The disproportionate case–fatality ratio of COVID-19 between countries with the highest vaccination rates and the rest of the world

Objectives: The global reported cumulative case–fatality ratios (rCFRs) and excess mortality rates of the 20 countries with the highest coronavirus disease 2019 (COVID-19) vaccination rates, the rest of the world and Sub-Saharan Africa (SSA) were compared before and after the commencement of vaccination programmes. Methods: A time series model was used to understand the trend of rCFR over time, and a generalized linear mixed model was used to understand the effect of vaccination on rCFR. Results: By 31 December 2022, an average of 260.3 doses of COVID-19 vaccine per 100 population had been administered in the top 20 vaccinated countries, compared with 152.1 doses in the rest of the world and 51.2 doses in SSA. The mean rCFR of COVID-19 had decreased by 69.0% in the top 20 vaccinated countries, 26.5% in the rest of the world and 7.6% in SSA. Excess mortality had decreased by 48.7% in the top 20 vaccinated countries, compared with 62.5% in the rest of the world and 60.7% in SSA. In a generalized linear mixed model, the reported number of vaccine doses administered (/100 population) (odds ratio 0.64) was associated with a steeper reduction in COVID-19 rCFR. Conclusions: Vaccine equity and faster roll-out across the world is critically important in reducing COVID-19 transmission and CFR

Structural basis for the RING catalyzed synthesis of K63 linked ubiquitin chains

This work was supported by grants from Cancer Research UK (C434/A13067), the Wellcome Trust (098391/Z/12/Z) and Biotechnology and Biological Sciences Research Council (BB/J016004/1).The RING E3 ligase catalysed formation of lysine 63 linked ubiquitin chains by the Ube2V2–Ubc13 E2 complex is required for many important biological processes. Here we report the structure of the RING domain dimer of rat RNF4 in complex with a human Ubc13~Ub conjugate and Ube2V2. The structure has captured Ube2V2 bound to the acceptor (priming) ubiquitin with Lys63 in a position that could lead to attack on the linkage between the donor (second) ubiquitin and Ubc13 that is held in the active “folded back” conformation by the RING domain of RNF4. The interfaces identified in the structure were verified by in vitro ubiquitination assays of site directed mutants. This represents the first view of the synthesis of Lys63 linked ubiquitin chains in which both substrate ubiquitin and ubiquitin-loaded E2 are juxtaposed to allow E3 ligase mediated catalysis.PostprintPeer reviewe

Dynamical tunneling in molecules: Quantum routes to energy flow

Dynamical tunneling, introduced in the molecular context, is more than two decades old and refers to phenomena that are classically forbidden but allowed by quantum mechanics. On the other hand the phenomenon of intramolecular vibrational energy redistribution (IVR) has occupied a central place in the field of chemical physics for a much longer period of time. Although the two phenomena seem to be unrelated several studies indicate that dynamical tunneling, in terms of its mechanism and timescales, can have important implications for IVR. Examples include the observation of local mode doublets, clustering of rotational energy levels, and extremely narrow vibrational features in high resolution molecular spectra. Both the phenomena are strongly influenced by the nature of the underlying classical phase space. This work reviews the current state of understanding of dynamical tunneling from the phase space perspective and the consequences for intramolecular vibrational energy flow in polyatomic molecules.Comment: 37 pages and 23 figures (low resolution); Int. Rev. Phys. Chem. (Review to appear in Oct. 2007

Habitat structure: a fundamental concept and framework for urban soil ecology

Habitat structure is defined as the composition and arrangement of physical matter at a location. Although habitat structure is the physical template underlying ecological patterns and processes, the concept is relatively unappreciated and underdeveloped in ecology. However, it provides a fundamental concept for urban ecology because human activities in urban ecosystems are often targeted toward management of habitat structure. In addition, the concept emphasizes the fine-scale, on-the-ground perspective needed in the study of urban soil ecology. To illustrate this, urban soil ecology research is summarized from the perspective of habitat structure effects. Among the key conclusions emerging from the literature review are: (1) habitat structure provides a unifying theme for multivariate research about urban soil ecology; (2) heterogeneous urban habitat structures influence soil ecological variables in different ways; (3) more research is needed to understand relationships among sociological variables, habitat structure patterns and urban soil ecology. To stimulate urban soil ecology research, a conceptual framework is presented to show the direct and indirect relationships among habitat structure and ecological variables. Because habitat structure serves as a physical link between sociocultural and ecological systems, it can be used as a focus for interdisciplinary and applied research (e.g., pest management) about the multiple, interactive effects of urbanization on the ecology of soils

The Global Case-Fatality Rate of COVID-19 Has Been Declining Since May 2020

Abstract.The objective of this study was to evaluate the trend of reported case fatality rate (rCFR) of COVID-19 over time, using globally reported COVID-19 cases and mortality data. We collected daily COVID-19 diagnoses and mortality data from the WHO’s daily situation reports dated January 1 to December 31, 2020. We performed three time-series models [simple exponential smoothing, auto-regressive integrated moving average, and automatic forecasting time-series (Prophet)] to identify the global trend of rCFR for COVID-19. We used beta regression models to investigate the association between the rCFR and potential predictors of each country and reported incidence rate ratios (IRRs) of each variable. The weekly global cumulative COVID-19 rCFR reached a peak at 7.23% during the 17th week (April 22–28, 2020). We found a positive and increasing trend for global daily rCFR values of COVID-19 until the 17th week (pre-peak period) and then a strong declining trend up until the 53rd week (post-peak period) toward 2.2% (December 29–31, 2020). In pre-peak of rCFR, the percentage of people aged 65 and above and the prevalence of obesity were significantly associated with the COVID-19 rCFR. The declining trend of global COVID-19 rCFR was not merely because of increased COVID-19 testing, because COVID-19 tests per 1,000 population had poor predictive value. Decreasing rCFR could be explained by an increased rate of infection in younger people or by the improvement of health care management, shielding from infection, and/or repurposing of several drugs that had shown a beneficial effect on reducing fatality because of COVID-19.</jats:p

Autologous neutralizing antibody responses to an HIV envelope glycan hole are not easily broadened in rabbits

Extensive studies with subtype A BG505-derived HIV Env immunogens have revealed that the dominant autologous neutralizing epitope in rabbits is located in an exposed region of the heavily glycosylated trimer that lacks potential N-linked glycosylation sites at positions 230, 241, and 289. The Env derived from B41, a subtype B virus, shares a glycan hole centered on positions 230 and 289. To test whether broader neutralization to the common glycan hole can be achieved, we immunized rabbits with B41 SOSIP alone, as well as B41 and BG505 co-immunization. We isolated autologous neutralizing antibodies (nAbs) and described their structure in complex with the B41 Env. Our data suggest that distinct autologous nAb lineages are induced by BG505 and B41 immunogens, even when both were administered together. In contrast to previously described BG505 glycan hole antibodies, the B41-specific nAbs accommodate the >97% conserved N241 glycan, which is present in B41. Single particle cryo-electron microscopy studies confirmed that B41 and BG505-specific nAbs bind to overlapping glycan hole epitopes. We then used our high-resolution data to guide mutations in the BG505 glycan hole epitope in an attempt to broaden the reactivity of a B41-specific nAb, but only recovered partial binding. Our data demonstrate that lack of cross-reactivity in glycan hole antibodies is due to amino acid differences within the epitope and our attempts to rationally design cross-reactive trimers resulted in only limited success. Thus, even for the immunodominant glycan hole shared between BG505 and B41 the prospect of designing prime-boost immunogens remains difficult

Structure and mechanism of human DNA polymerase η

The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Pol eta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Pol eta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Pol eta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Pol eta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Pol eta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Pol eta in replicating through D loop and DNA fragile sites

HIV envelope trimer-elicited autologous neutralizing antibodies bind a region overlapping the N332 glycan supersite

To date, immunization studies of rabbits with the BG505 SOSIP.664 HIV envelope glycoprotein trimers have revealed the 241/289 glycan hole as the dominant neutralizing antibody epitope. Here, we isolated monoclonal antibodies from a rabbit that did not exhibit glycan hole–dependent autologous serum neutralization. The antibodies did not compete with a previously isolated glycan hole–specific antibody but did compete with N332 glycan supersite broadly neutralizing antibodies. A 3.5-Å cryoEM structure of one of the antibodies in complex with the BG505 SOSIP.v5.2 trimer demonstrated that while the epitope recognized overlapped the N332 glycan supersite by contacting the GDIR motif at the base of V3, primary contacts were located in the variable V1 loop. These data suggest that strain-specific responses to V1 may interfere with broadly neutralizing responses to the N332 glycan supersite and vaccine immunogens may require engineering to minimize these off-target responses or steer them toward a more desirable pathway

Missing Features Reconstruction Using a Wasserstein Generative Adversarial Imputation Network

Missing data is one of the most common preprocessing problems. In this paper, we experimentally research the use of generative and non-generative models for feature reconstruction. Variational Autoencoder with Arbitrary Conditioning (VAEAC) and Generative Adversarial Imputation Network (GAIN) were researched as representatives of generative models, while the denoising autoencoder (DAE) represented non-generative models. Performance of the models is compared to traditional methods k-nearest neighbors (k-NN) and Multiple Imputation by Chained Equations (MICE). Moreover, we introduce WGAIN as the Wasserstein modification of GAIN, which turns out to be the best imputation model when the degree of missingness is less than or equal to 30%. Experiments were performed on real-world and artificial datasets with continuous features where different percentages of features, varying from 10% to 50%, were missing. Evaluation of algorithms was done by measuring the accuracy of the classification model previously trained on the uncorrupted dataset. The results show that GAIN and especially WGAIN are the best imputers regardless of the conditions. In general, they outperform or are comparative to MICE, k-NN, DAE, and VAEAC.Comment: Preprint of the conference paper (ICCS 2020), part of the Lecture Notes in Computer Scienc