Emergency and non-emergency routes to cancer diagnoses in 2020 and 2021: A Population-based study of 154,863 patients.

Introduction: The COVID-19 pandemic disrupted normal pathways to cancer diagnosis, particularly for screening and non-acute symptomatic patients. While reductions in overall cancer diagnoses have been reported elsewhere, any differential effects on emergency presentations, which are associated with poorer outcomes, have not been described.

Material And Methods: Cross-sectional descriptive study from 2015 to 2021, based on International Cancer Benchmarking Partnership methods, where emergency route to diagnosis is defined as presenting as an emergency admission in the 30 days prior to cancer incidence date.

British Gynaecological Cancer Society Recommendations for Evidence Based, Population Data Derived Quality Performance Indicators for Ovarian Cancer.

Ovarian cancer survival in the UK lags behind comparable countries. Results from the ongoing National Ovarian Cancer Audit feasibility pilot (OCAFP) show that approximately 1 in 4 women with advanced ovarian cancer (Stage 2, 3, 4 and unstaged cancer) do not receive any anticancer treatment and only 51% in England receive international standard of care treatment, i.e.

Fossil records of early solar irradiation and cosmolocation of the CAI factory: A reappraisal.

Calcium-aluminum–rich inclusions (CAIs) in meteorites carry crucial information about the environmental conditions of the nascent Solar System prior to planet formation. Based on models of V–Be co-production by in-situ irradiation, CAIs are considered to have formed within ~0.1 AU from the proto-Sun.

Distinct forms of the actin cross-linking protein α-actinin support macropinosome internalization and trafficking.

The α-actinin family of actin cross-linking proteins have been implicated in driving tumor cell metastasis through regulation of the actin cytoskeleton; however, there has been little investigation into whether these proteins can influence tumor cell growth. We demonstrate that α-actinin 1 and 4 are essential for nutrient uptake through the process of macropinocytosis in pancreatic ductal adenocarcinoma (PDAC) cells, and inhibition of these proteins decreases tumor cell survival in the presence of extracellular protein. The α-actinin proteins play essential roles throughout the macropinocytic process, where α-actinin 4 stabilizes the actin cytoskeleton on the plasma membrane to drive membrane ruffling and macropinosome internalization and α-actinin 1 localizes to actin tails on macropinosomes to facilitate trafficking to the lysosome for degradation.

Multidisciplinary management of anal intraepithelial neoplasia and rate of progression to cancer: A retrospective cohort study.

Purpose: To describe the regional burden of AIN and rate of progression to cancer in patients managed in specialist and non-specialist clinic settings.

Methods: Patients with a histopathological diagnosis of AIN between 1994 and 2018 were retrospectively identified. Clinicopathological characteristics including high-risk status (chronic immunosuppressant use or HIV positive), number and type of biopsy (punch/excision) and histopathological findings were recorded.

Dynamin 2 interacts with α-actinin 4 to drive tumor cell invasion.

The large GTPase Dynamin 2 (Dyn2) is known to increase the invasiveness of pancreatic cancer tumor cells, but the mechanisms by which Dyn2 regulates changes in the actin cytoskeleton to drive cell migration are still unclear. Here we report that a direct interaction between Dyn2 and the actin-bundling protein alpha-actinin (α-actinin) 4 is critical for tumor cell migration and remodeling of the extracellular matrix in pancreatic ductal adenocarcinoma (PDAC) cells. The direct interaction is mediated through the C-terminal tails of both Dyn2 and α-actinin 4, and these proteins interact at invasive structures at the plasma membrane.

Interleukin-6 promotes pancreatic cancer cell migration by rapidly activating the small GTPase CDC42.

Inflammation is a major driver of tumor progression and metastasis, although the mechanisms by which proinflammatory cytokines drive metastatic invasion are unknown. Interleukin-6 (IL-6) is a potent proinflammatory cytokine that is elevated in individuals with pancreatic cancer (PDAC), is required for PDAC progression in mice, and increases tumor cell invasion Here, we provide insights into the mechanisms by which IL-6 activates tumor cell invasion. We found that IL-6 stimulation rapidly and robustly activates the small GTPase cell division cycle 42 (CDC42) in human PDAC cells and promotes the formation of premigratory filopodia.

Mountain glaciation drives rapid oxidation of rock-bound organic carbon.

Over millions of years, the oxidation of organic carbon contained within sedimentary rocks is one of the main sources of carbon dioxide to the atmosphere, yet the controls on this emission remain poorly constrained. We use rhenium to track the oxidation of rock-bound organic carbon in the mountain watersheds of New Zealand, where high rates of physical erosion expose rocks to chemical weathering. Oxidative weathering fluxes are two to three times higher in watersheds dominated by valley glaciers and exposed to frost shattering processes, compared to those with less glacial cover; a feature that we also observe in mountain watersheds globally.

The Current Burden of Follow-up of Stage 1A1 Cervical Cancer.

Objective: The aim of this study was to assess the current burden and consistency of stage 1A1 cervical cancer follow-up within Greater Glasgow and Clyde Health Board.

Methods: A retrospective review was undertaken of women diagnosed with and treated of, between 2007 and 2011, stage 1A1 cervical cancer in Greater Glasgow and Clyde Health Board. Data were collected on referral cytology, definitive method of treatment, posttreatment cytology, and rate of recurrence.

HPV status and favourable outcome in vulvar squamous cancer.

It is universally accepted that high-risk human papillomavirus (HR-HPV) is the cause of cervical dysplasia and cancer. More recently, it has been shown that HPV is also a marker of clinical outcome in oropharyngeal cancer. However, contemporary information is lacking on both the prevalence of HPV infection in vulvar cancer (VSCC), its precursor lesion, vulvar intraepithelial neoplasia (VIN) and the influence of HPV-status on the prognosis of this malignancy.

A Site-Specific, Sustained-Release Drug Delivery System for Aneurysmal Subarachnoid Hemorrhage.

Nimodipine is the only drug approved for use by the Food and Drug Administration for improving outcome after aneurysmal subarachnoid hemorrhage (SAH). It has less than optimal efficacy, causes dose-limiting hypotension in a substantial proportion of patients, and is administered enterally 6 times daily. We describe development of site-specific, sustained-release nimodipine microparticles that can be delivered once directly into the subarachnoid space or cerebral ventricles for potential improvement in outcome of patients with aneurysmal SAH.

Multifocal FIGO Stage IA1 Squamous Carcinoma of the Cervix: Criteria for Identification, Staging, and its Good Clinical Outcome.

Multifocal squamous cervical carcinomas account for up to 25% of IA1 tumors identified on excisional biopsy, yet there are no uniformly accepted histopathologic criteria for defining and staging these lesions. Here, we use a strict case definition and meticulous specimen processing from colposcopist to pathologist to identify and follow-up 25 cases of multifocal IA1 cervical squamous carcinomas identified in excisional biopsies. We stage these tumors using the dimensions of the largest focus and a minimum of 2 mm between each foci to define multifocality.

Differential effect of estradiol and bisphenol A on and expression in prostate cancer.

Exposure to estrogenic compounds has been shown to epigenetically reprogram the prostate and may contribute to prostate cancer. The goal of this study was to determine the effect of physiological doses of estradiol and bisphenol A (BPA) on the expression of histone modifying enzymes (HMEs) in prostate cancer. Using two human prostate cancer cell lines we examined the expression of , a histone methyltransferase, and , a histone deacetylase, after exposure to estrogen or BPA.

Persistence of deeply sourced iron in the Pacific Ocean.

Biological carbon fixation is limited by the supply of Fe in vast regions of the global ocean. Dissolved Fe in seawater is primarily sourced from continental mineral dust, submarine hydrothermalism, and sediment dissolution along continental margins. However, the relative contributions of these three sources to the Fe budget of the open ocean remains contentious.

Intrathecal application of the nimodipine slow-release microparticle system eg-1962 for prevention of delayed cerebral ischemia and improvement of outcome after aneurysmal subarachnoid hemorrhage.

The effective reduction of delayed cerebral ischemia (DCI), a main contributor for poor outcome following aneurysmal subarachnoid hemorrhage (SAH), remains challenging. Previous clinical trials on systemic pharmaceutical treatment of SAH mostly failed to improve outcome, probably because of insensitive pharmaceutical targets and outcome measures, small sample size, insufficient subarachnoid drug concentrations and also detrimental, systemic effects of the experimental treatment per se. Interestingly, in studies that are more recent, intrathecal administration of nicardipine pellets following surgical aneurysm repair was suggested to have a beneficial effect on DCI and neurological outcome.

Fertility conserving management of early cervical cancer: our experience of LLETZ and pelvic lymph node dissection.

Background: Presently, for those diagnosed with early cervical cancer who wish to conserve their fertility, there is the option of radical trachelectomy. Although successful, this procedure is associated with significant obstetric morbidity. The recurrence risk of early cervical cancer is low and in tumors measuring less than 2 cm; if the lymphatics are negative, the likelihood of parametrial involvement is less than 1%.

"Unresectable" vulval cancers: is neoadjuvant chemotherapy the way forward?

Squamous cell carcinoma of the vulva is an uncommon gynaecological malignancy, but the incidence is increasing. A significant proportion of patients present with locally advanced disease, and management can prove challenging because of the size and/or location of the tumour. Surgery forms the mainstay of treatment, but the role of neoadjuvant therapy in minimizing morbidity is under investigation.

Vulvar reconstruction using the "lotus petal" fascio-cutaneous flap.

Introduction: Vulvar reconstruction using the "lotus petal" fascio-cutaneous flap offers a relatively novel means to restore symmetry and functionality after extirpative gynecologic or oncologic procedures. We sought to assess the success rates and morbidity in a large series of consecutively treated patients.

Methods: We performed a retrospective review of 59 consecutive cases of lotus petal flaps performed at a single institution to more accurately assess success and complication rates.

Late accretion on the earliest planetesimals revealed by the highly siderophile elements.

Late accretion of primitive chondritic material to Earth, the Moon, and Mars, after core formation had ceased, can account for the absolute and relative abundances of highly siderophile elements (HSEs) in their silicate mantles. Here we show that smaller planetesimals also possess elevated HSE abundances in chondritic proportions. This demonstrates that late addition of chondritic material was a common feature of all differentiated planets and planetesimals, irrespective of when they accreted; occurring ≤5 to ≥150 million years after the formation of the solar system.

Intrinsic cardiac origin of human cardiosphere-derived cells.

Aims: Cardiosphere-derived cells (CDCs) are in clinical development as a regenerative cell product which can be expanded ex vivo from patient cardiac biopsies. Cardiosphere-derived cells are clonogenic, exhibit multilineage differentiation, and exert functional benefits in preclinical models of heart failure. The origin of CDCs remains unclear: are these cells endogenous to the heart, or do they arise from cells that populate the heart via blood-borne seeding?

Methods And Results: Right ventricular endomyocardial biopsies were obtained from cardiac transplant recipients (n = 10, age 57 ± 15 years), and CDCs expanded from each biopsy.

Changes in left and right ventricular function of donor hearts during the first year after heart transplantation.

Objective: Expected values of tissue Doppler imaging (TDI) velocities and myocardial performance index (MPI) after heart transplantation (HTx) have not been evaluated. This study assessed left and right ventricular (LV and RV) structure and function during the first year after HTx using these indexes.

Methods And Results: Echocardiography including MPI and TDI systolic (S'), early (E') and late (A') diastolic velocities of RV and LV were performed in 20 donors (mean age 35 ± 13 years) and serially in 20 recipients (mean age 59 ± 9 years) during the first year after HTx.

An agonist of liver X receptor slows valvular disease in a hypercholesterolemia mouse model.

Background And Aim Of The Study: Cholesterol is a known risk factor in aortic stenosis and valve degeneration, and the liver X receptor (LXR) is a regulator of cholesterol and phospholipid metabolism. It was hypothesized that an LXR agonist would reduce calcium and lipid deposition in aortic valves.

Methods: Apolipoprotein E-/- (ApoE-/-) mice fed a high-fat diet were implanted with glutaraldehyde-fixed porcine valve fragments.