First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL)—a systematic review and individual patient data meta-analysis

Evidence for prognosis and treatment of elderly patient with primary central nervous system is limited. High-dose methotrexate should be applied whenever possible, especially combination with oral alkylating agents is a promising approach. Further combinations with other intravenous drugs do not seem to improve outcome. More prospective trials designed for elderly PCNSL patients are warrante

Application of REVEAL Lite 2 and COMPERA 2.0 risk scores to patients with pulmonary arterial hypertension switching to riociguat in the REPLACE study

\ua9 2024In Riociguat rEplacing PDE5i therapy evaLuated Against Continued PDE5i thErapy (REPLACE) (NCT02891850), improvements in risk status were observed in patients with pulmonary arterial hypertension (PAH) at intermediate risk switching to riociguat versus continuing phosphodiesterase-5 inhibitors (PDE5i). This post hoc study applied the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2 and Comparative Prospective Registry of Newly Initiated Therapies for Pulmonary (COMPERA) 2.0 risk-assessment tools to REPLACE to investigate the impact of baseline risk status on clinical improvement. The proportions of riociguat- and PDE5i-treated patients achieving the primary end-point at REVEAL Lite 2 low, intermediate, and high baseline risk reflected the overall population. Proportions of riociguat-treated patients achieving the primary end-point were comparable between the COMPERA 2.0 intermediate-low risk (39%) and intermediate-high risk (43%) groups. Our findings show that patients in REPLACE achieved clinical improvement by switching from PDE5i to riociguat across all COMPERA 2.0 and most REVEAL Lite 2 baseline risk strata

Warpfield population synthesis: The physics of (extra-)Galactic star formation and feedback-driven cloud structure and emission from sub-to-kpc scales

We present a novel method to model galactic-scale star formation and emission of star clusters and a multiphase interstellar medium (ISM). We combine global parameters, including star formation rate and metallicity, with the 1D cloud evolution code warpfield to model the sources of feedback within a star-forming galaxy. Within individual star-forming regions, we include stellar evolution, stellar winds, radiation pressure, and supernovae, all coupled to the dynamical evolution of the 1D parental cloud in a highly non-linear fashion. Heating of the diffuse galactic gas and dust is calculated self-consistently with the age-, mass-, and density-dependent escape fractions of photons from these fully resolved local star-forming regions. We construct the interstellar radiation field, and we employ the multifrequency radiative transfer code polaris to produce synthetic emission maps for a one-to-one comparison with observations. We apply this to a cosmological simulation of a Milky-Way-like galaxy built-up in a high-resolution MHD simulation of cosmic structure formation. From this, we produce the multiscale/phase distribution of ISM density and temperature and present a synthesized all-sky H α map. We use a multipole expansion to show that the resulting maps reproduce all observed statistical emission characteristics. Next, we predict [S iii] 9530 Å, a key emission line that will be observed in several large forthcoming surveys. It suffers less extinction than other lines and provides information about star formation in very dense environments that are otherwise observationally inaccessible optically. Finally, we explore the effects of differential extinction, and discuss the consequences for the interpretation of H α emission at different viewing angles by an extragalactic observer

Feedback in W49A diagnosed with radio recombination lines and models

We present images of radio recombination lines (RRLs) at wavelengths around 17 cm from the star-forming region W49A to determine the kinematics of ionized gas in the THOR survey (The H I/OH/Recombination line survey of the inner Milky Way) at an angular resolution of 16.′′8 x 13.′′8. The distribution of ionized gas appears to be affected by feedback processes from the star clusters in W49A. The velocity structure of the RRLs shows a complex behavior with respect to the molecular gas. We find a shell-like distribution of ionized gas as traced by RRL emission surrounding the central cluster of OB stars in W49A. We describe the evolution of the shell with the recent feedback model code WARPFIELD that includes the important physical processes and has previously been applied to the 30 Doradus region in the Large Magellanic Cloud. The cloud structure and dynamics of W49A are in agreement with a feedback-driven shell that is re-collapsing. The shell may have triggered star formation in other parts of W49A. We suggest that W49A is a potential candidate for star formation regulated by feedback-driven and re-collapsing shells.We would like to thank the referee for the detailed, helpful, and insightful comments, which considerably improved the paper. M.R.R. is a fellow of the International Max Planck Research School for Astronomy and Cosmic Physics (IMPRS) at the University of Heidelberg. H.B., M.R.R., Y.W., J.S. and J.C.M. acknowledge support from the European Research Council under the Horizon 2020 Framework Program via the ERC Consolidator Grant CSF-648505. M.R.R., D.R., H.B., E.W.P., S.C.O.G. and R.S.K. acknowledge support from the Deutsche Forschungsgemeinschaft (DFG) via Sonderforschungsbereich (SFB) 881 “The Milky Way System” (sub-projects B1, B2 and B8). S.C.O.G., E.W.P. and R.S.K. further acknowledge support from the DFG via Priority Program SPP 1573 “Physics of the Interstellar Medium” (grant numbers KL1358/18.1, KL 1358/19.2, and GL 668/2–1) and from the European Research Council via the ERC Advanced Grant STARLIGHT (project number 339177). The research was carried out in part at the Jet Propulsion Laboratory, which is operated forNASA by the California Institute of Technology. R.J.S. acknowledges support from an STFC Ernest Rutherford fellowship. S.E.R. acknowledges support from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement # 706390. F.B. acknowledges funding from the European Union’s Horizon 2020 research and innovation programme (grant agreement No 726384 – EMPIRE)

A reproduction of the Milky Way’s Faraday rotation measure map in galaxy simulations from global to local scales

Magnetic fields are of critical importance for our understanding of the origin and long-term evolution of the Milky Way. This is due to their decisive role in the dynamical evolution of the interstellar medium and their influence on the star-formation process1–3. Faraday rotation measures along many different sightlines across the Galaxy are a primary means to infer the magnetic field topology and strength from observations4–7. However, the interpretation of the data has been hampered by the failure of previous attempts to explain the observations in theoretical models and to synthesize a realistic multiscale all-sky rotation measures map8–10. We here utilize a cosmological magnetohydrodynamic simulation of the formation of the Milky Way, augment it with a new star-cluster population-synthesis model for a more realistic structure of the local interstellar medium11,12, and perform detailed polarized radiative transfer calculations on the resulting model13. This yields an accurate first-principles prediction of the Faraday sky as observed on Earth. The results reproduce the observations of the Galaxy not only on global scales but also on local scales of individual star-forming clouds. They also indicate that the Local Bubble14 containing our Sun dominates the rotation measures signal over large regions of the sky. Modern cosmological magnetohydrodynamic simulations of the Milky Way’s formation, combined with a plausible model for star formation, stellar feedback and the distribution of free electrons in the interstellar medium, explain the rotation measures observations remarkably well, and thus contribute to a better understanding of the origin of magnetic fields in our Galaxy

Claudin 7 expression and localization in the normal murine mammary gland and murine mammary tumors

INTRODUCTION: Claudins, membrane-associated tetraspanin proteins, are normally associated with the tight junctions of epithelial cells where they confer a variety of permeability properties to the transepithelial barrier. One member of this family, claudin 7, has been shown to be expressed in the human mammary epithelium and some breast tumors. To set the stage for functional experiments on this molecule, we examined the developmental expression and localization of claudin 7 in the murine mammary epithelium and in a selection of murine mammary tumors. METHOD: We used real-time polymerase chain reaction, in situ mRNA localization, and immunohistochemistry (IHC) to examine the expression and localization of claudin 7. Frozen sections were examined by digital confocal microscopy for colocalization with the tight-junction protein ZO1. RESULTS: Claudin 7 was expressed constitutively in the mammary epithelium at all developmental stages, and the ratio of its mRNA to that of keratin 19 was nearly constant through development. By IHC, claudin 7 was located in the basolateral part of the cell where it seemed to be localized to discrete vesicles. Scant colocalization with the tight-junction scaffolding protein ZO1 was observed. Similar results were obtained from IHC of the airway epithelium and some renal tubules; however, claudin 7 did partly colocalize with ZO1 in EPH4 cells, a normal murine mammary cell line, and in the epididymis. The molecule was localized in the cytoplasm of MMTV-neu and the transplantable murine tumor cell lines TM4, TM10, and TM40A, in which its ratio to cytokeratin was higher than in the normal mammary epithelium. CONCLUSION: Claudin 7 is expressed constitutively in the mammary epithelium at approximately equal levels throughout development as well as in the murine tumors examined. Although it is capable of localizing to tight junctions, in the epithelia of mammary gland, airway, and kidney it is mostly or entirely confined to punctate cytoplasmic structures, often near the basolateral surfaces of the cells and possibly associated with basolateral membranes. These observations suggest that claudin 7 might be involved in vesicle trafficking to the basolateral membrane, possibly stabilizing cytoplasmic vesicles or participating in cell–matrix interactions

Identification of claudin-4 as a marker highly overexpressed in both primary and metastatic prostate cancer

In the quest for markers of expression and progression for prostate cancer (PCa), the majority of studies have focussed on molecular data exclusively from primary tumours. Although expression in metastases is inferred, a lack of correlation with secondary tumours potentially limits their applicability diagnostically and therapeutically. Molecular targets were identified by examining expression profiles of prostate cell lines using cDNA microarrays. Those genes identified were verified on PCa cell lines and tumour samples from both primary and secondary tumours using real-time RT–PCR, western blotting and immunohistochemistry. Claudin-4, coding for an integral membrane cell-junction protein, was the most significantly (P<0.00001) upregulated marker in both primary and metastatic tumour specimens compared with benign prostatic hyperplasia at both RNA and protein levels. In primary tumours, claudin-4 was more highly expressed in lower grade (Gleason 6) lesions than in higher grade (Gleason ⩾7) cancers. Expression was prominent throughout metastases from a variety of secondary sites in fresh-frozen and formalin-fixed specimens from both androgen-intact and androgen-suppressed patients. As a result of its prominent expression in both primary and secondary PCas, together with its established role as a receptor for Clostridium perfringens enterotoxin, claudin-4 may be useful as a potential marker and therapeutic target for PCa metastases

Three-dimensional Huh7 cell culture system for the study of Hepatitis C virus infection

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens