Differentially Expressed Proteins in Primary Endothelial Cells Derived From Patients With Acute Myocardial Infarction

Endothelial dysfunction is one of the primary factors in the onset and progression of atherothrombosis resulting in acute myocardial infarction (AMI). However, the pathological and cellular mechanisms of endothelial dysfunction in AMI have not been systematically studied. Protein expression profiling in combination with a protein network analysis was used by the mass spectrometry-based label-free quantification approach. This identified and quantified 2246 proteins, of which 335 were differentially regulated in coronary arterial endothelial cells from patients with AMI compared with controls. The differentially regulated protein profiles reveal the alteration of (1) metabolism of RNA, (2) platelet activation, signaling, and aggregation, (3) neutrophil degranulation, (4) metabolism of amino acids and derivatives, (5) cellular responses to stress, and (6) response to elevated platelet cytosolic Ca2+ pathways. Increased production of oxidants and decreased production of antioxidant biomarkers as well as downregulation of proteins with antioxidant properties suggests a role for oxidative stress in mediating endothelial dysfunction during AMI. In conclusion, this is the first quantitative proteomics study to evaluate the cellular mechanisms of endothelial dysfunction in patients with AMI. A better understanding of the endothelial proteome and pathophysiology of AMI may lead to the identification of new drug targets

Dynamic Changes in High-Sensitivity Cardiac Troponin I in Response to Anthracycline-Based Chemotherapy

Aims: Treatment advances have improved cancer-related outcomes and shifted interest towards minimising long-term iatrogenic complications, particularly chemotherapy-related cardiotoxicity. High-sensitivity cardiac troponin I (hs-cTnI) assays accurately quantify very low concentrations of plasma troponin and enable early detection of cardiomyocyte injury prior to the development of myocardial dysfunction. The profile of hs-cTnI in response to anthracycline-based treatment has not previously been described. Materials and methods: This was a multicentre prospective observational cohort study. Female patients with newly diagnosed invasive breast cancer scheduled to receive anthracycline-based (epirubicin) chemotherapy were recruited. Blood sampling was carried out before and 24 h after each cycle. Hs-cTnI concentrations were measured using the Abbott ARCHITECTSTAT assay. Results: We recruited 78 women with a median (interquartile range) age of 52 (49–61) years. The median baseline troponin concentration was 1 (1–4) ng/l and the median cumulative epirubicin dose was 394 (300–405) mg/m2. Following an initial 33% fall 24 h after anthracycline dosing (P < 0.001), hs-cTnI concentrations increased by a median of 50% (P < 0.001) with each successive treatment cycle. In total, 45 patients had troponin measured immediately before the sixth treatment cycle, 21 (46.6%) of whom had hs-cTnI concentrations ≥16 ng/l, indicating myocardial injury. Plasma hs-cTnI concentrations before the second treatment cycle were a strong predictor of subsequent myocardial injury. Conclusions: Cardiotoxicity arising from anthracycline therapy is detectable in the earliest stages of breast cancer treatment and is cumulative with each treatment cycle. This injury is most reliably determined from blood sampling carried out before rather than after each treatment cycle

Gaming motivation and problematic video gaming: The role of needs frustration

Motivation is often used as a predictor of a problematic style of video game engagement, implying that individuals' gaming undermines optimal functioning. Drawing from recent advances in Self-Determination Theory (SDT), the present study explores the links between gaming motivations, the daily frustration of basic psychological needs, and reports of problematic video gaming (PVG). A sample of 1029 participants (72.8% male; M = 22.96 years; SD = 4.13 years) completed items regarding their gaming engagement and gaming motivation as well as their experience of needs frustration and PVG symptoms. Results revealed positive associations between gaming motivations and PVG, and between daily needs frustration and PVG. Finally, after comparing several competing models, a mediational model whereby needs frustration explained the association between individuals' gaming motivation and PVG emerged as best fitting the data. The discussion addresses the theoretical and practical implications of these findings in the context of recent research

Autotrophic denitrification of nitrate rich wastewater in fluidized bed reactors using pyrite and elemental sulfur as electron donors

This study compared denitrification performances and microbial communities in fluidized bed reactors (FBRs) carrying out autotrophic denitrification using elemental sulfur (S0) and pyrite (FeS2) as electron donors. The reactors were operated for 220 days with nitrate loading rates varying between 23 and 200 mg N-NO 3 − /L ⋅ d and HRT between 48 and 4 h. The highest denitrification rates achieved were 142.2 and 184.4 mg N-NO 3 − /L ⋅ d in pyrite and sulfur FBRs, respectively. Pyrite-driven denitrification produced less SO 4 2 − and no buffer addition was needed to regulate the pH. The sulfur FBR needed instead CaCO3 to maintain the pH neutral and consequentially more sludge was produced (CaSO4 precipitation). The active community of pyrite-based systems was investigated and Azospira sp., Ferruginibacter sp., Rhodococcus sp. and Pseudomonas sp. were the predominant genera, while Thiobacillus sp. and Sulfurovum sp. dominated the active community in the sulfur FBR. However, Thiobacillus sp. became more dominant when operating at elevated nitrogen loading rate. Patterns of diversity and microbial community assembly were assessed and revealed three distinct stages of microbial community succession which corresponded with the operation of a period of high influent nitrate concentration (13 5 mg N-NO 3 − /L). It is proposed that a high degree of functional redundancy in the initial microbial communities may have helped both reactors to respond better to such high influent nitrate concentration

Anthropogenic alteration of nutrient supply increases the global freshwater carbon sink

Lakes have a disproportionate effect on the global carbon (C) cycle relative to their area, mediating C transfer from land to atmosphere, and burying organic-C in their sediments. The magnitude and temporal variability of C burial is, however, poorly constrained, and the degree to which humans have influenced lake C cycling through landscape alteration has not been systematically assessed. Here, we report global and biome specific trajectories of lake C sequestration based on 516 lakes and show that some lake C burial rates (i.e., those in tropical forest and grassland biomes) have quadrupled over the last 100 years. Global lake C-sequestration (~0.12 Pg year-1) has increased by ~72 Tg year-1 since 1900, offsetting 20% of annual CO2 freshwater emissions rising to ~30% if reservoirs are included and contributing to the residual continental C sink. Nutrient availability explains ~70% of the observed increase, while rising temperatures have a minimal effect

Divided communities and contested landscapes: Mobility, development and shifting identities in migrant destination sites in Papua New Guinea

Internal conflicts at the local and national levels in several South Pacific countries have revealed the fragility of national unity and the difficulties nations face in governing and managing their own economic development. In Papua New Guinea, the focus of this paper, an uncertain economic future for many rural and urban communities, and rising inequalities in income opportunities and access to resources, have coincided with greater intolerance of migrants at sites of high in-migration by customary landowners and provincial and local authorities. This paper draws on fieldwork undertaken in the major oil palm growing regions of Papua New Guinea where migrants from densely populated regions of the country have settled on state land alienated from customary landowners. We examine how struggles over land, resource control and development are polarising migrant and landowner identities resulting in increasing tensions and episodic communal violence. A settler identity is emerging based on a narrative of nation building and national development, while an ethno-regional identity amongst customary landowners is undermining the citizen rights of migrants and challenging the role and authority of the state in land matters

Development of a long noncoding RNA-based machine learning model to predict COVID-19 in-hospital mortality

Tools for predicting COVID-19 outcomes enable personalized healthcare, potentially easing the disease burden. This collaborative study by 15 institutions across Europe aimed to develop a machine learning model for predicting the risk of in-hospital mortality post-SARS-CoV-2 infection. Blood samples and clinical data from 1286 COVID-19 patients collected from 2020 to 2023 across four cohorts in Europe and Canada were analyzed, with 2906 long non-coding RNAs profiled using targeted sequencing. From a discovery cohort combining three European cohorts and 804 patients, age and the long non-coding RNA LEF1-AS1 were identified as predictive features, yielding an AUC of 0.83 (95% CI 0.82-0.84) and a balanced accuracy of 0.78 (95% CI 0.77-0.79) with a feedforward neural network classifier. Validation in an independent Canadian cohort of 482 patients showed consistent performance. Cox regression analysis indicated that higher levels of LEF1-AS1 correlated with reduced mortality risk (age-adjusted hazard ratio 0.54, 95% CI 0.40-0.74). Quantitative PCR validated LEF1-AS1's adaptability to be measured in hospital settings. Here, we demonstrate a promising predictive model for enhancing COVID-19 patient management.</p

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Troponin in acute chest pain to risk stratify and guide effective use of computed tomography coronary angiography (TARGET-CTCA): a randomised controlled trial

Background The majority of patients with suspected acute coronary syndrome presenting to the emergency department will be discharged once myocardial infarction has been ruled out, although a proportion will have unrecognised coronary artery disease. In this setting, high-sensitivity cardiac troponin identifies those at increased risk of future cardiac events. In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been ruled out, this trial aims to investigate whether outpatient computed tomography coronary angiography (CTCA) reduces subsequent myocardial infarction or cardiac death. Methods TARGET-CTCA is a multicentre prospective randomised open label with blinded endpoint parallel group event driven trial. After myocardial infarction and clear alternative diagnoses have been ruled out, participants with intermediate cardiac troponin concentrations (5 ng/L to 99th centile upper reference limit) will be randomised 1:1 to outpatient CTCA plus standard of care or standard of care alone. The primary endpoint is myocardial infarction or cardiac death. Secondary endpoints include clinical, patient-centred, process and cost-effectiveness. Recruitment of 2270 patients will give 90% power with a two-sided P value of 0.05 to detect a 40% relative risk reduction in the primary endpoint. Follow-up will continue until 97 primary outcome events have been accrued in the standard care arm with an estimated median follow-up of 36 months. Discussion This randomised controlled trial will determine whether high-sensitivity cardiac troponin-guided CTCA can improve outcomes and reduce subsequent major adverse cardiac events in patients presenting to the emergency department who do not have myocardial infarction

Looking forward through the past: identification of 50 priority research questions in palaeoecology

1. Priority question exercises are becoming an increasingly common tool to frame future agendas in conservation and ecological science. They are an effective way to identify research foci that advance the field and that also have high policy and conservation relevance. 2. To date, there has been no coherent synthesis of key questions and priority research areas for palaeoecology, which combines biological, geochemical and molecular techniques in order to reconstruct past ecological and environmental systems on time-scales from decades to millions of years. 3. We adapted a well-established methodology to identify 50 priority research questions in palaeoecology. Using a set of criteria designed to identify realistic and achievable research goals, we selected questions from a pool submitted by the international palaeoecology research community and relevant policy practitioners. 4. The integration of online participation, both before and during the workshop, increased international engagement in question selection. 5. The questions selected are structured around six themes: human–environment interactions in the Anthropocene; biodiversity, conservation and novel ecosystems; biodiversity over long time-scales; ecosystem processes and biogeochemical cycling; comparing, combining and synthesizing information from multiple records; and new developments in palaeoecology. 6. Future opportunities in palaeoecology are related to improved incorporation of uncertainty into reconstructions, an enhanced understanding of ecological and evolutionary dynamics and processes and the continued application of long-term data for better-informed landscape management