Diet Content and Overlap of Six Species of Turtle Among the Wabash River

A community of six species of turtles from the Wabash River and its backwaters was studied to determine diet composition of each species and amount of dietary overlap among species. Species studied included: Trionyx muticus, Trionyx spiniferus, and Graptemys ouachitensis in the river; Trachemys scripta and Chrysemys picta in both the river and backwaters; and Chelydra serpentina in the backwaters only. Trionyx muticus, T. spiniferus, and G. ouachitensis all belong to a guild that specializes on aquatic insects. The highest diet overlap (69.6%) was between the two softshells, T. muticus and T. spiniferus. Coexistence is possible because T. spiniferus are rare and there is some indication that they are feeding in different microhabitats, with T. spiniferus utilizing the bottom of the river and T. muticus feeding in the water column. Moderate overlap occurred between T. muticus and G. ouachitensis, but 58% of the diet differed. Trachemys scripta are able to coexist with the other riverine species because they belong to a different guild. This species is highly herbivorous (93%) in the river, more so than in the sloughs (69%). Turtles occurring in the river had more diet overlap with T. scripta occurring in sloughs than with those in the riverine habitat. This could be due to niche partitioning in the river to reduce competition. The remaining species encountered showed little diet overlap with any other turtle. Chelydra serpentina were piscivorous, while Chrysemys picta were omnivorous. Turtle species of this community are able to coexist by feeding on different food items, foraging in different areas, and by occurring in small numbers

Land Transport Emergency Response Technology Report

Sandia National Laboratories was tasked by the Japan Nuclear Cycle Development Institute (JNC) to provide assistance in developing an emergency response plan for radioactive material transportation activities. Those tasks included compiling radioactive materials (RAM) transportation accident data from the open literature and databases, investigating emergency response plans for radioactive materials transport in the United States, and developing specific recommendations for the JNC' nuclear material transport emergency response plan, based on information gathered during the first two tasks. These recommendations include developing a RAM database, a public transparency Internet website, an emergency response infrastructure designed specifically for transportation needs, and a clear set of directives to provide authority in the case of transportation accidents or incidents involving RAM

Androgen receptor as a mediator and biomarker of radioresistance in triple-negative breast cancer.

Increased rates of locoregional recurrence have been observed in triple-negative breast cancer despite chemotherapy and radiation therapy. Thus, approaches that combine therapies for radiosensitization in triple-negative breast cancer are critically needed. We characterized the radiation therapy response of 21 breast cancer cell lines and paired this radiation response data with high-throughput drug screen data to identify androgen receptor as a top target for radiosensitization. Our radiosensitizer screen nominated bicalutamide as the drug most effective in treating radiation therapy-resistant breast cancer cell lines. We subsequently evaluated the expression of androgen receptor in >2100 human breast tumor samples and 51 breast cancer cell lines and found significant heterogeneity in androgen receptor expression with enrichment at the protein and RNA level in triple-negative breast cancer. There was a strong correlation between androgen receptor RNA and protein expression across all breast cancer subtypes (R2 = 0.72, p < 0.01). In patients with triple-negative breast cancer, expression of androgen receptor above the median was associated with increased risk of locoregional recurrence after radiation therapy (hazard ratio for locoregional recurrence 2.9-3.2)) in two independent data sets, but there was no difference in locoregional recurrence in triple-negative breast cancer patients not treated with radiation therapy when stratified by androgen receptor expression. In multivariable analysis, androgen receptor expression was most significantly associated with worse local recurrence-free survival after radiation therapy (hazard ratio of 3.58) suggesting that androgen receptor expression may be a biomarker of radiation response in triple-negative breast cancer. Inhibition of androgen receptor with MDV3100 (enzalutamide) induced radiation sensitivity (enhancement ratios of 1.22-1.60) in androgen receptor-positive triple-negative breast cancer lines, but did not affect androgen receptor-negative triple-negative breast cancer or estrogen-receptor-positive, androgen receptor-negative breast cancer cell lines. androgen receptor inhibition with MDV3100 significantly radiosensitized triple-negative breast cancer xenografts in mouse models and markedly delayed tumor doubling/tripling time and tumor weight. Radiosensitization was at least partially dependent on impaired dsDNA break repair mediated by DNA protein kinase catalytic subunit. Our results implicate androgen receptor as a mediator of radioresistance in breast cancer and identify androgen receptor inhibition as a potentially effective strategy for the treatment of androgen receptor-positive radioresistant tumors

Identification of a Novel Large Multigene Deletion and a Frameshift Indel in PDE6B as the Underlying Cause of Early-Onset Recessive Rod-Cone Degeneration

A family, with two affected identical twins with early-onset recessive inherited retinal degeneration, was analyzed to determine the underlying genetic cause of pathology. Exome sequencing revealed a rare and previously reported causative variant (c.1923_1969delinsTCTGGG; p.Asn643Glyfs*29) in th

Depressed mood predicts pulmonary rehabilitation completion among women, but not men

SummaryBackgroundAs many as 30% of patients who start pulmonary rehabilitation (PR) fail to complete it, and depressed mood has been associated with PR non-completion. Depression is more common in women than men with COPD and historically women with COPD have been under studied. However, no studies to date have investigated gender-specific predictors of PR completion.MethodsThe study included 111 patients with COPD who enrolled in a community based outpatient PR program in Providence, RI. Patients who attended 20 or more sessions were designated “completers”. Depression was measured using the CES-D. Logistic regression models were evaluated to test depressed mood as a predictor of PR completion. Analyses controlled for demographic and health variables found to differ between completers and non-completers.ResultsPatients were 95% white and 49.5% women, and 74% had a GOLD stage ≥3. Sixty-eight percent of patients were PR completers. A logistic regression model, showed that lower depressed mood independently predicted PR completion across all patients (adjusted OR = 0.92, p = .002). In gender-stratified analyses, lower depressed mood was an independent predictor of PR completion for women (adjusted OR = .91, p = .024) but not men (adjusted OR = .97, p = .45). Greater 6-min walk test distance was also an independent predictor of PR completion among women.ConclusionDepressed mood is an important predictor of completion of community based PR among women. Screening and brief treatment of depression should be considered in practice

Identification of altered growth phenotypes in human breast cancer cells using cell culture methods that support growth of normal and neoplastic mammary epithelial cells

Over the past several years our laboratory has been studying factors that regulate proliferation of normal human mammary epithelial (HME) cells in order to better understand the alterations in cellular growth control mechanisms that occur during breast cancer development. To perform these experiments, we have either modified or developed cell culture methods for the isolation and growth of normal and neoplastic HME cells obtained from patient biopsy specimens. From these studies we have found that normal HME cells of the luminal lineage (the lineage from which breast cancer arises) have strict requirements for specific growth factor combinations for in vitro growth. Furthermore, these cells have a finite proliferative lifespan in culture. By contrast, human breast cancer (HBC) cells isolated from primary and metastatic sites exhibit many growth phenotypes that distinguish them from normal cells. First, whereas normal HME cells proliferate in culture with doubling times of 24–36 hours, HBC cells obtained from patient samples proliferate with doubling times of 100–200 hours. These proliferation kinetics are consistent with the rate at which these cells proliferate in vivo . This observation indicates that there are fundamental differences in growth regulation between normal and neoplastic mammary epithelial cells. Second, the majority of HBC cells isolated from human samples exhibit an extended proliferative lifespan in culture. Whereas normal HME cells undergo cell senescence after 15–20 population doublings, HBC cells often give rise to cell lines with indefinite proliferative potential. Third, HBC cells become independent of growth factors which are strictly required by normal HME cells for growth under defined conditions. In our experiments, escape from the requirements of exogenous epidermal growth factor (EGF) has been observed in cells from four patient-derived samples. Interestingly, the cellular mechanisms by which cells become EGF-independent for growth is different in cell lines isolated from different patients. Two breast cancer cell lines isolated in our laboratory proliferate continuously in serum-free, EGF-free medium and do not express EGF receptors. Thus, these cells are completely independent of EGF-mediated signalling pathways for their growth. A third cell line isolated in our laboratory has an amplified EGF receptor gene and overexpresses EGF receptor protein. Western blot analysis indicates that the tyrosine residues of the EGF receptor proteins in these cells are highly phosphorylated. These cells do not secrete any EGF-like growth factors that could be activating the receptors in an autocrine manner. This suggests that amplification and overexpression of EGF receptors can yield constitutively activated receptors that provide a mitogenic signal in the absence of a stimulatory ligand. Finally, we have analyzed the EGF requirements of human breast cancer cells that overexpress the erb B-2 receptor as a result of gene amplification. The results of these experiments indicated that overexpression of erb B-2 is, by itself, insufficient to overcome the EGF requirements of human breast cancer cells. However, one cell line that has a 15- to 20-fold amplification of erb B-2 and which expresses very high levels of tyrosine phosphorylated erb B-2 protein, is EGF-independent for growth. Thus, cell culture systems that allow proliferation of normal HME cells and HBC cells under well-defined culture conditions can result in identification of altered growth phenotypes associated with the neoplastic progression of breast cancer cells. In addition, isolation of cells exhibiting altered growth phenotypes may lead to insights as to the genetic mechanisms resulting in altered growth regulation in breast cancer cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38456/1/240531151_ftp.pd

The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression.

Molecular classification of cancers into subtypes has resulted in an advance in our understanding of tumour biology and treatment response across multiple tumour types. However, to date, cancer profiling has largely focused on protein-coding genes, which comprise <1% of the genome. Here we leverage a compendium of 58,648 long noncoding RNAs (lncRNAs) to subtype 947 breast cancer samples. We show that lncRNA-based profiling categorizes breast tumours by their known molecular subtypes in breast cancer. We identify a cohort of breast cancer-associated and oestrogen-regulated lncRNAs, and investigate the role of the top prioritized oestrogen receptor (ER)-regulated lncRNA, DSCAM-AS1. We demonstrate that DSCAM-AS1 mediates tumour progression and tamoxifen resistance and identify hnRNPL as an interacting protein involved in the mechanism of DSCAM-AS1 action. By highlighting the role of DSCAM-AS1 in breast cancer biology and treatment resistance, this study provides insight into the potential clinical implications of lncRNAs in breast cancer

Racial Differences in Treatments and Toxicity in Non-Small Cell Lung Cancer Patients Treated with Thoracic Radiation Therapy

Background: Racial disparities are of particular concern for lung cancer patients given historical differences in surgery rates for African-American lung cancer patients that resulted in lower overall survival and higher recurrence rates compared with rates in White patients. Objectives: The overall objective of this study was to examine racial differences in thoracic radiation therapy (RT) treatments and toxicities in a large cohort of patients from a multi-institutional consortium database of non-small cell lung cancer (NSCLC) patients. Methods: A large multi-institutional statewide prospectively collected patient-level database of locally advanced (stage II or III) NSCLC patients who received thoracic RT from March 2012 to November 2019 was analyzed to assess the associations between race and treatment and toxicity variables. Race (White or African-American) was defined by patient self-report or if not available then by the electronic medical record system classification. Race categories other than White or African-American comprised a small minority of patients and were excluded from this analysis. Patient-reported toxicity was determined by validated tools including the Functional Assessment of Cancer Therapy-Lung (FACT-L) quality of life instrument. Provider-reported toxicity was determined by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Uni-variable and multi-variable regression models were then fitted to assess relationships between primary outcomes by race and indicators of high-quality treatment and secondary analysis of symptoms. Spearman rank correlation coefficients were calculated between provider reported toxicity and similar patient reported outcomes for each race category. Results: A total of 1441 patients from 24 institutions with mean age of 68 years (range 38-94) were evaluated; 226 patients were African-American, of whom 61% were treated at three facilities. Race was not significantly associated with RT treatment approach, use of concurrent chemotherapy, or the dose to the planning target volume (PTV) or organs at risk including the heart and lungs. However, there was increased patient-reported general pain in African-American patients (compared with White patients) at several time points including pre-RT (22% (vs 15%), P=0.02) and at the end of RT (30% (vs 17%), P=0.001). African-American patients were significantly less likely to have provider-reported grade 2+ radiation pneumonitis (odds ratio (OR) 0.36, P=0.03), despite similar levels of patient-reported respiratory toxicities such as cough and shortness of breath and even after controlling for known patient and treatment-related factors. Correlation coefficients between provider- and patient-reported toxicities were generally similar across race categories. Conclusions: In this large multi-institutional observational study, we reassuringly found no evidence of differences in radiation treatment or chemotherapy approaches by race, in contrast to historical differences by race in surgical care that led to worse survival and outcomes in minority race patients. However, we did unexpectedly find that African-American race was associated with lower odds of provider-reported grade 2+ radiation pneumonitis despite similar patient-reported toxicities of shortness of breath and cough. There are several possibilities for this finding including that pneumonitis is a multifactorial diagnosis that relies on clinical as well as radiologic information and clinical information alone may be insufficient. The Spearman correlation analysis also revealed stronger correlations between patient- and provider-reported toxicities in White patients compared with African-American patients, particularly for trouble swallowing/esophagitis. These findings together for pneumonitis and esophagitis discouragingly suggest possible under-recognition of symptoms in black patients. Further investigation is now warranted to better understand how these findings impact the care of racially diverse lung cancer patients