Structure, kinetics, and mechanism of Pseudomonas putida sulfoquinovose dehydrogenase, the first enzyme in the sulfoglycolytic Entner-Doudoroff pathway.

The sulfosugar sulfoquinovose (SQ) is catabolized through the sulfoglycolytic Entner-Doudoroff pathway, beginning with the oxidation of SQ to sulfogluconolactone by SQ dehydrogenase. We present a comprehensive structural and kinetic characterization of Pseudomonas putida SQ dehydrogenase (PpSQDH). PpSQDH is a tetrameric enzyme belonging to the short-chain dehydrogenase/reductase (SDR) superfamily with a strong preference for NAD+ over NADP+.

Using routine primary care data in research: (in)efficient case studies and perspectives from the Asthma UK Centre for Applied Research.

Aim: We aimed to identify enablers and barriers of using primary care routine data for healthcare research, to formulate recommendations for improving efficiency in knowledge discovery.

Background: Data recorded routinely in primary care can be used for estimating the impact of interventions provided within routine care for all people who are clinically eligible. Despite official promotion of 'efficient trial designs', anecdotally researchers in the Asthma UK Centre for Applied Research (AUKCAR) have encountered multiple barriers to accessing and using routine data.

Micro-vibration assisted dual-layer spiral microneedles to rapidly extract dermal interstitial fluid for minimally invasive detection of glucose.

Various hydrogels have been explored to create minimally invasive microneedles (MNs) to extract interstitial fluid (ISF). However, current methods are time-consuming and typically require 10-15 min to extract 3-5 mg of ISF. This study introduces two spiral-shaped swellable MN arrays: one made of gelatin methacryloyl (GelMA) and polyvinyl alcohol (PVA), and the other incorporating a combination of PVA, polyvinylpyrrolidone (PVP), and hyaluronic acid (HA) for fast ISF extraction.

A scoping review of the electronic collection and capture of patient reported outcome measures for children and young people in the hospital setting.

Patient reported outcome measures (PROMs) capture patients' views of their health status and the use of PROMs as part of standard care of children and young people has the potential to improve communication between patients/carers and clinicians and the quality of care. Electronic systems for the collection of or access to PROMs and integrating PROMs into electronic health records facilitates their implementation in routine care and could help maximise their value. Yet little is known about the technical aspects of implementation including the electronic systems available for collection and capture and how this may influence the value of PROMs in routine care which this scoping review aims to explore.

Evaluation and Treatment of Baseball Pitchers: There's More to Assess than the Arm.

Injuries are commonplace in the overhead athlete, with many occurring to the shoulder and elbow. The increasing prevalence of injuries to the shoulder and elbow has been discussed at length in recent years, with increased research focus being placed on arm care for rehabilitation and prevention strategies. Even though the pitching motion is well-established as a whole-body kinetic chain movement, most attention in rehabilitation and prevention efforts is often placed on the upper extremity.

Comparison of Systemic Inflammatory Indices With the Oncotype DX Recurrence Score and the Nottingam Prognostic Index in Early Hormone Receptor Positive Ductal Breast Cancer.

Background: Adjuvant therapy decisions in hormone receptor positive, HER2 negative breast cancer are evolving. Gene panel testing has reduced the number of patients recommended for chemotherapy by up to two thirds. Identifying low risk genomic cases before testing could represent a significant economic impact.

Internal Medicine Student Chief Elective.

Background: With increasing patient care responsibilities, administrative work and education demands, physicians may find it challenging to provide high-quality and engaging clinical education to third-year medical students on clerkships. Fourth-year students in the role of near-peer teachers can help fill this role, but they often also have competing responsibilities.

Approach: A 4-week Internal Medicine Student Chief (Student Chief) elective was created, designed such that fourth-year students would apply for dedicated time to serve as student leaders, coaches and educators for the third-year students on the Internal Medicine clerkship.

Direct and indirect effects of the COVID-19 pandemic on mortality: an individual-level population-scale analysis using linked electronic health records, Wales, United Kingdom, 2016 to 2022.

BackgroundThe COVID-19 pandemic resulted in increased mortality directly and indirectly associated with COVID-19.AimTo assess the impact of the COVID-19 pandemic on all-cause and disease-specific mortality and explore potential health inequalities associated with area-level deprivation in Wales.MethodsTwo population-based cohort studies were derived from multi-sourced, linked demographic, administrative and electronic health record data from 2016 to 2019 (n = 3,113,319) and 2020 to 2022 (n = 3,571,471).

Effects of gene dosage on cognitive ability: A function-based association study across brain and non-brain processes.

Copy-number variants (CNVs) that increase the risk for neurodevelopmental disorders also affect cognitive ability. However, such CNVs remain challenging to study due to their scarcity, limiting our understanding of gene-dosage-sensitive biological processes linked to cognitive ability. We performed a genome-wide association study (GWAS) in 258,292 individuals, which identified-for the first time-a duplication at 2q12.

Analysis of Time-to-Positivity Data in Tuberculosis Treatment Studies: Identifying a New Limit of Quantification.

Background: The BACTEC Mycobacteria Growth Indicator Tube (MGIT) machine is the standard globally for detecting viable mycobacteria in patients' sputum. Samples are observed for no longer than 42 days, at which point the sample is declared 'negative' for tuberculosis (TB). This time to detection of bacterial growth, referred to as time-to-positivity (TTP), is increasingly of interest, not solely as a diagnostic tool but also as a continuous biomarker wherein change in TTP can be used for comparing the bactericidal activity of different TB treatments.

Sub30: Feasibility study of a pre-hospital extracorporeal membrane oxygenation (ECMO) in patients with refractory out-of-hospital cardiac arrest in London, United Kingdom.

Aim: Sub30 study is an open-label, prospective, single-arm feasibility study with the primary objective of assessing the logistics, feasibility, and safety of ECPR delivery in a pre-hospital setting for refractory out-of-hospital cardiac arrest patients in London, United Kingdom.

Results: Forty-three eligible patients were identified by London Ambulance Service over 27 trial recruitment days during a 13-month study period resulting in the despatch of the pre-hospital ECPR team to 18 patients. Five patients met full criteria and were cannulated for ECPR.

Search for CP-Violating Neutrino Nonstandard Interactions with the NOvA Experiment.

This Letter reports a search for charge-parity (CP) symmetry violating nonstandard interactions (NSI) of neutrinos with matter using the NOvA Experiment, and examines their effects on the determination of the standard oscillation parameters. Data from ν_{μ}(ν[over ¯]_{μ})→ν_{μ}(ν[over ¯]_{μ}) and ν_{μ}(ν[over ¯]_{μ})→ν_{e}(ν[over ¯]_{e}) oscillation channels are used to measure the effect of the NSI parameters ϵ_{eμ} and ϵ_{eτ}. With 90% CL the magnitudes of the NSI couplings are constrained to be |ϵ_{eμ}|≲0.

Developing and testing a toolkit of interventions to improve adherence to non-invasive ventilation in children: the SPIRITUS study protocol.

Introduction: Non-invasive ventilation (NIV) is a known effective and safe treatment for children and young people with sleep disordered breathing (SDB). Adherence can be challenging and poor adherence risks undertreatment of SDB. While the risk factors for non-adherence have been widely reported, very few interventions have been tested in any capacity to address barriers to adherence.

High throughput application of the NanoBiT Biochemical Assay for the discovery of selective inhibitors of the interaction of PI3K-p110α with KRAS.

The NanoBiT Biochemical Assay (NBBA) was designed as a biochemical format of the NanoBiT cellular assay, aiming to screen weak protein-protein interactions (PPIs) in mammalian cell lysates. Here we present a High Throughput Screening (HTS) application of the NBBA to screen small molecule and fragment libraries to identify compounds that block the interaction of KRAS-G12D with phosphatidylinositol 3-kinase (PI3K) p110α. This interaction promotes PI3K activity, resulting in the promotion of cell growth, proliferation and survival, and is required for tumour initiation and growth in mouse lung cancer models, whilst having little effect on the health of normal adult mice, establishing the significance of the p110α/KRAS interaction as an oncology drug target.

Routine use of patient-reported experience and outcome measures for children and young people: a scoping review.

Background: Patient-reported outcome measures (PROMs) measure people's views of their health status whereas patient-reported experience measures (PREMs) are questionnaires measuring perceptions of their experience whilst receiving healthcare. PROMs/PREMs have the potential to enable children and young people (CYP) to be involved in decisions about their care and improve the quality of their care but it is not clear how often PROMs/PREMs are incorporated as part of standard care of CYP in the hospital setting. The aims of this scoping review were to understand the extent of the literature and map available evidence on the use, benefits, barriers and facilitators of PROMs/PREMs as part of standard care and treatment of CYP in hospitals.

Precision Activity-Based α-Amylase Probes for Dissection and Annotation of Linear and Branched-Chain Starch-Degrading Enzymes.

α-Amylases are the workhorse enzymes of starch degradation. They are central to human health, including as targets for anti-diabetic compounds, but are also the key enzymes in the industrial processing of starch for biofuels, corn syrups, brewing and detergents. Dissection of the activity, specificity and stability of α-amylases is crucial to understanding their biology and allowing their exploitation.

Search for Soft Unclustered Energy Patterns in Proton-Proton Collisions at 13 TeV.

The first search for soft unclustered energy patterns (SUEPs) is performed using an integrated luminosity of 138  fb^{-1} of proton-proton collision data at sqrt[s]=13  TeV, collected in 2016-2018 by the CMS detector at the LHC. Such SUEPs are predicted by hidden valley models with a new, confining force with a large 't Hooft coupling. In events with boosted topologies, selected by high-threshold hadronic triggers, the multiplicity and sphericity of clustered tracks are used to reject the background from standard model quantum chromodynamics.

Lifetime brain atrophy estimated from a single MRI: measurement characteristics and genome-wide correlates.

A measure of lifetime brain atrophy (LBA) obtained from a single magnetic resonance imaging (MRI) scan could be an attractive candidate to boost statistical power in uncovering novel genetic signals and mechanisms of neurodegeneration. We analysed data from five young and old adult cohorts (MRi-Share, Human Connectome Project, UK Biobank, Generation Scotland Subsample, and Lothian Birth Cohort 1936 [LBC1936]) to test the validity and utility of LBA inferred from cross-sectional MRI data, i.e.