Metabolic reprogramming, malignant transformation and metastasis: lessons from chronic lymphocytic leukaemia and prostate cancer.

Metabolic reprogramming is a hallmark of cancer, crucial for malignant transformation and metastasis. Chronic lymphocytic leukaemia (CLL) and prostate cancer exhibit similar metabolic adaptations, particularly in glucose and lipid metabolism. Understanding this metabolic plasticity is crucial for identifying mechanisms contributing to metastasis.

Gaining Insight into Operative Performance: Analysis of an Automated 360-Degree Feedback Tool Among Perioperative Staff.

Background: Surgery has seen limited adoption of 360-degree feedback tools, and no current tools evaluate intraoperative performance from a technical, nontechnical, or teaching skill perspective. We sought to evaluate the overall findings and perceived value of a novel 360-degree feedback tool for surgeons from their operating room colleagues.

Methods: The 'intraoperative 360' (i360) combined 3 previously validated scales of surgeon performance.

Content and face validity of preference-based quality of life instruments in indigenous youth experiencing mental health problems: a qualitative study.

Background: Mainstream preference-based quality of life (QoL) measures have been traditionally based on Western principles of health. It is critical to examine whether existing preference-based QoL measures capture what is important to Indigenous people while being comprehensive and culturally acceptable. This study aims to assess the content and face validity of the EuroQol-5 dimensions 5-levels (EQ-5D-5 L), 12-item short form survey (SF-12), assessment of quality of life-6 dimensions (AQoL-6D), and recovering quality of life 10-item (ReQoL-10) within the context of indigenous youth mental health.

Climate-conscious pharmacy practice: An exploratory study of community pharmacists in Ontario.

Background: Climate change remains a significant challenge to global health. The health care system is a major contributor of greenhouse gas (GHG) emissions. While pharmacists are aware of climate change as an important societal issue, there is little known about the level of implementation of climate-conscious practices in community pharmacies throughout Ontario.

Sex specific gene expression is present prior to metamorphosis in the sea urchin.

A profound collaboration between the germline and somatic cells of an organism is the creation of a functional gonad. Here we establish a foundation for studying molecular gonadogenesis in the sea urchin by use of RNA-seq, quantitative mRNA measurements, and in-situ hybridizations throughout the life cycle of the variegated sea urchin, Lytechinus variegatus (Lv). We found through three distinct analyses that the ovary and testis of this echinoderm expresses unique transcripts involved in gametogenesis, and also discovered uncharacterized gene products unique to each gonad.

The Problems (and possible solutions) of assessing risk, race and recidivism in long operating drug treatment courts.

Formal criminogenic risk tools can be an important control in assessing racial inequities in access to treatment courts and in evaluating both proximal and distal outcomes from those programs. To achieve this potential, however, it is important that risk tools themselves operate in a racially neutral fashion and that they operate consistently over the period assessed. Tools that are not properly calibrated by race and changes in the tools used over the life of a program are therefore significant evaluation concerns.

Altered expression of vesicular trafficking machinery in prostate cancer affects lysosomal dynamics and provides insight into the underlying biology and disease progression.

Background: This study focuses on the role of lysosomal trafficking in prostate cancer, given the essential role of lysosomes in cellular homoeostasis.

Methods: Lysosomal motility was evaluated using confocal laser scanning microscopy of LAMP-1-transfected prostate cells and spot-tracking analysis. Expression of lysosomal trafficking machinery was evaluated in patient cohort databases and through immunohistochemistry on tumour samples.

EXpanding Technology-Enabled, Nurse-Delivered Chronic Disease Care (EXTEND): Protocol and Baseline Data for a Randomized Trial.

Background: Approximately 10-15 % of individuals with type 2 diabetes have persistently poorly-controlled diabetes mellitus (PPDM) despite receiving available care, and frequently have comorbid hypertension. Mobile monitoring-enabled telehealth has the potential to improve outcomes in treatment-resistant chronic disease by supporting self-management and facilitating patient-clinician contact but must be designed in a manner amenable to real-world use.

Methods: Expanding Technology-Enabled, Nurse-Delivered Chronic Disease Care (EXTEND) is an ongoing randomized trial comparing two 12-month interventions for comorbid PPDM and hypertension: 1) EXTEND, a mobile monitoring-enabled self-management intervention; and 2) EXTEND Plus, a comprehensive, nurse-delivered telehealth program incorporating mobile monitoring, self-management support, and pharmacist-supported medication management.

Interprofessional Care Models for Pregnant and Early-Parenting Persons Who Use Substances: A Scoping Review.

Introduction: Use of substances during pregnancy is a global health concern. Interprofessional care teams can provide an optimal care approach to engage individuals who use substances during the perinatal period. The purpose of this scoping review is to provide a comprehensive summation of published literature reporting on interprofessional care models for perinatal individuals who use substances.

Assessment of embedded versus remote pharmacist versus remote student pharmacist outreach on statin prescribing.

Background: The Statin Use in Persons with Diabetes (SUPD) measure is a Star measure by the Center for Medicare & Medicaid Services. The Duke Population Health Management Office has a team of pharmacists and pharmacy students who conduct targeted outreach to patients at risk of failing statin quality measures. Pharmacy services are embedded in select primary care clinics and other clinics are supported remotely.

Drug-regulated CD33-targeted CAR T cells control AML using clinically optimized rapamycin dosing.

Chimeric antigen receptor (CAR) designs that incorporate pharmacologic control are desirable; however, designs suitable for clinical translation are needed. We designed a fully human, rapamycin-regulated drug product for targeting CD33+ tumors called dimerizaing agent-regulated immunoreceptor complex (DARIC33). T cell products demonstrated target-specific and rapamycin-dependent cytokine release, transcriptional responses, cytotoxicity, and in vivo antileukemic activity in the presence of as little as 1 nM rapamycin.

Improving glycemic control in diabetes through virtual interdisciplinary rounds.

Objective: A team-based disease management approach that considers comorbid conditions, social drivers of health, and clinical guidelines improves diabetes care but can be costly and complex. Developing innovative models of care is crucial to improving diabetes outcomes. The objective of this analysis was to evaluate the efficacy of virtual interdisciplinary diabetes rounds in improving glycemic control.

Interleukin-3 production by basal-like breast cancer cells is associated with poor prognosis.

Breast cancer represents a collection of pathologies with different molecular subtypes, histopathology, risk factors, clinical behavior, and responses to treatment. "Basal-like" breast cancers predominantly lack the receptors for estrogen and progesterone (ER/PR), lack amplification of human epidermal growth factor receptor 2 (HER2) but account for 10-15% of all breast cancers, are largely insensitive to targeted treatment and represent a disproportionate number of metastatic cases and deaths. Analysis of interleukin (IL)-3 and the IL-3 receptor subunits () reveals elevated expression in predominantly the basal-like group.

Parents' use of digital technology for social connection during the COVID-19 pandemic: A mixed-methods study.

Introduction: The COVID-19 pandemic (2020-2021) resulted in isolation due to social distancing rules and lockdowns, during which technology was used to enable families and friends to maintain contact. Despite loneliness being high in parents, little is known about which parents are more likely to experience loneliness and strategies to support them.

Method: This mixed-methods study examines which parents were lonely during the pandemic and how digital technologies were used to reduce loneliness and social isolation.

Working Memory Impairment in Transient Ischaemic Attack: N-back as a Sensitive Measure for Detection.

Background: Transient ischaemic attack (TIA) can lead to lasting changes in brain structure and function resulting in cognitive impairment. Cognitive screening tools may lack sensitivity for detecting cognitive impairments, particularly executive function, which tends to be the earliest affected domain in vascular cognitive impairment.

Aim: In this preliminary study, we examine a working memory (WMem) task as a sensitive measure of cognitive impairment in TIA.

The landscape of alternative polyadenylation during EMT and its regulation by the RNA-binding protein Quaking.

Epithelial-mesenchymal transition (EMT) plays important roles in tumour progression and is orchestrated by dynamic changes in gene expression. While it is well established that post-transcriptional regulation plays a significant role in EMT, the extent of alternative polyadenylation (APA) during EMT has not yet been explored. Using 3' end anchored RNA sequencing, we mapped the alternative polyadenylation (APA) landscape following Transforming Growth Factor (TGF)-β-mediated induction of EMT in human mammary epithelial cells and found APA generally causes 3'UTR lengthening during this cell state transition.

Diabetic muscle infarction: A case report.

Diabetes muscle infarction (DMI) is a rare complication of diabetes in which patients who present with DMI more commonly have some form of kidney disease in addition to diabetes mellitus. DMI typically presents with muscle pain and swelling. Diagnosis typically requires imaging (MRI with gadolinium contrast is the gold standard) and a variety of laboratory studies may aid in the diagnosis.

Quaking isoforms cooperate to promote the mesenchymal phenotype.

The RNA-binding protein Quaking (QKI) has widespread effects on mRNA regulation including alternative splicing, stability, translation, and localization of target mRNAs. Recently, QKI was found to be induced during epithelial-mesenchymal transition (EMT), where it promotes a mesenchymal alternative splicing signature that contributes to the mesenchymal phenotype. QKI is itself alternatively spliced to produce three major isoforms, QKI-5, QKI-6, and QKI-7.

ESRP1 controls biogenesis and function of a large abundant multiexon circRNA.

While the majority of circRNAs are formed from infrequent back-splicing of exons from protein coding genes, some can be produced at quite high level and in a regulated manner. We describe the regulation, biogenesis and function of circDOCK1(2-27), a large, abundant circular RNA that is highly regulated during epithelial-mesenchymal transition (EMT) and whose formation depends on the epithelial splicing regulator ESRP1. CircDOCK1(2-27) synthesis in epithelial cells represses cell motility both by diverting transcripts from DOCK1 mRNA production to circRNA formation and by direct inhibition of migration by the circRNA.

Basonuclin-2 regulates extracellular matrix production and degradation.

Epithelial-mesenchymal transition is essential for tissue patterning and organization. It involves both regulation of cell motility and alterations in the composition and organization of the ECM-a complex environment of proteoglycans and fibrous proteins essential for tissue homeostasis, signaling in response to chemical and biomechanical stimuli, and is often dysregulated under conditions such as cancer, fibrosis, and chronic wounds. Here, we demonstrate that basonuclin-2 (BNC2), a mesenchymal-expressed gene, that is, strongly associated with cancer and developmental defects across genome-wide association studies, is a novel regulator of ECM composition and degradation.