PHF6-mediated transcriptional control of NSC via Ephrin receptors is impaired in the intellectual disability syndrome BFLS.

The plant homeodomain zinc-finger protein, PHF6, is a transcriptional regulator, and PHF6 germline mutations cause the X-linked intellectual disability (XLID) Börjeson-Forssman-Lehmann syndrome (BFLS). The mechanisms by which PHF6 regulates transcription and how its mutations cause BFLS remain poorly characterized. Here, we show genome-wide binding of PHF6 in the developing cortex in the vicinity of genes involved in central nervous system development and neurogenesis.

MicroRNAs and long non-coding RNAs during transcriptional regulation and latency of HIV and HTLV.

Human immunodeficiency virus (HIV) and human T cell leukemia virus (HTLV) have replicative and latent stages of infection. The status of the viruses is dependent on the cells that harbour them and on different events that change the transcriptional and post-transcriptional events. Non-coding (nc)RNAs are key factors in the regulation of retrovirus replication cycles.

Nucleic acid therapeutics as differentiation agents for myeloid leukemias.

Differentiation therapy has proven to be a success story for patients with acute promyelocytic leukemia. However, the remaining subtypes of acute myeloid leukemia (AML) are treated with cytotoxic chemotherapies that have limited efficacy and a high likelihood of resistance. As differentiation arrest is a hallmark of AML, there is increased interest in developing differentiation-inducing agents to enhance disease-free survival.

A Simplified Proteomics LC-MRM-MS Assay for Determination of apoE Genotypes in Plasma Samples.

Apolipoprotein E (apoE), a polymorphic plasma protein, plays a pivotal role in lipid transportation. The human apoE gene possesses three major alleles (ε2, ε3, and ε4), which differ by single amino acid (cysteine to arginine) substitutions. The ε4 allele represents the primary genetic risk factor for Alzheimer's disease (AD), whereas the ε2 allele protects against the disease.

A Canadian Survey of Research on HIV-1 Latency-Where Are We Now and Where Are We Heading?

Worldwide, almost 40 million people are currently living with HIV-1. The implementation of cART inhibits HIV-1 replication and reduces viremia but fails to eliminate HIV-1 from latently infected cells. These cells are considered viral reservoirs from which HIV-1 rebounds if cART is interrupted.

Interrater Agreement between Bedside and Video Raters Using the CPOT-Neuro for Pain Assessment in Critically Ill Patients with a Brain Injury.

This study aimed to examine the interrater agreement of Critical-Care Pain Observation Tool-Neuro (CPOT-Neuro) scores as a newly developed tool for pain assessment in patients with critical illness and brain injury between raters using two methods of rating (bedside versus video) during standard care procedures (i.e., non-invasive blood pressure and turning).

Efficacy of interventions targeted at physician prescribers of opioids for chronic non-cancer pain: an overview of systematic reviews.

Background: To combat the opioid crisis, interventions targeting the opioid prescribing behaviour of physicians involved in the management of patients with chronic non-cancer pain (CNCP) have been introduced in clinical settings. An integrative synthesis of systematic review evidence is required to better understand the effects of these interventions. Our objective was to synthesize the systematic review evidence on the effect of interventions targeting the behaviours of physician opioid prescribers for CNCP among adults on patient and population health and prescriber behaviour.

The Clinical, Genomic, and Transcriptomic Landscape of BRAF Mutant Cancers.

Background: BRAF mutations are classified into four molecularly distinct groups, and Class 1 (V600) mutant tumors are treated with targeted therapies. Effective treatment has not been established for Class 2/3 or BRAF Fusions. We investigated whether BRAF mutation class differed according to clinical, genomic, and transcriptomic variables in cancer patients.

Genetic Mutations Associated with Inflammatory Response Caused by HPV Integration in Oropharyngeal Squamous Cell Carcinoma.

(1) Background: Head and neck cancer (HNC) ranks as the sixth most prevalent cancer in the world. In addition to the traditional risk factors such as alcohol and tobacco consumption, the implication of the human papillomavirus (HPV) is becoming increasingly significant, particularly in oropharyngeal cancer (OPC). (2) Methods: This study is based on a review analysis of different articles and repositories investigating the mutation profile of HPV-related OPC and its impact on patient outcomes.

Evaluating non-cognitive skills in medical school applicants.

Medical school candidates must have both the cognitive and professional competencies required to become good physicians. In this commentary, we outline the evidence and outcomes associated with the implementation of these selection methodologies and evaluate their ability to assess non-cognitive skills.

A Water-Soluble Chitosan Derivative for the Release of Bioactive Deferoxamine.

Deferoxamine (DFO) is a water-soluble iron chelator used pharmacologically for the management of patients with transfusional iron overload. However, DFO is not cell-permeable and has a short plasma half-life, which necessitates lengthy parenteral administration with an infusion pump. We previously reported the synthesis of chitosan (CS) nanoparticles for sustained slow release of DFO.

The Mutational Spectrum of Pre- and Post-Neoadjuvant Chemotherapy Triple-Negative Breast Cancers.

The response of triple-negative breast cancer (TNBC) patients to pre-operative (neoadjuvant chemotherapy) is a critical factor of their outcome. To determine the effects of chemotherapy on the tumor genome and to identify mutations associated with chemoresistance and sensitivity, we performed whole exome sequencing on pre/post-chemotherapy tumors and matched lymphocytes from 26 patients. We observed great inter-tumoral heterogeneity with no gene mutated recurrently in more than four tumors besides TP53.

Counselling Framework for Germline and Carriers Considering Risk-Reducing Mastectomy.

Female and germline pathogenic variant carriers have an increased lifetime risk of breast cancer and may wish to consider risk-reducing mastectomy (RRM) for surgical prevention. Quantifying the residual lifetime risk and absolute benefit from RRM requires careful consideration of a patient's age, pathogenic variant, and their personal history of breast or ovarian cancer. Historically, patients have been counselled that RRM does not necessarily prolong survival relative to high-risk surveillance, although recent studies suggest a possible survival benefit of RRM in carriers.

Cancer Care Team Functioning during COVID-19: A Narrative Literature Review and Synthesis.

Amid pandemics, health care teams face unprecedented challenges, requiring significant efforts to sustain optimal functioning and navigate rapid practice changes. It is therefore crucial to identify factors affecting team functioning in these contexts. The present narrative review more specifically summarizes the literature on key elements of cancer teams' functioning during COVID-19.

A second-generation eIF4A RNA helicase inhibitor exploits translational reprogramming as a vulnerability in triple-negative breast cancer.

In this study, we aimed to address the current limitations of therapies for macro-metastatic triple-negative breast cancer (TNBC) and provide a therapeutic lead that overcomes the high degree of heterogeneity associated with this disease. Specifically, we focused on well-documented but clinically underexploited cancer-fueling perturbations in mRNA translation as a potential therapeutic vulnerability. We therefore developed an orally bioavailable rocaglate-based molecule, MG-002, which hinders ribosome recruitment and scanning via unscheduled and non-productive RNA clamping by the eukaryotic translation initiation factor (eIF) 4A RNA helicase.

A Phase II Exploratory Study to Identify Biomarkers Predictive of Clinical Response to Regorafenib in Patients with Metastatic Colorectal Cancer Who Have Failed First-Line Therapy.

Single-agent regorafenib is approved in Canada for metastatic colorectal cancer (mCRC) patients who have failed previous lines of therapy. Identifying prognostic biomarkers is key to optimizing therapeutic strategies for these patients. In this clinical study (NCT01949194), we evaluated the safety and efficacy of single-agent regorafenib as a second-line therapy for mCRC patients who received it after failing first-line therapy with an oxaliplatin or irinotecan regimen with or without bevacizumab.

The Impact of Mutation Allele Frequency on the Histopathological Characteristics of Thyroid Cancer.

Background: A mutation in papillary thyroid cancer (PTC) has been shown to be associated with aggressive behavior. Nevertheless, not all PTCs behave aggressively. Allele frequency (AF) is the number of mutated molecules divided by the total number of wild-type molecules at a specific location in the genome.

Heterogeneous nuclear ribonucleoprotein K promotes cap-independent translation initiation of retroviral mRNAs.

Translation initiation of the human immunodeficiency virus-type 1 (HIV-1) genomic mRNA (vRNA) is cap-dependent or mediated by an internal ribosome entry site (IRES). The HIV-1 IRES requires IRES-transacting factors (ITAFs) for function. In this study, we evaluated the role of the heterogeneous nuclear ribonucleoprotein K (hnRNPK) as a potential ITAF for the HIV-1 IRES.

Patient Adherence to Oral Anticancer Agents: A Mapping Review of Supportive Interventions.

The development and use of oral anticancer agents (OAAs) continue to grow, and supporting individuals on OAAs is now a priority as they find themselves taking these drugs at home with little professional guidance. This mapping review provides an overview of the current evidence concerning OAA-supportive adherence interventions, identifying potential gaps, and making recommendations to guide future work. Four large databases and the grey literature were searched for publications from 2010 to 2022.

Prospective Associations between Maternal Depressive Symptoms during Early Infancy and Growth Deficiency from Childhood to Adolescence.

Maternal health represents an important predictor of child development; yet it often goes unnoticed during pediatric visits. Previous work suggests that mental state affects parenting. The relationship between infant exposure to maternal depressive symptoms suggests conflicting findings on physical growth.

MnO nanoparticles trigger hepatic lipotoxicity and mitophagy via mtROS-dependent Hsf1 phosphorylation.

Manganese (Mn) is an essential element for maintaining normal metabolism in vertebrates. Mn dioxide nanoparticles (MnO NPs), a novel Mn source, have shown great potentials in biological and biomedical applications due to their distinct physical and chemical properties. However, little is known about potential adverse effects on animal or cellular metabolism.

VEGF-C-expressing TAMs rewire the metastatic fate of breast cancer cells.

The expression of pro-lymphangiogenic VEGF-C in primary tumors is associated with sentinel lymph node metastasis in most solid cancer types. However, the impact of VEGF-C on distant organ metastasis remains unclear. Perivascular tumor-associated macrophages (TAMs) play a crucial role in guiding hematogenous spread of cancer cells by establishing metastatic pathways within the tumor microenvironment.