HTE-Enabled Development of an Ene-Reductase-Catalyzed Desymmetrization: Remote Control of All-Carbon Quaternary γ-Centers.

We report the remote stereocontrol of all-carbon quaternary γ-centers via an ene-reductase (ERED)-catalyzed desymmetrization of prochiral cyclohexadienones. By leveraging high-throughput experimentation (HTE) protocols, we were able to rapidly identify EREDs capable of desymmetrizing both spirocyclic cyclohexadienones and non-spirocyclic 2,6-disubstituted cyclohexadienone substrates in up to 85% yield with excellent levels of stereoselectivity (up to >99% ee and >20:1 dr) under mild reaction conditions.

The impact of cooking and burial on proteins: a characterisation of experimental foodcrusts and ceramics.

Foodcrusts have received relatively little attention in the burgeoning field of proteomic analysis of ancient cuisine. We remain ignorant of how cooking and burial impact protein survival, and crucially, the extent to which the extractome reflects the composition of input ingredients. Therefore, through experimental analogues, we explore the extent of protein survival in unburied and buried foodcrusts and ceramics using 'typical' Mesolithic ingredients (red deer, Atlantic salmon and sweet chestnut).

Lineage frequency time series reveal elevated levels of genetic drift in SARS-CoV-2 transmission in England.

Genetic drift in infectious disease transmission results from randomness of transmission and host recovery or death. The strength of genetic drift for SARS-CoV-2 transmission is expected to be high due to high levels of superspreading, and this is expected to substantially impact disease epidemiology and evolution. However, we don't yet have an understanding of how genetic drift changes over time or across locations.

Design, Synthesis, and Evaluation of Inhibitors of Hedgehog Acyltransferase.

Hedgehog signaling is involved in embryonic development and cancer growth. Functional activity of secreted Hedgehog signaling proteins is dependent on -terminal palmitoylation, making the palmitoyl transferase Hedgehog acyltransferase (HHAT), a potential drug target and a series of 4,5,6,7-tetrahydrothieno[3,2-]pyridines have been identified as HHAT inhibitors. Based on structural data, we designed and synthesized 37 new analogues which we profiled alongside 13 previously reported analogues in enzymatic and cellular assays.

Phylogenomic early warning signals for SARS-CoV-2 epidemic waves.

Background: Epidemic waves of coronavirus disease 2019 (COVID-19) infections have often been associated with the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Rapid detection of growing genomic variants can therefore serve as a predictor of future waves, enabling timely implementation of countermeasures such as non-pharmaceutical interventions (social distancing), additional vaccination (booster campaigns), or healthcare capacity adjustments. The large amount of SARS-CoV-2 genomic sequence data produced during the pandemic has provided a unique opportunity to explore the utility of these data for generating early warning signals (EWS).

The use of neurone specific enolase to prognosticate neurological recovery and long term neurological outcomes in OOHCA patients.

Introduction: Hypoxic-ischaemic brain injury (HIBI), is a common sequalae following out-of-hospital cardiac arrest (OOHCA), it is reported as the cause of death in 68% of patients who survive to ICU admission, while other patients can be left with permanent neurological disability. Prediction of neurological outcome follows a multimodal approach, including use of the biomarker, neurone specific enolase (NSE). There is however no definitive cut-off value for poor neurological outcome, and little research has analysed NSE and long-term outcomes in survivors.

Mortality and readmission rates of patients discharged in-hours and out-of-hours from a British ICU over a 3-year period.

Excess in-hospital mortality following out-of-hours ICU discharge has been reported worldwide. From preliminary data, we observed that magnitude of difference may be reduced when patients discharged for end-of-life care or organ donation are excluded. We speculated that these patients may be disproportionately discharged out-of-hours, biasing results.

The Natural Historian's Guide to the CT Galaxy: Step-by-Step Instructions for Preparing and Analyzing Computed Tomographic (CT) Data Using Cross-Platform, Open Access Software.

The decreasing cost of acquiring computed tomographic (CT) data has fueled a global effort to digitize the anatomy of museum specimens. This effort has produced a wealth of open access digital three-dimensional (3D) models of anatomy available to anyone with access to the Internet. The potential applications of these data are broad, ranging from 3D printing for purely educational purposes to the development of highly advanced biomechanical models of anatomical structures.

Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England.

The SARS-CoV-2 lineage B.1.1.

Database of epidemic trends and control measures during the first wave of COVID-19 in mainland China.

Objectives: In this data collation study, we aimed to provide a comprehensive database describing the epidemic trends and responses during the first wave of coronavirus disease 2019 (COVID-19) throughout the main provinces in China.

Methods: From mid-January to March 2020, we extracted publicly available data regarding the spread and control of COVID-19 from 31 provincial health authorities and major media outlets in mainland China. Based on these data, we conducted descriptive analyses of the epidemic in the six most-affected provinces.

Evidence of initial success for China exiting COVID-19 social distancing policy after achieving containment.

: The COVID-19 epidemic was declared a Global Pandemic by WHO on 11 March 2020. By 24 March 2020, over 440,000 cases and almost 20,000 deaths had been reported worldwide. In response to the fast-growing epidemic, which began in the Chinese city of Wuhan, Hubei, China imposed strict social distancing in Wuhan on 23 January 2020 followed closely by similar measures in other provinces.

The impact of COVID-19 and strategies for mitigation and suppression in low- and middle-income countries.

The ongoing coronavirus disease 2019 (COVID-19) pandemic poses a severe threat to public health worldwide. We combine data on demography, contact patterns, disease severity, and health care capacity and quality to understand its impact and inform strategies for its control. Younger populations in lower-income countries may reduce overall risk, but limited health system capacity coupled with closer intergenerational contact largely negates this benefit.

Safe prognostication following cardiac arrest: The role of the pharmacokinetics of fentanyl in patients treated with targeted temperature management.

Background: Neurological prognostication following cardiac arrest (CA) is complex and sedative agents may significantly impair responses to clinical examination. This study investigates the elimination of fentanyl in patients treated with targeted temperature management (TTM).

Methods: We measured the blood concentration of fentanyl in 23 post-cardiac arrest patients treated with TTM following discontinuation of continuous infusion.

Rhodacyclopentanones as Linchpins for the Atom Economical Assembly of Diverse Polyheterocycles.

We outline a conceptual blueprint that provides direct and atom economical access to a wide range of complex polyheterocycles. Our method capitalizes on the ambiphilic reactivity of rhodacyclopentanones that arise upon exposure of cyclopropanes to Rh(I) catalysts and CO. Using this approach, a wide array of polycyclizations are achieved, including variants that involve powerful dearomatizations and medium ring formations.

Modular Access to Eight-Membered N-Heterocycles by Directed Carbonylative C-C Bond Activation of Aminocyclopropanes.

Aminocyclopropanes equipped with pendant nucleophiles undergo carbonylative heterocyclization triggered by C-C bond activation to generate eight-membered N-heterocycles. In these processes, intramolecular "capture" of a rhodacyclopentanone intermediate by an aryl or N-based nucleophile is followed by C-C or C-N bond-forming "collapse" to the targets. These studies demonstrate how the combination of cyclopropane strain release and the templating effect of catalytically generated metallacycles can be harnessed to enable otherwise challenging medium ring closures.

Phylogeny of the beetle supertribe Trechitae (Coleoptera: Carabidae): Unexpected clades, isolated lineages, and morphological convergence.

Using data from two nuclear ribosomal genes and four nuclear protein-coding genes, we infer a well-resolved phylogeny of major lineages of the carabid beetle supertribe Trechitae, based upon a sampling of 259 species. Patrobini is the sister group of Trechitae, but the genus Lissopogonus appears to be outside of the Patrobini + Trechitae clade. We find that four enigmatic trechite genera from the Southern Hemisphere, Bembidarenas, Argentinatachoides, Andinodontis, and Tasmanitachoides, form a clade that is the sister group of Trechini; we describe this clade as a new tribe, Bembidarenini.

A haemocompatible and scalable nanoporous adsorbent monolith synthesised using a novel lignin binder route to augment the adsorption of poorly removed uraemic toxins in haemodialysis.

Nanoporous adsorbents are promising materials to augment the efficacy of haemodialysis for the treatment of end stage renal disease where mortality rates remain unacceptably high despite improvements in membrane technology. Complications are linked in part to inefficient removal of protein bound and high molecular weight uraemic toxins including key marker molecules albumin bound indoxyl sulphate (IS) and p-cresyl sulphate (PCS) and large inflammatory cytokines such as IL-6. The following study describes the assessment of a nanoporous activated carbon monolith produced using a novel binder synthesis route for scale up as an in line device to augment haemodialysis through adsorption of these toxins.

MonotomidGen - A matrix-based interactive key to the New World genera of Monotomidae (Coleoptera, Cucujoidea).

A matrix-based Lucid key is presented for the twelve genera of Monotomidae (Coleoptera: Cucujoidea) represented in the New World. A general overview is given for the features and technical specifications of an original interactive key for the identification of these genera. The list of terminal taxa included with the key provides a current summary of monotomid generic diversity for the Nearctic and Neotropical regions.