Most human transcription factors bind a small subset of potential genomic sites and often use different subsets in different cell types. To identify mechanisms that govern cell-type-specific ...transcription factor binding, we used an integrative approach to study estrogen receptor α (ER). We found that ER exhibits two distinct modes of binding. Shared sites, bound in multiple cell types, are characterized by high-affinity estrogen response elements (EREs), inaccessible chromatin, and a lack of DNA methylation, while cell-specific sites are characterized by a lack of EREs, co-occurrence with other transcription factors, and cell-type-specific chromatin accessibility and DNA methylation. These observations enabled accurate quantitative models of ER binding that suggest tethering of ER to one-third of cell-specific sites. The distinct properties of cell-specific binding were also observed with glucocorticoid receptor and for ER in primary mouse tissues, representing an elegant genomic encoding scheme for generating cell-type-specific gene regulation.
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•Two types of estrogen receptor α binding sites: shared and cell specific•Shared sites are encoded in the genome as high-affinity estrogen response elements•Cell-specific sites rely on interacting factors and depend on genomic context•Cell-specific binding is predicted from DNA sequence and chromatin accessibility
Diffusion‐weighted MRI (DWI) holds potential to improve the detection and biological characterization of breast cancer. DWI is increasingly being incorporated into breast MRI protocols to address ...some of the shortcomings of routine clinical breast MRI. Potential benefits include improved differentiation of benign and malignant breast lesions, assessment and prediction of therapeutic efficacy, and noncontrast detection of breast cancer. The breast presents a unique imaging environment with significant physiologic and inter‐subject variations, as well as specific challenges to achieving reliable high quality diffusion‐weighted MR images. Technical innovations are helping to overcome many of the image quality issues that have limited widespread use of DWI for breast imaging. Advanced modeling approaches to further characterize tissue perfusion, complexity, and glandular organization may expand knowledge and yield improved diagnostic tools.
Level of Evidence: 5
J. Magn. Reson. Imaging 2016 J. Magn. Reson. Imaging 2017;45:337–355.
Summary
Young adults in Western countries are gaining weight faster than their parents and are more likely to gain weight than any other age cohort. Despite this, investigation into the complex young ...adults' food choice motives, which enable and prevent healthy eating, has not been widely investigated. A scoping review was conducted involving an extensive literature search of four major electronic databases: Medline, Embase, PsychInfo and CINAHL. Data were collected from 34 articles: study descriptions numerically analysed and key findings thematically analysed. The key barriers found included: male apathy towards diet; unhealthy diet of friends and family; expected consumption of unhealthy foods in certain situations; relative low cost of unhealthy foods; lack of time to plan, shop, prepare and cook healthy foods; lack of facilities to prepare, cook and store healthy foods; widespread presence of unhealthy foods; lack of knowledge and skills to plan, shop, prepare and cook healthy foods; lack of motivation to eat healthily (including risk‐taking behaviour). The key enablers found included: female interest in a healthy diet; healthy diet of friends and family; support/encouragement of friends and family to eat healthy; desire for improved health; desire for weight management; desire for improved self‐esteem; desire for attractiveness to potential partners and others; possessing autonomous motivation to eat healthy and existence and use of self‐regulatory skills. This research provides evidence that can be used to tailor interventions for healthy eating and overweight and obesity in this population. However, government intervention in addressing food access, affordability, marketing and taxation remains essential to any significant change.
Breast cancer is a heterogeneous disease comprised of four molecular subtypes defined by whether the tumor-originating cells are luminal or basal epithelial cells. Breast cancers arising from the ...luminal mammary duct often express estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor 2 (HER2). Tumors expressing ER and/or PR are treated with anti-hormonal therapies, while tumors overexpressing HER2 are targeted with monoclonal antibodies. Immunohistochemical detection of ER, PR, and HER2 receptors/proteins is a critical step in breast cancer diagnosis and guided treatment. Breast tumors that do not express these proteins are known as "triple negative breast cancer" (TNBC) and are typically basal-like. TNBCs are the most aggressive subtype, with the highest mortality rates and no targeted therapy, so there is a pressing need to identify important TNBC tumor regulators. The signal transducer and activator of transcription 3 (STAT3) transcription factor has been previously implicated as a constitutively active oncogene in TNBC. However, its direct regulatory gene targets and tumorigenic properties have not been well characterized. By integrating RNA-seq and ChIP-seq data from 2 TNBC tumors and 5 cell lines, we discovered novel gene signatures directly regulated by STAT3 that were enriched for processes involving inflammation, immunity, and invasion in TNBC. Functional analysis revealed that STAT3 has a key role regulating invasion and metastasis, a characteristic often associated with TNBC. Our findings suggest therapies targeting STAT3 may be important for preventing TNBC metastasis.
The European Society of Breast Radiology (EUSOBI) established an International Breast DWI working group. The working group consists of clinical breast MRI experts, MRI physicists, and representatives ...from large vendors of MRI equipment, invited based upon proven expertise in breast MRI and/or in particular breast DWI, representing 25 sites from 16 countries. The aims of the working group are (a) to promote the use of breast DWI into clinical practice by issuing consensus statements and initiate collaborative research where appropriate; (b) to define necessary standards and provide practical guidance for clinical application of breast DWI; (c) to develop a standardized and translatable multisite multivendor quality assurance protocol, especially for multisite research studies; (d) to find consensus on optimal methods for image processing/analysis, visualization, and interpretation; and (e) to work collaboratively with system vendors to improve breast DWI sequences. First consensus recommendations, presented in this paper, include acquisition parameters for standard breast DWI sequences including specifications of
b
values, fat saturation, spatial resolution, and repetition and echo times. To describe lesions in an objective way, levels of diffusion restriction/hindrance in the breast have been defined based on the published literature on breast DWI. The use of a small ROI placed on the darkest part of the lesion on the ADC map, avoiding necrotic, noisy or non-enhancing lesion voxels is currently recommended. The working group emphasizes the need for standardization and quality assurance before ADC thresholds are applied. The working group encourages further research in advanced diffusion techniques and tailored DWI strategies for specific indications.
Key Points
• The working group considers breast DWI an essential part of a multiparametric breast MRI protocol and encourages its use.
• Basic requirements for routine clinical application of breast DWI are provided, including recommendations on b values, fat saturation, spatial resolution, and other sequence parameters.
• Diffusion levels in breast lesions are defined based on meta-analysis data and methods to obtain a reliable ADC value are detailed.
Prior studies have suggested a higher prevalence of high grade, ER-negative, HER2-positive, and basal-like carcinomas in young women with breast cancer. However, the precise distribution of poor ...prognostic features in this population remains unclear. We examined the pathologic features and distribution of molecular phenotype in relation to patient age in a large group of young women (≤40 years) with invasive breast cancer. Medical records were reviewed for clinical characteristics, tumor stage, and receptor status. Pathologic features, including those features associated with basal-like carcinomas, were examined by central review. Using tumor grade and biomarker expression, cancers were categorized as luminal A (ER+ and/or PR+ and HER2−, histologic grade 1 or 2); luminal B (ER+ and/or PR+ and HER2+, or ER and/or PR+, HER2− and grade 3); HER2 (ER and PR− and HER2+); and triple negative (ER−, PR−, and HER2−). Among 399 women of ≤40 years, 33% had luminal A tumors, 35% luminal B, 11% HER2 (ER-negative), and 21% triple negative. Compared to published results for all breast cancers, a greater proportion of young women had luminal B tumors, and a lesser proportion had luminal A. There were no significant differences in molecular phenotype, tumor stage or grade among the different age groups of young women. However, this population of young women presented with a different distribution of molecular phenotypes compared to the general population of women with breast cancer. These findings may have implications with regard to the etiology and prognosis of breast cancer in young women.
In the developed world, extreme prematurity is the leading cause of neonatal mortality and morbidity due to a combination of organ immaturity and iatrogenic injury. Until now, efforts to extend ...gestation using extracorporeal systems have achieved limited success. Here we report the development of a system that incorporates a pumpless oxygenator circuit connected to the fetus of a lamb via an umbilical cord interface that is maintained within a closed 'amniotic fluid' circuit that closely reproduces the environment of the womb. We show that fetal lambs that are developmentally equivalent to the extreme premature human infant can be physiologically supported in this extra-uterine device for up to 4 weeks. Lambs on support maintain stable haemodynamics, have normal blood gas and oxygenation parameters and maintain patency of the fetal circulation. With appropriate nutritional support, lambs on the system demonstrate normal somatic growth, lung maturation and brain growth and myelination.
Sea spray is one of the largest natural aerosol sources and plays an important role in the Earth's radiative budget. These particles are inherently hygroscopic, that is, they take-up moisture from ...the air, which affects the extent to which they interact with solar radiation. We demonstrate that the hygroscopic growth of inorganic sea salt is 8-15% lower than pure sodium chloride, most likely due to the presence of hydrates. We observe an increase in hygroscopic growth with decreasing particle size (for particle diameters <150 nm) that is independent of the particle generation method. We vary the hygroscopic growth of the inorganic sea salt within a general circulation model and show that a reduced hygroscopicity leads to a reduction in aerosol-radiation interactions, manifested by a latitudinal-dependent reduction of the aerosol optical depth by up to 15%, while cloud-related parameters are unaffected. We propose that a value of κ
=1.1 (at RH=90%) is used to represent the hygroscopicity of inorganic sea salt particles in numerical models.
Most research addressing needs and concerns of young patients with breast cancer (≤40 years) is retrospective. The HOHO European protocol is a prospective multicenter cohort study of young women with ...newly diagnosed breast cancer, about fertility, psychosocial and quality of life concerns. Here we report the baseline data and focus on predictors of fertility concerns.
Patient surveys and medical record review were used. The baseline survey included sociodemographic, medical and treatment data as well as questions on fertility concerns and preservation strategies. Subscales from the CAncer Rehabilitation Evaluation System-Short Form (CARES-SF) were administered to measure specific quality of life aspects. Uni- and multivariable modeling were used to investigate predictors of greater fertility concern.
Among 297 eligible respondents, 67% discussed fertility issues before starting therapy, 64% were concerned about becoming infertile after treatment, and 15% decided not to follow prescribed therapies. Fifty-four percent of women wished future children before diagnosis; of these, 71% still desired biologic children afterwards. In multivariable analysis, not having children was the only patient characteristic significantly associated with fertility concerns at diagnosis. Twenty-seven percent used fertility preservation strategies. Women who received chemotherapy reported greater physical (p = 0.021) and sexual difficulties (p = 0.039) than women who did not. Women who were married or had a partner reported less psychosocial problems than single women (p = 0.039).
Young women with newly diagnosed breast cancer have several concerns, including, but not limited to, fertility. The HOHO European study provides valuable information to develop targeted interventions.
•Many young women desire future biologic children after breast cancer.•Sixty-four percent of study patients had fertility concerns.•A low proportion of patients took fertility preservation measures.•Women treated with chemotherapy reported greater physical and sexual difficulties.•Women with stable relationships reported less psychosocial problems than single women.
The 4th International Consensus Conference for Breast Cancer in Young Women (BCY4) took place in October 2018, in Lugano, Switzerland, organized by the European School of Oncology (ESO) and the ...European Society of Medical Oncology (ESMO). Consensus recommendations for the management of breast cancer in young women were updated from BCY3 with incorporation of new evidence to inform the guidelines. Areas of research priorities were also identified. This article summarizes the ESO–ESMO international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA).
•Breast cancer in young women should be treated based on stage and biology of disease.•Management of breast cancer in young women requires special considerations including psychological, reproductive and genetic.•Breast cancer in young women necessitates multi-disciplinary care at diagnosis, during treatment and during survivorship.
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