Novel biomarkers for risk stratification of Barrett's oesophagus associated neoplastic progression-epithelial HMGB1 expression and stromal lymphocytic phenotype

The preparation of this paper was funded in part by the Pathological Society of Great Britain and Ireland (intercalated degree educational studentship to R.J.P.). All data is published within this paper and within accompanying supporting files (indicated in text) and accessed via weblink on the journal site.Peer reviewedPublisher PD

Optical properties and spatial distribution of MgII absorbers from SDSS image stacking

We present a statistical analysis of the photometric properties and spatial distribution of more than 2,800 MgII absorbers with 0.37<z<1 and rest equivalent width W_0(\lambda2796)>0.8\AA detected in SDSS quasar spectra. Using an improved image stacking technique, we measure the cross-correlation between MgII gas and light (in the g, r, i and z-bands) from 10 to 200 kpc and infer the light-weighted impact parameter distribution of MgII absorbers. Such a quantity is well described by a power-law with an index that strongly depends on W_0, ranging from ~-1 for W_0~ 1.5\AA. At redshift 0.37<z<0.55, we find the average luminosity enclosed within 100 kpc around MgII absorbers to be M_g=-20.65+-0.11 mag, which is ~0.5 L_g*. The global luminosity-weighted colors are typical of present-day intermediate type galaxies. However, while the light of weaker absorbers originates mostly from red passive galaxies, stronger systems display the colors of blue star-forming galaxies. Based on these observations, we argue that the origin of strong MgII absorber systems might be better explained by models of metal-enriched gas outflows from star-forming/bursting galaxies. Our analysis does not show any redshift dependence for both impact parameter and rest-frame colors up to z=1. However, we do observe a brightening of the absorbers related light at high redshift (~50% from z~0.4 to 1). We argue that MgII absorbers are a phenomenon typical of a given evolutionary phase that more massive galaxies experience earlier than less massive ones, in a downsizing fashion. (abridged)Comment: ApJ in press, 28 pages, 16 figures, using emulateapj. Only typo corrections wrt the original submission (v1

Interleukin-27 regulates the function of the gastrointestinal epithelial barrier in a human tissue derived organoid model

Funding: This research was funded by CICRA (CICRA: better lives for children with crohns and colitis. Available online: https://www.cicra.org (last accessed on 23 January 2022); Ph.D. studentship to DBP) and an NHS Grampian Endowment project grant. Acknowledgments: We wish to acknowledge the Grampian Tissue Biorepository for assistance in tissue preparation. Organoids were stored at −80 ◦C at the University of Aberdeen. Graphical abstract was created using Biorender with a licence for use in publication (agreement number AD22YOD1N6). DBP now at Lydia Becker Institute of Immunology and Inflammation and Wellcome Centre for Cell-Matrix Research, University of Manchester, UKPeer reviewedPublisher PD

Subcellular Epithelial HMGB1 Expression Is Associated with Colorectal Neoplastic Progression, Male Sex, Mismatch Repair Protein Expression, Lymph Node Positivity, and an ‘Immune Cold’ Phenotype Associated with Poor Survival

Acknowledgments: The authors would like to thank NHS Grampian Biorepository, in particular Joan Wilson, Victoria Morrison, Kristine Nellany, and Nadine Hay, for their assistance in preparing tissue for this project. The authors also thank Tasneem O Atezia and Christina A Christopoulou for their contribution to this project during their time in the McLean laboratory. The laboratory work was instigated when M.H.M., R.J.P. and D.P.B. were based at the Institute of Medical Sciences, University of Aberdeen. Funding This work was funded by project grants from NHS Grampian Endowments and Friends of Anchor (https://www.friendsofanchor.org, charity no. SC025332). Within the McLean laboratory at the University of Aberdeen, SH received a Medical Research Scotland Summer Studentship, and AH received an Aberdeen Summer Research Studentship (University of Aberdeen).Peer reviewedPublisher PD

Multiomics modeling of the immunome, transcriptome, microbiome, proteome and metabolome adaptations during human pregnancy.

MotivationMultiple biological clocks govern a healthy pregnancy. These biological mechanisms produce immunologic, metabolomic, proteomic, genomic and microbiomic adaptations during the course of pregnancy. Modeling the chronology of these adaptations during full-term pregnancy provides the frameworks for future studies examining deviations implicated in pregnancy-related pathologies including preterm birth and preeclampsia.ResultsWe performed a multiomics analysis of 51 samples from 17 pregnant women, delivering at term. The datasets included measurements from the immunome, transcriptome, microbiome, proteome and metabolome of samples obtained simultaneously from the same patients. Multivariate predictive modeling using the Elastic Net (EN) algorithm was used to measure the ability of each dataset to predict gestational age. Using stacked generalization, these datasets were combined into a single model. This model not only significantly increased predictive power by combining all datasets, but also revealed novel interactions between different biological modalities. Future work includes expansion of the cohort to preterm-enriched populations and in vivo analysis of immune-modulating interventions based on the mechanisms identified.Availability and implementationDatasets and scripts for reproduction of results are available through: https://nalab.stanford.edu/multiomics-pregnancy/.Supplementary informationSupplementary data are available at Bioinformatics online

Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma

Hodgkin, 9p24Purpose Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1-blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods KEYNOTE-087 ( ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation. Patients received pembrolizumab 200 mg once every 3 weeks. Response was assessed every 12 weeks. The primary end points were ORR by central review and safety. Results A total of 210 patients were enrolled and treated (69 in cohort 1, 81 in cohort 2, and 60 in cohort 3). At the time of analysis, patients received a median of 13 treatment cycles. Per central review, the ORR was 69.0% (95% CI, 62.3% to 75.2%), and the complete response rate was 22.4% (95% CI, 16.9% to 28.6%). By cohort, ORRs were 73.9% for cohort 1, 64.2% for cohort 2, and 70.0% for cohort 3. Thirty-one patients had a response 65 6 months. The safety profile was largely consistent with previous pembrolizumab studies. Conclusion Pembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease

Exploring the atmospheric dynamics of the extreme ultra-hot Jupiter KELT-9b using TESS photometry

We carry out a phase-curve analysis of the KELT-9 system using photometric observations from NASA's Transiting Exoplanet Survey Satellite (TESS). The measured secondary eclipse depth and peak-to-peak atmospheric brightness modulation are $650^{+14}_{-15}$ ppm and $566\pm16$ ppm, respectively. The planet's brightness variation reaches maximum $31\pm5$ minutes before the midpoint of the secondary eclipse, indicating a $5\overset{\circ}{.}2\pm0\overset{\circ}{.}9$ eastward shift in the dayside hot spot from the substellar point. We also detect stellar pulsations on KELT-9 with a period of $7.58695\pm0.00091$ hours. The dayside emission of KELT-9b in the TESS bandpass is consistent with a blackbody brightness temperature of $4600\pm100$ K. The corresponding nightside brightness temperature is $3040\pm100$ K, comparable to the dayside temperatures of the hottest known exoplanets. In addition, we detect a significant phase-curve signal at the first harmonic of the orbital frequency and a marginal signal at the second harmonic. While the amplitude of the first harmonic component is consistent with the predicted ellipsoidal distortion modulation assuming equilibrium tides, the phase of this photometric variation is shifted relative to the expectation. Placing KELT-9b in the context of other exoplanets with phase-curve observations, we find that the elevated nightside temperature and relatively low day-night temperature contrast agree with the predictions of atmospheric models that include H$_{2}$ dissociation and recombination. The nightside temperature of KELT-9b implies an atmospheric composition containing about 50% molecular and 50% atomic hydrogen at 0.1 bar, a nightside emission spectrum that deviates significantly from a blackbody, and a 0.5-2.0 $\mu$m transmission spectrum that is featureless at low resolution.Comment: Published in AJ, updated with proof corrections. 17 pages, 8 figure

Exploring the Atmospheric Dynamics of the Extreme Ultrahot Jupiter KELT-9b Using TESS Photometry

We carry out a phase-curve analysis of the KELT-9 system using photometric observations from NASA's Transiting Exoplanet Survey Satellite (TESS). The measured secondary eclipse depth and peak-to-peak atmospheric brightness modulation are 650⁺¹⁴₋₁₅ and 566 ± 16 ppm, respectively. The planet's brightness variation reaches maximum 31 ± 5 minutes before the midpoint of the secondary eclipse, indicating a 5.°2 ± 0.°9 eastward shift in the dayside hot spot from the substellar point. We also detect stellar pulsations on KELT-9 with a period of 7.58695 ± 0.00091 hr. The dayside emission of KELT-9b in the TESS bandpass is consistent with a blackbody brightness temperature of 4600 ± 100 K. The corresponding nightside brightness temperature is 3040 ± 100 K, comparable to the dayside temperatures of the hottest known exoplanets. In addition, we detect a significant phase-curve signal at the first harmonic of the orbital frequency and a marginal signal at the second harmonic. While the amplitude of the first harmonic component is consistent with the predicted ellipsoidal distortion modulation assuming equilibrium tides, the phase of this photometric variation is shifted relative to the expectation. Placing KELT-9b in the context of other exoplanets with phase-curve observations, we find that the elevated nightside temperature and relatively low day–night temperature contrast agree with the predictions of atmospheric models that include H₂ dissociation and recombination. The nightside temperature of KELT-9b implies an atmospheric composition containing about 50% molecular and 50% atomic hydrogen at 0.1 bar, a nightside emission spectrum that deviates significantly from a blackbody, and a 0.5–2.0 μm transmission spectrum that is featureless at low resolution