Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

Genesis of the Western Samoa seamount province: age, geochemical fingerprint and tectonics

The Samoan volcanic lineament has many features that are consistent with a plume-driven hotspot model, including the currently active submarine volcano Vailulu'u that anchors the eastern extremity. Proximity to the northern end of the Tonga trench, and the presence of voluminous young volcanism on what should be the oldest (∼5 my) western island (Savai'i) has induced controversy regarding a simple plume/hotspot model. In an effort to further constrain this debate, we have carried out geochronological, geochemical and isotopic studies of dredge basalts from four seamounts and submarine banks that extend the Samoan lineament 1300 km further west from Savai'i. 40Ar/39Ar plateau ages from Combe and Alexa Banks (11.1 my—940 km, and 23.4 my—1690 km from Vailulu'u, respectively) fit a Pacific age progression very well. The oldest volcanism (9.8 my) on Lalla Rookh (725 km from Vailulu'u) also fits this age progression, but a new age is much younger (1.6 my). Isotopically, these three seamounts, along with Pasco Bank (590 km from Vailulu'u), all lie within, or closely along extensions of, the Sr–Nd–Pb fields for shield basalts from the Eastern Samoan Province (Savai'i to Vailulu'u); this clearly establishes a Samoan pedigree for this western extension of the Samoan hotspot chain, and pushes the inception of Samoan volcanism back to at least 23 my. From geodetic reconstructions of the Fiji–Tonga–Samoa region, we show that the northern terminus of the Tonga arc was too far west of the Samoa hotspot up until 1–2 my ago to have been a factor in its volcanism. Young rejuvenated volcanism on Lalla Rookh and Savai'i may be related to the rapid eastward encroachment of the Trench corner. The Vitiaz Lineament, previously thought to mark a proto-Tongan subduction zone, was more likely created by the eastward propagation of the tear in the Pacific Plate at the northern end of the arc

Radiation hydrodynamics with backscatter and beam spray in gas filled hohlraum experiments at the National Ignition Facility

Several experiments using either CO$_{2}$ or propane gas filled halfraums [i.e. hohlraums with a single laser entry hole (LEH)] have been shot at the National Ignition Facility (NIF) in a joint Los Alamos/Livermore collaboration. The experiments have been modeled by the Lasnex code. The possibility of beam spray due to filamentation of the incident laser beam is assessed through simulations which parametrically decrease the f-number of the beam at times of high intensity. The uncertainty in heat transport is evaluated through parametric variations in the electron thermal flux limit (fe). Each calculation in the resulting two parameter set is post-processed to simulate outputs which can be compared with Dante detector results for the soft X-ray flux through the LEH, and gated, framed images of hard X-rays (FXI) through the hohlraum side walls. Simulations which well match the data for both gases indicate that the laser energy is penetrating the gas filled hohlraum even towards the end of the pulse. This suggests that the gas fill is useful in keeping the hohlraum open to laser energy throughout the pulse