tbuckley/cabot-search huggingface dataset:
Abstract 16685: Evolution of Paroxysmal Atrial Fibrillation From a Pulmonary Vein-Centric Arrhythmia to a Predominantly Non-pv Trigger-Driven Rhythm Disorder Over a Period of 15 Years
Authors: Sanghamitra Mohanty, Chintan Trivedi, Carola Gianni, Domenico G Della Rocca, John D Burkhardt, Javier Sanchez, Rodney Horton, G J Gallinghouse, Richard Hongo, Salwa Beheiry, Amin Al-Ahmad, Luigi Di Biase, Andrea Natale
Journal: Circulation (2017)

Background: Pulmonary veins (PV) are the major site of ectopic foci initiating paroxysmal atrial fibrillation (PAF). Thus, PV antrum isolation (PVAI) is the mainstay of ablative therapy in PAF pati...
Abstract P211: Association Between Urbanization-related Change in Diet, the Gut Microbiota and Microbiome-related Metabolites in a Rapidly Urbanizing Environment in China
Authors: Annie Green Howard, Anthony Fodor, Shan Sun, Yiqing Wang, Matthew Tsilimigras, Shufa Du, Huijun Wang, Penny Gordon-Larsen
Journal: Circulation (2020)

Introduction: Numerous studies suggest that there are rural-urban differences in gut microbial community, partially due the Westernization of diet. However, most studies are based on short-term follow-up and cannot assess how the transition from traditional to Western diets over time shapes human gut microbiota and whether these microbiota changes subsequently impact the metabolomic profile of the host. Hypothesis: We hypothesize that trajectories in diet shape components of the gut microbial community, with strong associations for microbiota and microbiome-mediated metabolites. Methods: We used growth mixture models to estimate individual-specific intercepts (current % calories from animal source food in 2015) and slopes (change in % calories from animal source food from 1991-2015) in 1,468 adults from the population-based China Health and Nutrition Survey (CHNS) across 20 years of urbanization-related change. We then tested the association between the gut microbiota genera in 2015 with these intercepts and slopes in linear regression models, allowing for interactions between the intercepts and slopes. In the subset of the sample with metabolomic measures collected (n = 500), we then tested whether bacteria associated with change in diet (FDR corrected p-values &lt; 0.05 from the joint test of both main effect and interaction) were associated with microbiome-related metabolites using linear regression models. Results: Controlling for current % calories from animal source food, we found 57 gut microbiota measures that were significantly associated with the rate of change in % animal source calories, with the majority (19%) coming from the order Clostridiales. For 55 gut microbiota measures, we found evidence that the association between current diet and gut microbiota was modified by the rate of change in diet. Thirty-two microbiome-related metabolites, over 50% of which were involved in the benzoate metabolism or food component pathways, were associated with these gut microbiota measures. Conclusions: Our findings suggest that long-term change in calories consumed from animal source foods may shape the composition of the gut microbial community. Further, our metabolome findings suggest that pathways linking diet and the microbiome through microbial metabolites may be particularly relevant.
Vertically Coated Graphene Oxide Micro‐Well Arrays for Highly Efficient Cancer Spheroid Formation and Drug Screening
Authors: Cheol‐Hwi Kim, Intan Rosalina Suhito, Novi Angeline, Yoojoong Han, Hyungbin Son, Zhengtang Luo, Tae‐Hyung Kim
Journal: Advanced Healthcare Materials (2020)

Abstract Research on the 3D culturing of cancer cells that better mimic in vivo solid tumors is important for efficient drug screening. Herein, a new platform that effectively facilitates the formation of cancer spheroids for anticancer drug screening is reported. Cytophilic graphene oxide (GO), when selectively coated on the sidewalls of micro‐wells fabricated from a cell‐adhesion‐resistive polymer, is found to efficiently initiates distinct donut‐like formation of cancer cell spheroids. Scanning electron microscopy and Raman mapping are used to analyze vertically coated GO micropatterns (vGO‐MPs) of different sizes (100–250 µm) on polymer platforms, and human liver cancer cells (HepG2), as a model cancer, are seeded on these platforms. Remarkably, the 150 µm‐sized platform is found to easily and rapidly generate 3D spheroids in the absence of cell‐adhesion proteins. In addition, owing to the unique characteristics of GO, vGO‐MPs are highly stable for long periods of time (≈1 month), even under harsh conditions (&gt;70 °C). Moreover, the anticancer effects of two drugs (hydroxyurea and cisplatin) and the potential anticancer compound (curcumin) on HepG2 cells are demonstrated by simply measuring decreases in spheroid sizes. Hence, this new platform is highly promising as a cancer spheroid‐forming material for rapid drug screening.
Abstract P250: The Impact of Recreational Cannabis Legalization on All-cause Hospitalizations and Acute Cardiovascular Event Hospitalizations in Colorado
Authors: Abra M Jeffers, James Lightwood, Salomeh Keyhani
Journal: Circulation (2020)

Background: Cannabis may have adverse consequences for cardiovascular health. Colorado decriminalized cannabis on November 2012 and retail sales of cannabis began in January 2014. We examined whether the overall rate of hospitalizations and hospitalizations for acute cardiovascular events (ACE) increased in Colorado after legalization. Hypothesis: We hypothesized that the rates of all-cause hospitalizations and ACE would increase post legalization of recreational cannabis. Methods: The State Inpatient Database (SID) for Colorado, available through Healthcare Cost and Utilization Project was analyzed using interrupted time-series methods to assess whether increases in sales of marijuana affected the rates of overall hospitalization and hospitalization for ACE, post legalization of cannabis. The time analyzed included January 2008 through September 2015. We ended the data of analysis on October 1 2015, because ICD-10 codes were implemented in October 2015. The primary outcome, rate of hospitalizations, was measured by total unique inpatient admissions within the SID for each monthly time period. The secondary outcome, ACE, was identified using ICD-9 diagnostic codes for myocardial infarction (410), stroke (430, 431, 433, 434, 436), and ICD-9 procedure codes for coronary artery bypass surgery (36.1x), and percutaneous coronary intervention (36.0x, 0.66). In the interrupted time series regression models we accounted for seasonality and consumption of cigarettes and alcohol using a proxy of sales tax collected each month for cigarettes and alcohol. In the ACE models, we controlled for seasonality, sales of cigarettes and average monthly air temperature. We also examined the effect of legalization on the same outcomes in men and women and different age subgroups. Results: While overall rates of hospitalizations decreased somewhat over the study period, there was no statistically significant difference in hospitalizations rates, neither in the regression intercept (for immediate change) (p=0.94) or slope (p=0.97), after the legalization of recreational cannabis. Similarly, ACE rates decreased over the time frame, but there were no significant changes in rate intercept (p=0.80) or slope (p=0.71) post legalization. The subgroup analyses by age category and gender for hospitalizations and ACE also showed no significant differences in rates pre and post legalization. Conclusions: We found no evidence that overall hospitalizations and hospitalizations for ACE increased due to legalizing recreational cannabis in Colorado. A limitation of our study was that Colorado had already implemented a medical marijuana program in 2000. Recreational legalization may not have led to a significant increase in users. Future studies should examine the link between legalization and cardiovascular events in other states with a different trajectory of legalization.
Lobular invasive pleomorphic breast cancer (BC) should be isolated from the classic type
Authors: E. Gil Deza, H. Japaze, C. García Gerardi, C. Diaz, N. Gercovich, E. Morgenfeld, E. Rivarola, M. Russo, I. Frahm, F. G. Gercovich
Journal: Journal of Clinical Oncology (2007)

17024 Background: Lobular invasive BC represents between 5 and 10% of all breast tumors. The MD Anderson Hospital has published a study of 122 pt with lobular invasive carcinoma classic type (LIC) with a better long-term outcome than pt with invasive ductal carcinoma (JCO 23:41, 2005). In most papers, the lobular invasive pleomorphic type (LIP) represents a small number of cases and can be easily confused with the NOS carcinoma. The aim of this study is to compare the onset and prognosis of patients (pt) with LIP vs LIC breast cancer. Methods: A search in the IOHM database of 1169 BC was carried out. All of them had been reviewed by two pathologists and classified according the USA Association of Directors of Anatomic and Surgical Pathology's recommendations. The entire cohort was diagnosed and treated at the IOHM. Only those with lobular invasive BC were included in this paper. Results: Between Oct 97 and Nov 06, 116/1169 pt (10%) were diagnosed with invasive lobular carcinoma. Seventy pt (60%) were LIC, and 46 pt (40%) were LIP. Characteristics of the Population: All pt were females. Both groups were comparable in terms of age (median age for both groups = 60 yo) Staging: LIP presented in more advanced stages: A) LIP group: Stage I: 14 pt; II: 22 pt; III: 8 pt; IV: 2 pt B) LIC group: Stage I: 42 pt ; II:13 pt; III: 15 pt; (p:0,001). The LIP group had a higher histological grade (p:0,0001), and more multifocality (p: 0.023), and vascular invasion (p:0,0001) than the LIC group. There were no differences in hormonal receptors status or the ductal extensive component. The retrospective determination of the Her2/neu status is underway. Treatment: Both groups were treated similarly according to the different stages of the illness. Follow-Up: The average follow up time was 23 months (range 4–102) and the LIP group showed a worse prognosis than the LIC group as measured by a higher rate of metastasis (LIP: 12 pt - LIC: 4 pt) (p:0,002) and a higher mortality rate (LIP: 6 pt - LIC: 0) (p:0,003). Conclusions: 1- The LIP carcinoma is a more aggressive variant and has a worse prognosis than the LIC. 2- The incidence for LIP is higher than expected, as it stands for 40% of the total cases in our study. 3- The results justify the establishment of a clear cut differentiation between the classical and pleomorphic types. No significant financial relationships to disclose.
Allosteric inhibition of CRISPR-Cas9 by bacteriophage-derived peptides
Authors: Yan-ru Cui, Shao-jie Wang, Jun Chen, Jie Li, Wenzhang Chen, Shuyue Wang, Bing Meng, Wei Zhu, Zhuhong Zhang, Bei Yang, Biao Jiang, Guang Yang, Peixiang Ma, Jia Liu
Journal: Genome biology (2020)

Abstract Background CRISPR-Cas9 has been developed as a therapeutic agent for various infectious and genetic diseases. In many clinically relevant applications, constitutively active CRISPR-Cas9 is delivered into human cells without a temporal control system. Excessive and prolonged expression of CRISPR-Cas9 can lead to elevated off-target cleavage. The need for modulating CRISPR-Cas9 activity over time and dose has created the demand of developing CRISPR-Cas off switches. Protein and small molecule-based CRISPR-Cas inhibitors have been reported in previous studies. Results We report the discovery of Cas9-inhibiting peptides from inoviridae bacteriophages. These peptides, derived from the periplasmic domain of phage major coat protein G8P (G8P PD ), can inhibit the in vitro activity of Streptococcus pyogenes Cas9 (SpCas9) proteins in an allosteric manner. Importantly, the inhibitory activity of G8P PD on SpCas9 is dependent on the order of guide RNA addition. Ectopic expression of full-length G8P (G8P FL ) or G8P PD in human cells can inactivate the genome-editing activity of SpyCas9 with minimum alterations of the mutation patterns. Furthermore, unlike the anti-CRISPR protein AcrII4A that completely abolishes the cellular activity of CRISPR-Cas9, G8P co-transfection can reduce the off-target activity of co-transfected SpCas9 while retaining its on-target activity. Conclusion G8Ps discovered in the current study represent the first anti-CRISPR peptides that can allosterically inactivate CRISPR-Cas9. This finding may provide insights into developing next-generation CRISPR-Cas inhibitors for precision genome engineering.
Abstract P275: Growth Differentiation Factor (gdf)-15 and Metabolic Outcomes: The ARIC Study
Authors: Justin B Echouffo Tcheugui, Natalie R Daya, Kunihiro Matsushita, Chiadi E Ndumele, Ron C Hoogeveen, Mahmoud S Al Rifai, Christie M Ballantyne, Elizabeth Selvin
Journal: Circulation (2020)

Introduction: Mechanistic studies suggest an involvement of growth differentiation factor 15 (GDF-15) in metabolic dysregulation. However, the potential utility of GDF-15 as a marker of diabetes or metabolic syndrome (MetS) risk remains unclear, especially in older adults. Hypothesis: GDF-15 is positively associated with biomarkers of hyperglycemia, diabetes, and MetS. Methods: We conducted a cross-sectional analysis of older adults who attended visit 6 (2016-2017) of the Atherosclerosis Risk in Communities (ARIC) Study. GDF-15 was measured using electrochemiluminescence immunoassay (Elecsys, Roche Diagnostics). Linear regression was used to assess continuous outcomes after appropriate transformations, and multivariable-adjusted odds of diabetes or MetS by quartiles of GDF-15 were derived using logistic regression. Results: Among 3,792 participants (mean age 80 years, 59% women, 23% blacks and 77% whites), higher GDF-15 concentrations (per 1-unit increase in ln[GDF-15]) were associated with higher levels of fasting plasma glucose (mg/dL) (adjusted β coefficient : 10.98, 95% CI:8.86 - 13.09) and HbA 1C (%)(0.41, 95% CI: 0.35 - 0.48). Higher GDF-15 was associated with greater odds of diabetes (adjusted odds ratio [OR]: 5.81 for highest vs. lowest GDF-15 quartile, 95% CI 4.43-7.61) and of MetS syndrome (adjusted OR: 2.57, 95% CI 2.01-3.20) among individuals without diabetes (Figure). Conclusions: In this sample of older adults, elevated GDF-15 was strongly associated with diabetes and metabolic syndrome. These data strongly suggest that GDF-15 could be a robust biomarker of adverse metabolic states.
Abstract 311: Opposing Roles TCF7/LEF1 and TCF7L2 in Wnt/β-Catenin and BMP Signaling During Late Heart Development
Authors: Bo Ye, Haodong Xu, Faqian Li
Journal: Circulation Research (2016)

T-cell factor (TCF) and lymphoid enhancer factor (LEF) family transcriptional factors are important nuclear mediators of Wnt/β-catenin signaling. Their roles in cardiac development and diseases remain to be determined. We found that these TCF/LEF family members, including LEF1, TCF7, TCF7L1, and TCF7L2 had unique expression pattern during mouse heart development. At embryonic day (E) 13.5, LEF1 was one of the most abundant TCF/LEF members at mRNA level in the murine heart. By immunohistochemical staining, mesenchymal cells in valvular regions had much stronger intensity of LEF1 than cardiomyocytes in ventricles. Cardiomyocytes with weak to moderate nuclear staining for LEF1 were scattered in compact and trabecular layers. At E17.5, LEF1 mRNA levels dropped dramatically and its protein was no longer detected in cardiomyocytes. TCF7L1 mRNA levels also decreased from E13.5 to E17.5. Weak cytoplasmic, but not nuclear TCF7L1 signal was detected in cardiomyocytes at E13.5 by immunochemistry. TCF7 mRNA was the lowest among all four TCF/LEF members at E13.5 and it further decreased at E17.5. TCF7 protein was only detected by immunohistochemistry in mesothelial and endothelial cells, but not in cardiomyocytes or mesenchymal cells. TCF7L2 mRNA became the most abundant TCF/LEFs at E17.5. Immunolocalization revealed that TCF7L2 formed an intensity gradient with the highest levels at the inner trabecular layer, opposite to the distribution of β-catenin. Wnt signaling activation by cardiac deletion of adenomatosis polyposis coli ( Apc ), a negative Wnt regulator, led to a dramatic increase in cyclin D2, Bmp4, LEF1, and TCF7. BMP mediators, SMAD1/5/8, were increasingly phosphorylated. Chromatin immunoprecipitation revealed that TCF7L2 was removed from and replaced by LEF1 and TCF7 in the promoter of cyclin D2 and Bmp4 to promote β-catenin recruitment. Furthermore, there was co-occupancy of TCF/LEF and SMAD in the adjacent TCF/LEF and SMAD binding sites of Wnt target genes. Finally, we proved that TCF7L2 was a transcriptional suppressor of cyclin D2 and Bmp 4 in a cardiac cell line by overexpression and knockdown experiments. Our results indicate that TCF7L2 is transcriptional repressor of Wnt/β-Catenin pathway in the heart.
Predictors of toxicity to concurrent chemoradiation (CRT) in patients (pts) with locally advanced head and neck squamous cell cancer (HNSCC)
Authors: R. Yelamanchili, S. Hotte, J. Julian, J. Wright
Journal: Journal of Clinical Oncology (2007)

16540 Background: A number of studies have evaluated the impact of prognostic factors on survival but very few have studied their role as determinants of toxicity, especially outside of the context of clinical trials. We set out to identify patient characteristics that are likely to predict toxicity to chemotherapy (CT) with daily cisplatin 6mg/m2 and radiation therapy (RT) in pts with locally advanced HNSCC. Methods: Retrospective chart review of above pts at the Juravinski Cancer Center from 2000 through 2004. A number of pt characteristics were analysed. Toxicity outcomes evaluated were completion of CT and of RT, rise in serum Cr , hematologic suppression, need for extra hydration, and need for extra antiemetics. Results: The charts of 108 pts were reviewed. Median follow-up was 36 months. Five year projected OS and PFS were 78% and 57% in our study compared to 53% and 47% in a published EORTC trial (NEJM, 2004). Median duration of PFS was 64 months in our study compared to 55 months in the EORTC trial. Median OS was not reached in our study. Nineteen percent completed CT and 81% completed RT, 17% had full course of CRT. Thirty-nine percent required extra hydration and 50% required extra antiemetics. Twenty four percent had elevated creatinine levels and 20.4% had hematologic suppression. Logistic regression was used to search for significant correlations between pt characteristics and outcomes. Pts with occasional alcohol intake were more likely to complete RT than heavy alcohol abusers (OR 8.9; P 0.04). Pts with occasional alcohol intake were more likely to get extra hydration than heavy alcohol abusers (OR 5.1; P 0.008).Hematologic suppression was more likely with increasing age (OR 1.08;P 0.015).No significant difference in toxicity outcomes was observed between males and females. Conclusions: This review demonstrated that CRT with daily cisplatin is associated with significant toxicity and most pts are unable to receive full treatment . A number of pt variables might predict increased susceptibility to toxicity. This should be validated in a prospective study. Median PFS in our series appear to be at least as good as previously published reports of CRT using daily cisplatin as well as dose schedules but toxicity does not appear greatly reduced. No significant financial relationships to disclose.
A phase II study of docetaxel in combination with ZD1839 (gefitinib) in previously treated patients with metastatic pancreatic cancer
Authors: L. S. Blaszkowsky, D. P. Ryan, C. Earle, E. Kwak, C. Fuchs, J. A. Meyerhardt, K. Stuart, A. X. Zhu, P. Enzinger, M. H. Kulke
Journal: Journal of Clinical Oncology (2007)

15080 Background: The reported activity of docetaxel in pancreatic cancer and high level of EGFR expression in pancreatic carcinomas led us to examine the efficacy of combination docetaxel and gefitinib in patients with metastatic pancreatic cancer. Methods: Eligibility criteria included PS = 1, failed prior adjuvant ot metastatic gemcitabine-containing regimen, = 1 prior regimen for metastatic disease, no prior taxane or EGFR inhibitor, and adequate organ function. Patients received docetaxel 40 mg/m2 intravenously weekly for 2 of every 3 weeks and daily oral gefitinib 250 mg. The primary endpoint was CA19–9 response (&gt;50% decrease in tumor marker CA19–9 levels). Additional endpoints included radiologic response, toxicity, and survival. Results: Fifteen patients received docetaxel and gefitinib between 11/2/04 and 11/26/05. The median age of patients was 60 (46–76), and included 7 women and 8 men. The regimen was generally well tolerated, and there were no unanticipated toxicities. Grade 3 or 4 toxicities included lymphopenia (6 pts), hyperglycemia (3 pts), leucopenia (3 pts), infection (2 pts), fatigue (2 pts), elevated transaminases (2 pts), neutropenia (2 pts), pleural effusion (2 pts), irregular menses (1 pt), anorexia (1 pt), dysphagia/esophagitis (1 pt), diarrhea (1 pt), alkaline phosphatase (1 pt), and sensory neuropathy (1 pt). No treatment-related deaths occurred. No patient experienced a biochemical (CA 19–9) response to treatment. All 15 patients were evaluable for radiologic response, of which 9 experienced stable disease and 6 progressive disease as their best response to therapy. The trial was stopped due to lack of efficacy, in accordance with an early stopping rule incorporated into the trial design. Conclusions: In the doses and schedule used in this trial, the combination of docetaxel and gefitinib does not appear to be active in patients with pancreatic cancer who have failed prior gemcitabine-based chemotherapy. No significant financial relationships to disclose.
Comparison of Assays for Therapeutic Monitoring of Infliximab and Adalimumab in Patients With Inflammatory Bowel Diseases
Authors: Konstantinos Papamichael, William T. Clarke, Niels Vande Casteele, Katharine A. Germansky, Joseph D. Feuerstein, Gil Y. Melmed, Corey A. Siegel, Peter M. Irving, Adam S. Cheifetz
Journal: Clinical Gastroenterology and Hepatology (2020)
‘Into the Wild’: A meta-synthesis of talking therapy in natural outdoor spaces
Authors: Sam J. Cooley, Ceri R. Jones, Arabella Kurtz, Noelle Robertson
Journal: Clinical Psychology Review (2020)

Time spent in natural outdoor spaces has physiological and psychological benefits, such as reduced stress responses and improved mood. Mental health practitioners have begun to harness nature's restorative capacity by challenging convention and taking talking therapies outdoors. This review synthesises the experiences of these practitioners and their clients, with the aim of establishing a framework for best practice. A thematic synthesis was used to provide a systematic and integrative exploration of multiple therapy professions. Articles (N = 38, published from 1994 to 2019) comprised 322 practitioners and 163 clients. A mixed-method meta-synthesis resulted in a framework of higher and lower level themes. The outdoor context for therapy ranged in intensity from sitting or walking in urban parks and woodland to remote wilderness expeditions. The outdoors provided either a passive backdrop to therapy or was more actively incorporated through behavioural analysis, relationship building, metaphor, narrative therapy, role play, modelling, and stabilisation. Practical, therapeutic, and organisational issues were mitigated through assessment and formulation, informed consent, process contracting, enhancing predictability where possible, and awareness of professional competency. Therapy was subsequently enriched by added mutuality, freedom of expression, mind-body holism, interconnectedness with the natural world, and practitioner well-being. The question of whether therapy in natural spaces should become a more mainstream option for clients and practitioners is discussed.