tbuckley/cabot-search huggingface dataset:
Identification and characterization of the interaction between tetratricopeptide repeat domain 9 (TTC9) and Tm5NM-1.
Authors: Sheng-Lan Cao, Valerie Lin
Journal: Cancer Research (2007)

3173  TTC9 protein is a recently identified 25 kD protein which contains three tetratricopeptide repeats (TPRs) on its C-terminal. Studies have shown that the expression of TTC9 was regulated by steroid hormones and growth factors in different breast cancer cell lines. TTC9 was also ubiquitously expressed in different tissues and was expressed at a higher level in breast cancer tissues compared with adjacent normal tissues. To further elucidate the function of TTC9, we performed yeast-two-hybrid screening and identified Tm5NM-1 as one of the partner proteins that interact with full length and truncated TTC9 in yeast. Tm5NM-1 is a non-muscle tropomyosin encoded by γ-tropomyosin gene. It has been shown to be associated with stress fibers and is involved in promoting cell spreading and stress fiber formation in rat cortical neuronal cells. The interaction between TTC9 and Tm5NM-1 was further confirmed by pull-down assay with GST-TTC9 and co-immunoprecipitation in mammalian cells. Truncation studies revealed that the segment between amino acids 85-115, which lies between the first two TPR domains, was critical for the interaction. Amino acids 1-50 were also required for the interaction, possibly by maintaining the protein in proper conformation. Since the primary function of tropomyosin family proteins is to stabilize actin filament, its interaction with TTC9 may play a role in cell shape and motility. Indeed, adherent cells express higher level of TTC9 compared with suspension cells, and progesterone-induced TTC9 expression is associated with increased cell motility and cell spreading. We speculate that TTC9 act as a chaperone protein to facilitate the function of tropomyosins in stabilizing microfilament and it may play a role in cancer cell invasion and metastasis.
Calibration of CTS5 in Women With Early Estrogen Receptor–Positive Breast Cancer
Authors: Mitch Dowsett, Ivana Sestak, Jack Cuzick
Journal: Journal of Clinical Oncology (2020)

Calibration of CTS5 in Women With Early Estrogen Receptor-Positive Breast CancerNoordhoek et al 1 have expressed interest in assessing the validity of the Clinical Treatment Score post-5 years (CTS5), but unfortunately we disagree that their data reliably support their key conclusion that the CTS5 overestimates risk in high-risk patients with estrogen receptor-positive breast cancer who remain free of distant recurrence after 5 years of endocrine therapy.
The pyruvate-lactate axis modulates cardiac hypertrophy and heart failure
Authors: Ahmad A. Cluntun, Rachit Badolia, Sandra Lettlova, K. Mark Parnell, Thirupura S. Shankar, Nikolaos A. Diakos, Kristofor A. Olson, Iosif Taleb, Sean M. Tatum, Jordan A. Berg, Corey N. Cunningham, Tyler Van Ry, Alex J. Bott, Aspasia Thodou Krokidi, Sarah Fogarty, Sophia Skedros, Wojciech I. Swiatek, Xuejing Yu, Bai Luo, Shannon Merx, Sutip Navankasattusas, James E. Cox, Gregory S. Ducker, William L. Holland, Stephen H. McKellar, Jared Rutter, Stavros G. Drakos
Journal: Cell Metabolism (2020)
SURG-20. USE OF NICO MYRIAD NOVUS DEVICE WITH LIGHT SOURCE AND REAL-TIME STEREOTACTIC NAVIGATION TO OPTIMIZE SURGICAL RESECTION OF DEEP-SEATED TUMORS
Authors: Lee Hwang, Alireza Mohammadi
Journal: Neuro-Oncology (2020)

Abstract Maximal and safe surgical resection remains a critical component of the standard of care for patients with brain tumors. Stereotactic navigation tools are often incorporated into the surgical planning and implementation. The NICO Myriad NOVUS device couples a light source with the resecting tip to allow enhanced visualization of the surgical cavity and surrounding anatomical structures. At the Cleveland Clinic, we were the first group in the U.S. to start utilizing this augmented technology to maximize the resection of particularly deep-seated brain tumors, using the xenon light and real-time stereotactic navigation of the tool tip with the BrainLAB cranial setting. The navigated tip allows us to reach the deep corners of tumors with or without a tubular retracting device by sparing large corticotomies. Furthermore, the light source within the handheld device is easier to handle and manipulate than a large microscope to illuminate the surgical cavity. In addition, this new tool allows for automated tumor and peri-tumoral tissue harvesting, annotating each sample by location intraoperatively, as well as biological preservation of the harvested tissue for post-surgical molecular analysis. We describe the techniques and advantages of using this novel technology in patients while following and preliminarily reporting their surgical outcomes. With the emergence of novel technological advances, we must adapt as neurosurgeons and develop innovative methods to optimize the surgical resection of brain tumors.
MBCL-20. DETECTION OF SOMATIC MUTATIONS BY USING RNA-SEQ DATA IN CHILDHOOD MEDULLOBLASTOMA AND ITS POTENTIAL CLINICAL APPLICATION: A COHORT SERIES OF 52 CASES STUDY IN TAIWAN
Authors: Tai-Tong Wong, Kuo-Sheng Wu, Donald Ming-Tak Ho, Shih-Chieh Lin, Wen-Chang Huang, Muh-Lii Laing, Hsin-Hung Chen
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND In 2016, a project was initiated in Taiwan to adopt molecular diagnosis of childhood medulloblastoma (MB). Part of our aim was to explore the clinical application for drug target identification and finding clues to genetic predisposition. METHODS In total, 52 frozen tumor tissues of childhood MBs were collected. RNA-Seq and DNA methylation array data were generated. Molecular subgrouping was performed. We selected 51 clinically relevant genes for somatic variant calling using RNA-Seq data. Correlated clinical findings to genetic predisposition were defined. Potential drug targets and genetic predispositions were explored. RESULTS Four core molecular subgroups (WNT, SHH, Group 3, and Group 4) were identified. Potential drug targets were detected in the pathways of DNA damage response. Five patients with relevant clinical findings to genetic predisposition clustered in SHH MBs. The corresponding somatic driver mutations involved TP53, MSH6, PTEN, PTCH1, and TERT promoter (suspicious). For validation, whole exome sequencing (WES) of blood and tumor tissue was used in 10 patients with SHH MBs in the cohort series. This study included the five patients with potential genetic predispositions. Four patients exhibited relevant germline mutations named as TP53, MSH6, PTEN, and SUFU. CONCLUSION The findings of this study provide valuable information for personalized care of childhood MB in our cohort series and in Taiwan.
MBRS-29. PROSPECTIVE MOLECULAR PROFILING IN PEDIATRIC MEDULLOBLASTOMA PATIENTS ENROLLED ON THE “HEAD START 4” PROTOCOL
Authors: Jessica Fleming, Erica Bell, Richard Graham, Amy Webb, Joseph McElroy, Cynthia Timmers, Aline Becker, Yingshi Guo, Girish Dhall, Jonathan Finlay, Arnab Chakravarti
Journal: Neuro-Oncology (2020)

Abstract Medulloblastoma is the most common malignant embryonal brain tumor in children with only modest improvements in outcomes achieved over the last 20 years. The implementation of irradiation-avoiding strategies, including trials by the “Head Start” consortium, have demonstrated improved cure rates along with enhanced quality of life. Simultaneously, the classification of medulloblastomas has undergone a dramatic shift as molecular testing has made it possible to divide these tumors into distinctive subtypes. Currently, the WHO recognizes four medulloblastoma molecular subgroups; however it remains unclear how patients within these subgroups respond to modern irradiation-avoiding therapies. This study aims to demonstrate the feasibility of prospective molecular profiling in medulloblastoma patients enrolled on the “Head Start 4” trial. Whole-exome sequencing (SureSelect Human All Exon V6+COSMIC) and DNA methylation (Illumina EPIC Array) profiling were performed on 10 paired tumor/blood samples and 4 tumor samples, respectively. High-quality mutational and copy number data were produced for each of the 10 subjects demonstrating well-described gene mutations (SUFU) and chromosomal losses (9q and 10q). Four subjects had methylation profiling which successfully separated them into the WHO subgroups (two SHH and two Group 3). These data showed the feasibility of prospective high-dimensional mutational and DNA methylation analysis using “Head Start 4” patients. Future work will focus on finalizing these profiling efforts, enabling the development of models that predict response to irradiation-avoiding treatment and, in general, a better understanding of the molecular mechanisms underlying treatment resistance and tumor progression, leading to more personalized approaches to treating children with medulloblastoma.
BIOM-59. TERT PROMOTER MUTATION AND MGMT PROMOTER METHYLATION-MEDIATED SENSITIVITY TO TEMOZOLOMIDE IN IDH-WILDTYPE GLIOBLASTOMA: IS THERE A LINK?
Authors: Dorothee Gramatzki, Jörg Felsberg, Bettina Hentschel, Marietta Wolter, Gabriele Schackert, Manfred Westphal, Luca Regli, Niklas Thon, Marcos Tatagiba, Wolfgang Wick, Uwe Schlegel, Dietmar Krex, Jakob Matschke, Patrick Roth, Marian Suresh, Marcel Kamp, Elisabeth Rushing, Torsten Pietsch, Andreas von Deimling, Michael Sabel, Markus Loeffler, Michael Weller, Guido Reifenberger
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Benefit from temozolomide (TMZ) chemotherapy in the treatment of isocitrate dehydrogenase (IDH)-wildtype glioblastoma is essentially limited to patients with O6-methylguanine DNA methyltransferase (MGMT) promoter-methylated tumors. Recent studies suggest that the impact of the MGMT status on chemosensitivity may be modulated by telomerase reverse transcriptase (TERT) promoter hotspot mutations. METHODS MGMT promoter methylation and TERT promoter mutation status were assessed in an exploratory prospective cohort of IDH-wildtype glioblastoma patients of the German Glioma Network (GGN) (n=298) and validated in a retrospective cohort from Düsseldorf, Germany, and Zurich, Switzerland (n=302). RESULTS In the prospective GGN discovery cohort of patients with MGMT promoter-unmethylated tumors, TERT promoter mutation showed inferior outcome (p=0.044). In contrast, TERT promoter mutations were not associated with improved outcome in patients with MGMT promoter-methylated tumors. Different TERT promoter hotspot mutations were not associated with distinct outcomes. The association of TERT promoter mutation in MGMT promoter-unmethylated tumors was not confirmed in the retrospective validation cohort. CONCLUSIONS Analysis of two independent cohorts of glioblastoma patients, including the prospective GGN cohort, did not confirm previous data suggesting that TERT promoter mutations confer an enhanced benefit from TMZ in patients with MGMT promoter-methylated glioblastoma. Thus, diagnostic testing for TERT promoter mutations may not be required for prediction of TMZ sensitivity in IDH-wildtype glioblastoma patients.
Estimating my equilibrium energy intake during lockdown: very introspective study
Authors: R A Lewis
Journal: BMJ (2020)

Abstract Objective To estimate the daily dietary energy intake for me to maintain a constant body weight. How hard can it be? Design Very introspective study. Setting At home. In lockdown. (Except every Tuesday afternoon and Saturday morning, when I went for a run.) Participants Me. n=1. Main outcome measures My weight, measured each day. Results Sleeping, I shed about a kilogram each night (1.07 (SD 0.25) kg). Running 5 km, I shed about half a kilogram (0.57 (SD 0.15) kg). My daily equilibrium energy intake is about 10 000 kJ (10 286 (SD 201) kJ). Every kJ above (or below) 10 000 kJ adds (or subtracts) about 40 mg (35.4 (SD 3.2) mg). Conclusions Body weight data show persistent variability, even when the screws of control are tightened and tightened.
NCOG-18. IS THE RANO CRITERIA FOR LOW-GRADE GLIOMA RELIABLE IN THE CLINICAL SETTING? – A RELIABILITY STUDY
Authors: Erika Horta, Yueren Zhou, Laila M Poisson, Brent Griffith, Michael Stone, James Snyder, Tobias Walbert
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Magnetic resonance imaging (MRI) is a fundamental component of longitudinal neuro-oncology evaluation and decision-making. The Response Assessment in Neuro-Oncology criteria for low-grade gliomas (RANOLGG) was designed as an outcome measure for clinical trials. Thus, this project intends to study the reliability of RANOLGG in the clinic setting. METHODS 21 pairs of brain MRIs, that averaged three years apart, were selected from 21 patients with tissue diagnosis of WHO grade 2 gliomas. Two neuro-oncologists and two neuro-radiologists reviewed and independently scored the MRI pairs according to RANOLGG categories of progressive disease, stable disease, minor response, partial response, and complete response. Kappa-Fleiss (KF) was used to evaluate agreement among reviewers. RESULTS Reviewers awarded identical scores in only 33% of MRI pairs and there was a complete disagreement in one MRI pair. Overall reliability of the criteria in the clinical setting is moderate (KF = 0.44). Agreement between neuroradiologists (KF = 0.51) and between neuro-oncologists (KF = 0.48) were similar. Interpretation of post-contrast T1-weighted images had a better agreement (KF = 0.31) than T2/FLAIR-weighted images which had a poor agreement (KF = -0.02). Classification of progression versus non-progression had only a moderate agreement (KF= 0.49). History of radiation therapy or chemotherapy did not influence the criteria reliability (fisher exact text, p = 0.58, p =0.27, respectively). CONCLUSION RANOLGG reliability in the clinical setting is moderate, therefore it should be used cautiously for clinical decision-making. Other tools that can support the neuro-oncologist in the follow-up of patients with low-grade glioma are additional MRI sequences other than T2/FLAIR and contrast – weighted images, computer-aided diagnosis such as volumetrics, spectroscopy, positron emission tomography, and multidisciplinary tumor boards. Likewise, when image criteria for low-grade gliomas are designed, T2/FLAIR should be used guardedly, due to low interpretation agreement.
Integrated photodynamic Raman theranostic system for cancer diagnosis, treatment, and post-treatment molecular monitoring
Authors: Conor C. Horgan, Mads S. Bergholt, Anika Nagelkerke, May Zaw Thin, Isaac J. Pence, Ulrike Kauscher, Tammy L. Kalber, Daniel J. Stuckey, Molly M. Stevens
Journal: Theranostics (2020)

Theranostics, the combination of diagnosis and therapy, has long held promise as a means to achieving personalised precision cancer treatments.However, despite its potential, theranostics has yet to realise significant clinical translation, largely due the complexity and overriding toxicity concerns of existing theranostic nanoparticle strategies.Methods: Here, we present an alternative nanoparticle-free theranostic approach based on simultaneous Raman spectroscopy and photodynamic therapy (PDT) in an integrated clinical platform for cancer theranostics.Results: We detail the compatibility of Raman spectroscopy and PDT for cancer theranostics, whereby Raman spectroscopic diagnosis can be performed on PDT photosensitiser-positive cells and tissues without inadvertent photosensitiser activation/photobleaching or impaired diagnostic capacity.We further demonstrate that our theranostic platform enables in vivo tumour diagnosis, treatment, and post-treatment molecular monitoring in real-time.Conclusion: This system thus achieves effective theranostic performance, providing a promising new avenue towards the clinical realisation of theranostics.
Amyloidosis and 30-Day Outcomes Among Patients With Heart Failure
Authors: Sameer Arora, Nikita S. Patil, Paula D. Strassle, Arman Qamar, Muthiah Vaduganathan, Amber Fatima, Kalyan Mogili, Deepak Garipalli, Justin L. Grodin, John P. Vavalle, Gregg C. Fonarow, Deepak L. Bhatt, Ambarish Pandey
Journal: JACC CardioOncology (2020)

The burden of amyloidosis among hospitalized patients is increasing over time. However, amyloidosis remains an underdiagnosed cause of heart failure (HF) hospitalization among older adults.We investigated the prevalence and prognostic implications of amyloidosis among patients hospitalized with HF.All hospitalizations for primary diagnosis of HF between January 1, 2010, and August 31, 2015, identified in the Nationwide Readmissions Database were categorized into those with and without a secondary diagnosis of amyloidosis. HF hospitalizations with amyloidosis were then matched in a 3:1 fashion to HF hospitalizations without amyloidosis using the year of admission, discharge quarter, age, sex, and Charlson comorbidity index. Primary outcomes were inpatient mortality and 30-day readmission. Multivariable logistic regression was used to estimate the association between HF with amyloidosis and clinical outcomes.Of 1,593,360 HF hospitalizations that met inclusion criteria, 2,846 (0.18%) had HF with a secondary diagnosis of amyloidosis and were matched to 8,515 hospitalizations for HF without amyloidosis. Hospitalizations for HF with amyloidosis were associated with higher prevalence of kidney disease (56% vs. 45%), malignancy (20% vs. 4%), and higher inpatient mortality (6% vs. 3%) as compared with HF without amyloidosis. In adjusted analyses, HF with amyloidosis was associated with higher odds of in-hospital mortality (odds ratio: 1.46; 95% confidence interval [CI]: 1.17 to 1.82), 30-day readmission (odds ratio: 1.17; 95% CI: 1.05 to 1.31), and longer mean length of stay (least-squares mean difference: 1.46; 95% CI: 1.12 to 1.80).In patients hospitalized with decompensated HF, presence of amyloidosis was associated with higher risk of inpatient mortality and 30-day readmission.
36P Progression-free survival as a surrogate for overall survival in trials of immune checkpoint inhibitors in pan cancer evaluated by RECIST 1.1
Authors: L. Lin, H. Xu, J. Ding, T. Qin, M. Xu, J. Shen, W. Jiang, J. Wang, D. Cheng, Z. Li, H. Hu, Y. Yu, H. Yao
Journal: Annals of Oncology (2020)
Turning Nature’s own processes into design strategies for living bone implant biomanufacturing: a decade of Developmental Engineering
Authors: Ioannis Papantoniou, Gabriella Nilsson Hall, Niki Loverdou, Raphaelle Lesage, Tim Herpelinck, Luis Mendes, Liesbet Geris
Journal: Advanced Drug Delivery Reviews (2020)

A decade after the term developmental engineering (DE) was coined to indicate the use of developmental processes as blueprints for the design and development of engineered living implants, a myriad of proof-of-concept studies demonstrate the potential of this approach in small animal models. This review provides an overview of DE work, focusing on applications in bone regeneration. Enabling technologies allow to quantify the distance between in vitro processes and their developmental counterpart, as well as to design strategies to reduce that distance. By embedding Nature's robust mechanisms of action in engineered constructs, predictive large animal data and subsequent positive clinical outcomes can be gradually achieved. To this end, the development of next generation biofabrication technologies should provide the necessary scale and precision for robust living bone implant biomanufacturing.
The role of circulating eosinophils on COVID‐19 mortality varies by race/ethnicity
Authors: Jacob W. Glickman, Ana B. Pavel, Emma Guttman‐Yassky, Rachel L. Miller
Journal: Allergy (2020)

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EPCO-18. MULTI-MODAL AND MULTI-TISSUE PROFILING OF GBM PATIENTS TREATED WITH CAR T CELL THERAPY TO ELUCIDATE MOLECULAR MECHANISMS OF VARIATION IN TREATMENT RESPONSE
Authors: Stephanie Yahn, Sophia Zhang, Lance Peter, Mei-I Chung, Austin Gutierrez, Renate Starr, Darya Alizadeh, Christine Brown, Nicholas Banovich
Journal: Neuro-Oncology (2020)

Abstract Recent advances in immunotherapy, particularly chimeric antigen receptor (CAR)-engineered T cell therapy, have shown promise for the treatment of many tumor types including progressive recurrent glioblastoma (GBM). While early phase clinical trials have illuminated the potential for CAR T cell therapy to effectively treat GBM, they have also highlighted the unique challenges regarding the efficacy and safety of immunotherapy for brain tumors, and many patients continue to progress during therapy. We seek to overcome these challenges and ultimately extend the time of survival for patients diagnosed with GBM by investigating the immune- and tumor-mediated mechanisms driving variation in response to CAR T cell therapy. We generated the first multi-omics time-series dataset of CAR T cells, endogenous immune cells, and tumor cells from 59 GBM patients treated with CAR T cell therapy. Using single cell RNA-sequencing and simultaneous quantification of nearly 200 cell surface proteins, we comprehensively profiled the cellular phenotypes and signaling pathways within tumor and circulating immune cells that are associated with treatment response. The combination of mRNA and protein expression allowed us to resolve cell states beyond what either modality was capable of alone. Additionally, we found differentially expressed genes and proteins between tumor biopsies collected before and after CAR T cell therapy as well as differential expression between pre-infusion CAR T cells and those identified within the tumor following infusion. By evaluating the CAR T cell phenotypes prior to and during treatment we sought to address the outstanding question of how intrinsic variability impacts the activity and persistence of CAR T cells and to determine the phenotypes that confer the greatest therapeutic benefit for patients with GBM. Our results have direct implications for precision medicine and future clinical trials investigating the use of CAR T cell therapy for GBM as well as other solid tumors.
Coronary Angiographic Evaluation of Low-Risk Chest Pain in the Emergency Department: CT-STAT, or Maybe Not Quite That Fast?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Michael Salerno, Jamieson M. Bourque, George A. Beller
Journal: Journal of the American College of Cardiology (2011)