The upper Miocene Deurne Member of the Diest Formation revisited : unexpected results from the study of a large temporary outcrop near Antwerp International Airport, Belgium

A 5.50 m thick interval of fossiliferous intensely bioturbated heterogenous glauconiferous sand of the upper Miocene Diest Formation is documented from a very large temporary outcrop just southeast of Antwerp International Airport (northern Belgium), allowing to observe lateral variations over several hundreds of meters and to collect many vertebrate and invertebrate fossils. This paper documents observations on lithology, sedimentary and post-sedimentary structures, and discusses the results of the multi-proxy analyses of the sediment (granulometry, glauconite content, clay mineralogy, Fe content and Fe3+/Fe2+ ratios), the interpretation of the trace fossil assemblage and the sedimentary structures as well as of the large-scale samplings of micro-, meso- and macrofossils. We evidence that the Diest Formation in the Antwerp area consists of two different lithological entities, and that this twofold character can be extrapolated to all previously recorded Deurne Member outcrops. A revised lithostratigraphic scheme for the Diest Formation in the Antwerp area is proposed, with the new Borsbeek member at the base and a redefmed Deurne Member at the top

What is the best way to fix a polyurethane meniscal scaffold?: a biomechanical evaluation of different fixation modes

Ingrowth of meniscal tissue into a meniscal scaffold can be optimized by securely fixing the scaffold into the meniscal remnants. The purpose of this research was to test and compare commonly used suture types and suture materials to fix a meniscal scaffold. Forty fresh porcine menisci were used. All tests used the same polyurethane-based scaffold. The load to failure of horizontal, vertical and diagonal sutures with PDS 0 and with Ethibond 0, and diagonal sutures with Ultra Fast-Fix(A (R)) and Sequent(A (R)) to fix a meniscal scaffold were tested. Five tests were conducted for each configuration. All constructs failed in the scaffold at a mean pullout force of 50.6 N (SD 12.7). Inferior results were noted for vertical sutures (40.1 N, SD 6.3) compared to horizontal (49.8 N, SD 5.5, p = 0.0007) and diagonal (51.7 N, SD 15.6, p = 0.024) sutures and for Ethibond 0 (41.4 N, SD 6.2) compared to PDS 0 (51.3 N, SD 12.9, p = 0.001). When comparing the diagonal suture placements, only Ethibond 0 (42.9 N, SD 5.4) showed significantly inferior results compared to PDS 0 (60.1 N, SD 16.9, p = 0.03), Ultra Fast-Fix(A (R)) (60.1 N, SD 9.3, p = 0.004) and Sequent(A (R)) (65.8 N, SD 4.4, p < 0.0001). The most common failure mode when fixing a polyurethane-based meniscal scaffold is suture pull-through of the scaffold in the distraction mode. This happens at a rather low pullout force and might preclude the use of this scaffold clinically. Vertical sutures and Ethibond 0 multifilament braided sutures fail at lower forces, and the tested commercial devices show promising results

Elastin fragmentation inatheroscleroticmice leads to intraplaque neovascularization, plaque rupture, myocardial infarction, stroke, and sudden death

AIMS: There is a need for animal models of plaque rupture. We previously reported that elastin fragmentation, due to a mutation (C1039G(+/−)) in the fibrillin-1 (Fbn1) gene, promotes atherogenesis and a highly unstable plaque phenotype in apolipoprotein E deficient (ApoE(−/−)) mice on a Western-type diet (WD). Here, we investigated whether plaque rupture occurred in ApoE(−/−)Fbn1(C1039G+/−) mice and was associated with myocardial infarction, stroke, and sudden death. METHODS AND RESULTS: Female ApoE(−/−)Fbn1(C1039G+/−) and ApoE(−/−) mice were fed a WD for up to 35 weeks. Compared to ApoE(−/−) mice, plaques of ApoE(−/−)Fbn1(C1039G+/−) mice showed a threefold increase in necrotic core size, augmented T-cell infiltration, a decreased collagen I content (70 ± 10%), extensive neovascularization, intraplaque haemorrhage, and a significant increase in matrix metalloproteinase-2, -9, -12, and -13 expression or activity. Plaque rupture was observed in 70% of ascending aortas and in 50% of brachiocephalic arteries of ApoE(−/−)Fbn1(C1039G+/−) mice. In ApoE(−/−) mice, plaque rupture was not seen in ascending aortas and only in 10% of brachiocephalic arteries. Seventy percent of ApoE(−/−)Fbn1(C1039G+/−) mice died suddenly, whereas all ApoE(−/−) mice survived. ApoE(−/−)Fbn1(C1039G+/−) mice showed coronary plaques and myocardial infarction (75% of mice). Furthermore, they displayed head tilt, disorientation, and motor disturbances (66% of cases), disturbed cerebral blood flow (73% of cases; MR angiograms) and brain hypoxia (64% of cases), indicative of stroke. CONCLUSIONS: Elastin fragmentation plays a key role in plaque destabilization and rupture. ApoE(−/−)Fbn1(C1039G+/−) mice represent a unique model of acute plaque rupture with human-like complications

Multiomics and spatial mapping characterizes human CD8 ⁺ T cell states in cancer

Clinically relevant immunological biomarkers that discriminate between diverse hypofunctional states of tumor-associated CD8+ T cells remain disputed. Using multiomics analysis of CD8+ T cell features across multiple patient cohorts and tumor types, we identified tumor niche–dependent exhausted and other types of hypofunctional CD8+ T cell states. CD8+ T cells in “supportive” niches, like melanoma or lung cancer, exhibited features of tumor reactivity–driven exhaustion (CD8+ TEX). These included a proficient effector memory phenotype, an expanded T cell receptor (TCR) repertoire linked to effector exhaustion signaling, and a cancer-relevant T cell–activating immunopeptidome composed of largely shared cancer antigens or neoantigens. In contrast, “nonsupportive” niches, like glioblastoma, were enriched for features of hypofunctionality distinct from canonical exhaustion. This included immature or insufficiently activated T cell states, high wound healing signatures, nonexpanded TCR repertoires linked to anti-inflammatory signaling, high T cell–recognizable self-epitopes, and an antiproliferative state linked to stress or prodeath responses. In situ spatial mapping of glioblastoma highlighted the prevalence of dysfunctional CD4+:CD8+ T cell interactions, whereas ex vivo single-cell secretome mapping of glioblastoma CD8+ T cells confirmed negligible effector functionality and a promyeloid, wound healing–like chemokine profile. Within immuno-oncology clinical trials, anti–programmed cell death protein 1 (PD-1) immunotherapy facilitated glioblastoma’s tolerogenic disparities, whereas dendritic cell (DC) vaccines partly corrected them. Accordingly, recipients of a DC vaccine for glioblastoma had high effector memory CD8+ T cells and evidence of antigen-specific immunity. Collectively, we provide an atlas for assessing different CD8+ T cell hypofunctional states in immunogenic versus nonimmunogenic cancers