bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B008: Activation of the bile acid pathway promotes tumorigenesis in clear cell renal cell carcinoma
Authors: Riscal Romain , Gardner Sarah , Carens Madeleine , Mesaros Clementina , Xu Jimmy , Coffey Nate , Davis Leah , Vogt Austin , Olia Adam , Finan Jennifer , Godfrey Jason , Blair Ian , Keith Brian , Marmorstein Ronen , Skuli Nicolas , Simon Celeste 
Published: August 2023

Abstract
Clear cell renal cell carcinoma (ccRCC) incidence has risen steadily over the last decade. We and others have demonstrated that elevated lipid uptake and storage is required for ccRCC cell viability; however, the role of stored cholesterol, the most abundant component in ccRCC intracellular lipid droplets, remains unclear. We recently demonstrated that ccRCC cells acquire exogenous cholesterol through the HDL receptor SCARB1, inhibition or suppression of which induces apoptosis. Here, we show that elevated expression of 3 beta-hydroxy steroid dehydrogenase type 7 (HSD3B7), which metabolizes cholesterol-derived oxysterols in the bile acid biosynthetic pathway, is essential for ccRCC cell survival. Repressing HSD3B7 expression genetically, or treating ccRCC cells with a newly identified HSD3B7 inhibitor, resulted in toxic oxysterol accumulation, impaired proliferation, and increased apoptosis in vitro and in vivo. These data demonstrate that bile acid synthesis regulates cholesterol homeostasis in ccRCC and identifies HSD3B7 as a plausible therapeutic target.
Citation Format: Romain Riscal, Sarah Gardner, Madeleine Carens, Clementina Mesaros, Jimmy Xu, Nate Coffey, Leah Davis, Austin Vogt, Adam Olia, Jennifer Finan, Jason Godfrey, Ian Blair, Brian Keith, Ronen Marmorstein, Nicolas Skuli, Celeste Simon. Activation of the bile acid pathway promotes tumorigenesis in clear cell renal cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Advances in Kidney Cancer Research; 2023 Jun 24-27; Austin, Texas. Philadelphia (PA): AACR; Cancer Res 2023;83(16 Suppl):Abstract nr B008.
Abstract B011: An atlas of cellular heterogeneity in primary and metastatic renal cell carcinomas
Authors: Madrigal Ariel , Kim Minjun , Osakwe Adrien , Lu Tianyuan , Mehrjoo Zohreh , Moslemi Elham , Farouni Rick , Morales-Soto Larisa , Wang Yu Chang , Dankner Matthew , Djambazian Haig , Petrecca Kevin , Spicer Jonathan , Brimo Fadi , Siegel Peter , Park Morag , Ragoussis Jiannis , Tanguay Simon , Riazalhosseini Yasser , Najafabadi Hamed S. 
Published: August 2023

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR005) of the Conference Program/Proceedings.
Citation Format: Ariel Madrigal, Minjun Kim, Adrien Osakwe, Tianyuan Lu, Zohreh Mehrjoo, Elham Moslemi, Rick Farouni, Larisa Morales-Soto, Yu Chang Wang, Matthew Dankner, Haig Djambazian, Kevin Petrecca, Jonathan Spicer, Fadi Brimo, Peter Siegel, Morag Park, Jiannis Ragoussis, Simon Tanguay, Yasser Riazalhosseini, Hamed S. Najafabadi. An atlas of cellular heterogeneity in primary and metastatic renal cell carcinomas [abstract]. In: Proceedings of the AACR Special Conference: Advances in Kidney Cancer Research; 2023 Jun 24-27; Austin, Texas. Philadelphia (PA): AACR; Cancer Res 2023;83(16 Suppl):Abstract nr B011.
Abstract IA004: Identification of potential new therapeutic targets in kidney cancer
Authors: Zhang Qing 
Published: August 2023

Abstract
VHL is the most important tumor suppressor in clear cell renal cell carcinoma (ccRCC). In the majority of ccRCC, as a result of VHL loss, HIF2a stabilization is sufficient and necessary for promoting ccRCC tumor growth. Despite the development of HIF2a specific inhibitors, the intrinsic and extrinsic resistance do exist, highlighting the importance of identifying additional therapeutic vulnerabilities in ccRCC. We have recently performed some genome-wide screening and identified new signaling pathways regulated by VHL, including ZHX2 and SFMBT1 that play important roles in ccRCC. In addition, we also identified some synthetic lethality binding partners for VHL loss in kidney cancer, including TBK1. However, it is challenging to target TBK1 in clinical practice due to lack of selectivity for TBK1 inhibitors and its role involved in innate immune signaling. To overcome this difficulty, one approach would be to identify a critical upstream regulator of TBK1 that can be targeted therapeutically, especially in ccRCC displaying hyper-activated TBK1 activity due to VHL loss. We have performed a kinome-wide screening and identified Doublecortin like kinase 2 (DCLK2), an enigmatic kinase involved in neuronal survival and growth cone regeneration upon injury, as a novel TBK1 regulator in ccRCC. Our functional assays demonstrate that DCLK2 is necessary and sufficient to promote ccRCC tumorigenesis through activating TBK1. In addition, we also characterized a DCLK2 short isoform (DCLK2203) that play a predominant role in ccRCC tumorigenesis. Our work suggests that DCLK2 is a novel TBK1 activator and potential therapeutic target in ccRCC.
Citation Format: Qing Zhang. Identification of potential new therapeutic targets in kidney cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Kidney Cancer Research; 2023 Jun 24-27; Austin, Texas. Philadelphia (PA): AACR; Cancer Res 2023;83(16 Suppl):Abstract nr IA004.
Abstract IA009: Development of HIF2 inhibitors: Bench to bedside and back
Authors: Brugarolas James 
Published: August 2023

Abstract
Arguably the most important driver of clear cell renal cell carcinoma (ccRCC), HIF2a was traditionally regarded as undruggable. However, structural analyses at UT Southwestern Medical Center found a vulnerability leading to the identification of small molecule inhibitors, and eventually the development of highly related PT drugs by Peloton Therapeutics (PT2385 and PT2977, also called belzutifan). PT drugs bind to HIF2a and induce a conformational change that triggers its dissociation from HIF1b, thereby inhibiting DNA binding and gene transactivation. PT drugs have shown activity in patients, but resistance develops over time. Resistance mutations have been identified, initially in preclinical models, and subsequently in patients. This has spurred the development of second-generation inhibitors, including siRNA-based therapeutics. Recently, we reported a tumor-directed HIF2a-targeting siRNA drug (siHIF2) developed by Arrowhead Pharmaceuticals that effectively depleted both wild-type and mutant HIF2a. siHIF2 showed activity against ccRCC in preclinical models and in patients. Overall, these studies establish HIF2a as a core dependency and therapeutic target, and set a paradigm for tumor-directed RNA-based therapeutics in cancer.
Citation Format: James Brugarolas. Development of HIF2 inhibitors: Bench to bedside and back [abstract]. In: Proceedings of the AACR Special Conference: Advances in Kidney Cancer Research; 2023 Jun 24-27; Austin, Texas. Philadelphia (PA): AACR; Cancer Res 2023;83(16 Suppl):Abstract nr IA009.
Abstract IA013: A zebrafish model for VHL and hypoxia signaling
Authors: van Rooijien Ellen , Schulte-Merker Stefan , Logister Ive , Voest Emile , Giles Rachel 
Published: August 2023

Abstract
he von Hippel-Lindau (VHL) tumor suppressor gene encodes an adaptor protein that regulates an array of transcription-dependent and -independent cellular and physiological processes. Mutations in this gene cause VHL disease, congenital polycythemia, renal cell carcinoma (RCC), and several other sporadic tumor types. Although different animal models for VHL disease have been adapted, the zebrafish VHL model offers distinct opportunities. Zebrafish vhl mutants develop key aspects of the human disease condition, including activation of the hypoxia-inducible factor (HIF) signaling pathway, polycythemia, excessive neovascularization, macular edema, and pronephric abnormalities resembling early stages of RCC. The zebrafish vhl model offers a platform for the identification of genetic pathways, modifiers, and interactors involved in the development of VHL-associated neoplasms. Vhl mutants represent a unique and clinically relevant in vivo model for studying genotype-phenotype correlations and the identification of prognostic biomarkers. The amenability of zebrafish for chemical genetic screens will not only be helpful to identify novel therapeutic agents but may also reveal novel processes that require regulation by VHL.
Citation Format: Ellen van Rooijien, Stefan Schulte-Merker, Ive Logister, Emile Voest, Rachel Giles. A zebrafish model for VHL and hypoxia signaling [abstract]. In: Proceedings of the AACR Special Conference: Advances in Kidney Cancer Research; 2023 Jun 24-27; Austin, Texas. Philadelphia (PA): AACR; Cancer Res 2023;83(16 Suppl):Abstract nr IA013.
Abstract IA019: Metabolic adaptations in renal cell carcinoma
Authors: Rathmell W. Kimryn 
Published: August 2023

Abstract
Clear cell renal cell carcinoma (ccRCC) is characterized by deregulated hypoxic signaling, metabolic defects, and a complex tumor microenvironment (TME) highly enriched in both lymphoid and myeloid immune subsets. Loss of the oxygen sensing gene, von Hippel Lindau (VHL), is a critical early event in ccRCC pathogenesis and promotes stabilization of hypoxia inducible (transcription) factors (HIF) that upregulate pro-growth signaling pathways, including angiogenesis and aerobic glycolysis. However, whether Vhl loss in cancer cells impacts the frequency, energetic requirements, or other functional properties of immune subsets in the TME remains unclear. Here, using Vhl WT and Vhl KO in vivo murine kidney cancer models, we found that Vhl KO tumors across multiple clones were slower growing and promoted increased immune cell infiltration in the TME. Enhanced proinflammatory signatures in tumor associated macrophage (TAM) subsets from Vhl deficient tumors were also observed, and these features were rescued when Vhl was reintroduced to the cancer cells. Moreover, in vivo quantification of the PET tracer and glucose analog, [18F]fluorodeoxyglucose (FDG), revealed that both myeloid derived suppressor cells (MDSC) and TAM populations from Vhl KO tumors consume more glucose than myeloid subsets from Vhl intact tumors. Notably, Vhl loss did not confer increased glucose uptake in cancer cells or lymphoid subsets in vivo. Overall, these data are consistent with enhanced metabolism and proinflammatory properties observed in the myeloid compartment of human ccRCC and highlight cancer cell intrinsic mechanisms driving environmental reprograming as a means of shaping the immune landscape in ccRCC.
Citation Format: W. Kimryn Rathmell. Metabolic adaptations in renal cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Advances in Kidney Cancer Research; 2023 Jun 24-27; Austin, Texas. Philadelphia (PA): AACR; Cancer Res 2023;83(16 Suppl):Abstract nr IA019.
Abstract PR003: PBRM1-deficient PBAF complexes target aberrant genomic loci to activate NF-κB pathway in clear cell renal cell carcinoma
Authors: Yao Xiaosai , Hong Jing Han , Nargund Amrita , Ng Michelle S.W. , Teh Bin Tean 
Published: August 2023

Abstract
PBRM1 encodes an accessory subunit of the PBAF subclass of the SWI/SNF chromatin remodeler and the inactivation of PBRM1 is the second most frequent mutational event in kidney cancer. However, the impact of PBRM1 loss on chromatin remodeling, especially pertaining to kidney tumorigenesis, has not been well examined. Here we show that in VHL-deficient renal tumors, PBRM1 deficiency results in ectopic PBAF complexes that localize to de novo genomic loci and activate the pro-tumorigenic NF-κB pathway. PBRM1-deficient PBAF complexes, despite retaining the association between SMARCA4 and ARID2, have loosely tethered BRD7. The PBAF complexes redistribute from promoter proximal regions to distal enhancers containing NF-κB motifs; subsequently, PBRM1-deficient cells display heightened NF-κB activity in multiple models and clinical samples. The ATPase function of SMARCA4 maintains chromatin occupancy of both pre-existing and newly acquired RELA specific to PBRM1 loss, and activates downstream target gene expression. Proteasome inhibitor bortezomib abrogates RELA occupancy, suppresses NF-κB activation and delays growth of PBRM1-deficient tumors. In conclusion, PBRM1 safeguards the chromatin by repressing aberrant liberation of pro-tumorigenic NF-κB target genes by residual PBRM1-deficient PBAF complexes.
Citation Format: Xiaosai Yao, Jing Han Hong, Amrita Nargund, Michelle S.W. Ng, Bin Tean Teh. PBRM1-deficient PBAF complexes target aberrant genomic loci to activate NF-κB pathway in clear cell renal cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Advances in Kidney Cancer Research; 2023 Jun 24-27; Austin, Texas. Philadelphia (PA): AACR; Cancer Res 2023;83(16 Suppl):Abstract nr PR003.
Abstract PR012: SETD2 safeguards the genome against isochromosome formation
Authors: Mason Frank M. , Tebeje Anteneh T. , Kounlavong Emily S. , Dahiya Rashmi , Vlach Logan , Guess Tiffany , Dere Ruhee , Ohi Ryoma , Ly Peter , Walker Cheryl L. , Rathmell W. Kimryn 
Published: August 2023

Abstract
Chromosome mis-segregation during cell division occurs in diverse tumor types, promoting aneuploidy and intratumoral genetic heterogeneity. While the mechanisms that govern chromosome segregation are well-established, how changes in the activities of tumor suppressors or oncogenes drive mitotic errors remain poorly understood. Loss of the tumor suppressor SETD2, the methyltransferase responsible for tri-methylation of histone 3 lysine 36 (H3K36me3), correlates with clear cell renal cell carcinoma (ccRCC) tumors exhibiting extensive intratumoral heterogeneity. Yet, how loss of H3K36me3 or SETD2 promotes heterogeneity is unknown. Here, we show that loss of SETD2 promotes chromosome mis-segregation during mitosis and interphase DNA bridges driven by the formation of dicentric chromosomes. Cytogenetic analyses revealed that these dicentrics loss were largely comprised of mirror-imaged isodicentric chromosomes that contain two active centromeres. In addition to isodicentrics, cells lacking SETD2 or H36K36me3 generated iso- and acentric chromosomes, however loss of SETD2 protein additionally caused chromosome instability. These data directly link loss of a tumor suppressor to these mutable chromatin structures that initiate intratumor heterogeneity by promoting gross chromosomal rearrangements.
Citation Format: Frank M. Mason, Anteneh T. Tebeje, Emily S. Kounlavong, Rashmi Dahiya, Logan Vlach, Tiffany Guess, Ruhee Dere, Ryoma Ohi, Peter Ly, Cheryl L. Walker, W. Kimryn Rathmell. SETD2 safeguards the genome against isochromosome formation [abstract]. In: Proceedings of the AACR Special Conference: Advances in Kidney Cancer Research; 2023 Jun 24-27; Austin, Texas. Philadelphia (PA): AACR; Cancer Res 2023;83(16 Suppl):Abstract nr PR012.
As “Officinas de Optica e de Instrumentos Scientificos” de José Hermida Pazos e o Telescópio Equatorial do Observatório do Valongo
Authors: Campos José Adolfo Snajdauf de 
Published: August 2023

O Observatório do Valongo possui em seu acervo um telescópio de valor histórico, instalado em seu campus: um pequeno refrator com 11,5 cm de abertura, chamado de telescópio “Pazos”, que se acredita feito em 1880 e cuja construção é atribuída às “Oficinas” de José Hermida Pazos. Ele seria o primeiro e único telescópio de montagem equatorial com mecanismo de acompanhamento feito no Brasil no século XIX. O artigo visa a contribuir para a preservação da memória institucional e apresenta os resultados da investigação feita para responder às questões sobre o telescópio: quem comprou, quando e por quê; e se as “Oficinas” de José Hermida Pazos foram realmente responsáveis pela sua construção.
Fracture Risk Increases After Stroke or Transient Ischemic Attack and Is Associated With Reduced Quality of Life
Authors: Dalli Lachlan L. , Borschmann Karen , Cooke Shae , Kilkenny Monique F. , Andrew Nadine E. , Scott David , Ebeling Peter R. , Lannin Natasha A. , Grimley Rohan , Sundararajan Vijaya , Katzenellenbogen Judith M. , Cadilhac Dominique A. ,   on behalf of the Stroke123 Investigators, Anderson Craig , Donnan Geoffrey , Levi Christopher , Thrift Amanda , Middleton Sandy , Faux Steven , Denisenko Sonia , Dewey Helen , Godecke Erin , Katzenellenbogen Judy , Lalor Erin , Lee Andrew , Longworth Mark , Cadigan Greg , Dilworth Cindy , Price Chris , Hill Kelvin , Page Matthew , Egan Jen , Grabsch Brenda , Kung Francis , Moss Karen , Street Steven , Tod Emma , Gibbs Adele , Purvis Tara , Reyneke Megan 
Published: August 2023

BACKGROUND:
Fractures are a serious consequence following stroke, but it is unclear how these events influence health-related quality of life (HRQoL). We aimed to compare annualized rates of fractures before and after stroke or transient ischemic attack (TIA), identify associated factors, and examine the relationship with HRQoL after stroke/TIA.

METHODS:
Retrospective cohort study using data from the Australian Stroke Clinical Registry (2009–2013) linked with hospital administrative and mortality data. Rates of fractures were assessed in the 1-year period before and after stroke/TIA. Negative binomial regression, with censoring at death, was used to identify factors associated with fractures after stroke/TIA. Respondents provided HRQoL data once between 90 and 180 days after stroke/TIA using the EuroQoL 5-dimensional 3-level instrument. Adjusted logistic regression was used to assess differences in HRQoL at 90 to 180 days by previous fracture.

RESULTS:
Among 13 594 adult survivors of stroke/TIA (49.7% aged ≥75 years, 45.5% female, 47.9% unable to walk on admission), 618 fractures occurred in the year before stroke/TIA (45 fractures per 1000 person-years) compared with 888 fractures in the year after stroke/TIA (74 fractures per 1000 person-years). This represented a relative increase of 63% (95% CI, 47%–80%). Factors associated with poststroke fractures included being female (incidence rate ratio [IRR], 1.34 [95% CI, 1.05–1.72]), increased age (per 10-year increase, IRR, 1.35 [95% CI, 1.21–1.50]), history of prior fracture(s; IRR, 2.56 [95% CI, 1.77–3.70]), and higher Charlson Comorbidity Scores (per 1-point increase, IRR, 1.18 [95% CI, 1.10–1.27]). Receipt of stroke unit care was associated with fewer poststroke fractures (IRR, 0.67 [95% CI, 0.49–0.93]). HRQoL at 90 to 180 days was worse among patients with prior fracture across the domains of mobility, self-care, usual activities, and pain/discomfort.

CONCLUSIONS:
Fracture risk increases substantially after stroke/TIA, and a history of these events is associated with poorer HRQoL at 90 to 180 days after stroke/TIA.
Transnational Governing at the Climate–Biodiversity Frontier: Employing a Governmentality Perspective
Authors: Fransen Anouk , Bulkeley Harriet 
Published: August 2023

Abstract
Transnational governance initiatives (TGIs) are increasingly recognized as central actors in the governing of climate change and biodiversity loss. Yet, their role in linking these domains has yet to be explored. As the climate crisis comes to be increasingly interlinked with the loss of biodiversity, such initiatives are increasingly combining this challenge of climate change with action on biodiversity loss through the deployment of nature-based solutions, with significant consequences for the ways in which the nature problem and its solutions are framed and implemented. Employing a governmentality approach, this research reveals two overarching rationales by TGIs of biodiversity as a means to climate change and “asset-at-risk” that are rendered governable through myriad techniques “at a distance” and “in proximity.” By revealing how biodiversity is made to fit with the climate arena, this research finds that these governable biodiversity spaces could generate rather regrettable solutions along these shifting and unfolding climate–biodiversity frontiers.
Valuing Nature to Save It? The Centrality of Valuation in the New Spirit of Conservation
Authors: Maechler Sylvain , Boisvert Valérie 
Published: August 2023

Abstract
For thirty years, advocates of the economic valuation of nature have been claiming that it contributes to making the ecological crisis more tangible. The valuation framing fosters a shared vision of nature as capital amenable to management and protection. Yet, this approach has scarcely been applied in practice and has therefore not yielded tangible conservation outcomes. Why is economic valuation of nature consistently presented as a panacea in the absence of the slightest evidence to that effect? Beyond conventional answers—policy path dependency, alignment with the dominant balance of power—we propose to analyze the centrality of nature valuation in conservation discourses using the notion of valuation-centrism forged from Gibson-Graham’s capitalocentrism. By valuation-centrism, we mean a system of discourse and knowledge that subverts all exit strategies from the ecological crisis into valuation practices, that reinforces hegemonic capitalist representations of nature, and that thwarts the imagining of “other natures.”
Exploring the phylogenetic signal in the cranial variation of European populations of grayling (Actinopterygii, Salmonidae)
Authors: Jojić Vida , Bajić Aleksandar , Barišić Klisarić Nataša , Bugarski-Stanojević Vanja , Snoj Aleš , Miljanović Branko , Askeyev Oleg , Askeyev Igor , Marić Saša 
Published: August 2023

Abstract
This is a preliminary and exploratory study of cranial variation in European populations of grayling. We investigated the correspondence between size/shape variation of the dorsal (dc), ventral (vc) and occipital (oc) cranium and phylogenetic relationships (inferred from mitochondrial control region – mtDNA cr and microsatellite dna data) of six grayling populations: three from Balkan phylogenetic clade and two from Caspian phylogenetic clade of the European grayling Thymallus thymallus and one population of the Adriatic grayling Thymallus aeliani, which until recently was considered the Adriatic phylogenetic clade of T. thymallus. Significant size and shape differences were found between populations in all three cranial views. However, significant size-related shape variation (allometry) was found for dc and vc, but not for oc. The size variation of each cranial view does not contain phylogenetic signal, but size variation of oc is consistent with genetic variation inferred from microsatellite dna. Regarding shape variation, a significant phylogenetic signal was detected only for oc, and only the shape variation of oc is consistent with the genetic variation inferred from the mtDNA cr. Moreover, the Adriatic grayling T. aeliani (Soča population) was clearly separated from the three T. thymallus populations of the Balkan phylogenetic clade and the two T. thymallus populations of the Caspian phylogenetic clade only at the level of oc. Thus, our results suggest that different cranial regions differ in allometry, reflect phylo(genetic) relationships differently, and exhibit differences in ecophenotypic plasticity, with oc seeming best suited to represent the phylogenetic relationships of the grayling populations studied.
Le féminisme et son trouble
Authors: Decousu Cécile 
Published: August 2023

Résumé
Le sexe a été théoriquement et discursivement institué comme binarité biologique et invariant anthropologique, fondements de relations nécessaires. Extrapolé des corps, le « savoir du sexe » les réintègre en normativité – et donc en possibles pathologies de la sexualité. De Beauvoir à Butler, c’est à l’interstice de ces intrications qu’agit le féminisme, en venant les troubler. C’est alors une herméneutique du trouble que cet article tente de retracer, et que l’écriture de Violette Leduc vient incarner.