Statins inhibit onco-dimerization of the 4Ig isoform of B7-H3.

B7-H3 (CD276), a member of the B7-family of immune checkpoint proteins, has been shown to have immunological and non-immunological effects promoting tumorigenesis [1, 2] and expression correlates with poor prognosis for many solid tumors, including cervical, ovarian and breast cancers [3-6]. We recently identified a tumor-cell autochthonous tumorigenic role for dimerization of the 4Ig isoform of B7-H3 (4Ig-B7-H3) [7], where 4Ig-B7-H3 dimerization activated tumor-intrinsic cellular proliferation and tumorigenesis pathways, providing a novel opportunity for therapeutic intervention. Herein, a live cell split-luciferase complementation strategy was used to visualize 4Ig-B7-H3 homodimerization in a high-throughput small molecule screen (HTS) to identify modulators of this protein-protein interaction (PPI).

Illuminating immunotherapy response via precision T cell-targeted PET imaging.

Traditionally, immunotherapy agent selection and treatment strategies are guided by biopsy-based histological information. However, biopsies are limited in that they are invasive, provide static information regarding the tumor immune microenvironment, and only sample a small part of one tumor site. The tumor microenvironment is dynamic and heterogenous.

Financial Stressors for Parents of Children and Emerging Adults With Congenital Heart Disease: A Qualitative Study.

Introduction: Congenital heart disease (CHD) is the most prevalent congenital disability globally. This study aimed to describe parents' perspectives on financial stressors related to having a child with CHD using a descriptive qualitative approach.

Method: Qualitative data were obtained from parents of children with CHD in a cross-sectional web-based survey study.

Impact of COVID-19 pandemic on sleep parameters and characteristics in individuals living with overweight and obesity.

Coronavirus disease 2019 (COVID-19) has been very challenging for those living with overweight and obesity. The magnitude of this impact on sleep requires further attention to optimise patient care and outcomes. This study assessed the impact of the COVID-19 lockdown on sleep duration and quality as well as identify predictors of poor sleep quality in individuals with reported diagnoses of obstructive sleep apnoea and those without sleep apnoea.

Dimerization of the 4Ig isoform of B7-H3 in tumor cells mediates enhanced proliferation and tumorigenic signaling.

B7-H3 (CD276) has two isoforms (2Ig and 4Ig), no confirmed cognate receptor, and physiological functions that remain elusive. While differentially expressed on many solid tumors correlating with poor survival, mechanisms of how B7-H3 signals in cis (tumor cell) versus in trans (immune cell co-regulator) to elicit pro-tumorigenic phenotypes remain poorly defined. Herein, we characterized a tumorigenic and signaling role for tumor cell-expressed 4Ig-B7-H3, the dominant human isoform, in gynecological cancers that could be abrogated upon CRISPR/Cas9 knockout of B7-H3; tumorigenesis was rescued upon re-expression of 4Ig-B7-H3.

Feasibility and acceptability of an online parenting intervention to address behaviour problems in moderately to extremely preterm pre-school and school-age children.

Background: Preterm birth is associated with adverse mental health outcomes, including internalizing problems, social difficulties and inattention. Interventions are needed beyond infancy and toddlerhood to support children and their families. We examined the feasibility and acceptability of the I-InTERACT Preterm pilot study, an online parenting intervention for preterm children ages 3-8.

Melatonin Use in Pediatric Intensive Care Units: A Single-Center Experience.

Growing evidence indicates that altered melatonin secretion during critical illness may influence the quality and quantity of sleep, delirium, and overall recovery. However, limited data exist regarding the use of melatonin in pediatric critical illness. Data were reviewed over a 5-year period at a tertiary pediatric intensive care unit for pediatric patients (ages 0-18 years) who were prescribed melatonin with the aim of identifying the frequency of and indications for use.

Parenting Interventions Targeting Behavior for Children Born Preterm or Low Birth Weight: A Systematic Review.

Objective: To systematically review and summarize the outcomes of parenting interventions designed to improve child and/or parenting behavior for children born preterm and/or low birth weight (LBW).

Methods: We conducted systematic searches of Embase, Scopus, PubMed, PsycInfo, and CINAHL in September 2021. We identified articles published at any time that describe the outcomes of parenting interventions targeting the child and/or parenting behavior of children born preterm/LBW and their caregivers.

Evaluation of Zr-Labeled Anti-PD-L1 Monoclonal Antibodies Using DFO and Novel HOPO Analogues as Chelating Agents for Immuno-PET.

Programmed death ligand 1 (PD-L1) is a type 1 transmembrane immunosuppressive protein that is expressed on a wide range of cell types, including cancer cells. Anti-PD-L1 antibodies have revolutionized cancer therapy and have led to improved outcomes for subsets of cancer patients, including triple-negative breast cancer (TNBC) patients. As a result, PET imaging of PD-L1 protein expression in cancer patients has been explored for noninvasive detection of PD-L1 expressing tumors as well as monitoring response to anti-PD-L1 immune checkpoint therapy.

TLR5 agonists enhance anti-tumor immunity and overcome resistance to immune checkpoint therapy.

Primary and adaptive resistance to immune checkpoint therapies (ICT) represent a considerable obstacle to achieving enhanced overall survival. Innate immune activators have been actively pursued for their antitumor potential. Herein we report that a syngeneic 4T1 mammary carcinoma murine model for established highly-refractory triple negative breast cancer showed enhanced survival when treated intra-tumorally with either the TLR5 agonist flagellin or CBLB502, a flagellin derivative, in combination with antibodies targeting CTLA-4 and PD-1.

Weight gain, weight management and medical care for individuals living with overweight and obesity during the COVID-19 pandemic (EPOCH Study).

Objective: Medical care and weight related experiences have been challenged by the coronavirus disease 2019 (COVID-19) pandemic for those living with obesity. The magnitude of this impact requires further attention in order to optimize patient care and outcomes. The aim of this study was to assess the impact of the COVID-19 pandemic and lockdown on access to, and experience of, medical care, weight gain and management strategies, as well as predictors of weight gain.

The associations between resilience and socio-demographic factors in parents who care for their children with congenital heart disease.

Objective: To examine the resilience of parents of children with congenital heart disease and to investigate socio-demographic factors that may influence parents' resilience.

Methods: This is a web-based survey study using a cross-sectional design. A purposive sampling method was utilized to recruit 515 parents who care for children with congenital heart disease.

Guidelines for Canadian bariatric surgical and medical centres: a statement from the Canadian Association of Bariatric Physicians and Surgeons.

The goal of this statement is to offer standardization in bariatric care across Canada, to provide patients with optimal access to obesity treatment and potentially improve outcomes by reducing complications, length of hospital stay and readmission rate. The definition of Canadian standards also aims to promote a comprehensive, multidisciplinary approach to patients with obesity, to define the minimal qualifications for surgical and medical training and to offer credentialling for bariatric surgical and medical centres. In addition, we emphasize the importance of developing a national registry for the assessment of quality of care across the country and to evaluate outcomes of long-term treatment.

A Novel Method for the Production of an Autologous Anti-Inflammatory and Anti-Catabolic Product (Cytorich) from Human Blood: A Prospective Treatment for the COVID-19-Induced Cytokine Storm.

BACKGROUND Autologous blood-derived products can target specific inflammatory molecular pathways and have potentially beneficial therapeutic effects on inflammatory pathologies. The purpose of this study was to assess in vitro the anti-inflammatory and anti-catabolic potential of an autologous blood product as a possible treatment for COVID-19-induced cytokine storm. MATERIAL AND METHODS Blood samples from healthy donors and donors who had recovered from COVID-19 were incubated using different techniques and analyzed for the presence of anti-inflammatory, anti-catabolic, regenerative, pro-inflammatory, and procatabolic molecules.

Lessons from bariatric surgery: Can increased GLP-1 enhance vascular repair during cardiometabolic-based chronic disease?

Type 2 diabetes (T2D) and obesity represent entangled pandemics that accelerate the development of cardiovascular disease (CVD). Given the immense burden of CVD in society, non-invasive prevention and treatment strategies to promote cardiovascular health are desperately needed. During T2D and obesity, chronic dysglycemia and abnormal adiposity result in systemic oxidative stress and inflammation that deplete the vascular regenerative cell reservoir in the bone marrow that impairs blood vessel repair and exacerbates the penetrance of CVD co-morbidities.

Adaptation and Psychometric Cross-Cultural Validation of a Workplace Cyberbullying Questionnaire in Spain and Germany.

As nonessential workers are working from home and connected to colleagues through means of computer technology, cyberbullying, which has only recently been investigated in workplace settings, is likely to become more prevalent. Organizations are also reconsidering work structures that would keep workers remote. Workplace cyberbullying (WCB) can have a detrimental impact on victims' mental health, more than traditional face-to-face bullying.

Protecting individuals living with overweight and obesity: Attitudes and concerns toward COVID-19 vaccination in Canada.

Objective: The aim of this study was to assess attitudes toward coronavirus disease 2019 (COVID-19) vaccination and the degree of fear of COVID-19 among those living with obesity.

Methods: Two samples were recruited for an online survey: one sample was a representative sample of Canadians living with overweight and obesity (n = 1,089), and the second was a convenience sample of individuals recruited from obesity clinical services or patient organizations (n = 980). Respondents completed ratings of their comfort receiving a COVID-19 vaccination along with the Vaccine Hesitancy Scale and the Fear of COVID-19 Scale.

Vascular Risk Reduction in Obesity through Reduced Granulocyte Burden and Improved Angiogenic Monocyte Content following Bariatric Surgery.

Bariatric surgery, in addition to the benefit of sustained weight loss, can also reduce cardiometabolic risk and mortality. Lifelong vessel maintenance is integral to the prevention of cardiovascular disease. Using aldehyde dehydrogenase activity, an intracellular detoxifying enzyme present at high levels within pro-vascular progenitor cells, we observed an association between chronic obesity and "regenerative cell exhaustion" (RCE), a pathology whereby chronic assault on circulating regenerative cell types can result in adverse inflammation and diminished vessel repair.

Baseline cortisol predicts drunkorexia in female but not male college students.

"Drunkorexia" or compensatory eating behaviors in response to alcohol consumption, resembles a subclinical eating disorder, and is a current public health concern. Eating disorders and alcohol abuse are associated with dysfunction of the hypothalamic-pituitary-adrenal axis (HPA). One index of HPA function is cortisol.