefit of psychotherapy for 41% of patients. In 32%, the benefit was unclear, and 27% would have improved similarly without receiving CBT., Conclusions: The SWL is a viable new approach that provides between-group outcome estimates similar to those reported in the literature comparing psychotherapy with high-intensity control interventions. It holds the potential to mitigate common limitations of routine outcome data analysis.

Chipless radio frequency identification (RFID) technology is expected to replace barcode technology due to its ability to read in non-line-of-sight (NLOS) situations, long reading range, and low cost. Currently, there is extensive research being conducted on frequency-coded (FC) co-polarized radar cross-section (RCS)-based tags, which are widely used. However, detecting co-polarized chipless RFID tags in cluttered environments is still a challenge, as confirmed by measuring two co-polarized tags in front of a perfect metal reflector (30.5cm×22.5cm). To address this challenge, a realistic mathematical model for a chipless RFID system has been developed that takes into account the characteristics of the reader and the tag, as well as reflections from cluttered objects. This extensive mathematical model developed for linear chipless RFID systems in clutter scenarios holds the potential to greatly assist researchers in their exploration of RCS-based tags. By relying solely on simulations, this model provides a tool to effectively analyze and understand RCS-based tags, ultimately simplifying the process of generating more authentic tag designs. This model has been simulated and verified with measurement results by placing a single flat metal reflector behind two co-polarized one-bit designs: a dipole array tag and a square patch tag. The results showed that the interfering signal completely overlaps the ID of the co-polarized tag, severely limiting its detectability. To solve this issue, the proposed solution involves reading the tag in cross-polarization mode by etching a diagonal slot in the square patch tag. This proposed tag provides high immunity to the environment and can be detected in front of both dielectric and metallic objects.

Background: Considered one of the highest levels of evidence, results of randomized controlled trials (RCTs) remain an essential building block in mental health research. They are frequently used to confirm that an intervention "works" and to guide treatment decisions. Given their importance in the field, it is concerning that the quality of many RCT evaluations in mental health research remains poor. Common errors range from inadequate missing data handling and inappropriate analyses (e.g., baseline randomization tests or analyses of within-group changes) to unduly interpretations of trial results and insufficient reporting. These deficiencies pose a threat to the robustness of mental health research and its impact on patient care. Many of these issues may be avoided in the future if mental health researchers are provided with a better understanding of what constitutes a high-quality RCT evaluation., Methods: In this primer article, we give an introduction to core concepts and caveats of clinical trial evaluations in mental health research. We also show how to implement current best practices using open-source statistical software., Results: Drawing on Rubin's potential outcome framework, we describe that RCTs put us in a privileged position to study causality by ensuring that the potential outcomes of the randomized groups become exchangeable. We discuss how missing data can threaten the validity of our results if dropouts systematically differ from non-dropouts, introduce trial estimands as a way to co-align analyses with the goals of the evaluation, and explain how to set up an appropriate analysis model to test the treatment effect at one or several assessment points. A novice-friendly tutorial is provided alongside this primer. It lays out concepts in greater detail and showcases how to implement techniques using the statistical software R, based on a real-world RCT dataset., Discussion: Many problems of RCTs already arise at the design stage, and we examine some avoidable and unavoidable "weak spots" of this design in mental health research. For instance, we discuss how lack of prospective registration can give way to issues like outcome switching and selective reporting, how allegiance biases can inflate effect estimates, review recommendations and challenges in blinding patients in mental health RCTs, and describe problems arising from underpowered trials. Lastly, we discuss why not all randomized trials necessarily have a limited external validity and examine how RCTs relate to ongoing efforts to personalize mental health care., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The refeeding syndrome (RFS) is an oftentimes-unrecognized complication of reintroducing nutrition in malnourished patients that can lead to fatal cardiovascular failure. We hypothesized that a clinical decision support system (CDSS) can improve RFS recognition and management., Methods: We developed an algorithm from current diagnostic criteria for RFS detection, tested the algorithm on a retrospective dataset and combined the final algorithm with therapy and referral recommendations in a knowledge-based CDSS. The CDSS integration into clinical practice was prospectively investigated for six months., Results: The utilization of the RFS-CDSS lead to RFS diagnosis in 13 out of 21 detected cases (62%). It improved patient-related care and documentation, e.g., RFS-specific coding (E87.7), increased from once coded in 30 month in the retrospective cohort to four times in six months in the prospective cohort and doubled the rate of nutrition referrals in true positive patients (retrospective referrals in true positive patients 33% vs. prospective referrals in true positive patients 71%)., Conclusion: CDSS-facilitated RFS diagnosis is possible and improves RFS recognition. This effect and its impact on patient-related outcomes needs to be further investigated in a large randomized-controlled trial.

Analyses of health and health care (hereafter referred to as "health care analyses") usually aim to make transparent the structures, processes, results and interrelationships of health care and to record the degree to which health care systems and their actors have achieved their goals. Health care-related data are an indispensable source of data for many health care analyses. A prerequisite for the examination of a degree of goal achievement is first of all an agreement on those goals that are to be achieved by the system and its substructures, as well as the identification of the determinants of the achievement of the objectives. Primarily it must be examined how safely, effectively and patient-centred systems, facilities and service providers are operating. It also addresses issues of need, accessibility, utilisation, timeliness, appropriateness, patient safety, coordination, continuity, and health economic efficiency and equity of health care. The results of health care include system services (outputs), on the one hand, and results (outcomes), on the other, whereby the results (patient-reported outcomes) and experiences (patient-reported experiences) reported are of particular importance. Health care analyses answer basic questions of health care research: who does what, when, how, why and with which resources and effects in routine health care. Health care analyses thus provide the necessary findings and key figures to further develop health care in order to improve the quality of health care. The applications range from capacity analyses to following innovations up to the concept of regional and supra-regional monitoring of the quality of care given to the population. Given the progress of digitalisation in Health Care, direct data from the care processes will be increasingly available for health care research. This can support care givers significantly if the findings of the studies are applied precisely and correctly within an adequate methodological frame. This can lead to measurable improved health care quality for patients. Data from the process of health care provision have a high potential. Their use needs the same scientific scrutiny as in all other scientific studies., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

How can we improve the interoperability of medical guidelines and the implementation and measurement of outcomes in medical health care for cancer patients as well as for care providers? This is the aim of the working group "Quality and Cross-linking". The following publication gives an overview of the targets reached in the development of guidelines together with quality indicators and documentation in cancer registries., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

(1) Background: Prioritization of patients for liver transplantation in Germany relies on the MELD (model for end-stage liver disease) scoring system that does not consider the patient's sex. Many studies have shown that women are disadvantaged by the MELD score. Using a large patient cohort from a German liver transplant centre, we investigated options to reduce gender inequality in the patient prioritization for liver transplantation. (2) Methods: We calculated female-as-male MELD scores in our cohort by substituting the serum creatinine of a female patient with that of their male equivalent to test for the fairness of the scores. We investigated the effects of the female-as-male scores compared to the original MELD score of 1759 patients listed for liver transplantation. (3) Results: Serum creatinine sex correction (female-as-male) for MELD scores added up to 5.4 points in females, while the median changed by +1.6 points for females. We identified 72 females with an original MELD score < 20, for whom the adjusted female-as-male MELD score would be >20, thus giving them a better chance to receive a liver transplant. (4) Conclusions: Mathematical conversion of female to male creatinine concentrations identified disadvantages in liver transplantation prioritization for females and ascertained MELD 3.0 as having high potential to compensate for these inequalities.

Objectives: Upper reference limits of high-sensitivity cardiac troponin T (hs-cTnT) are derived from healthy, population-based cohorts, and are frequently exceeded in hospitalized patients. In this study we aim to systematically examine the differences between in-hospital patients with no diagnosed cardiac diseases and a population-based cohort., Methods: Retrospective analyses were performed in two independent cohorts. We included 5,652 participants of the prospective population-based LIFE cohort as well as 9,300 patients having been treated at our hospital between 2014 and 2021. In both cohorts, subjects with diagnosed or suspected cardiac diseases were excluded. We used Spearman's rank correlation for correlation analyses of hs-cTnT serum concentrations and age. Sex- and age-adjusted 99th percentiles for hs-cTnT in subjects with preserved renal function were obtained in both cohorts., Results: In both cohorts, hs-cTnT serum concentrations positively correlated with age. Male sex was associated with higher hs-cTnT serum concentrations. Persons treated in hospital showed significantly higher hs-cTnT concentrations in females and males aged above 50. While in the population-based cohort only 99th percentile hs-cTnT results of females aged above 70 and males aged above 60 years exceeded the assay's upper reference limit, the 99th percentiles of in-hospital females over 40 years and males of all age groups exceeded this threshold., Conclusions: Besides age and sex, hospitalization per se is correlated with higher serum concentrations of hs-cTnT in most age groups. Our results indicate, that unconditionally applying current hs-cTnT cut-offs to inpatients might overestimate myocardial infarction and potentially lead to overdiagnosis., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Dysfunctional expectations are a particularly important subset of cognitions that influence the development and maintenance of various mental disorders. This study aimed to develop and validate a scale to assess dysfunctional expectations in posttraumatic stress disorder (PTSD), the "Posttraumatic Expectations Scale" (PTES). In a cross-sectional study, 70 PTSD patients completed the PTES, the Posttraumatic Cognitions Inventory (PTCI), as well as measures of the severity of symptoms of PTSD and depression. The results show that the PTES has excellent internal consistency and correlates significantly with the PTCI and PTSD symptom severity. A regression analysis revealed that the PTES explained variance of PTSD symptom severity above the PTCI, supporting the incremental validity of the PTES. While the original version of the PTES comprises 81 items, short scales were constructed using the BISCUIT (best items scales that are cross-validated, unit-weighted, informative and transparent) method. The current findings provide preliminary psychometric evidence suggesting that the PTES is an internally consistent and valid novel self-report measure in patients with PTSD. However, conclusions about the psychometric properties of the PTES are limited because of the absence of criterion-related validity, factor structure evidence, variability over time/response to intervention, and test-retest reliability. Future research should use the PTES in large-scale longitudinal studies to address these aspects to further validate the scale.

(1) Background: Cystic fibrosis (CF) is a disease with well-documented clinical differences between female and male patients. However, this gender gap is very poorly studied at the molecular level. (2) Methods: Expression differences in whole blood transcriptomics between female and male CF patients are analyzed in order to determine the pathways related to sex-biased genes and assess their potential influence on sex-specific effects in CF patients. (3) Results: We identify sex-biased genes in female and male CF patients and provide explanations for some sex-specific differences at the molecular level. (4) Conclusion: Genes in key pathways associated with CF are differentially expressed between sexes, and thus may account for the gender gap in morbidity and mortality in CF.

Competing Interests: Competing interests: We have read and understood the BMJ policy on declaration of interests and have no interests to declare.

In this proof-of-principle study, we systematically studied the potential of Raman spectroscopy for detecting pre-analytical delays in blood serum samples. Spectra from 330 samples from a liver cirrhosis cohort were acquired over the course of eight days, stored one day at room temperature, and stored subsequently at 4 °C. The spectra were then used to train Convolutional Neural Networks (CNN) to predict the delay to sample examination. We achieved 90% accuracy for binary classification of the serum samples in the groups "without delay" versus "delayed". Spectra recorded on the first day could be distinguished clearly from all subsequent measurements. Distinguishing between spectra taken in the range from the second to the last day seems to be possible as well, but currently, with an accuracy of approximately 70% only. Importantly, filtering out the fluorescent background significantly reduces the precision of detection.

Chronic inflammation of the colon (colitis) is a known risk factor for inflammatory-driven colorectal cancers (id-CRCs), and intestinal microbiota has been implicated in the etiology of id-CRCs. Manipulation of the microbiome is a clinically viable therapeutic approach to limiting id-CRCs. To understand the microbiome changes that occur over time in id-CRCs, we used a mouse model of id-CRCs with the treatment of azoxymethane (AOM) and dextran sodium sulfate (DSS) and measured the microbiome over time. We included cohorts where the microbiome was restored using cage bedding swapping and where the microbiome was depleted using antibiotics to compare to untreated animals. We identified consistent increases in Akkermansia in mice receiving horizontal microbiome transfer (HMT) via cage bedding swapping, while the control cohort had consistent longitudinal increases in Anaeroplasma and Alistipes. Additionally, fecal lipocalin-2 (Lcn-2), a marker of intestinal inflammation, was elevated in unrestored animals compared to restored and antibiotic-treated counterparts following HMT. These observations suggest a potential role for Akkermansia, Anaeroplasma, and Alistipes in regulating colonic inflammation in id-CRCs.