The single cell transcriptional landscape of esophageal adenocarcinoma and its modulation by neoadjuvant chemotherapy

Immune checkpoint blockade has recently proven effective in subsets of patients with esophageal adenocarcinoma (EAC) but little is known regarding the EAC immune microenvironment. We determined the single cell transcriptional profile of EAC in 8 patients who were treatment-naive (n = 4) or had received neoadjuvant chemotherapy (n = 4). Analysis of 52,387 cells revealed 10 major cell subsets of tumor, immune and stromal cells. Prior to chemotherapy tumors were heavy infiltrated by T regulatory cells and exhausted effector T cells whilst plasmacytoid dendritic cells were markedly expanded. Two dominant cancer-associated fibroblast populations were also observed whilst endothelial populations were suppressed. Pathological remission following chemotherapy associated with broad reversal of immune abnormalities together with fibroblast transition and an increase in endothelial cells whilst a chemoresistant epithelial stem cell population correlated with poor response. These findings reveal features that underlie and limit the response to current immunotherapy and identify a range of novel opportunities for targeted therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12943-022-01666-x

Definitive chemoradiotherapy versus neoadjuvant chemoradiotherapy followed by radical surgery for locally advanced oesophageal squamous cell carcinoma:meta-analysis

Background: The literature lacks robust evidence comparing definitive chemoradiotherapy (dCRT) with neoadjuvant chemoradiotherapy and surgery (nCRS) for oesophageal squamous cell carcinoma (ESCC). This study aimed to compare long-term survival of these approaches in patients with ESCC.Methods: A systematic review performed according to PRISMA guidelines included studies identified from PubMed, Scopus, and Cochrane CENTRAL databases up to July 2021 comparing outcomes between dCRT and nCRS for ESCC. The main outcome measure was overall survival (OS), secondary outcome was disease-free survival (DFS). A meta-analysis was conducted using random-effects modelling to determine pooled adjusted multivariable hazard ratios (HRs).Results: Ten studies including 14 092 patients were included, of which 30 per cent received nCRS. Three studies were randomized clinical trials (RCTs) and the remainder were retrospective cohort studies. dCRT and nCRS regimens were reported in six studies and surgical quality control was reported in two studies. Outcomes for OS and DFS were reported in eight and three studies respectively. Following meta-analysis, nCRS demonstrated significantly longer OS (HR 0.68, 95 per cent c.i. 0.54 to 0.87, P < 0.001) and DFS (HR 0.50, 95 per cent c.i. 0.36 to 0.70, P < 0.001) compared with dCRT.Conclusion: Neoadjuvant chemoradiotherapy followed by oesophagectomy correlated with improved survival compared with definitive chemoradiation in the treatment of ESCC; however, there is a lack of literature on RCTs

Interfacial tension and nucleation in mixtures of colloids and long ideal polymer coils

Mixtures of ideal polymers with hard spheres whose diameters are smaller than the radius of gyration of the polymer, exhibit extensive immiscibility. The interfacial tension between demixed phases of these mixtures is estimated, as is the barrier to nucleation. The barrier is found to scale linearly with the radius of the polymer, causing it to become large for large polymers. Thus for large polymers nucleation is suppressed and phase separation proceeds via spinodal decomposition, as it does in polymer blends.Comment: 4 pages (v2 includes discussion of the scaling of the interfacial tension along the coexistence curve and its relation to the Ginzburg criterion

Essentially English : Sherlock Holmes at the BBC

Sir Arthur Conan Doyle’s Sherlock Holmes stories, currently enjoying renewed popularity on television via the BBC’s Sherlock (2010- ), have been adapted for the screen countless times around the world. Arguably best remembered are Granada’s long-running strand with Jeremy Brett (1984-94), and the Universal film series of the 1940s, featuring Basil Rathbone and Nigel Bruce. Less frequently cited, however, are the two series produced by the BBC between 1965 and 1968, in which first Douglas Wilmer and later Peter Cushing took on the mantle of the Baker Street detective. Typically for the time – but against the wishes of the Conan Doyle estate - these programmes adopted a multi-camera studio model; a mode of production which made them less attractive to US networks than the single camera 35mm film output of commercial rivals such as ITC. Drawing upon material from the BBC’s Written Archives Centre, this article investigates the motivations underpinning the Corporation’s refusal to accommodate the estate’s exhortations to seek American co-production and utilise single camera filming, not least of which was the BBC’s stated desire to maintain the ‘essentially English’ quality of Sherlock Holmes. This decision would have significant repercussions for the series’ overseas saleability, and – despite impressive viewing figures and positive audience reaction at home in the UK – helped contribute to its ‘forgotten’ status with regard to the television canon

Hubble Space Telescope Observations of the Draco Dwarf Spheroidal

We present an F606W-F814W color-magnitude diagram for the Draco dwarf spheroidal galaxy based on Hubble Space Telescope WFPC2 images. The luminosity function is well-sampled to 3 magnitudes below the turn-off. We see no evidence for multiple turnoffs and conclude that, at least over the field of the view of the WFPC2, star formation was primarily single-epoch. If the observed number of blue stragglers is due to extended star formation, then roughly 6% (upper limit) of the stars could be half as old as the bulk of the galaxy. The color difference between the red giant branch and the turnoff is consistent with an old population and is very similar to that observed in the old, metal-poor Galactic globular clusters M68 and M92. Despite its red horizontal branch, Draco appears to be older than M68 and M92 by 1.6 +/- 2.5 Gyrs, lending support to the argument that the ``second parameter'' which governs horizontal branch morphology must be something other than age. Draco's observed luminosity function is very similar to that of M68, and the derived initial mass function is consistent with that of the solar neighborhood.Comment: 16 pages, AASTeX, 9 postscript figures, figures 1 and 2 available at ftp://bb3.jpl.nasa.gov/pub/draco/. Accepted for publication in the Astronomical Journa

WFPC2 Observations of the Cooling Flow Elliptical in Abell 1795

We present WFPC2 images of the core of the cooling flow cD galaxy in Abell 1795. An irregular, asymmetric dust lane extends 7 \h75 kpc in projection to the north-northwest. The dust shares the morphology observed in the H$\alpha$ and excess UV emission. We see both diffuse and knotty blue emission around the dust lane, especially at the ends. The dust and emission features lie on the edge of the radio lobes, suggesting star formation induced by the radio source or the deflection of the radio jets off of pre-existing dust and gas. We measure an apparent R$_V$ significantly less than 3.1, implying that the extinction law is not Galactic in the dust lane, or the presence of line emission which is proportional to the extinction. The dust mass is at least 2$\times10^{5} h_{75}^{-2}$ M\solar\ and is more likely to be 6.5$\times10^{5} h_{75}^{-2}$ M\solar.Comment: 14 pages, LaTeX, Figure 4 included, Postscript Figs. 1-3 available at ftp://astro.nmsu.edu/pub/JASON/A1795/, accepted for publication in ApJ Letter

On the elastic constants of the zeolite chlorosodalite

The use of force-field based molecular modeling to predict the elastic constants of the zeolite chlorosodalite is described. Theoretical predictions of the on-axis and off-axis elastic constants strongly suggest that an error exists in the published elastic constants of the material. When the previous experimental data are corrected by transposing the published directional ultrasound velocities, excellent agreement is observed between the off-axis plots of sodalite produced by experiment and modeling. Further confirmation of the prediction is supplied by considering the Zener ratios of other inorganic materials that possess cubic symmetry. ©2006 American Institute of Physics

Tree-mycorrhizal associations detected remotely from canopy spectral properties

A central challenge in global ecology is the identification of key functional processes in ecosystems that scale, but do not require, data for individual species across landscapes. Given that nearly all tree species form symbiotic relationships with one of two types of mycorrhizal fungi – arbuscular mycorrhizal (AM) and ectomycorrhizal (ECM) fungi – and that AM- and ECM-dominated forests often have distinct nutrient economies, the detection and mapping of mycorrhizae over large areas could provide valuable insights about fundamental ecosystem processes such as nutrient cycling, species interactions, and overall forest productivity. We explored remotely sensed tree canopy spectral properties to detect underlying mycorrhizal association across a gradient of AM- and ECM-dominated forest plots. Statistical mining of reflectance and reflectance derivatives across moderate/high-resolution Landsat data revealed distinctly unique phenological signals that differentiated AM and ECM associations. This approach was trained and validated against measurements of tree species and mycorrhizal association across ~130 000 trees throughout the temperate United States. We were able to predict 77% of the variation in mycorrhizal association distribution within the forest plots (P \u3c 0.001). The implications for this work move us toward mapping mycorrhizal association globally and advancing our understanding of biogeochemical cycling and other ecosystem processes