Pharmacogenetic-guided dosing for fluoropyrimidine (DPYD) and irinotecan (UGT1A1*28) chemotherapies for patients with cancer (PACIFIC-PGx): A multicenter clinical trial.

PACIFIC-PGx evaluated the feasibility of implementing pharmacogenetics (PGx) screening in Australia and the impact of DPYD/UGT1A1 genotype-guided dosing on severe fluoropyrimidine (FP) and irinotecan-related toxicities and hospitalizations, compared to historical controls. This prospective single arm trial enrolled patients starting FP/irinotecan for any cancer between 7 January 2021 and 25 February 2022 from four Australian hospitals (one metropolitan, three regional). During the accrual period, 462/487 (95%) consecutive patients screened for eligibility for DPYD and 50/109 (46%) for UGT1A1 were enrolled and genotyped (feasibility analysis), with 276/462 (60%) for DPYD and 30/50 (60%) for UGT1A1 received FP/irinotecan (safety analysis).

Predictive value of homologous recombination deficiency status for survival outcomes in primary tubo-ovarian high-grade serous carcinoma.

This is a protocol for a Cochrane Review (prognosis). The objectives are as follows: To evaluate the predictive value of the prognostic factor HRD status, as determined by various clinically validated HRD assays at the time of staging laparotomy, compared to BRCA1/2 mutation status for progression-free survival and overall survival in patients with tubo-ovarian high-grade serous carcinoma treated in the first-line setting with a combination of surgery and platinum-based chemotherapy and/or maintenance with PARP inhibitors.

Stromal lymphocytes are associated with upgrade of B3 breast lesions.

Various histopathological, clinical and imaging parameters have been evaluated to identify a subset of women diagnosed with lesions with uncertain malignant potential (B3 or BIRADS 3/4A lesions) who could safely be observed rather than being treated with surgical excision, with little impact on clinical practice. The primary reason for surgery is to rule out an upgrade to either ductal carcinoma in situ or invasive breast cancer, which occurs in up to 30% of patients. We hypothesised that the stromal immune microenvironment could indicate the presence of carcinoma associated with a ductal B3 lesion and that this could be detected in biopsies by counting lymphocytes as a predictive biomarker for upgrade.

Universal genetic testing for women with newly diagnosed breast cancer in the context of multidisciplinary team care.

Objective: To determine the feasibility of universal genetic testing of women with newly diagnosed breast cancer, to estimate the incidence of pathogenic gene variants and their impact on patient management, and to evaluate patient and clinician acceptance of universal testing.

Design, Setting, Participants: Prospective study of women with invasive or high grade in situ breast cancer and unknown germline status discussed at the Parkville Breast Service (Melbourne) multidisciplinary team meeting. Women were recruited to the pilot (12 June 2020 - 22 March 2021) and expansion phases (17 October 2021 - 8 November 2022) of the Mutational Assessment of newly diagnosed breast cancer using Germline and tumour genomICs (MAGIC) study.

Tumor-Infiltrating Neutrophils after Neoadjuvant Therapy are Associated with Poor Prognosis in Esophageal Cancer.

Background: In esophageal cancer (EC), there is a paucity of knowledge regarding the interplay between the tumor immune microenvironment and response to neoadjuvant treatment and, therefore, which factors may influence outcomes. Thus, our goal was to investigate the changes in the immune microenvironment with neoadjuvant treatment in EC by assessing the expression of immune related genes and their association with prognosis.

Methods: We examined the transcriptome of paired pre- and post-neoadjuvant treated EC specimens.

Molecular characterization of low-grade serous ovarian carcinoma identifies genomic aberrations according to hormone receptor expression.

Hormone receptor expression is a characteristic of low-grade serous ovarian carcinoma (LGSOC). Studies investigating estrogen receptor (ER) and progesterone receptor (PR) expression levels suggest its prognostic and predictive significance, although their associations with key molecular aberrations are not well understood. As such, we sought to describe the specific genomic profiles associated with different ER/PR expression patterns and survival outcomes in a cohort of patients with advanced disease.

Effectiveness of the conservation areas on the Mornington Peninsula for the common resident shorebird species using citizen science data.

Conservation areas are critical for biodiversity conservation, but few citizen science studies have evaluated their efficiency. In the absence of thorough survey data, this study assessed which species benefit most from conservation areas using citizen science bird counts extracted from the Atlas of Living Australia. This was accomplished by fitting temporal models using citizen science data taken from ALA for the years 2010-2019 using the INLA approach.

Loss of SMAD4 Is Sufficient to Promote Tumorigenesis in a Model of Dysplastic Barrett's Esophagus.

Background & Aims: Esophageal adenocarcinoma (EAC) develops from its precursor Barrett's esophagus through intermediate stages of low- and high-grade dysplasia. However, knowledge of genetic drivers and molecular mechanisms implicated in disease progression is limited. Herein, we investigated the effect of Mothers against decapentaplegic homolog 4 (SMAD4) loss on transforming growth factor β (TGF-β) signaling functionality and in vivo tumorigenicity in high-grade dysplastic Barrett's cells.

Detecting possible persons of interest in a physical activity program using step entries: Including a web-based application for outlier detection and decision-making.

According to recent statistics from the World Health Organization, 23% of people aged 18 years and over are not sufficiently physically active. Strangely, this is at a time when, due to the improvement in sensor technology, physical activity programs that track physical activity have become popular. However, some participants who enroll in these programs cheat by manipulating the data they enter.

Insulin resistance in prostate cancer patients and predisposing them to acute ischemic heart disease.

Lack of insulin or insulin resistance (IR) plays a central role in diabetes mellitus and makes diabetics prone to acute ischemic heart disease (AIHD). It has likewise been found that many cancer patients, including prostate cancer patients die of AIHD. Previously it has been delineated from our laboratory that dermcidin could induce anomalous platelet aggregation in AIHD and also impaired nitric oxide and insulin activity and furthermore dermcidin was also found in a few types of cancer patients.

Predictors of Success of Workplace Physical Activity Interventions: A Systematic Review.

Background: Despite holding great potential for addressing concerns regarding public health, recent systematic reviews have found effect sizes for interventions targeting physical activity to be small. Before interventions can be improved, the factors influencing outcomes must be identified. This systematic review aimed to identify predictors of success, measured in terms of engagement (eg, involvement duration) and health behavior change (eg, increased step counts), of workplace interventions targeting physical activity.

Statistical methods to model and evaluate physical activity programs, using step counts: A systematic review.

Background: Physical activity reduces the risk of noncommunicable diseases and is therefore an essential component of a healthy lifestyle. Regular engagement in physical activity can produce immediate and long term health benefits. However, physical activity levels are not as high as might be expected.

Promoting Psychological Well-Being at Work by Reducing Stress and Improving Sleep: Mixed-Methods Analysis.

Background: Workplace programs designed to improve the health and psychological well-being of employees are becoming increasingly popular. However, there are mixed reports regarding the effectiveness of such programs and little analysis of what helps people to engage with such programs.

Objective: This evaluation of a particularly broad, team-based, digital health and well-being program uses mixed methods to identify the elements of the program that reduce work stress and promote psychological well-being, sleep quality, and productivity of employees.