Phylogeny and paleobiogeography of the enigmatic North American primate Ekgmowechashala illuminated by new fossils from Nebraska (USA) and Guangxi Zhuang Autonomous Region (China).

Ekgmowechashala is a poorly documented but very distinctive primate known only from the late early Oligocene (early Arikareean) of western North America. Because of its highly autapomorphous dentition and spatiotemporal isolation, the phylogenetic and biogeographic affinities of Ekgmowechashala have long been debated. Here, we describe the oldest known fossils of Ekgmowechashala from the Brown Siltstone Beds of the Brule Formation, White River Group of western Nebraska. We also describe a new ekgmowechashaline taxon from the Nadu Formation (late Eocene) in the Baise Basin of Guangxi Zhuang Autonomous Region in southern China. Phylogenetic analysis suggests that North American Ekgmowechashala and the new Chinese taxon are sister taxa that are nested within a radiation of southern Asian adapiforms that also includes Gatanthropus, Muangthanhinius, and Bugtilemur. The new Chinese ekgmowechashaline helps fill the considerable disparity in dental morphology between Ekgmowechashala and more primitive ekgmowechashalids known from southern Asia. Our study underscores the fundamental role of southern Asia as a refugium for multiple primate clades during the cooler and drier climatic regime that prevailed after the Eocene-Oligocene transition. The colonization of North America by Ekgmowechashala helps define the beginning of the Arikareean Land Mammal Age and corresponds to an example of the Lazarus effect, whereby a taxon (in this case, the order Primates) reappears suddenly in the fossil record after a lengthy hiatus.

Combination of immunotherapy, radiotherapy and denosumab as the best approach even for NSCLC poor prognosis patients: a case report with strong response, prolonged survival and a review of literature.

Non-Small Cell Lung Cancer (NSCLC) with bone metastasis and poor performance status has the worst prognosis even in strong PD-L1 expression patients. Treatment approach includes immuno- or chemo-immunotherapy, Radiotherapy (RT) and Bone-Targeted Therapy (BTT) but there is insufficient data to suggest the best time to use each of them, alone or in combination. Using an integrated and synergistic treatment strategy with immunotherapy, radiotherapy, and Denosumab as BTT is probably the best treatment planning for metastatic NSCLC for both good and poor performance status patients, although more data are needed to confirm this approach. Here we describe an interesting case report on patient with extensive bone involvement from NSCLC and PS >2 treated simultaneously with radiotherapy, immunotherapy and BTT, achieving an excellent clinical benefit, radiological and metabolic complete response, as a sort of Lazarus effect. We analyzed our result comparing with currently published data about radio-immunotherapy or immunotherapy and BTT combination even though there is no published experience about integration of all 3 treatments. Approval studies often do not represent real-world experience (RWE), so we analyzed data from both RWE and clinical trials.

The Revolution of Immunotherapy in Gynecological Cancers: The Lazarus Effect in Endometrial Cancer.

Patients with solid tumors and mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H) are eligible for immunotherapy. Recently, different reports described patients with poor performance status (PS), unrelated to comorbidities, which showed a rapid improvement of their clinical conditions under immunotherapy, which evoked a Lazarus response. Very few data on the efficacy and safety of immunotherapy in patients with gynecological malignancies and poor PS are available. Based on the GARNET trial, Dostarlimab, a monoclonal antibody anti-programmed death receptor-1 (PD-1), has been approved in advanced or recurrent mismatch repair deficient endometrial cancer (EC) which progressed after platinum-based therapy. For the first time, in gynecological oncology, an immune checkpoint inhibitor drastically changed the clinical practice. We collected a multicenter case series of six patients with advanced endometrial carcinoma and PS ECOG 3-4 treated with Dostarlimab, showing exceptionally quick responses and significant improvement of PS to configure a Lazarus response.

A new stem group echinoid from the Triassic of China leads to a revised macroevolutionary history of echinoids during the end-Permian mass extinction.

The Permian-Triassic bottleneck has long been thought to have drastically altered the course of echinoid evolution, with the extinction of the entire echinoid stem group having taken place during the end-Permian mass extinction. The Early Triassic fossil record of echinoids is, however, sparse, and new fossils are paving the way for a revised interpretation of the evolutionary history of echinoids during the Permian-Triassic crisis and Early Mesozoic. A new species of echinoid, Yunnanechinus luopingensis n. sp. recovered from the Middle Triassic (Anisian) Luoping Biota fossil Lagerstätte of South China, displays morphologies that are not characteristic of the echinoid crown group. We have used phylogenetic analyses to further demonstrate that Yunnanechinus is not a member of the echinoid crown group. Thus a clade of stem group echinoids survived into the Middle Triassic, enduring the global crisis that characterized the end-Permian and Early Triassic. Therefore, stem group echinoids did not go extinct during the Palaeozoic, as previously thought, and appear to have coexisted with the echinoid crown group for at least 23 million years. Stem group echinoids thus exhibited the Lazarus effect during the latest Permian and Early Triassic, while crown group echinoids did not.