MAGPIE: A Machine Learning Approach to Decipher Protein-Protein Interactions in Human Plasma.

Immunoprecipitation coupled to tandem mass spectrometry (IP-MS/MS) methods are often used to identify protein-protein interactions (PPIs). While these approaches are prone to false positive identifications through contamination and antibody nonspecific binding, their results can be filtered using negative controls and computational modeling. However, such filtering does not effectively detect false-positive interactions when IP-MS/MS is performed on human plasma samples.

EPA and DHA inhibit LDL-induced upregulation of human adipose tissue NLRP3 inflammasome/IL-1β pathway and its association with diabetes risk factors.

Elevated numbers of atherogenic lipoproteins (apoB) predict the incidence of type 2 diabetes (T2D). We reported that this may be mediated via the activation of the NLRP3 inflammasome, as low-density lipoproteins (LDL) induce interleukin-1 beta (IL-1β) secretion from human white adipose tissue (WAT) and macrophages. However, mitigating nutritional approaches remained unknown.

Pandemic-related prenatal maternal stress, model of maternity care and postpartum mental health: The Australian BITTOC study.

Problem: Women pregnant during the COVID-19 pandemic may be at risk of elevated postpartum mental health problems.

Background: Social support protects maternal mental health during a pandemic. It is possible that formal supports, such as continuity maternity models of care, may also support maternal wellbeing.

Feasibility and accuracy of at-home glucose tolerance tests for cystic fibrosis related diabetes screening.

Background: Adult people living with Cystic Fibrosis (CF) undergo annual screening for CF-related diabetes. These tests represent a burden and can lead to undesirable effects resulting in low adherence. The objectives of this study were to 1) compare gold-standard in-hospital oral glucose tolerance testing (OGTT) with at-home options, and 2) evaluate acceptability of at-home options.

Senescent Macrophages Release Inflammatory Cytokines and RNA-Loaded Extracellular Vesicles to Circumvent Fibroblast Senescence.

Senescent cells, which accumulate with age, exhibit a pro-inflammatory senescence-associated secretory phenotype (SASP) that includes the secretion of cytokines, lipids, and extracellular vesicles (EVs). Here, we established an in vitro model of senescence induced by Raf-1 oncogene in RAW 264.7 murine macrophages (MΦ) and compared them to senescent MΦ found in mouse lung tumors or primary macrophages treated with hydrogen peroxide.

Conserved role of hnRNPL in alternative splicing of epigenetic modifiers enables B cell activation.

The multifunctional RNA-binding protein hnRNPL is implicated in antibody class switching but its broader function in B cells is unknown. Here, we show that hnRNPL is essential for B cell activation, germinal center formation, and antibody responses. Upon activation, hnRNPL-deficient B cells show proliferation defects and increased apoptosis.

Living ethics: a stance and its implications in health ethics.

Moral or ethical questions are vital because they affect our daily lives: what is the best choice we can make, the best action to take in a given situation, and ultimately, the best way to live our lives? Health ethics has contributed to moving ethics toward a more experience-based and user-oriented theoretical and methodological stance but remains in our practice an incomplete lever for human development and flourishing. This context led us to envision and develop the stance of a "living ethics", described in this inaugural collective and programmatic paper as an effort to consolidate creative collaboration between a wide array of stakeholders. We engaged in a participatory discussion and collective writing process known as instrumentalist concept analysis.

Yeast zinc cluster transcription factors involved in the switch from fermentation to respiration show interdependency for DNA binding revealing a novel type of DNA recognition.

In budding yeast, fermentation is the most important pathway for energy production. Under low-glucose conditions, ethanol is used for synthesis of this sugar requiring a shift to respiration. This process is controlled by the transcriptional regulators Cat8, Sip4, Rds2 and Ert1.

Native low-density lipoproteins are priming signals of the NLRP3 inflammasome/interleukin-1β pathway in human adipose tissue and macrophages.

Elevated plasma numbers of atherogenic apoB-lipoproteins (apoB), mostly as low-density lipoproteins (LDL), predict diabetes risk by unclear mechanisms. Upregulation of the NLRP3 inflammasome/interleukin-1 beta (IL-1β) system in white adipose tissue (WAT) is implicated in type 2 diabetes (T2D); however, metabolic signals that stimulate it remain unexplored. We hypothesized that (1) subjects with high-apoB have higher WAT IL-1β-secretion than subjects with low-apoB, (2) WAT IL-1β-secretion is associated with T2D risk factors, and (3) LDL prime and/or activate the WAT NLRP3 inflammasome.

The effects of branched-chain amino acids on muscle protein synthesis, muscle protein breakdown and associated molecular signalling responses in humans: an update.

Branched-chain amino acids (BCAA: leucine, isoleucine and valine) are three of the nine indispensable amino acids, and are frequently consumed as a dietary supplement by athletes and recreationally active individuals alike. The popularity of BCAA supplements is largely predicated on the notion that they can stimulate rates of muscle protein synthesis (MPS) and suppress rates of muscle protein breakdown (MPB), the combination of which promotes a net anabolic response in skeletal muscle. To date, several studies have shown that BCAA (particularly leucine) increase the phosphorylation status of key proteins within the mechanistic target of rapamycin (mTOR) signalling pathway involved in the regulation of translation initiation in human muscle.

Lysergic Acid Diethylamide (LSD) for the Treatment of Anxiety Disorders: Preclinical and Clinical Evidence.

Anxiety disorders (ADs) represent the sixth leading cause of disability worldwide, resulting in a significant global economic burden. Over 50% of individuals with ADs do not respond to standard therapies, making the identification of more effective anxiolytic drugs an ongoing research priority. In this work, we review the preclinical literature concerning the effects of lysergic acid diethylamide (LSD) on anxiety-like behaviors in preclinical models, and the clinical literature on anxiolytic effects of LSD in healthy volunteers and patients with ADs.

Eye movements and the perceptual span in disordered reading: A comparison of schizophrenia and dyslexia.

Increasing evidence of a common neurodevelopmental etiology between schizophrenia and developmental dyslexia suggests that neurocognitive functions, such as reading, may be similarly disrupted. However, direct comparisons of reading performance in these disorders have yet to be conducted. To address this gap in the literature, we employed a gaze-contingent moving window paradigm to examine sentence-level reading fluency and perceptual span (breadth of parafoveal processing) in adults with schizophrenia (dataset from Whitford et al.

Intravenous ketamine for treatment-resistant depression patients who have failed to respond to transcranial magnetic stimulation: A case series.

Background: For individuals with treatment-resistant depression (TRD), transcranial magnetic stimulation (TMS) has become a well-established approach. In the past decade, intravenous (IV) racemic ketamine has also emerged as a potential treatment for TRD. Currently, little data is available on the clinical effects of IV racemic ketamine in TRD patients who experienced TMS-failure.

Adaptive partitioning of a gene locus to the nuclear envelope in Saccharomyces cerevisiae is driven by polymer-polymer phase separation.

Partitioning of active gene loci to the nuclear envelope (NE) is a mechanism by which organisms increase the speed of adaptation and metabolic robustness to fluctuating resources in the environment. In the yeast Saccharomyces cerevisiae, adaptation to nutrient depletion or other stresses, manifests as relocalization of active gene loci from nucleoplasm to the NE, resulting in more efficient transport and translation of mRNA. The mechanism by which this partitioning occurs remains a mystery.

A unique presentation of NLRP3-associated autoinflammatory disease: case report.

Background: NLRP3-associated autoinflammatory diseases (NLRP3-AID) are rare genetic autoinflammatory diseases characterized by chronic inflammation and an urticaria-like rash. We report an unusual presentation of severe NLRP3-AID resulting in a significant diagnostic delay of more than three decades.

Case Presentation: The patient presented with early-onset serositis as well as prominent peripheral eosinophilia with organ infiltration, in the absence of the classic urticaria-like rash.

Development and psychometric evaluation of the CanSmart questionnaire to measure chronic disease self-management tasks.

Background: Psychometrically sound measures of chronic disease self-management tasks are needed to improve identification of patient needs and to tailor self-management programs. This study aimed to develop and conduct a preliminary psychometric analysis of the CanSMART questionnaire among a diverse, multimorbid Canadian population.

Methods: The data were drawn from a cross-sectional online survey to examine self-management needs and support preferences.

The Revised Identification of Seniors At Risk screening tool predicts readmission in older hospitalized patients: a cohort study.

Background: The Identification of Seniors at Risk (ISAR) screening tool is a widely-used risk stratification tool for older adults in the emergency department (ED). Few studies have investigated the use of ISAR to predict outcomes of hospitalized patients. To improve usability a revised version of ISAR (ISAR-R), was developed in a quality improvement project.

Influence of severe hypoglycemia definition wording on reported prevalence in adults and adolescents with type 1 diabetes: a cross-sectional analysis from the BETTER patient-engagement registry analysis.

Aims: Compare the self-reported prevalence of severe hypoglycemia (level-3-H) in people with type 1 diabetes (PWT1D) according to two wording of definition: by the International Hypoglycemia Study Group (IHSG) and an alternate simplified version developed by patient-partners (PP).

Methods: Cross-sectional study (PWT1D >  = 14 years) self-reporting risk factors, patient-year incidence and annual prevalence of level-3-H were defined according to either IHSG's wording (low sugar levels requiring help from another person, or use of glucagon, or hospitalization, or loss of consciousness) or with an alternative simpler wording developed by PP (low sugar levels that you would have been unable to treat).

Results: Among 1430 eligible participants, in the last 12 months, the annual prevalence of level-3-H (IHSG: 242/100 vs.

Single-cell mass cytometry analysis reveals stem cell heterogeneity.

Cellular heterogeneity is fundamental to both developmental differentiation and disease establishment. Recent advances in high-throughput single-cell technology have been rapidly revolutionizing the resolution of our understanding of development and disease. However, while the study of single-cell transcriptomes is easily accessible, the analysis of single-cell proteomes is still in its infancy.

Atorvastatin lowers serum calcium levels in lithium-users: results from a randomized controlled trial.

Background: Although lithium is considered the gold-standard treatment for bipolar disorder (BD), it is associated with a variety of major endocrine and metabolic side effects, including parathyroid hormone (PTH) dependent hypercalcemia. Aside from surgery and medication discontinuation, there are limited treatments for hypercalcemia. This paper will assess data from a randomized controlled trial (RCT).

Efficacy of ketamine intervention to decrease alcohol use, cravings, and withdrawal symptoms in adults with problematic alcohol use or alcohol use disorder: A systematic review and comprehensive analysis of mechanism of actions.

Background: Alcohol use disorder is highly prevalent and has important economical, societal, psychiatric, and medical consequences. All currently approved therapeutic approaches targeting alcohol dependence have relatively modest effects and high relapse rates. Recent evidence suggests that ketamine may be an effective intervention to treat alcohol use disorder and alcoholic withdrawal.