Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the immune compartment of 16 tissues from 12 adult donors by ...single-cell RNA sequencing and VDJ sequencing generating a dataset of ~360,000 cells. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of finely phenotyped immune cell types, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multitissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis, and antigen receptor sequencing.
The Human Cell Atlas is a large international collaborative effort to map all cell types of the human body. Single-cell RNA sequencing can generate high-quality data for the delivery of such an ...atlas. However, delays between fresh sample collection and processing may lead to poor data and difficulties in experimental design.
This study assesses the effect of cold storage on fresh healthy spleen, esophagus, and lung from ≥ 5 donors over 72 h. We collect 240,000 high-quality single-cell transcriptomes with detailed cell type annotations and whole genome sequences of donors, enabling future eQTL studies. Our data provide a valuable resource for the study of these 3 organs and will allow cross-organ comparison of cell types. We see little effect of cold ischemic time on cell yield, total number of reads per cell, and other quality control metrics in any of the tissues within the first 24 h. However, we observe a decrease in the proportions of lung T cells at 72 h, higher percentage of mitochondrial reads, and increased contamination by background ambient RNA reads in the 72-h samples in the spleen, which is cell type specific.
In conclusion, we present robust protocols for tissue preservation for up to 24 h prior to scRNA-seq analysis. This greatly facilitates the logistics of sample collection for Human Cell Atlas or clinical studies since it increases the time frames for sample processing.
Maternal infection during pregnancy increases the risk of schizophrenia and other brain disorders of neurodevelopmental origin in the offspring. A multitude of infectious agents seem to be involved ...in this association. Therefore, it has been proposed that factors common to the immune response to a wide variety of bacterial and viral pathogens may be the critical link between prenatal infection and postnatal brain and behavioral pathology. More specifically, it has been suggested that the maternal induction of pro-inflammatory cytokines may mediate the neurodevelopmental effects of maternal infections. Here, we review recent findings from in vitro and in vivo investigations supporting this hypothesis and further emphasize the influence of enhanced anti-inflammatory cytokine signaling on early brain development. Disruption of the fetal brain balance between pro- and anti-inflammatory cytokine signaling may thus represent a key mechanism involved in the precipitation of schizophrenia-related pathology following prenatal maternal infection and innate immune imbalances.
Intravenous vitamin D is standard therapy for secondary hyperparathyroidism in hemodialysis (HD) patients. In for-profit dialysis clinics, mortality was higher for patients on calcitriol compared to ...paricalcitol. Doxercalciferol, a second vitamin D2 analog, is currently available. We assessed mortality associated with each vitamin D analog and with lack of vitamin D therapy in patients who began HD at Dialysis Clinic Inc. (DCI), a not-for-profit dialysis provider. During the 1999–2004 study period we studied 7731 patients (calcitriol: n=3212; paricalcitol: n=2087; doxercalciferol: n=2432). Median follow-up was 37 weeks. Mortality rates (deaths/100 patient-years) were identical in patients on doxercalciferol (15.4, 95% confidence interval (13.6–17.1)) and paricalcitol (15.3 (13.6–16.9)) and higher in patients on calcitriol (19.6 (18.2–21.1)) (P<0.0001). In all models mortality was similar for paricalcitol versus doxercalciferol (hazard ratios=1.0). In unadjusted models, mortality was lower in patients on doxercalciferol (0.80 (0.66, 0.96)) and paricalcitol (0.79 (0.68, 0.92)) versus calcitriol (P<0.05). In adjusted models, this difference was not statistically significant. In all models mortality was higher for patients who did not receive vitamin D versus those who did (1.2 (1.1–1.3)). Mortality in doxercalciferol- and paricalcitol-treated patients was virtually identical. Differences in survival between vitamin D2 and D3 may be smaller than previously reported.
Abstract
Aims
To perform the first psychometric analysis of the Norwegian version of the eHLQ using confirmative factor analysis (CFA) procedures in a population of patients admitted to hospital ...using a cross-sectional design. The eHLQ consists of 35 items capturing the 7-dimensional eHealth Literacy Framework (eHLF) which describes users' attributes, user's interaction with technologies and user's experience with digital health systems.
Methods
The 7 independent scales of the eHLQ was translated from Danish and culturally adapted into the Norwegian language following a standardised protocol. Assessment of construct validity of the eHLQ was undertaken using data from a cross-sectional survey of 260 patients hospitalized at a Norwegian University Hospital in the Oslo area during a two-week period in June 2021. The analysis included using correlation analysis (Pearsons R), internal consistency (Cronbach’s alpha) and confirmatory factor analysis (CFA).
Results
All factor loadings were high to acceptable (i.e. > 0.6), except for five items which had somewhat lower loadings. Regarding internal consistency, alpha ranged from 0.73 to 0.90. For optimal CFA fit for the different scale models, correlated residuals were required for five of the seven scales. Overall our analysis shows an intermediate fit of the orginal construct. Scale intercorrelations were all below 0.8, indicating an overall acceptable discriminant validity between the 7 dimensions.
Conclusions
The results from the CFA analysis indicate that for almost all 7 eHLQ scales, an acceptable model fit was achieved. The 260 hospitalized patients included in this study represented a variety of diagnoses, recruited from a geographically limited area. Further studies on psychometric properties of the Norwegian version of eHLQ in larger samples, diverse settings and by using more comprehensive approaches are warranted.
Maternal infections during pregnancy increase the risk for schizophrenia and related disorders of putative neurodevelopmental origin in the offspring. This association has been attributed to enhanced ...expression of pro-inflammatory cytokines in the fetal environment in response to maternal immunological stimulation. In contrast, the specific roles of anti-inflammatory cytokines are virtually unknown in this context. Here, we demonstrate that genetically enforced expression of the anti-inflammatory cytokine interleukin (IL)-10 by macrophages attenuates the long-term behavioral and pharmacological consequences of prenatal immune activation in a mouse model of prenatal viral-like infection by polyriboinosinic-polyribocytidilic acid (PolyI:C; 2 mg/kg, intravenously). In the absence of a discrete prenatal inflammatory stimulus, however, enhanced levels of IL-10 at the maternal-fetal interface by itself also precipitates specific behavioral abnormalities in the grown offspring. This highlights that in addition to the disruptive effects of excess pro-inflammatory molecules, a shift toward enhanced anti-inflammatory signaling in prenatal life can similarly affect cognitive and behavioral development. Hence, shifts of the balance between pro- and anti-inflammatory cytokine classes may be a critical determinant of the final impact on neurodevelopment following early life infection or innate immune imbalances.
Objectives
Measurement of the Eustachian tube (ET) function is a challenge. The demand for a precise and meaningful diagnostic tool increases—especially because more and more operative therapies are ...being offered without objective evidence. The measurement of the ET function by continuous impedance recording in a pressure chamber is an established method, although the reliability of the measurements is still unclear.
Methods
Twenty‐five participants (50 ears) were exposed to phases of compression and decompression in a hypo‐ and hyperbaric pressure chamber. The ET function reflecting parameters—ET opening pressure (ETOP), ET opening duration (ETOD) and ET opening frequency (ETOF)—were determined under exactly the same preconditions three times in a row. The intraclass correlation coefficient (ICC) and Bland and Altman plot were used to assess test‐retest reliability.
Results
ICCs revealed a high correlation for ETOP and ETOF in phases of decompression (passive equalisation) as well as ETOD and ETOP in phases of compression (active induced equalisation). Very high correlation could be shown for ETOD in decompression and ETOF in compression phases. The Bland and Altman graphs could show that measurements provide results within a 95 % confidence interval in compression and decompression phases.
Conclusions
We conclude that measurements in a pressure chamber are a very valuable tool in terms of estimating the ET opening and closing function. Measurements show some variance comparing participants, but provide reliable results within a 95 % confidence interval in retest. This study is the basis for enabling efficacy measurements of ET treatment modalities.
Copper‐oxide compound semiconductors provide a unique possibility to tune the optical and electronic properties from insulating to metallic conduction, from bandgap energies of 2.1 eV to the infrared ...at 1.40 eV, i.e., right into the middle of the efficiency maximum for solar‐cell applications. Three distinctly different phases, Cu2O, Cu4O3, and CuO, of this binary semiconductor can be prepared by thin‐film deposition techniques, which differ in the oxidation state of copper. Their material properties as far as they are known by experiment or predicted by theory are reviewed. They are supplemented by new experimental results from thin‐film growth and characterization, both will be critically discussed and summarized. With respect to devices the focus is on solar‐cell performances based on Cu2O. It is demonstrated by photoelectron spectroscopy (XPS) that the heterojunction system p‐Cu2O/n‐AlGaN is much more promising for the application as efficient solar cells than that of p‐Cu2O/n‐ZnO heterojunction devices that have been favored up to now.
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