Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation

BACKGROUND: The lung microbiome of healthy individuals frequently harbors oral organisms. Despite evidence that microaspiration is commonly associated with smoking-related lung diseases, the effects of lung microbiome enrichment with upper airway taxa on inflammation has not been studied. We hypothesize that the presence of oral microorganisms in the lung microbiome is associated with enhanced pulmonary inflammation. To test this, we sampled bronchoalveolar lavage (BAL) from the lower airways of 29 asymptomatic subjects (nine never-smokers, 14 former-smokers, and six current-smokers). We quantified, amplified, and sequenced 16S rRNA genes from BAL samples by qPCR and 454 sequencing. Pulmonary inflammation was assessed by exhaled nitric oxide (eNO), BAL lymphocytes, and neutrophils. RESULTS: BAL had lower total 16S than supraglottic samples and higher than saline background. Bacterial communities in the lower airway clustered in two distinct groups that we designated as pneumotypes. The rRNA gene concentration and microbial community of the first pneumotype was similar to that of the saline background. The second pneumotype had higher rRNA gene concentration and higher relative abundance of supraglottic-characteristic taxa (SCT), such as Veillonella and Prevotella, and we called it pneumotype(SCT). Smoking had no effect on pneumotype allocation, α, or β diversity. Pneumotype(SCT) was associated with higher BAL lymphocyte-count (P= 0.007), BAL neutrophil-count (P= 0.034), and eNO (P= 0.022). CONCLUSION: A pneumotype with high relative abundance of supraglottic-characteristic taxa is associated with enhanced subclinical lung inflammation

Express method for isolation of ready-to-use 3D chitin scaffolds from aplysina archeri (aplysineidae: verongiida) demosponge

Sponges are a valuable source of natural compounds and biomaterials for many biotechnological applications. Marine sponges belonging to the order Verongiida are known to contain both chitin and biologically active bromotyrosines. Aplysina archeri (Aplysineidae: Verongiida) is well known to contain bromotyrosines with relevant bioactivity against human and animal diseases. The aim of this study was to develop an express method for the production of naturally prefabricated 3D chitin and bromotyrosine-containing extracts simultaneously. This new method is based on microwave irradiation (MWI) together with stepwise treatment using 1% sodium hydroxide, 20% acetic acid, and 30% hydrogen peroxide. This approach, which takes up to 1 h, made it possible to isolate chitin from the tube-like skeleton of A. archeri and to demonstrate the presence of this biopolymer in this sponge for the first time. Additionally, this procedure does not deacetylate chitin to chitosan and enables the recovery of ready-to-use 3D chitin scaffolds without destruction of the unique tube-like fibrous interconnected structure of the isolated biomaterial. Furthermore, these mechanically stressed fibers still have the capacity for saturation with water, methylene blue dye, crude oil, and blood, which is necessary for the application of such renewable 3D chitinous centimeter-sized scaffolds in diverse technological and biomedical fields. © 2019 by the authors

Erratum to: "Double volume reflection of a proton beam by a sequence of two bent crystals" [Phys. Lett. B 658 (2008) 109]

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DIAPH1-MFN2 Interaction Regulates Mitochondria-SR/ER Contact and Modulates Ischemic/Hypoxic Stress

Inter-organelle contact and communication between mitochondria and sarco/endoplasmic reticulum (SR/ER) maintain cellular homeostasis and are profoundly disturbed during tissue ischemia. We tested the hypothesis that the formin Diaphanous-1 (DIAPH1), which regulates actin dynamics, signal transduction and metabolic functions, contributes to these processes. We demonstrate that DIAPH1 interacts directly with Mitofusin-2 (MFN2) to shorten mitochondria-SR/ER distance, thereby enhancing mitochondria-ER contact in cells including cardiomyocytes, endothelial cells and macrophages. Solution structure studies affirm the interaction between the Diaphanous Inhibitory Domain and the cytosolic GTPase domain of MFN2. In male rodent and human cardiomyocytes, DIAPH1-MFN2 interaction regulates mitochondrial turnover, mitophagy, and oxidative stress. Introduction of synthetic linker construct, which shorten the mitochondria-SR/ER distance, mitigated the molecular and functional benefits of DIAPH1 silencing in ischemia. This work establishes fundamental roles for DIAPH1-MFN2 interaction in the regulation of mitochondria-SR/ER contact networks. We propose that targeting pathways that regulate DIAPH1-MFN2 interactions may facilitate recovery from tissue ischemia

Strong reduction of the off-momentum halo in crystal assisted collimation of the SPS beam

A study of crystal assisted collimation has been continued at the CERN SPS for different energies of stored beams using 120 GeV/. c and 270 GeV/. c protons and Pb ions with 270 GeV/. c per charge. A bent silicon crystal used as a primary collimator deflected halo particles using channeling and directing them into the tungsten absorber. A strong correlation of the beam losses in the crystal and off-momentum halo intensity measured in the first high dispersion (HD) area downstream was observed. In channeling conditions, the beam loss rate induced by inelastic interactions of particles with nuclei is significantly reduced in comparison with the non-oriented crystal. A maximal reduction of beam losses in the crystal larger than 20 was observed with 270 GeV/. c protons. The off-momentum halo intensity measured in the HD area was also strongly reduced in channeling conditions. The reduction coefficient was larger than 7 for the case of Pb ions. A strong loss reduction was also detected in regions of the SPS ring far from the collimation area. It was shown by simulations that the miscut angle between the crystal surface and its crystallographic planes doubled the beam losses in the aligned crystal.peer-reviewe

A Multiclass Radiomics Method-Based WHO Severity Scale for Improving COVID-19 Patient Assessment and Disease Characterization From CT Scans.

OBJECTIVES The aim of this study was to evaluate the severity of COVID-19 patients' disease by comparing a multiclass lung lesion model to a single-class lung lesion model and radiologists' assessments in chest computed tomography scans. MATERIALS AND METHODS The proposed method, AssessNet-19, was developed in 2 stages in this retrospective study. Four COVID-19-induced tissue lesions were manually segmented to train a 2D-U-Net network for a multiclass segmentation task followed by extensive extraction of radiomic features from the lung lesions. LASSO regression was used to reduce the feature set, and the XGBoost algorithm was trained to classify disease severity based on the World Health Organization Clinical Progression Scale. The model was evaluated using 2 multicenter cohorts: a development cohort of 145 COVID-19-positive patients from 3 centers to train and test the severity prediction model using manually segmented lung lesions. In addition, an evaluation set of 90 COVID-19-positive patients was collected from 2 centers to evaluate AssessNet-19 in a fully automated fashion. RESULTS AssessNet-19 achieved an F1-score of 0.76 ± 0.02 for severity classification in the evaluation set, which was superior to the 3 expert thoracic radiologists (F1 = 0.63 ± 0.02) and the single-class lesion segmentation model (F1 = 0.64 ± 0.02). In addition, AssessNet-19 automated multiclass lesion segmentation obtained a mean Dice score of 0.70 for ground-glass opacity, 0.68 for consolidation, 0.65 for pleural effusion, and 0.30 for band-like structures compared with ground truth. Moreover, it achieved a high agreement with radiologists for quantifying disease extent with Cohen κ of 0.94, 0.92, and 0.95. CONCLUSIONS A novel artificial intelligence multiclass radiomics model including 4 lung lesions to assess disease severity based on the World Health Organization Clinical Progression Scale more accurately determines the severity of COVID-19 patients than a single-class model and radiologists' assessment

Comparative results on collimation of the SPS beam of protons and Pb ions with bent crystals

New experiments on crystal assisted collimation have been carried out at the CERN SPS with stored beams of 120 GeV/. c protons and Pb ions. Bent silicon crystals of 2 mm long with about 170 μrad bend angle and a small residual torsion were used as primary collimators. In channeling conditions, the beam loss rate induced by inelastic interactions of particles with the crystal nuclei is minimal. The loss reduction was about 6 for protons and about 3 for Pb ions. Lower reduction value for Pb ions can be explained by their considerably larger ionization losses in the crystal. In one of the crystals, the measured fraction of the Pb ion beam halo deflected in channeling conditions was 74%, a value very close to that for protons. The intensity of the off-momentum halo leaking out from the collimation station was measured in the first high dispersion area downstream. The particle population in the shadow of the secondary collimator-absorber was considerably smaller in channeling conditions than for amorphous orientations of the crystal. The corresponding reduction was in the range of 2-5 for both protons and Pb ions.peer-reviewe

Identifying quality improvement intervention publications - A comparison of electronic search strategies

Abstract Background The evidence base for quality improvement (QI) interventions is expanding rapidly. The diversity of the initiatives and the inconsistency in labeling these as QI interventions makes it challenging for researchers, policymakers, and QI practitioners to access the literature systematically and to identify relevant publications. Methods We evaluated search strategies developed for MEDLINE (Ovid) and PubMed based on free text words, Medical subject headings (MeSH), QI intervention components, continuous quality improvement (CQI) methods, and combinations of the strategies. Three sets of pertinent QI intervention publications were used for validation. Two independent expert reviewers screened publications for relevance. We compared the yield, recall rate, and precision of the search strategies for the identification of QI publications and for a subset of empirical studies on effects of QI interventions. Results The search yields ranged from 2,221 to 216,167 publications. Mean recall rates for reference publications ranged from 5% to 53% for strategies with yields of 50,000 publications or fewer. The 'best case' strategy, a simple text word search with high face validity ('quality' AND 'improv*' AND 'intervention*') identified 44%, 24%, and 62% of influential intervention articles selected by Agency for Healthcare Research and Quality (AHRQ) experts, a set of exemplar articles provided by members of the Standards for Quality Improvement Reporting Excellence (SQUIRE) group, and a sample from the Cochrane Effective Practice and Organization of Care Group (EPOC) register of studies, respectively. We applied the search strategy to a PubMed search for articles published in 10 pertinent journals in a three-year period which retrieved 183 publications. Among these, 67% were deemed relevant to QI by at least one of two independent raters. Forty percent were classified as empirical studies reporting on a QI intervention. Conclusions The presented search terms and operating characteristics can be used to guide the identification of QI intervention publications. Even with extensive iterative development, we achieved only moderate recall rates of reference publications. Consensus development on QI reporting and initiatives to develop QI-relevant MeSH terms are urgently needed

Observation of parametric X-rays produced by 400 GeV/c protons in bent crystals

Spectral maxima of parametric X-ray radiation (PXR) produced by 400 GeV/c protons in bent silicon crystals aligned with the beam have been observed in an experiment at the H8 external beam of the CERN SPS. The total yield of PXR photons was about 10-6 per proton. Agreement between calculations and the experimental data shows that the PXR kinematic theory is valid for bent crystals with sufficiently small curvature as used in the experiment. The intensity of PXR emitted from halo protons in a bent crystal used as a primary collimator in a circular accelerator may be considered as a possible tool to control its crystal structure, which is slowly damaged because of irradiation. The intensity distribution of PXR peaks depends on the crystal thickness intersected by the beam, which changes for different orientations of a crystal collimator. This dependence may be used to control crystal collimator alignment by analyzing PXR spectra produced by halo protons.peer-reviewe

First-In-Human Study in Cancer Patients Establishing the Feasibility of Oxygen Measurements in Tumors Using Electron Paramagnetic Resonance With the OxyChip

Objective: The overall objective of this clinical study was to validate an implantable oxygen sensor, called the ‘OxyChip’, as a clinically feasible technology that would allow individualized tumor-oxygen assessments in cancer patients prior to and during hypoxia-modification interventions such as hyperoxygen breathing. Methods: Patients with any solid tumor at ≤3-cm depth from the skin-surface scheduled to undergo surgical resection (with or without neoadjuvant therapy) were considered eligible for the study. The OxyChip was implanted in the tumor and subsequently removed during standard-of-care surgery. Partial pressure of oxygen (pO2) at the implant location was assessed using electron paramagnetic resonance (EPR) oximetry. Results: Twenty-three cancer patients underwent OxyChip implantation in their tumors. Six patients received neoadjuvant therapy while the OxyChip was implanted. Median implant duration was 30 days (range 4–128 days). Forty-five successful oxygen measurements were made in 15 patients. Baseline pO2 values were variable with overall median 15.7 mmHg (range 0.6–73.1 mmHg); 33% of the values were below 10 mmHg. After hyperoxygenation, the overall median pO2 was 31.8 mmHg (range 1.5–144.6 mmHg). In 83% of the measurements, there was a statistically significant (p ≤ 0.05) response to hyperoxygenation. Conclusions: Measurement of baseline pO2 and response to hyperoxygenation using EPR oximetry with the OxyChip is clinically feasible in a variety of tumor types. Tumor oxygen at baseline differed significantly among patients. Although most tumors responded to a hyperoxygenation intervention, some were non-responders. These data demonstrated the need for individualized assessment of tumor oxygenation in the context of planned hyperoxygenation interventions to optimize clinical outcomes