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Recent research indicates that paired comparisons can accelerate perceptual learning of challenging dermatological lesion categories. Here we investigated whether the role of object categories as targets or distractors differentially influences learning outcomes. The frequency with which a given category occupied the target position was manipulated across three learning conditions: Always-Never, where half of 10 categories were always shown as target and the other half never shown as target; Often-Rarely, where half of categories appeared 75% as targets and 25% as distractors, with reversed presentation frequency for the other half; and Equal Split learning, in which all categories appeared as targets or distractors equally often. After learning, transfer results indicated that all conditions yielded equivalent overall learning, but categories prioritized more often as targets exhibited greater learning gains. These findings implicate differential processing of images in comparisons, even when no information regarding target vs. distractor was given prior to feedback.

Abstract Metformin is an antihyperglycemic used to treat type 2 diabetes mellitus (T2DM). Patients with T2DM are at increased risk of cardiovascular disease. We explored the association between metformin use and cardiovascular magnetic resonance (CMR) derived stress myocardial blood flow (MBF), myocardial perfusion reserve (MPR) and major adverse cardiovascular events (MACE; all cause death, MI, stroke, heart failure hospitalisation and coronary revascularisation) in patients with T2DM. Multi-centre study of patients with T2DM, and healthy controls, underwent quantitative myocardial perfusion CMR using an artificial intelligence supported process. Multivariable regression analysis, and cox proportional hazard models of propensity score weighted patients quantified associations between metformin use, MBF, MPR, all cause death and MACE. Analysis included 572 patients with T2DM (68% prescribed metformin) with median follow-up 851 days (IQR 935 − 765). Metformin use was associated with an increase of MPR of 0.12 [0.08–0.40], p = 0.004. There were 82 MACE events (14.3%) including 25 (4.4%) deaths of which 16 were in those not prescribed metformin (8.7%), compared to 9 in patients prescribed metformin (2.3%): adjusted hazard ratio 0.24 (95% CI 0.08–0.70, p = 0.009). MACE events were similar between groups. This multicentre, inverse probability weighting propensity score analysis study showed that in patients with T2DM, metformin use is associated with higher MPR and improved all cause survival.

Abstract Aortic valve replacement (AVR) leads to reverse cardiac remodeling in patients with aortic stenosis (AS). The aim of this secondary pooled analysis was to assess the degree and determinants of changes in myocardial perfusion post AVR, and its link with exercise capacity, in patients with severe AS. A total of 68 patients underwent same-day echocardiography and cardiac magnetic resonance imaging with adenosine stress pre and 6–12 months post-AVR. Of these, 50 had matched perfusion data available (age 67 ± 8 years, 86% male, aortic valve peak velocity 4.38 ± 0.63 m/s, aortic valve area index 0.45 ± 0.13cm2/m2). A subgroup of 34 patients underwent a symptom-limited cardiopulmonary exercise test (CPET) to assess maximal exercise capacity (peak VO2). Baseline and post-AVR parameters were compared and linear regression was used to determine associations between baseline variables and change in myocardial perfusion and exercise capacity. Following AVR, stress myocardial blood flow (MBF) increased from 1.56 ± 0.52 mL/min/g to 1.80 ± 0.62 mL/min/g (p

Abstract Categorical learning is important and often challenging in both specialized domains, such as medical image interpretation, and commonplace ones, such as face recognition. Research has shown that comparing items from different categories can enhance the learning of perceptual classifications, particularly when those categories appear highly similar. Here, we developed and tested novel adaptively triggered comparisons (ATCs), in which errors produced during interactive learning dynamically prompted the presentation of active comparison trials. In a facial identity paradigm, undergraduate participants learned to recognize and name varying views of 22 unknown people. In Experiment 1, single-item classification trials were compared to a condition in which ATC trials were generated whenever a participant repeatedly confused two faces. Comparison trials required discrimination between simultaneously presented exemplars from the confused categories. In Experiment 2, an ATC condition was compared to a non-adaptive comparison condition. Participants learned to accuracy and speed criteria, and completed immediate and delayed posttests. ATCs substantially enhanced learning efficiency in both experiments. These studies, using a novel adaptive procedure guided by each learner’s performance, show that adaptively triggered comparisons improve category learning.

Abstract Aims Patients with a reduced left ventricular ejection fraction (LVEF) following an acute myocardial infarction (MI) are at risk of progressive adverse cardiac remodelling that can lead to the development of heart failure and death. The early addition of a sodium‐glucose cotransporter 2 (SGLT2) inhibitor to standard treatment may delay or prevent progressive adverse remodelling in these patients. Methods and results EMpagliflozin to PREvent worSening of left ventricular volumes and Systolic function after Myocardial Infarction (EMPRESS‐MI) is a randomized, double‐blind, placebo‐controlled, multi‐centre trial designed to assess the effect of empagliflozin on cardiac remodelling evaluated using cardiovascular magnetic resonance (CMR) in 100 patients with left ventricular systolic dysfunction following MI. Eligible patients were those ≥12 h and ≤14 days following acute MI, with an LVEF

Abstract Background Pulmonary transit time (PTT) can be measured automatically from arterial input function (AIF) images of dual sequence first-pass perfusion imaging. PTT has been validated against invasive cardiac catheterisation correlating with both cardiac output and left ventricular filling pressure (both important prognostic markers in heart failure). We hypothesized that prolonged PTT is associated with clinical outcomes in patients with heart failure. Methods We recruited outpatients with a recent diagnosis of non-ischaemic heart failure with left ventricular ejection fraction (LVEF)

GlyCompareCT is a portable command-line tool to facilitate downstream glycomic data analyses, by addressing data inherent sparsity and non-independence. Inputting glycan abundances, users can run GlyCompareCT with one line of code to obtain the abundances of a minimal substructure set, named glycomotif, thereby quantifying hidden biosynthetic relationships between measured glycans. Optional parameters tuning and annotation are supported for personal preference. For complete details on the use and execution of this protocol, please refer to Bao et al. (2021).1.

The symposium ‘Advances in the Study of Visual and Multisensory Objects’ provides convergent focus of research from a broad range of subject areas. Using both nuanced philosophical analysis and informed empirical work, the symposium offers an interdisciplinary look at different aspects of visual and multisensory objects. It integrates three methodological approaches in a well-balanced way: philosophy of perception, experimental psychology, and cognitive neuroscience. Presenting a crucial part of the forthcoming collection (A. Mroczko-Wąsowicz & R. Grush (Eds.) Sensory Individuals: Unimodal and Multimodal Perspectives. Oxford: OUP), the symposium focuses on specific and closely related questions.

Combining perceptual learning techniques with adaptive learning algorithms has been shown to accelerate the development of expertise in medical and STEM learning domains (Kellman & Massey, 2013; Kellman, Jacoby, Massey & Krasne, 2022). Virtually all adaptive learning systems have relied on simple accuracy data that does not take into account response bias, a problem that may be especially consequential in multi-category perceptual classifications. We investigated whether adaptive perceptual learning in skin cancer screening can be enhanced by incorporating signal detection theory (SDT) methods that separate sensitivity from criterion. SDT-style concepts were used to alter sequencing, and separately to define mastery (category retirement). SDT retirement used a running d’ estimate calculated from a recent window of trials based on hit and false alarm rates. Undergraduate participants used a Skin Cancer PALM (perceptual adaptive learning module) to learn classification of 10 cancerous and readily-confused non-cancerous skin lesion types. Four adaptive conditions varied either the type of adaptive sequencing (standard vs. SDT) or retirement criteria (standard vs. SDT). A non-adaptive control condition presented didactic instruction on dermatologic screening in video form, including images, classification schemes, and detailed explanations. All adaptive conditions robustly outperformed the non-adaptive control in both learning efficiency and fluency (large effect sizes). Between adaptive conditions, SDT retirement criteria produced greater learning efficiency than standard, accuracy-based mastery criteria at both immediate and delayed posttests (medium effect sizes). SDT sequencing and standard adaptive sequencing did not differ. SDT enhancements to adaptive perceptual learning procedures have potential to enhance learning efficiency.

Understanding cellular metabolism is important across biotechnology and biomedical research and has critical implications in a broad range of normal and pathological conditions. Here, we introduce the user-friendly web-based platform ImmCellFie, which allows the comprehensive analysis of metabolic functions inferred from transcriptomic or proteomic data. We explain how to set up a run using publicly available omics data and how to visualize the results. The ImmCellFie algorithm pushes beyond conventional statistical enrichment and incorporates complex biological mechanisms to quantify cell activity. For complete details on the use and execution of this protocol, please refer to Richelle et al. (2021).1.

Vertebrate sialic acids (Sias) display much diversity in modifications, linkages, and underlying glycans. Slide microarrays allow high-throughput explorations of sialoglycan-protein interactions. A microarray presenting ~150 structurally defined sialyltrisaccharides with various Sias linkages and modifications still poses challenges in planning, data sorting, visualization, and analysis. To address these issues, we devised a simple 9-digit code for sialyltrisaccharides with terminal Sias and underlying two monosaccharides assigned from the nonreducing end, with 3 digits assigning a monosaccharide, its modifications, and linkage. Calculations based on the encoding system reveal >113,000 likely linear sialyltrisaccharides in nature. Notably, a biantennary N-glycan with 2 terminal sialyltrisaccharides could thus have >1010 potential combinations and a triantennary N-glycan with 3 terminal sequences, >1015 potential combinations. While all possibilities likely do not exist in nature, sialoglycans encode enormous diversity. While glycomic approaches are used to probe such diverse sialomes, naturally occurring bacterial AB5 toxin B subunits are simpler tools to track the dynamic sialome in biological systems. Sialoglycan microarray was utilized to compare sialoglycan-recognizing bacterial toxin B subunits. Unlike the poor correlation between B subunits and species phylogeny, there is stronger correlation with Sia-epitope preferences. Further supporting this pattern, we report a B subunit (YenB) from Yersinia enterocolitica (broad host range) recognizing almost all sialoglycans in the microarray, including 4-O-acetylated-Sias not recognized by a Yersinia pestis orthologue (YpeB). Differential Sia-binding patterns were also observed with phylogenetically related B subunits from Escherichia coli (SubB), Salmonella Typhi (PltB), Salmonella Typhimurium (ArtB), extra-intestinal E.coli (EcPltB), Vibrio cholera (CtxB), and cholera family homologue of E. coli (EcxB).

Abstract With the continued emergence of variants of concern, the global threat of COVID-19 persists, particularly in low- and middle-income countries with limited vaccine access. Protein-based vaccines, such as SCB-2019, can be produced on a large scale at a low cost while antigen design and adjuvant use can modulate efficacy and safety. While effective humoral immunity against SARS-CoV-2 variants has been shown to depend on both neutralization and Fc-mediated immunity, data on the effectiveness of protein-based vaccines with enhanced Fc-mediated immunity is limited. Here, we assess the humoral profile, including antibody isotypes, subclasses, and Fc receptor binding generated by a boosting with a recombinant trimer-tag protein vaccine SCB-2019. Individuals who were primed with 2 doses of the ChAdOx1 vaccine were equally divided into 4 groups and boosted with following formulations: Group 1: 9 μg SCB-2019 and Alhydrogel; Group 2: 9 μg SCB-2019, CpG 1018, and Alhydrogel; Group 3: 30 μg SCB-2019, CpG 1018, and Alhydrogel; Group 4: ChAdOx1. Group 3 showed enhanced antibody FcγR binding against wild-type and variants compared to Groups 1 and 2, showing a dose-dependent enhancement of immunity conferred by the SCB-2019 vaccine. Moreover, from day 15 after vaccination, Group 3 exhibited higher IgG3 and FcγR binding across variants of concerns, including Omicron and its subvariants, compared to the ChAdOx1-boosted individuals. Overall, this highlights the potential of SCB-2019 as a cost-efficient boosting regimen effective across variants of concerns.

With a brief half-second presentation, a medical expert can determine at above chance levels whether a medical scan she sees is abnormal based on a first impression arising from an initial global image process, termed "gist." The nature of gist processing is debated but this debate stems from results in medical experts who have years of perceptual experience. The aim of the present study was to determine if gist processing for medical images occurs in naïve (non-medically trained) participants who received a brief perceptual training and to tease apart the nature of that gist signal. We trained 20 naïve participants on a brief perceptual-adaptive training of histology images. After training, naïve observers were able to obtain abnormality detection and abnormality categorization above chance, from a brief 500 ms masked presentation of a histology image, hence showing "gist." The global signal demonstrated in perceptually trained naïve participants demonstrated multiple dissociable components, with some of these components relating to how rapidly naïve participants learned a normal template during perceptual learning. We suggest that multiple gist signals are present when experts view medical images derived from the tens of thousands of images that they are exposed to throughout their training and careers. We also suggest that a directed learning of a normal template may produce better abnormality detection and identification in radiologists and pathologists.

IntroductionA remarkable phenomenon in perception is that the visual system spontaneously organizes sets of discrete elements into abstract shape representations. We studied perceptual performance with dot displays to discover what spatial relationships support shape perception.MethodsIn Experiment 1, we tested conditions that lead dot arrays to be perceived as smooth contours vs. having vertices. We found that the perception of a smooth contour vs. a vertex was influenced by spatial relations between dots beyond the three points that define the angle of the point in question. However, there appeared to be a hard boundary around 90° such that any angle 90° or less was perceived as a vertex regardless of the spatial relations of ancillary dots. We hypothesized that dot arrays whose triplets were perceived as smooth curves would be more readily perceived as a unitary object because they can be encoded more economically. In Experiment 2, we generated dot arrays with and without such “vertex triplets” and compared participants’ phenomenological reports of a unified shape with smooth curves vs. shapes with angular corners. Observers gave higher shape ratings for dot arrays from curvilinear shapes. In Experiment 3, we tested shape encoding using a mental rotation task. Participants judged whether two dot arrays were the same or different at five angular differences. Subjects responded reliably faster for displays without vertex triplets, suggesting economical encoding of smooth displays. We followed this up in Experiment 4 using a visual search task. Shapes with and without vertex triplets were embedded in arrays with 25 distractor dots. Participants were asked to detect which display in a 2IFC paradigm contained a shape against a distractor with random dots. Performance was better when the dots were sampled from a smooth shape than when they were sampled from a shape with vertex triplets.Results and discussionThese results suggest that the visual system processes dot arrangements as coherent shapes automatically using precise smoothness constraints. This ability may be a consequence of processes that extract curvature in defining object shape and is consistent with recent theory and evidence suggesting that 2D contour representations are composed of constant curvature primitives.

3D phase imaging recovers an object's volumetric refractive index from intensity and/or holographic measurements. Partially coherent methods, such as illumination-based differential phase contrast (DPC), are particularly simple to implement in a commercial brightfield microscope. 3D DPC acquires images at multiple focus positions and with different illumination source patterns in order to reconstruct 3D refractive index. Here, we present a practical extension of the 3D DPC method that does not require a precise motion stage for scanning the focus and uses optimized illumination patterns for improved performance. The user scans the focus by hand, using the microscope's focus knob, and the algorithm self-calibrates the axial position to solve for the 3D refractive index of the sample through a computational inverse problem. We further show that the illumination patterns can be optimized by an end-to-end learning procedure. Combining these two, we demonstrate improved 3D DPC with a commercial microscope whose only hardware modification is LED array illumination.

Abstract Left ventricular fibrosis can be identified by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) in some veteran athletes. We aimed to investigate prevalence of ventricular fibrosis in veteran athletes and associations with cardiac arrhythmia. 50 asymptomatic male endurance athletes were recruited. They underwent CMR imaging including volumetric analysis, bright blood (BB) and dark blood (DB) LGE, motion corrected (MOCO) quantitative stress and rest perfusion and T1/T2/extracellular volume mapping. Athletes underwent 12-lead electrocardiogram (ECG) and 24-h ECG. Myocardial fibrosis was identified in 24/50 (48%) athletes. All fibrosis was mid-myocardial in the basal-lateral left ventricular wall. Blood pressure was reduced in athletes without fibrosis compared to controls, but not athletes with fibrosis. Fibrotic areas had longer T2 time (44 ± 4 vs. 40 ± 2 ms, p

Human Milk Oligosaccharides (HMOs) are abundant carbohydrates fundamental to infant health and development. Although these oligosaccharides were discovered more than half a century ago, their biosynthesis in the mammary gland remains largely uncharacterized. Here, we use a systems biology framework that integrates glycan and RNA expression data to construct an HMO biosynthetic network and predict glycosyltransferases involved. To accomplish this, we construct models describing the most likely pathways for the synthesis of the oligosaccharides accounting for >95% of the HMO content in human milk. Through our models, we propose candidate genes for elongation, branching, fucosylation, and sialylation of HMOs. Our model aggregation approach recovers 2 of 2 previously known gene-enzyme relations and 2 of 3 empirically confirmed gene-enzyme relations. The top genes we propose for the remaining 5 linkage reactions are consistent with previously published literature. These results provide the molecular basis of HMO biosynthesis necessary to guide progress in HMO research and application with the goal of understanding and improving infant health and development.

Recent work suggests that learning perceptual classifications canbe enhanced by combining single item classifications with adaptivecomparisons triggered by each learner’s confusions. Here, weasked whether learning might work equally well using allcomparison trials. In a face identification paradigm, we testedsingle item classifications, paired comparisons, and dual instanceclassifications that resembled comparisons but required twoidentification responses. In initial results, the comparisonscondition showed evidence of greater efficiency (learning gaindivided by trials or time invested). We suspected that this effectmay have been driven by easier attainment of mastery criteria inthe comparisons condition, and a negatively accelerated learningcurve. To test this idea, we fit learning curves and found dataconsistent with the same underlying learning rate in all conditions.These results suggest that paired comparison trials may be aseffective in driving learning of multiple perceptual classificationsas more demanding single item classifications.