Harnessing digital footprint data for population health: a discussion on collaboration, challenges and opportunities in the UK.

Digital footprint data are inspiring a new era in population health and well-being research. Linking these novel data with other datasets is critical for future research wishing to use these data for the public good. In order to succeed, successful collaboration among industry, academics and policy-makers is vital.

Identification and characterization of human GDF15 knockouts.

Growth differentiation factor 15 (GDF15) is a secreted protein that regulates food intake, body weight and stress responses in pre-clinical models. The physiological function of GDF15 in humans remains unclear. Pharmacologically, GDF15 agonism in humans causes nausea without accompanying weight loss, and GDF15 antagonism is being tested in clinical trials to treat cachexia and anorexia.

Assessing the value of integrating national longitudinal shopping data into respiratory disease forecasting models.

The COVID-19 pandemic led to unparalleled pressure on healthcare services. Improved healthcare planning in relation to diseases affecting the respiratory system has consequently become a key concern. We investigated the value of integrating sales of non-prescription medications commonly bought for managing respiratory symptoms, to improve forecasting of weekly registered deaths from respiratory disease at local levels across England, by using over 2 billion transactions logged by a UK high street retailer from March 2016 to March 2020.

Using Shopping Data to Improve the Diagnosis of Ovarian Cancer: Computational Analysis of a Web-Based Survey.

Background: Shopping data can be analyzed using machine learning techniques to study population health. It is unknown if the use of such methods can successfully investigate prediagnosis purchases linked to self-medication of symptoms of ovarian cancer.

Objective: The aims of this study were to gain new domain knowledge from women's experiences, understand how women's shopping behavior relates to their pathway to the diagnosis of ovarian cancer, and inform research on computational analysis of shopping data for population health.

Public attitudes towards sharing loyalty card data for academic health research: a qualitative study.

Background: A growing number of studies show the potential of loyalty card data for use in health research. However, research into public perceptions of using this data is limited. This study aimed to investigate public attitudes towards donating loyalty card data for academic health research, and the safeguards the public would want to see implemented.

Circumventing the "Ick" Factor: A Randomized Trial of the Effects of Omitting Affective Attitudes Questions to Increase Intention to Become an Organ Donor.

Including or excluding certain questions about organ donation may influence peoples' intention to donate. We investigated the effect of omitting certain affective attitudinal items on potential donors' intention and behavior for donation. A cross-sectional survey with a subgroup nested randomized trial.

The synthesis and evaluation of indolylureas as PKCα inhibitors.

PKCα and PKA have crucial but opposing roles in the regulation of calcium handling within myocytes. Identification of compounds that inhibit PKCα, but not PKA, are potential therapeutic targets for the treatment of heart disease. The synthesis of indolylureas are described, and a compound displaying nanomolar inhibition towards PKCα with significant selectivity over PKA has been identified.

Treatment with a corticotrophin releasing factor 2 receptor agonist modulates skeletal muscle mass and force production in aged and chronically ill animals.

Background: Muscle weakness is associated with a variety of chronic disorders such as emphysema (EMP) and congestive heart failure (CHF) as well as aging. Therapies to treat muscle weakness associated with chronic disease or aging are lacking. Corticotrophin releasing factor 2 receptor (CRF2R) agonists have been shown to maintain skeletal muscle mass and force production in a variety of acute conditions that lead to skeletal muscle wasting.

Ammonia-oxidizing archaea involved in nitrogen removal.

Ammonia oxidation is critical to global nitrogen cycling and is often thought to be driven only by ammonia-oxidizing bacteria. The recent finding of new ammonia-oxidizing organisms belonging to the archaeal domain challenges this perception. Two major microbial groups are now believed to be involved in ammonia oxidation: chemolithotrophic ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA).

Corticortophin releasing factor 2 receptor agonist treatment significantly slows disease progression in mdx mice.

Background: Duchenne muscular dystrophy results from mutation of the dystrophin gene, causing skeletal and cardiac muscle loss of function. The mdx mouse model of Duchenne muscular dystrophy is widely utilized to evaluate the potential of therapeutic regimens to modulate the loss of skeletal muscle function associated with dystrophin mutation. Importantly, progressive loss of diaphragm function is the most consistent striated muscle effect observed in the mdx mouse model, which is the same as in patients suffering from Duchenne muscular dystrophy.

ICAT-MS-MS time course analysis of atrophying mouse skeletal muscle cytosolic subproteome.

Skeletal muscle atrophy is a process in which protein degradation exceeds protein synthesis, resulting in a decrease of the muscle's physiological cross-sectional area and mass, and is often a serious consequence of numerous health problems. We used the isotope-coded affinity tag (ICAT) labelling approach and MS-MS to protein profile cytosolic subcellular fractions from mouse tibialis anterior skeletal muscle undergoing 0, 4, 8, or 16 days of immobilisation-induced atrophy. For the validation of peptide and protein identifications statistical algorithms were applied to the sequence database search results in order to obtain consistent sensitivity/error rates for protein and peptide identifications at each immobilisation time point.

MALDI-TOF MS as a label-free approach to rapid inhibitor screening.

Mass Spectrometry (MS) has been widely reported for measuring the conversion of substrates to products for enzyme assays. These measurements are typically performed by time-consuming LC-MS to eliminate buffer salts that interfere with electrospray ionization MS. However, matrix-assisted laser desorption ionization, time-of-flight MS (MALDI-TOF MS) offers a label-free and direct readout of substrate and product, a fast sampling rate, and is tolerant of many buffer salts, reagents, and compounds that are typically found in enzyme reaction mixtures.

Modifications of the human urocortin 2 peptide that improve pharmacological properties.

Recently, we demonstrated that the corticotropin releasing factor 2 receptor agonist, urocortin 2, demonstrated anti-atrophy effects in rodent skeletal muscle atrophy models. Compared to other CRF2R agonists however, the in vivo pharmacological potency of urocortin 2 is poor when it is administered by continuous subcutaneous infusion. Therefore, we attempted to modify the structure of urocortin 2 to improve in vivo efficacy when administered by subcutaneous infusion.

Phosphodiesterase 4 inhibition reduces skeletal muscle atrophy.

Several GTP-binding protein (G-protein)-coupled receptors that signal through Galphas (GTP-binding protein alpha stimulatory) and the cyclic adenosine monophosphate (cAMP) pathway increase skeletal muscle mass. In order to further evaluate the role of the cAMP pathway in the regulation of skeletal muscle mass, we utilized inhibitors of phosphodiesterase 4 (PDE 4), the major cAMP-modifying PDE found in skeletal muscle, to modulate skeletal muscle cAMP levels. We found that PDE 4 inhibitors reduced the loss of muscle mass and force resulting from denervation and casting in rats and mice.

Protein control of electron transfer rates via polarization: molecular dynamics studies of rubredoxin.

The protein matrix of an electron transfer protein creates an electrostatic environment for its redox site, which influences its electron transfer properties. Our studies of Fe-S proteins indicate that the protein is highly polarized around the redox site. Here, measures of deviations of the environmental electrostatic potential from a simple linear dielectric polarization response to the magnitude of the charge are proposed.

Simulations of membranes and other interfacial systems using P2(1) and Pc periodic boundary conditions.

We demonstrate the ease and utility of simulating heterogeneous interfacial systems with P2(1) and Pc periodic boundary conditions which allow, for example, lipids in a membrane to switch leaflets. In preliminary tests, P2(1) was shown to yield equivalent results to P1 in simulations of bulk water, a water/vacuum interface, and pure DPPC bilayers with an equal number of lipids per leaflet; equivalence of Pc and P1 was also demonstrated for the former two systems. P2(1) was further tested in simulations involving the spreading of an octane film on water, and equilibration of a DPPC bilayer from an initial condition containing different numbers of lipids in the two leaflets.