Miracle-dz/UniFAR-FTUs huggingface dataset:
Detecting unstable plaques in humans using cardiac CT: Can it guide treatments?

Advances in imaging technology have driven the rapid expansion in the use of CT in the assessment of coronary atherosclerotic plaque. Based on a rapidly growing evidence base, current guidelines recommend coronary CT angiography as the first‐line diagnostic test for patients presenting with stable chest pain. There is a growing need to refine current methods for diagnosis and risk stratification to improve the individualisation of preventative therapies. Imaging assessments of high‐risk plaque with CT can be used to differentiate stable from unstable patterns of coronary atherosclerosis and potentially to improve patient risk stratification. This review will focus on coronary imaging with CT with a specific focus on the detection of coronary atherosclerosis, high‐risk plaque features, and the implications for patient management.
Tryptophan metabolite 5-methoxytryptophan ameliorates arterial denudation-induced intimal hyperplasia via opposing effects on vascular endothelial and smooth muscle cells

Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, particularly among older adults. Despite the advent of medical technology, restenosis is still an issue after interventional procedures. Tryptophan metabolite 5-methoxytryptophan (5-MTP) has recently been shown to protect against systemic inflammatory responses. This study aimed to investigate the function and mechanisms of 5-MTP in interventional procedure-induced restenosis. We found that after mouse femoral artery denudation with a guide wire, 5-MTP accelerated recovery of endothelium in the denuded area and reduced vascular leakage and intimal thickening. 5-MTP increased endothelial cell proliferation in the denuded arteries and rescued TNF-α-reduced endothelial cell proliferation and migration, likely via maintaining vascular endothelial growth factor receptor 2 activation. In contrast, 5-MTP preserved differentiated phenotype of medial vascular smooth muscle cells (VSMCs) and decreased VSMC proliferation and migration. Furthermore, 5-MTP maintained expression levels of critical transcription factors for VSMC marker gene expressions via attenuated activation of p38 MAPK and NFκB-p65. Our findings uncover a novel protective mechanism of 5-MTP in restenosis. In response to denudation injury, 5-MTP attenuates intimal hyperplasia via concerted but opposing actions on endothelial cells and VSMCs. Taken together, our results suggest that 5-MTP is a valuable therapeutic target for arterial injury-induced restenosis.
The optimal drug adherence to maximize the efficacy and safety of non-vitamin K antagonist oral anticoagulant in real-world atrial fibrillation patients.

AIMS To investigate the association between adherence to non-vitamin K antagonist oral anticoagulant (NOAC) and clinical outcomes and to determine the optimal cut-off level of NOAC adherence among patients with atrial fibrillation (AF). METHODS AND RESULTS Using the Korean National Health Insurance Service database, we identified 96 197 patients with non-valvular AF who initiated NOAC or warfarin in 2013-16. We compared clinical outcomes between adherent [proportion of days covered (PDC) ≥80%] vs. non-adherent (PDC <80%) NOAC users, and further with warfarin users. We assessed the outcomes according to different levels of adherence. The proportion of adherent NOAC users was 64.0%. Compared with non-adherent NOAC users, adherent NOAC users were at lower risks of ischaemic stroke/systemic embolism (SE) [adjusted hazard ratio (aHR) 0.73, 95% confidence interval (CI) 0.69-0.79], and myocardial infarction (aHR 0.82, 95% CI 0.72-0.93), whereas there was no significant risk alteration for major bleeding (aHR 1.01, 95% CI 0.91-1.11). Compared with warfarin, non-adherent NOAC use failed to have better efficacy against ischaemic stroke/SE (aHR 0.99, 95% CI 0.93-1.05) and rather had increased risk of myocardial infarction (aHR 1.13, 95% CI 1.03-1.25). In NOAC users, the risks of adverse outcomes decreased according to gradual increase of adherence rates with the lowest risks in ≥90%, except for major bleeding in which there were no significant associations. CONCLUSIONS In an adherence level-dependent fashion, adherent use of NOAC showed better clinical outcomes without increasing bleeding risk. Maintaining ≥90% of adherence optimizes effectiveness of NOAC therapy without compromising its safety.
First‐in‐man controlled rewarming and normothermic perfusion with cell‐free solution of a kidney prior to transplantation

Cold preservation sensitizes organ grafts to exacerbation of tissue injury upon reperfusion. This reperfusion injury is not fully explained by the mere re‐introduction of oxygen but rather is pertinent to the immediate rise in metabolic turnover associated with the abrupt restoration of normothermia. Here we report the first clinical case of gradual resumption of graft temperature upon ex vivo machine perfusion from hypothermia up to normothermic conditions using cell‐free buffer as a perfusate. A kidney graft from an extended criteria donor was put on the machine after 12.5 hours of cold storage. During ex vivo perfusion, perfusion pressure and temperature were gradually elevated from 30 mm Hg and 8°C to 75 mm Hg and 35°C, respectively. Perfusate consisted of diluted Steen solution, oxygenated with 100% oxygen. Final flow rates at 35°C were 850 mL/min. The kidney was transplanted without complications and showed good immediate function. Serum creatinine fell from preoperative 720 µmol/L to 506 µmol/L during the first 24 hours after transplantation. Clearance after 1 week was 43.1 mL/min. Controlled oxygenated rewarming prior to transplantation can be performed up to normothermia without blood components or artificial oxygen carriers and may represent a promising tool to mitigate cold‐induced reperfusion injury or to evaluate graft performance.
Deferoxamine Enhanced Mitochondrial Iron Accumulation and Promoted Cell Migration in Triple-Negative MDA-MB-231 Breast Cancer Cells Via a ROS-Dependent Mechanism

In our previous study, Deferoxamine (DFO) increased the iron concentration by upregulating the expression levels of TfR1 and DMT1 and exacerbated the migration of triple-negative breast cancer cells. However, the mechanisms of iron distribution and utilization in triple-negative breast cancer cells with a DFO-induced iron deficiency are still unclear. In this study, triple-negative MDA-MB-231 and estrogen receptor (ER)-positive MCF-7 breast cancer cells were used to investigate the mechanisms of iron distribution and utilization with a DFO-induced iron deficiency. We found that the mitochondrial iron concentration was elevated in MDA-MB-231 cells, while it was decreased in MCF-7 cells after DFO treatment. The cellular and mitochondrial reactive oxygen species (ROS) levels increased in both breast cancer cell types under DFO-induced iron-deficient conditions. However, the increased ROS levels had different effects on the different breast cancer cell types: Cell viability was inhibited and apoptosis was enhanced in MCF-7 cells, but cell viability was maintained and cell migration was promoted in MDA-MB-231 cells through the ROS/NF-κB and ROS/TGF-β signaling pathways. Collectively, this study suggests that under DFO-induced iron-deficient conditions, the increased mitochondrial iron levels in triple-negative MDA-MB-231 breast cancer cells would generate large amounts of ROS to activate the NF-κB and TGF-β signaling pathways to promote cell migration.
Comparing computational models of vision to human behaviour

Biological vision and computational models of vision can be split into three independent components (image description, decision process, and image set). The thesis presented here aimed to investigate the influence of each of these core components on computational model’s similarity to human behaviour. Chapter 3 investigated the similarity of different computational image descriptors to their biological counterparts, using an image matching task. The results showed that several of the computational models could explain a significant amount of the variance in human performance on individual images. The deep supervised convolutional neural net explained the most variance, followed by GIST, HMAX and then PHOW. Chapter 4 investigated which computational decision process best explained observers’ behaviour on an image categorization task. The results showed that Decision Bound theory produced behaviour the closest to that of observers. This was followed by Exemplar theory and Prototype theory. Chapter 5 examined whether the naturally differing image set between computational models and observers could partially account for the difference in their behaviour. The results showed that, indeed, the naturally differing image set between computational models and observers was affecting the similarity of their behaviour. This gap did not alter which image descriptor best fit observers’ behaviour and could be reduced by training observers on the image set the computational models were using. Chapter 6 investigated, using computational models of vision, the impact of the neighbouring (masking) images on the target images in a RSVP task. This was done by combining the neighbouring images with the target image for the computational models’ simulation for each trial. The results showed that models behaviour became closer to that of the human observers when the neighbouring mask images were included in the computational simulations, as would be expected given an integration period for neural mechanisms. This thesis has shown that computational models can show quite similar behaviours to human observers, even at the level of how they perform with individual images. While this shows the potential utility in computational models as a tool to study visual processing, It has also shown the need to take into account many aspects of the overall model of the visual process and task; not only the image description, but the task requirements, the decision processes, the images being used as stimuli and even the sequence in which they are presented.
Synergy between EphA2-ILs-DTXp, a Novel EphA2-Targeted Nanoliposomal Taxane, and PD-1 Inhibitors in Preclinical Tumor Models

Combinations of chemotherapy with immunotherapy have seen recent clinical success, including two approvals of anti–PD-1/L1 agents in combination with taxane-based chemotherapy in non–small cell lung cancer and triple-negative breast cancer. Here, we present a study on the combination activity and mechanistic rationale of a novel EphA2-targeted liposomal taxane (EphA2-ILs-DTXp) and anti–PD-1. This combination was highly active in mouse syngeneic tumor models, with complete responses observed in 3 of 5 models. In the EMT-6 tumor model, combination of EphA2-ILs-DTXp with anti–PD-1 resulted in a 60% complete response rate, with durable responses that were resistant to rechallenge. These responses were not observed in the absence of CD8+ T cells. Characterization of the immune infiltrates in EMT-6 tumors reveals increased CD8+ T cells, increased CD8+ IFNγ+ CTLs, and an increased CD8/regulatory T-cell (Treg) ratio. These immunomodulatory effects were not observed in mice treated with a combination of docetaxel and anti–PD-1. Pharmacokinetic analysis revealed that the AUC of docetaxel was increased 15 times, from 52.1 to 785 ng/mL/hour, when delivered by EphA2-ILs-DTXp. A dose reduction study of EphA2-ILs-DTXp showed a dose–response relationship for both tumor growth inhibition and the CD8/Treg ratio. Our data indicate that synergism between docetaxel and anti–PD-1 is achievable with nanoliposomal delivery.
Moderating Effect of Dynamic Environment in the Relationship between Guanxi, Trust, and Repurchase Intention of Agricultural Materials

Repurchasing intention of agricultural materials is a key to a sustainable food business system. The novel contribution of this study is that we go beyond technical aspect and look into human capital dynamics in a general context, by examining how different dimensions of ‘guanxi’ (i.e., personal relations and instrumentality) between farmers and agricultural retailers affect trust between the two and, in turn, repeated purchase intention of agricultural materials by farmers in China. To further generate implications for food system as a whole, we also examined how dynamic environment moderates the effects mentioned above. Adopting survey method and multivariate analyses, this study tests the hypotheses with a collected data set of 578 farmers from representative rural areas of China. The results show that guanxi between farmers and agricultural retailers has a positive effect on trust between them and on repeated purchase intentions of farmers. While instrumentality has a negative effect on trust between them and on repeated purchase intentions of farmers. The trust between farmers and agricultural retailers promotes farmers’ repeated purchase intentions. The intensity of competition negatively moderates the positive relation between trust and repeated purchases. Demand uncertainty does not moderate the positive effect of trust on repeated purchases. The results and discussion shed light on agricultural food system sustainability from a dynamic environment embedded business relationship perspective.
Predicting student satisfaction and perceived learning within online learning environments

ABSTRACT Student satisfaction is used as one of the key elements to evaluate online courses, while perceived learning is considered as an indicator of learning. This study aimed to explore how online learning self-efficacy (OLSE), learner–content interaction (LCI), learner–instructor interaction (LII), and learner–learner interaction (LLI) can predict student satisfaction and perceived learning. A total of 167 students participated in this study. Regression results revealed that the overall model with all four predictor variables (OLSE, LCI, LII, and LLI) was significantly predictive of satisfaction and perceived learning. The study found that LCI was the strongest and most significant predictor of student satisfaction, while OLSE was the strongest and most significant predictor of perceived learning. However, LLI was not predictive of student satisfaction and perceived learning. This study suggests that instructors employ strategies that enhance students’ OLSE, LCI, and LII. Research is needed to understand how LLI fosters student learning and satisfaction.
Temporal Analysis of Amylase Expression in Control, Autoantibody-Positive, and Type 1 Diabetes Pancreatic Tissues

Within the human pancreas, exocrine and endocrine cells control secretion of digestive enzymes and production of hormones to maintain metabolic homeostasis, respectively. While the vast majority of type 1 diabetes research efforts have focused on endocrine function and autoimmunity, recent studies identified a series of unique features (e.g., reduced weight and volume, increased density of leukocytes) within the exocrine pancreas in this disease, but the mechanisms underlying these aberrancies are unknown. Therefore, we histologically assessed amylase, insulin, glucagon, lipase, and/or trypsinogen in 78 organ donor pancreata from birth through adulthood in control subjects and those at various stages of type 1 diabetes. While amylase-positive (AMY+) acinar cells were detectable in pancreata from all study groups, tissues from individuals >2 years of age contained clusters of acinar cells devoid of amylase (AMY−). A majority of these AMY− cell clusters localized proximal to islets (i.e., peri-islet). Additionally, most AMY− clusters were positive for the exocrine enzymes lipase and trypsinogen. Interestingly, type 1 diabetes pancreata displayed significant reductions in the frequency of these AMY− cell clusters. These results support a contribution of the islet-acinar axis in pancreatic development and underscore a potential role for the exocrine pancreas in the pathogenesis of type 1 diabetes.
Celiac Disease and the Microbiome

Growing evidence supports the hypothesis that changes in both the composition and function of the intestinal microbiome are associated with a number of chronic inflammatory diseases including celiac disease (CD). One of the major advances in the field of microbiome studies over the last few decades has been the development of culture-independent approaches to identify and quantify the components of the human microbiota. The study of nucleic acids DNA and RNA found in feces or other biological samples bypasses the need for tissue cultures and also allows the characterization of non-cultivable microbes. Current evidence on the composition of the intestinal microbiome and its role as a causative trigger for CD is highly heterogeneous and sometimes contradictory. This review is aimed at summarizing both pre-clinical (basic science data) and clinical (cross-sectional and prospective studies) evidence addressing the relationship between the intestinal microbiome and CD.
Urinary chemokine C-X-C motif ligand 16 and endostatin as predictors of tubulointerstitial fibrosis in patients with advanced diabetic kidney disease.

BACKGROUND Interstitial fibrosis and tubular atrophy (IFTA) is a well-recognized risk factor for poor renal outcome in patients with diabetic kidney disease (DKD). However, a noninvasive biomarker for IFTA is currently lacking. The purpose of this study was to identify urinary markers of IFTA and to determine their clinical relevance as predictors of renal prognosis. METHODS Seventy patients with biopsy-proven isolated DKD were enrolled in this study. We measured multiple urinary inflammatory cytokines and chemokines by multiplex enzyme-linked immunosorbent assay in these patients and evaluated their association with various pathologic features and renal outcomes. RESULTS Patients enrolled in this study exhibited advanced DKD at the time of renal biopsy, characterized by moderate to severe renal dysfunction [mean estimated glomerular filtration rate (eGFR) 36.1 mL/min/1.73 m2] and heavy proteinuria (mean urinary protein:creatinine ratio 7.8 g/g creatinine). Clinicopathologic analysis revealed that higher IFTA scores were associated with worse baseline eGFR (P < 0.001) and poor renal outcome (P = 0.002), whereas glomerular injury scores were not. Among measured urinary inflammatory markers, C-X-C motif ligand 16 (CXCL16) and endostatin showed strong correlations with IFTA scores (P = 0.001 and P < 0.001, respectively), and patients with higher levels of urinary CXCL16 and/or endostatin experienced significantly rapid renal progression compared with other patients (P < 0.001). Finally, increased urinary CXCL16 and endostatin were independent risk factors for poor renal outcome after multivariate adjustments (95% confidence interval 1.070-3.455, P = 0.029). CONCLUSIONS Urinary CXCL16 and endostatin could reflect the degree of IFTA and serve as biomarkers of renal outcome in patients with advanced DKD.
Clearing vs. burning for restoring Pyrenean grasslands after shrub encroachment

Anthropogenic activities have modified vegetation on subalpine belts for a long time, lowering the treeline ecotone and influencing the landscape mainly through grazing and fire. The abandonment of these traditional land use practices during the last decades and global warming are contributing largely to the colonization of woody species in subalpine grasslands, causing irreversible changes in ecosystem functioning. A variety of management strategies requiring the use of fire and/or clear-cutting are carried out to prevent the expansion of highly encroaching shrubs and improve the conservation status of subhumid high-productive grasslands ecosystems. However, it is still poorly understood how different management strategies affect the recovery of subalpine grasslands, which is influenced concurrently by the vegetation community involved. In this study we used field experiments to test the impact of management treatments on soil properties and vegetation responses in subalpine Bromion erecti grassland communities colonized by the pyrophyte shrub Echinospartum horridum (Vahl) Rothm. on the southern Pyrenees. Vegetation was monitored for 5 years in E. horridum plots (two plots per treatment) where the vegetation was removed by prescribed fire (Burnt treatment) or by mechanical removal (Clear-cut treatment). Undisturbed E. horridum plots were used as a control (C-Erizón) for shrub removal treatments and a Bromion erecti grassland community regularly grazed (C-Grass) was used as a control for subalpine grassland. Clear-cut treatment of E. horridum community was more effective to control E. horridum colonization than Burnt treatment and contributed to a higher extent to recover original grassland vegetation, because E. horridum seedling performed worse (lower germination rates) and plant species were more similar to the original grassland (legumes, non-legume forbs, and grasses). Shrubs and sub-shrubs cover in Burnt areas increased faster than in Clear-cut areas during the 5 years following the treatment, although it did not reach the level of C-Erizón. Species richness and diversity increased in comparison with C-Erizón in both treatments, but they were significantly lower than those in the C-Grass. Network connectivity was larger in well preserved grasslands, i.e, C-Grass, than in any other treatments, mainly dominated by negative plant-plant association. Soils nutrients declined in Burnt sites 4 years after the fire treatment and no difference was observed between Clear-cut and C-Erizón sites, although they did not reach the soil fertility values of C-Grass in terms of organic matter and C/N ratio. This study showed that grazing favors plant diversity and community complexity in subalpine grasslands. It also demonstrated that clearing is a better strategy than burning to restore grasslands after shrub encroachment because burning entails deeper soil degradation and faster recovering of the pyrophyte shrub, E. horridum.
Deep Neck Inflammation: Probable Kawasaki Disease in Korean Children

Objectives Deep neck infections (DNIs) can cause life-threatening complications, and prompt diagnosis and management are necessary. Kawasaki disease (KD) may be accompanied by deep neck inflammation; making it difficult to distinguish from DNIs. This study was performed to evaluate clinical features and outcomes of children with parapharyngeal and retropharyngeal inflammation. Methods Medical records of the children diagnosed with parapharyngeal and retropharyngeal cellulitis or abscess using cervical computed tomography (CT) between 2013 and 2017 were retrospectively reviewed. Results A total of 47 children were diagnosed with parapharyngeal and retropharyngeal inflammation. Eleven (23.4%) of them were eventually diagnosed with KD, and 36 (76.6%) were diagnosed with DNIs. There were no significantly different clinical and laboratory characteristics on admission between children diagnosed with KD and DNIs; however, significantly more children with KD were febrile for ≥3 days after admission compared to those with DNIs (P=0.009). Deep neck abscesses on CT were observed in 16 children with DNIs (44.4%) and in no child with KD (P=0.009). Among the 36 children with DNIs, 30 (83.3%) were cured with antibiotic therapy only. Conclusion A quarter of children presenting with deep neck inflammation were diagnosed with KD. KD should be considered in children showing deep neck inflammation unresponsive to empirical antibiotic therapy after 3 days, especially in those presenting with deep neck cellulitis rather than deep neck abscess.