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Metastatic urothelial carcinoma (mUC) is a lethal cancer, with limited therapeutic options. Large-scale studies in early settings provided critical insights into the genomic and transcriptomic characteristics of non-metastatic UC. The genomic landscape of mUC remains however unclear. Using Whole Exome (WES) and mRNA sequencing (RNA-seq) performed on metastatic biopsies from 111 patients, we show that driver genomic alterations from mUC were comparable to primary UC (TCGA data). APOBEC, platin, and HRD mutational signatures are the most prevalent in mUC, identified in 56%, 14%, and 9% of mUC samples, respectively. Molecular subtyping using consensus transcriptomic classification in mUC shows enrichment in neuroendocrine subtype. Paired samples analysis reveals subtype heterogeneity and temporal evolution. We identify potential therapeutic targets in 73% of mUC patients, of which FGFR3 (26%), ERBB2 (7%), TSC1 (7%), and PIK3CA (13%) are the most common. NECTIN4 and TACSTD2 are highly expressed regardless of molecular subtypes, FGFR3 alterations and sites of metastases. Metastasis of urothelial carcinoma remains incurable due to insufficient treatment options for advanced disease. Here, the authors combine whole exome sequencing and RNA-seq from metastatic biopsies, and show temporal evolution when compared with primary tumour.

Background High tumor mutational burden (TMB) was reported to predict the efficacy of immune checkpoint inhibitors (ICIs). Pembrolizumab, an anti-PD-1, received FDA-approval for the treatment of unresectable/metastatic tumors with high TMB as determined by the FoundationOne®CDx test. It remains to be determined how TMB can also be calculated using other tests. Results FFPE/frozen tumor samples from various origins were sequenced in the frame of the Institut Curie (IC) Molecular Tumor Board using an in-house next-generation sequencing (NGS) panel. A TMB calculation method was developed at IC (IC algorithm) and compared to the FoundationOne® (FO) algorithm. Using IC algorithm, an optimal 10% variant allele frequency (VAF) cut-off was established for TMB evaluation on FFPE samples, compared to 5% on frozen samples. The median TMB score for MSS/POLE WT tumors was 8.8 mut/Mb versus 45 mut/Mb for MSI/POLE-mutated tumors. When focusing on MSS/POLE WT tumor samples, the highest median TMB scores were observed in lymphoma, lung, endometrial, and cervical cancers. After biological manual curation of these cases, 21% of them could be reclassified as MSI/POLE tumors and considered as “true TMB high.” Higher TMB values were obtained using FO algorithm on FFPE samples compared to IC algorithm (40 mut/Mb [10–3927] versus 8.2 mut/Mb [2.5–897], p  < 0.001). Conclusions We herein propose a TMB calculation method and a bioinformatics tool that is customizable to different NGS panels and sample types. We were not able to retrieve TMB values from FO algorithm using our own algorithm and NGS panel.

\"This edited collection by leading data scientists and higher ed leaders explains what data analytics can contribute to improving the administration of colleges and universities. The book includes several case studies of effective data analytics as applied to the areas of admissions, enrollment and retention, student life and engagement, academic advising, and learning assessment\"--. Contents: Data analytics and the imperatives for data-informed decision-making in higher education / Karen L. Webber and Henry Zheng -- Big data and the transformation of decision-making in higher education / Braden Hosch -- Predictive analytics and its uses in higher education / Henry Zheng and Ying Zhou -- Limitations in data analytics : potential misuse and misunderstanding in data reports and visualizations / Karen L. Webber and Jillian Morn -- Guiding your organization's data strategy : the roles of university senior leaders and trustees in strategic analytics / Gail Marsh and Rachit Thariani -- Data governance, data stewardship and the building of an analytics organizational culture / Rana Glasgal and Valentina Nestor -- Data analytics and decision-making in admissions and enrollment management / Tom Gutman and Brian P. Hinote -- Predictive analytics, academic advising, early alerts, and student success / Timothy M. Renick -- Constituent relationship management and student engagement lifecycle / Cathy O'Bryan, Chris Tompkins, and Carrie Hancock Marcinkevage -- Learning analytics for learning assessment : complexities in efficacy, implementation, and broad use / Carrie Klein, Jaime Lester, Huzefa Rangwala, and Aditya Johri -- Using data analytics to support institutional financial and operational efficiency / Lindsay K. Wayt, Susan M. Menditto, J. Michael Gower, and Charles Tegen -- Data-informed decision-making and the pursuit of analytics maturity in higher education / Karen L. Webber and Henry Y. Zheng.

We prove an equivariant version of the classical Menger-Nöbeling theorem regarding topological embeddings: Whenever a group G acts on a finite-dimensional compact metric space X , a generic continuous equivariant function from X into$$([0,1]^r)^G$$( [ 0 , 1 ] r ) G is a topological embedding, provided that for every positive integer N the space of points in X with orbit size at most N has topological dimension strictly less than$$\\frac{rN}{2}$$rN 2 . We emphasize that the result imposes no restrictions whatsoever on the acting group G (beyond the existence of an action on a finite-dimensional space). Moreover if G is finitely generated then there exists a finite subset$$F\\subset G$$F ⊂ G so that for a generic continuous map$$h:X\\rightarrow [0,1]^{r}$$h : X → [ 0 , 1 ] r , the map$$ h^{F}:X\\rightarrow ([0,1]^{r})^{F}$$h F : X → ( [ 0 , 1 ] r ) F given by$$x\\mapsto (f(gx))_{gın F}$$x ↦ ( f ( g x ) ) g ∈ F is an embedding. This constitutes a generalization of the Takens delay embedding theorem into the topological category.

We prove an equivariant version of the classical Menger-Nöbeling theorem regarding topological embeddings: Whenever a group G acts on a finite-dimensional compact metric space X , a generic continuous equivariant function from X into ( [ 0 , 1 ] r ) G is a topological embedding, provided that for every positive integer N the space of points in X with orbit size at most N has topological dimension strictly less than rN 2 . We emphasize that the result imposes no restrictions whatsoever on the acting group G (beyond the existence of an action on a finite-dimensional space). Moreover if G is finitely generated then there exists a finite subset F ⊂ G so that for a generic continuous map h : X → [ 0 , 1 ] r , the map h F : X → ( [ 0 , 1 ] r ) F given by x ↦ ( f ( g x ) ) g ∈ F is an embedding. This constitutes a generalization of the Takens delay embedding theorem into the topological category.

De-identification of medical images intended for research is a core requirement for data sharing initiatives, particularly as the demand for data for artificial intelligence (AI) applications grows. The Center for Biomedical Informatics and Information Technology (CBIIT) of the United States National Cancer Institute (NCI) convened a two half-day virtual workshop with the intent of summarizing the state of the art in de-identification technology and processes and exploring interesting aspects of the subject. This paper summarizes the highlights of the second day of the workshop, the recordings and presentations of which are publicly available for review. The topics covered included pathology whole slide image de-identification, de-facing, the role of AI in image de-identification, and the NCI Medical Image De-Identification Initiative (MIDI) datasets and pipeline.

Abstract BackgroundChildren with chronic kidney disease (CKD) generally have worse educational and psychosocial outcomes compared with their healthy peers. This can impair their ability to manage their treatment, which in turn can have long-term health consequences through to adulthood. We attempted to capture the experiences of children with CKD and to describe the perspectives of their parents and caregivers on access to educational and psychosocial support.MethodsChildren with CKD (n = 34) and their caregivers (n = 62) were sampled via focus groups from pediatric hospitals in Australia, Canada, and the USA. Sixteen focus groups were convened and the transcripts were analyzed thematically.ResultsWe identified four themes: disruption to self-esteem and identity (emotional turmoil of adolescence, wrestling with the sick self, powerlessness to alleviate child’s suffering, balancing normality and protection); disadvantaged by lack of empathy and acceptance (alienated by ignorance, bearing the burden alone); a hidden and inaccessible support system (excluded from formal psychological support, falling behind due to being denied special considerations); and building resilience (finding partners in the journey, moving towards acceptance of the illness, re-establishing childhood).ConclusionsChildren with CKD and their caregivers encountered many barriers in accessing psychosocial and educational support and felt extremely disempowered and isolated as a consequence. Improved availability and access to psychosocial and educational interventions are needed to improve the wellbeing and educational advancement of children with CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

[...] population ageing provides opportunities to rethink health policy for the benefi t of all-old and young. The failure of national governments and international agencies to prioritise these cheap and eff ective treatments represents a missed opportunity to reduce mortality, illness, and disability on an unprecedented scale.

Quotes: QUOTE OF DAY. 'They have brought this upon themselves. They forced the federal government to take action...They have no legal right at all, and I think not much moral right.' - Gregory Craig, attorney for the Elian Gonzalez' father, Juan Miguel Gonzalez, on requests by Elian's Miami relatives to see the boy. (A02 ALL) Washington-Miami relatives of Elian Gonzalez, joined by mostly Republican leaders, yesterday attacked the Clinton administration's predawn snatch of the young shipwreck survivor as unlawful brutality, but the Justice Department said the only valid criticism was that it had waited too long. One day after the dramatic seizure by 151 agents, which provoked disturbances into the night in Miami, 6-year-old Elian spent Easter with his father-Juan Miguel Gonzalez-his stepmother and half-brother at a sealed-off Andrews Air Force base outside Washington.