Additional file 1. Table S1: Detailed summary of RRBS QC parameters and patient data from cohort 1, cohort 2, and normal kidney. Table S2: List of differentially methylated CpGs and the gene(s) they are associated with from cohort 1. Table S3: Full list of GO biological pathways to which the 5929 DMCpGs were associated using GREAT. Table S4: List of kidney-related GO biological pathways to which the 5929 DMCpGs were associated using GREAT. Table S5: Full list of canonical pathways to which the 5744 genes obtained from GREAT were associated in IPA. Table S6: List of differentially methylated CpGs and the gene(s) they are associated with from cohort 2. Table S7: List of 43 CpGs separating aggressive from less aggressive KIRC tumors. Table S8: List of PCR and pyrosequencing primers used in this study.
To investigate the relationship between sleep disturbance, fatigue, and urinary incontinence (UI) and overactive bladder (OAB) symptoms among patients with OAB.Patients who were diagnosed with OAB and age-matched control subjects without OAB were enrolled. Sleep disturbance and fatigue symptoms were assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) short forms. UI and OAB symptoms were assessed using the International Consultation on Incontinence Questionnaire—Urinary Incontinence (ICIQ-UI), the International Consultation on Incontinence Questionnaire—Overactive Bladder (ICIQ-OAB), the Overactive Bladder Questionnaire (OAB-q), the Urogenital Distress Inventory Short Form (UDI-6), and the Incontinence Impact Questionnaire Short Form (IIQ-7). Psychosocial health (depression, anxiety, and perceived stress level) was also assessed.Patients with OAB reported a significantly greater sleep disturbance compared with controls (PROMIS 8b T-scores: 54.3 ± 10.3 vs 43.8 ± 9.2). Patients with OAB also reported a significantly greater fatigue compared with controls (PROMIS 7a T-scores: 54.7 ± 9.6 vs 46.0 ± 6.4). After adjusting for nocturia, the differences in sleep disturbance between OAB and controls became insignificant (P = .21), whereas the differences in fatigue between OAB and controls remained significant (P = .014). Among patients with OAB, there were positive correlations between sleep disturbance and the severity of OAB symptoms (ICIQ-OAB), poorer health-related quality of life (OAB-q QOL), the severity of UI symptoms (ICIQ-UI), greater incontinence impact (IIQ-7), and urinary bother (UDI-6). Positive correlations were also observed between fatigue and worse UI and OAB symptoms and quality of life. Both sleep disturbance and fatigue were associated with poor psychosocial health (depression, anxiety, and higher stress level) among patients with OAB.Sleep disturbance and fatigue are present in substantial percentages of patients with OAB. Among patients with OAB, sleep disturbance and fatigue were associated with more severe UI and OAB symptoms, worse health-related quality of life, and poorer psychosocial health.
With the increasing world population and living standards the demand for mineral and energy resources continues to grow. Future exploration will need to target resources at increasing depths and in areas with cover, and will require an improved understanding of mineral and energy systems and advances in exploration methods and approaches. The Economic Geology Research Centre (EGRU) at James Cook University has organized the FUTORES II conference to summarise recent developments in the exploration and understanding of major types of mineral deposits, to examine the key issues and techniques critical to future minerals and energy exploration, and to discuss the way forward. The conference is being held in tropical Townsville, Queensland, Australia, on 4-7 June 2017. It is following on from the inaugural and highly successful FUTORES conference held in Townsville in 2013.FUTORES II will bring together researchers, explorers and government agencies to address issues related to the sustainable supply and utilisation of mineral and energy resources. The conference has three symposia: the David Groves Symposium - New Insights in Mineral Deposit Understanding, the New Technologies and Approaches in Mineral Exploration Symposium, and the Tectonics, Basins and Resources Symposium. The conference is convened by EGRU, an organisation that was established in 1982 to strengthen the links between research and exploration, to promote exploration-oriented research, and to facilitate knowledge transfer. EGRU has a track record of organising successful major conferences to facilitate the exchange of knowledge and ideas and to stimulate new ideas for cutting-edge research and exploration. The Hydrothermal Odyssey conference in 2001, and the STOMP (Structure, Tectonics and Ore Mineralization Processes) conference in 2005, both attracted over 200 participants. In 2009 EGRU collaborated with the SGA to host the tenth biennial SGA conference in Townsville - Smart Science for Exploration and Mining - which attracted over 480 delegates from around the world. In 2013 the first FUTORES conference attracted around 250 participants from 15 countries. FUTORES II is looking to be equally successful and has so far attracted around 265 registrants. This conference abstract volume contains 134 abstracts covering a wide range of topics related to mineral and energy resources, tectonics and metallogenesis. The abstracts have been reviewed and edited by the Editorial Committee and, in this volume, are organised in alphabetical order of the first author. We thank the delegates for their abstracts and the reviewers for ensuring the quality of the abstract volume.
414 Background: While mutations in PBRM1 (~40%) and BAP1(~10%) are associated with clinical outcomes and pathologic features in clear cell renal cell carcinoma (ccRCC), the impact of protein expression of these genes remains unknown. Herein, we quantify PBRM1/BAP1 protein expression in a large cohort of patients with localized ccRCC and associate expression with cancer-specific survival (CSS) and pathologic features. Methods: We utilized the Mayo Clinic Renal Registry and identified 1,416 patients who underwent nephrectomy to treat clinically localized ccRCC between 1/3/1990 and 4/14/2009. We used immunohistochemistry (IHC) to detect PBRM1/BAP1 expression, and a central pathologist blinded to the outcomes scored tumors as either positive or negative. Tumors with heterogeneous or equivocal staining were excluded from this analysis. We generated Cox proportional hazard regression models for associations with ccRCC-SS, and we employed Mann-Whitney U tests for associations with pathologic features. Results: Of the 1,416 samples, 1,232 (87%) were PBRM1/BAP1 positive or negative, 163 (11%) had heterogeneous staining, and 21 (1%) could not be assessed. The distribution and association of PBRM1/BAP1 phenotypes with clinical outcomes are listed in the table below. PBRM1+/BAP1+ tumors have the best CSS, and PBRM1-/BAP1- have the worst. In addition, PBRM1/BAP1 expression strongly associated with the tumor size, stage, grade, and tumor necrosis (p<0.0001). Conclusions: This study is the first and largest to quantify PRBM1/BAP1 protein expression in ccRCC tumors. We were able to quantify PBRM1/BAP1 through IHC in the vast majority of tumors (87%), and PRBM1/BAP1 expression strongly associates with both CSS and pathologic tumor characteristics. Our data confirms our previous findings of the importance of PRBM1/BAP1 in the molecular pathogenesis of ccRCC. [Table: see text]
Hidradenocarcinoma is a rare malignancy of the sweat glands with only a few cases reported in literature. The management of these tumors is based on the extent of disease with local disease managed with surgical resection. These can tumors carry a high potential of lymphatic and vascular spread and local and distant metastases are not uncommon. Given the rarity of the tumor and lack of genetic and clinical data about these tumors, there is no consensus on the proper management of metastatic disease. Here in we report the first case of metastatic hidradenocarcinoma with detailed molecular profiling including whole exome sequencing. We identified mutations in multiple genes including two that are potentially targetable: PTCH1 and TCF7L1. Further work is necessary to not only confirm the presence of these mutations but also to confirm the clinical significance.
