Miracle-dz/UniFAR-FTUs huggingface dataset:
Serveur Académique Lausannois SERVAL serval.unil.ch

Recent studies have uncovered important cross talk between inflammation, generation of reactive oxygen and nitrogen species, and lipid metabolism in the pathogenesis of cardiovascular aging. Inhibition of the endocannabinoid anandamide metabolizing enzyme, the fatty acid amide hydrolase (FAAH), is emerging as a promising novel approach for the treatment of various inflammatory disorders. In this study, we have investigated the age-associated decline of cardiac function and changes in inflammatory gene expression, nitrative stress, and apoptosis in FAAH knockout (FAAH − / − ) mice and their wild-type (FAAH +/+ ) littermates. Additionally, we have explored the effects of anandamide on TNF- α -induced ICAM-1 and VCAM-1 expression and monocyte-endothelial adhesion in human coronary artery endothelial cells (HCAECs). There was no difference in the cardiac function (measured by the pressure-volume conductance catheter system) between 2-to 3-mo-old (young) FAAH − / − and FAAH +/+ mice. In contrast, the aging-associated decline in cardiac function and increased myocardial gene expression of TNF- α , gp91phox, matrix metalloproteinase (MMP)-2, MMP-9, caspase-3 and caspase-9, myocardial inducible nitric oxide synthase protein expression, nitrotyrosine formation, poly (ADP-ribose)polymerase cleavage and caspase-3/9 activity, observed in 28- to 31-mo-old (aging) FAAH +/+ mice, were largely attenuated in knockouts. There was no difference in the myocardial cannabinoid CB 1 and CB 2 receptor gene expression between young and aging FAAH − / − and FAAH +/+ mice. Anandamide dose dependently attenuated the TNF- α -induced ICAM-1 and VCAM-1 expression, NF- κ B activation in HCAECs, and the adhesion of monocytes to HCAECs in a CB 1 -and CB 2 -dependent manner. These findings suggest that pharmacological inhibition of FAAH may represent a novel protective strategy against chronic inflammation, oxidative/nitrative stress, and apoptosis associated with cardiovascular aging and atherosclerosis. the age-dependent decline of cardiac function and associated changes in myocardial inflammatory gene expression, nitrative stress, and apoptosis in FAAH knockout (FAAH − / − ) mice and their wild-type (FAAH +/+ ) littermates. We have also investigated the effects of anandamide on TNF- α -induced intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) expression and monocyte-endothelial adhesion in human coronary artery endothelial cells (HCAECs). These results indicate that 28-to 31-mo-old aging mice lacking FAAH have less myocardial oxidative/nitrative stress, inflammation, and apoptosis and better preservation of the cardiac function compared with their wild-type littermates. Furthermore, anandamide attenuates TNF- α -induced ICAM-1 and VCAM-1 expression, NF- κ B activation in HCAECs, and the adhesion of monocytes to HCAECs in a CB 1 - and CB 2 -dependent manner.
New techniques for estimating household climate preferences (and the benefits and costs of climate change)

In order to make an informed decision on the optimal reduction in greenhouse gas emissions it is necessary to understand fully the damage costs of climate change. However, current modelling techniques fail to provide adequate emphasis on important components of the costs and benefits of avoided climate change. This approach risks over or underestimating true damage costs. Disregard for the amenity value that climate may hold and assumptions that restrict geographic mobility and determine the rate of social discounting may all contribute to significant error. Using spatial variations as an analogue for future climate change, this thesis finds that climate is important in determining the desirability of migration destinations and holds substantial amenity value. It also concludes that more work is required to be confident in assuming an elasticity of marginal utility equal to unity. Alternative techniques, including subjective wellbeing and hypothetical equivalence scales, are utilised to avoid having to make potentially restrictive assumptions on preferences for climate. Finally, this thesis stresses the importance of accounting for measurement error in cross-sectional survey data on household income. It seeks to inform how an econometrician can seek to implement appropriate instrumental variables to overcome this error.
Toward Convex Manifolds: A Geometric Perspective for Deep Graph Clustering of Single-cell RNA-seq Data

The deep clustering paradigm has shown great potential for discovering complex patterns that can reveal cell heterogeneity in single-cell RNA sequencing data. This paradigm involves two training phases: pretraining based on a pretext task and fine-tuning using pseudo-labels. Although current models yield promising results, they overlook the geometric distortions that regularly occur during the training process. More precisely, the transition between the two phases results in a coarse flattening of the latent structures, which can deteriorate the clustering performance. In this context, existing methods perform euclidean-based embedding clustering without ensuring the flatness and convexity of the latent manifolds. To address this problem, we incorporate two mechanisms. First, we introduce an overclustering loss to flatten the local curves. Second, we propose an adversarial mechanism to adjust the global geometric configuration. The second mechanism gradually transforms the latent structures into convex ones. Empirical results on a variety of gene expression datasets show that our model outperforms state-of-the-art methods.
Cost-effectiveness analysis of selexipag for the combined treatment of pulmonary arterial hypertension

Objective: Adding selexipag to the combined treatment of endothelin receptor antagonists (ERA) and phosphodiesterase 5 inhibitor (PDE5i) reduces the risk of clinical worsening events in patients with pulmonary arterial hypertension (PAH) but at a considerably higher cost. This study evaluated the cost-effectiveness of adding selexipag to the combined treatment of ERA and PDE5i in patients with PAH from a Chinese healthcare system perspective. Methods: A Markov model was developed to assess costs and quality-adjusted life years (QALYs) of macitentan + tadalafil + selexipag vs. macitentan + tadalafil for the treatment of PAH. Markov states included WHO Functional Class (FC) (I–IV) and death. Transition probabilities were based on data from the TRITON trial. Mortality rates, costs, and utilities were obtained from published literature and public databases. Results: In the base case analysis, compared with macitentan + tadalafil, selexipag + macitentan + tadalafil increased costs ($357,807.588 vs. $116,534.543, respectively) and QALYs (7.234 QALYs vs. 6.666 QALYs, respectively). The resulting incremental cost-effectiveness ratio was $424,746.070 per QALY, which was higher than the willingness-to-pay (WTP) of $38,223.339 per QALY. The results were most sensitive to HR for mortality of patients with FC IV relative to the general population, discount rate, and the cost of selexipag. The probability was greater than 50% for the selexipag + macitentan + tadalafil only if the WTP was more significant than $426,019.200 per QALY. Conclusion: In China, adding selexipag may not be cost-effective for patients with PAH who failed to control their condition after combined treatment of ERA and PDE5i. Results of the analysis can aid discussions on the value and position of selexipag for the combined treatment of PAH.
Drug Expenditure, Price, and Utilization in US Medicaid: A Trend Analysis for New Multiple Myeloma Medications from 2016 to 2022

Introduction: Multiple myeloma (MM) is the most common plasma cell tumor type. In late 2015, the FDA approved three new medications for MM. These medications were ixazomib, daratumumab, and elotuzumab. However, their utilization, reimbursement, and price in the Medicaid program have not been analyzed before. Methods: A retrospective drug utilization study using the national Medicaid pharmacy claims data from 2016 to 2022 in the US. The primary metrics of analysis were utilization (number of prescriptions), reimbursement (total spending), and price (reimbursement per prescription). Results: The overall Medicaid utilization of MM medications increased from 1671 prescriptions in 2016 to 34,583 prescriptions in 2022 (1970% increase). Moreover, the overall Medicaid reimbursement for the new MM medications increased from USD 9,250,000 in 2016 to over USD 214,449,000 in 2022 (2218% increase). Daratumumab had much higher utilization, reimbursement, and market shares than its competitors. Ixazomib was the most expensive medication compared to daratumumab and elotuzumab. Conclusion: The results of this study demonstrate that CMS utilization and spending on MM medications have significantly grown since 2016. Daratumumab has by far the highest utilization, spending, and market share. The utilization of and spending on specific pharmaceuticals are clearly impacted by policy and clinical guideline recommendations.
The role of glucagon after bariatric/metabolic surgery: much more than an “anti-insulin” hormone

The biological activity of glucagon has recently been proposed to both stimulate hepatic glucose production and also include a paradoxical insulinotropic effect, which could suggest a new role of glucagon in the pathophysiology type 2 diabetes mellitus (T2DM). An insulinotropic role of glucagon has been observed after bariatric/metabolic surgery that is mediated through the GLP-1 receptor on pancreatic beta cells. This effect appears to be modulated by other members of the proglucagon family, playing a key role in the beneficial effects and complications of bariatric/metabolic surgery. Glucagon serves a dual role after sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). In addition to maintaining blood glucose levels, glucagon exhibits an insulinotropic effect, suggesting that glucagon has a more complex function than simply an “anti-insulin hormone”.
A Diffusion Model with Contrastive Learning for ICU False Arrhythmia Alarm Reduction

The high rate of false arrhythmia alarms in intensive care units (ICUs) can negatively impact patient care and lead to slow staff response time due to alarm fatigue. To reduce false alarms in ICUs, previous works proposed conventional supervised learning methods which have inherent limitations in dealing with high-dimensional, sparse, unbalanced, and limited data. We propose a deep generative approach based on the conditional denoising diffusion model to detect false arrhythmia alarms in the ICUs. Conditioning on past waveform data of a patient, our approach generates waveform predictions of the patient during an actual arrhythmia event, and uses the distance between the generated and the observed samples to classify the alarm. We design a network with residual links and self-attention mechanism to capture long-term dependencies in signal sequences, and leverage the contrastive learning mechanism to maximize distances between true and false arrhythmia alarms. We demonstrate the effectiveness of our approach on the MIMIC II arrhythmia dataset for detecting false alarms in both retrospective and real-time settings.
Blood–Brain Barrier Breakdown in Neuroinflammation: Current In Vitro Models

The blood–brain barrier, which is formed by tightly interconnected microvascular endothelial cells, separates the brain from the peripheral circulation. Together with other central nervous system-resident cell types, including pericytes and astrocytes, the blood–brain barrier forms the neurovascular unit. Upon neuroinflammation, this barrier becomes leaky, allowing molecules and cells to enter the brain and to potentially harm the tissue of the central nervous system. Despite the significance of animal models in research, they may not always adequately reflect human pathophysiology. Therefore, human models are needed. This review will provide an overview of the blood–brain barrier in terms of both health and disease. It will describe all key elements of the in vitro models and will explore how different compositions can be utilized to effectively model a variety of neuroinflammatory conditions. Furthermore, it will explore the existing types of models that are used in basic research to study the respective pathologies thus far.
Discovering Sounding Objects by Audio Queries for Audio Visual Segmentation

Audio visual segmentation (AVS) aims to segment the sounding objects for each frame of a given video. To distinguish the sounding objects from silent ones, both audio-visual semantic correspondence and temporal interaction are required. The previous method applies multi-frame cross-modal attention to conduct pixel-level interactions between audio features and visual features of multiple frames simultaneously, which is both redundant and implicit. In this paper, we propose an Audio-Queried Transformer architecture, AQFormer, where we define a set of object queries conditioned on audio information and associate each of them to particular sounding objects. Explicit object-level semantic correspondence between audio and visual modalities is established by gathering object information from visual features with predefined audio queries. Besides, an Audio-Bridged Temporal Interaction module is proposed to exchange sounding object-relevant information among multiple frames with the bridge of audio features. Extensive experiments are conducted on two AVS benchmarks to show that our method achieves state-of-the-art performances, especially 7.1% M_J and 7.6% M_F gains on the MS3 setting.
Inversión en recursos para crear valor: ¿Pero valor para quién?

La creación de valor ha sido durante mucho tiempo un tema de gran interés en la gestión en general, y en la toma de decisiones estratégicas en particular. Aunque muchos enfoques de gestión han descrito y explicado el significado de “creación” de valor, algunos de ellos se han concentrado en mejorar las operaciones y, por lo tanto, en la “entrega” de valor: cómo alinear recursos y actividades para convertir materias primas en productos terminados. Otros enfoques se centran en la “creación” de valor para un tipo particular de partes interesadas (stakeholders). Este trabajo enfatiza la cuestión de la creación de valor como valor potencial, que gira en torno a la estrategia de la empresa; y también enfatiza la necesidad de tener un enfoque sistémico y holístico que considere a los diferentes stakeholders de la empresa. Si la gerencia no comprende el significado de valor, podría crear algo que sea irrelevante para los stakeholders. Se mostrará que, en un ambiente competitivo, para crear valor para los inversionistas en el largo plazo, la gerencia primero debe crear valor para los otros stakeholders: clientes, proveedores, empleados y la sociedad.
Centile reference curves of the ultrasound-based characteristics of the rectus femoris muscle composition in children at 4–11 years old

Quantitative diagnostic ultrasound has been proposed as a way to characterize muscle structure, but there is a lack of normative data for children. This study aims to establish age-specific normal ranges for echo-intensity (EI), cross-sectional area (CSA), muscular thickness (MT), and subcutaneous adipose thickness (SAT) values of the rectus femoris muscle in typically developing children. The study recruited 497 children (288 boys and 209 girls) aged 4–10.9 years (mean age 7.39 years), and muscle parameters were measured using 2D B-mode ultrasound. Percentile values and reference curves were calculated using the Lambda, Mu, and Sigma method (LMS). The results showed small variation between measurements for boys compared to girls, with the most significant difference in EI, CSA, and MT values. EI decreased with age, with the most pronounced curve in boys. SAT increased in both sexes, with a slightly higher increase in girls after the age of 9.0 years. This study provides the first age-specific reference norms for the rectus femoris muscle architecture in children, and further research is needed to validate these curves and determine their clinical utility.
Mind needs body! Practicing positive psychology in English language teaching

Positive emotions are recognised as important for successful foreign language learning. Learners develop a positive attitude towards a language, are motivated to learn, and experience enjoyment through regular, meaningful, and positive engagement. Little attention, however, has so far been paid to the links between Positive Psychology, one of the reasons for the growth of interest in emotions, and embodied cognition which advocates the importance of the body and positive sensations for successful learning. While methods such as Total Physical Response (TPR) can help to get learners moving in class, learning through drama seems to be particularly apt to facilitate embodied learning. Students physically engage with situations, characters, and feelings as they inhabit different spaces, often collaboratively. This paper first introduces embodied cognition. It then discusses the links between embodiment and Positive Psychology, taking Seligman's PERMA MODEL as a point of reference. Following this, it shows how embodied learning can be integrated in the English as a foreign language classroom by using techniques from improvisational theatre.
Maximum Likelihood Coordinates

Any point inside a d‐dimensional simplex can be expressed in a unique way as a convex combination of the simplex's vertices, and the coefficients of this combination are called the barycentric coordinates of the point. The idea of barycentric coordinates extends to general polytopes with n vertices, but they are no longer unique if n > d+1. Several constructions of such generalized barycentric coordinates have been proposed, in particular for polygons and polyhedra, but most approaches cannot guarantee the non‐negativity of the coordinates, which is important for applications like image warping and mesh deformation. We present a novel construction of non‐negative and smooth generalized barycentric coordinates for arbitrary simple polygons, which extends to higher dimensions and can include isolated interior points. Our approach is inspired by maximum entropy coordinates, as it also uses a statistical model to define coordinates for convex polygons, but our generalization to non‐convex shapes is different and based instead on the project‐and‐smooth idea of iterative coordinates. We show that our coordinates and their gradients can be evaluated efficiently and provide several examples that illustrate their advantages over previous constructions.
Dynamic DAG Scheduling Under Memory Constraints for Shared-Memory Platforms

This work focuses on dynamic DAG scheduling under memory constraints. We target a shared-memory platform equipped with $p$ parallel processors. The goal is to bound the maximum amount of memory that may be needed by any schedule using p processors to execute the DAG. We refine the classical model that computes maximum cuts by introducing two types of memory edges in the DAG, black edges for regular precedence constraints and red edges for actual memory consumption during execution. A valid edge cut cannot include more than $p$ red edges. This limitation had never been taken into account in previous works, and dramatically changes the complexity of the problem, which was polynomial and becomes NP-hard. We introduce an Integer Linear Program (ILP) to solve it, together with an efficient heuristic based on rounding the rational solution of the ILP. In addition, we propose an exact polynomial algorithm for series-parallel graphs. We further study the extension of the approach where the scheduler is dynamically constrained to select tasks (among ready tasks) so that the total memory used does not exceed some threshold. We provide an extensive set of experiments, both with randomly-generated graphs and with graphs arising from practical applications, which demonstrate the impact of resource constraints on peak memory usage.
Relationship of Mitochondrial-Related Protein Expression with the Differentiation, Metastasis, and Poor Prognosis of Oral Squamous Cell Carcinoma

Simple Summary Mitochondrial dysfunction and respiratory function changes have been associated with the initiation and progression of cancer. However, no study has comprehensively investigated the relationship between these mitochondrial-related factors and prognosis in a large number of patients with oral squamous cell carcinoma (OSCC). Here, we retrospectively investigated the expression of mitochondrial tumor-suppressor and DNA-repair proteins (PGC-1α, TFAM, OGG1, MTUS1, and SIRT3) in patients with OSCC and evaluated the relationship between their expression and prognosis. The expression levels of the five proteins were associated with patient outcomes. The 3-year disease-specific survival (DSS) rates of patients showing positive expression of all selected proteins were significantly higher than those of patients showing a lack of expression. Particularly, based on the results of multivariate analysis, negative expression of PGC-1α is related to a poor prognosis of OSCC. Low PGC-1α expression and vascular invasion may be clinically effective predictors of oral cancer prognosis. Abstract Mitochondrial dysfunction and respiratory function changes have been consistently associated with the initiation and progression of cancer. The purpose of this study was to retrospectively investigate the expression of mitochondrial tumor-suppressor and DNA-repair proteins in patients with oral squamous cell carcinoma (OSCC) and to evaluate the relationship between their expression and prognosis. We enrolled 197 patients with OSCC who underwent surgical resection between August 2013 and October 2018. Clinical, pathological, and epidemiological data were retrospectively collected from hospital records. The expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), mitochondrial transcription factor A, mitochondrial tumor suppressor gene 1, silent information regulator 3, and 8-hydroxyguanine DNA glycosylase was investigated using immunochemistry. The 3-year disease-specific survival (DSS) rates of patients showing positive expression of all selected proteins were significantly higher than those of patients showing a lack of expression. Multivariate analysis revealed that the expression of PGC-1α (hazard ratio, 4.684) and vascular invasion (hazard ratio, 5.690) can predict the DSS rate (p < 0.001). Low PGC-1α expression and vascular invasion are potential clinically effective predictors of the prognosis of OSCC.
Sterile inflammation in liver transplantation

Sterile inflammation is the immune response to damage-associated molecular patterns (DAMPs) released during cell death in the absence of foreign pathogens. In the setting of solid organ transplantation, ischemia-reperfusion injury results in mitochondria-mediated production of reactive oxygen and nitrogen species that are a major cause of uncontrolled cell death and release of various DAMPs from the graft tissue. When properly regulated, the immune response initiated by DAMP-sensing serves as means of damage control and is necessary for initiation of recovery pathways and re-establishment of homeostasis. In contrast, a dysregulated or overt sterile inflammatory response can inadvertently lead to further injury through recruitment of immune cells, innate immune cell activation, and sensitization of the adaptive immune system. In liver transplantation, sterile inflammation may manifest as early graft dysfunction, acute graft failure, or increased risk of immunosuppression-resistant rejection. Understanding the mechanisms of the development of sterile inflammation in the setting of liver transplantation is crucial for finding reliable biomarkers that predict graft function, and for development of therapeutic approaches to improve long-term transplant outcomes. Here, we discuss the recent advances that have been made to elucidate the early signs of sterile inflammation and extent of damage from it. We also discuss new therapeutics that may be effective in quelling the detrimental effects of sterile inflammation.