Prolonged viral pneumonia and high mortality in COVID-19 patients on anti-CD20 monoclonal antibody therapy.

PURPOSE: In clinical practice, we observed an apparent overrepresentation of COVID-19 patients on anti-CD20 monoclonal antibody therapy. The aim of this study was to characterize the clinical picture of COVID-19 in these patients. METHODS: All adult patients from Turku University Hospital, Turku, Finland, with COVID-19 diagnosis and/or positive SARS-CoV-2 PCR test result up to March 2023, and with anti-CD20 therapy within 12 months before COVID-19 were included. Data was retrospectively obtained from electronic patient records. RESULTS: Ninety-eight patients were identified. 44/93 patients (47.3%) were hospitalized due to COVID-19. Patients with demyelinating disorder (n = 20) were youngest (median age 36.5 years, interquartile range 33-45 years), had less comorbidities, and were least likely to be hospitalized (2/20; 10.0%) or die (n = 0). COVID-19 mortality was 13.3% in the whole group, with age and male sex as independent risk factors. Persistent symptoms were documented in 33/94 patients (35.1%) alive by day 30, in 21/89 patients (23.6%) after 60 days, and in 15/85 after 90 days (17.6%), mostly in patients with haematological malignancy or connective tissue disease. Prolonged symptoms after 60 days predisposed to persistent radiological findings (odds ratio 64.0; 95% confidence interval 6.3-711; p < 0.0001) and persistently positive PCR (odds ratio 45.5, 95% confidence interval 4.0-535; p < 0.0001). Several patients displayed rapid response to late antiviral therapy. CONCLUSION: Anti-CD20 monoclonal antibody therapy is associated with high COVID-19 mortality and with a phenotype consistent with prolonged viral pneumonia. Our study provides rationale for retesting of immunocompromised patients with prolonged COVID-19 symptoms and considering antiviral therapy.

Differential interactions of age and sleep deprivation in driving and spatial perception by male drivers in a virtual reality environment.

We determined the effects of age and sleep deprivation on driving and spatial perception in a virtual reality environment. Twenty-two young (mean age: 22 years, range: 18-35) and 23 old (mean age: 71 years, range: 65-79) participants were tested after a normal night of sleep and a night of sleep deprivation. The participants drove a virtual car while responding to uni- and bilateral visual and auditory stimuli. Driving errors (crossing the lane borders), reaction times and accuracy to visual and auditory stimuli, performance in psychological tests, and subjective driving ability and tiredness were measured. Age had no effect on the number of driving errors, whereas sleep deprivation increased significantly especially the number of left lane border crossings. Age increased the number of stimulus detection errors, while sleep deprivation increased the number of errors particularly in the young and in the auditory modality as response omissions. Age and sleep deprivation together increased the number of response omissions in both modalities. Left side stimulus omissions suggest a bias to the right hemispace. The subjective evaluations were consistent with the objective measures. The psychological tests were more sensitive to the effects of age than to those of sleep deprivation. Driving simulation in a virtual reality setting is sensitive in detecting the effects of deteriorating factors on both driving and simultaneous spatial perception.

Does Differentially Private Synthetic Data Lead to Synthetic Discoveries?

BACKGROUND: Synthetic data have been proposed as a solution for sharing anonymized versions of sensitive biomedical datasets. Ideally, synthetic data should preserve the structure and statistical properties of the original data, while protecting the privacy of the individual subjects. Differential Privacy (DP) is currently considered the gold standard approach for balancing this trade-off. OBJECTIVES: The aim of this study is to investigate how trustworthy are group differences discovered by independent sample tests from DP-synthetic data. The evaluation is carried out in terms of the tests' Type I and Type II errors. With the former, we can quantify the tests' validity, i.e., whether the probability of false discoveries is indeed below the significance level, and the latter indicates the tests' power in making real discoveries. METHODS: We evaluate the Mann-Whitney U test, Student's t-test, chi-squared test, and median test on DP-synthetic data. The private synthetic datasets are generated from real-world data, including a prostate cancer dataset (n = 500) and a cardiovascular dataset (n = 70,000), as well as on bivariate and multivariate simulated data. Five different DP-synthetic data generation methods are evaluated, including two basic DP histogram release methods and MWEM, Private-PGM, and DP GAN algorithms. CONCLUSION: A large portion of the evaluation results expressed dramatically inflated Type I errors, especially at levels of ϵ ≤ 1. This result calls for caution when releasing and analyzing DP-synthetic data: low p-values may be obtained in statistical tests simply as a byproduct of the noise added to protect privacy. A DP Smoothed Histogram-based synthetic data generation method was shown to produce valid Type I error for all privacy levels tested but required a large original dataset size and a modest privacy budget (ϵ ≥ 5) in order to have reasonable Type II error levels.

50 Hz magnetic field influences caspase-3 activity and cell cycle distribution in ionizing radiation exposed SH-SY5Y neuroblastoma cells.

PURPOSE: Earlier evidence suggests that extremely low frequency magnetic fields (ELF MFs) can modify the effects of carcinogenic agents. However, the studies conducted so far with ionizing radiation as the co-exposure agent are sparse and have provided inconclusive results. We investigated whether 50 Hz MFs alone, or in combination with ionizing radiation alter cell biological variables relevant to cancer and the biological effects of ionizing radiation. MATERIALS AND METHODS: Human SH-SY5Y neuroblastoma cells were sham exposed or exposed to 100 or 500 µT MF for 24 h either before or after ionizing radiation exposure (0, 0.4 or 2 Gy). After the exposures, cells were assayed for viability, clonogenicity, reactive oxygen species, caspase-3 activity, and cell cycle distribution. Cell cycle distribution was assayed with propidium iodide staining followed by flow cytometry analysis and ROS levels were assayed together with cell viability by double staining with DeepRed and Sytox Blue followed by flow cytometry analysis. RESULTS: Increased caspase-3 activity was observed in cells exposed to 500 µT MF before or after ionizing radiation. Furthermore, exposure to the 500 µT MF after the ionizing radiation decreased the percentage of cells in S-phase. No changes in the ROS levels, clonogenicity, or viability of the cells were observed in the MF exposed groups compared to the corresponding sham exposed groups, and no MF effects were observed in cells exposed at 100 µT. CONCLUSIONS: Only the 500 µT magnetic flux density affected SH-SY5Y cells significantly. The effects were small but may nevertheless help to understand how MFs modify the effects of ionizing radiation. The increase in caspase-3 activity may not reflect effects on apoptosis, as no changes were observed in the subG1 phase of the cell cycle. In contrast to some earlier findings, 50 Hz MF exposure after ionizing radiation was not less effective than MF treatment given prior to ionizing radiation.

Static or 50 Hz magnetic fields at 100 µT do not modify the clonogenic survival of doxorubicin-treated MCF-7 cancer cells.

The objective of this study was to evaluate whether static or 50 Hz magnetic fields (MFs) modify responses to the chemotherapeutic agent doxorubicin in human MCF-7 breast cancer cells. To this end, cells were exposed to static or 50 Hz MFs at 100 µT with or without doxorubicin for 3 h. Following the exposures, cytosolic and mitochondrial superoxide levels, DNA damage levels, and the clonogenic survival of the cells were evaluated. It was found that static MFs decreased the DNA damage level induced by doxorubicin treatment (p = 0.023), but no effects were observed for either cytosolic and mitochondrial superoxide levels or the clonogenic survival of the cells. On the other hand, 50 Hz MF increased doxorubicin-induced cytosolic superoxide levels (p = 0.016), while the mitochondrial superoxide level, DNA damage level, and clonogenic survival were unaffected. In conclusion, we found that static and 50 Hz MFs may modify responses to doxorubicin treatment, but the subsequent survival of the doxorubicin-treated cancer cells was unaffected by both types of MFs. Therefore, the present results suggest that static or 50 Hz MFs for 3 h do not modify the efficacy of doxorubicin in MCF-7 cancer cells.