In the appropriate clinical setting, the diagnosis of idiopathic pulmonary fibrosis (IPF) requires a pattern of usual interstitial pneumonia to be present on high-resolution chest CT (HRCT) or ...surgical lung biopsy. A molecular usual interstitial pneumonia signature can be identified by a machine learning algorithm in less-invasive transbronchial lung biopsy samples. We report prospective findings for the clinical validity and utility of this molecular test.
We prospectively recruited 237 patients for this study from those enrolled in the Bronchial Sample Collection for a Novel Genomic Test (BRAVE) study in 29 US and European sites. Patients were undergoing evaluation for interstitial lung disease and had had samples obtained by clinically indicated surgical or transbronchial biopsy or cryobiopsy for pathology. Histopathological diagnoses were made by experienced pathologists. Available HRCT scans were reviewed centrally. Three to five transbronchial lung biopsy samples were collected from all patients specifically for this study, pooled by patient, and extracted for transcriptomic sequencing. After exclusions, diagnostic histopathology and RNA sequence data from 90 patients were used to train a machine learning algorithm (Envisia Genomic Classifier, Veracyte, San Francisco, CA, USA) to identify a usual interstitial pneumonia pattern. The primary study endpoint was validation of the classifier in 49 patients by comparison with diagnostic histopathology. To assess clinical utility, we compared the agreement and confidence level of diagnosis made by central multidisciplinary teams based on anonymised clinical information and radiology results plus either molecular classifier or histopathology results.
The classifier identified usual interstitial pneumonia in transbronchial lung biopsy samples from 49 patients with 88% specificity (95% CI 70-98) and 70% sensitivity (47-87). Among 42 of these patients who had possible or inconsistent usual interstitial pneumonia on HRCT, the classifier showed 81% positive predictive value (95% CI 54-96) for underlying biopsy-proven usual interstitial pneumonia. In the clinical utility analysis, we found 86% agreement (95% CI 78-92) between clinical diagnoses using classifier results and those using histopathology data. Diagnostic confidence was improved by the molecular classifier results compared with histopathology results in 18 with IPF diagnoses (proportion of diagnoses that were confident or provisional with high confidence 89% vs 56%, p=0·0339) and in all 48 patients with non-diagnostic pathology or non-classifiable fibrosis histopathology (63% vs 42%, p=0·0412).
The molecular test provided an objective method to aid clinicians and multidisciplinary teams in ascertaining a diagnosis of IPF, particularly for patients without a clear radiological diagnosis, in samples that can be obtained by a less invasive method. Further prospective clinical validation and utility studies are planned.
Veracyte.
On 27 August 2016, the NASA Juno spacecraft performed its first close‐up observations of Jupiter during its perijove. Here we present the UV images and color ratio maps from the Juno‐UVS UV imaging ...spectrograph acquired at that time. Data were acquired during four sequences (three in the north, one in the south) from 5:00 UT to 13:00 UT. From these observations, we produced complete maps of the Jovian aurorae, including the nightside. The sequence shows the development of intense outer emission outside the main oval, first in a localized region (255°–295° System III longitude) and then all around the pole, followed by a large nightside protrusion of auroral emissions from the main emission into the polar region. Some localized features show signs of differential drift with energy, typical of plasma injections in the middle magnetosphere. Finally, the color‐ratio map in the north shows a well‐defined area in the polar region possibly linked to the polar cap.
Key Points
During Perijove 1, Juno‐UVS acquired the first spatially and spectrally resolved Far‐UV observations of Jupiter's nightside aurorae
During the 10 h sequences, large and intense outer emissions progressively developed and a protrusion formed with the southern main oval
A well‐defined area identified in the northern polar region resembles the shape, location, and area of the predicted open field line region
The two main ultraviolet‐signatures resulting from the Io‐magnetosphere interaction are the local auroras on Io's atmosphere, and the Io footprints on Jupiter. We study here how Io's daily eclipses ...affect the footprint. Previous observations showed that its atmosphere collapses in eclipse. While remote observers can observe Io's local auroras briefly when Io disappears behind Jupiter, Juno is able to follow the Io footprint in the unlit hemisphere. Theoretical models of the variability of the energy flux fed into the Alfvén wings, ultimately powering the footprints, are not sufficiently constrained by observations. For the first time, we use observations of Io's footprint from the Ultraviolet Spectrograph (UVS) on Juno recorded as Io went into eclipse. We benchmark the trend of the footprint brightness using observations by UVS taken over Io's complete orbit and find that the footprint emitted power variation with Jupiter's rotation shows fairly consistent trends with previous observations. Two exploitable data sets provided measurements when Io was simultaneously in eclipse. No statistically significant changes were recorded as Io left and moved into eclipse, respectively, suggesting either that (i) Io's atmospheric densities within and outside eclipse are large enough to produce a saturated plasma interaction, that is, in the saturated state, changes in Io's atmospheric properties to first order do not control the total Alfvénic energy flux, (ii) the atmospheric collapse during the Juno observations was less than previously observed, or (iii) additional processes of the Alfvén wings in addition to the Poynting flux generated at Io control the footprint luminosity.
Key Points
Juno‐UVS observed for the first time the Io footprints while Io went into eclipse
The effect of Io's atmospheric collapse on the footprint emitted power is investigated
No significant variation of the footprint emitted power is observed during eclipse
On 7 June 2021, Juno‐UVS mapped Ganymede's auroral emissions near a closest approach altitude of 1,046 km. The high spatial resolution map exhibits bright, 200–1,000 R, oxygen emissions organized ...into northern and southern auroral ovals. Though the map has incomplete global coverage, UVS observed longitudinal structure similar to that described by McGrath et al. (2013), https://doi.org/10.1002/jgra.50122 and latitudinal and vertical structure never before resolved. The mapped auroral emissions (a) display an intense narrow auroral curtain with a sharp poleward boundary, (b) have a more slowly decreasing equatorial edge on the leading hemisphere, (c) appear to originate near the surface with a vertical extent of 25–50 km, and (d) are slightly brighter in the north than the south. Additionally, we present UVS observations from the more distant Juno Ganymede flyby on 20 July 2021. We describe the observations, compare them to previous Hubble Space Telescope observations and current model predictions of the open‐closed‐field line‐boundary.
Plain Language Summary
Observations of Ganymede by Juno‐UVS during a close flyby (during Juno's 34th Jupiter orbit) captured unique high‐spatial‐resolution measurements of Ganymede's auroral emissions. Organized into two polar ovals, the positions and intensities of the auroral emissions are consistent with previous Hubble Space Telescope observations. The observed morphology of the auroras on the leading hemisphere of Ganymede exhibits latitudinal structure never before resolved. Previous studies suggest the poleward edge of the emissions trace the poleward most position of the magnetic field lines that have both ends rooted to Ganymede. We show that a magnetic field model of Ganymede within Jupiter's larger magnetosphere predicts last‐closed field‐lines very close to the observed auroral emissions, as expected. More distant observations taken during Juno's following orbit (orbit 35) capture auroral emissions at slightly different longitudes. They too show similar agreement with previous observations and current magnetic field models.
Key Points
The high spatial resolution observations revealed auroral emissions of over 1000 Rayleighs, brighter than previously observed
The leading hemisphere aurora exhibits an intense auroral curtain with a sharp poleward boundary and more slowly tapering equatorial edge
Juno‐UVS observed Ganymede's auroral emissions extending up to a maximum of 50 km altitude
A new assessment criterion for docking poses is proposed in which experimental electron density is taken into account when evaluating the ability of docking programs to reproduce experimentally ...observed binding modes. Three docking programs (Gold, Glide, and Fred) were used to generate poses for a set of 88 protein−ligand complexes for which the crystal structure is known. The new criterion is based on the real space R-factor (RSR), which measures how well a group of atoms−in our case the ligand−fits the experimental electron density by comparing that density to the expected density, calculated from the model (i.e., the predicted ligand pose). The RSR-based measure is compared to the traditional criterion, the root-mean-square distance (RMSD) between the docking pose and the binding configuration in the crystallographic model. The results highlight several shortcomings of the RMSD criterion that do not affect the RSR-based measure. Examples illustrate that the RSR-derived approach allows a more meaningful a posteriori assessment of docking methods and results. Practical implications for docking evaluations and for methodological development work in this field are discussed.
Juno‐UVS approach observations of Jupiter's auroras Gladstone, G. R.; Versteeg, M. H.; Greathouse, T. K. ...
Geophysical research letters,
16 August 2017, Letnik:
44, Številka:
15
Journal Article, Web Resource
Recenzirano
Odprti dostop
Juno ultraviolet spectrograph (UVS) observations of Jupiter's aurora obtained during approach are presented. Prior to the bow shock crossing on 24 June 2016, the Juno approach provided a rare ...opportunity to correlate local solar wind conditions with Jovian auroral emissions. Some of Jupiter's auroral emissions are expected to be controlled or modified by local solar wind conditions. Here we compare synoptic Juno‐UVS observations of Jupiter's auroral emissions, acquired during 3–29 June 2016, with in situ solar wind observations, and related Jupiter observations from Earth. Four large auroral brightening events are evident in the synoptic data, in which the total emitted auroral power increases by a factor of 3–4 for a few hours. Only one of these brightening events correlates well with large transient increases in solar wind ram pressure. The brightening events which are not associated with the solar wind generally have a risetime of ~2 h and a decay time of ~5 h.
Plain Language Summary
Juno ultraviolet spectrograph (UVS) observations of Jupiter's aurora obtained during approach are presented. Jupiter's auroras are thought to be controlled in part by the solar wind, a stream of charged particles flowing outward from the Sun. The Juno approach was a rare opportunity to compare solar wind conditions near Jupiter with the Jovian ultraviolet aurora, using observations made during June 2016. Although Jupiter's aurora is always present, four brightening events were seen in the data, in which the total auroral power increased to several times the typical level for a few hours. Only one of these brightening events appears well connected with solar wind activity. The brightening events which are not associated with the solar wind all increase in brightness in about 2 h and then dim back down again in about another 5 h.
Key Points
Jupiter's aurora and the solar wind have a complex relationship
The single solar wind structure that correlated with an auroral brightening event was a CIR
Auroral brightening events which are not related to solar wind conditions have a similar time evolution
Jupiter's polar auroral region hosts UV auroral emissions that relate to the magnetospheric dynamics from the outer magnetosphere. Juno‐UVS has discovered intriguing features characterized by ...expanding emission circles of UV‐brightness <140 kR. These events are located at the border of the previously defined swirl region, nearby the polar dark region. The features expand into a circular shape up to ∼1,000 km in radius, at expansion velocities from 3.3 ± 1.7 up to 7.7 ± 3.5 km/s, as measured over the four best observed cases. Using color ratio measurements as a proxy for the depth of the recorded features, the mean electron energy responsible for these emissions is 80–160 keV. Events occurring in the outer magnetosphere at distances >100 RJ are likely causing for these features. Dayside magnetopause reconnection and Kelvin‐Helmholtz instabilities resulting from the shear flows near the magnetopause are expected to generate field‐aligned currents that could potentially be the cause of these features.
Key Points
Juno‐UVS discovered expanding auroral emission circles with typical brightness up to 140 kR
The features are located in the auroral swirl region, magnetically mapping to the outer magnetosphere
Their origin would be consistent with dayside reconnection or signatures of Kelvin‐Helmholtz instabilities
Usual interstitial pneumonia (UIP) is the defining morphology of idiopathic pulmonary fibrosis (IPF). Guidelines for IPF diagnosis conditionally recommend surgical lung biopsy for histopathology ...diagnosis of UIP when radiology and clinical context are not definitive. A "molecular diagnosis of UIP" in transbronchial lung biopsy, the Envisia Genomic Classifier, accurately predicted histopathologic UIP.
We evaluated the combined accuracy of the Envisia Genomic Classifier and local radiology in the detection of UIP pattern.
Ninety-six patients who had diagnostic lung pathology as well as a transbronchial lung biopsy for molecular testing with Envisia Genomic Classifier were included in this analysis. The classifier results were scored against reference pathology. UIP identified on high-resolution computed tomography (HRCT) as documented by features in local radiologists' reports was compared with histopathology.
In 96 patients, the Envisia Classifier achieved a specificity of 92.1% (confidence interval CI,78.6-98.3%) and a sensitivity of 60.3% (CI, 46.6-73.0%) for histology-proven UIP pattern. Local radiologists identified UIP in 18 of 53 patients with UIP histopathology, with a sensitivity of 34.0% (CI, 21.5-48.3%) and a specificity of 96.9% (CI, 83.8-100%). In conjunction with HRCT patterns of UIP, the Envisia Classifier results identified 24 additional patients with UIP (sensitivity 79.2%; specificity 90.6%).
In 96 patients with suspected interstitial lung disease, the Envisia Genomic Classifier identified UIP regardless of HRCT pattern. These results suggest that recognition of a UIP pattern by the Envisia Genomic Classifier combined with HRCT and clinical factors in a multidisciplinary discussion may assist clinicians in making an interstitial lung disease (especially IPF) diagnosis without the need for a surgical lung biopsy.
Structure‐based design usually focuses upon the optimization of ligand affinity. However, successful drug design also requires the optimization of many other properties. The primary source of ...structural information for protein–ligand complexes is X‐ray crystallography. The uncertainties introduced during the derivation of an atomic model from the experimentally observed electron density data are not always appreciated. Uncertainties in the atomic model can have significant consequences when this model is subsequently used as the basis of manual design, docking, scoring, and virtual screening efforts. Docking and scoring algorithms are currently imperfect. A good correlation between observed and calculated binding affinities is usually only observed only when very large ranges of affinity are considered. Errors in the correlation often exceed the range of affinities commonly encountered during lead optimization. Some structure‐based design approaches now involve screening libraries by using technologies based on NMR spectroscopy and X‐ray crystallography to discover small polar templates, which are used for further optimization. Such compounds are defined as leadlike and are also sought by more traditional high‐throughput screening technologies. Structure‐based design and HTS technologies show important complementarity and a degree of convergence.
A main source of information on protein–ligand complexes is X‐ray crystallography. In the structure shown oleic acid (orange) is complexed to an IFABP mutant (green); the experimentally determined electron density is represented by a blue mesh. Uncertainties in the atomic model can have far‐reaching consequences when this model is subsequently used in manual design, docking, scoring, and virtual screening.
Malnutrition and sarcopenia commonly overlap and contribute to adverse health outcomes. Previously, chronic supplementation with two oral nutritional supplements (ONS), control (C
) and experimental ...ONS enriched with protein, vitamin D and β-hydroxy β-methylbutyrate (HMB) (E
), improved muscle strength and quality in malnourished sarcopenic older adults, with E
demonstrating early strength benefits at 12 weeks. To understand the underlying biological mechanisms contributing to the observed early strength benefits of E
, we examined serum biomarker changes in response to 12-week supplementation. Serum samples (E
(
= 90) and C
(
= 103)) collected at baseline and 12 weeks were analyzed. Biomarkers (
= 243) were measured using multiplexed immunoassay, commercial immunoassays and ELISAs. Sixty markers were excluded with levels below assay detection limits. Sixteen biomarkers significantly changed in response to both interventions including nutritional and metabolic markers. Thirteen biomarkers significantly changed in response to E
but not C
. Increases in immunoglobulins, myoglobin, total protein, vitamin E and magnesium were observed with E
. Inflammation-related ferritin and osteopontin decreased, while soluble receptors for cytokines increased, suggesting decreased inflammation. Sex hormone-binding globulin associated with sarcopenia also decreased with E
Biomarkers reflective of multiple biological systems were impacted by nutritional intervention in sarcopenic older adults. Incremental biomarker changes were observed in response to E
containing HMB that possibly link to improvements in skeletal muscle health.
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