Cancer-cell derived S100A11 promotes macrophage recruitment in ER+ breast cancer.

Macrophages are pivotal in driving breast tumor development, progression, and resistance to treatment, particularly in estrogen receptor-positive (ER+) tumors, where they infiltrate the tumor microenvironment (TME) influenced by cancer cell-secreted factors. By analyzing single-cell RNA sequencing data from 25 ER+ tumors, we elucidated interactions between cancer cells and macrophages, correlating macrophage density with epithelial cancer cell density. We identified that S100A11, a previously unexplored factor in macrophage-cancer crosstalk, predicts high macrophage density and poor outcomes in ER+ tumors.

Refining the definition of miliary/disseminated tuberculosis in Canada.

Objectives: Although a "multisite" definition of disseminated tuberculosis (DTB) exists, there is limited evidence to support its use. Herein, we sought to generate that evidence.

Methods: We evaluated treatment outcomes and reporting requirements against two distinct definitions of DTB in a 15-year population-based cohort of consecutively diagnosed patients with tuberculosis (TB) in Canada.

The association between phylogenetic lineage and the subclinical phenotype of pulmonary tuberculosis: A retrospective 2-cohort study.

Background: Subclinical pulmonary tuberculosis (PTB) is an asymptomatic disease state between established TB infection and symptomatic (clinical) TB disease. It is present in 20-25% of PTB patients in high-income countries. Mycobacterium tuberculosis complex (MTBC) genetic heterogeneity, and differential host immunological responses, have been implicated in its pathogenesis.

Immunomodulatory Effects of Nanoparticles on Dendritic Cells in a Model of Allergic Contact Dermatitis - Importance of PD-L2 Expression.

Nanoparticle (NP) skin exposure is linked to the increased prevalence of allergic contact dermatitis. In prior studies using the mouse contact hypersensitivity (CHS) model, we reported that silica 20 nm (Si20nm) suppressed the allergic response and TiO2 doped with manganese (mTiO2) exacerbated it. In this work, we conducted in vitro experiments using bone marrow-derived dendritic cells (BMDCs) to study the combinatorial effect of the potent 2, 4-dinitrofluorobenzene (DNFB) hapten sensitizer with Si20nm and mTiO2 NPs on BMDC cytotoxicity, cytokine secretion and phenotype using the B7 family ligands.

Limitations of Chest Radiography in Diagnosing Subclinical Pulmonary Tuberculosis in Canada.

Subclinical pulmonary tuberculosis (PTB) is defined as "…a state of disease due to viable that does not cause TB-related symptoms but does cause other abnormalities that can be detected using existing radiologic and mycobacteriologic assays." In high-income countries, subclinical PTB is usually diagnosed during active case finding, is acid-fast bacilli smear negative, and associated with minimal or no lung parenchymal abnormality on chest radiograph. In the absence of symptoms, the epidemiologic risk of TB and chest radiograph are critical to making the diagnosis.

The prevalence, risk factors, and public health consequences of peripheral lymph node-associated clinical and subclinical pulmonary tuberculosis.

Objectives: Relatively little is known about the prevalence, risk factors, and public health consequences of peripheral lymph node (PLN)-associated pulmonary tuberculosis (PTB).

Methods: We developed a 10-year (2010-2019) population-based cohort of PLNTB patients in Canada. We used systematically collected primary source data and expert reader chest radiograph interpretations in a multivariable logistic regression to determine associations between sputum culture positivity and demographic, clinical, and radiographic features.

Reliability and validity of the post COVID-19 condition stigma questionnaire: A prospective cohort study.

Background: Many of the 10-20% percent of COVID-19 survivors who develop Post COVID-19 Condition (PCC, or Long COVID) describe experiences suggestive of stigmatization, a known social determinant of health. Our objective was to develop an instrument, the Post COVID-19 Condition Stigma Questionnaire (PCCSQ), with which to quantify and characterise PCC-related stigma.

Methods: We conducted a prospective cohort study to assess the reliability and validity of the PCCSQ.

A comparison of the chest radiographic and computed tomographic features of subclinical pulmonary tuberculosis.

Subclinical pulmonary tuberculosis (PTB) is a recently described intermediate state of great interest, but about which little is known. This study sought to describe and compare the frequency of key radiologic features of subclinical PTB on chest radiograph (CXR) versus computed tomographic scan (CT), and to interpret the clinical and public health relevance of the differences. Diagnostic CXRs and CT scans of the thorax and neck in a 16-year cohort of subclinical PTB patients in Canada were re-acquired and read by two independent readers and arbitrated by a third reader.

The Radiographic and Mycobacteriologic Correlates of Subclinical Pulmonary TB in Canada: A Retrospective Cohort Study.

Background: Very little is known about subclinical pulmonary TB (PTB), a recently described intermediate state, in high-income countries.

Research Question: What is the prevalence of subclinical PTB in Canada? What are its diagnostic chest radiography features? What is the relationship between those features and time to culture positivity, and what is the association between DNA fingerprint clustering, a measure of local transmission, and radiographic or other features in the foreign-born?

Study Design And Methods: We used primary source data to identify a 16-year retrospective cohort of patients with PTB. Demographic and mycobacteriologic features in patients with subclinical and clinical disease were compared, and the reason for assessment of patients with subclinical disease was described.

COVID-19 hospitalization is associated with pulmonary/diffusion abnormalities but not post-acute sequelae of COVID-19 severity.

Coronavirus disease-19 (COVID-19) has resulted in much acute morbidity and mortality worldwide. There is now a growing recognition of the post-acute sequela of COVID-19, termed long COVID. However, the risk factors contributing to this condition remain unclear.

The surveillance of spike protein for patients with COVID-19 detected in Hong Kong in 2020.

In 2020, numerous fast-spreading severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have been reported. These variants had unusually high genetic changes in the spike (S) protein. In an attempt to understand the genetic background of SARS-CoV-2 viruses in Hong Kong, especially before vaccination, the purpose of this study is to summarize the S protein mutations detected among coronavirus disease 2019 (COVID-19) patients in Hong Kong in 2020.

Local Transmission Plays No Important Role in the Occurrence of Multidrug-Resistant Tuberculosis in Immigrants to Canada: An In-depth Epidemiologic Analysis.

Background: Multidrug-resistant (MDR) tuberculosis has increased among migrants in Canada. The cause(s) of this increase is unknown.

Methods: We performed a retrospective cohort study in a Canadian province with substantially increased immigration between 1982-2001 and 2002-2019.

BRCA1 Mutation Status and Follicular Fluid Exposure Alters NFκB Signaling and ISGylation in Human Fallopian Tube Epithelial Cells.

Germline BRCA1 or BRCA2 mutations (mtBRCA1 and mtBRCA2) increase risk for high-grade serous ovarian cancer (HGSOC), the most commonly diagnosed epithelial ovarian cancer histotype. Other identified risk factors for this cancer, which originates primarily in the distal fallopian tube epithelium (FTE), implicate ovulation, during which the FTE cells become transiently exposed to follicular fluid (FF). To test whether mtBRCA1 or mtBRCA2 nonmalignant FTE cells respond differently to periovulatory FF exposure than control patient FTE cells, gene expression profiles from primary FTE cultures derived from BRCA1 or BRCA2 mutation carriers or control patients were compared at baseline, 24 hours after FF exposure, and 24 hours after FF replacement with culture medium.

Towards the elimination of paediatric tuberculosis in high-income, immigrant-receiving countries: a 25-year conventional and molecular epidemiological case study.

The epidemiology of tuberculosis (TB) in high-income countries is increasingly dictated by immigration. The influence of this trend on paediatric TB and TB elimination are not well defined. We undertook a 25-year conventional and molecular epidemiologic study of paediatric TB in Alberta, one of four major immigrant-receiving provinces in Canada.

Chest Radiographic Patterns and the Transmission of Tuberculosis: Implications for Automated Systems.

Background: Computer-aided detection to identify and diagnose pulmonary tuberculosis is being explored. While both cavitation on chest radiograph and smear-positivity on microscopy are independent risk factors for the infectiousness of pulmonary tuberculosis it is unknown which radiographic pattern, were it detectable, would provide the greatest public health benefit; i.e.

Improved glucose metabolism in vitro and in vivo by an allosteric monoclonal antibody that increases insulin receptor binding affinity.

Previously we reported studies of XMetA, an agonist antibody to the insulin receptor (INSR). We have now utilized phage display to identify XMetS, a novel monoclonal antibody to the INSR. Biophysical studies demonstrated that XMetS bound to the human and mouse INSR with picomolar affinity.

Inhibition of insulin receptor function by a human, allosteric monoclonal antibody: a potential new approach for the treatment of hyperinsulinemic hypoglycemia.

Novel therapies are needed for the treatment of hypoglycemia resulting from both endogenous and exogenous hyperinsulinema. To provide a potential new treatment option, we identified XMetD, an allosteric monoclonal antibody to the insulin receptor (INSR) that was isolated from a human antibody phage display library. To selectively obtain antibodies directed at allosteric sites, panning of the phage display library was conducted using the insulin-INSR complex.

Altered expression of inflammation-associated genes in oviductal cells following follicular fluid exposure: implications for ovarian carcinogenesis.

Evidence indicates that high-grade serous ovarian carcinoma (HGSOC) may originate from lesions within the distal fallopian tube epithelium (FTE). Our previous studies indicate that fallopian tube epithelial cells from carriers of germline mutations in breast cancer susceptibility genes exhibit a pro-inflammatory gene expression signature during the luteal phase, suggesting that delayed resolution of postovulatory inflammatory signaling may contribute to predisposition to this ovarian cancer histotype. To determine whether exposure of tubal epithelial cells to periovulatory follicular fluid alters expression of inflammation-associated genes, we used an ex vivo culture system of bovine oviductal epithelial cells.

Marked disparity in the epidemiology of tuberculosis among Aboriginal peoples on the Canadian prairies: the challenges and opportunities.

Background: While it is established that Aboriginal peoples in the prairie provinces of Canada are disproportionately affected by tuberculosis (TB), little is known about the epidemiology of TB either within or across provincial borders.

Methods: Provincial reporting systems for TB, Statistics Canada censuses and population estimates of Registered Indians provided by Aboriginal Affairs and Northern Development Canada were used to estimate the overall (2004 to 2008) and pulmonary (2007 to 2008) TB rates in the prairie provinces. The place of residence at diagnosis of pulmonary TB cases in 2007 to 2008 was also documented.

An acute, double-blind, placebo-controlled crossover study of 320 mg and 640 mg doses of a special extract of Bacopa monnieri (CDRI 08) on sustained cognitive performance.

Standardized extracts of the traditional Ayurvedic medicine Bacopa monnieri (BM) (Brahmi) have been recently shown to have cognitive enhancing effects in chronic administration studies. Pre-clinical work has also identified a number of acute anxiolytic, nootropic, and cardiovascular effects of BM. There has, however, been little research on the acute effects of BM on cognitive function.

A fully human, allosteric monoclonal antibody that activates the insulin receptor and improves glycemic control.

Many patients with diabetes mellitus (both type 1 and type 2) require therapy to maintain normal fasting glucose levels. To develop a novel treatment for these individuals, we used phage display technology to target the insulin receptor (INSR) complexed with insulin and identified a high affinity, allosteric, human monoclonal antibody, XMetA, which mimicked the glucoregulatory, but not the mitogenic, actions of insulin. Biophysical studies with cultured cells expressing human INSR demonstrated that XMetA acted allosterically and did not compete with insulin for binding to its receptor.

Fertility preservation practices among Ontario oncologists.

This study explores the attitudes, knowledge, and referring behaviors in fertility preservation among Ontario physicians providing adult cancer care. Ontario physicians with specialties in medical oncology, radiation oncology, gynaecologic oncology, and urology were invited to complete a 48-item questionnaire. A total of 152 questionnaires were available for analysis with a response rate of 23.