Impact of cancer diagnosis on life expectancy by area-level socioeconomic groups in New South Wales, Australia: a population-based study.

Objective: Improvement in cancer survival over recent decades has not been accompanied by a narrowing of socioeconomic disparities. This study aimed to quantify the loss of life expectancy (LOLE) resulting from a cancer diagnosis and examine disparities in LOLE based on area-level socioeconomic status (SES).

Methods: Data were collected for all people between 50 and 89 years of age who were diagnosed with cancer, registered in the NSW Cancer Registry between 2001 and 2019, and underwent mortality follow-up evaluations until December 2020.

Treatment intervals and survival for women diagnosed with early breast cancer in Queensland: the Breast Cancer Outcomes Study, a population-based cohort study.

Objectives: To assess associations between breast cancer-specific survival and timeliness of treatment, based on 2020 Australian guidelines for the treatment of early breast cancer.

Design: Population-based cohort study; analysis of linked Queensland Cancer Register, patient medical record, and National Death Index data, supplemented by telephone interviews.

Setting, Participants: Women aged 20-79 years diagnosed with invasive breast cancer during 1 March 2010 - 30 June 2013, followed to 31 December 2020.

Severity and risk factors of interval breast cancer in Queensland, Australia: a population-based study.

Background: Interval breast cancers (BC) are those diagnosed within 24 months of a negative mammogram. This study estimates the odds of being diagnosed with high-severity BC among screen-detected, interval, and other symptom-detected BC (no screening history within 2 years); and explores factors associated with being diagnosed with interval BC.

Methods: Telephone interviews and self-administered questionnaires were conducted among women (n = 3,326) diagnosed with BC in 2010-2013 in Queensland.

Discovery of Ervogastat (PF-06865571): A Potent and Selective Inhibitor of Diacylglycerol Acyltransferase 2 for the Treatment of Non-alcoholic Steatohepatitis.

Discovery efforts leading to the identification of ervogastat (PF-06865571), a systemically acting diacylglycerol acyltransferase (DGAT2) inhibitor that has advanced into clinical trials for the treatment of non-alcoholic steatohepatitis (NASH) with liver fibrosis, are described herein. Ervogastat is a first-in-class DGAT2 inhibitor that addressed potential development risks of the prototype liver-targeted DGAT2 inhibitor PF-06427878. Key design elements that culminated in the discovery of ervogastat are (1) replacement of the metabolically labile motif with a 3,5-disubstituted pyridine system, which addressed potential safety risks arising from a cytochrome P450-mediated -dearylation of PF-06427878 to a reactive quinone metabolite precursor, and (2) modifications of the amide group to a 3-THF group, guided by metabolite identification studies coupled with property-based drug design.

A prognostic survival model for women diagnosed with invasive breast cancer in Queensland, Australia.

Purpose: Prognostic models can help inform patients on the future course of their cancer and assist the decision making of clinicians and patients in respect to management and treatment of the cancer. In contrast to previous studies considering survival following treatment, this study aimed to develop a prognostic model to quantify breast cancer-specific survival at the time of diagnosis.

Methods: A large (n = 3323), population-based prospective cohort of women were diagnosed with invasive breast cancer in Queensland, Australia between 2010 and 2013, and followed up to December 2018.

Factors influencing participants' engagement with an interactive text-message intervention to improve sun protection behaviors: "SunText" randomized controlled trial.

There is growing evidence suggesting that text-message-based interventions are effective to promote sun protection behaviors. However, it is still unclear how engagement and adherence with the intervention messages can be optimized through intervention design. This study evaluated the effect of different combinations of personalized and two-way interactive messages on participant engagement with a theory-based skin cancer prevention intervention.

ACC inhibitor alone or co-administered with a DGAT2 inhibitor in patients with non-alcoholic fatty liver disease: two parallel, placebo-controlled, randomized phase 2a trials.

Alterations in lipid metabolism might contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, no pharmacological agents are currently approved in the United States or the European Union for the treatment of NAFLD. Two parallel phase 2a studies investigated the effects of liver-directed ACC1/2 inhibition in adults with NAFLD.

Optimizing Texting Interventions for Melanoma Prevention and Early Detection: A Latin Square Crossover RCT.

Introduction: Text messaging is an effective way to reach large populations with health promotion support. This study aims to establish the optimal text messaging intervention to achieve behavior change in young adults at risk of skin cancer.

Study Design: Latin square crossover RCT.

Crude probability of death for cancer patients by spread of disease in New South Wales, Australia 1985 to 2014.

Background: To estimate trends in the crude probability of death for cancer patients by sex, age and spread of disease over the past 30 years in New South Wales, Australia.

Methods: Population-based cohort of 716,501 people aged 15-89 years diagnosed with a first primary cancer during 1985-2014 were followed up to 31 December 2015. Flexible parametric relative survival models were used to estimate the age-specific crude probability of dying from cancer and other causes by calendar year, sex and spread of disease for all solid tumours combined and cancers of the colorectum, lung, female breast, prostate and melanoma.

Pharmacologic inhibition of ketohexokinase prevents fructose-induced metabolic dysfunction.

Objective: Recent studies suggest that excess dietary fructose contributes to metabolic dysfunction by promoting insulin resistance, de novo lipogenesis (DNL), and hepatic steatosis, thereby increasing the risk of obesity, type 2 diabetes (T2D), non-alcoholic steatohepatitis (NASH), and related comorbidities. Whether this metabolic dysfunction is driven by the excess dietary calories contained in fructose or whether fructose catabolism itself is uniquely pathogenic remains controversial. We sought to test whether a small molecule inhibitor of the primary fructose metabolizing enzyme ketohexokinase (KHK) can ameliorate the metabolic effects of fructose.

Impact of area-level socioeconomic status and accessibility to treatment on life expectancy after a cancer diagnosis in Queensland, Australia.

Aims: This study quantifies geographic inequities in loss of life expectancy (LOLE) by area-level socioeconomic status (SES) and accessibility to treatment.

Methods: Analysis was conducted using a population-based cancer-registry cohort (n = 371,570) of Queensland (Australia) residents aged 50-89 years, diagnosed between 1997-2016. Flexible parametric survival models were used to estimate LOLE by area-level SES and accessibility for all invasive cancers and the five leading cancers.

Factors associated with being diagnosed with high severity of breast cancer: a population-based study in Queensland, Australia.

Purpose: This study explores factors that are associated with the severity of breast cancer (BC) at diagnosis.

Methods: Interviews were conducted among women (n = 3326) aged 20-79 diagnosed with BC between 2011 and 2013 in Queensland, Australia. High-severity cancers were defined as either Stage II-IV, Grade 3, or having negative hormone receptors at diagnosis.

Quantifying the Number of Cancer Deaths Avoided Due to Improvements in Cancer Survival since the 1980s in the Australian Population, 1985-2014.

Background: This study quantifies the number of potentially "avoided"cancer deaths due to differences in 10-year relative survival between three time periods, reflecting temporal improvements in cancer diagnostic and/or treatment practices in Australia.

Methods: National population-based cohort of 2,307,565 Australians ages 15 to 89 years, diagnosed with a primary invasive cancer from 1985 to 2014 with mortality follow-up to December 31, 2015. Excess mortality rates and crude probabilities of cancer deaths were estimated using flexible parametric relative survival models.

Temporal trends in loss of life expectancy after a cancer diagnosis among the Australian population.

Background: Loss of life expectancy (LOLE) provides valuable insights into the impact of cancer. We evaluated the temporal trends in LOLE for Australian cancer patients and the gain in life years for recently diagnosed patients due to survival improvements.

Methods: Analysis was conducted using an Australian population-based cohort (n = 1,865,154) aged 50-89 years, who were primarily diagnosed with one of 19 leading cancers between 1982-2015.

Temporal Trends in Population-Level Cure of Cancer: The Australian Context.

Background: With the improvements in cancer diagnosis and treatment, more patients with cancer are surviving for longer periods than before. This study aims to quantify the proportion cured and median survival time for those who are not cured for major cancers in Australia.

Methods: Australian population-based cohort of 2,164,172 cases, ages 15 to 89 years, whose first cancer diagnosis between 1982 and 2014 was one of 22 leading cancers, were followed up to December 2014.

Temporal trends in net and crude probability of death from cancer and other causes in the Australian population, 1984-2013.

Background: While net probabilities of death in the relative survival framework ignore competing causes of death, crude probabilities allow estimation of the real risk of cancer deaths. This study quantifies temporal trends in net and crude probabilities of death.

Methods: Australian population-based cohort of 2,015,903 people aged 15-89 years, diagnosed with a single primary invasive cancer from 1984 to 2013 with mortality follow-up to 31 December 2014.

Individual- and Area-Level Socioeconomic Inequalities in Esophageal Cancer Survival in Shandong Province, China: A Multilevel Analysis.

Background: China contributes to almost half of the esophageal cancer cases diagnosed globally each year. However, the prognosis information of this disease in this large population is scarce.

Methods: Data on a population-based cohort consisting of residents of Shandong Province, China who were diagnosed with esophageal cancer during the period from 2005 to 2014 were analyzed.

The Effect of Choice on Motor Learning for Learners With Different Levels of Intrinsic Motivation.

This study examines whether the positive effect of choice on motor learning in a dart-throwing task varies by intrinsic motivation. Participants were allocated to a highly motivated or less-motivated group based on measured task motivation and randomly to a Choice or No Choice group. In Experiment 1, participants in the Choice group chose their dart color.

Area socioeconomic status is independently associated with esophageal cancer mortality in Shandong, China.

Esophageal cancer (EC) is a leading cause of cancer death in China. Within Shandong Province, a geographic cluster with high EC mortality has been identified, however little is known about how area-level socioeconomic status (SES) is associated with EC mortality in this province. Multilevel models were applied to EC mortality data in 2011-13 among Shandong residents aged 40+ years.

Spatial Analysis of Esophageal Cancer Mortality in a High-risk Population in China: Consistent Clustering Pattern in 1970-74 and 2011-13.

Purpose: Almost half of the global esophageal cancer (EC) deaths occurred in China. This study aims to examine the geographic spread of EC mortality in two periods in a large Chinese population. Methods: Age-standardized mortality rates (ASMRs) for 140 county-level units in Shandong Province during the periods 1970-74 and 2011-13 were derived using data from the First National Cause-of-Death Survey and the Shandong Death Registration System, respectively.

The gap between cause-of-death statistics and Household Registration reports in Shandong, China during 2011-2013: Evaluation and adjustment for underreporting in the mortality data for 262 subcounty level populations.

Underreporting is a quality concern in mortality statistics. The purpose of this study was to assess and adjust underreporting in the population-based cause-of-death statistics. The total population (96 million) in Shandong, China was divided into 262 subcounty level populations geographically and by residence type (urban/rural).

Characterization of a Novel Intestinal Glycerol-3-phosphate Acyltransferase Pathway and Its Role in Lipid Homeostasis.

Dietary triglycerides (TG) are absorbed by the enterocytes of the small intestine after luminal hydrolysis into monacylglycerol and fatty acids. Before secretion on chylomicrons, these lipids are reesterified into TG, primarily through the monoacylglycerol pathway. However, targeted deletion of the primary murine monoacylglycerol acyltransferase does not quantitatively affect lipid absorption, suggesting the existence of alternative pathways.

Doctor's Knowledge and Practices of Traumatic Brain Injury Management in Chinese Prehospital Settings.

Objectives: The incidence and mortality of traumatic brain injury (TBI) has increased rapidly in the last decade in China. Appropriate ambulance service can reduce case-fatality rates of TBI significantly. This study aimed to explore the factors (age, gender, education level, clinical experience, professional title, organization, specialty before prehospital care, and training frequency) that could influence prehospital doctors' knowledge level and practices in TBI management in China, Hubei Province.

Discovery and Optimization of Imidazopyridine-Based Inhibitors of Diacylglycerol Acyltransferase 2 (DGAT2).

The medicinal chemistry and preclinical biology of imidazopyridine-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) is described. A screening hit 1 with low lipophilic efficiency (LipE) was optimized through two key structural modifications: (1) identification of the pyrrolidine amide group for a significant LipE improvement, and (2) insertion of a sp(3)-hybridized carbon center in the core of the molecule for simultaneous improvement of N-glucuronidation metabolic liability and off-target pharmacology. The preclinical candidate 9 (PF-06424439) demonstrated excellent ADMET properties and decreased circulating and hepatic lipids when orally administered to dyslipidemic rodent models.