Non-adiabatic effects in periodically driven-dissipative open quantum systems

We present a general method to calculate the quasi-stationary state of a driven-dissipative system coupled to a transmission line (and more generally, to a reservoir) under periodic modulation of its parameters. Using Floquet's theorem, we formulate the differential equation for the system's density operator which has to be solved for a single period of modulation. On this basis we also provide systematic expansions in both the adiabatic and high-frequency regime. Applying our method to three different systems -- two- and three-level models as well as the driven nonlinear cavity -- we propose periodic modulation protocols of parameters leading to a temporary suppression of effective dissipation rates, and study the arising non-adiabatic features in the response of these systems.Comment: 12 pages, 8 figure

Code Generation for Big Data Processing in the Web using WebAssembly

Traditional clusters for cloud computing are quite hard to configure and setup, and the number of cluster nodes is limited by the available hardware in the cluster. We hence envision the concept of a Browser Cloud: One just has to visit with his/her web browser a certain webpage in order to connect his/her computer to the Browser Cloud. In this way the setup of the Browser Cloud is much easier than those of traditional clouds. Furthermore, the Browser Cloud has a much larger number of potential nodes, as any computer running a browser may connect to and be integrated in the Browser Cloud. New challenges arise when setting up a cloud by web browsers: Data is processed within the browser, which requires to use the technologies offered by the browser for this purpose. The typically used JavaScript runtime environment may be too slow, because JavaScript is an interpreted language. Hence we investigate the possibilities for computing the work-intensive part of the query processing inside a virtual machine of the web browser. The technology WebAssemby for virtual machines is recently supported by all major browsers and promises high speedups in comparison with JavaScript. Recent approaches to efficient Big Data processing generate code for the data processing steps of queries. To run the generated code in a WebAssembly virtual machine, an online compiler is needed to generate the WebAssembly bytecode from the generated code. Hence our main contribution is an online compiler to WebAssembly bytecode especially developed to run in the web browser and for Big Data processing based on code generation of the processing steps. In our experiments, the runtimes of Big Data processing using JavaScript is compared with running WebAssembly technologies in the major web browsers

Searching of clinical trials made easier in cBioPortal using patients' genetic and clinical profiles

Background: Molecular tumor boards (MTBs) cope with the complexity of an increased usage of genome sequencing data in cancer treatment. As for most of these patients, guideline-based therapy options are exhausted, finding matching clinical trials is crucial. This search process is often performed manually and therefore time consuming and complex due to the heterogeneous and challenging dataset. Objectives: In this study, a prototype for a search tool was developed to demonstrate how cBioPortal as a clinical and genomic patient data source can be integrated with ClinicalTrials.gov, a database of clinical studies to simplify the search for trials based on genetic and clinical data of a patient. The design of this tool should rest on the specific needs of MTB participants and the architecture of the integration should be as lightweight as possible and should not require manual curation of trial data in advance with the goal of quickly and easily finding a matching study. Methods: Based on a requirements analysis, interviewing MTB experts, a prototype was developed. It was further refined using a user-centered development process with multiple feedback loops. Finally, the usability of the application was evaluated with user interviews including the thinking-aloud protocol and the system usability scale (SUS) questionnaire. Results: The integration of ClinicalTrials.gov in cBioPortal is achieved by a new tab in the patient view where the genomic profile for the search is prefilled and additional parameters can be adjusted. These parameters are then used to query the application programming interface (API) of ClinicalTrials.gov. The returned search results subsequently are ranked and presented to the user. The evaluation of the application resulted in an SUS score of 83.5. Conclusion: This work demonstrates the integration of cBioPortal with ClinicalTrials.gov to use clinical and genomic patient data to search for appropriate trials within an MTB.Publikationsfonds ML

Case report: Tenosynovial giant cell tumor

Tenosynovial giant cell tumor (TGCT) is a rare type of tumor that originates from the synovium of joints and tendon sheaths. It is characterized by recurring genetic abnormalities, often involving the CSF1 gene. Common symptoms include pain and swelling, which are not specific to TGCT, so MRI and a pathological biopsy are needed for an accurate diagnosis. We report the case of a 45-year-old man who experienced painful swelling in his right hip for six months. Initially, this was diagnosed as Erdheim-Chester disease. However, whole exome sequencing (WES) and RNA-Sequencing revealed a CSF1::GAPDHP64 fusion, leading to a revised diagnosis of TGCT. The patient was treated with pegylated interferon and imatinib, which resulted in stable disease after three months. Single-cell transcriptome analysis identified seven distinct cell clusters, revealing that neoplastic cells expressing CSF1 attract macrophages. Analysis of ligand-receptor interactions showed significant communication between neoplastic cells and macrophages mediated by CSF1 and CSF1R. Our findings emphasize the importance of comprehensive molecular analysis in diagnosing and treating rare malignancies like TGCT

Time of day for vaccination, outcomes, and relative effectiveness of high-dose vs. standard-dose quadrivalent influenza vaccine: a post-hoc analysis of the DANFLU-1 randomized clinical trial

Objectives Morning influenza vaccination enhances antibody response. In this posthoc analysis of the DANFLU-1 trial, we sought to evaluate the association between time of day for vaccination (ToV) and outcomes, and whether ToV modified the relative effectiveness of high-dose (QIV-HD) vs. standard-dose (QIV-SD) quadrivalent influenza vaccine. Methods DANFLU-1 was a pragmatic feasibility trial of QIV-HD vs. QIV-SD. Outcomes included hospitalizations and mortality. For subgroup analysis, the population was dichotomized at median ToV into two groups (early and late). Results The study population included 12,477 participants. Mean age was 71.7±3.9 years with 5,877 (47.1%) female participants. Median ToV was 11.29AM. Earlier ToV was associated with fewer respiratory hospitalizations independent of vaccine type, which persisted in adjusted analysis (IRR 0.88 per 1-hour decrement (95% CI 0.78- 0.98, p=0.025). No effect modification by continuous or dichotomous ToV was found. In subgroup analysis, effects consistently favored QIV-HD against hospitalizations for pneumonia or influenza (early: IRR 0.30; late: 0.29), all-cause hospitalizations (early: IRR 0.87; late: 0.86), and mortality (early: HR 0.53; late: 0.50). Conclusion In this exploratory post-hoc analysis, earlier ToV was associated with fewer respiratory hospitalizations. The relative effectiveness of QIV-HD vs. QIV-SD was not modified by ToV. Further research is needed to confirm findings. Trial Registration Clinicaltrials.gov: NCT0504858

UBTF::ATXN7L3 gene fusion defines novel B cell precursor ALL subtype with CDX2 expression and need for intensified treatment

Genomic aberrations—gene fusions in the majority of cases—and corresponding transcriptional regulations define an increasingly complex landscape of molecular subtypes in B cell precursor acute lymphoblastic leukemia (BCP-ALL) [1]. Up to 15% of patients cannot be allocated to established subtypes, suggesting the presence of unrecognized drivers—especially in adult patients who have been less studied so far

Effects of high-dose versus standard-dose quadrivalent influenza vaccine among patients with diabetes: a post-hoc analysis of the DANFLU-1 trial

Aim: High-dose quadrivalent influenza vaccine (QIV-HD) has been shown to be more effective than standard-dose (QIV-SD) in reducing influenza infection, but whether diabetes status affects relative vaccine effectiveness (rVE) is unknown. We aimed to assess rVE on change in glycated haemoglobin [HbA1c (∆HbA1c)], incident diabetes, total all-cause hospitalizations (first + recurrent), and a composite of all-cause mortality and hospitalization for pneumonia or influenza. Methods: DANFLU-1 was a pragmatic, open-label trial randomizing adults (65-79 years) 1:1 to QIV-HD or QIV-SD during the 2021/22 influenza season. Cox proportional hazards regression was used to estimate rVE against incident diabetes and the composite endpoint, negative binomial regression to estimate rVE against all-cause hospitalizations, and ANCOVA when assessing rVE against ∆HbA1c. Results: Of the 12 477 participants, 1162 (9.3%) had diabetes at baseline. QIV-HD, compared with QIV-SD, was associated with a reduction in the rate of all-cause hospitalizations irrespective of diabetes [overall: 647 vs. 742 events, incidence rate ratio (IRR): 0.87, 95% CI (0.76-0.99); diabetes: 93 vs. 118 events, IRR: 0.80, 95% CI (0.55-1.15); without diabetes: 554 vs. 624 events, IRR: 0.88, 95% CI (0.76-1.01), pinteraction = 0.62]. Among those with diabetes, QIV-HD was associated with a lower risk of the composite outcome [2 vs. 11 events, HR: 0.18, 95% CI (0.04-0.83)] but had no effect on ∆HbA1c; QIV-HD adjusted mean difference: ∆ + 0.2 mmol/mol, 95% CI (−0.9 to 1.2). QIV-HD did not affect the risk of incident diabetes [HR 1.18, 95% CI (0.94-1.47)]. Conclusions: In this post-hoc analysis, QIV-HD versus QIV-SD was associated with an increased rVE against the composite of all-cause death and hospitalization for pneumonia/influenza, and the all-cause hospitalization rate irrespective of diabetes status

Effectiveness of high-dose versus standard-dose quadrivalent influenza vaccine against recurrent hospitalizations and mortality in relation to influenza circulation: a post-hoc analysis of the DANFLU-1 randomized clinical trial

Objectives: To evaluate the relative effectiveness of high-dose quadrivalent influenza vaccine (QIV-HD) versus standard-dose quadrivalent influenza vaccine (QIV-SD) against recurrent hospitalizations and its potential variation in relation to influenza circulation. Methods: We did a post-hoc analysis of a pragmatic, open-label, randomized trial of QIV-HD versus QIV-SD performed during the 2021–2022 influenza season among adults aged 65–79 years. Participants were enrolled in October 2021–November, 2021 and followed for outcomes from 14 days postvaccination until 31 May, 2022. We investigated the following outcomes: Hospitalizations for pneumonia or influenza, respiratory hospitalizations, cardio-respiratory hospitalizations, cardiovascular hospitalizations, all-cause hospitalizations, and all-cause death. Outcomes were analysed as recurrent events. Cumulative numbers of events were assessed weekly. Cumulative relative effectiveness estimates were calculated and descriptively compared with influenza circulation. The trial is registered at Clinicaltrials.gov: NCT05048589. Results: Among 12,477 randomly assigned participants, receiving QIV-HD was associated with lower incidence rates of hospitalizations for pneumonia or influenza (10 vs. 33 events, incidence rate ratio [IRR] 0.30 [95% CI, 0.14–0.64]; p 0.002) and all-cause hospitalizations (647 vs. 742 events, IRR 0.87 [95% CI, 0.76–0.99]; p 0.032) compared with QIV-SD. Trends favouring QIV-HD were consistently observed over time including in the period before active influenza transmission; i.e. while the first week with a ≥10% influenza test positivity rate was calendar week 10, 2022, the first statistically significant reduction in hospitalizations for pneumonia or influenza was already observed by calendar week 3, 2022 (5 vs. 15 events, IRR 0.33 [95% CI, 0.11–0.94]; p 0.037). Discussion: In a post-hoc analysis, QIV-HD was associated with lower incidence rates of hospitalizations for pneumonia or influenza and all-cause hospitalizations compared with QIV-SD, with trends evident independent of influenza circulation levels. Our exploratory results correspond to a number needed to treat of 65 (95% CI 35–840) persons vaccinated with QIV-HD compared with QIV-SD to prevent one additional all-cause hospitalization per season. Further research is needed to confirm these hypothesis-generating findings

High-dose vs. standard-dose inactivated influenza vaccine and cardiovascular outcomes in persons with or without pre-existing atherosclerotic cardiovascular disease: the DANFLU-2 trial

Background and Aims: The aim was to evaluate and compare the relative vaccine effectiveness (rVE) of high-dose (HD-IIV) vs. standard-dose inactivated influenza vaccination (SD-IIV) on respiratory and cardiovascular outcomes in persons with or without pre-existing atherosclerotic cardiovascular disease (ASCVD). Methods: A prespecified exploratory analysis of a pragmatic, open-label, individually randomized trial conducted in Denmark during three influenza seasons. Adults ≥65 years were randomized 1:1 to HD-IIV or SD-IIV. Baseline and outcome data were collected through nationwide registries. The primary outcome was hospitalization for influenza or pneumonia. Major adverse cardiovascular events (MACE) was defined as a composite of cardiovascular death, hospitalization for myocardial infarction, or hospitalization for stroke. Heterogeneity in rVE among participants with vs. without ASCVD was assessed. Results: The incidence of all outcomes was higher in participants with pre-existing ASCVD (n = 46 825) vs. those without (n = 285 613). rVE was consistent among participants with and without ASCVD (all Pinteraction ≥ .05). The rVE for the primary outcome was 6.87% [95% confidence interval (CI), −2.52 to 15.42] among individuals without ASCVD and 4.71% (95% CI, −11.58 to 18.63) in those with (Pinteraction = .80). For influenza hospitalizations, the rVE was 42.88% (95% CI, 22.07–58.44) vs. 45.73% (95% CI, 16.68–65.16) in those without vs. with ASCVD (Pinteraction = .84). For MACE, the rVE was 4.29% (95% CI, −6.50 to 14.00) in participants without, and 0.30% (95% CI, −17.56 to 15.44) in participants with, pre-existing ASCVD (Pinteraction = .68). Conclusions: Among individuals ≥65 years, the rVE of HD-IIV vs. SD-IIV against respiratory and cardiovascular outcomes was similar among those with vs. without pre-existing ASCVD

High-dose vs. standard-dose influenza vaccine in heart failure: a prespecified analysis of the DANFLU-2 trial

Background: Influenza contributes substantially to disease burden in individuals with heart failure (HF) and is an established trigger of cardiovascular (CV) and HF events. Standard-dose inactivated influenza vaccine (SD-IIV) is recommended for HF, though immune responses may be attenuated. High-dose IIV (HD-IIV) was developed to enhance immunogenicity, but its effectiveness compared with SD-IIV against hospitalization for influenza and CV disease by HF status remains uncertain. Methods: This was a prespecified analysis of a pragmatic, prospective, individually randomized, open-label trial with registry-based endpoint-evaluation conducted in Denmark across the 2022/2023 to 2024/2025 influenza seasons. Citizens ≥65 years were randomized 1:1 to HD-IIV or SD-IIV. Outcomes included hospitalization for influenza-related illness, laboratory-confirmed influenza (LCI), any CV disease, cardio-respiratory disease, and HF, assessed by HF status. Effect of HD-IIV vs. SD-IIV in reducing risk of outcomes assessed was expressed as risk ratios (RR). Results: The trial randomized 332,438 participants (48.6% female, mean age 73.7±5.8 years), including 10,410 with HF at baseline (27.4% female, mean age 76.0±6.3 years). Overall, HD-IIV was associated with a statistically significant lower incidence of hospitalization for influenza-related illness, LCI, cardio-respiratory disease, CV disease, and HF compared with SD-IIV. In participants with HF, effect estimates were similar: RR for influenza-related hospitalization was 0.48 (95%CI, 0.20-1.06; pinteraction=0.64), for LCI hospitalization 0.55 (95%CI, 0.29-1.02; pinteraction=0.59), for cardio-respiratory hospitalization 0.89 (95%CI, 0.77-1.02; pinteraction=0.34), for CV hospitalization 0.86 (95%CI, 0.72-1.02; pinteraction=0.34), and for HF hospitalization 0.82 (95%CI, 0.61-1.11; pinteraction=0.83). Findings were consistent across HF subgroups by disease duration, recency of hospitalization, most recent N-terminal pro-B-type natriuretic peptide, and presence of device therapy. Conclusions: In this prespecified exploratory analysis of the largest individually randomized influenza vaccine trial ever conducted, HD-IIV was associated with lower rates of influenza and CV hospitalizations compared with SD-IIV, with effect estimates similar across HF status at baseline and HF subgroups