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Prion Protein Endoproteolysis: Cleavage Sites, Mechanisms and Connections to Prion Disease.

Highly abundant in neurons, the cellular prion protein (PrPC) is an obligatory precursor to the disease-associated misfolded isoform denoted PrPSc that accumulates in the rare neurodegenerative disorders referred to either as transmissible spongiform encephalopathies (TSEs) or as prion diseases. The ability of PrPC to serve as a substrate for this template-mediated conversion process depends on several criteria but importantly includes the presence or absence of certain endoproteolytic events performed at the cell surface or in acidic endolysosomal compartments. The major endoproteolytic events affecting PrPC are referred to as α- and β-cleavages, and in this review we outline the sites within PrPC at which the cleavages occur, the mechanisms potentially responsible and their relevance to pathology. Although the association of α-cleavage with neuroprotection is well-supported, we identify open questions regarding the importance of β-cleavage in TSEs and suggest experimental approaches that could provide clarification. We also combine findings from invitro cleavage assays and mass spectrometry-based studies of prion protein fragments in the brain to present an updated view in which α- and β-cleavages may represent two distinct clusters of proteolytic events that occur at multiple neighbouring sites rather than at single positions. Furthermore, we highlight the candidate proteolytic mechanisms best supported by the literature; currently, despite several proteases identified as capable of processing PrPC invitro, in cell-based models and in some cases, invivo, none have been shown conclusively to cleave PrPC in the brain. Addressing this knowledge gap will be crucial for developing therapeutic interventions to drive PrPC endoproteolysis in a neuroprotective direction. Finally, we end this review by briefly addressing other cleavage events, specifically ectodomain shedding, γ-cleavage, the generation of atypical pathological fragments in the familial prion disorder Gerstmann-Sträussler-Scheinker syndrome and the possibility of an additional form of endoproteolysis close to the PrPC N-terminus.

Influence of academic stress associated with student performance of students in graduation status from uniandes, ibarra campus

The present study aimed to thoroughly examine the influence of academic stress on the academic performance of undergraduate students at the Universidad Regional Autónoma de los Andes, Ibarra campus, in Ecuador. The study followed a qualitative approach based on documentary evidence through a systematic review embedded in the PRISMA method. Stress was measured through the documentary analysis of principal components, utilizing triangulation, verification, and reflexivity of academic performance demonstrated during the defense of final degree projects. The sample consisted of a focus group of students prior to the defense of their law degree projects. The results show that students who experience higher levels of stress are more likely to report a decline in their grades. Previous studies were analyzed, and empirical references were reviewed to better understand how stress affects the academic performance of these students. Additionally, potential mediating and moderating variables that may influence this relationship were explored. It was concluded that the information gathered through this analysis provided a comprehensive and updated view of the topic, which could be useful for designing strategies and intervention programs to help students manage stress and improve their academic performance

An Updated Overview of the Austroasiatic Components of Vietnamese

This article presents an updated view of the language history of Vietnamese from its native Austroasiatic roots, including key historical phonological, morphological, and syntactic features and developments; a characterization of its Austroasiatic etyma; and the context of this information in Vietnamese linguistic ethnohistory. It is now possible to make better supported claims and more precise characterizations due to improved understanding of the history of Austroasiatic and Vietic and their reconstructions, the nature and effect of language contact with Chinese, and the process of typological convergence of the ancestral language of Vietnamese. This study shows that, while Vietnamese is not a typologically characteristic Austroasiatic language, the Austroasiatic components of the Vietnamese lexicon and linguistic structure are more prominent than previously supposed.

Evaluation of photosynthetic Taxa in the Venice Lagoon from the nineteenth century to present day

The Venice Lagoon is the largest transitional environment within the Mediterranean Sea (almost 550 km2). Being a transitional environment, it contains many different ecological niches, hence the biodiversity in this environment is very high. However, at the same time, this lagoon system is under constant pressure from human activities, and it has been greatly modified by humans during the centuries. Examples are the construction of the city of Venice, the digging of the canals for commercial ships, and the modifications of the three inlets to the lagoon. All these activities altered the circulation inside the lagoon, modifying the equilibrium between river and sea inputs, also influencing the sediment intake, fundamental for saltmarshes stability. During the centuries, many authors monitored the photosynthetic taxa (seaweeds, halophytes, and seagrasses) inhabiting the Venice Lagoon. In this study, we reviewed works from the nineteenth century to the present time to obtain a complete and updated view of the photosynthetic species that inhabit this environment, observing a decrease in the presence of charophytes and heterokontophytes and an increase in rhodophytes in the analyzed period. Moreover, we also considered the ecological valence of the species reported in this environment through two different ecological indexes (Macroalgae Quality Index – MaQI, Ecological Evaluation Index – EEI), observing a decrease in the relative contribution of the species with high ecological valence along the centuries. We also reviewed the presence of threatened and non-indigenous species, observing some differences in the considered works. Finally, we also considered the molecular resources available on online databases, finding only half macroalgal species with a reference sequence, compared to almost 90% for higher plants.

The role for ω-3 polyunsaturated and short chain fatty acids in hypertension: an updated view on the interaction with gut microbiota

As of 2024, arterial hypertension is still considered the leading modifiable cardiovascular risk factor and, due to high rates of undertreatment and poor blood pressure control, the major contributor to human morbidity and mortality. Development of new treatment options and better interventions in lifestyle correction have become a priority of experimental and clinical research. In the last decades, dietary supplementation of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and generation of gut microbiota-derived short chain fatty acids (SCFAs) have surged as potential and promising interventions for hypertension and cardiovascular prevention. ω-3 PUFAs are considered “essential” fatty acids that can be obtained only from dietary sources. Although previous intervention trials were not consistent in reporting a significant benefit of ω-3 PUFAs, the recent REDUCE-IT trial has provided robust evidence in support of their role in cardiovascular prevention. Recent studies have also identified the intestinal microbiota as a potential player in the pathophysiology and progression of hypertension. Although this might occur through many pathways, generation of SCFAs that is highly dependent on dietary fiber intake is primarily involved, providing an additional target for the development of novel therapeutic strategies. For these reasons, some scientific societies currently recommend dietary supplementation of ω-3 PUFAs and fiber-containing foods in patients with hypertension. In this narrative review, we summarize the results of studies that examined the effects of ω-3 PUFAs and SCFAs on blood pressure, highlighting the mechanisms of action on the vascular system and their possible impact on hypertension, hypertension-related organ damage and, ultimately, cardiovascular outcomes.

Update on the connectivity of the paraventricular nucleus of the thalamus and its position within limbic corticostriatal circuits.

The paraventricular nucleus of the thalamus (PVT) is generating interest because of evidence establishing a role for this midline thalamic nucleus in behavior. Early tracing studies demonstrated that afferent fibers from the PVT and limbic cortex converge with dopamine fibers within subcompartments of the ventral striatum. Subsequent tracing studies expanded on these observations by establishing that the PVT provides a dense projection to a continuum of striatal-like regions that include the nucleus accumbens and the extended amygdala. These findings have been complemented by recent tracing evidence examining the organization of the PVT's efferent and afferent connections. An updated view of the organization of projection neurons in PVT is provided with a focus on the input-output relationship of these neurons. The review emphasizes recent findings demonstrating that the PVT is composed of intermixed populations of neurons with axons that collateralize to densely innervate limbic striatal regions while being reciprocally connected with limbic cortical areas that innervate the same regions of the striatum. An updated perspective of the PVT's anatomical relationship with limbic corticostriatal circuits is presented to stimulate research on how the PVT regulates behavioral responses associated with emotion and motivation.

Cancer-induced systemic pre-conditioning of distant organs: building a niche for metastatic cells.

From their early genesis, tumour cells integrate with the surrounding normal cells to form an abnormal structure that is tightly integrated with the host organism via blood and lymphatic vessels and even neural associations. Using these connections, emerging cancers send a plethora of mediators that efficiently perturb the entire organism and induce changes in distant tissues. These perturbations serendipitously favour early metastatic establishment by promoting a more favourable tissue environment (niche) that supports the persistence of disseminated tumour cells within a foreign tissue. Because the establishment of early metastatic niches represents a key limiting step for metastasis, the creation of a more suitable pre-conditioned tissue strongly enhances metastatic success. In this Review, we provide an updated view of the mechanisms and mediators of primary tumours described so far that induce a pro-metastatic conditioning of distant organs, which favours early metastatic niche formation. We reflect on the nature of cancer-induced systemic conditioning, considering that non-cancer-dependent perturbations of tissue homeostasis are also able to trigger pro-metastatic conditioning. We argue that a more holistic view of the processes catalysing metastatic progression is needed to identify preventive or therapeutic opportunities.

Green High-Rise Buildings

Objectives: The study aims to critically analyze green high-rise buildings and their associated challenges based on peer-reviewed journals published between 2020 and 2024, in order to understand the effectiveness of sustainable practices applied to tall buildings. Theoretical Framework: The study explores the concepts of green and sustainable buildings, differentiating their respective short- and long-term approaches in the context of building, occupant, and environmental interactions. It also considers the concept of green retrofitting, which involves upgrading existing buildings to improve their efficiency and reduce their environmental impact. Method: The research was conducted through a bibliographic review of peer-reviewed articles, focusing on terms such as “green high-rise building” and “green skyscraper.” The analysis included 72 articles categorized into four main areas: economic sustainability, water management, energy efficiency, and environmental comfort. Results and Discussion: The results indicate that elements such as green facades and renewable energy systems are widely used to reduce the environmental impact of tall buildings. Key themes discussed include energy efficiency and the economic value of green buildings. Technical and economic challenges are emphasized, but it is believed that local-scale research can help overcome these obstacles. The benefits of green retrofitting are highlighted, as it improves energy efficiency, increases property value, and contributes to climate change mitigation. Research Implications: The research suggests that sustainable practices in tall buildings are essential for sustainable urban development and mitigating the effects of climate change. Legal and public incentives are recommended to support these initiatives, promoting more resilient cities. Originality/Value: This article contributes by demonstrating how sustainable practices applied to tall buildings can address urban environmental challenges and foster conscious development. It also offers an updated and critical view of green high-rise buildings and their challenges. By identifying the most effective practices and technical and economic obstacles, it contributes to the evolution of knowledge in sustainable construction, providing a foundation for future local and interdisciplinary research.

Individual Pharmacotherapy Management (IPM-II) for Patient and Drug Safety in Polypharmacy via Clinical Electronic Health Record Is Associated with Significant Fall Prevention.

Falls and fractures are emerging as a near-pandemic and major global health concern, placing an enormous burden on ageing patients and public health economies. Despite the high risk of polypharmacy in the elderly patients, falls are usually attributed to age-related changes. For the "Individual Pharmacotherapy Management (IPM)" established at the University Hospital Halle, the IPM medication adjustments and their association with in-hospital fall prevention were analysed. On the basis of the most updated digital overall patient view via his inpatient electronic health record (EHR), IPM adapts each drug's Summary of Product Characteristics to the patient's condition. A retrospective pre-post intervention study in geriatric traumatology on ≥70 years old patients compared 200 patients before IPM implementation (CG) with 204 patients from the IPM intervention period (IG) for the entire medication list, organ, cardiovascular and vital functions and fall risk parameters. Statistically similar baseline data allowed a comparison of the average 80-year-old patient with a mean of 11.1 ± 4.9 (CG) versus 10.4 ± 3.6 (IG) medications. The IPM adjusted for drug-drug interactions, drug-disease interactions, overdoses, anticholinergic burden, adverse drug reactions, esp. from opioids inducing increased intrasynaptic serotonin, psychotropic drugs, benzodiazepines, contraindications and missing prescriptions. IPM was associated with a significant reduction in in-hospital falls from 18 (9%) in CG to 3 (1.5%) in IG, a number needed to treat of 14, relative risk reduction 83%, OR 0.17 [95% CI 0.04; 0.76], p = 0.021 in multivariable regression analysis. Factors associated with falls were antipsychotics, digitoxin, corticosteroids, Würzburg pain drip (combination of tramadol, metamizole, metoclopramide), head injury, cognitive impairment and aspects of the Huhn Fall Risk Scale including urinary catheter. The results indicate medication risks constitute a major iatrogenic cause of falls in this population and support the use of EHR-based IPM in standard care for the prevention of falls in the elderly and for patient and drug safety. In terms of global efforts, IPM contributes to the running WHO and United Nations Decade of Healthy Ageing (2021-2030).

ANGI-08. SPATIAL TRANSCRIPTOMIC COMPARISONS OF GLIOBLASTOMA TISSUE REVEAL UPREGULATION OF NEURODEVELOPMENTAL PATHWAYS AND SYNAPTIC GENES IN INFILTRATING TUMOR CELLS

Abstract Glioblastoma remains one of the deadliest brain malignancies. First-line therapy consists of maximal surgical tumor resection, chemotherapy, and radiotherapy. Malignant cells escape surgical resection by migrating into the surrounding healthy brain tissue, where they give rise to the recurrent tumor. Gene expression profiling allows glioblastoma tumor cores to be classified into mesenchymal, proneural, and classical subtypes, each with distinct genetic alterations and cellular compositions. In contrast, the adjacent brain parenchyma where infiltrating malignant cells escape surgical resection is less characterized in patients. Using single-cell and multicellular resolution spatial transcriptomics on tissues from both the tumor core and infiltrated brain tissue (n = 11), we compared the transcriptional profiles of malignant cells in these regions. Malignant cells near regions with microvascular proliferation showed increased expression of genes related to vascular homeostasis. Within tumor cores, proneural and mesenchymal subtypes exhibited distinct spatial gene expression patterns, although these differences were reduced in the infiltrated brain tissue, apart from gene expression due to chromosomal alterations specific to the proneural subtype. We identified two transcriptional patterns of brain infiltration, with the dominant pattern showing a transition from mesenchymal to proneural states. This transition was accompanied by increased expression of genes linked to neurodevelopmental pathways and glial cell differentiation. Additionally, one gene module upregulated in infiltrating malignant cells was predictive of poor patient survival and enriched for genes associated with differentiated neuronal cells. Together, our findings provide an updated view of the spatial landscape of glioblastomas and infiltrated brain tissue, furthering our understanding of the malignant cells that invade healthy brain. This insight offers new avenues for targeted therapy after surgical resection of the primary tumor.

Determinants of health and pregnancy and birth outcomes: an overview

Abstract Introduction This study examines the influence of health determinants on pregnancy and birth outcomes. The aim is to provide a clear and updated view of the overall framework characterizing the birth experience, with crucial implications for clinical practice, research, and health policy. Methods Data analysis pertains to the Certificate of Assistance for Birth (CAP) concerning residents in the territory of AUSL South-East Tuscany in the years 2021 and 2022. The number of women of childbearing age in Tuscany in 2022 is 150,959, while the number of births analyzed in the study is 9,053. The study conducts multivariate analysis between factors and pregnancy-related outcomes. Results Controlling for age, citizenship and others factors, the risk of cesarean section is significantly higher (p < 0.05) among mothers: over 40 years old (OR = 2.09), with education levels of lower secondary (OR = 1.21) and upper secondary (OR = 1.23) compared to a degree, not employed (OR = 1.25) and homemakers (OR = 1.45) compared to employed, overweight/obese (OR = 1.41), with gestational diabetes (OR = 1.16), smoking during pregnancy (OR = 1.27), with gestational hypertension (OR = 2.81). Controlling for age, citizenship and others factors, the risk of term low birth weight is significantly higher (p < 0.05) among mothers: over 40 years old (OR = 1.76), not employed (OR = 1.76) and homemakers (OR = 1.34) compared to employed, smoking more than 3 cigarettes daily during pregnancy (OR = 1.31) not significant, with gestational hypertension (OR = 5.57), nulliparous (OR = 1.42). Controlling for age, citizenship and other factors, the risk of premature birth is significantly higher (p < 0.05) among mothers: with gestational hypertension (OR = 5.22), nulliparous (OR = 1.89), smoking during pregnancy (OR = 1.59). Conclusions The results underscore the importance of carefully monitoring and managing these risk factors during pregnancy to improve outcomes for both mother and baby. Key messages • Understanding the determinants that influence birth outcomes plays a fundamental role. • The importance of Early Childhood Development and early interventions can improve children’s health and well-being.

BATERIAS DE CARROS ELÉTRICOS: MANUTENÇÕES E DESCARTES

The rapid growth in the adoption of electric vehicles brings to light challenges related to the maintenance and disposal of batteries, which are essential components for the operation of these vehicles. The central issue addressed is the sustainability of the battery life cycle, considering both the efficiency of their maintenance and the environmental impacts resulting from inadequate disposal. The context involves the transition to a greener economy and the demands for clean technologies, which makes it essential to discuss appropriate practices to extend the useful life of batteries and ensure their safe disposal. The main objective of this study is to analyze the maintenance practices of electric car batteries and disposal strategies, focusing on minimizing environmental impacts and optimizing the life cycle of components. The research seeks to identify effective methods to extend the useful life of batteries, in addition to evaluating existing recycling policies and processes. The methodology used includes a literature review of current battery maintenance and disposal practices, in addition to the analysis of case studies that exemplify different approaches and results in international contexts. The research also incorporates interviews with industry experts, aiming to obtain a comprehensive and updated view of best practices and challenges faced. This work contributes to the discussion on sustainability in the automotive sector and to the formulation of more efficient policies for the management of technological waste.

An updated view on the influence of initial opioid prescription characteristics on long-term opioid use among opioid naïve patients

ObjectivesThis retrospective cohort study provides an updated view on the association between the likelihood of long-term opioid use (LTOU) and characteristics of the initial opioid prescription (dose, opioid type) and initial opioid prescription episode (days’ supplied) among opioid-naïve patients utilizing IQVIA PharMetrics®Plus for Academics database representative of commercially insured patients in the US. MethodsKaplan-Meier estimates were used to determine opioid continuation likelihood at 365 days stratified by the characteristics of the initial opioid prescription and initial opioid prescription episode. Cox-proportional hazard models were estimated to determine the strength of association between initial opioid prescription characteristics and opioid continuation. ResultsA total of 578,403 cancer-free, SUD-free, opioid-naïve subjects aged ≥14 years that filled ≥1 opioid prescriptions between April 13, 2016 and April 18, 2020 were identified and categorized based on time to opioid discontinuation. After accounting for censoring, 5.05 % of persons continued opioid use for ≥365 days. Compared to a 1–2 days’ supply (DS), the likelihood of opioid discontinuation was consistently lower with higher DS [HRs (CIs): 3–4 days' supply = 0.66 (0.65–0.66); 5–7 DS = 0.41 (0.41–0.41); 8–10 DS = 0.33 (0.33–0.34); 11–14 DS = 0.30 (0.29–0.31); 15–21 DS = 0.26 (0.26–0.27); ≥22 DS = 0.17 (0.17–0.18)]. These associations between increased DS and decreased likelihood of discontinuing opioid remained consistent across different pain etiologies. ConclusionsIn this era of more conservative opioid prescribing, increases in DS remains the strongest factor associated with a higher likelihood of LTOU.

Molecular mechanisms of mitochondrial dynamics.

Mitochondria not only synthesize energy required for cellular functions but are also involved in numerous cellular pathways including apoptosis, calcium homoeostasis, inflammation and immunity. Mitochondria are dynamic organelles that undergo cycles of fission and fusion, and these transitions between fragmented and hyperfused networks ensure mitochondrial function, enabling adaptations to metabolic changes or cellular stress. Defects in mitochondrial morphology have been associated with numerous diseases, highlighting the importance of elucidating the molecular mechanisms regulating mitochondrial morphology. Here, we discuss recent structural insights into the assembly and mechanism of action of the core mitochondrial dynamics proteins, such as the dynamin-related protein 1 (DRP1) that controls division, and the mitofusins (MFN1 and MFN2) and optic atrophy 1 (OPA1) driving membrane fusion. Furthermore, we provide an updated view of the complex interplay between different proteins, lipids and organelles during the processes of mitochondrial membrane fusion and fission. Overall, we aim to present a valuable framework reflecting current perspectives on how mitochondrial membrane remodelling is regulated.

The hearts of large mammals generate higher pressures, are less efficient and use more energy than those of small mammals.

A prevailing assumption in the cardiovascular field is that the metabolic rate of the heart is a constant proportion of a mammal's whole-body aerobic metabolic rate. In this Commentary, we assemble previously published cardiovascular, metabolic and body mass data from matched terrestrial mammalian species, at rest and during heavy exercise, and reveal scaling relationships that challenge this assumption. Our analyses indicate that the fractional metabolic cost of systemic perfusion compared with whole-body metabolic rate increases significantly with body size among resting mammals, from ∼2.5% in a mouse to ∼10% in an elephant. We propose that two significant body size-dependent effects contribute to this conclusion; namely, that larger species generate higher mean systemic arterial blood pressure and that their myocardium operates with lower external mechanical efficiencies compared with those of smaller species. We discuss potential physiological and mechanical explanations, including the additional energy needed to support the arterial blood column above the heart in larger species, especially those with long necks, as well as the possible sources of greater internal energy losses from the heart of larger species. Thus, we present an updated view of how increasing blood pressure and decreasing efficiency of the myocardium result in an increasing fractional metabolic cost of perfusion as body size increases among resting mammals.

Ecological niche assessment and conservation status of colocolo pampas cat Leopardus colocola (Molina 1782)

Until 2021, Leopardus colocola was considered a species distributed across much of South America. However, recent studies have shown that it is a monotypic species, apparently restricted in its distribution to the central-northern region of Chile, distinct from other felines of the same genus. This change in its classification and distribution has sparked debate regarding its conservation status, which now requires a detailed assessment. In this study, we analyzed the species’ geographic distribution using ecological niche modeling and evaluated its conservation status according to the guidelines of the International Union for Conservation of Nature, considering the impact of mining concessions and Chile's road network. Presence records of the species were systematized, and a new ecological niche model was developed. Additionally, the Extent of Occurrence (EOO) and the Area of Occupancy (AOO) were calculated. The fragmentation and projected reduction of the niche model, along with the EOO and AOO, place the species under the Criteria B2ab (i, ii, iii), leading to its classification as “Endangered.” This study provides an updated view of the species' geographic distribution and conservation status in Chile. The results are crucial for future conservation efforts and offer a solid foundation for effective management strategies.

Statistical-Mechanics Analyses on Thermodynamics of Protein Folding Constructed by Privalov and Co-Workers.

Privalov and co-workers estimated the changes in hydration enthalpy and entropy upon ubiquitin unfolding and their temperature dependences denoted by ΔHhyd(T) and ΔShyd(T), respectively, from experimentally measured enthalpies and entropies of transfer of various model compounds from gaseous phase to water. We calculate ΔHhyd(T) and ΔShyd(T) for ubiquitin by our statistical-mechanics theory where molecular and atomistic models are employed for water and protein structure, respectively. ΔHhyd(T) and ΔShyd(T) calculated are in remarkably good agreement with those estimated by Privalov and co-workers. By examining relative magnitudes and signs of the changes in a variety of constituents of ΔHhyd(T) and ΔShyd(T), we confirm that the hydrophobic effect is an essential force driving a protein to fold. Detailed and comprehensive explanations are given for our claim that the prevailing views of the hydrophobic effect are not capable of elucidating its weakening at low temperatures, whereas our updated view is. We find out problematic points of the changes in enthalpy and entropy upon protein unfolding denoted by ΔH°(T) and ΔS°(T), respectively, which are measured using the differential scanning calorimetry at low pH, suggesting a theoretical method of calculating ΔH°(T) and ΔS°(T) at pH ∼ 7.

The bronchoalveolar lavage dilution conundrum: an updated view on a long-standing problem.

Bronchoalveolar lavage (BAL) is used by researchers to study molecular interactions within healthy and diseased human lungs. However, the utility of BAL fluid measurements may be limited by difficulties accounting for dilution of the epithelial lining fluid (ELF) sampled and inconsistent collection techniques. The use of endogenous markers to estimate ELF dilution has been proposed as a potential method to normalize acellular molecule measurements in BAL fluid, but these markers are also imperfect and prone to inaccuracy. The focus of this report is to review factors that affect the interpretation of acellular molecule measurements in lung ELF and present original data comparing the performance of several BAL dilution markers during health and in a human endobronchial endotoxin challenge model of acute inflammation. Our findings suggest that incomplete ELF and lavage fluid mixing, flux of markers across the alveolar barrier, and lung inflammation are all possible factors that can affect marker performance. Accounting for these factors, we show that commonly used markers including urea, total protein, albumin, and immunoglobulin M are likely unreliable BAL dilution markers. In contrast, surfactant protein D appears to be less affected by these factors and may be a more accurate and biologically plausible marker to improve the reproducibility of acellular BAL component measurements across individuals during health and inflammatory states.NEW & NOTEWORTHY In this report, mathematical prediction models and real-world measurements are used to compare the performance of molecular markers of dilution in bronchoalveolar lavage fluid samples. Effects of acute inflammation within individual subjects are highlighted. These findings inform recommendations for normalizing measurements across bronchoalveolar lavage samples and highlight the need for additional markers to improve the rigor of translational studies utilizing bronchoalveolar lavage measurements.

Graph Contrastive Learning With Adaptive Proximity-Based Graph Augmentation.

Graph neural networks (GNNs) have been successful in a variety of graph-based applications. Recently, it is shown that capturing long-range relationships between nodes helps improve the performance of GNNs. The phenomenon is mostly confirmed in a supervised learning setting. In this article, inspired by contrastive learning (CL), we propose an unsupervised learning pipeline, in which different types of long-range similarity information are injected into the GNN model in an efficient way. We reconstruct the original graph in feature and topology spaces to generate three augmented views. During training, our model alternately picks an augmented view, and maximizes an agreement between the representations of the view and the original graph. Importantly, we identify the issue of diminishing utility of the augmented views as the model gradually learns useful information from the views. Hence, we propose a view update scheme that adaptively adjusts the augmented views, so that the views can continue to provide new information that helps with CL. The updated augmented views and the original graph are jointly used to train a shared GNN encoder by optimizing an efficient channel-level contrastive objective. We conduct extensive experiments on six assortative graphs and three disassortative graphs, which demonstrate the effectiveness of our method.

Energy commodities spillover analysis for assessing the functioning of the European Union Emissions Trading System trade network of carbon allowances

The European Union Emissions Trading System (EU ETS) is designed to promote carbon reduction in a cost-effective and economically efficient manner. To meet their compliance requirements, participants within the EU ETS can either invest in carbon abatement, thereby improving their environmental performances, or purchase carbon allowances from the market. Our analysis aims to investigate the structural features of the EU ETS trade network of allowances and assess its robustness to spillovers propagated from energy commodities. We build the EU ETS trade network of allowances on a daily basis by leveraging a granular dataset comprising over 32k accounts that performed approximately 720k trades, involving more than 127 billion of allowances from 2005 to 2020. Importantly, our analysis is able to cover entirely the first three phases of the EU ETS, thus providing an updated view on the functioning of the EU ETS. We find that the EU ETS trade network of allowances is disassortative and characterized by very active nodes belonging to the energy sector. Moreover, we detect that energy commodity transmission channels can be substantial and may shape the way nodes transfer allowances, with the configuration of the EU ETS often being a net receiver of spillovers. These findings are robust even when we analyze extreme quantiles of the distribution to account for distressed periods. Our study shows how the functioning of the EU ETS can be influenced by spillovers imported from energy commodity markets. We discuss how investors can build portfolios that either hedge or amplify the impact of such spillovers, depending on their risk appetite. Given that energy commodities are significant inputs in the production processes of energy firms—who are highly active participants in the trade network of allowances—analyzing market responses to shocks in energy commodities is crucial for the effective implementation of the policy.