tbuckley/cabot-search huggingface dataset:
Abstract LB143: BNZ-2, a dual specific IL15/IL21 inhibitor, rescues humanized NOG-IL15 transgenic mice from intestinal acute graft versus host disease without disrupting NK and CD8 T cell engraftment
Authors: Kevin R. Kipp, Nick Doerr, Laith Q. Al-Mawsawi, Woo Jae Kim, Adrian J. Giovannone, Nazli Azimi
Journal: Cancer Research (2021)

Abstract Advances in adoptive transfer immunotherapy have found beneficial effects for Interleukin-15 (IL-15) in the graft versus tumor (GvT) activity of NK and cytotoxic T cells. However, the benefits of this activity must be weighed against the increased risk of acute graft versus host disease (GvHD) in patients. We propose that BNZ-2, a peptide antagonist of IL-15 and IL-21 signaling, as a therapeutic option for GvHD that may relieve intestinal pathologies while retaining adoptive transfer activity. As a novel model of intestinal inflammatory disease, we have found that humanization with peripheral blood mononuclear cells (PBMCs) of NOG mice with transgenic expression of human IL-15 (NOG-IL15) consistently catalyzes the onset of intestinal GvHD within twenty days of engraftment. To investigate whether BNZ-2 can inhibit IL-15-catalized intestinal GvHD we treated NOG-IL15 mice and assessed the degree of intestinal GvHD and the immunophenotype of engrafted cells following twenty days of humanization with four million unmanipulated PBMCs. BNZ-2 treatment inhibited with equal efficacy to anti-IL-15 the localization of immune cells to the intestinal lamina propria protecting the tissue from inflammation-induced loss of tissue integrity. However, BNZ-2 treatment retained the systemic engraftment of the blood and spleen, including NK and CD8 cytotoxic T-cells. These data support BNZ-2 as a therapeutic candidate for GvHD treatment, describe a new model of intestinal GvHD, and suggest that a therapeutic window exists that separates intestinal GvHD pathologies from the benefits of adoptive cell transfer. Citation Format: Kevin R. Kipp, Nick Doerr, Laith Q. Al-Mawsawi, Woo Jae Kim, Adrian J. Giovannone, Nazli Azimi. BNZ-2, a dual specific IL15/IL21 inhibitor, rescues humanized NOG-IL15 transgenic mice from intestinal acute graft versus host disease without disrupting NK and CD8 T cell engraftment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB143.
Socioeconomic inequalities in the incidence of alcohol-related liver disease: A nationwide Danish study
Authors: Gro Askgaard, Kate M. Fleming, Colin Crooks, Frederik Kraglund, Camilla B. Jensen, Joe West, Peter Jepsen
Journal: The Lancet Regional Health - Europe (2021)

There is socio-economic inequality in total alcohol-related harm, but knowledge of inequality in the incidence of specific alcohol-related diseases would be beneficial for prevention. Registry-based studies with nationwide coverage may reveal the full burden of socioeconomic inequality compared to what can be captured in questionnaire-based studies. We examined the incidence of alcohol-related liver disease (ALD) according to socioeconomic status and age.We used national registries to identify patients with an incident diagnosis of ALD and their socioeconomic status in 2009-2018 in Denmark. We computed ALD incidence rates by socioeconomic status (education and employment status) and age-group (30-39, 40-49, 50-59, 60-69 years) and quantified the inequalities as the absolute and relative difference in incidence rates between low and high socioeconomic status.Of 17,473 patients with newly diagnosed ALD, 78% of whom had cirrhosis, 86% had a low or medium-low educational level and only 20% were employed. ALD patients were less likely to be employed in the 10 years prior to diagnosis than controls. The incidence rate of ALD correlated inversely with educational level, from 181 (95% CI, 167-197) to 910 (95% CI, 764-1086) per million person-years from the highest to the lowest educational level. By employment status, the incidence rate per million person-years was 211 (95% CI, 189-236) for employed and 3449 (95% CI, 2785-4271) for unemployed. Incidence rates increased gradually with age leading to larger inequalities in absolute numbers for older age-groups. Although ALD was rare in the younger age-groups, the relative differences in incidence rates between high and low socioeconomic status were large for these ages. The pattern of socioeconomic inequality in ALD incidence was similar for men and women.This study showed substantial socioeconomic inequalities in ALD incidence for people aged 30-69 years.The study was supported by grants from the Novo Nordisk Foundation (NNF18OC0054612) and the Research Fund of Bispebjerg Hospital.
Patient perspective on serving on the steering committee of the AURORAX-0087A trial for non-metastatic clear cell renal cell carcinoma
Authors: R. Giles, R. Nair, N.H. Azawi, N. Barber, A. Bex, R. Campi, U. Capitanio, F. Gatto, A.A. Hakimi, P. Järvinen, J. Karam, B. Ljungberg, L. Lund, S.B. Maddineni, L. Marconi, V. Master, A. Minervini, T.K. Nielsen, H Nisen, M. Rochester, G. Stewart, S. Dabestani
Journal: European Urology (2021)
国家癌管理計画:グローバル分析【JST・京大機械翻訳】
Authors: Romero Yannick, Trapani Dario, Johnson Sonali, Tittenbrun Zuzanna, Given Leslie, Hohman Karin, Stevens Lisa, Torode Julie S, Boniol Mathieu, Ilbawi Andre M
Journal: The Lancet Oncology (2018)
Abstract 180: Identifying signatures of vulnerability through machine learning in an umbrella trial for glioblastoma
Authors: Matthew Eric Lee, Nanyun Tang, Manmeet Ahluwalia, Ekokobe Fonkem, Karen Fink, Harshil Dhurv, Harshil Dhurv, Michael E. Berens, Sen Peng
Journal: Cancer Research (2021)

Abstract Glioblastoma is characterized by intra- and inter-tumoral heterogeneity. An umbrella trial tests multiple investigational treatment arms depending on corresponding biomarker signatures. A contingency of an efficient umbrella trial is a suite of preferably orthogonal molecular biomarkers to classify patients into the likely-most-beneficial arm. Assigning thresholds of molecular signatures to classify a patient as a “most-likely responder” for one specific treatment arm is a crucial task. Gene Set Variation Analysis (GSVA) of specimens from a GBM clinical trial of methoxyamine associated differential enrichment in DNA repair pathways activities with patient response. However, the large number of DNA-repair related pathways confound confident “high” enrichment of responder, as well as obscuring to what degree each feature contributes to the likelihood of a patient's response. Here, we utilized semi-supervised machine learning, Entropy-Regularized Logistic Regression (ERLR) to predict vulnerability classification. By first training all available data using semi-supervised algorithms we transformed unclassified TCGA GBM samples with highest certainty of predicted response into a self-labeled dataset. In this case, we developed a predictive model which has a larger sample size and potential better performance. Our umbrella trial design currently includes three treatment arms for GBM patients: arsenic trioxide, methoxyamine, and pevonedistat. Each treatment arm manifests its own signature developed by the above (or similar) machine learning pipeline based on selected gene mutation status and whole transcriptome data. In order to increase the robustness and scalability (with future more treatment arms), we also developed a multi-label classification ensemble model that's capable of predicting a probability of “fitness” of each novel therapeutic agent for each patient. By expansion to three, independent treatment arms within a single umbrella trial, a “mock” stratification of TCGA GBM patients labeled 56% of all cases into at least one “high likelihood of response” arm. Predicted vulnerability using genomic data from preclinical PDX models placed 4 out of 6 models into a “high likelihood of response” regimen. Our utilization of multiple vulnerability signatures in an umbrella trial demonstrates how a precision medicine model can support an efficient clinical trial for heterogeneous diseases such as GBM. Citation Format: Matthew Eric Lee, Nanyun Tang, Manmeet Ahluwalia, Ekokobe Fonkem, Karen Fink, Harshil Dhurv, Harshil Dhurv, Michael E. Berens, Sen Peng. Identifying signatures of vulnerability through machine learning in an umbrella trial for glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 180.
Abstract 2096: Genome wide remodeling of DNA methylation and CpG hypermethylation is tightly linked to acquired resistance in testicular cancer
Authors: Zeeshan Fazal, Ratnakar Singh, Megan Tomlin, Doha Shokry, Aleyah Hattab, Sarah Spinella, Michael Spinella
Journal: Cancer Research (2021)

Abstract Acquired resistance to chemotherapy is perhaps the major barrier to cure of advanced cancers. Testicular germ cell tumors (TGCTs) are the most common cancers of young males. TGCTs are one of the few solid tumors that are cured at a high rate with standard cisplatin-based chemotherapy. However, TGCTs become resistance to cisplatin resulting in poor outcomes. While the mechanisms accounting for cisplatin hypersensitivity in TGCT remain elusive, it has been suggested that DNA hypermethylation may play a role. However, there is little direct experimental evidence to support this claim. In the present study, we have leveraged unique isogenic cell models to provide strong evidence for net DNA hypermethylation as a key mechanism leading to acquired cisplatin resistance in TGCT cells. Genome-wide DNA methylation analysis revealed that hypomethylated CpG loci were enriched for SUZ12 and EZH2 binding and H3K27me3 sites. In contrast hypermethylated CpG loci were significantly enriched for CTCF and RAD21 domains as well as repressive DNA segments indicating the global remodeling of nuclear chromatin structure in resistant cells. Integrative computational analysis of RNA-seq and EPIC DNA methylation array data revealed a strong inverse correlation between gene expression and CpG gene promoter methylation. This analysis also revealed a strong bidirectional shift between gene promoter and gene body DNA methylation that correlated closely with upregulated expression of PRC2 target genes and down regulation of tumor suppression genes in resistant cells. Hence the data further suggests a functional interplay between DNA methylation and the PRC2 pathway that modulates cisplatin sensitivity of TGCTs. Further studies including H3K27me3 ChIP-seq are ongoing to further elucidate this relationship. In conclusion, our finding supports the hypothesis that genome wide remodeling of DNA methylation is associated with cisplatin hypersensitivity and resistance of TGCTs and further supports the use of hypomethylation therapy for relapsed TGCT patients. Citation Format: Zeeshan Fazal, Ratnakar Singh, Megan Tomlin, Doha Shokry, Aleyah Hattab, Sarah Spinella, Michael Spinella. Genome wide remodeling of DNA methylation and CpG hypermethylation is tightly linked to acquired resistance in testicular cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2096.
COVID-19 Vaccination of Minors Without Parental Consent
Authors: Larissa Morgan, Jason L. Schwartz, Dominic A. Sisti
Journal: JAMA Pediatrics (2021)

In May 2021, the Pfizer-BioNTech COVID-19 vaccine received emergency use authorization from the US Food and Drug Administration in adolescents aged 12 to 15 years, with authorization for younger children expected later this year. 1 Despite reported clinical trial data indicating that the vaccine is safe and 100% efficacious for this age range, some parents and guardians may remain hesitant or outright opposed to vaccinating their children, particularly in politically and culturally conservative communities. 2hildren and adolescents account for approximately 22% of positive COVID-19 cases reported to date, and hospitalizations among this population have recently spiked. 3Since July 2020, weekly reported case rates for individuals aged 14 to 17 years have generally mirrored or exceeded rates among adults. 4As cases decline in adults owing to vaccination, the current case rate in teenagers now exceeds that of adults 55 years and older. 5Although COVID-19 illness is generally less severe in younger people, the disease has nonetheless caused substantial morbidity and more than 325 deaths among US children and adolescents, a burden of disease greater than that of many diseases for which vaccines are routinely recommended in this age group. 6pproximately one-third of confirmed COVID-19 cases in minors have been asymptomatic, creating an opportunity for minors to spread the virus unknowingly.The reduction of asymptomatic transmission is essential to slowing the spread of the virus, and growing evidence suggests that vaccination provides substantial public health benefits by decreasing transmission in addition to its direct, individual benefits. 7For these reasons, there is an urgent need for increased immunization in younger age groups.Vaccinating minors is critical to protecting them from the virus, reducing transmission-especially to higher-risk populations-and continuing progress toward herd immunity.Children and adolescents have the capacity to understand and reason about low-risk and high-benefit health care interventions.State laws should therefore authorize minors to consent to COVID-19 vaccination without parental permission.
Transpancreatic biliary sphincterotomy for difficult biliary cannulation: can it be better than other methods?
Authors: Hsiu-Po Wang
Journal: Endoscopy (2021)

Selective biliary cannulation is the critical step when endoscopic retrograde cholangiopancreatography (ERCP) is used to manage pancreaticobiliary diseases. However, difficult cannulation and failure of initial biliary cannulation can occur in 10 %–20 % of patients with a native major papilla [1]. Difficult biliary cannulation increases the risk of post-ERCP adverse events, such as post-ERCP pancreatitis (PEP), post-ERCP bleeding, and perforation.
Glioblastoma: clinical presentation, diagnosis, and management
Authors: Chris McKinnon, Meera Nandhabalan, Scott A Murray, Puneet Plaha
Journal: BMJ (2021)

What you need to know1. Early symptoms of brain tumours in adults are non-specific and patients may present multiple times to primary care services before they are referred for investigation.Look out for symptoms of raised intracranial pressure (e.g.headaches exacerbated by lying down, triggered by Valsalva maneuver or associated with vomiting or visual disturbance), combinations of symptoms (e.g.headache plus cognitive impairment, headache plus weakness, headache plus personality change) and symptoms which progress over time.New-onset focal or generalized seizures in adulthood also warrant investigation for a brain tumour.2. In patients with symptoms or signs suggestive of a brain tumour, arrange an urgent MRI head with and without contrast through a rapid-access 'suspected cancer' pathway, when available.In patients with suspicion of raised intracranial pressure, arrange a same-day clinical assessment and contrast-enhanced CT head scan.3. Glioblastoma (GBM) is the most common primary brain cancer.Standard treatment includes maximal safe resection followed by concomitant radiotherapy and temozolomide (TMZ) chemotherapy and then adjuvant TMZ.Disease progression is expected in all cases and consideration of further treatment should take into account the patient's performance status, tumour size, location and time since first treatment 4. Key supportive medications may include corticosteroids for vasogenic oedema and anti-epileptic medication if seizures occur 5. Due to the incurable and rapidly progressive nature of glioblastoma, close collaboration between multidisciplinary teams in tertiary care hospitals and primary care services is recommended.Early involvement of GPs and specialist community palliative care teams can assist patients and caregivers with advance care planning as well as management of symptoms, physical and cognitive impairment, communication difficulties and the innate uncertainties about disease progression.
How to follow patients with negative targeted prostate biopsy but positive multi-parametric MRI? Results from a large, single institution series
Authors: A. Stabile, G. Gandaglia, N. Fossati, G. Sorce, F. Pellegrino, L. Nocera, S. Scuderi, G.O. Cirulli, V. Cucchiara, E. Zaffuto, R. Leni, D. Cannoletta, M. De Angelis, S. Comana, G. Brembilla, A. Esposito, F. De Cobelli, F. Montorsi, A. Briganti
Journal: European Urology (2021)
Abstract LB216: Targeted brachyury degradation disrupts a highly specific autoregulatory program controlling chordoma cell identity
Authors: Hadley E. Sheppard, Alessandra Dall'Agnese, Woojun D. Park, Hamza Shamim, Julien Dubrulle, Hannah L. Johnson, Fabio Stossi, Patricia Cogswell, Josh Sommer, Joan Levy, Tanaz Sharifnia, Mathias J. Wawer, Paul A. Clemons, Behnam Nabet, Nathanael S. Gray, Stuart L. Schreiber, Paul Workman, Richard A. Young, Charles Y. Lin
Journal: Cancer Research (2021)

Abstract Chordomas are rare spinal tumors addicted to expression of the developmental transcription factor brachyury. In chordomas, brachyury is super-enhancer associated and preferentially downregulated by pharmacologic transcriptional CDK inhibition leading to cell death. To understand the underlying basis of this sensitivity, we dissect the brachyury transcription regulatory network and compare the consequences of brachyury degradation with transcriptional CDK inhibition. Brachyury defines the chordoma super-enhancer landscape, autoregulates through binding its super-enhancer, and its locus forms a transcriptional condensate. Both transcriptional CDK inhibition and brachyury degradation disrupt brachyury autoregulation, leading to loss of its transcriptional condensate and transcriptional program. Compared with transcriptional CDK inhibition which globally downregulates transcription leading to cell death, brachyury degradation is much more selective, inducing senescence and sensitizing cells to anti-apoptotic inhibition. These data suggest that brachyury downregulation is a core tenet of transcriptional CDK inhibition and motivates developing strategies to target brachyury and its autoregulatory feedback loop. Citation Format: Hadley E. Sheppard, Alessandra Dall'Agnese, Woojun D. Park, Hamza Shamim, Julien Dubrulle, Hannah L. Johnson, Fabio Stossi, Patricia Cogswell, Josh Sommer, Joan Levy, Tanaz Sharifnia, Mathias J. Wawer, Paul A. Clemons, Behnam Nabet, Nathanael S. Gray, Stuart L. Schreiber, Paul Workman, Richard A. Young, Charles Y. Lin. Targeted brachyury degradation disrupts a highly specific autoregulatory program controlling chordoma cell identity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB216.
Abstract 15458: Cardiomyocyte-Specific Disruption of the Circadian Clock Gene, Bmal1, Alters Cardiomyocyte Stiffness and Gives Rise to a Transient Cardiac Hypertrophy
Authors: Mellani Lefta, Elizabeth A Schroder, Karyn A Esser
Journal: Circulation (2011)

Circadian rhythms are oscillations in behavior and physiology with a periodicity of approximately 24 hours. Disruption of circadian rhythms, in both humans and animal models, is correlated with an ...
Retroperitoneal vs. transperitoneal robotic partial nephrectomy for postero-lateral renal masses: An international multicenter analysis
Authors: U. Carbonara, U. Capitanio, D. Eun, I.. Derweesh, A. Celia, C. Fiori, A. Larcher, F. Crocerossa, L.J. Hampton, F. Montorsi, F. Porpiglia, R. Autorino
Journal: European Urology (2021)
Abstract 2044: Genomic scar score: a robust model to predict recombination repair deficient based on genomic instability
Authors: Hao Wen, Shuang Yang, Xuejun Chen, Ying Weng, Changbin Zhu, Li Ruan, Hua Dong, Xiaohua Wu
Journal: Cancer Research (2021)

Abstract Background: Clinical benefit of PARP inhibitors or Platinum-based chemotherapy has been observed and well proved in BRCA mutation patients. However, there are other mechanisms to induce recombination repair deficient (HRD), such as BRCA methylation, ATM expression loss; HRR gene mutation in addition to BRCA mutation. Whether these complicated HRD events or phenotype could be measured by a unified model to accurately identify HRD positive patients is important. Methods: In this study, we use support vector machine method to build genomic scar (GS) model to predict HRD events, which takes different types of chromosomal copy number into consideration to evaluate genomic instability. The accuracy of GS model was tested by different NGS platform from WGS to two captured SNP Panel. GS status association with Cisplatin-based chemotherapy was also preliminarily validated. Results: GS model displayed more than 95% accuracy to detect BRCA-ness events and is also able to enrich different types of HRR dysfunction, such as HRR-related mutation or BRCA1 promoter methylation. Moreover, GS model can identify patient benefits from Cisplatin-based chemotherapy, and GS score (GSS) high group had longer progression free survival (PFS) than GSS low group (11 vs 8.5 months, HR=0.5, P=0.05). Meanwhile, GSS showed the high concordance among different NGS platform including WGS; two captured SNP Panels, which implied the high robustness of GS model. Conclusion: GS was a robust model to predict HRD and had the clinical potential to enrich patients who will response to PARP inhibitors and/or Platinum-based chemotherapy. Citation Format: Hao Wen, Shuang Yang, Xuejun Chen, Ying Weng, Changbin Zhu, Li Ruan, Hua Dong, Xiaohua Wu. Genomic scar score: a robust model to predict recombination repair deficient based on genomic instability [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2044.
エンジニアリング3D骨組織のための生物印刷した骨形成と血管パターン【Powered by NICT】
Authors: Byambaa Batzaya, Annabi Nasim, Yue Kan, Trujillo-de Santiago Grissel, Alvarez Mario Moises, Jia Weitao, Kazemzadeh-Narbat Mehdi, Shin Su Ryon, Tamayol Ali, Khademhosseini Ali
Journal: Advanced Healthcare Materials (2017)