Super-high-resolution Earth observation datasets of North American permafrost landscapes

While temperatures are increasing on the global scale, the Arctic regions are especially vulnerable to this changing climate and landscapes underlain by permafrost experience increased thaw and degradation. The enhanced warming of organic-rich frozen ground can have severe consequences on infrastructure and ecosystems and is projected to become a highly relevant driver of greenhouse gas fluxes into the atmosphere. Degrading permafrost landscapes occur extensively in vast areas of the North American Arctic, directly affecting communities and ecosystems. To identify and quantify these widespread degradation phenomena over vast areas, we require highest-resolution Earth observation dataset that we collect during aerial imaging campaigns. We here report on observations and first results from three airborne campaigns in 2018, 2019 and 2021. We performed large-scale monitoring of permafrost-affected areas in northern Canada and Alaska, focusing on sites that experienced disturbances in the past or recently. This included sites with vulnerable settlements, coastal erosion, thaw slumping, lake expansion and drainage, ice-wedge degradation and thaw subsidence, fire scars, pingos, methane seeps, and sites affected by beaver activities. All surveys were flown with the Alfred Wegener Institute's Polar-5 and -6 scientific airplanes at 500-1500 m altitude above terrain. The onboard sensor, the Modular Aerial Camera System (MACS), a very-high-resolution multispectral camera developed by the German Aerospace Center, operated in the visible (RGB) and near-infrared (NIR) domain. From the comprehensive collection of multiple TB of gathered data, super-high-resolution (up to 7 cm/px) RGB+NIR image mosaics and stereophotogrammetric digital surface models were derived. By presenting the data and first analyses, we would like to invite the community to discuss best use for maximized benefit of the data, in order to substantially contribute to our understanding of permafrost thaw dynamics

Correction to: Bioaerosol sampling of patients with suspected pulmonary tuberculosis: a study protocol

An amendment to this paper has been published and can be accessed via the original articl

GPR Expression in Intestinal Biopsies From SCT Patients Is Upregulated in GvHD and Is Suppressed by Broad-Spectrum Antibiotics

Microbiota can exert immunomodulatory effects by short-chain fatty acids (SCFA) in experimental models of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT). Therefore we aimed to analyze the expression of SCFAs sensing G-protein coupled receptor GPR109A and GPR43 by quantitative PCR in 338 gastrointestinal (GI) biopsies obtained from 199 adult patients undergoing allo-SCT and assessed the interaction of GPR with FOXP3 expression and regulatory T cell infiltrates. GPR expression was strongly upregulated in patients with stage II-IV GvHD (p=0.000 for GPR109A, p=0.01 for GPR43) and at the onset of GvHD (p 0.000 for GPR109A, p=0.006 for GPR43) and correlated strongly with FOXP3 and NLRP3 expression. The use of broad-spectrum antibiotics (Abx) drastically suppressed GPR expression as well as FOXP3 expression in patients’ gut biopsies (p=0.000 for GPRs, FOXP3 mRNA and FOXP3+ cellular infiltrates). Logistic regression analysis revealed treatment with Abx as an independent factor associated with GPR and FOXP3 loss. The upregulation of GPRs was evident only in the absence of Abx (p=0.001 for GPR109A, p=0.014 for GPR43) at GvHD onset. Thus, GPR expression seems to be upregulated in the presence of commensal bacteria and associates with infiltration of FOXP3+ T regs, suggesting a protective, regenerative immunomodulatory response. However, Abx, which has been shown to induce dysbiosis, interferes with this protective response

Severe T cell hyporeactivity in ventilated COVID-19 patients correlates with prolonged virus persistence and poor outcomes

Coronavirus disease 2019 (COVID-19) can lead to pneumonia and hyperinflammation. Here we show a sensitive method to measure polyclonal T cell activation by downstream effects on responder cells like basophils, plasmacytoid dendritic cells, monocytes and neutrophils in whole blood. We report a clear T cell hyporeactivity in hospitalized COVID-19 patients that is pronounced in ventilated patients, associated with prolonged virus persistence and reversible with clinical recovery. COVID-19-induced T cell hyporeactivity is T cell extrinsic and caused by plasma components, independent of occasional immunosuppressive medication of the patients. Monocytes respond stronger in males than females and IL-2 partially restores T cell activation. Downstream markers of T cell hyporeactivity are also visible in fresh blood samples of ventilated patients. Based on our data we developed a score to predict fatal outcomes and identify patients that may benefit from strategies to overcome T cell hyporeactivity.Coronavirus disease 2019 (COVID-19) can lead to pneumonia and hyperinflammation. Here we show a sensitive method to measure polyclonal T cell activation by downstream effects on responder cells like basophils, plasmacytoid dendritic cells, monocytes and neutrophils in whole blood. We report a clear T cell hyporeactivity in hospitalized COVID-19 patients that is pronounced in ventilated patients, associated with prolonged virus persistence and reversible with clinical recovery. COVID-19-induced T cell hyporeactivity is T cell extrinsic and caused by plasma components, independent of occasional immunosuppressive medication of the patients. Monocytes respond stronger in males than females and IL-2 partially restores T cell activation. Downstream markers of T cell hyporeactivity are also visible in fresh blood samples of ventilated patients. Based on our data we developed a score to predict fatal outcomes and identify patients that may benefit from strategies to overcome T cell hyporeactivity

Molecular mechanisms of DNA repair in Mycobacterium tuberculosis

The mycobacterial DNA damage and repair pathways involved in the emergence of drug-resistance during host infection remain poorly understood, yet are critical to any efforts to develop novel "anti-evolution" drugs aimed at reducing the capacity of Mycobacterium tuberculosis to adapt genetically during tuberculosis (TB) treatment. The thesis presented here aimed to investigate the contribution of the DNA damage (SOS) response in adaptive mutagenesis, and focused on two specific components: the role of the specialist translesion synthesis DNA polymerase, DnaE2, in mutagenesis under stress and, secondly, the function of the mycobacterial homologue of a putative SOS response associated peptidase (SRAP) protein which has been identified in comparative genomics analyses of organisms possessing a DnaE2-type C family DNA polymerase. This work focused on the putative SRAP protein which was predicted to form part of the mycobacterial DNA damage response as a functional switch by binding DNA in an autoproteolytic dependent manner. To this end, SRAP deletion mutants were generated for both M. smegmatis (MSMEG_1891) and M. tuberculosis (Rv3226c). Despite the fact that SRAP was upregulated in both M. smegmatis and M. tuberculosis following genotoxic stress, no DNA damage phenotype was detected in any SRAP deletion mutant using a variety of DNA damaging agents. In parallel, an eGFP-tagged M. smegmatis SRAP allele was constructed to enable visualisation of SRAP upregulation and sub-cellular recruitment using fluorescent microscopy; however no eGFP expression could be visualised after MMC treatment. It was not clear whether this was due to faulty eGFP expression in the fusion protein, or to low-level induction of SRAP. In a biochemical approach to elucidate SRAP function, soluble M. smegmatis SRAP protein was expressed and purified using a N-terminal hexa-histidine tag. No proteolytic activity was detected in gelatine or casein zymography, perhaps indicating that SRAP has a very specific substrate. Moreover, while it was predicted that autocatalytic cleavage of the C-terminus was required for activation of SRAP, no such cleavage was detected using hexa-histidine tag staining, possibly pointing to a set of very specific conditions for activation. In combination, therefore, neither microbiological nor biochemical assays could elucidate a definitive role for SRAP in the mycobacterial DNA damage response. DnaE2 has been directly implicated in induced mutagenesis to rifampicin (Rif) resistance in Mycobacterium tuberculosis following exposure of bacilli to genotoxic stress. In previous work in our group, a vitamin B₁₂-sensitive ΔmetH strain was found to form "B₁₂-resistant" suppressor mutants at a frequency higher than could be explained by spontaneous mutagenesis alone. The first part of this thesis investigated the potential role of DnaE2 in the high-frequency emergence of B₁₂-resistance by mutating DnaE2 in the ΔmetH background. Whereas elimination of polymerase function in a DnaE2ᴬᴵᴬ mutant abrogated DNA damage-induced mutagenesis to Rif resistance, no change in B₁₂ sensitivity was detected in a ΔmetH dnaE2ᴬᴵᴬ double mutant. PCR sequencing of spontaneous B₁₂-resistant mutants revealed mutations in genes previously associated with the suppressor phenotype; moreover, there was no apparent difference in the nature of mutations observed in both parental and dnaE2ᴬᴵᴬ mutant strains. Instead, these results suggest that an alternative mechanism must exist to enable adaptive mutagenesis in methionine-starved mycobacteria

Effects of computerized decision support system implementations on patient outcomes in inpatient care: a systematic review

Varghese J, Kleine M, Gessner SI, Sandmann S, Dugas M. Effects of computerized decision support system implementations on patient outcomes in inpatient care: a systematic review. JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION. 2018;25(5):593-602.Objectives: To systematically classify the clinical impact of computerized clinical decision support systems (CDSSs) in inpatient care. Materials and Methods: Medline, Cochrane Trials, and Cochrane Reviews were searched for CDSS studies that assessed patient outcomes in inpatient settings. For each study, 2 physicians independently mapped patient outcome effects to a predefined medical effect score to assess the clinical impact of reported outcome effects. Disagreements were measured by using weighted kappa and solved by consensus. An example set of promising disease entities was generated based on medical effect scores and risk of bias assessment. To summarize technical characteristics of the systems, reported input variables and algorithm types were extracted as well. Results: Seventy studies were included. Five (7%) reported reduced mortality, 16 (23%) reduced life-threatening events, and 28 (40%) reduced non-life-threatening events, 20 (29%) had no significant impact on patient outcomes, and 1 showed a negative effect (weighted kappa: 0.72, P<.001). Six of 24 disease entity settings showed high effect scores with medium or low risk of bias: blood glucose management, blood transfusion management, physiologic deterioration prevention, pressure ulcer prevention, acute kidney injury prevention, and venous thromboembolism prophylaxis. Most of the implemented algorithms (72%) were rule-based. Reported input variables are shared as standardized models on a metadata repository. Discussion and Conclusion: Most of the included CDSS studies were associated with positive patient outcomes effects but with substantial differences regarding the clinical impact. A subset of 6 disease entities could be filtered in which CDSS should be given special consideration at sites where computer-assisted decision-making is deemed to be underutilized

Aerosolization of Mycobacterium tuberculosis by Tidal Breathing

RATIONALE: Interrupting tuberculosis (TB) transmission requires an improved understanding of how and when the causative organism, Mycobacterium tuberculosis (Mtb), is aerosolized. Although cough is commonly assumed to be the dominant source of Mtb aerosols, recent evidence of cough-independent Mtb release implies the contribution of alternative mechanisms. OBJECTIVES: To compare the aerosolization of Mtb bacilli and total particulate matter from patients with TB during three separate respiratory maneuvers: tidal breathing (TiBr), FVC, and cough. METHODS: Bioaerosol sampling and Mtb enumeration by live-cell, fluorescence microscopy were combined with real-time measurement of CO2 concentration and total particle counts from 38 patients with GeneXpert-positive TB before treatment initiation. MEASUREMENTS AND MAIN RESULTS: For all maneuvers, the proportions of particles detected across five size categories were similar, with most particles falling between 0.5-5 Rm. Although total particle counts were 4.8-fold greater in cough samples than either TiBr or FVC, all three maneuvers returned similar rates of positivity for Mtb. No correlation was observed between total particle production and Mtb count. Instead, for total Mtb counts, the variability between individuals was greater than the variability between sampling maneuvers. Finally, when modelled using 24-hour breath and cough frequencies, our data indicate that TiBr might contribute more than 90% of the daily aerosolized Mtb among symptomatic patients with TB. CONCLUSIONS: Assuming the number of viable Mtb organisms released offers a reliable proxy of patient infectiousness, our observations imply that TiBr and interindividual variability in Mtb release might be significant contributors to TB transmission among active cases

Hydrocortisone fails to abolish NF-κB1 protein nuclear translocation in deletion allele carriers of the NFKB1 promoter polymorphism (-94ins/delATTG) and is associated with increased 30-day mortality in septic shock.

BACKGROUND:Previous investigations and meta-analyses on the effect of glucocorticoids on mortality in septic shock revealed mixed results. This heterogeneity might be evoked by genetic variations. Such candidate is a promoter polymorphism (-94ins/delATTG) of the gene encoding the ubiquitous transcription-factor nuclear-factor-κB (NF-κB) which binds to recognition elements in the promoter of several genes encoding for the innate immune-system. In turn, hydrocortisone inhibits NF-κB nuclear translocation and thus transcription of key immune-response regulators. Accordingly, we tested the hypotheses that hydrocortisone has a NFKB1 genotype dependent effect on 1) NF-κB1 nuclear translocation evoked by lipopolysaccharide (LPS) in monocytes in vitro, and 2) mortality in septic shock. METHODS:Monocytes of volunteers with the homozygous insertion (II; n = 5) or deletion (DD; n = 6) NFKB1 genotype were incubated with 10 µgml-1 LPS ± hydrocortisone (10-5M), and NF-κB1 nuclear translocation was assessed (immunofluorescence). Furthermore, we analyzed 30-day-mortality in 160 patients with septic shock stratified for both genotype and hydrocortisone therapy. RESULTS:Hydrocortisone inhibited LPS induced nuclear translocation of NF-κB1 in II (25%±11;p = 0.0001) but not in DD genotypes (51%±15;p = n.s.). Onehundredandfour of 160 patients with septic shock received hydrocortisone, at the discretion of the intensivist. NFKB1 deletion allele carriers (ID/DD) receiving hydrocortisone had a much greater 30-day-mortality (57.6%) than II genotypes (24.4%; HR:3.18, 95%-CI:1.61-6.28;p = 0.001). In contrast, 30-day mortality was 22.2% in ID/DD and 25.0% in II genotypes without hydrocortisone therapy. Results were similar when using propensity score matching to account for possible bias in the intensivists' decision to administer hydrocortisone. CONCLUSION:Hydrocortisone fails to inhibit LPS induced nuclear NF-κB1 translocation in deletion allele carriers of the NFKB1 promoter polymorphism (-94ins/delATTG). In septic shock, hydrocortisone treatment is associated with markedly increased 30-day-mortality only in such carriers. Accordingly, previous heterogeneous results regarding the benefit of hydrocortisone in septic shock may be reconciled by genetic variation of the NFKB1 promoter polymorphism

Super-high-resolution Earth observation datasets of North American permafrost landscapes

While temperatures are increasing on the global scale, the Arctic regions are especially vulnerable to this changing climate and landscapes underlain by permafrost experience increased thaw and degradation. The enhanced warming of organic-rich frozen ground can have severe consequences on infrastructure and ecosystems and is projected to become a highly relevant driver of greenhouse gas fluxes into the atmosphere. Degrading permafrost landscapes occur extensively in vast areas of the North American Arctic, directly affecting communities and ecosystems. To identify and quantify these widespread degradation phenomena over vast areas, we require highest-resolution Earth observation dataset that we collect during aerial imaging campaigns. We here report on observations and first results from three airborne campaigns in 2018, 2019 and 2021. We performed large-scale monitoring of permafrost-affected areas in northern Canada and Alaska, focusing on sites that experienced disturbances in the past or recently. This included sites with vulnerable settlements, coastal erosion, thaw slumping, lake expansion and drainage, ice-wedge degradation and thaw subsidence, fire scars, pingos, methane seeps, and sites affected by beaver activities. All surveys were flown with the Alfred Wegener Institute's Polar-5 and -6 scientific airplanes at 500-1500 m altitude above terrain. The onboard sensor, the Modular Aerial Camera System (MACS), a very-high-resolution multispectral camera developed by the German Aerospace Center, operated in the visible (RGB) and near-infrared (NIR) domain. From the comprehensive collection of multiple TB of gathered data, super-high-resolution (up to 7 cm/px) RGB+NIR image mosaics and stereophotogrammetric digital surface models were derived. By presenting the data and first analyses, we would like to invite the community to discuss best use for maximized benefit of the data, in order to substantially contribute to our understanding of permafrost thaw dynamics