tbuckley/cabot-search huggingface dataset:
Mex3a promotes oncogenesis through the RAP1/MAPK signaling pathway in colorectal cancer and is inhibited by hsa‐miR‐6887‐3p
Authors: Haixia Li, Jinghui Liang, Jiang Wang, Jingyi Han, Shuang Li, Kai Huang, Chuanyong Liu
Journal: Cancer Communications (2021)

Abstract Background Although Mex3 RNA‐binding family member A (Mex3a) has demonstrated an important role in multiple cancers, its role and regulatory mechanism in CRC is unclear. In this study, we aimed to investigate the role and clinical significance of Mex3a in CRC and to explore its underlying mechanism. Methods Western blotting and quantitative real‐time polymerase chain reaction (qRT‐PCR) were performed to detect the expression levels of genes. 5‐Ethynyl‐2'‐deoxyuridine (EDU) and transwell assays were utilized to examine CRC cell proliferation and metastatic ability. The R software was used to do hierarchical clustering analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Overexpression and rescue experiments which included U0126, a specific mitogen activated protein kinase kinase/extracellular regulated protein kinase (MEK/ERK) inhibitor, and PX‐478, a hypoxia‐inducible factor 1 subunit alpha (HIF‐1α) inhibitor, were used to study the molecular mechanisms of Mex3a in CRC cells. Co‐immunoprecipitation (Co‐IP) assay was performed to detect the interaction between two proteins. Bioinformatics analysis including available public database and Starbase software (starbase.sysu.edu.cn) were used to evaluate the expression and prognostic significance of genes. TargetScan ( www.targetscan.org ) and the miRDB (mirdb.org) website were used to predict the combination site between microRNA and target mRNA. BALB/c nude mice were used to study the function of Mex3a and hsa‐miR‐6887‐3p in vivo . Results Clinicopathological and immunohistochemical (IHC) studies of 101 CRC tissues and 79 normal tissues demonstrated that Mex3a was a significant prognostic factor for overall survival (OS) in CRC patients. Mex3a knockdown substantially inhibited the migration, invasion, and proliferation of CRC cells. Transcriptome analysis and mechanism verification showed that Mex3a regulated the RAP1 GTPase activating protein (RAP1GAP)/MEK/ERK/HIF‐1α pathway. Furthermore, RAP1GAP was identified to interact with Mex3a in Co‐IP experiments. Bioinformatics and dual‐luciferase reporter experiments revealed that hsa‐miR‐6887‐3p could bind to the 3'‐untranslated regions (3'‐UTR) of the Mex3a mRNA. hsa‐miR‐6887‐3p downregulated Mex3a expression and inhibited the tumorigenesis of CRC both in vitro and in vivo . Conclusions Our study demonstrated that the hsa‐miR‐6887‐3p/Mex3a/RAP1GAP signaling axis was a key regulator of CRC and Mex3a has the potential to be a new diagnostic marker and treatment target for CRC.
The association of objectively measured physical activity and sedentary behavior with skeletal muscle strength and muscle power in older adults: A systematic review and meta-analysis
Authors: Keenan A. Ramsey, Anna G.M. Rojer, Luke D’Andrea, René H.J. Otten, Martijn W. Heymans, Marijke C. Trappenburg, Sjors Verlaan, Anna C. Whittaker, Carel G.M. Meskers, Andrea B. Maier
Journal: Ageing Research Reviews (2021)

Engaging in physical activity (PA) and avoiding sedentary behavior (SB) are important for healthy ageing with benefits including the mitigation of disability and mortality. Whether benefits extend to key determinants of disability and mortality, namely muscle strength and muscle power, is unclear.This systematic review aimed to describe the association of objective measures of PA and SB with measures of skeletal muscle strength and muscle power in community-dwelling older adults.Six databases were searched from their inception to June 21st, 2020 for articles reporting associations between objectively measured PA and SB and upper body or lower body muscle strength or muscle power in community dwelling adults aged 60 years and older. An overview of associations was visualized by effect direction heat maps, standardized effect sizes were estimated with albatross plots and summarized in box plots. Articles reporting adjusted standardized regression coefficients (β) were included in meta-analyses.A total of 112 articles were included representing 43,796 individuals (range: 21 to 3726 per article) with a mean or median age from 61.0 to 88.0 years (mean 56.4 % female). Higher PA measures and lower SB were associated with better upper body muscle strength (hand grip strength), upper body muscle power (arm curl), lower body muscle strength, and lower body muscle power (chair stand test). Median standardized effect sizes were consistently larger for measures of PA and SB with lower compared to upper body muscle strength and muscle power. The meta-analyses of adjusted β coefficients confirmed the associations between total PA (TPA), moderate-to-vigorous PA (MVPA) and light PA (LPA) with hand grip strength (β = 0.041, β = 0.057, and β = 0.070, respectively, all p ≤ 0.001), and TPA and MVPA with chair stand test (β = 0.199 and β = 0.211, respectively, all p ≤ 0.001).Higher PA and lower SB are associated with greater skeletal muscle strength and muscle power, particularly with the chair stand test.
Plant-Based Beverages in the Diets of Infants and Young Children
Authors: Lisa M. Bodnar, Elizabeth Y. Jimenez, Susan S. Baker
Journal: JAMA Pediatrics (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Abstract PD9-12: Concordance and use patterns of tissue and cell-free based genomic testing in metastatic breast cancer
Authors: Minetta Liu, Jeff Schaffer, Aneta Piwowarczyk, Nike Beaubier, Kimberly Blackwell, Ben Park
Journal: Cancer Research (2021)

Abstract Genomic testing has transformed clinical care in metastatic breast cancer. Cell-free DNA (cfDNA) has made sequential testing feasible, however, concordance between tissue and cfDNA, sensitivity of cfDNA, and optimal sampling frequency have not been examined on large data sets with clinical annotation. Of the 648 genes in the tissue NGS Tempus xT assay, 105 genes are also included in the Tempus xF cfDNA plasma-based test. Both platforms are run on Illumina and detect SNVs, indels, CNVs, and rearrangements/fusions with high sensitivity and specificity (&amp;gt;90%). This study used the Tempus Labs LENS™ tool to identify the most recent ~3,300 metastatic breast cancer patients who underwent clinical testing and had either tissue-based testing, cfDNA testing or both. Of the 212 patients with xF and xT testing, 87 had xT before xF, 135 had xF before xT, and 7 had the testing performed at the same time. The most common pathogenic germline versus somatic alterations on tissue-based testing and their concordance will also be reported. In summary, this data suggests a variable amount of concordance between tissue-based and plasma-based assays. Timing of assay performance and inclusion of germline DNA might play an important role in contributing to these differences which need further exploration. Table: Count of Reported Variants and xT/xF Concordance by GeneSomatic GenesxF frequency (n)xT frequency(n)Concordance Between xF and xTTP5313911043%PIK3CA848058%ESR1584141%BRCA238217%ERBB2372629%NF1322113%RB1272416%ATM30165%GATA3213441%FGFR13353%PTEN193036%ARID1A251823% Citation Format: Minetta Liu, Jeff Schaffer, Aneta Piwowarczyk, Nike Beaubier, Kimberly Blackwell, Ben Park. Concordance and use patterns of tissue and cell-free based genomic testing in metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD9-12.
Abstract 3410: B-type Natriuretic Peptide, Subclinical Atherosclerosis and Prognosis
Authors: Donna M Polk, Torry A Kahute, Leslee J Shaw, Nathan D Wong, Johanna H Moon, Daniel S Berman
Journal: Circulation (2006)

Intro: B-type Natiuretic Peptide (BNP) has prognostic implications in pts with heart failure. Its prognostic role in asymptomatic pts with subclinical disease remains unclear. Methods: We studied 2...
The ideal location of the male nipple-areolar complex: A pinpointing algorithm
Authors: F. W. Timmermans, B. A. M. Jansen, S. E. Mokken, M. H. de Heer, K. M. Veen, M. B. Bouman, M. Mullender, T. C. van de Grift
Journal: International Journal of Transgender Health (2021)

In the treatment of gender dysphoria, appropriate nipple-areola complex (NAC) positioning is essential for achieving a natural appearing male chest after subcutaneous mastectomy. An accurate predictive model for the ideal personalized position of the NAC is still lacking. The aim of this study is to determine the anthropometry of the male chest to create individualized guidelines for appropriate NAC positioning in the preoperative setting.Cisgender male participants were recruited. Multiple chest measurements were manually recorded. Best subset regression using linear models was used to select predictors for the horizontal coordinate (nipple-nipple distance; NN) and vertical coordinate (sternal notch-nipple distance; SNN) of the NAC. Internal validation was assessed using bootstrapping. Furthermore, a cohort of transgender men who had received a mastectomy with replantation of nipples according to current practice was identified. Comparison testing between the algorithm and standard practice was performed to test the limitations of standard practice.One hundred and fifty cis male participants were included (median age: 26, IQR: 22-34 years). Four predictors were found to predict NN (age, weight, chest circumference (CC), anterior-axillar fold to anterior-axillar fold (AUX-AUX)) and reads as follows: NN = 4.11 + 0.035*age + 0.041*weight + 0.093*CC + 0.140*AUX-AUX Two predictors were found to predict SNN (NN and weight), and reads as follows: SNN = 7.248 + 0.303*NN + 0.072*weight. Both models performed well (Bootstrapped R2: 0.63 (NN), 0.50 (SNN)) and outperformed previous models predicting NAC position. Ninety-six transgender men were eligible for evaluation of current practice and showed an average placement error of -0.9 cm for NN and +2.2 cm for SNN.The non-standardized approach of NAC repositioning results in a significant error of nipple placement. We suggest that the two predictive models for NN and SNN can be used to optimize NAC positioning on the masculinized chest wall.Supplemental data for this article is available online at https://doi.org/10.1080/26895269.2021.1884926.
IRF4 modulates the response to BCR activation in chronic lymphocytic leukemia regulating IKAROS and SYK
Authors: Rossana Maffei, Stefania Fiorcari, Stefania Benatti, Claudio Giacinto Atene, Silvia Martinelli, Patrizia Zucchini, Leonardo Potenza, Mario Luppi, Roberto Marasca
Journal: Leukemia (2021)
Clonal evolution of acute myeloid leukemia with <i>FLT3</i>-ITD mutation under treatment with midostaurin
Authors: Laura K. Schmalbrock, Anna Dolnik, Sibylle Cocciardi, Eric Sträng, Frauke Theis, Nikolaus Jahn, Ekaterina Panina, Tamara J. Blätte, Julia Herzig, Sabrina Skambraks, Frank G. Rücker, Verena I. Gaidzik, Peter Paschka, Walter Fiedler, Helmut R. Salih, Gerald Wulf, Thomas Schroeder, Michael Lübbert, Richard F. Schlenk, Felicitas Thol, Michael Heuser, Richard A. Larson, Arnold Ganser, Hendrik G. Stunnenberg, Saverio Minucci, Richard M. Stone, Clara D. Bloomfield, Hartmut Döhner, Konstanze Döhner, Lars Bullinger
Journal: Blood (2021)
Cardiovascular Findings on Chest Computed Tomography Predict Clinical Outcomes in COVID-19
Authors: M. I. C. Planek, S. Kyung, M. A. Ruge, J. D. De Lavallaz, A. S. Volgman, K. A. Williams, T. B. Suboc, J. A. Simmons, A. Rao
Journal: Circulation (2020)
Challenges and Possibilities of Cell-Based Tissue-Engineered Vascular Grafts
Authors: Junichi Saito, Makoto Kaneko, Yoshihiro Ishikawa, Utako Yokoyama
Journal: Cyborg and Bionic Systems (2021)

There is urgent demand for biologically compatible vascular grafts for both adult and pediatric patients. The utility of conventional nonbiodegradable materials is limited because of their thrombogenicity and inability to grow, while autologous vascular grafts involve considerable disadvantages, including the invasive procedures required to obtain these healthy vessels from patients and insufficient availability in patients with systemic atherosclerosis. All of these issues could be overcome by tissue-engineered vascular grafts (TEVGs). A large body of evidence has recently emerged in support of TEVG technologies, introducing diverse cell sources (e.g., somatic cells and stem cells) and novel fabrication methods (e.g., scaffold-guided and self-assembled approaches). Before TEVG can be applied in a clinical setting, however, several aspects of the technology must be improved, such as the feasibility of obtaining cells, their biocompatibility and mechanical properties, and the time needed for fabrication, while the safety of supplemented materials, the patency and nonthrombogenicity of TEVGs, their growth potential, and the long-term influence of implanted TEVGs in the body must be assessed. Although recent advances in TEVG fabrication have yielded promising results, more research is needed to achieve the most feasible methods for generating optimal TEVGs. This article reviews multiple aspects of TEVG fabrication, including mechanical requirements, extracellular matrix components, cell sources, and tissue engineering approaches. The potential of periodic hydrostatic pressurization in the production of scaffold-free TEVGs with optimal elasticity and stiffness is also discussed. In the future, the integration of multiple technologies is expected to enable improved TEVG performance.
Abstract PS4-46: Homologous recombination deficiency score predicts patient characteristics and outcomes of triple negative breast cancer in China
Authors: Xue Wang, Feng Du, Jian Yue, Yiran Si, Lina Cui, Peng Yuan
Journal: Cancer Research (2021)

Abstract BackgroundPrevious studies found homologous recombination deficiency (HRD) score could predict response to platinum-containing neoadjuvant chemotherapy in patients with triple negative breast cancer (TNBC), but its predictive effects of adjuvant chemotherapy is unexplored. Methods We developed the 3DMed-HRD algorithm, which combines loss of heterozygosity score (LOH), telomeric allelic imbalance score (TAI) and large-scale state transition score (LST) to characterize genomic instability using over 10000 SNPs, adjusted by tumor ploidy and purity. HRD positive is defined by deleterious mutation in BRCA1/2 or HRD score above the threshold (cut-off ≥30). Tumor samples were retrospectively obtained from 149 TNBC patients who received platinum-based (paclitaxel and cisplatin, TP) or platinum-free (cyclophosphamide and adriamycin, EC) adjuvant chemotherapy after surgery. All patients underwent the 3DMed-HRD testing. ResultsIn 25.5% (38/149) of TNBC patients deleterious germline or somatic mutation in BRCA 1/2 was detected. HRD results were available for all patients and 81of the 149 patients (54.4%) were defined as HRD positive. HRD-positive patients had younger age at diagnosis (median 46.7 years vs 51.5 years, P=0.002), higher differentiated (59.8% vs 39.5%; p=0.037), lower N-stage (55.7% vs 33.3%; p=0.006) and more common at high expression of Ki67 (64.7% vs 39.0%; p=0.015). In TP treatment group, patients with HRD positive tumors had a lower 5-year recurrence rate although the difference was not statistically significant (8.82% vs 16.1%; p=0.463). Patients in EC treatment cohort, 5-year recurrence rate was comparable between HRD positive and negative subgroups (15.4% vs 13.3%; p=1.0). In the 81 patients in HRD-positive cohort, patients in TP treatment group showed a numerical lower 5-year recurrence rates compared with patients in EC treatment group (8.82% vs 15.4%; p=0.489). Conclusions54.5% patients were characterized as HRD positive in TNBC patients in our cohort. HRD was associated with clinicopathologic characteristics. Our results suggested that HRD status mightguide chemotherapy treatment decisions. Prospective validation with larger sample size is needed. Citation Format: Xue Wang, Feng Du, Jian Yue, Yiran Si, Lina Cui, Peng Yuan. Homologous recombination deficiency score predicts patient characteristics and outcomes of triple negative breast cancer in China [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-46.
Abstract SP037: New insights to cancer-associated systemic inflammation
Authors: KE de Visser
Journal: Cancer Research (2021)

Abstract The occurrence of distant metastases accounts for over 90% of breast cancer deaths. Despite these devastating effects, metastatic disease is poorly understood and incurable. Clearly, there is an urgent need for novel therapeutic strategies that prevent and/or cure metastatic disease. For successful dissemination and metastasis, cancer cells must evade detection and destruction by the immune system and adapt to a foreign tissue environment. This process is enabled by factors secreted by the primary tumor that shape both the intratumoral microenvironment and the systemic immune landscape. By manipulating systemic immune responses and creating conditions of chronic inflammation, tumors can have a long-distance reach and transform distant tissues that are intrinsically hostile to metastatic colonization into niches that are more hospitable for metastatic lesions to grow out. Key feature of this systemic process - often referred to as pre-metastatic niche formation- is the mobilization and polarization of (immature) myeloid immune cells from the bone marrow to the circulation, tumor and distant organs. We and others have used preclinical tumor models to demonstrate that these tumor-mobilized myeloid cells, including neutrophils and macrophages, contribute to a systemic immunosuppressive environment that inhibits anti-tumor immune responses and fosters metastasis formation. The pro-metastatic function of systemic inflammation is supported by clinical observations demonstrating that neutrophil accumulation in blood of cancer patients is strongly associated with poor survival and increased risk for metastasis. Targeting pro-metastatic inflammation represents an attractive strategy to prevent or treat metastatic disease. Importantly, the oncology field can benefit from compounds that have already been developed for the treatment of inflammatory diseases. In this Educational Session talk, I will discuss current insights into how tumors engage the immune system systemically, how systemic inflammation impacts disease progression and therapy response and how we can utilize these insights for the design of novel therapeutic opportunities. A great challenge in the field of immuno-oncology is the unexplained inter-patient heterogeneity in the intratumoral and systemic composition and functional state of the immune system. I will share some of our recent insights into how cancer cell-intrinsic mechanisms lie at the basis of this heterogeneity in the immune milieu of breast cancer, which may set the stage for personalized immune-intervention strategies. Citation Format: KE de Visser. New insights to cancer-associated systemic inflammation [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP037.
Abstract OT-15-01: A phase II trial with safety run-in of neoadjuvant therapy with an aromatase inhibitor in combination with durvalumab (MEDI4736) in postmenopausal patients with hormone-receptor-positive (HR+) breast cancer
Authors: Hung T Khong, Dawn N Goodridge, Nazanin Khakpour, M. Catherine Lee, Christine Laronga, Avan J Armaghani, Aixa E Soyano-Muller, Hyo Han, Hatem Soliman, Ricardo Costa, Loretta Loftus, Susan J Hoover, John V Kiluk, Zena Jameel, Brian J Czerniecki
Journal: Cancer Research (2021)

Abstract Background: HR+ breast cancer has a long dormancy and steady rate of recurrence over decades from initial diagnosis. It is a misconception to think that HR+ disease has good prognosis since long term PFS and OS are only a few percent better for HR+ disease compared with HR- disease over a follow up of 20 years. Neoadjuvant endocrine therapy has been shown to be equivalent to chemotherapy but less toxicity. Aromatase inhibitors have also been shown to have immunomodulatory activity. In order to improve short term and long term outcomes, we started an investigator-initiated study using anastrozole plus the anti-PD-L1 antibody durvalumab in the neoadjuvant treatment of HR+/HER2- breast cancer. Methods: This is an open label, phase II with safety run-in trial conducted at Moffitt Cancer Center. The primary objective is modified Preoperative Endocrine Prognostic Index (mPEPI) score of 0. Secondary objectives are clinical response rate, pathologic response rate, recurrence free survival. Correlative objectives include phenotypic changes in immune cells and cytokine patterns pre-, during- and post-treatment. Inclusion criteria include postmenopausal females, ECOG 0-1, HR+ with Allred score of 6 to 8, HER2-, cT2-cT4, any N, M0, appropriate lab values, agreeing to research biopsies. Exclusion criteria include multicentric disease, bilateral disease, autoimmunity or inflammatory disease, use of immunosuppressant, known HIV, Hep B/C infection, history of TB, h/o interstitial lung disease or pneumonitis, clinically significant cardiovascular disease, mean QTcF &amp;gt; 470 ms. Patients will receive anastrozole 1 mg PO daily for 6 months concurrently with durvalumab 1500 mg IV every 4 weeks for 6 cycles, followed by definitive surgery. Results: This is a trial in progress. However, limited preliminary results will be presented. Conclusion: The combination of anastrozole and durvalumab may lead to improved mPEPI score in the short term and improved RFS in the long term. Citation Format: Hung T Khong, Dawn N Goodridge, Nazanin Khakpour, M. Catherine Lee, Christine Laronga, Avan J Armaghani, Aixa E Soyano-Muller, Hyo Han, Hatem Soliman, Ricardo Costa, Loretta Loftus, Susan J Hoover, John V Kiluk, Zena Jameel, Brian J Czerniecki. A phase II trial with safety run-in of neoadjuvant therapy with an aromatase inhibitor in combination with durvalumab (MEDI4736) in postmenopausal patients with hormone-receptor-positive (HR+) breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-15-01.
Grounded separation: can the sensorimotor be grounded in the symbolic?
Authors: Michael Gilead, Yaacov Trope, Nira Liberman
Journal: Behavioral and Brain Sciences (2021)

Abstract According to Lee and Schwarz, the sensorimotor experience of cleansing involves separating one physical entity from another and grounds mental separation of one psychological entity from another. We propose that cleansing effects may result from symbolic cognition. Instead of viewing abstract meanings as emerging from concrete physical acts of cleansing, this physical act may be appended with pre-existing, symbolic meaning.