Distinct fibroblast functional states drive clinical outcomes in ovarian cancer and are regulated by TCF21.

Recent studies indicate that cancer-associated fibroblasts (CAFs) are phenotypically and functionally heterogeneous. However, little is known about CAF subtypes, the roles they play in cancer progression, and molecular mediators of the CAF "state." Here, we identify a novel cell surface pan-CAF marker, CD49e, and demonstrate that two distinct CAF states, distinguished by expression of fibroblast activation protein (FAP), coexist within the CD49e+ CAF compartment in high-grade serous ovarian cancers.

A serial PFASs sorption technique coupled with adapted high volume direct aqueous injection LCMS method.

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous global environmental contaminants, environmentally persistent, mobile, can bioaccumulate and are toxic. Increasing emphasis is placed on the immobilisation and removal of PFAS from contaminated environmental matrices such as: potable water, surface water, groundwater, wastewater, sediments and soils (Dauchy et al., 2017; Cao et al.

Osteoporosis Management in the Era of COVID-19.

Osteoporosis is a chronic condition that reflects reduced bone strength and an associated increased risk for fracture. As a chronic condition, osteoporosis generally requires sustained medical intervention(s) to limit the risks for additional bone loss, compromise of skeletal integrity, and fracture occurrence. Further complicating this issue is the fact that the abrupt cessation of some therapies can be associated with an increased risk for harm.

Optimizing Access to Heart Failure Care in Canada During the COVID-19 Pandemic.

The traditional model of heart failure (HF) care in Canada, which relies upon a multidisciplinary team and clinic-based care processes, has been undermined as a result of the COVID-19 pandemic. As the pandemic continues, we will be challenged to improve or maintain the health status of those with HF by optimizing guideline-directed care despite physical distancing constraints and a reduction in the health care workforce. This will require development of new strategies specifically targeted at decreasing the risk of decompensation and resultant HF hospitalization.

Obstructive sleep apnea is not an independent determinant of testosterone in men.

Objective: Obstructive sleep apnea (OSA) is generally considered to lower serum testosterone concentration in men, although data supporting this as a direct effect are limited. The aim of this study was to determine the relationship between the presence and severity of OSA and testosterone in a community-based cohort of men aged over 40 years.

Design And Methods: Anthropometry, polysomnography and biomedical information were collected from enrolled, consenting men from the prospective, longitudinal MAILES study cohort.

Biomechanical Computed Tomography analysis (BCT) for clinical assessment of osteoporosis.

The surgeon general of the USA defines osteoporosis as "a skeletal disorder characterized by compromised bone strength, predisposing to an increased risk of fracture." Measuring bone strength, Biomechanical Computed Tomography analysis (BCT), namely, finite element analysis of a patient's clinical-resolution computed tomography (CT) scan, is now available in the USA as a Medicare screening benefit for osteoporosis diagnostic testing. Helping to address under-diagnosis of osteoporosis, BCT can be applied "opportunistically" to most existing CT scans that include the spine or hip regions and were previously obtained for an unrelated medical indication.

Validity of the Medi-StuNTS behavioural marker system: assessing the non-technical skills of medical students during immersive simulation.

Background: The Medical Students' Non-Technical Skills (Medi-StuNTS) behavioural marker system (BMS) is the first BMS to be developed specifically for medical students to facilitate training in non-technical skills (NTS) within immersive simulated acute care scenarios. In order to begin implementing the tool in practice, validity evidence must be sought. We aimed to assess the validity of the Medi-StuNTS system with reference to Messick's contemporary validity framework.

Interlaboratory Concordance of ProMisE Molecular Classification of Endometrial Carcinoma Based on Endometrial Biopsy Specimens.

Molecular classifiers improve the consistency of categorization of endometrial carcinoma and provide valuable prognostic information. We aimed to evaluate the interlaboratory agreement in ProMisE assignment across 3 dedicated Canadian gynecologic oncology centers. Fifty cases of endometrial carcinoma diagnosed on biopsy were collected from 3 centers and 3 unstained sections were provided to each participating site so that immunohistochemistry for MSH6, PMS2, and p53 could be performed and interpreted at each center, blinded to the original diagnoses and the results from other centers.

Equivalent Survival of p53 Mutated Endometrial Endometrioid Carcinoma Grade 3 and Endometrial Serous Carcinoma.

TP53 status is the most important prognostic biomarker in endometrial carcinoma. We asked the question whether p53 mutated endometrial endometrioid carcinomas grade 3 (EEC3) or endometrial serous carcinomas (ESC), the latter ubiquitously harboring TP53 mutation, have different outcomes. TP53 mutation status was assessed by surrogate p53 immunohistochemistry on 326 EEC3 and ESC from 2 major cancer centers in Canada.

Trusting Infrastructure: The Emergence of Computer Security Incident Response, 1989-2005.

Historians have tended to analyze maintenance as an intrinsically local activity, something very unlike the development of large technological systems. This article challenges this historiographic dichotomy by examining efforts to construct a global infrastructure for maintaining computer security. In the mid-1990s, as the internet rapidly grew, commercialized, and internationalized, a small community of computer security incident responders sought to scale up their system of coordination, which had been based on interpersonal trust, by developing trusted infrastructure that could facilitate the worldwide coordination of incident response work.

Characterisation of Peste Des Petits Ruminants Disease in Pastoralist Flocks in Ngorongoro District of Northern Tanzania and Bluetongue Virus Co-Infection.

Peste des petits ruminants (PPR) disease was first confirmed in Tanzania in 2008 in sheep and goats in Ngorongoro District, northern Tanzania, and is now endemic in this area. This study aimed to characterise PPR disease in pastoralist small ruminant flocks in Ngorongoro District. During June 2015, 33 PPR-like disease reports were investigated in different parts of the district, using semi-structured interviews, clinical examinations, PPR virus rapid detection test (PPRV-RDT), and laboratory analysis.

Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition.

Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fractureamong people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature.

Using Direct Observation to Document "Practice-Based Evidence" of Evidence-Based Mathematics Instruction.

Implementation of evidence-based practices (EBPs) is paramount to students' development of mathematics proficiency. This study investigated "practice-based evidence" of interventionists' actual use of explicit mathematics instruction, a well-established EBP. Specifically, this study analyzed direct observation data collected in a federally funded efficacy trial involving a Tier 2 first-grade mathematics intervention to examine whether the quantity and quality of explicit mathematics instruction was associated with the mathematics outcomes of 470 first-grade students with or at risk for mathematics learning disabilities.

Initial Canadian Experience With Bilateral Minithoracotomy Approach for HeartMate 3 Left Ventricular Assist Device Implantation.

Left ventricular assist devices provide hemodynamic support to improve quality of life and long-term survival in patients with end-stage heart failure. The HeartMate 3 (Abbott, Abbott Park, IL) left ventricular assist device uses magnetically levitated impeller technology, improving durability and reducing pump thrombosis. Sternum-sparing implantation may reduce perioperative bleeding and infection, improve mobility, decrease hospitalization duration, and reduce right ventricular dysfunction.

Bone metastases in thyroid cancer.

Whereas preemptive screening for the presence of lymph node and lung metastases is standard-of-care in thyroid cancer patients, bone metastases are less well studied and are often neglected in thyroid cancer patient surveillance. Bone metastases in thyroid cancer are, however, independently associated with poor/worse prognosis with a median overall survival from detection of only 4 years despite an otherwise excellent prognosis for the vast majority of thyroid cancer patients. In this review we summarize the state of current knowledge as pertinent to bony metastatic disease in thyroid cancer, including clinical implications, impacts on patient function and quality of life, pathogenesis, and therapeutic opportunities, proposing approaches to patient care accordingly.

A bifunctional O-antigen polymerase structure reveals a new glycosyltransferase family.

Lipopolysaccharide O-antigen is an attractive candidate for immunotherapeutic strategies targeting antibiotic-resistant Klebsiella pneumoniae. Several K. pneumoniae O-serotypes are based on a shared O2a-antigen backbone repeating unit: (→ 3)-α-Galp-(1 → 3)-β-Galf-(1 →).

Canadian Cardiovascular Society/Canadian Cardiac Transplant Network Position Statement on Heart Transplantation: Patient Eligibility, Selection, and Post-Transplantation Care.

Significant practice-changing developments have occurred in the care of heart transplantation candidates and recipients over the past decade. This Canadian Cardiovascular Society/Canadian Cardiac Transplant Network Position Statement provides evidence-based, expert panel recommendations with values and preferences, and practical tips on: (1) patient selection criteria; (2) selected patient populations; and (3) post transplantation surveillance. The recommendations were developed through systematic review of the literature and using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.

Vasotocin and the origins of the vasopressin/oxytocin receptor gene family.

We previously characterized the arginine vasotocin receptor sequences in the jawless vertebrate sea lamprey. These gene and protein sequences provide clues to the origins of the various arginine vasopressin and oxytocin receptor family members in jawed vertebrates. However, orthological relationships between the jawless and jawed receptors is unclear.

Persistent organic pollutants sorbed in plastic resin pellet - "Nurdles" from coastal areas of Central Chile.

Plastic resin pellets were collected from coastal areas (n = 7) of central Chile. Pellets were analyzed using Fourier-transform infrared spectroscopy for polymer identification and gas chromatography-mass spectrometry for Persistent Organic Pollutants (POPs) determination. Screened compounds were PBDEs (n = 10), PCBs (n = 7), and OCPs (n = 13).

Biochar sorption of PFOS, PFOA, PFHxS and PFHxA in two soils with contrasting texture.

The ability to immobilise PFAS in soil may be an essential interim tool while technologies are developed for effective long-term treatment of PFAS contaminated soils. Serial sorption experiments were undertaken using a pine derived biochar produced at 750 °C (P750). All experiments were carried out either in individual mode (solution with one PFAS at 5 μg/L) or mix mode (solution with 5 μg/L of each: PFOS, PFOA, PFHxS and PFHxA), and carried out in 2:1 water to soil solutions.

IL6 Induces an IL22 CD8 T-cell Subset with Potent Antitumor Function.

CD8 T cells can be polarized into several different subsets as defined by the cytokines they produce and the transcription factors that govern their differentiation. Here, we identified the polarizing conditions to induce an IL22-producing CD8 Tc22 subset, which is dependent on IL6 and the aryl hydrocarbon receptor transcription factor. Further characterization showed that this subset was highly cytolytic and expressed a distinct cytokine profile and transcriptome relative to other subsets.

Exploring transformative learning when developing medical students' non-technical skills.

Context: Non-technical skills (NTS) training should be incorporated into medical students' education and simulation-based approaches are often utilised to facilitate this. Such experiences have the potential to foster transformative learning by facilitating a reassessment of one's prior assumptions and a significant shift in one's outlook, referred to as the process of perspective transformation. The aim of this research was to explore how NTS training might facilitate transformative learning in final-year medical students.

Understanding the LiveLighter® obesity prevention policy processes: An investigation using political science and systems thinking.

The health and economic burden associated with overweight and obesity warrants comprehensive policy action; however, to date, there has been limited policy progress globally. This study sought to advance obesity prevention policy research and practice by applying theories of the policy process to study decision-making processes involved in the adoption of the contentious LiveLighter® social marketing campaign by the Victorian government in Australia. Through analysis of documents and interviews with policy makers, this qualitative study aimed to gain a better understanding of the dynamic influences on policy decision-making.

Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism.

Bone remodeling consists of resorption by osteoclasts followed by formation by osteoblasts, and osteoclasts are a source of bone formation-stimulating factors. Here we utilize osteoclast ablation by denosumab (DMAb) and RNA-sequencing of bone biopsies from postmenopausal women to identify osteoclast-secreted factors suppressed by DMAb. Based on these analyses, LIF, CREG2, CST3, CCBE1, and DPP4 are likely osteoclast-derived coupling factors in humans.