A prospective multi-site study to evaluate the performance and usability of an oral fluid-based HIV self-test in Canada.

Background: Blood and oral fluid-based HIV self-tests are important for reaching the undiagnosed living with HIV. The study objectives were to evaluate the oral fluid-based OraQuick® HIV Self-Test (HIV-ST) performance in comparison to laboratory reference testing; determine if laypersons can correctly perform the HIV-ST; document if intended users can successfully interpret pre-made contrived positive, negative, and invalid results; and document if intended users can understand the key messages in the product labeling.

Methods: This prospective study enrolled consenting adult intended users of HIV self-testing from six community health centres in four Canadian provinces between June 2022 and January 2024.

Comprehensive discovery and functional characterization of the noncanonical proteome.

The systematic identification and functional characterization of noncanonical translation products, such as novel peptides, will facilitate the understanding of the human genome and provide new insights into cell biology. Here, we constructed a high-coverage peptide sequencing reference library with 11,668,944 open reading frames and employed an ultrafiltration tandem mass spectrometry assay to identify novel peptides. Through these methods, we discovered 8945 previously unannotated peptides from normal gastric tissues, gastric cancer tissues and cell lines, nearly half of which were derived from noncoding RNAs.

Third-party evaluators perceive AI as more compassionate than expert humans.

Empathy connects us but strains under demanding settings. This study explored how third parties evaluated AI-generated empathetic responses versus human responses in terms of compassion, responsiveness, and overall preference across four preregistered experiments. Participants (N = 556) read empathy prompts describing valenced personal experiences and compared the AI responses to select non-expert or expert humans.

Impaired insight in schizophrenia is associated with higher frontoparietal cerebral blood flow: an arterial spin labeling study.

Impaired insight into illness occurs in up to 98% of patients with schizophrenia, depending on the stage of illness, and leads to negative clinical outcomes. Previous neuroimaging studies suggest that impaired insight in patients with schizophrenia may be related to structural and functional anomalies in frontoparietal brain regions. To date, limited studies have investigated the association between regional cerebral blood flow (CBF) and impaired insight in schizophrenia.

Integrating artificial intelligence with mechanistic epidemiological modeling: a scoping review of opportunities and challenges.

Integrating prior epidemiological knowledge embedded within mechanistic models with the data-mining capabilities of artificial intelligence (AI) offers transformative potential for epidemiological modeling. While the fusion of AI and traditional mechanistic approaches is rapidly advancing, efforts remain fragmented. This scoping review provides a comprehensive overview of emerging integrated models applied across the spectrum of infectious diseases.

Lentivirus-mediated gene therapy for Fabry disease: 5-year End-of-Study results from the Canadian FACTs trial.

Background: Fabry disease is an X-linked lysosomal storage disorder due to a deficiency of α-galactosidase A (α-gal A) activity. Our goal was to correct the enzyme deficiency in Fabry patients by transferring the cDNA for α-gal A into their CD34+ hematopoietic stem/progenitor cells (HSPCs). Overexpression of α-gal A leads to secretion of the hydrolase; which can be taken up and used by uncorrected bystander cells.

Evaluation of point-of-care haemoglobin measurement accuracy in surgery (PREMISE) and implications for transfusion practice: a prospective cohort study.

Background: Point-of-care testing devices to measure haemoglobin (Hgb) frequently inform transfusion decision-making in surgery. This study aimed to examine their accuracy in surgery, focusing on Hgb concentrations of 60-100 g L, a range with higher potential for transfusion.

Methods: This was a prospective diagnostic cohort study focused on method comparison, conducted at two academic hospitals.

INDOLENT CLONAL LYMPHOID DISORDERS.

Indolent clonal lymphoid disorders are not recognized as lymphomas as they generally need no systemic treatment, and depending on the lesion, need only limited clinical follow-up. These lesions are usually incidentally diagnosed during the work up for other disease. The recognition of indolent clonal lymphoid disorders is important to avoid misdiagnosis as lymphoma and unnecessary treatment.

Thoracic Surgery Outcomes Research Network (ThORN) Consensus Document on Defining a High Quality Wedge Resection for Early Stage Lung Cancer.

With the publication of CALGB 140503, an increase in wedge resections for small, peripheral non-small cell lung cancer is expected; however, a relative paucity of data exists as to what defines a high quality oncologic wedge resection. The Thoracic Surgery Outcomes Research Network (ThORN), through expert discussion, guided by review of what limited data does exist, and through use of a modified Delphi process, provides these consensus statements defining an oncologically sound, high quality wedge resection. The statements are classified into five categories: 1) Preoperative Considerations 2) Technical Aspects 3) Lymph Node Assessment 4) Margin Assessment and 5) Tissue Handling by Pathology.

Day-to-day variability in sleep and activity predict the onset of a hypomanic episode in patients with bipolar disorder.

Detecting transitions in bipolar disorder (BD) is essential for implementing early interventions. Our aim was to identify the earliest indicator(s) of the onset of a hypomanic episode in BD. We hypothesized that objective changes in sleep would be the earliest indicator of a new hypomanic or manic episode.

Perspectives on vaccination among unvaccinated members of a Canadian indigenous population.

From the beginning of the COVID-19 pandemic, the potential impact on Indigenous (First Nations, Métis and Inuit) communities in Canada was a major concern. Evidence from previous pandemics, particularly H1N1, suggested that more cases and poorer outcomes among Indigenous Peoples was likely and that there might be barriers to Indigenous Peoples' vaccination. In this short report we consider the non-vaccination decisions of a sample of unvaccinated Métis Nation of Ontario citizens.

A first-in-human phase 1/2 dose-escalation study of MAK683 (EED inhibitor) in patients with advanced malignancies.

Purpose: MAK683, a first-in-class and highly selective allosteric inhibitor of the embryonic ectoderm development subunit of polycomb repressive complex 2, has shown sustained antitumor activity in tumor xenograft models. This first-in-human phase 1/2 study evaluated the safety, pharmacokinetics (PK), and clinical activity of single-agent MAK683 in advanced malignancies.

Methods: MAK683 was administered fasted once daily or twice daily continuously in 28-day treatment cycles.

Microplastic pollution in the marine environment: Distribution factors and mitigation strategies in different oceans.

As the COVID-19 pandemic began in 2020, plastic usage spiked, and microplastic (MP) generation has increased dramatically. It is documented that MP can transfer from the source to the ocean environment where they accumulate as the destination. Therefore, it is essential to understand their transferring pathways and effective environmental factors to determine the distribution of MPs in the marine environment.

Examining the association between fentanyl use and perceived adequacy of methadone dose: A retrospective cohort study.

Background: People exposed to fentanyl may report that the dose of methadone in the commonly accepted therapeutic range feels too low. We examined self-reported methadone dose adequacy.

Methods: We conducted a retrospective cohort study of individuals prescribed methadone at a dose of at least 60mg daily using data from three community-recruited prospective cohort studies of people who use drugs in Vancouver, Canada from December 2016 through March 2020.

Global human exposure of atmospheric polybrominated diphenyl ethers: Variation patterns of exposure pathways and phase contributions.

At present, there are still certain limitations in the research on the pathways and phase contributions of semi-volatile organic compounds (SVOCs) to human exposure in the atmosphere. This study clarified the contribution rates of inhalation and dermal exposure of particulate and gaseous polybrominated diphenyl ethers (PBDEs) on a global scale, as well as their influencing factors and mechanisms. Data on gaseous PBDEs were collected from 125 cities across 38 countries and regions to predict size-resolved particulate exposure levels, utilizing our previous method for inhalation alongside a size-dependent prediction method for dermal exposure developed in this study.

Adenomas from individuals with pathogenic biallelic variants in the MUTYH and NTHL1 genes demonstrate base excision repair tumour mutational signature profiles similar to colorectal cancers, expanding potential diagnostic and variant classification applications.

Background: Colorectal cancers (CRCs) from people with biallelic germline likely pathogenic/pathogenic variants in MUTYH or NTHL1 exhibit specific single base substitution (SBS) mutational signatures, namely combined SBS18 and SBS36 (SBS18+SBS36), and SBS30, respectively. The aim was to determine if adenomas from biallelic cases demonstrated these mutational signatures at diagnostic levels.

Methods: Whole-exome sequencing of FFPE tissue and matched blood-derived DNA was performed on 9 adenomas and 15 CRCs from 13 biallelic MUTYH cases, on 7 adenomas and 2 CRCs from 5 biallelic NTHL1 cases and on 27 adenomas and 26 CRCs from 46 non-hereditary (sporadic) participants.

Testing organ-specific responses to therapies in tissues differentiated from Cystic Fibrosis patient derived iPSCs.

Cystic Fibrosis (CF) is a life-shortening disease that is caused by mutations in the CFTR gene, a gene that is expressed in multiple organs. There are several primary tissue models of CF disease, including nasal epithelial cultures and rectal organoids, that are effective in reporting the potential efficacy of mutation-targeted therapies called CFTR modulators. However, there is the well-documented variation in tissue dependent, therapeutic response amongst CF patients, even those with the same CF-causing mutation.

Intraoperative Anesthetic Care During Emergent/Urgent Craniotomy or Craniectomy for Intracranial Hypertension or Herniation: A Systematic Review.

This systematic review aimed to identify and describe best practice for the intraoperative anesthetic management of patients undergoing emergent/urgent decompressive craniotomy or craniectomy for any indication. The PubMed, Scopus, EMBASE, and Cochrane databases were searched for articles related to urgent/emergent craniotomy/craniectomy for intracranial hypertension or brain herniation. Only articles focusing on intraoperative anesthetic management were included; those investigating surgical or intensive care unit management were excluded.

Things Latinas need to plan for safety: A dual-site concept mapping study.

Background: Latina women in the United States experience intimate partner violence (IPV) at high rates, but evidence suggests Latinas seek help for IPV at lower rates than other communities. Safety planning is an approach that provides those experiencing IPV with concrete actions to increase their safety and referrals to formal services. While safety planning is shown to reduce future incidences of violence, little is known about the safety planning priorities of Latinas.

Reduced circulating sphingolipids and activity are linked to T2D risk and impaired insulin secretion.

Gestational diabetes mellitus (GDM), a transient form of diabetes that resolves postpartum, is a major risk factor for type 2 diabetes (T2D) in women. While the progression from GDM to T2D is not fully understood, it involves both genetic and environmental components. By integrating clinical, metabolomic, and genome-wide association study (GWAS) data, we identified associations between decreased sphingolipid biosynthesis and future T2D, in part through the allele of the gene in Hispanic women shortly after a GDM pregnancy.

Beyond Increasing Sample Sizes: Optimizing Effect Sizes in Neuroimaging Research on Individual Differences.

Linking neurobiology to relatively stable individual differences in cognition, emotion, motivation, and behavior can require large sample sizes to yield replicable results. Given the nature of between-person research, sample sizes at least in the hundreds are likely to be necessary in most neuroimaging studies of individual differences, regardless of whether they are investigating the whole brain or more focal hypotheses. However, the appropriate sample size depends on the expected effect size.

Differentiation of Related Events in Hippocampus Supports Memory Reinstatement in Development.

Adults are capable of either differentiating or integrating similar events in memory based on which representations are optimal for a given situation. Yet how children represent related memories remains unknown. Here, children (7-10 years old) and adults formed memories for separate yet overlapping events.

Beyond Routine Maintenance: Current Trends in Working Memory Research.

Working memory (WM) is an evolving concept. Our understanding of the neural functions that support WM develops iteratively alongside the approaches used to study it, and both can be profoundly shaped by available tools and prevailing theoretical paradigms. Here, the organizers of the 2024 Working Memory Symposium-inspired by this year's meeting-highlight current trends and looming questions in WM research.