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Narrative is fundamental to human thought, yet in many classrooms, expository texts are commonly used to support learning in content-based subjects, such as history. Given the importance of narrative, it might be harnessed as a powerful tool to support learning. This research compares the impact of narrative nonfiction (NNF) and expository text (ET) on the development and retention of conceptual understanding relating to World War I (WWI). In an experiment involving 78 participants (mean age = 10.2 years, standard deviation = 0.29), pupils were placed into one of two conditions: in one, information about WWI was conveyed primarily through NNF texts, and in the other, through ETs. Participants completed written pre-, post- and delayed post-assessments to assess development and retention of conceptual understanding. It was found that participants in the NNF condition showed greater chronological and causal thinking skills. In addition, participants in the NNF condition retained significantly more conceptual understanding at delayed post-assessments than those in the ET condition. Overall, these findings suggest that narrative texts have the potential to be powerful learning tools. Implications for how texts are selected and utilised to support learning in the primary, history classroom are discussed.

Abstract Aims Heart failure (HF) and chronic kidney disease (CKD) place significant challenges on the healthcare system, and their co‐existence is associated with shared adverse outcomes. The multinational CaReMe project was initiated to provide contemporary, real‐world epidemiological data on cardiovascular and reno‐metabolic diseases. Utilizing data from the German CaReMe cohort, we characterize a multicentric HF population and describe in‐hospital outcomes stratified for co‐morbid CKD. Methods and results This retrospective, observational study analysed administrative data from inpatient cases hospitalized in 87 German Helios hospitals between 1 January 2016 and 31 August 2022. The first hospitalization of patients aged ≥18 years with a primary discharge diagnosis of HF, based on ICD‐10 codes, were considered the index cases, and subsequent hospitalizations were considered as readmissions. Baseline characteristics and outcomes were stratified for co‐morbid CKD using ICD‐10‐encoding from the index cases. Cox regression was utilized for readmission endpoints and in‐hospital mortality. In total, 174 829 index cases (mean age 79 ± 15 years, 49.9% female) were included; of these, 55.0% had coexisting CKD. Patients with CKD were older, suffered from worse HF‐related symptoms, had a higher co‐morbidity burden, and in‐hospital mortality was increased at index and during follow‐up. Prevalent CKD was associated with higher rehospitalization rates and was an independent predictor for in‐hospital death. Conclusions Within this HF inpatient cohort from a multicentric German database, CKD was diagnosed in more than half of the patients and was associated with increased in‐hospital mortality at baseline and during follow‐up. Rehospitalizations were observed earlier and more frequently in patients with HF and co‐morbid CKD.

Johannes Leiner,1,2 Vincent Pellissier,2 Sebastian König,1,2 Lars Stellmacher,2 Sven Hohenstein,2 Carolin Schanner,2 Stefan Kwast,2 Ralf Kuhlen,3,4 Andreas Bollmann1– 3 1Department of Electrophysiology, Heart Center Leipzig at University of Leipzig, Leipzig, Saxony, Germany; 2Real World Evidence and Health Technology Assessment, Helios Health Institute, Berlin, Germany; 3Helios Health Institute, Berlin, Germany; 4Helios Health, Berlin, GermanyCorrespondence: Johannes Leiner, Heart Centre Leipzig at University of Leipzig, Department of Electrophysiology, Struempellstrasse 39, Leipzig, 04289, Germany, Tel +49 341 865 251573, Email johannes.leiner@helios-gesundheit.deIntroduction: Type 2 diabetes mellitus (T2DM) is a leading cause of chronic kidney disease (CKD) globally. Both conditions substantially worsen patients’ prognosis. Current data on German in-hospital CKD cohorts are scarce. The multinational CaReMe study was initiated to evaluate the current epidemiology and healthcare burden of cardiovascular, renal and metabolic diseases. In this substudy, we share real-world data on CKD inpatients stratified for coexisting T2DM derived from a large German hospital network.Methods: This study used administrative data of inpatient cases from 89 Helios hospitals from 01/01/2016 to 28/02/2022. Data were extracted from ICD-10-encoded discharge diagnoses and OPS-encoded procedures. The first case meeting a previously developed CKD definition (defined by ICD-10- and OPS-codes) was considered the index case for a particular patient. Subsequent hospitalizations were analysed for readmission statistics. Patient characteristics and pre-defined endpoints were stratified for T2DM at index case.Results: In total, 48,011 patients with CKD were included in the present analysis (mean age ± standard deviation, 73.8 ± 13.1 years; female, 44%) of whom 47.9% had co-existing T2DM. Patients with T2DM were older (75 ± 10.6 vs 72.7 ± 14.9 years, p < 0.001), but gender distribution was similar to patients without T2DM. The burden of cardiovascular disease was increased in patients with T2DM, and index and follow-up in-hospital mortality rates were higher. Non-T2DM patients were characterised by more advanced CKD at baseline. Patients with T2DM had consistently higher readmission numbers for all events of interest, except for readmissions due to kidney failure/dialysis, which were more common in non-T2DM patients.Conclusion: In this study, we present recent data on hospitalized patients with CKD in Germany. In this CKD cohort, nearly half had T2DM, which substantially affected cardiovascular disease burden, rehospitalization frequency and mortality. Interestingly, non-diabetic patients had more advanced underlying renal disease, which affected renal outcomes. Keywords: chronic kidney disease, type 2 diabetes mellitus, administrative data, in-hospital mortality, kidney failure, rehospitalization

ObjectivesThe COVID-19 pandemic affected patients’ access to health services, including patients with severe chronic pain. Since limited data on pandemic-caused changes in pain therapy is available, we analyzed its effect on hospital-based pain treatment.MethodsFor this retrospective claims data analysis conducted in n = 37 hospitals, we included patients treated for a chronic pain-related diagnosis. Discharge rates stratified by region and pain unit size were analyzed for different time periods between January 2019 and June 2022.ResultsThere was a significant decrease in day-care, inpatient interdisciplinary multimodal pain management, from a total of 5,533 hospital pre-pandemic treatments in 2019, to 3,942 in 2020 and 4,262 in 2021, with a slight increase in the first half of 2022. The extent of COVID-19-related changes differed depending on region and pain unit size.ConclusionThe decreased number of hospital pain treatments during the pandemic implies a relevant analgesic undertreatment. During future pandemics, the ethical dimension of potentially non-sufficient pain treatment should be weighted against social, medical and hygienic restrictions influencing the hospitalization rate.

To examine the ways that 6- to 11-year-old children's conversation with their parents support their developing understandings of evolution, 49 parent-child dyads participated in a study with two elicited discussion tasks: origins of species and potential species change. Conversational data were transcribed, coded, and qualitatively and quantitatively analyzed to compare the appearance of reasoning in each type of task. Quantitative analyses revealed correlations between tasks in informed naturalistic reasoning as well as differences in the way reasoning was expressed in each task. In addition, parent-child dyads with older children were more likely to use informed naturalistic reasoning than parent-child dyads with younger children. A subset of the data was analyzed qualitatively and showed that irrespective of how much evolution reference was present in the conversation, parents supported their children's learning through scaffolding. However, greater amounts of nonscientific reasoning appeared in the groups with less evolution talk. This study demonstrates that family talk about evolution varies with context both within and between families.

Objective Cholecystectomy is one of the most frequently performed surgeries in Germany and is performed as a treatment of acute cholecystitis (guideline S3 IIIB.8) and after endoscopic retrograde cholangiopancreatography for choledocholithiasis with simultaneous cholecystolithiasis (guideline S3 IIIC.6). This article examines the effects of a guideline update from 2017, which recommends prompt cholecystectomy within 24 hours of admission due to cholecystitis or within 72 hours after bile duct repair. In addition, it aims to identify reasons (eg, financial disincentives) and potential for improvement for non-adherence to the guidelines.Design Methodologically, a retrospective analysis based on routine billing data from 84 Helios Group hospitals from 2016 and 2022, with a total of 45 393 included cases, was applied. The guideline adherence rate is used as the main outcome measure.Results Results show the guideline updates led to a statistically significant increase in the proportion of cholecystectomy performed in a timely manner (guideline S3 IIIB.8: increase from 43% to 49%, p

The Vajo Salsone site is located at an altitude of 376m a.s.l. on the right slope of the Valpantena valley, in the Veneto Pre-Alps, north of the town of Verona. The site was discovered in 2017 during the construction of a truckable road. It is a small and narrow karst cavity filled with Pleistocene sediments that yield abundant Middle Palaeolithic artefacts and faunal remains, often coated by carbonate encrustations. The lithic assemblage shows the predominance of the Levallois method and is characterised by a large number of retouched elements, including foliated points. These artefacts, typical of the Late Middle Palaeolithic period in central and south-eastern Europe, make Vajo Salsone an exceptional case, as their recovery is rather sporadic west of the Balkan Peninsula and south of the Alps. The fauna is dominated by ungulates, the most abundant being the red deer followed by roe deer, chamois and elk. Among the carnivores, wolf is common, while fox and bear are rare. This fauna suggests an environment characterised by open glades and closed forests, with a discontinuous presence of alpine grasslands and wetlands. Taphonomic analysis of the bone surfaces is complicated by the presence of concretions on most of the remains, which also show a high degree of fragmentation. Post-depositional fractures are common, and weathering is light. Only cervid bones show anthropogenic modifications related to hunting and hominin exploitation such as cut marks, scraping, impacts and burnt modifications. Some long bone diaphysis bear marks testifying to the use of these fragments as retouchers for flint artefacts. Such use has been evidenced at other Middle Palaeolithic sites in the area. Furthermore, the good state of preservation of the occlusal surface enamel of the cervid teeth allowed us to carry out meso and microwear analyses which provided data on seasonality and site occupation. With regard to dental wear analysis, the red deer from Vajo Salsone had mesowear suggesting a mixed feeding and grazing diets, whereas microwear analysis showed that the individuals had a diet between mixed feeding and browsing. The taphonomic study of the site has been integrated by X–RFS analysis of the alterations occurred to the lithic artefacts, which include deep patination and the formation of calcareous crusts. All the data presented here are consistent with the hypothesis of a short-distance displacement of the material from a single archaeological deposit possibly related to human occupation during the warm season.

Modern cetaceans are considered the best anatomical and ecological analogue for many Mesozoic secondary aquatic reptiles. Such similarities extend also after the death of these phylogenetically distant amniotes, when the sinking and decomposition of large carcasses in marine environments (deadfalls) follow common biostratinomic processes. Most taphonomic studies on Mesozoic deadfalls have been limited to shallow-water settings, often neglecting deeper waters. Here we provide a detailed taphonomic survey of ichthyosaurs, pliosaurs and metriorhynchoids from the pelagic Middle-Upper Jurassic Rosso Ammonitico Veronese (RAV) of northeastern Italy. Our taphonomic revision of the RAV tetrapod record highlights a common poor state of preservation of the bones, often associated with abundant macrofossils, consistent with a prolonged exposure of carcasses on a well-oxygenated seafloor. For the first time we confirm the role of nautiloids as active mobile scavengers by means of tens of beak elements found closely associated with, or even piercing, the bones. Hexanchiform shark teeth are also found associated with the carcasses, supporting a distinctive deep-water mobile scavenging community. Echinoids, sponges and other bioeroders are identified as representative of the enrichment-opportunist stage, and a high concentration of belemnites is believed to be indicative of mass-spawning deaths in the surroundings of the carcasses. Abundant crinoids are recognized as part of the reef stage by colonization of the eroded bones. While some of our data deviate from previous Mesozoic reptile-falls from shallow-waters, they are consistent with findings at Recent whale-falls in bathyal zones, and overall represent a precious window into the complex ecology of Jurassic open seas.

BackgroundEmergency department (ED) workers have an increased seroprevalence of SARS-CoV-2 antibodies. However, breakthrough infections in ED workers have led to a reduced workforce within a strained healthcare system. By measuring levels of IgG antibodies to the SARS-CoV-2 nucleocapsid and spike antigens in ED workers, we determined the incidence of infection and described the course of antibody levels. We also measured the antibody response to vaccination and examined factors associated with immunogenicity.MethodsWe conducted a prospective cohort study of ED workers conducted at a single ED from September 2020-April 2021. IgG antibodies to the SARS-CoV-2 nucleocapsid antigen were measured at baseline, 3, and 6 months, and IgG antibodies to the SARS-CoV-2 spike antigen were measured at 6 months.ResultsAt baseline, we found 5 out of 139 (3.6%) participants with prior infection. At 6 months, 4 of the 5 had antibody results below the test manufacturer's positivity threshold. We identified one incident case of SARS-COV-2 infection out of 130 seronegative participants (0.8%, 95% CI 0.02-4.2%). In 131 vaccinated participants (125 BNT162b2, 6 mRNA-1273), 131 tested positive for anti-spike antibodies. We identified predictors of anti-spike antibody levels: time since vaccination, prior COVID-19 infection, age, and vaccine type. Each additional week since vaccination was associated with an 11.1% decrease in anti-spike antibody levels. (95% CI 6.2-15.8%).ConclusionED workers experienced a low incidence of SARS-CoV-2 infection and developed antibodies in response to vaccines and prior infection. Antibody levels decreased markedly with time since infection or vaccination.

PurposeThe aim was to develop a novel artificial intelligence (AI)-guided clinical decision support system, to predict radiation doses to subsites of the mandible using diagnostic computed tomography scans acquired before any planning of head and neck radiation therapy (RT).Methods and materialsA dose classifier was trained using RT plans from 86 patients with oropharyngeal cancer; the test set consisted of an additional 20 plans. The classifier was trained to predict whether mandible subsites would receive a mean dose >50 Gy. The AI predictions were prospectively evaluated and compared with those of a specialist head and neck radiation oncologist for 9 patients. Positive predictive value (PPV), negative predictive value (NPV), Pearson correlation coefficient, and Lin concordance correlation coefficient were calculated to compare the AI predictions to those of the physician.ResultsIn the test data set, the AI predictions had a PPV of 0.95 and NPV of 0.88. For 9 patients evaluated prospectively, there was a strong correlation between the predictions of the AI algorithm and physician (P = .72, P < .001). Comparing the AI algorithm versus the physician, the PPVs were 0.82 versus 0.25, and the NPVs were 0.94 versus 1.0, respectively. Concordance between physician estimates and final planned doses was 0.62; this was 0.71 between AI-based estimates and final planned doses.ConclusionAI-guided decision support increased precision and accuracy of pre-RT dental dose estimates.

Aims: Endemic SARS-CoV-2 infections still burden the healthcare system and represent a considerable threat to vulnerable patient cohorts, in particular immunocompromised (IC) patients. This study aimed to analyze the in-hospital outcome of IC patients with severe SARS-CoV-2 infection in Germany. Methods: This retrospective, observational study, analyzed administrative data from inpatient cases (n = 146,324) in 84 German Helios hospitals between 1 January 2022 and 31 December 2022 with regard to in-hospital outcome and health care burden in IC patients during the first 12 months of Omicron dominance. As the primary objective, in-hospital outcomes of patients with COVID-19-related severe acute respiratory infection (SARI) were analyzed by comparing patients with (n = 2037) and without IC diagnoses (n = 14,772). Secondary analyses were conducted on IC patients with (n = 2037) and without COVID-19-related SARI (n = 129,515). A severe in-hospital outcome as a composite endpoint was defined per the WHO definition if one of the following criteria were met: intensive care unit (ICU) treatment, mechanical ventilation (MV), or in-hospital death. Results: In total, 12% of COVID-related SARI cases were IC patients, accounting for 15% of ICU admissions, 15% of MV use, and 16% of deaths, resulting in a higher prevalence of severe in-hospital courses in IC patients developing COVID-19-related SARI compared to non-IC patients (Odds Ratio, OR = 1.4, p < 0.001), based on higher in-hospital mortality (OR = 1.4, p < 0.001), increased need for ICU treatment (OR = 1.3, p < 0.001) and mechanical ventilation (OR = 1.2, p < 0.001). Among IC patients, COVID-19-related SARI profoundly increased the risk for severe courses (OR = 4.0, p < 0.001). Conclusions: Our findings highlight the vulnerability of IC patients to severe COVID-19. The persistently high prevalence of severe outcomes in these patients in the Omicron era emphasizes the necessity for continuous in-hospital risk assessment and monitoring of IC patients.

We propose the regularized compressed double factorization (RC-DF) method to classically compute compressed representations of molecular Hamiltonians that enable efficient simulation with noisy intermediate scale (NISQ) and error corrected quantum algorithms. We find that already for small systems with 12 to 20 qubits, the resulting NISQ measurement scheme reduces the number of measurement bases by roughly a factor of three and the shot count to reach chemical accuracy by a factor of three to six compared to truncated double factorization (DF) and we see order of magnitude improvements over Pauli grouping schemes. We demonstrate the scalability of our approach by performing RC-DF on the CpdI species of cytochrome P450 with 58 orbitals and find that using the resulting compressed Hamiltonian cuts the run time of qubitization and truncated DF based error corrected algorithms almost in half and even outperforms the lambda parameters achievable with tensor hypercontraction (THC) while at the same time reducing the CCSD(T) energy error heuristic by an order of magnitude.

There is accumulating evidence that pathogenic T cells in T1D recognize epitopes formed by post-translational modifications of β-cell antigens, including hybrid insulin peptides (HIPs). The ligands for several CD4 T-cell clones derived from the NOD mouse are HIPs composed of a fragment of proinsulin joined to peptides from endogenous β-cell granule proteins. The diabetogenic T-cell clone BDC-6.9 reacts to a fragment of C-peptide fused to a cleavage product of pro-islet amyloid polypeptide (6.9HIP). In this study, we used a monoclonal antibody (MAb) to the 6.9HIP to determine when and where HIP antigens are present in NOD islets during disease progression and with which immune cells they associate. Immunogold labeling of the 6.9HIP MAb and organelle-specific markers for electron microscopy were employed to map the subcellular compartment(s) in which the HIP is localized within β-cells. While the insulin B9-23 peptide was present in nearly all islets, the 6.9HIP MAb stained infiltrated islets only in NOD mice at advanced stages of T1D development. Islets co-stained with the 6.9HIP MAb and antibodies to mark insulin, macrophages, and dendritic cells indicate that 6.9HIP co-localizes within insulin-positive β-cells as well as intra-islet antigen-presenting cells (APCs). In electron micrographs, the 6.9HIP co-localized with granule structures containing insulin alone or both insulin and LAMP1 within β-cells. Exposing NOD islets to the endoplasmic reticulum (ER) stress inducer tunicamycin significantly increased levels of 6.9HIP in subcellular fractions containing crinosomes and dense-core granules (DCGs). This work demonstrates that the 6.9HIP can be visualized in the infiltrated islets and suggests that intra-islet APCs may acquire and present HIP antigens within islets.

Johannes Leiner,1,2 Sven Hohenstein,2 Vincent Pellissier,2 Sebastian König,1,2 Claudia Winklmair,3 Irit Nachtigall,4 Andreas Bollmann,1,2,5 Ralf Kuhlen3,5,6 On behalf of the scientific advisory board of the Initiative of Quality Medicine (IQM)1Heart Centre Leipzig at University of Leipzig, Department of Electrophysiology, Leipzig, Germany; 2Real World Evidence and Health Technology Assessment at Helios Health Institute, Berlin, Germany; 3Initiative of Quality Medicine, Berlin, Germany; 4Department of Infectious Diseases and Infection Prevention, HELIOS Hospital Emil-von-Behring, Berlin, Germany and Charité - Universitaetsmedizin Berlin, Institute of Hygiene and Environmental Medicine, Berlin, Germany; 5Helios Health Institute, Berlin, Germany; 6Helios Health, Berlin, GermanyCorrespondence: Ralf Kuhlen, Initiative Qualitaetsmedizin e.V, Alt-Moabit 104, Berlin, 10559, Germany, Tel +49 30 7262 152 - 0, Email ralf.kuhlen@initiative-qualitaetsmedizin.deIntroduction: Reliable surveillance systems to monitor trends of COVID-19 case numbers and the associated healthcare burden play a central role in efficient pandemic management. In Germany, the federal government agency Robert-Koch-Institute uses an ICD-code-based inpatient surveillance system, ICOSARI, to assess temporal trends of severe acute respiratory infection (SARI) and COVID-19 hospitalization numbers. In a similar approach, we present a large-scale analysis covering four pandemic waves derived from the Initiative of Quality Medicine (IQM), a German-wide network of acute care hospitals.Methods: Routine data from 421 hospitals for the years 2019– 2021 with a “pre-pandemic” period (01– 01-2019 to 03– 03-2020) and a “pandemic” period (04– 03-2020 to 31– 12-2021) was analysed. SARI cases were defined by ICD-codes J09-J22 and COVID-19 by ICD-codes U07.1 and U07.2. The following outcomes were analysed: intensive care treatment, mechanical ventilation, in-hospital mortality.Results: Over 1.1 million cases of SARI and COVID-19 were identified. Patients with COVID-19 and additional codes for SARI were at higher risk for adverse outcomes when compared to non-COVID SARI and COVID-19 without any coding for SARI. During the pandemic period, non-COVID SARI cases were associated with 28%, 23% and 27% higher odds for intensive care treatment, mechanical ventilation and in-hospital mortality, respectively, compared to pre-pandemic SARI.Conclusion: The nationwide IQM network could serve as an excellent data source to enhance COVID-19 and SARI surveillance in view of the ongoing pandemic. Future developments of COVID-19/SARI case numbers and associated outcomes should be closely monitored to identify specific trends, especially considering novel virus variants.Graphical Abstract: Keywords: initiative of quality medicine, Germany, COVID-19, SARI, inpatient, hospital network

Abstract Artificial intelligence (AI) is already widely used in daily communication, but despite concerns about AI’s negative effects on society the social consequences of using it to communicate remain largely unexplored. We investigate the social consequences of one of the most pervasive AI applications, algorithmic response suggestions (“smart replies”), which are used to send billions of messages each day. Two randomized experiments provide evidence that these types of algorithmic recommender systems change how people interact with and perceive one another in both pro-social and anti-social ways. We find that using algorithmic responses changes language and social relationships. More specifically, it increases communication speed, use of positive emotional language, and conversation partners evaluate each other as closer and more cooperative. However, consistent with common assumptions about the adverse effects of AI, people are evaluated more negatively if they are suspected to be using algorithmic responses. Thus, even though AI can increase the speed of communication and improve interpersonal perceptions, the prevailing anti-social connotations of AI undermine these potential benefits if used overtly.

The significant heterogeneity of Wilms’ tumors between different patients is thought to arise from genetic and epigenetic distortions that occur during various stages of fetal kidney development in a way that is poorly understood. To address this, we characterized the heterogeneity of alternative mRNA splicing in Wilms’ tumors using a publicly available RNAseq dataset of high-risk Wilms’ tumors and normal kidney samples. Through Pareto task inference and cell deconvolution, we found that the tumors and normal kidney samples are organized according to progressive stages of kidney development within a triangle-shaped region in latent space, whose vertices, or “archetypes”, resemble the cap mesenchyme, the nephrogenic stroma, and epithelial tubular structures of the fetal kidney. We identified a set of genes that are alternatively spliced between tumors located in different regions of latent space and found that many of these genes are associated with the epithelial-to-mesenchymal transition (EMT) and muscle development. Using motif enrichment analysis, we identified putative splicing regulators, some of which are associated with kidney development. Our findings provide new insights into the etiology of Wilms’ tumors and suggest that specific splicing mechanisms in early stages of development may contribute to tumor development in different patients.