Miracle-dz/UniFAR-FTUs huggingface dataset:
Derivation and validation of a new visceral adiposity index for predicting visceral obesity and cardiometabolic risk in a Korean population

Objectives The visceral adiposity index (VAI), an indirect marker of visceral adipose tissue, serves as a model associated with cardiometabolic risk, but has limitations regarding the Asian population. We sought to develop a new VAI (NVAI) for the Korean population and compare it to VAI for prediction of atherosclerotic cardiovascular disease (ASCVD) risk and development of major cardiovascular diseases (CVD) and stroke. Methods Patients (969) who underwent visceral fat area measurement were analyzed. After exclusion, 539 patients (142 men, 397 women) were randomly divided into internal (n = 374) and external validation (n = 165) data set. The NVAI was developed using univariate and multivariate logistic regression with backward selection of predictors. Receiver operating characteristic (ROC) curve analysis and comparison of the area under the curve (AUC) verified the better predictor of ASCVD risk score. Additionally, nationwide population-based cross-sectional survey data (Korean National Health and Nutrition Examination Survey [KNHANES] 2008–2010, n = 29,235) was used to validate the NVAI’s ability to predict ASCVD risk and major CVD and stroke. Results The NVAI better reflected visceral fat area in internal and external data sets, with AUCs of 0.911 (95% confidence interval [CI]: 0.882–0.940) and 0.879 (95% CI: 0.828–0.931), respectively. NVAI better discriminated for ASCVD risk (AUC = 0.892, 95% CI: 0.846–0.938) compared to VAI (0.559, 95% CI: 0.439–0.679). The NVAI also better predicted MI or angina, and stroke with AUCs of 0.771 (95% CI: 0.752–0.789), and 0.812 (95% CI: 0.794–0.830), respectively, compared with waist circumference (WC), body mass index (BMI), TG to HDL ratio, and VAI via KNHANES, in a statistically significant manner. Conclusions The NVAI has advantages as a predictor of visceral obesity and is significantly associated with ASCVD risks and development of major CVD and stroke in the Korean population. The NVAI could be a screening tool for improved risk estimation related to visceral obesity.
Von Willebrand disease in the elderly: clinical perspectives

Von Willebrand disease (VWD) is an inherited bleeding disorder that affects up to 1% of the population. In most cases, VWD results from a mutation in the von Willebrand Factor (VWF) gene, which alters the amount and function of VWF, a key glycoprotein in both primary and secondary hemostasis. A comprehensive analysis of patients with VWD should include VWF activity, antigen levels, platelet function, and a careful bleeding history. Treatment options include antifibrinolytics, desmopressin, and VWF replacement therapy. VWF levels fluctuate due to age, stress, environmental exposures, and pharmacologic treatment. Treatment guidelines exist to treat and prevent bleeding for patients undergoing surgery and medical procedures, but often these must be reevaluated in the setting of age-related comorbidities including cardiovascular events, venous thrombosis, and malignancy. In addition, many age-related complications are associated with a secondary acquired von Willebrand syndrome (AVWS), including malignancies, hypothyroidism, cardiovascular diseases, and cardiac replacement devices. The current literature is limited by a lack of older patients in clinical trials. Larger studies are needed to determine if age-related comorbidities affect VWD patients at different frequencies than the general elderly population. There is also a significant need for registry-based studies to evaluate many age-related comorbidities in VWD patients.
The Closed Loop Between Opinion Formation and Personalized Recommendations

In online platforms, recommender systems are responsible for directing users to relevant content. In order to enhance the users’ engagement, recommender systems adapt their output to the reactions of the users, who are, in turn, affected by the recommended content. In this article, we study a tractable analytical model of a user that interacts with an online news aggregator, with the purpose of making explicit the feedback loop between the evolution of the user’s opinion and the personalized recommendation of content. More specifically, we assume that the user is endowed with a scalar opinion about a certain issue and receives news about it from a news aggregator: her opinion is influenced by all received pieces of news, which are characterized by a binary position on the issue at hand. The user is affected by a confirmation bias, that is, a preference for news that confirms her current opinion. The news aggregator recommends items with the goal of maximizing the number of user’s clicks (as a measure of her engagement): in order to fulfill its goal, the recommender has to compromise between exploring the user’s preferences and exploiting what it has learned so far. After defining suitable metrics for the effectiveness of the recommender systems (such as the click-through rate) and for its impact on the opinion, we perform both extensive numerical simulations and a mathematical analysis of the model. We find that personalized recommendations markedly affect the evolution of opinions and favor the emergence of more extreme ones: the intensity of these effects is inherently related to the effectiveness of the recommender. We also show that by tuning the amount of randomness in the recommendation algorithm, one can seek a balance between the effectiveness of the recommendation system and its impact on the opinions.
Sumoylation-deficient Prdx6 repairs aberrant Sumoylation-mediated Sp1 dysregulation-dependent Prdx6 repression and cell injury in aging and oxidative stress

Progressive deterioration of antioxidant response in aging is a major culprit in the initiation of age-related pathobiology induced by oxidative stress. We previously reported that oxidative stress leads to a marked reduction in transcription factor Sp1 and its mediated Prdx6 expression in lens epithelial cells (LECs) leading to cell death. Herein, we examined how Sp1 activity goes awry during oxidative stress/aging, and whether it is remediable. We found that Sp1 is hyper-Sumoylated at lysine (K) 16 residue in aging LECs. DNA binding and promoter assays revealed, in aging and oxidative stress, a significant reduction in Sp1 overall binding, and specifically to Prdx6 promoter. Expression/overexpression assay revealed that the observed reduction in Sp1-DNA binding activity was connected to its hyper-Sumoylation due to increased reactive oxygen species (ROS) and Sumo1 levels, and reduced levels of Senp1, Prdx6 and Sp1. Mutagenesis of Sp1 at K16R (arginine) residue restored steady-state, and improved Sp1-DNA binding activity and transactivation potential. Extrinsic expression of Sp1K16R increased cell survival and reduced ROS levels by upregulating Prdx6 expression in LECs under aging/oxidative stress, demonstrating that Sp1K16R escapes the aberrant Sumoylation processes. Intriguingly, the deleterious processes are reversible by the delivery of Sumoylation-deficient Prdx6, an antioxidant, which would be a candidate molecule to restrict aging pathobiology.
An Improved Inhaled Mucolytic to Treat Airway Muco‐obstructive Diseases

Rationale: Airways obstruction with thick, adherent mucus is a pathophysiologic and clinical feature of muco‐obstructive respiratory diseases, including chronic obstructive pulmonary disease, asthma, and cystic fibrosis (CF). Mucins, the dominant biopolymer in mucus, organize into complex polymeric networks via the formation of covalent disulfide bonds, which govern the viscoelastic properties of the mucus gel. For decades, inhaled N‐acetylcysteine (NAC) has been used as a mucolytic to reduce mucin disulfide bonds with little, if any, therapeutic effects. Improvement of mucolytic therapy requires the identification of NAC deficiencies and the development of compounds that overcome them. Objectives: Elucidate the pharmacological limitations of NAC and test a novel mucin‐reducing agent, P3001, in preclinical settings. Methods: The study used biochemical (e.g., Western blotting, mass spectrometry) and biophysical assays (e.g., microrheology/macrorheology, spinnability, mucus velocity measurements) to test compound efficacy and toxicity in in vitro and in vivo models and patient sputa. Measurements and Main Results: Dithiothreitol and P3001 were directly compared with NAC in vitro and both exhibited superior reducing activities. In vivo, P3001 significantly decreased lung mucus burden in &bgr;ENaC‐overexpressing mice, whereas NAC did not (n = 6‐24 mice per group). In NAC‐treated CF subjects (n = 5), aerosolized NAC was rapidly cleared from the lungs and did not alter sputum biophysical properties. In contrast, P3001 acted faster and at lower concentrations than did NAC, and it was more effective than DNase in CF sputum ex vivo. Conclusions: These results suggest that reducing the viscoelasticity of airway mucus is an achievable therapeutic goal with P3001 class mucolytic agents.
The Autonomous Shipping Era. Operational, Regulatory, and Quality Challenges

The article provides a description of the Autonomous ship, studies existing relevant projects, and examines the related Operational, Regulatory, and Quality assurance challenges raised due to the development and actual deployment of such vessels in the near future. After reviewing the main operational procedures, existing regulations, and quality assurance standards, a number of possible solutions and approaches to overcome the identified challenges are indicated. Some of the conclusions may be used not only in the Autonomous ships but also in traditionally manned vessels. http://www.transnav. eu the International Journal on Marine Navigation and Safety of Sea Transportation Volume 12
Associations between the gut microbiota and host responses to high altitude

Hypobaric hypoxia and dietary protein and fat intakes have been independently associated with an altered gastrointestinal (GI) environment and gut microbiota, but little is known regarding host-gut microbiota interactions at high altitude (HA) and the impact of diet macronutrient composition. This study aimed to determine the effect of dietary protein:fat ratio manipulation on the gut microbiota and GI barrier function during weight loss at high altitude (HA) and to identify associations between the gut microbiota and host responses to HA. Following sea-level (SL) testing, 17 healthy males were transported to HA (4,300 m) and randomly assigned to consume provided standard protein (SP; 1.1 g·kg−1·day−1, 39% fat) or higher protein (HP; 2.1 g·kg−1·day−1, 23% fat) carbohydrate-matched hypocaloric diets for 22 days. Fecal microbiota composition and metabolites, GI barrier function, GI symptoms, and acute mountain sickness (AMS) severity were measured. Macronutrient intake did not impact fecal microbiota composition, had only transient effects on microbiota metabolites, and had no effect on increases in small intestinal permeability, GI symptoms, and inflammation observed at HA. AMS severity was also unaffected by diet but in exploratory analyses was associated with higher SL-relative abundance of Prevotella, a known driver of interindividual variability in human gut microbiota composition, and greater microbiota diversity after AMS onset. Findings suggest that the gut microbiota may contribute to variability in host responses to HA independent of the dietary protein:fat ratio but should be considered preliminary and hypothesis generating due to the small sample size and exploratory nature of analyses associating the fecal microbiota and host responses to HA. NEW & NOTEWORTHY This study is the first to examine interactions among diet, the gut microbiota, and host responses to weight loss at high altitude (HA). Observed associations among the gut microbiota, weight loss at HA, and acute mountain sickness provide evidence that the microbiota may contribute to variability in host responses to HA. In contrast, dietary protein:fat ratio had only minimal, transient effects on gut microbiota composition and bacterial metabolites which were likely not of clinical consequence.
On-Demand Service Platforms

An on-demand service platform connects waiting-time sensitive customers with independent service providers (agents). This paper examines how two defining features of an on-demand service platform -- congestion-driven delay disutility and agent independence -- impact the platform's optimal per-service price and wage. Congestion reduces expected utility for customers and agents, which suggests that the platform respond by decreasing the price (to encourage participation of customers) and increasing the wage (to encourage participation of agents). These intuitive price and wage prescriptions are valid in a benchmark setting without uncertainty in the customers' valuation or the agents' opportunity costs. However, uncertainty in either dimension can reverse the prescriptions: Congestion increases the optimal price when customer valuation uncertainty is moderate. Congestion decreases the optimal wage when agent opportunity cost uncertainty is high and expected opportunity cost is moderate. Under agent opportunity cost uncertainty, agent independence decreases the price. Under customer valuation uncertainty, agent independence increases the price if and only if valuation uncertainty is sufficiently high.
Coordination-driven Learning in Multi-agent Problem Spaces

We discuss the role of coordination as a direct learning objective in multi-agent reinforcement learning (MARL) domains. To this end, we present a novel means of quantifying coordination in multi-agent systems, and discuss the implications of using such a measure to optimize coordinated agent policies. This concept has important implications for adversary-aware RL, which we take to be a sub-domain of multi-agent learning.
Wall Shear Stress and T1 Contrast Ratio Are Associated With Embolic Signals During Carotid Exposure in Endarterectomy

Background and Purpose— The frictional force because of blood flow may dislodge masses present on the surface of a plaque. Such frictional force is calculated as wall shear stress (WSS) using computational fluid dynamics. The aims of the present study were to determine whether, in addition to carotid plaque intensity on T1-weighted magnetic resonance (MR) imaging, WSS calculated using computational fluid dynamics analysis for carotid arteries is associated with development of an embolism during exposure of carotid arteries during carotid endarterectomy. Methods— One hundred patients with internal carotid artery stenosis (≥70%) underwent carotid plaque imaging with MR, and 54 patients with a vulnerable plaque (intraplaque hemorrhage or lipid/necrotic core) displayed as a high-intensity lesion underwent additional cervical 3-dimensional MR angiography. The maximum value of WSS within the most severe stenotic segment of the internal carotid artery was calculated using MR angiography. Transcranial Doppler monitoring of microembolic signals (MES) in the ipsilateral middle cerebral artery was performed during carotid endarterectomy. Results— Although none of the 46 patients with a nonvulnerable carotid plaque had MES during exposure of carotid arteries, 24 of the 54 patients with a vulnerable carotid plaque (44%) had MES. Logistic regression analysis showed that higher plaque intensity (P=0.0107) and higher WSS (P=0.0029) were significantly associated with the development of MES. When both cutoff points of plaque intensity and WSS in the receiver operating characteristic curves for predicting development of MES were combined, specificity (from 63% to 93%) and positive predictive value (from 66% to 90%) became greater than those for plaque intensity alone. Conclusions— In addition to carotid plaque intensity on T1-weighted MR imaging, WSS calculated using computational fluid dynamics analysis for carotid arteries is associated with development of an embolism during exposure of carotid arteries during carotid endarterectomy.
Unique Physicochemical Patterns of Residues in Protein-Protein Interfaces

Protein-protein interactions can be characterized by high-resolution structures of complexes, from which diverse features of the interfaces can be derived. For the majority of protein-protein interactions identified, however, there is no information on the structure of the complex or the interface involved in the interaction. Understanding what surface properties drive certain interactions is crucial in the functional evaluation of protein complexes. Here we show that the local patterning of the physicochemical properties of amino acids within surface patches is characteristic of interfaces. To describe this feature in a quantitative manner, we have defined a statistical potential, iPat, as a measure of surface patterning. iPat, which does not take evolutionary conservation or knowledge of the interaction partner into consideration, represents a function principally different from algorithms that consider intermolecular contacts. We assess its suitability for characterizing protein and peptide interfaces, and we demonstrate that iPat is uniquely descriptive for interfaces of proteins that undergo large conformational changes or that are involved in the binding of intrinsically disordered protein (IDP) partners. We suggest that as a stand-alone propensity or in combination with other features, iPat represents a new feature in analyzing the functional binding specificity of protein-protein interactions that has better predictive potential than other simple 1D features, such as hydrophobicity or stickiness.
Graph powering and spectral robustness

Spectral algorithms, such as principal component analysis and spectral clustering, typically require careful data transformations to be effective: upon observing a matrix $A$, one may look at the spectrum of $\psi(A)$ for a properly chosen $\psi$. The issue is that the spectrum of $A$ might be contaminated by non-informational top eigenvalues, e.g., due to scale` variations in the data, and the application of $\psi$ aims to remove these. Designing a good functional $\psi$ (and establishing what good means) is often challenging and model dependent. This paper proposes a simple and generic construction for sparse graphs, $$\psi(A) = \1((I+A)^r \ge1),$$ where $A$ denotes the adjacency matrix and $r$ is an integer (less than the graph diameter). This produces a graph connecting vertices from the original graph that are within distance $r$, and is referred to as graph powering. It is shown that graph powering regularizes the graph and decontaminates its spectrum in the following sense: (i) If the graph is drawn from the sparse Erd\H{o}s-R\'enyi ensemble, which has no spectral gap, it is shown that graph powering produces a `maximal' spectral gap, with the latter justified by establishing an Alon-Boppana result for powered graphs; (ii) If the graph is drawn from the sparse SBM, graph powering is shown to achieve the fundamental limit for weak recovery (the KS threshold) similarly to \cite{massoulie-STOC}, settling an open problem therein. Further, graph powering is shown to be significantly more robust to tangles and cliques than previous spectral algorithms based on self-avoiding or nonbacktracking walk counts \cite{massoulie-STOC,Mossel_SBM2,bordenave,colin3}. This is illustrated on a geometric block model that is dense in cliques.
Survey on Sketch Based Image Retrieval

— Sketch Based Image Retrieval technique is used to retrieve the images from database, Based on Sketch as query image, There are several techniques which are used to retrieve images, Such as content based image retrieval, Text based image retrieval, Sketch Based Image Retrieval. Among Sketch base image retrieval technique is one of the popular and most efficient method used to retrieve the images from the database. It’s useful when there is no natural scene query image, to draw the query sketch need not to have high drawing skills, a rough hand written sketch composed of black and white is enough to retrieve relevant images from database. Sketch based image retrieval technique is used in our day to day life, In the fields of Biometric Security, Shapes Identification, Medical diagnosis – Tumors detection, Investigation – helps the police to detect the culprit, Search engines etc. In this survey paper we have summarizes different Sketch based methods used to retrieve the images, and comparison among them.
Novel multi-drug delivery hydrogel using scar-homing liposomes improves spinal cord injury repair

Proper selection and effective delivery of combination drugs targeting multiple pathophysiological pathways key to spinal cord injury (SCI) hold promise to address the thus far scarce clinical therapeutics for improving recovery after SCI. In this study, we aim to develop a clinically feasible way for targeted delivery of multiple drugs with different physiochemical properties to the SCI site, detail the underlying mechanism of neural recovery, and detect any synergistic effect related to combination therapy. Methods: Liposomes (LIP) modified with a scar-targeted tetrapeptide (cysteine-alanine-glutamine-lysine, CAQK) were first constructed to simultaneously encapsulate docetaxel (DTX) and brain-derived neurotrophic factor (BDNF) and then were further added into a thermosensitive heparin-modified poloxamer hydrogel (HP) with affinity-bound acidic fibroblast growth factor (aFGF-HP) for local administration into the SCI site (CAQK-LIP-GFs/DTX@HP) in a rat model. In vivo fluorescence imaging was used to examine the specificity of CAQK-LIP-GFs/DTX binding to the injured site. Multiple comprehensive evaluations including biotin dextran amine anterograde tracing and magnetic resonance imaging were used to detect any synergistic effects and the underlying mechanisms of CAQK-LIP-GFs/DTX@HP both in vivo (rat SCI model) and in vitro (primary neuron). Results: The multiple drugs were effectively delivered to the injured site. The combined application of GFs and DTX supported neuro-regeneration by improving neuronal survival and plasticity, rendering a more permissive extracellular matrix environment with improved regeneration potential. In addition, our combination therapy promoted axonal regeneration via moderation of microtubule function and mitochondrial transport along the regenerating axon. Conclusion: This novel multifunctional therapeutic strategy with a scar-homing delivery system may offer promising translational prospects for the clinical treatment of SCI.