A genome-wide association study of total child psychiatric problems scores.

Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium.

Machine learning forecasting for COVID-19 pandemic-associated effects on paediatric respiratory infections.

Objective: The COVID-19 pandemic and subsequent government restrictions have had a major impact on healthcare services and disease transmission, particularly those associated with acute respiratory infection. This study examined non-identifiable routine electronic patient record data from a specialist children's hospital in England, UK, examining the effect of pandemic mitigation measures on seasonal respiratory infection rates compared with forecasts based on open-source, transferable machine learning models.

Methods: We performed a retrospective longitudinal study of respiratory disorder diagnoses between January 2010 and February 2022.

1,6--Cyclophellitol Cyclosulfamidate Is a Bona Fide Lysosomal α-Glucosidase Stabilizer for the Treatment of Pompe Disease.

α-Glucosidase inhibitors are potential therapeutics for the treatment of diabetes, viral infections, and Pompe disease. Herein, we report a 1,6--cyclophellitol cyclosulfamidate as a new class of reversible α-glucosidase inhibitors that displays enzyme inhibitory activity by virtue of its conformational mimicry of the substrate when bound in the Michaelis complex. The α-d-configured cyclophellitol cyclosulfamidate binds in a competitive manner the human lysosomal acid α-glucosidase (GAA), ER α-glucosidases, and, at higher concentrations, intestinal α-glucosidases, displaying an excellent selectivity over the human β-glucosidases GBA and GBA2 and glucosylceramide synthase (GCS).

Cryo-EM structures of human fucosidase FucA1 reveal insight into substrate recognition and catalysis.

Enzymatic hydrolysis of α-L-fucose from fucosylated glycoconjugates is consequential in bacterial infections and the neurodegenerative lysosomal storage disorder fucosidosis. Understanding human α-L-fucosidase catalysis, in an effort toward drug design, has been hindered by the absence of three-dimensional structural data for any animal fucosidase. Here, we have used cryoelectron microscopy (cryo-EM) to determine the structure of human lysosomal α-L-fucosidase (FucA1) in both an unliganded state and in complex with the inhibitor deoxyfuconojirimycin.

Search for Flavor-Changing Neutral Current Interactions of the Top Quark and Higgs Boson in Final States with Two Photons in Proton-Proton Collisions at sqrt[s]=13 TeV.

Proton-proton interactions resulting in final states with two photons are studied in a search for the signature of flavor-changing neutral current interactions of top quarks (t) and Higgs bosons (H). The analysis is based on data collected at a center-of-mass energy of 13 TeV with the CMS detector at the LHC, corresponding to an integrated luminosity of 137  fb^{-1}. No significant excess above the background prediction is observed.

Development of a Monoclonal Antibody and a Serodiagnostic Lateral-Flow Device Specific to (Syn. ), the Principal Global Agent of Mucormycosis in Humans.

Mucormycosis is a highly aggressive angio-invasive disease of humans caused by fungi in the zygomycete order, Mucorales. Though a number of different species can cause mucormycosis, the principal agent of the disease worldwide is , which accounts for the majority of rhino-orbital-cerebral, pulmonary, and disseminated infections in immunocompromised individuals. It is also the main cause of life-threatening infections in patients with poorly controlled diabetes mellitus, and in corticosteroid-treated patients with SARS-CoV-2 infection, where it causes the newly described disease, COVID-19-associated mucormycosis (CAM).

Mechanism-based heparanase inhibitors reduce cancer metastasis in vivo.

Heparan sulfate proteoglycans (HSPGs) mediate essential interactions throughout the extracellular matrix (ECM), providing signals that regulate cellular growth and development. Altered HSPG composition during tumorigenesis strongly aids cancer progression. Heparanase (HPSE) is the principal enzyme responsible for extracellular heparan sulfate catabolism and is markedly up-regulated in aggressive cancers.

Fabrication and testing of polymer microneedles for transdermal drug delivery.

Microneedle (MN) patches have considerable potential for medical applications such as transdermal drug delivery, point-of-care diagnostics, and vaccination. These miniature microdevices should successfully pierce the skin tissues while having enough stiffness to withstand the forces imposed by penetration. Developing low-cost and simple manufacturing processes for MNs is of considerable interest.

Probing Charm Quark Dynamics via Multiparticle Correlations in Pb-Pb Collisions at sqrt[s_{NN}]=5.02 TeV.

Multiparticle azimuthal correlations of prompt D^{0} mesons are measured in Pb-Pb collisions at a nucleon-nucleon center-of-mass energy of sqrt[s_{NN}]=5.02  TeV. For the first time, a four-particle cumulant method is used to extract the second Fourier coefficient of the azimuthal distribution (v_{2}) of D^{0} mesons as a function of event centrality and the D^{0} transverse momentum.

Search for Resonances Decaying to Three W Bosons in Proton-Proton Collisions at sqrt[s]=13 TeV.

A search for resonances decaying into a W boson and a radion, where the radion decays into two W bosons, is presented. The data analyzed correspond to an integrated luminosity of 138  fb^{-1} recorded in proton-proton collisions with the CMS detector at sqrt[s]=13  TeV. One isolated charged lepton is required, together with missing transverse momentum and one or two massive large-radius jets, containing the decay products of either two or one W bosons, respectively.

Scintillation light detection in the 6-m drift-length ProtoDUNE Dual Phase liquid argon TPC.

DUNE is a dual-site experiment for long-baseline neutrino oscillation studies, neutrino astrophysics and nucleon decay searches. ProtoDUNE Dual Phase (DP) is a 6   6   6 m liquid argon time-projection-chamber (LArTPC) that recorded cosmic-muon data at the CERN Neutrino Platform in 2019-2020 as a prototype of the DUNE Far Detector. Charged particles propagating through the LArTPC produce ionization and scintillation light.

Oxidative cleavage of polysaccharides by a termite-derived boosts the degradation of biomass by glycoside hydrolases.

Wood-feeding termites effectively degrade plant biomass through enzymatic degradation. Despite their high efficiencies, however, individual glycoside hydrolases isolated from termites and their symbionts exhibit anomalously low effectiveness in lignocellulose degradation, suggesting hereto unknown enzymatic activities in their digestome. Herein, we demonstrate that an ancient redox-active enzyme encoded by the lower termite , a Cu/Zn superoxide dismutase (SOD-1), plays a previously unknown role in plant biomass degradation.

Observation of the B_{c}^{+} Meson in Pb-Pb and pp Collisions at sqrt[s_{NN}]=5.02 TeV and Measurement of its Nuclear Modification Factor.

The B_{c}^{+} meson is observed for the first time in heavy ion collisions. Data from the CMS detector are used to study the production of the B_{c}^{+} meson in lead-lead (Pb-Pb) and proton-proton (pp) collisions at a center-of-mass energy per nucleon pair of sqrt[s_{NN}]=5.02  TeV, via the B_{c}^{+}→(J/ψ→μ^{+}μ^{-})μ^{+}ν_{μ} decay.

SARS-CoV-2 infection risk among 77,587 healthcare workers: a national observational longitudinal cohort study in Wales, United Kingdom, April to November 2020.

Objectives: To better understand the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among healthcare workers, leading to recommendations for the prioritisation of personal protective equipment, testing, training and vaccination.

Design: Observational, longitudinal, national cohort study.

Setting: Our cohort were secondary care (hospital-based) healthcare workers employed by NHS Wales (United Kingdom) organisations from 1 April 2020 to 30 November 2020.

Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis.

Background: Historically, human monkeypox virus cases in the UK have been limited to imported infections from west Africa. Currently, the UK and several other countries are reporting a rapid increase in monkeypox cases among individuals attending sexual health clinics, with no apparent epidemiological links to endemic areas. We describe demographic and clinical characteristics of patients diagnosed with human monkeypox virus attending a sexual health centre.

Identification of a female murder victim found in Burgenland, Austria in 1993.

In 1993, the skeletal remains of a female corpse were found in Burgenland, Austria. Initial identification of the approximately 25-35-year-old female appeared impossible, but the case was reopened 23 years later. By applying biogeochemical isotope methods to her body tissues, the geographical origin of the unknown corpse could be predicted.

The effect of community water fluoridation on dental caries in children and young people in England: an ecological study.

Background: The protective effect of community water fluoridation (CWF) against dental caries may be modified by secular changes in health behaviour. We aimed to determine the contemporary association between fluoride in public water supplies (PWS) and dental caries indicators and inequalities in England.

Methods: We estimated exposure to CWF and PWS fluoride concentrations from national monitoring data, using Geographic Information Systems and water supply boundaries, categorizing mean period exposure into <0.

Impact of COVID-19 pandemic on community medication dispensing: a national cohort analysis in Wales, UK.

Background: Population-level information on dispensed medication provides insight on the distribution of treated morbidities, particularly if linked to other population-scale data at an individual-level.

Objective: To evaluate the impact of COVID-19 on dispensing patterns of medications.

Methods: Retrospective observational study using population-scale, individual-level dispensing records in Wales, UK.

Observation of B (2S)K and B (2S)K decays.

Using a data sample of proton-proton collisions collected by the CMS experiment at the LHC in 2017 and 2018 with an integrated luminosity of , the and decays are observed with significances exceeding 5 standard deviations. The resulting branching fraction ratios, measured for the first time, correspond to and , where the last uncertainty in the first ratio is related to the uncertainty in the ratio of production cross sections of and mesons, .

Deletion of AA9 Lytic Polysaccharide Monooxygenases Impacts A. nidulans Secretome and Growth on Lignocellulose.

Lytic polysaccharide monooxygenases (LPMOs) are oxidative enzymes found in viruses, archaea, and bacteria as well as eukaryotes, such as fungi, algae and insects, actively contributing to the degradation of different polysaccharides. In Aspergillus nidulans, LPMOs from family AA9 (LPMO9s), along with an AA3 cellobiose dehydrogenase (CDH1), are cosecreted upon growth on crystalline cellulose and lignocellulosic substrates, indicating their role in the degradation of plant cell wall components. Functional analysis revealed that three target LPMO9s (LPMO9C, LPMO9F and LPMO9G) correspond to cellulose-active enzymes with distinct regioselectivity and activity on cellulose with different proportions of crystalline and amorphous regions.

Experiences and behaviours of patients with asthma requesting prescriptions from primary care during medication shortages linked to the COVID-19 lockdown: insights from a qualitative analysis of a UK asthma online community.

Background: Inhaler shortages were reported in the UK following declaration of the COVID-19 pandemic, prompting advice against stockpiling.

Aim: To understand experiences and behaviours of patients with asthma requesting prescriptions from primary care during asthma medication shortages.

Design & Setting: UK asthma online community, between March and December 2020.

Audit of flexible laryngoscopy use and decontamination using a chlorine dioxide wipe system during COVID-19: Assessing the risk of disease transmission.

Aim: To assess the efficiency of decontamination of flexible nasoendoscopes using a chlorine dioxide wipe system and assessing the risk of disease transmission during the COVID-19 pandemic.

Method: Prospective and retrospective review of 544 patient episodes of nasoendoscopy and a study of 41 patient procedures and 22 members of staff at an ENT Outpatient Department from September 2020 to March 2021.

Results: Among 41 randomly selected episodes of nasoendoscopy in the clinic, there was 93%-100% compliance with decontamination guidelines suggested by ENT UK.