Prognostic value of hepatocyte growth factor for muscle-invasive bladder cancer

Purpose The HGF/MET pathway is involved in cell motility, angiogenesis, proliferation, and cancer invasion. We assessed the clinical utility of plasma HGF level as a prognostic biomarker in patients with MIBC. Methods We retrospectively analyzed 565 patients with MIBC who underwent radical cystectomy. Logistic regression and Cox regression models were used, and predictive accuracies were estimated using the area under the curve and concordance index. To estimate the clinical utility of HGF, DCA and MCID were applied. Results Plasma HGF level was significantly higher in patients with advanced pathologic stage and LN metastasis (p = 0.01 and p < 0.001, respectively). Higher HGF levels were associated with an increased risk of harboring LN metastasis and non-organ-confined disease (OR1.21, 95%CI 1.12–1.32, p < 0.001, and OR1.35, 95%CI 1.23–1.48, p < 0.001, respectively) on multivariable analyses; the addition of HGF improved the predictive accuracies of a standard preoperative model (+ 7%, p < 0.001 and + 8%, p < 0.001, respectively). According to the DCA and MCID, half of the patients had a net benefit by including HGF, but the absolute magnitude remained limited. In pre- and postoperative predictive models, a higher HGF level was significant prognosticator of worse RFS, OS, and CSS; in the preoperative model, the addition of HGF improved accuracies by 6% and 5% for RFS and CSS, respectively. Conclusion Preoperative HGF identified MIBC patients who harbored features of clinically and biologically aggressive disease. Plasma HGF could serve, as part of a panel, as a biomarker to aid in preoperative treatment planning regarding intensity of treatment in patients with clinical MIBC.

SN 2015bq: A Luminous Type Ia Supernova with Early Flux Excess

We present optical and ultraviolet (UV) observations of a luminous type Ia supernova (SN Ia) SN 2015bq characterized by early flux excess. This SN reaches a B-band absolute magnitude at M B = −19.68 ± 0.41 mag and a peak bolometric luminosity at L = (1.75 ± 0.37) × 1043 erg s−1, with a relatively small post-maximum decline rate [Δm 15(B) = 0.82 ± 0.05 mag]. The flux excess observed in the light curves of SN 2015bq a few days after the explosion, especially seen in the UV bands, might be due to the radioactive decay of 56Ni mixed into the surface. The radiation from the decay of the surface 56Ni heats the outer layer of this SN. It produces blue U − B color followed by monotonically reddening in the early phase, dominated iron-group lines, and weak intermediate-mass element absorption features in the early spectra. The scenario of enhanced 56Ni in the surface is consistent with a large amount of 56Ni ( M 56 Ni = 0.97 ± 0.20 M ☉) synthesized during the explosion. The properties of SN 2015bq are found to locate between SN 1991T and SN 1999aa, suggesting the latter two subclasses of SNe Ia may have a common origin.

The relative strength of selection on modifiers of genetic architecture under migration load

Gene flow between populations adapting to differing local environmental conditions creates a "migration load" because individuals might disperse to habitats where their survival is low or because they might reproduce with locally maladapted individuals. The amount by which the mean relative population fitness is kept below one creates an opportunity for modifiers of the genetic architecture to spread due to selection. Prior work that separately considered modifiers changing dispersal or recombination rates, or altering dominance or epistasis, has typically focused on the direction of selection rather than its absolute magnitude. We here develop methods to determine the strength of selection on modifiers of the genetic architecture, including modifiers of the dispersal rate, after populations evolved local adaptation. We consider scenarios with up to five loci contributing to local adaptation and derive a matrix model for the deterministic spread of modifiers. We find that selection for modifiers of epistasis and dominance is stronger than selection for decreased recombination, and that selection for partial reductions in recombination are extremely weak, regardless of the number of loci contributing to local adaptation. The spread of modifiers for a reduction in dispersal depends on the number of loci, pre-existing epistasis and extent of migration load. We identify a novel effect, that modifiers of dominance are more strongly selected when they are unlinked to the locus that they modify. Overall, these results help explain population differentiation and reproductive isolation and provide a benchmark to compare selection on genetic architecture modifiers in finite population sizes and under demographic stochasticity.

Detection of a Cross-correlation between Cosmic Microwave Background Lensing and Low-density Points

Low-density points (LDPs), obtained by removing high-density regions of observed galaxies, can trace the large-scale structures (LSSs) of the universe. In particular, it offers an intriguing opportunity to detect weak gravitational lensing from low-density regions. In this work, we investigate the tomographic cross-correlation between Planck cosmic microwave background (CMB) lensing maps and LDP-traced LSSs, where LDPs are constructed from the DR8 data release of the DESI legacy imaging survey, with about 106–107 galaxies. We find that, due to the large sky coverage (20,000 deg2) and large redshift depth (z ≤ 1.2), a significant detection (10σ–30σ) of the CMB lensing–LDP cross-correlation in all six redshift bins can be achieved, with a total significance of ∼53σ over ℓ ≤ 1024. Moreover, the measurements are in good agreement with a theoretical template constructed from our numerical simulation in the WMAP 9 yr ΛCDM cosmology. A scaling factor for the lensing amplitude A lens is constrained to A lens = 1 ± 0.12 for z < 0.2, A lens = 1.07 ± 0.07 for 0.2 < z < 0.4, and A lens = 1.07 ± 0.05 for 0.4 < z < 0.6, with the r-band absolute magnitude cut of −21.5 for LDP selection. A variety of tests have been performed to check the detection reliability against variations in LDP samples and galaxy magnitude cuts, masks, CMB lensing maps, multipole ℓ cuts, sky regions, and photo-z bias. We also perform a cross-correlation measurement between CMB lensing and galaxy number density, which is consistent with the CMB lensing–LDP cross-correlation. This work therefore further convincingly demonstrates that LDP is a competitive tracer of LSS.

The Gravity Collective: A Search for the Electromagnetic Counterpart to the Neutron Star–Black Hole Merger GW190814

We present optical follow-up imaging obtained with the Katzman Automatic Imaging Telescope, Las Cumbres Observatory Global Telescope Network, Nickel Telescope, Swope Telescope, and Thacher Telescope of the LIGO/Virgo gravitational wave (GW) signal from the neutron star–black hole (NSBH) merger GW190814. We searched the GW190814 localization region (19 deg2 for the 90th percentile best localization), covering a total of 51 deg2 and 94.6% of the two-dimensional localization region. Analyzing the properties of 189 transients that we consider as candidate counterparts to the NSBH merger, including their localizations, discovery times from merger, optical spectra, likely host galaxy redshifts, and photometric evolution, we conclude that none of these objects are likely to be associated with GW190814. Based on this finding, we consider the likely optical properties of an electromagnetic counterpart to GW190814, including possible kilonovae and short gamma-ray burst afterglows. Using the joint limits from our follow-up imaging, we conclude that a counterpart with an r-band decline rate of 0.68 mag day−1, similar to the kilonova AT 2017gfo, could peak at an absolute magnitude of at most −17.8 mag (50% confidence). Our data are not constraining for “red” kilonovae and rule out “blue” kilonovae with M > 0.5 M ⊙ (30% confidence). We strongly rule out all known types of short gamma-ray burst afterglows with viewing angles <17° assuming an initial jet opening angle of ∼5.°2 and explosion energies and circumburst densities similar to afterglows explored in the literature. Finally, we explore the possibility that GW190814 merged in the disk of an active galactic nucleus, of which we find four in the localization region, but we do not find any candidate counterparts among these sources.

3D Parameter Maps of Red Clump Stars in the Milky Way: Absolute Magnitudes and Intrinsic Colors

Red clump stars (RCs) are useful tracers of distances, extinction, chemical abundances, and Galactic structures and kinematics. Accurate estimation of RC parameters—absolute magnitude and intrinsic color—is the basis for obtaining high-precision RC distances. By combining astrometric data from Gaia; spectroscopic data from APOGEE and LAMOST; and multiband photometric data from Gaia, APASS, Pan-STARRS1, 2MASS, and WISE surveys, we use a Gaussian process regression to train machine learners to derive the multiband absolute magnitudes M λ and intrinsic colors ( λ 1 − λ 2 ) 0 for each spectral RC. The dependence of M λ on metallicity decreases from optical to infrared bands, while the dependence of M λ on age is relatively similar in each band. ( λ 1 − λ 2 ) 0 are more affected by metallicity than age. The RC parameters are not suitable to be represented by simple constants but are related to the Galactic stellar population structure. By analyzing the variation of M λ and ( λ 1 − λ 2 ) 0 in the spatial distribution, we construct (R, z) dependent maps of mean absolute magnitudes and mean intrinsic colors of the Galactic RCs. Through external and internal validation, we find that using three-dimensional (3D) parameter maps to determine RC parameters avoids systematic bias and reduces dispersion by about 20% compared to using constant parameters. Based on Gaia's EDR3 parallax, our 3D parameter maps, and extinction–distance profile selection, we obtain a photometric RC sample containing 11 million stars with distance and extinction measurements.

Sex differences in power decrement identified across the lifespan

Muscular power has been shown to be a significant predictor of physical function in older adults, but assessments of power have traditionally been performed in movements not specific to activities of daily living (ADLs). Recent research examined power in the context of ADL-specific movements, but it is unclear how ADL-specific lower-body power differs over lifespan in males and females. This investigation sought to describe ADL-specific power decline across the lifespan and analyze differences between the sexes. Adults (n = 557) aged 18-89 volunteered and were divided into age cohorts (18-30, 50-59, 60-69, 70-79, and 80-89 years). Participants performed a sit-to-stand (STS) task with as much velocity as possible while connected to a linear position transducer (LPT). The LPT calculated average and peak power. The average result of 5 individual STS trials was analyzed for each of the power variables. The first significant decrement in average STS power (p &lt; .01) was observed at an earlier age cohort in males than females (60-69 in males vs. 70-79 in females). The per decade magnitude of power decrement after age 60 was larger in males than females in both absolute magnitude and percent decrease (11.74 vs. 10.09% decrease per decade). As power and physical function are correlated, this may have implications for the rate and age of functional decline in males. Additionally, understanding the differences in ADL-specific power decline between males and females gives clinicians and health professionals valuable information for developing preventative fitness paradigms specific to members of a given sex.

A Comprehensive Comparison of Period Extraction Algorithms for Asteroids with Long Term Observation

The light curve period of an asteroid plays an important role in determining the rotation period, the collision evolution and the YORP effect. There are many period extraction algorithms used to find the light curve period of asteroids with long term observation, which are mainly based on the frequency, time and time–frequency domains. This paper presents a comprehensive and unparalleled comparison of the popular algorithms based on the DAMIT (Database of Asteroid Models from Inversion Techniques) data set to show the statistical results. Considering the quoted period, absolute magnitude, diameter, albedo, time span and number of observations, we analyze the accuracy of five popular methods using the light curve data of 2902 asteroids. We find that although the performance of all the algorithms varies little, Phase Dispersion Minimization (PDM) performs better, followed by Lomb-Scargle (LS), while Conditional Entropy (CE) is not better than the others under certain conditions. We also analyze the cases which are more suitable for searching by frequencies or by periods.

Physical Characterization of Main-belt Comet (248370) 2005 QN173

We report results from new and archival observations of the newly discovered active asteroid (248370) 2005 QN173 (also now designated Comet 433P), which has been determined to be a likely main-belt comet based on a subsequent discovery that it is recurrently active near perihelion. From archival data analysis, we estimate g ′ -, r ′ -, i ′ -, and z ′ -band absolute magnitudes for the nucleus of H g = 16.62 ± 0.13, H r = 16.12 ± 0.10, H i = 16.05 ± 0.11, and H z = 15.93 ± 0.08, corresponding to nucleus colors of g ′ − r ′ = 0.50 ± 0.16 , r ′ − i ′ = 0.07 ± 0.15 , and i ′ − z ′ = 0.12 ± 0.14 ; an equivalent V-band absolute magnitude of H V = 16.32 ± 0.08; and a nucleus radius of r n = 1.6 ± 0.2 km (using a V-band albedo of p V = 0.054 ± 0.012). Meanwhile, we find mean near-nucleus coma colors when 248370 is active of g ′ − r ′ = 0.47 ± 0.03 , r ′ − i ′ = 0.10 ± 0.04 , and i ′ − z ′ = 0.05 ± 0.05 and similar mean dust tail colors, suggesting that no significant gas coma is present. We find approximate ratios between the scattering cross sections of near-nucleus dust (within 5000 km of the nucleus) and the nucleus of A d /A n = 0.7 ± 0.3 on 2016 July 22 and 1.8 < A d /A n < 2.9 in 2021 July and August. During the 2021 observation period, the coma declined in intrinsic brightness by ∼0.35 mag (or ∼25%) in 37 days, while the surface brightness of the dust tail remained effectively constant over the same period. Constraints derived from the sunward extent of the coma and width of the tail as measured perpendicular to the orbit plane suggest that the terminal velocities of ejected dust grains are extremely slow (∼1 m s−1 for 1 μm particles), suggesting that the observed dust emission may be aided by rapid rotation of the nucleus lowering the effective escape velocity.

Prognostic Value of Hepatocyte Growth Factor for Muscle-invasive Bladder Cancer

PurposeThe HGF/MET pathway is involved in cell motility, angiogenesis, proliferation, and cancer invasion. We assessed the clinical utility of plasma HGF level as a prognostic biomarker in patients with MIBC.MethodsWe retrospectively analyzed 565 patients with MIBC who underwent radical cystectomy. Logistic regression and Cox regression models were used, and predictive accuracies were estimated using the area under the curve and concordance index. To estimate the clinical utility of HGF, DCA and MCID were applied.ResultsPlasma HGF level was significantly higher in patients with advanced pathologic stage and LN metastasis (p=0.01 and p<0.001, respectively). Higher HGF levels were associated with an increased risk of harboring LN metastasis and non-organ-confined disease (OR1.21, 95%CI 1.12-1.32, p<0.001, and OR1.35, 95%CI 1.23-1.48, p<0.001, respectively) on multivariable analyses; the addition of HGF improved the predictive accuracies of a standard preoperative model (+7%, p<0.001 and +8%, p<0.001, respectively). According to the DCA and MCID, half of the patients had a net benefit by including HGF, but the absolute magnitude remained limited. In pre- and postoperative predictive models, a higher HGF level was significant prognosticator of worse RFS, OS, and CSS; in the preoperative model, the addition of HGF improved accuracies by 6% and 5% for RFS and CSS, respectively.ConclusionPreoperative HGF identified MIBC patients who harbored features of clinically and biologically aggressive disease. Plasma HGF could serve, as part of a panel, as a biomarker to aid in preoperative treatment planning regarding intensity of treatment in patients with clinically MIBC.