An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection.peer-reviewe

Calcareous nannofossil biostratigraphy of Cretaceous sediments from ODP Leg 198 sites

Eight sites were drilled on Shatsky Rise during Ocean Drilling Program Leg 198. All sites (1207-1214) recovered Cretaceous sediments ranging in age from Maastrichtian to Berriasian. In the Upper Cretaceous, Maastrichtian-Campanian nannofossil oozes were recovered at Sites 1207-1212. At Sites 1207 and 1212 Santonian-Cenomanian oozes were also recovered from chert-dominated sequences, but this interval contains multiple hiatuses. Sites 1209-1211 terminated in chert. Calcareous nannofossil assemblages are abundant, diverse, and relatively well preserved throughout, but biostratigraphy is problematic in places due to missing or rare and sporadically distributed marker species. In the upper Maastrichtian, the first occurrences (FOs) of Micula murus and Lithraphidites quadratus appear to be reversed in most sections, and in the Campanian, Reinhardtites levis, Misceomarginatus pleniporus, and Eiffellithus parallelus are absent or virtually absent, probably due to biogeographic limitations. However, a number of previously unused bioevents were recognized that may prove to be useful Pacific-wide, including the FO of Ceratolithoides ultimus (in Subzone UC20dTP) and the last occurrence (LO) of Tegumentum stradneri (in Subzone UC20bTP) in the upper Maastrichtian; the FOs of Micula praemurus and consistent Cribrocorona gallica, the LOs of Zeugrhabdotus bicrescenticus and Cribrocorona echinus, and the FO of C. echinus lower in the Maastrichtian; and the LO of Rucinolithus? magnus (in Zone UC16), FO of R.? magnus (in Subzone UC15bTP), FO of Perchnielsenella stradneri (in Subzone UC15a/bTP), and FO of Ceratolithoides indiensis (Subzone UC14d-UC15dTP) in the Campanian. The assemblages are distinctly different in composition from those of the Atlantic Ocean and its marginal basins but show similarities with some Indian Ocean nannofloras, and so these sections will provide important insights into the paleobiogeography and paleoecology of Late Cretaceous nannoplankton. The assemblages are broadly dominated by cosmopolitan taxa such as Prediscosphaera, Watznaueria, and Retecapsa, but abundance data together with key occurrences and absences reveal a distinct paleobiogeographic character. High-latitude species such as Seribiscutum primitivum, Repagulum parvidentatum, and Nephrolithus frequens are completely absent from the Shatsky sites. The common presence of Ceratolithoides, Uniplanarius, Micula, and Cylindralithus/Perchnielsenella are indicative of tropical to subtropical paleolatitudes and reflect an open-ocean setting