Heterogeneity of glycan biomarker clusters as an indicator of recurrence in pancreatic cancer

IntroductionOutcomes following tumor resection vary dramatically among patients with pancreatic ductal adenocarcinoma (PDAC). A challenge in defining predictive biomarkers is to discern within the complex tumor tissue the specific subpopulations and relationships that drive recurrence. Multiplexed immunofluorescence is valuable for such studies when supplied with markers of relevant subpopulations and analysis methods to sort out the intra-tumor relationships that are informative of tumor behavior. We hypothesized that the glycan biomarkers CA19-9 and STRA, which detect separate subpopulations of cancer cells, define intra-tumoral features associated with recurrence.MethodsWe probed this question using automated signal thresholding and spatial cluster analysis applied to the immunofluorescence images of the STRA and CA19-9 glycan biomarkers in whole-block sections of PDAC tumors collected from curative resections.ResultsThe tumors (N = 22) displayed extreme diversity between them in the amounts of the glycans and in the levels of spatial clustering, but neither the amounts nor the clusters of the individual and combined glycans associated with recurrence. The combined glycans, however, marked divergent types of spatial clusters, alternatively only STRA, only CA19-9, or both. The co-occurrence of more than one cluster type within a tumor associated significantly with disease recurrence, in contrast to the independent occurrence of each type of cluster. In addition, intra-tumoral regions with heterogeneity in biomarker clusters spatially aligned with pathology-confirmed cancer cells, whereas regions with homogeneous biomarker clusters aligned with various non-cancer cells.ConclusionThus, the STRA and CA19-9 glycans are markers of distinct and co-occurring subpopulations of cancer cells that in combination are associated with recurrence. Furthermore, automated signal thresholding and spatial clustering provides a tool for quantifying intra-tumoral subpopulations that are informative of outcome

TOI-3785 b: A Low-Density Neptune Orbiting an M2-Dwarf Star

Using both ground-based transit photometry and high-precision radial velocity (RV) spectroscopy, we confirm the planetary nature of TOI-3785 b. This transiting Neptune orbits an M2-Dwarf star with a period of ~4.67 days, a planetary radius of 5.14 +/- 0.16 Earth Radii, a mass of 14.95 +4.10, -3.92 Earth Masses, and a density of 0.61 +0.18, -0.17 g/cm^3. TOI-3785 b belongs to a rare population of Neptunes (4 Earth Radii < Rp < 7 Earth Radii) orbiting cooler, smaller M-dwarf host stars, of which only ~10 have been confirmed. By increasing the number of confirmed planets, TOI-3785 b offers an opportunity to compare similar planets across varying planetary and stellar parameter spaces. Moreover, with a high transmission spectroscopy metric (TSM) of ~150 combined with a relatively cool equilibrium temperature of 582 +/- 16 K and an inactive host star, TOI-3785 b is one of the more promising low-density M-dwarf Neptune targets for atmospheric follow-up. Future investigation into atmospheric mass loss rates of TOI-3785 b may yield new insights into the atmospheric evolution of these low-mass gas planets around M-dwarfs.Comment: 22 pages, 6 figures, 6 tables, Submitted to A

TOI-5205b: A Jupiter transiting an M dwarf near the Convective Boundary

We present the discovery of TOI-5205b, a transiting Jovian planet orbiting a solar metallicity M4V star, which was discovered using TESS photometry and then confirmed using a combination of precise radial velocities, ground-based photometry, spectra and speckle imaging. The host star TOI-5205 sits near the eponymous `Jao gap', which is the transition region between partially and fully-convective M dwarfs. TOI-5205b has one of the highest mass ratio for M dwarf planets with a mass ratio of almost 0.3$\%$, as it orbits a host star that is just $0.392 \pm 0.015$ $M_{\odot}$. Its planetary radius is $1.03 \pm 0.03~R_J$, while the mass is $1.08 \pm 0.06~M_J$. Additionally, the large size of the planet orbiting a small star results in a transit depth of $\sim 7\%$, making it one of the deepest transits of a confirmed exoplanet orbiting a main-sequence star. The large transit depth makes TOI-5205b a compelling target to probe its atmospheric properties, as a means of tracing the potential formation pathways. While there have been radial velocity-only discoveries of giant planets around mid M dwarfs, this is the first transiting Jupiter with a mass measurement discovered around such a low-mass host star. The high mass of TOI-5205b stretches conventional theories of planet formation and disk scaling relations that cannot easily recreate the conditions required to form such planets.Comment: Submitted to ApJ. Comments are welcome. arXiv admin note: text overlap with arXiv:2203.0717

TOI-3984 A b and TOI-5293 A b: two temperate gas giants transiting mid-M dwarfs in wide binary systems

We confirm the planetary nature of two gas giants discovered by TESS to transit M dwarfs with stellar companions at wide separations. TOI-3984 A ($J=11.93$) is an M4 dwarf hosting a short-period ($4.353326 \pm 0.000005$ days) gas giant ($M_p=0.14\pm0.03~\mathrm{M_{J}}$ and $R_p=0.71\pm0.02~\mathrm{R_{J}}$) with a wide separation white dwarf companion. TOI-5293 A ($J=12.47$) is an M3 dwarf hosting a short-period ($2.930289 \pm 0.000004$ days) gas giant ($M_p=0.54\pm0.07~\mathrm{M_{J}}$ and $R_p=1.06\pm0.04~\mathrm{R_{J}}$) with a wide separation M dwarf companion. We characterize both systems using a combination of ground-based and space-based photometry, speckle imaging, and high-precision radial velocities from the Habitable-zone Planet Finder and NEID spectrographs. TOI-3984 A b ($T_{eq}=563\pm15$ K and $\mathrm{TSM}=138_{-27}^{+29}$) and TOI-5293 A b ($T_{eq}=675_{-30}^{+42}$ K and $\mathrm{TSM}=92\pm14$) are two of the coolest gas giants among the population of hot Jupiter-sized gas planets orbiting M dwarfs and are favorable targets for atmospheric characterization of temperate gas giants and three-dimensional obliquity measurements to probe system architecture and migration scenarios.Comment: Submitted to AJ, 42 pages, 14 figures. arXiv admin note: substantial text overlap with arXiv:2201.0996

The unusual M-dwarf Warm Jupiter TOI-1899~b: Refinement of orbital and planetary parameters

TOI-1899~b is a rare exoplanet, a temperate Warm Jupiter orbiting an M-dwarf, first discovered by \citet{Canas2020_toi1899} from a TESS single-transit event. Using new radial velocities (RVs) from the precision RV spectrographs HPF and NEID, along with additional TESS photometry and ground-based transit follow-up, we are able to derive a much more precise orbital period of $P = 29.090312_{-0.000035}^{+0.000036}$~d, along with a radius of $R_p = 0.99\pm0.03$~\unit{R_{J}}. We have also improved the constraints on planet mass, $M_p = 0.67\pm{0.04}$~\unit{M_{J}}, and eccentricity, which is consistent with a circular orbit at 2$\sigma$ ($e = 0.044_{-0.027}^{+0.029}$). TOI-1899~b occupies a unique region of parameter space as the coolest known ($T_{eq} \approx$ 380~K) Jovian-sized transiting planet around an M-dwarf; we show that it has great potential to provide clues regarding the formation and migration mechanisms of these rare gas giants through transmission spectroscopy with JWST as well as studies of tidal evolution.Comment: 19 pages, 7 figures, 3 tables, submitted to AJ (comments welcome

Association of blood lipids with Alzheimer's disease: A comprehensive lipidomics analysis

Introduction: The aim of this study was to (1) replicate previous associations between six blood lipids and Alzheimer’s disease (AD) (Proitsi et al 2015) and (2) identify novel associations between lipids, clinical AD diagnosis, disease progression and brain atrophy (left/right hippocampus/entorhinal cortex). Methods: We performed untargeted lipidomic analysis on 148 AD and 152 elderly control plasma samples and used univariate and multivariate analysis methods. Results: We replicated our previous lipids associations and reported novel associations between lipids molecules and all phenotypes. A combination of 24 molecules classified AD patients with .70% accuracy in a test and a validation data set, and we identified lipid signatures that predicted disease progression (R2 5 0.10, test data set) and brain atrophy (R2 0.14, all test data sets except left entorhinal cortex). We putatively identified a number of metabolic features including cholesteryl esters/triglycerides and phosphatidylcholines. Discussion: Blood lipids are promising AD biomarkers that may lead to new treatment strategies

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

An Introduction to Research Methods: Needs Assessment, Surveys, Focus Groups and Personas

Provides basic, introductory information about four research methods used in libraries. Prepared for the University of Pittsburgh's University Library System (ULS) Leadership Program