Monitoring Temporal Changes in SARS-CoV-2 Spike Antibody Levels and Variant-Specific Risk for Infection, Dominican Republic, March 2021-August 2022

To assess changes in SARS-CoV-2 spike binding antibody prevalence in the Dominican Republic and implications for immunologic protection against variants of concern, we prospectively enrolled 2,300 patients with undifferentiated febrile illnesses in a study during March 2021-August 2022. We tested serum samples for spike antibodies and tested nasopharyngeal samples for acute SARS-CoV-2 infection using a reverse transcription PCR nucleic acid amplification test. Geometric mean spike antibody titers increased from 6.6 (95% CI 5.1-8.7) binding antibody units (BAU)/mL during March-June 2021 to 1,332 (95% CI 1,055-1,682) BAU/mL during May-August 2022. Multivariable binomial odds ratios for acute infection were 0.55 (95% CI 0.40-0.74), 0.38 (95% CI 0.27-0.55), and 0.27 (95% CI 0.18-0.40) for the second, third, and fourth versus the first anti-spike quartile; findings were similar by viral strain. Combining serologic and virologic screening might enable monitoring of discrete population immunologic markers and their implications for emergent variant transmission

Observation of substrate diffusion and ligand binding in enzyme crystals using high-repetition-rate mix-and-inject serial crystallography

18 pags, 11 figs, 5 tabsHere, we illustrate what happens inside the catalytic cleft of an enzyme when substrate or ligand binds on single-millisecond timescales. The initial phase of the enzymatic cycle is observed with near-atomic resolution using the most advanced X-ray source currently available: the European XFEL (EuXFEL). The high repetition rate of the EuXFEL combined with our mix-and-inject technology enables the initial phase of ceftriaxone binding to the Mycobacterium tuberculosis β-lactamase to be followed using time-resolved crystallography in real time. It is shown how a diffusion coefficient in enzyme crystals can be derived directly from the X-ray data, enabling the determination of ligand and enzyme-ligand concentrations at any position in the crystal volume as a function of time. In addition, the structure of the irreversible inhibitor sulbactam bound to the enzyme at a 66 ms time delay after mixing is described. This demonstrates that the EuXFEL can be used as an important tool for biomedically relevant research.This work was supported by the National Science Foundation Science and Technology Center 'BioXFEL' through award STC-1231306, and in part by the US Department of Energy, Office of Science, Basic Energy Sciences under contract DESC0002164 (AO, algorithm design and development) and by the National Science Foundation under contract Nos. 1551489 (AO, underlying analytical models) and DBI-2029533 (AO, functional conformations). This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. 1450681 to JLO. The work was also supported by funds from the National Institutes of Health grant R01 GM117342-0404. Funding and support are also acknowledged from the National Institutes of Health grant R01 GM095583, from the Biodesign Center for Applied Structural Discovery at ASU, from National Science Foundation award No. 1565180 and the US Department of Energy through Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344. KAZ was supported by the Cornell Molecular Biophysics Training Program (NIH T32-GM008267). This work was also supported by the Cluster of Excellence 'CUI: Advanced Imaging of Matter' of the Deutsche Forschungsgemeinschaft (DFG), EXC 2056, project ID 390715994. CFEL is supported by the Gottfried Wilhelm Leibniz Program of the DFG, the 'X-probe' project funded by the European Union 2020 Research and Innovation Program under Marie Sklodowska-Curie grant agreement 637295, the European Research Council, 'Frontiers in Attosecond X-ray Science: Imaging and Spectroscopy (AXSIS)', ERC-2013-SyG 609920, and the Human Frontiers Science Program grant RGP0010 2017. This work is also supported by the AXSIS project funded by the European Research Council under the European Union Seventh Framework Program (FP/2007-2013)/ERC Grant Agreement No. 609920.Peer reviewe

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Search for strongly interacting massive particles generating trackless jets in proton-proton collisions at s = 13 TeV

A search for dark matter in the form of strongly interacting massive particles (SIMPs) using the CMS detector at the LHC is presented. The SIMPs would be produced in pairs that manifest themselves as pairs of jets without tracks. The energy fraction of jets carried by charged particles is used as a key discriminator to suppress efficiently the large multijet background, and the remaining background is estimated directly from data. The search is performed using proton-proton collision data corresponding to an integrated luminosity of 16.1 fb - 1 , collected with the CMS detector in 2016. No significant excess of events is observed above the expected background. For the simplified dark matter model under consideration, SIMPs with masses up to 100 GeV are excluded and further sensitivity is explored towards higher masses

Measurement of single-diffractive dijet production in proton-proton collisions at root s=8 TeV with the CMS and TOTEM experiments

A Publisher's Erratum to this article was published on 03 May 2021. https://doi.org/10.1140/epjc/s10052-021-08863-wPeer reviewe

Measurement of single-diffractive dijet production in proton–proton collisions at s=8 TeV\sqrt{s} = 8\,\text {Te}\text {V} with the CMS and TOTEM experiments

Measurements are presented of the single-diffractive dijet cross section and the diffractive cross section as a function of the proton fractional momentum loss ξ ξ and the four-momentum transfer squared t. Both processes p p → p X p p → p X and p p → X p p p → X p , i.e. with the proton scattering to either side of the interaction point, are measured, where X X includes at least two jets; the results of the two processes are averaged. The analyses are based on data collected simultaneously with the CMS and TOTEM detectors at the LHC in proton–proton collisions at s √ =8TeV s=8TeV during a dedicated run with β ∗ =90m β∗=90m at low instantaneous luminosity and correspond to an integrated luminosity of 37.5nb −1 37.5nb−1 . The single-diffractive dijet cross section σ p X jj σjj p X , in the kinematic region ξ<0.1 ξ<0.1 , 0.03<|t|<1GeV 2 0.03<|t|<1GeV2 , with at least two jets with transverse momentum p T >40GeV pT>40GeV , and pseudorapidity |η|<4.4 |η|<4.4 , is 21.7±0.9(stat) +3.0 −3.3 (syst)±0.9(lumi)nb 21.7±0.9(stat)−3.3+3.0(syst)±0.9(lumi)nb . The ratio of the single-diffractive to inclusive dijet yields, normalised per unit of ξ ξ , is presented as a function of x, the longitudinal momentum fraction of the proton carried by the struck parton. The ratio in the kinematic region defined above, for x values in the range −2.9≤log 10 x≤−1.6 −2.9≤log10⁡x≤−1.6 , is R=(σ p X jj /Δξ)/σ jj =0.025±0.001(stat)±0.003(syst) R=(σjj p X /Δξ)/σjj=0.025±0.001(stat)±0.003(syst) , where σ p X jj σjj p X and σ jj σjj are the single-diffractive and inclusive dijet cross sections, respectively. The results are compared with predictions from models of diffractive and nondiffractive interactions. Monte Carlo predictions based on the HERA diffractive parton distribution functions agree well with the data when corrected for the effect of soft rescattering between the spectator partons

Search for strongly interacting massive particles generating trackless jets in proton–proton collisions at s√ = 13 TeV

Data Availability Statement: This manuscript has no associated data or the data will not be deposited. [Authors’ comment: Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS policy as stated in “CMS data preservation, re-use and open access policy” (https://cms-docdb.cern.ch/cgi-bin/ PublicDocDB/RetrieveFile?docid=6032&filename=CMSDataPolicyV1. 2.pdf&version=2).]Copyright © 2022 The Authors. A search for dark matter in the form of strongly interacting massive particles (SIMPs) using the CMS detector at the LHC is presented. The SIMPs would be produced in pairs that manifest themselves as pairs of jets without tracks. The energy fraction of jets carried by charged particles is used as a key discriminator to suppress efficiently the large multijet background, and the remaining background is estimated directly from data. The search is performed using proton–proton collision data corresponding to an integrated luminosity of 16.1fb−1, collected with the CMS detector in 2016. No significant excess of events is observed above the expected background. For the simplified dark matter model under consideration, SIMPs with masses up to 100GeV are excluded and further sensitivity is explored towards higher masses.SCOAP3

Rapid and efficient room temperature serial synchrotron crystallography using the CFEL TapeDrive

Serial crystallography at conventional synchrotron light sources (SSX) offers the possibility to routinely collect data at room temperature using micron sized crystals of biological macromolecules. However, it suffers from the fact that data collection is not yet as routine and takes currently significantly longer as the standard rotation series cryo-crystallography. Thus its use for high-throughput approaches, such as fragment-based drug screening, where the possibility to measure at physiological temperatures would be a great benefit, is impaired. On the way to high-throughput serial synchrotron crystallography, it is shown here, using a conveyor belt based sample delivery system – the CFEL TapeDrive – with three different proteins of biological relevance (K. pneumoniae CTX-M-14 β-lactamase, Nectria haematococca xylanase GH11 and Aspergillus flavus urate oxidase), that complete data sets can be collected in less than a minute and that only minimal amounts of sample are required