Publications by authors named "Paul Cohen"

The gustatory system allows animals to assess the nutritive value and safety of foods prior to ingestion. The first step in gustation is the interaction of taste stimuli with one or more specific sensory receptors, that are generally believed to be present on the apical surface of the taste receptor cells. However, this assertion is rarely tested.

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Findings from clinical trials have led to advancement of care for patients with gynecologic malignancies. However, restrictive inclusion of patients into trials has been widely criticized for inadequate representation of the real-world population. Ideally, patients enrolled in clinical trials should represent a broader population to enhance external validity and facilitate translation of outcomes across all relevant groups.

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Leptin is an adipose tissue hormone that maintains homeostatic control of adipose tissue mass by regulating the activity of specific neural populations controlling appetite and metabolism. Leptin regulates food intake by inhibiting orexigenic agouti-related protein (AGRP) neurons and activating anorexigenic pro-opiomelanocortin (POMC) neurons. However, whereas AGRP neurons regulate food intake on a rapid time scale, acute activation of POMC neurons has only a minimal effect.

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  • Brown adipose tissue (BAT) allows mammals to regulate body temperature through a process called adaptive thermogenesis, which is stimulated by cold exposure.
  • Researchers identified a factor called Slit3 that facilitates communication between adipocyte progenitors, blood vessel cells, and sympathetic nerves, which is vital for BAT's thermogenic function.
  • The study reveals that Slit3 not only aids the growth of blood vessels and nerves in BAT but also involves a special cleaving process that releases fragments of Slit3 to activate different receptors, highlighting a complex interaction within adipose tissue that influences its response to cold.
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Endocervical adenocarcinomas (EACs) are a group of malignant neoplasms associated with diverse pathogenesis, morphology, and clinical behavior. As a component of the International Society of Gynecological Pathologists International Endocervical Adenocarcinoma Project, a large international retrospective cohort of EACs was generated in an effort to study potential clinicopathological features with prognostic significance that may guide treatment in these patients. In this study, we endeavored to develop a robust human papillomavirus (HPV)-associated EAC prognostic model for surgically treated International Federation of Gynecology and Obstetrics (FIGO) stage IA2 to IB3 adenocarcinomas incorporating patient age, lymphovascular space invasion (LVSI) status, FIGO stage, and pattern of invasion according to the Silva system (traditionally a 3-tier system).

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Objectives: In ovarian and other cancers, low muscle mass and density are associated with poorer clinical outcomes. However, screening for cancer-related sarcopenia (typically defined as low muscle mass) is not routinely conducted. The European Working Group on Sarcopenia in Older People (EWGSOP) recommends an algorithm for sarcopenia screening and diagnosis in clinical settings, with sarcopenia based on muscle strength and mass, and severity on physical performance.

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The skeleton has been suggested to function as an endocrine organ controlling whole organism energy balance, however the mediators of this effect and their molecular links remain unclear. Here, utilizing Schnurri-3 (Shn3) mice with augmented osteoblast activity, we show Shn3mice display resistance against diet-induced obesity and enhanced white adipose tissue (WAT) browning. Conditional deletion of Shn3 in osteoblasts but not adipocytes recapitulates lean phenotype of Shn3mice, indicating this phenotype is driven by skeleton.

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As medical treatment increasingly focuses on improving health-related quality of life, patient-reported outcome measures (PROMs) are an essential component of clinical research. The National Gynae-Oncology Registry (NGOR) is an Australian clinical quality registry. A suitable PROM was required for the NGOR ovarian cancer module to complement clinical outcomes and provide insights into outcomes important to patients.

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  • Obesity is identified as a significant risk factor for endometrial cancer (EC), but its effect on patient responses to immune checkpoint inhibitors (ICI) is not well understood; this study examines the link between BMI, body fat distribution, and clinical outcomes in EC patients undergoing ICI treatment.* -
  • The analysis of 524 EC patients shows that those who are overweight or obese have notably better progression-free survival (PFS) and overall survival (OS) compared to those with normal BMI, especially in the CN-H/TP53abn molecular subtype.* -
  • The study finds that obesity not only correlates with improved treatment outcomes for EC patients receiving ICI but also leads to a higher incidence of immune-related adverse
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Background: Obesity is the foremost risk factor in the development of endometrial cancer (EC). However, the impact of obesity on the response to immune checkpoint inhibitors (ICI) in EC remains poorly understood. This retrospective study investigates the association between body mass index (BMI), body fat distribution, and clinical and molecular characteristics of EC patients treated with ICI.

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Unlabelled: Reducing growth and limiting metabolism are strategies that allow bacteria to survive exposure to environmental stress and antibiotics. During infection, uropathogenic (UPEC) may enter a quiescent state that enables them to reemerge after the completion of successful antibiotic treatment. Many clinical isolates, including the well-characterized UPEC strain CFT073, also enter a metabolite-dependent, quiescent state that is reversible with cues, including peptidoglycan-derived peptides and amino acids.

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High-grade serous ovarian carcinoma (HGSOC) is genetically unstable and characterised by the presence of subclones with distinct genotypes. Intratumoural heterogeneity is linked to recurrence, chemotherapy resistance, and poor prognosis. Here, we use spatial transcriptomics to identify HGSOC subclones and study their association with infiltrating cell populations.

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Surgical decision making is complex and involves a combination of analytic, intuitive, and cognitive processes. Medicolegal, infrastructural, and financial factors may influence these processes depending on the context and setting, but to what extent can they influence surgical decision making in gynecologic oncology? This scoping review evaluates existing literature related to medicolegal, infrastructural, and financial aspects of gynecologic cancer surgery and their implications in surgical decision making. Our objective was to summarize the findings and limitations of published research, identify gaps in the literature, and make recommendations for future research to inform policy.

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Introduction: The study examined whether increased physical activity (PA) in nonmetropolitan cancer survivors was maintained 12 weeks following the PPARCS intervention.

Methods: PA outcomes were assessed using an accelerometer at baseline, end of the intervention, and at 24 weeks. Linear mixed models were used to examine between-group changes in PA outcomes.

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In this chapter, we update our 2004 review of "The Life of Commensal in the Mammalian Intestine" (https://doi.org/10.1128/ecosalplus.

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Oxytocin (OXT), a nine-amino-acid peptide produced in the hypothalamus and released by the posterior pituitary, has well-known actions in parturition, lactation and social behaviour, and has become an intriguing therapeutic target for conditions such as autism and schizophrenia. Exogenous OXT has also been shown to have effects on body weight, lipid levels and glucose homeostasis, suggesting that it may also have therapeutic potential for metabolic disease. It is unclear, however, whether endogenous OXT participates in metabolic homeostasis.

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Background: Less than two percent of pancreatic neuroendocrine tumors (NETs) produce serotonin. Serotonin can cause carcinoid syndrome and less commonly carcinoid heart disease (CHD). CHD is associated with increased mortality and requires a more aggressive approach.

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Article Synopsis
  • The current staging system for endometrial cancer by the International Federation of Gynecology and Obstetrics has unresolved issues recognized by both pathologists and clinicians, mainly due to limitations in existing research.
  • A survey of 307 professionals aimed to identify key areas for improvement, highlighting the need to differentiate outcomes for stage IIIA and IIIC patients based on specific criteria to avoid over-treatment and enhance prognostic accuracy.
  • While most professionals agreed on the importance of lymphovascular space invasion as a prognostic factor and the need for better staging protocols, there was no consensus on specific diagnostic criteria or a universally accepted protocol for sentinel lymph node ultra-staging.
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Objective: Poly-ADP ribose polymerase inhibitors (PARPi) have expanded the management armamentarium against high grade serous tubo-ovarian cancer (HGSOC) in patients with germline and somatic pathogenic variants (PVs). Germline testing has been available in Western Australia (WA) since July 2015, whilst somatic testing was previously only available through interstate laboratories. We hypothesized that due to complexity of referral, testing rates for somatic would be low.

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  • The study aimed to investigate the variation in pain management and prevention of nausea and vomiting post-surgery for patients undergoing major abdominal procedures in Perth, Australia.
  • Researchers found significant differences in prescribing practices for postoperative pain relief and PONV prevention, highlighting a disconnect between evidence-based guidelines and actual clinical practice.
  • The authors suggest that more randomized clinical trials are needed to evaluate the impact of these variations on patient outcomes and healthcare costs.
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Objective: Our primary aim was to compare muscle morphology (skeletal muscle mass and density) between patients who underwent primary cytoreductive surgery versus interval cytoreductive surgery for advanced high-grade serous ovarian cancer. Secondarily, we explored the associations of muscle morphology with survival outcomes.

Methods: We retrospectively analysed computed tomography (CT) images for 88 ovarian cancer patients (aged 38-89 years) to calculate skeletal muscle index (cm/m) and skeletal muscle density (Hounsfield units (HU)).

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Reducing growth and limiting metabolism are strategies that allow bacteria to survive exposure to environmental stress and antibiotics. During infection, uropathogenic (UPEC) may enter a quiescent state that enables them to reemerge after completion of successful antibiotic treatment. Many clinical isolates, including the well characterized UPEC strain CFT073, also enter a metabolite-dependent, quiescent state in vitro that is reversible with cues, including peptidoglycan-derived peptides and amino acids.

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Objectives: In ovarian cancer (OC), suboptimal muscle morphology (i.e., low muscle mass and density) is associated with poor clinical outcomes, yet little is known about the effect of interventions aimed at improving these measures.

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