Prospektiv randomisierte, verblindete Studie zwischen Brotlaibhistologie und 3D-Histologie beim Basalzellkarzinom bis 30 mm Durchmesser mit besonderer Berücksichtigung der Rezidivrate

Das Basalzellkarzinom ist der häufigste, maligne Tumor des Menschen in den mitteleuropäischen Regionen und wird in der Inzidenz in Zukunft steigen. Vor allem UV-Exposition gilt als Risikofaktor, weswegen ein Auftreten in der UV-begünstigten H-Zone im Gesicht prädisponiert ist. Therapeutisch existieren mehrere Varianten, wovon die chirurgische Exzision mit lückenloser, histologischer Randschnittbeurteilung mit der größten Evidenz belegt ist. Allerdings gibt es bisher in der Literatur nur eine randomisierte Studie der Autoren Smeets, Mosterd und van Loo zum Vergleich dieser Methode zur konventionellen Brotlaibhistologie, die ebenfalls etabliert und wissenschaftlich anerkannt ist. In dieser großen, prospektiv-randomisierten und erstmals verblindeten Studie wurden 569 Basalzellkarzinome untersucht. Die histologische Begutachtung erfolgte entweder mittels 3D-Histologie oder per Brotlaibhistologie in Paraffineinbettung. Die Gruppen unterschieden sich statistisch weder im Alter der Patienten noch in Tumorlokalisation, Tumortyp, Tumor-Durchmesser oder des primären Sicherheitsabstands bei Entnahme. In der Brotlaib-Gruppe war in 21% der Fälle eine Re-OP notwendig, in der 3D-Gruppe sogar in mehr als 39%. Die Summe der Sicherheitsabstände der Exzision war in der 3D-Gruppe, entgegen der aktuellen Meinung der Literatur, größer als in der konventionellen Gruppe. Hierbei ist allerdings zu beachten, dass aufgrund der in der Literatur einmaligen Verblindung kein Unterschied der Exzisionsabstände bei der Primärexzision bestand. Rezidive traten im Durchschnitt von ca. 3,6 Jahren nach der Exzision auf, signifikant (p<0,013) häufiger in der Gruppe der Brotlaib-Histologie (24 vs. 10). Auch in der Kaplan-Meier-Kurve zeigte sich ein signifikanter Überlebensvorteil für den Arm der 3D-Histologie. Es bestand eine Tendenz zu häufigeren Rezidiven in der H-Zone und bei größeren Tumoren. Es konnte gezeigt werden, dass im Gegensatz zur genannten randomisierten Studie zu diesem Thema, in der Kryostatschnitte verwendet wurden, schon nach 4,5 Jahren Nachbeobachtung die Rezidivrate bei primären Basalzellkarzinomen mit der Anwendung der 3D-Histologie im Vergleich zur Brotlaibhistologie signifikant geringer ist

Phylogeography of the second plague pandemic revealed through analysis of historical Yersinia pestis genomes

The second plague pandemic, caused by Yersinia pestis, devastated Europe and the nearby regions between the 14th and 18th centuries AD. Here we analyse human remains from ten European archaeological sites spanning this period and reconstruct 34 ancient Y. pestis genomes. Our data support an initial entry of the bacterium through eastern Europe, the absence of genetic diversity during the Black Death, and low within-outbreak diversity thereafter. Analysis of post-Black Death genomes shows the diversification of a Y. pestis lineage into multiple genetically distinct clades that may have given rise to more than one disease reservoir in, or close to, Europe. In addition, we show the loss of a genomic region that includes virulence-related genes in strains associated with late stages of the pandemic. The deletion was also identified in genomes connected with the first plague pandemic (541–750 AD), suggesting a comparable evolutionary trajectory of Y. pestis during both events

Targeting immune checkpoints potentiates immunoediting and changes the dynamics of tumor evolution

The cancer immunoediting hypothesis assumes the immune system sculpts the cancer genome. Here the authors show, in a mouse model, that neutral evolution outweighs the effects of immunoselection and that immune checkpoint blockade potentiates the immunoediting, switching the system to non-neutral evolution

Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma

Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways