Clinical Validation of Digitally Acquired Clinical Data and Machine Learning Models for Remote Measurement of Psoriasis and Psoriatic Arthritis: A Proof-of-Concept Study.

OBJECTIVE: Psoriatic disease remains underdiagnosed and undertreated. We developed and validated a suite of novel, sensor-based smartphone assessments (Psorcast app) that can be self-administered to measure cutaneous and musculoskeletal signs and symptoms of psoriatic disease. METHODS: Participants with psoriasis (PsO) or psoriatic arthritis (PsA) and healthy controls were recruited between June 5, 2019, and November 10, 2021, at 2 academic medical centers. Concordance and accuracy of digital measures and image-based machine learning models were compared to their analogous clinical measures from trained rheumatologists and dermatologists. RESULTS: Of 104 study participants, 51 (49%) were female and 53 (51%) were male, with a mean age of 42.3 years (SD 12.6). Seventy-nine (76%) participants had PsA, 16 (15.4%) had PsO, and 9 (8.7%) were healthy controls. Digital patient assessment of percent body surface area (BSA) affected with PsO demonstrated very strong concordance (Lin concordance correlation coefficient [CCC] 0.94 [95% CI 0.91-0.96]) with physician-assessed BSA. The in-clinic and remote target plaque physician global assessments showed fair-to-moderate concordance (CCCerythema 0.72 [0.59-0.85]; CCCinduration 0.72 [0.62-0.82]; CCCscaling 0.60 [0.48-0.72]). Machine learning models of hand photos taken by patients accurately identified clinically diagnosed nail PsO with an accuracy of 0.76. The Digital Jar Open assessment categorized physician-assessed upper extremity involvement, considering joint tenderness or enthesitis (AUROC 0.68 [0.47-0.85]). CONCLUSION: The Psorcast digital assessments achieved significant clinical validity, although they require further validation in larger cohorts before use in evidence-based medicine or clinical trial settings. The smartphone software and analysis pipelines from the Psorcast suite are open source and freely available.

Ordering Eyeglasses Using 3D Head Scan Technology versus Established Online and Storefront Clinic Methods.

SIGNIFICANCE: This study investigates how a new smartphone scanning technology compares with established online and storefront vendors in providing remote measurement and adjustment of prescription eyeglasses. PURPOSE: This study aimed to evaluate a new technology for ordering prescription eyeglasses online. METHODS: Thirty participants with 2.00 to 2.75 D of presbyopia (aged 49 to 74 years) were asked to order eyeglasses with progressive addition lenses from four vendors: one online vendor using a new head scan technology (Topology, San Francisco, CA), two established Web site-based vendors (vendors A and B), and one storefront vendor: Université de Montréal's Vision Clinic (UMVC). The resulting measurements were compared with those of opticians. Participant-reported preferences on visual and physical comfort of eyeglasses were collected after 15-minute trials of eyeglasses from each vendor. RESULTS: Pupillary half-distance measured with Topology matched optician measurements, but online vendors A and B diverged (mean difference, - 0.80 mm [ Z = -2.79; P = .005]). Topology and vendor B segment addition heights were similar to optician measurements, but vendor A diverged (mean, -1.40 mm [ Z = -2.58; P = .01]). The personalization parameter values obtained with Topology were different from optician measurements for pantoscopic angle (-5.30° [ Z = -4.12; P < .001]) and face wrap angle (+1.25° [ Z = -2.94; P = .003]). The UMVC eyeglasses scored best for adjustment (8.71/10 [ Z = -5.53; P < .001]), with Topology coming second (7.23/10). Topology scores were equivalent to UMVC scores for all eight items of patient-reported preferences (nonparametric Friedman analysis of variance, P < .05). CONCLUSIONS: Basic lens centration measurements obtained with Topology compare well with those of opticians, but some aspects of the methodology for measuring personalization parameters could be improved. In comparison with two established online vendors, resulting measurements with Topology are more consistent. Initial wearer satisfaction with Topology eyeglasses was also better.

Tetrahymena Poc5 is a transient basal body component that is important for basal body maturation.

Basal bodies (BBs) are microtubule-based organelles that act as a template for and stabilize cilia at the cell surface. Centrins ubiquitously associate with BBs and function in BB assembly, maturation and stability. Human POC5 (hPOC5) is a highly conserved centrin-binding protein that binds centrins through Sfi1p-like repeats and is required for building full-length, mature centrioles. Here, we use the BB-rich cytoskeleton of Tetrahymena thermophila to characterize Poc5 BB functions. Tetrahymena Poc5 (TtPoc5) uniquely incorporates into assembling BBs and is then removed from mature BBs prior to ciliogenesis. Complete genomic knockout of TtPOC5 leads to a significantly increased production of BBs, yet a markedly reduced ciliary density, both of which are rescued by reintroduction of TtPoc5. A second Tetrahymena POC5-like gene, SFR1, is similarly implicated in modulating BB production. When TtPOC5 and SFR1 are co-deleted, cell viability is compromised and BB overproduction is exacerbated. Overproduced BBs display defective transition zone formation and a diminished capacity for ciliogenesis. This study uncovers a requirement for Poc5 in building mature BBs, providing a possible functional link between hPOC5 mutations and impaired cilia.This article has an associated First Person interview with the first author of the paper.

Combinatorial Interactions of Essential Oils Enriched with Individual Polyphenols, Polyphenol Mixes, and Plant Extracts: Multi-Antioxidant Systems.

With the aim to develop essential oil (EO) multi-antioxidant systems, combinatorial interactions of selected phenol and terpene-rich EOs (from Pimento Berry, Ceylon Cinnamon, Clove, Sage, White thyme; Oregano) enriched with individual polyphenols, crude plant extracts, and mixtures of their major polyphenols were investigated using single electron transfer (SET)-based DPPH and hydrogen atom transfer (HAT)-based ORAC assays. Polyphenols that enriched Eos the most favorably were rosmarinic acid (IC50 of 0.0891-0.1448 mg enriched EO/mg DPPH; 5772-17,879 µmol TE/g enriched EO) and quercetin (IC50 of 0.0682-0.1060 mg enriched EO/mg DPPH; Trolox Equivalents (TE) of 9776-14,567µmol /g enriched EO), whereas p-coumaric acid (IC50 of 0.1865-1.1424 mg enriched EO/mg DPPH; 7451.00-11,588 µmol TE/g enriched EO) and rutin hydrate (IC50 of 0.1140-0.3112 mg enriched EO/mg DPPH; 2298-6227 µmol TE/g enriched EO) were the least favorable. Enrichments with polyphenol mixes and crude extracts exhibited synergistic and additive effects in the SET-based DPPH assay. In the HAT-based ORAC assay, EO enrichments with crude extracts exhibited more additive effects, as well as less antagonistic effects, than enrichments with their major polyphenol mixes, revealing the significant contributions of minor compounds. EOs enriched with crude green tea and apple extracts exhibited synergistic or additive effects, whereas EOs enriched with grape seed and rosemary extracts exhibited equal antagonistic effects. Predictive models were developed to explain the variability between the observed and predicted antioxidant activities of enriched EOs.

Intracranial internal carotid artery calcification is not predictive of future cognitive decline.

BACKGROUND: Intracranial internal carotid artery (ICA) calcification is a common incidental finding in non-contrast head CT. We evaluated the predictive value of ICAC (ICAC) for future risk of cognitive decline and compared the results with conventional imaging biomarkers of dementia. METHODS: In a retrospective observational cohort, we included 230 participants with a PET-CT scan within 18 months of a baseline clinical assessment and longitudinal imaging assessments. Intracranial ICAC was quantified on baseline CT scans using the Agatson calcium score, and the association between baseline ICA calcium scores and the risk of conversion from a CDR of zero in baseline to a persistent CDR > 0 at any follow-up visit, as well as longitudinal changes in cognitive scores, were evaluated through linear and mixed regression models. We also evaluated the association of conventional imaging biomarkers of dementia with longitudinal changes in cognitive scores and a potential indirect effect of ICAC on cognition through these biomarkers. RESULTS: Baseline ICA calcium score could not distinguish participants who converted to CDR > 0. ICA calcium score was also unable to predict longitudinal changes in cognitive scores, imaging biomarkers of small vessel disease such as white matter hyperintensities (WMH) volume, or AD such as hippocampal volume, AD cortical signature thickness, and amyloid burden. Severity of intracranial ICAC increased with age and in men. Higher WMH volume and amyloid burden as well as lower hippocampal volume and AD cortical signature thickness at baseline predicted lower Mini-Mental State Exam scores at longitudinal follow-up. Baseline ICAC was indirectly associated with longitudinal cognitive decline, fully mediated through WMH volume. CONCLUSIONS: In elderly and preclinical AD populations, atherosclerosis of large intracranial vessels as demonstrated through ICAC is not directly associated with a future risk of cognitive impairment, or progression of imaging biomarkers of AD or small vessel disease.

The impact of social enterprise on food insecurity - An Australian case study.

Like many high-income countries, in Australia there are a range of programmes in place, from social security to food banks, to help address food insecurity. So far, they have been unable to adequately alleviate and prevent this growing nutrition challenge. This paper presents an evaluation of a new type of intervention in the food security landscape, the social enterprise. The Community Grocer is a social enterprise that operates weekly fresh fruit and vegetable markets in Melbourne, Australia. The aim of the study was to examine the market's ability to increase access, use and availability of nutritious food in a socially acceptable way, for low socioeconomic status urban-dwelling individuals. The mixed-method evaluation included: comparative price audits (n = 27) at local (<1 km) stores; analysis of operational data from sample markets (n = 3); customer surveys (n = 91) and customer interviews (n = 12), collected in two phases (Autumn 2017, Summer 2018). The results found common (n = 10) fruit and vegetables cost, on average, approximately 40% less at the social enterprise, than local stores. Over twenty per cent of customers were food insecure and 80% of households were low income. Thirty-four different nationalities shopped at the market, and just over half (54%) shopped there weekly. More than 50 types of vegetables and fruit were available to purchase, varying for cultural preferences and seasonality, which supported variety and choice. Overall, this enterprise promotes food security in a localised area through low-cost, convenient, dignified and nutritious offerings.

Structural characterization of site-modified nanocapsid with monodispersed gold clusters.

Hepatitis E Virus-like particles self-assemble in to noninfectious nanocapsids that are resistant to proteolytic/acidic mucosal delivery conditions. Previously, the nanocapsid was engineered to specifically bind and enter breast cancer cells, where successful tumor targeting was demonstrated in animal models. In the present study, the nanocapsid surface was modified with a solvent-exposed cysteine to conjugate monolayer protected gold nanoclusters (AuNC). Unlike commercially available gold nanoparticles, AuNCs monodisperse in water and are composed of a discrete number of gold atoms, forming a crystalline gold core. Au102 pMBA44 (Au102) was an ideal conjugate given its small 2.5 nm size and detectability in cryoEM. Au102 was bound directly to nanocapsid surface cysteines via direct ligand exchange. In addition, Au102 was functionalized with a maleimide linker (Au102_C6MI) for maleimide-thiol conjugation to nanocapsid cysteines. The AuNC-bound nanocapsid constructs were conjugated in various conditions. We found Au102_C6MI to bind nanocapsid more efficiently, while Au102 remained more soluble over time. Nanocapsids conjugated to Au102_C6MI were imaged in cryoEM for single particle reconstruction to localize AuNC position on the nanocapsid surface. We resolved five unique high intensity volumes that formed a ring-shaped density at the 5-fold symmetry center. This finding was further supported by independent rigid modeling.