tbuckley/cabot-search huggingface dataset:
Abstract 663: Longitudinal AXL assessment of circulating tumor cells (CTCs) and its clinical implication in the patients with EGFR mutated non-small cell lung cancer (NSCLC)
Authors: Mi Young Choi, Da Hye Moon, Hae Ung Lee, Jong Min Jo, Young Woong Sohn, Byung Hee Jeon, Sang-We Kim
Journal: Cancer Research (2021)

Abstract Gefitinib for EGFR mutated non-small cell lung cancer (NSCLC) is showing acquired resistance after 8-11 months, and about 60% of its mechanisms have been reported due to T790M mutation. In about a third of NSCLC, AXL expression can be observed at baseline status. And because AXL expression could be a mechanism of drug resistance, we decided to monitor AXL expression before and after Gefitinib treatment in EGFR mutated NSCLC patients through circulating tumor cells (CTCs). Herein, Thirty-seven out of 55 participants who showed acquired resistance to EGFR-TKI were selected in this prospective analysis. To evaluate the AXL expression on the CTCs, serial blood was obtained (tracking for 4, 12, 24 and 36 weeks after EGFR-TKIs). Baseline tumor tissues were also obtained for genetic analysis. Progression-free survival (PFS) and overall survival (OS) were explored according to the baseline AXL expression. AXL expression was analyzed by observation and quantitative intensity-dependent fold change analysis using immunofluorescence analysis. CTCs were isolated and analyzed by CytoGen's Smart Liquid Biopsy platform that uses the size-based gravity filtration for CTC isolation. We found out that there were ten cases (27%) of the increasing pattern of AXL expression in CTCs during longitudinal monitoring in patients with progressive disease (PD). The most remarkable aspect is that AXL up-regulation in CTCs preceded the time point of clinical PD. These results imply that the expectation of clinical PD by blood CTC (liquid biopsy-based examination) can be combined with the T790M. Moreover, the PFS (p= 0.002) and OS (p= 0.007) were both worse in patients with AXL expression at the baseline status compared with patients without AXL expression (N=55). Conclusively, this study implicates that AXL in CTCs could be deployed for prognostic evaluation. And the clinical monitoring of specific target marker in CTC could help for further treatment strategy. Citation Format: Mi Young Choi, Da Hye Moon, Hae Ung Lee, Jong Min Jo, Young Woong Sohn, Byung Hee Jeon, Sang-We Kim. Longitudinal AXL assessment of circulating tumor cells (CTCs) and its clinical implication in the patients with EGFR mutated non-small cell lung cancer (NSCLC) [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 663.
Accelerated biodegradation of iron-based implants via tantalum-implanted surface nanostructures
Authors: Min-Kyu Lee, Hyun Lee, Cheonil Park, In-Gu Kang, Jinyoung Kim, Hyoun-Ee Kim, Hyun-Do Jung, Tae-Sik Jang
Journal: Bioactive Materials (2021)

In recent years, pure iron (Fe) has attracted significant attention as a promising biodegradable orthopedic implant material due to its excellent mechanical and biological properties. However, in physiological conditions, Fe has an extremely slow degradation rate with localized and irregular degradation, which is problematic for practical applications. In this study, we developed a novel combination of a nanostructured surface topography and galvanic reaction to achieve uniform and accelerated degradation of an Fe implant. The target-ion induced plasma sputtering (TIPS) technique was applied on the Fe implant to introduce biologically compatible and electrochemically noble tantalum (Ta) onto its surface and develop surface nano-galvanic couples. Electrochemical tests revealed that the uniformly distributed nano-galvanic corrosion cells of the TIPS-treated sample (nano Ta-Fe) led to relatively uniform and accelerated surface degradation compared to that of bare Fe. Furthermore, the mechanical properties of nano Ta-Fe remained almost constant during a long-term in vitro immersion test (~40 weeks). Biocompatibility was also assessed on surfaces of bare Fe and nano Ta-Fe using in vitro osteoblast responses through direct and indirect contact assays and an in vivo rabbit femur medullary cavity implantation model. The results revealed that nano Ta-Fe not only enhanced cell adhesion and spreading on its surface, but also exhibited no signs of cellular or tissue toxicity. These results demonstrate the immense potential of Ta-implanted surface nanostructures as an effective solution for the practical application of Fe-based orthopedic implants, ensuring long-term biosafety and clinical efficacy.
Multicellular modeling of ciliopathy by combining iPS cells and microfluidic airway-on-a-chip technology
Authors: Naoyuki Sone, Satoshi Konishi, Koichi Igura, Koji Tamai, Satoshi Ikeo, Yohei Korogi, Shuhei Kanagaki, Toshinori Namba, Yuki Yamamoto, Yifei Xu, Kazuhiko Takeuchi, Yuichi Adachi, Toyofumi F. Chen-Yoshikawa, Hiroshi Date, Masatoshi Hagiwara, Sachiko Tsukita, Toyohiro Hirai, Yu-suke Torisawa, Shimpei Gotoh
Journal: Science Translational Medicine (2021)

Combined induced pluripotent stem cells and airway-on-a-chip establish the global axis of planar cell polarity in patient-derived airway cell sheet.
Induction of CD45 expression on bone marrow-derived mesenchymal stem cells
Authors: 葉士芃(Shih-Peng Yeh), 張建國(Chien-Kuo Chang), 羅文吉(Wen-Chi Lo), 廖宇青(Yu-Chin Liao), 林嬌玲(Chiao-Ling Lin), 邱昌芳(Chang-Fang Chiu)
Journal: Leukemia (2006)
Differences in health care resource utilization and costs for keratinocyte carcinoma among racioethnic groups: A population-based study
Authors: Tiffany J. Sierro, Laura Y. Blumenthal, Joshua Hekmatjah, Vipawee S. Chat, Ari A. Kassardjian, Charlotte Read, April W. Armstrong
Journal: Journal of the American Academy of Dermatology (2021)
Abstract 259: Comparison of Illumina NovaSeq 6000 and MGISEQ-2000 in profiling xenograft models
Authors: Wubin Qian, Xiaobo Chen, Henry Q. Li, Sheng Guo
Journal: Cancer Research (2021)

Abstract BACKGROUND: Comprehensive genomic profiling of tumor models, including patient-derived xenografts, cell lines and organoids, is an integral prerequisite for productive in vivo studies. There are now two leading sequencing platforms from Illumina and MGI Tech. In this study, we compared the performance of the two platforms in sequencing xenograft tumors, which contain both human tumor cells and mouse stromal cells. METHODS: We performed genomic profiling on several xenograft tumors by both sequencers, including RNA-seq and whole-exome sequencing (WES) for 3 samples, and whole-genome sequencing (WGS) for 1 sample. We then performed a comprehensive assessment of sequencer performance using multiple criteria. RESULTS: The mouse ratios from the two sequencers were very close in all RNA-seq/WES/WGS datasets, indicating no or similar species bias for both platforms. The RNA-seq datasets showed high gene expression concordance, with Pearson correlation coefficients of 0.993, 0.992 and 0.993. The WES datasets showed high mutation concordance, with the mutation overlapping rates of 98.9%, 99.3% and 99.1%, and the mutation ratio correlation coefficients of 0.971, 0.976 and 0.977. The WGS data showed overall overlapping rate of 95.5%, and mutation ratio correlation coefficient of 0.955, while for SNPs and INDELs, the overlapping rate was 97.1% and 86.1%. CONCLUSIONS: Our study shows that the MGISEQ and Illumina sequencers have comparable performance in sequencing xenograft tumors. Citation Format: Wubin Qian, Xiaobo Chen, Henry Q. Li, Sheng Guo. Comparison of Illumina NovaSeq 6000 and MGISEQ-2000 in profiling xenograft models [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 259.
Abstract 1603: Discover potent and functional human antibodies against a new B7-family member target for cancer immunotherapy
Authors: Xiaodong Wu, Yongqiang Wang, Xiaocheng Lv, Fei Chen, Yun He, Jiuqiao Zhao, Yiping Rong
Journal: Cancer Research (2021)

Abstract Immunotherapeutics targeting immune checkpoints such as PD1/PD-L1 and CTLA4 offer effective treatment alternatives to the traditional cancer therapies. However, a considerable proportion of patients remain unresponsive to treatment indicating that a more complex immune suppressive tumor microenvironment is involved. Developing novel immune checkpoint inhibitors for combination with current approaches can provide more efficient therapies and expanded indications. A novel B7 family member B7y was recently reported to be highly expressed on a variety of human cancers such as colon, pancreas, breast, bladder, lung cancers and associated with metastatic disease and poor survival. Its co-inhibitory function makes it a new checkpoint and candidate for cancer immunotherapy other than PD-L1 or other immune checkpoints. Here we report the development of functional antibodies targeting this novel B7 family member with potent anti-tumor effect. Generated with H2L2 Harbour Mice® platform, these fully human anti-B7y antibodies specifically bind to cell lines that over-express human or cynomolgus B7y, as well as human tumor cell lines that express endogenous B7y, with high selectivity against other B7 family members. Antibodies that blocked the interaction between B7y and its receptors potently promoted T cell activation in vitro dependent on B7y expression on APC cells. Furthermore, these antibodies in ADCC null versions showed potent anti-tumor activity in humanized murine tumor model. In conclusion, we generated highly potent human antibodies targeting the new immune checkpoint B7 family member and showed good anti-tumor efficacy. Anti-B7y antibody presents a promising novel anti-tumor agent as monotherapy and/or combination therapy with currently established IO agents. Citation Format: Xiaodong Wu, Yongqiang Wang, Xiaocheng Lv, Fei Chen, Yun He, Jiuqiao Zhao, Yiping Rong. Discover potent and functional human antibodies against a new B7-family member target for cancer immunotherapy [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 1603.
Abstract 2034: Patient-specific enhancer-gene networks for hundreds of primary cancer samples
Authors: Duo Xu, Andre Neil Forbes, Sandra Cohen, Ann Palladino, Tatiana Karadimitriou, Ekta Khurana
Journal: Cancer Research (2021)

Abstract Epigenomic alterations at regulatory elements have been implicated in cancer tumorigenesis. As a hallmark for epigenetic changes, chromatin accessibility profiles are generated for cancer patients. However, not all accessible regions are active regulatory elements. We developed a computational model that uses machine learning to integrate ATAC-seq and RNA-seq data and is trained using 3D genomic data. Our model is able to classify accessible regions into active regulatory elements with links to target genes and poised elements with no links to target genes. We used multi-omics data including histone modification profiles from ENCODE to validate our results. Application of our model on chromatin accessibility and transcriptomic data from 400 cancer patients of 22 cancer types revealed novel cancer-type and -subtype-specific enhancer-gene connections for known cancer genes. In one example, we identified two enhancers that regulate the expression of ESR1 in only ER+ breast cancer samples but not in ER- samples. These enhancers explain the high expression of ESR1 in 93% of ER+samples. Functional validation using CRISPRi confirms that inhibition of these enhancers decreases the expression of ESR1 in ER+ samples. Overall, our model predicts the connections of active enhancers to their target genes in a patient-type specific manner revealing key regulatory loci that modulate the expression of key genes. Citation Format: Duo Xu, Andre Neil Forbes, Sandra Cohen, Ann Palladino, Tatiana Karadimitriou, Ekta Khurana. Patient-specific enhancer-gene networks for hundreds of primary cancer samples [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 2034.
Quantifying and Understanding the Higher Risk of Atherosclerotic Cardiovascular Disease Among South Asian Individuals
Authors: Aniruddh P. Patel, Minxian Wang, Uri Kartoun, Kenney Ng, Amit V. Khera
Journal: Circulation (2021)

Background: Individuals of South Asian ancestry represent 23% of the global population, corresponding to 1.8 billion people, and have substantially higher risk of atherosclerotic cardiovascular disease compared with most other ethnicities. US practice guidelines now recognize South Asian ancestry as an important risk-enhancing factor. The magnitude of enhanced risk within the context of contemporary clinical care, the extent to which it is captured by existing risk estimators, and its potential mechanisms warrant additional study. Methods: Within the UK Biobank prospective cohort study, 8124 middle-aged participants of South Asian ancestry and 449 349 participants of European ancestry who were free of atherosclerotic cardiovascular disease at the time of enrollment were examined. The relationship of ancestry to risk of incident atherosclerotic cardiovascular disease—defined as myocardial infarction, coronary revascularization, or ischemic stroke—was assessed with Cox proportional hazards regression, along with examination of a broad range of clinical, anthropometric, and lifestyle mediators. Results: The mean age at study enrollment was 57 years, and 202 405 (44%) were male. Over a median follow-up of 11 years, 554 of 8124 (6.8%) individuals of South Asian ancestry experienced an atherosclerotic cardiovascular disease event compared with 19 756 of 449 349 (4.4%) individuals of European ancestry, corresponding to an adjusted hazard ratio of 2.03 (95% CI, 1.86–2.22; P &lt;0.001). This higher relative risk was largely consistent across a range of age, sex, and clinical subgroups. Despite the &gt;2-fold higher observed risk, the predicted 10-year risk of cardiovascular disease according to the American Heart Association/American College of Cardiology Pooled Cohort equations and QRISK3 equations was nearly identical for individuals of South Asian and European ancestry. Adjustment for a broad range of clinical, anthropometric, and lifestyle risk factors led to only modest attenuation of the observed hazard ratio to 1.45 (95% CI, 1.28–1.65, P &lt;0.001). Assessment of variance explained by 18 candidate risk factors suggested greater importance of hypertension, diabetes, and central adiposity in South Asian individuals. Conclusions: Within a large prospective study, South Asian individuals had substantially higher risk of atherosclerotic cardiovascular disease compared with individuals of European ancestry, and this risk was not captured by the Pooled Cohort Equations.
Harmful Choices, the Case of C, and Decision-Making Competence
Authors: Neil Pickering, GIles Newton-Howes, Greg Young
Journal: The American Journal of Bioethics (2021)

In this paper, we make the case that a person who is considering or has already made a decision that appears seriously harmful to that person should in some cases be judged incapable of making that decision because of the harmfulness of the decision. We focus on the English case of C of 2015. C refused life-saving dialysis. The hospital wanted her declared incompetent to make this decision under the English Mental Capacity Act of 2005. The Judge argued that the consequences for a person's welfare of their decision are irrelevant to the assessment of competence, a position labeled "internalism." This aligns with an assessment of decision-making competence on a strictly cognitivist model. However, internalism misrepresents decision-making. The outcomes of decision-making processes should be part and parcel of judgments of decision-making competence, and in some cases are necessary for any judgment of incompetence to be made.
Infrared Thermography in the Diagnosis of Pathological Changes in the Breast (Literature Review)
Authors: T. V. Pavlova, D. M. Shkatulova
Journal: Radiology - Practice (2021)

A review of the foreign literature of the latter is presented, devoted to determining the place of the method of infrared thermography in the diagnosis of pathological conditions of the breast. Having analyzed the results of using this method in the diagnosis of various changes in the breast, it can be argued that at the moment infrared thermography cannot be used as the only and independent diagnostic method for examining the breast, but its use will help to be useful in solving a number of diagnostic tasks.
2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Giant Cell Arteritis and Takayasu Arteritis
Authors: Mehrdad Maz, Sharon A. Chung, Andy Abril, Carol A. Langford, Mark Gorelik, Gordon Guyatt, Amy M. Archer, Doyt L. Conn, Kathy A. Full, Peter C. Grayson, Maria F. Ibarra, Lisa F. Imundo, Susan Kim, Peter A. Merkel, Rennie L. Rhee, Philip Seo, John H. Stone, Sangeeta Sule, Robert P. Sundel, Omar I. Vitobaldi, Ann Warner, Kevin Byram, Anisha B. Dua, Nedaa Husainat, Karen E. James, Mohamad A. Kalot, Yih Chang Lin, Jason M. Springer, Marat Turgunbaev, Alexandra Villa‐Forte, Amy S. Turner, Reem A. Mustafa
Journal: Arthritis & Rheumatology (2021)

Objective To provide evidence‐based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel vasculitis. Methods Clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for GCA and TAK (27 for GCA, 27 for TAK). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. Recommendations were developed by the Voting Panel, comprising adult and pediatric rheumatologists and patients. Each recommendation required ≥70% consensus among the Voting Panel. Results We present 22 recommendations and 2 ungraded position statements for GCA, and 20 recommendations and 1 ungraded position statement for TAK. These recommendations and statements address clinical questions relating to the use of diagnostic testing, including imaging, treatments, and surgical interventions in GCA and TAK. Recommendations for GCA include support for the use of glucocorticoid‐sparing immunosuppressive agents and the use of imaging to identify large vessel involvement. Recommendations for TAK include the use of nonglucocorticoid immunosuppressive agents with glucocorticoids as initial therapy. There were only 2 strong recommendations; the remaining recommendations were conditional due to the low quality of evidence available for most PICO questions. Conclusion These recommendations provide guidance regarding the evaluation and management of patients with GCA and TAK, including diagnostic strategies, use of pharmacologic agents, and surgical interventions.
Abstract 1117: Acquired resistance to ATP-competitive and irreversible FGFR inhibitors (FGFRi's): A library-based approach
Authors: Hiroshi Sootome, Suzuko Kato, Masanori Kato, Hiroshi Hirai
Journal: Cancer Research (2021)

Abstract Background: The emergence of secondary FGFR kinase domain (KD) mutations with FGFRi's leads to drug resistance and disease progression. The frequency of resistance mutations with individual FGFRi's is unknown. Using an unbiased library-based approach, we examined the development of acquired resistance with the irreversible FGFRi futibatinib and the ATP-competitive FGFRi's erdafitinib (ERD) and pemigatinib (PEM). Methods: Mutant (mt) libraries were generated with random mutagenesis in two FGFR2 KD regions: #1 (amino acids [aa] 540-569), and #2 (aa 640-669). Library were transfected as TEL-fusions into Ba/F3 cells, resulting in FGFR2-dependent cell growth. Transfected cells were treated with FGFRi's at concentrations suppressing parental cell line growth. Surviving drug-resistant clones were counted, isolated, and sequenced to identify the KD mutation. The inhibitory activity of FGFRi's against resistant clones was assessed using phospho-FGFR2 ELISA. Results: Treatment of the library-transfected Ba/F3-TEL-FGFR2 KD cells with PEM, ERD, and futibatinib resulted in an average (n=2) of 93, 27, and 13 resistant clones in region #1 and 28, 21 and 1 resistant in region #2, respectively. Sequencing (table) identified, among others, the following aa mutations: N549, E565, and K641 (regulatory triad), V564 (gatekeeper region) and K659 (activation loop), also seen in patients who developed resistance to Debio1347, infigratinib, and PEM. Among FGFR mts shown (table), futibatinib inhibited 8/10, and ERD, 5/10 mts at IC50 values comparable to wild type (wt) FGFR; however, PEM activity against all FGFR mts was attenuated by ≥5-fold vs wt. Conclusions: Resistance mutations identified with this unbiased library-based in vitro approach were consistent with those observed in the clinic. Acquired drug resistance mutations were less frequent with futibatinib than with ATP-competitive FGFRi's. Futibatinib demonstrated the most robust inhibition of drug resistant mts. FGFR mutationKD regionFutibatinib IC50 (nM)Erdafitinib IC50 (nM)Pemigatinib IC50 (nM)Wild-type (parent)-2.12.51.5N549DRegulatory triad4.225.5153.2N549KRegulatory triad16.732.0246.2V562L-6.32.97.7V564IGatekeeper8.32.762.4V564LGatekeeper91.956.5502.3E565ARegulatory triad6.82.911.8E565GRegulatory triad3.93.09.0K641IRegulatory triad3.855.829.6K641RRegulatory triad4.73.210.3K659MActivation loop9.546.633.8 Citation Format: Hiroshi Sootome, Suzuko Kato, Masanori Kato, Hiroshi Hirai. Acquired resistance to ATP-competitive and irreversible FGFR inhibitors (FGFRi's): A library-based approach [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 1117.