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FIGO stage IVA cervical cancer is a unique diagnosis that conveys a poor prognosis. Despite the use of PET/CT for staging, concurrent chemotherapy, and image-guided brachytherapy, overall survival (OS) in these patients is low. Treatment requires aggressive use of radiotherapy and chemotherapy. We report results of a prospective observational cohort study for patients with de novo stage IVA cervical cancer treated at a single institution.Patients with a new diagnosis of stage IVA cervical cancer treated at an academic institution between 1997 and 2020 were prospectively monitored. Staging was retroactively assigned using the 2018 FIGO staging system. All patients had a PET/CT prior to treatment and were treated with definitive intent radiotherapy with or without chemotherapy. The primary outcome of interest was OS. Secondary outcomes were local control, progression-free survival (PFS), and disease-specific survival (DSS).32 patients with de novo stage IVA cervical cancer were treated with definitive intent radiotherapy. Median follow-up time was 4.27 years (1.31-10.35). 22/32 (69%) of patients received brachytherapy as a part of their definitive treatment, and 28/32 (88%) received chemotherapy concurrently with radiotherapy. 14/32 (44%) of patients had no evidence of disease at last follow-up. The 5-year local control, PFS, DFS, and OS estimates were 79%, 49%, 53%, and 48%, respectively. On multivariate analysis, complete metabolic response was associated with a statistically significant improvement in PFS (HR = 0.256, 95% CI = 0.078-0.836, p = 0.024) and OS (HR = 0.273, 95% CI 0.081-0.919).These data demonstrate a robust OS in patients with stage IVA cervical cancer when treated with definitive chemoradiotherapy.

Purpose Fertility preservation is an increasingly important topic in adolescent and young adult cancer survivorship, yet treatments remain under-utilized, possibly due to lack of awareness and understanding. The internet is widely used by adolescents and young adults and has been proposed to fill knowledge gaps and advance high-quality, more equitable care. As a first step, this study analyzed the quality of current fertility preservation resources online and identified opportunities for improvement. Methods We conducted a systematic analysis of 500 websites to assess the quality, readability, and desirability of website features, and the inclusion of clinically relevant topics. Results The majority of the 68 eligible websites were low quality, written at college reading levels, and included few features that younger patients find desirable. Websites mentioned more common fertility preservation treatments than promising experimental treatments, and could be improved with cost information, socioemotional impacts, and other equity-related fertility topics. Conclusions Currently, the majority of fertility preservation websites are about, but not for, adolescent and young adult patients. High-quality educational websites are needed that address outcomes that matter to teens and young adults, with a priority on solutions that prioritize equity. Implications for Cancer Survivors: Adolescent and young adult survivors have limited access to high-quality fertility preservation websites that are designed for their needs. There is a need for the development of fertility preservation websites that are clinically comprehensive, written at appropriate reading levels, inclusive, and desirable. We include specific recommendations that future researchers can use to develop websites that could better address AYA populations and improve the fertility preservation decision making process.

Spatially-resolved gene expression profiling provides valuable insight into tissue organization and cell-cell crosstalk; however, spatial transcriptomics (ST) lacks single-cell resolution. Current ST analysis methods require single-cell RNA sequencing data as a reference for a rigorous interpretation of cell states and do not utilize associated histology images. Significant sample variation further complicates the integration of ST datasets, which is essential for identifying commonalities across tissues or altered cellular wiring in disease. Here, we present Starfysh, the first comprehensive computational toolbox for joint modeling of ST and histology data, dissection of refined cell states, and systematic integration of multiple ST datasets from complex tissues. Starfysh uses an auxiliary deep generative model that incorporates archetypal analysis and any known cell state markers to avoid the need for a single-cell-resolution reference in characterizing known or novel tissue-specific cell states. Additionally, Starfysh improves the characterization of spatial dynamics in complex tissues by leveraging histology images and enables the comparison of niches as spatial “hubs” across tissues. Integrative analysis of primary estrogen receptor-positive (ER+) breast cancer, triple-negative breast cancer (TNBC), and metaplastic breast cancer (MBC) tumors using Starfysh led to the identification of heterogeneous patient- and disease-specific hubs as well as a shared stromal hub with varying spatial orientation. Our results show the ability to delineate the spatial co-evolution of tumor and immune cell states and their crosstalk underlying intratumoral heterogeneity in TNBC and revealed metabolic reprogramming shaping immunosuppressive hubs in aggressive MBC. Starfysh is publicly available (https://github.com/azizilab/starfysh).

STARFYSH model v 1.0.0 : Spatial Transcriptomic Analysis using Reference-Free auxiliarY deep generative modeling and Shared Histology

The goal of the study was to develop and test an automated short message service (SMS) and web service platform using CareSignal for remote symptom monitoring in a diverse population of patients with cancer. Twenty-eight patients with cancer undergoing radiotherapy were recruited at the start of their treatment regimen. Patients received a weekly SMS symptom survey to assess the severity of the side effects they experienced from treatment. An assessment of patient perceptions of the system in terms of patient-provider communication, feasibility, and overall satisfaction was conducted, finding overall good compliance in a sick patient population and patient willingness to engage with the software in the future.

Background Hormones impact breast tissue proliferation. Studies investigating the associations of circulating hormone levels with mammographic breast density have reported conflicting results. Due to the limited number of studies, we investigated the associations of hormone gene expression as well as their downstream mediators within the plasma with mammographic breast density in postmenopausal women. Methods We recruited postmenopausal women at their annual screening mammogram at Washington University School of Medicine, St. Louis. We used the NanoString nCounter platform to quantify gene expression of hormones (prolactin, progesterone receptor (PGR), estrogen receptor 1 (ESR1), signal transducer and activator of transcription (STAT1 and STAT5), and receptor activator of nuclear factor-kB (RANK) pathway markers (RANK, RANKL, osteoprotegerin, TNFRSF18, and TNFRSF13B) in plasma. We used Volpara to measure volumetric percent density, dense volume, and non-dense volume. Linear regression models, adjusted for confounders, were used to evaluate associations between gene expression (linear fold change) and mammographic breast density. Results One unit increase in ESR1, RANK, and TNFRSF18 gene expression was associated with 8% (95% CI 0–15%, p value = 0.05), 10% (95% CI 0–20%, p value = 0.04) and % (95% CI 0–9%, p value = 0.04) higher volumetric percent density, respectively. There were no associations between gene expression of other markers and volumetric percent density. One unit increase in osteoprotegerin and PGR gene expression was associated with 12% (95% CI 4–19%, p value = 0.003) and 7% (95% CI 0–13%, p value = 0.04) lower non-dense volume, respectively. Conclusion These findings provide new insight on the associations of plasma hormonal and RANK pathway gene expression with mammographic breast density in postmenopausal women and require confirmation in other studies.

Prior to its closure, the base-metal smelter in Flin Flon, Manitoba, Canada was one of the North America's largest mercury (Hg) emission sources. Our project objective was to understand the exchange of Hg between the soil and the air before and after the smelter closure. Field and laboratory Hg flux measurements were conducted to identify the controlling variables and used for spatial and temporal scaling. Study results showed that deposition from the smelter resulted in the surrounding soil being enriched in Hg (up to 99 μg g(-1)) as well as other metals. During the period of smelter operation, air concentrations were elevated (30 ± 19 ng m(-3)), and the soil was a net Hg sink (daily flux: -3.8 ng m(-2) h(-1)). Following the smelter closure, air Hg(0) concentrations were reduced, and the soils had large emissions (daily flux: 108 ng m(-2) h(-1)). The annual scaling of soil Hg emissions following the smelter closure indicated that the landscape impacted by smelter deposition emitted or re-emitted almost 100 kg per year. Elevated soil Hg concentrations and emissions are predicted to continue for hundreds of years before background concentrations are re-established. Overall, the results indicate that legacy Hg deposition will continue to cycle in the environment long after point-source reductions.

The Lake Wabamun area, in Alberta, is unique within Canada as there are four coal-fired power plants within a 500 km(2) area. Continuous monitoring of ambient total gaseous mercury (TGM) concentrations in the Lake Wabamun area was undertaken at two sites, Genesee and Meadows. The data were analyzed in order to characterise the effect of the coal-fired power plants on the regional TGM. Mean concentrations of 1.57 ng/m(3) for Genesee and 1.50 ng/m(3) for Meadows were comparable to other Canadian sites. Maximum concentrations of 9.50 ng/m(3) and 4.43 ng/m(3) were comparable to maxima recorded at Canadian sites influenced by anthropogenic sources. The Genesee site was directly affected by the coal-fired power plants with the occurrence of northwest winds, and this was evident by episodes of elevated TGM, NO(x) and SO(2) concentrations. NO(x)/TGM and SO(2)/TGM ratios of 21.71 and 19.98 microg/ng, respectively, were characteristic of the episodic events from the northwest wind direction. AERMOD modeling predicted that coal-fired power plant TGM emissions under normal operating conditions can influence hourly ground-level concentrations by 0.46-1.19 ng/m(3)(.) The effect of changes in coal-fired power plant electricity production on the ambient TGM concentrations was also investigated, and was useful in describing some of the episodes.

Due to the complex relationships and the necessity for forecasts in atmospheric studies, air pollution modeling is a task for which fuzzy logic methods are amicably suited. This research investigates the ability to predict surface ozone concentration with the use of an automated fuzzy logic method, termed modified learning from examples (MLFE). Hourly ozone concentrations during summer months in the city of Edmonton are predicted with MLFE models and the results are compared to models used by Environment Canada. The root mean square error, mean absolute error and scatter plots are used to compare the results of the MLFE, CHRONOS and CANFIS models. The newly developed model captures the trends in ozone concentrations, and based on the statistical comparisons, the MLFE consistently shows good agreement with the measured data. The MLFE model compares favourably with CHRONOS and CANFIS and is easier to implement.

We present a novel approach to teaching astronomy and planetary sciences, centered on visual images and simulations of planetary objects. The basic idea of the “Thinking Journey” concept is to take the students to other celestial objects as tourists, and to teach science through the observatio of various natural phenomena in these new environments. The power of scientific visualization, through still and dynamic images, makes such a journey an exciting learning experience. The introduction of new technologies (3D animations, virtual reality) greatly enhances the visualization capabilities the teacher can use, allowing him to simulate actual flights over the terrain of other planets and to study them as if observing from a spaceship in orbit. The present program focuses on the study of the Moon and of the planet Mars, by means of observation, interpretation, and comparison to planet Earth. Students learn to recognize geological and atmospheric processes, discuss astronomic phenomena, and discover that the same basic physical laws govern all objects in the solar system.

The Flin Flon, Manitoba copper smelter was Canada's largest point source of mercury emissions until its closure in 2010 after ~80 years of operation. The objective of this study was to understand the variables controlling the local ground-level air mercury concentrations before and after this major point source reduction. Total gaseous mercury (TGM) in air, mercury in precipitation, and other ancillary meteorological and air quality parameters were measured pre- and postsmelter closure, and mercury speciation measurements in air were collected postclosure. The results showed that TGM was significantly elevated during the time period when the smelter operated (4.1 ± 3.7 ng m(-3)), decreased only 20% during the year following its closure, and remained ~2-fold above background levels. Similar trends were observed for mercury concentrations in precipitation. Several lines of evidence indicated that while smelter stack emissions would occasionally mix down to the surface resulting in large spikes in TGM concentrations (up to 61 ng m(-3)), the largest contributor to elevated TGM concentrations before and after smelter closure was from surface-air fluxes from mercury-enriched soils and/or tailings. These findings highlight the ability of legacy mercury, deposited to local landscapes over decades from industrial activities, to significantly affect local air concentrations via emissions/re-emissions.

The present study was conducted for two purposes. The first was to test the relations between the schema of atomism and the concept of density, and to examine the effects of Piagetian stage and M-capacity on these relations. This was accomplished by giving training for the schema of atomism to children at different stages and with varying M- capacities. The second purpose was to test the effects of age (9–10 versus 11–12 years) and IQ (gifted versus nongified children) as variables that would influence the outcome of training. A total of 120 children were tested. The findings were that the effects of the training and the IQ variables were significant while the effect of the age variable was not. When stage and M-capacity were covaried the effects of training and IQ remained significant. Implications for issues of developmental theory and educational practice are discussed.