tbuckley/cabot-search huggingface dataset:
Association of genetic polymorphisms in the COX-2 (PTGS2), prostaglandin E synthase (PTGES), and prostacyclin synthase (PTGIS) genes with risk of breast cancer.
Authors: Qiuyin Cai, Xiao-Ou Shu, Wanqing Wen, Zefang Ren, Regina Courtney, Yu-Tang Gao, Wei Zheng
Journal: Cancer Research (2006)

5398  Considerable evidence from in vitro, animal model, and epidemiologic studies suggests that COX-2 (PTGS2) may play an important role in breast cancer initiation and progression. The COX-2 enzyme catalyzes a key step in the conversion of arachidonic acid to prostaglandin H2 (PGH2), which is further converted by prostaglandin systhases to bioactive prostaglandins including PGE2, PGI2, PGF2α, PGD2, and TXA2. Of them, PGE2 is a major downstream COX-2 mediator that promotes carcinogenesis, while PGI2, which differs from other prostaglandins, may exert cancer-inhibitory effects. In this study, we evaluated genetic polymorphisms in the genes involved in the production of PGH2 (PTGS2), PGE2 (prostaglandin E synthase, PTGES), and PGI2 (prostacyclin synthase, PTGIS) in relation to breast cancer risk using data from the Shanghai Breast Cancer Study, a large population-based case-control study conducted in urban Shanghai during 1996 to 1998. Included in this study were 1103 cases and 1160 age-matched community controls who had completed an in-person interview and donated a blood sample to the study. Genotyping of polymorphisms in the PTGS2 (C8473T in 3’UTR, rs5275), PTGES (C→A in 3’UTR, rs2302821), and PTGIS (C1117A, Arg373Arg, rs5629) genes was performed using TaqMan assays. For the PTGIS C1117A polymorphism, the AA genotype was associated with an increased risk of breast cancer (OR=1.49, 95% CIs: 1.00-2.23) compared to the CC genotype, and the elevated risk was mainly confined to pre-menopausal women. For the PTGES C→A polymorphism, however, the AA genotype was associated with increased risk of breast cancer primarily in post-menopausal women (OR=1.61, 95% CI: 1.03-2.52) compared to the CC genotype. No significant association of the PTGS2 C8473T polymorphism with breast cancer risk was found. Results of this study indicate that the PTGES and PTGIS genes may be involved in the development of breast cancer and their effect may differ by menopausal status.
Electrophysiologic Studies in Patients with Ventricular Tachycardia
Authors: R. Freedman
Journal: Annual Review of Medicine (1986)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Plaque Temperature, Arterial Remodeling, and Inflammation: Understanding “Hot-Spots” in the Coronary Arteries⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Paul Schoenhagen
Journal: Journal of the American College of Cardiology (2007)
PATH-44. AN UNUSUAL PRESENTATION OF A PEDIATRIC MIDLINE H3K27M-MUTANT TUMOR WITH DISSEMINATED CRANIOSPINAL LEPTOMENINGEAL DISEASE
Authors: Ralph Navarro, Danielle Golub, Travis Hill, Michelle McQuinn, Nora Kim, Karen Tang, Stephanie Livingston, Benjamin Cooper, Sharon Gardner, Theodore Nicolaides, Christopher William, David Zagzag, E Teresa Hidalgo
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND H3K27M-mutant midline lesions were recently reclassified by the WHO as “Diffuse Midline Glioma” (DMG) based on their molecular signature. DMG is one of the most common and most lethal pediatric brain tumors; terminal progression is typically caused by local progression or secondary leptomeningeal dissemination. H3K27M mutations have also been infrequently associated with a histologically diverse set of lesions, particularly spinal masses with early leptomeningeal spread, but the role of H3K27M in these atypical lesions remains poorly understood. CASE PRESENTATION A 15-year-old girl was found to have a T2/FLAIR-hyperintense and heterogeneously contrast-enhancing thalamic mass accompanied by severe leptomeningeal enhancement along the entire neuraxis. Initial infectious workup was negative, and open intracranial biopsy was inconclusive. Follow-up spinal arachnoid biopsy was diagnostic for H3K27M neuroepithelial tumor, thereafter classified as DMG. Biopsy also showed focal p53 immunopositivity, variable immunoreactivity for GFAP and synaptophysin, and an increased proliferation index, altogether suggestive of a glioneuronal origin. She received craniospinal irradiation (CSI) to 41.4Gy with a boost to the thalamic lesion to 54Gy. Imaging 1-month post-radiation demonstrated significant treatment response only with residual enhancement at the conus. CONCLUSIONS This case report describes the unique presentation of an H3K27M-mutant midline lesion with significant craniospinal leptomeningeal spread on admission and atypical glioneuronal histopathological markers. Given her avid leptomeningeal disease, spinal dural biopsy could have been considered earlier given its diagnostic yield in classifying the lesion as DMG. This lesion, however, additionally demonstrated synaptophysin positivity. Per extensive literature review, this histopathology is also potentially consistent with diffuse leptomeningeal glioneuronal tumor (DLGNT). This patient’s uniquely marked treatment response to CSI is also not typically observed in DMG, further supporting the possibility of an alternative molecular identity. In atypical DMG cases, particularly with early leptomeningeal spread, additional consideration of clinical and histopathological context is warranted for accurate diagnosis and prognostication.
INNV-02. RADIOGRAPHIC CHARACTERISTICS AND STEROID USAGE IN LASER INTERSTITIAL THERMAL THERAPY VERSUS MEDICAL MANAGEMENT FOR BIOPSY-PROVEN RADIATION NECROSIS AFTER STEREOTACTIC RADIOSURGERY OF BRAIN METASTASES
Authors: Ethan Srinivasan, Eric Sankey, Matthew Grabowski, Andrew Griffin, Elizabeth Howell, Balint Otvos, Vadim Tsvankin, Ahmet Atik, Krishna Joshi, Gene Barnett, Peter Fecci, Alirezza Mohammadi
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Radiation necrosis (RN) occurs in 9–14% of patients after stereotactic radiosurgery (SRS) for brain metastases (BM). Medical management (MM) with steroids is a common first-line therapy, with variable response and numerous side effects, especially regarding immunotherapy. Laser interstitial thermal therapy (LITT) has been introduced as an efficacious, steroid-reducing alternative, however limited data exists comparing LITT to MM. METHODS Patients with biopsy-proven RN after SRS for BM who received LITT or MM at two academic centers were retrospectively reviewed. Treatment failure was defined as radiographic progression that necessitated a change in management. Measurements of total (TLV) and contrast-enhancing lesion volume (ceLV) were obtained from MRI by semi-automated analysis using the BrainLab iPlan Cranial 3.0 software. RESULTS Eighty-one patients were followed for 11.7 (4.3–27.0) months and 57 (70%) received LITT. Steroid cessation occurred at a median of 37 days post-LITT compared to 162 days after MM (p&amp;lt; 0.01). Treatment failure occurred in 5% of LITT patients at 4.0 (3.2–4.8) months and 13% of MM patients at 4.4 (4.1–5.3) months (p &amp;gt;0.05). Patients were 3.2 times more likely to be weaned off steroids when treated with LITT compared to MM (p&amp;lt; 0.01), when controlled for age, pre-operative ceLV, and post-operative seizure on multivariate analysis. Both groups demonstrated decreasing TLV and ceLV between baseline and last follow-up MRI. At 6–9 months, the LITT cohort demonstrated a -59% change in ceLV compared to -7% with MM (p &amp;gt;0.05). The LITT cohort demonstrated a significant decrease in ceLV between scans at 0–2 and 6–9 months (p&amp;lt; 0.01). The MM group did not demonstrate a statistically significant decrease in ceLV until 12 months. CONCLUSION This study suggests that LITT for RN significantly reduces the time to steroid cessation, and earlier radiographic response to treatment by LITT. Large, prospective trials are needed to validate these findings.
Inflammatory Bowel Disease and Atherosclerotic Cardiovascular Disease
Authors: Miguel Cainzos-Achirica, Kerri Glassner, Hassan Syed Zawahir, Amit K. Dey, Tanushree Agrawal, Eamonn M.M. Quigley, Bincy P. Abraham, Isaac Acquah, Tamer Yahya, Nehal N. Mehta, Khurram Nasir
Journal: Journal of the American College of Cardiology (2020)
Abstract P288: Parent-child Associations In Cardiovascular Health
Authors: Norrina B Allen, Megan McCabe, Amy Krefman, Donald M Lloyd-jones, Bradley S Marino, Linda VAN HORN, Lifang HOU, Darwin R Labarthe, Amanda Perak, Matthew Davis, Rachel Flynn, Lauren Wakschlag
Journal: Circulation (2020)

Introduction: Shared genetics may explain some of the strong heritability of cardiovascular (CV) disease, however, excess risk is largely due to intergenerational transmission of poor lifestyles leading to the increased presence of cardiovascular risk factors. We examined the association between parental and child CV health (CVH), including behavioral and clinical factors. Methods: Participants of the Multidimensional Assessment of Preschoolers Study (MAPS) and a parent (predominantly mothers) were recruited for a CVH exam when the child was 9-11 yrs (in 2018-19). Five CVH metrics were collected in children and parents: BMI and blood pressure via standardized measurements, and diet, physical activity and smoking via questionnaire. CVH was defined as the sum of ideal (2 points), intermediate (1 point) and poor (0 points) levels of the 5 metrics, as defined by the AHA. The overall CVH score (range: 0-10) was stratified into high (9-10), moderate (5-8) and low (0-4). Logistic regression was used to examine relationships between ideal CVH in children and various predictors, including parental employment, income, and ideal CVH. Results: Among 185 participants (53% female, 12% Non-Hispanic White, 52% non-Hispanic Black and 30% Hispanic; mean age 11) 5% had low, 75% moderate and 20% had high CVH. Looking at the metrics individually, poor diet was the most common (43%), followed by BMI (22%), physical activity (18%), smoking (2%), and BP (1%). Among the parents, 19% were in low, 71% moderate and 10% high CVH. After adjusting for race, age, and sex, the strongest predictor of a child’s CVH score was parental CVH score (p=0.007). If a parent had high CVH, the child was 5 times more likely to have high CVH (OR: 5.03, 95% CI: 1.55-16.33). Conclusions: In this MAPS cohort, there was an association between ideal CVH in parents and ideal pre-adolescence CVH in children. These results suggest that interventions to preserve and restore CVH must be family-based.
CTIM-02. TWO OUNCES OF PREVENTION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF VEGF AND IMMUNE CHECK POINT INHIBITION FOR PRIMARY AND SECONDARY PREVENTION OF BRAIN METASTASES
Authors: Alireza Mansouri, Alireza Mansouri, Timothy Brown, Dawit Aregawi, Brad Zacharia, Michael Glantz
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION As treatments for cancer outside of the central nervous system improve, brain metastases (BMs) are becoming increasingly frequent. Despite novel treatment options, BMs remain a frequent cause of death for many advanced malignancies, and both the metastases and their treatments are associated with profound cognitive, quality of life, and economic costs. METHODS We conducted exhaustive, PRISMA-compliant systematic reviews of the literature from January 2000 to June 2020 for studies comparing the frequency of new BM in patients treated with chemotherapy regimens including and not including bevacizumab (“primary prevention”), and for studies comparing the frequency of new outside-of-treatment-field metastases in patients treated with stereotactic radiosurgery (SRS) with or without immune checkpoint inhibitors (“secondary prevention”). Pre-specified data was extracted and summary statistics were calculated using the inverse variance method and random effects model. RESULTS Seven studies (n=6,212) reported on BMs in breast, lung, and colon cancer patients treated with chemotherapy with or without bevacizumab. The relative risk (RR) and 95% confidence intervals [95% CI] for the development of new brain metastases was 0.71 [0.55–0.91, p=0.001]. A sensitivity analysis performed on the 3 breast cancer trials (n=2,350) showed a RR of 0.57 [0.34–0.94, p=0.027]. Seven studies (n=609) reported on patients with melanoma BM receiving SRS without or without an ICI. The RR for the development of new out-of-treatment field brain metastases was 0.70 [0.51–0.94, p=0.017]. Results were similar in sensitivity analyses examining only class I and class II trials. CONCLUSION This analysis suggests that the addition of bevacizumab to chemotherapy or ICI SRS+/- chemotherapy can reduce the development of first-ever or new BM by 30% in patients with advanced stage breast, lung, or colon cancer. Prospective trials of primary and secondary prevention in patient groups at high risk of developing BMs, and examining additional predictors of response, are currently underway.
TAMI-41. PI3K-GAMMA INHIBITION SUPPRESSES ACCUMULATION OF GLIOBLASTOMA-ASSOCIATED MICROGLIA TO RECAPITULATE THE MICROENVIRONMENT OF EXCEPTIONAL RESPONDERS
Authors: Jie Li, Megan Kaneda, Jun Ma, Ming Li, Kunal Patel, Tomoyuki Koga, Aaron Sarver, Frank Furnari, Beibei Xu, Sanjay Dhawan, Jianfang Ning, Hua Zhu, Anhua Wu, Gan You, Tao Jiang, Andrew Venteicher, Christopher Glass, Judith Varner, Clark Chen
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Exceptional responders refer to the rare subset of patients who derive extraordinary benefits from a therapy compared to most treated patients. Understanding the basis for such responses represents a key pillar in the framework of precision medicine. OBJECTIVE Here, we examine the molecular basis underlying exceptional responses in glioblastoma patients who underwent concurrent radiation and temozolomide (TMZ) therapy. METHODS mRNA profiles derived from clinically annotated glioblastoma specimens were analyzed by Single sample gene set enrichment (ssGSEA) and Gene Cluster Expression Summary Score (GCESS). Key results were confirmed using cell-based assays and murine glioblastoma models. RESULTS Integrated, multi-platform analyses of RNA profiles derived from clinically annotated glioblastoma samples revealed decreased accumulation of microglia/macrophages in the tumor microenvironment of exceptional responders. Further analysis revealed that glioblastoma-associated microglia/macrophages secreted interleukin 11 (IL11) activate a STAT3-MYC signaling axis in glioblastoma cells. This signaling facilitated glioblastoma transition into stem cell states that confer enhanced tumorigenicity as well as resistance to the TMZ. Pharmacologic inhibition or genetic inactivation of a myeloid cell restricted isoform of PI3K, PI3K-gamma, disrupted this signaling axis by suppressing microglia/macrophage accumulation and IL11 secretion in the glioblastoma microenvironment. Mirroring the clinical outcome of exceptional responders, PI3K-gamma inhibition synergistically enhanced the anti-neoplastic effects of TMZ in orthotopic murine glioblastoma models. Moreover, inhibition or genetic inactivation of PI3K-gamma in murine glioblastoma models recapitulated expression profiles observed in clinical specimens isolated from exceptional responders. CONCLUSIONS Our results suggest key contributions from tumor-associated microglia/macrophages in exceptional responses and highlight the translational potential for PI3K-gamma inhibition as a glioblastoma therapy.
Abstract 15997: First-phase Ejection Fraction is a Powerful Predictor of All-cause Mortality in Patients With Covid-19
Authors: Mingxing XIE, Zhenxing Sun, Lingyun Fang, Yuji Xie, Li Zhang
Journal: Circulation (2020)

Background: Right ventricular (RV) strain in COVID-19 is predictive of outcome but whether the presence of left ventricular (LV) dysfunction is associated with outcomes is not known. Objective: The objective of the present study was to examine the association of first-phase ejection fraction (EF1), a robust and simple measure of early left ventricular systolic function, that may be a more sensitive marker of left ventricular systolic function than previously described imaging indices. Methods: Consecutive patients with COVID-19 (n=129) hospitalised at the West Branch of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, who underwent echocardiography were studied. Association of EF1, with clinical and laboratory characteristic and outcomes was performed using Cox regression analysis. Results: No patient with preserved EF1 (≥ 25%, a pre-defined threshold) died but 21 patients with reduced EF1 (&lt;25%) died (P&lt;0.001). In Cox multiple regression analysis (incorporating all factors that were associated with mortality on univariate analysis), survival was associated with RV longitudinal strain (HR: 1.23, 95%CI: 1.05-1.44, p=0.009), EF1 (HR: 0.87, 95%CI:0.76-0.99, p=0.038) and high sensitivity cardiac troponin (HR: 1.34, 95%CI: 1.07-1.69, p=0.012) but not with patient demographics, clinical characteristics or other echocardiographic measures. Conclusion: Early LV systolic dysfunction is a powerful predictor of outcomes in patients with COVID-19.
Refitting the Model for End‐Stage Liver Disease for the Eurotransplant Region
Authors: Ben F. J. Goudsmit, Hein Putter, Maarten E. Tushuizen, Serge Vogelaar, Jacques Pirenne, Ian P. J. Alwayn, Bart van Hoek, Andries E. Braat
Journal: Hepatology (2020)

The United Network for Organ Sharing's Model for End-Stage Liver Disease (UNOS-MELD) score is the basis of liver allocation in the Eurotransplant region. It was constructed 20 years ago in a small US cohort and has remained unchanged ever since. The best boundaries and coefficients were never calculated for any region outside the United States. Therefore, this study refits the MELD (reMELD) for the Eurotransplant region.All adult patients listed for a first liver transplantation between January 1, 2007, and December 31, 2018, were included. Data were randomly split in a training set (70%) and a validation set (30%). In the training data, generalized additive models with splines were plotted for each MELD parameter. The lower and upper bound combinations with the maximum log-likelihood were chosen for the final models. The refit models were tested in the validation data with C-indices and Brier scores. Through likelihood ratio tests the refit models were compared to UNOS-MELD. The correlation between scores and survival of prioritized patients was calculated. A total of 6,684 patients were included. Based on training data, refit parameters were capped at creatinine 0.7-2.5, bilirubin 0.3-27, international normalized ratio 0.1-2.6, and sodium 120-139. ReMELD and reMELD-Na showed C-indices of 0.866 and 0.869, respectively. ReMELD-Na prioritized patients with 1.6 times higher 90-day mortality probabilities compared to UNOS-MELD.Refitting MELD resulted in new lower and upper bounds for each parameter. The predictive power of reMELD-Na was significantly higher than UNOS-MELD. ReMELD prioritized patients with higher 90-day mortality rates. Thus, reMELD(-Na) should replace UNOS-MELD for liver graft allocation in the Eurotransplant region.
Evaluation of Neighborhood Socioeconomic Characteristics and Advance Care Planning Among Older Adults
Authors: Sarah Nouri, Courtney R. Lyles, Anna D. Rubinsky, Kanan Patel, Riya Desai, Jessica Fields, Mindy C. DeRouen, Aiesha Volow, Kirsten Bibbins-Domingo, Rebecca L. Sudore
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Advance care planning (ACP) is low among older adults with socioeconomic disadvantage. There is a need for tailored community-based approaches to increase ACP, but community patterns of ACP are poorly understood. <h3>Objective</h3> To examine the association between neighborhood socioeconomic status (nSES) and ACP and to identify communities with both low nSES and low rates of ACP. <h3>Design, Setting, and Participants</h3> This cross-sectional study examined University of California San Francisco electronic health record (EHR) data and place-based data from 9 San Francisco Bay Area counties. Participants were primary care patients aged 65 years or older and living in the San Francisco Bay Area in July 2017. Statistical analysis was performed from May to June 2020. <h3>Exposures</h3> Patients’ home addresses were geocoded and assigned to US Census tracts. The primary factor, nSES, an index combining area-level measures of income, education, poverty, employment, occupation, and housing or rent values, was divided into quintiles scaled to the distribution of all US Census tracts in the Bay Area (Q1 = lowest nSES). Covariates were from the EHR and included health care use (primary care, outpatient specialty, emergency department, and inpatient encounters in the prior year). <h3>Main Outcomes and Measures</h3> ACP was defined as a scanned document (eg, advance directive), ACP<i>Current Procedural Terminology</i>code, or ACP note type in the EHR. <h3>Results</h3> There were 13 104 patients included in the cohort—mean (SD) age was 75 (8) years, with 7622 female patients (58.2%), 897 patients (6.8%) identified as Black, 913 (7.0%) as Latinx, 3788 (28.9%) as Asian/Pacific Islander, and 748 (5.7%) as other minority race/ethnicity, and 2393 (18.3%) self-reported that they preferred to speak a non-English language. Of these, 3827 patients (29.2%) had documented ACP. The cohort was distributed across all 5 quintiles of nSES (Q1: 1426 patients [10.9%]; Q2: 1792 patients [13.7%]; Q3: 2408 patients [18.4%]; Q4: 3330 patients [25.4%]; Q5: 4148 patients [31.7%]). Compared with Q5 and after adjusting for health care use, all lower nSES quintiles showed a lower odds of ACP in a graded fashion (Q1: adjusted odds ratio [aOR] = 0.71 [95% CI, 0.61-0.84], Q2: aOR = 0.74 [95% CI, 0.64-0.86], Q3: aOR = 0.81 [95% CI, 0.71-0.93], Q4: aOR = 0.82 [95% CI, 0.72-0.93]. A bivariable map of ACP by nSES allowed identification of 5 neighborhoods with both low nSES and ACP. <h3>Conclusions and Relevance</h3> In this study, lower nSES was associated with lower ACP documentation after adjusting for health care use. Using EHR and place-based data, communities of older adults with both low nSES and low ACP were identified. This is a first step in partnering with communities to develop targeted, community-based interventions to meaningfully increase ACP.
The Bidirectional Relationship between Vision and Cognition
Authors: Tai Anh Vu, Eva K. Fenwick, Alfred T.L. Gan, Ryan E.K. Man, Benjamin K.J. Tan, Preeti Gupta, Kam Chun Ho, Carlos A. Reyes-Ortiz, Stella Trompet, Jacobijn Gussekloo, Joan M. O’Brien, Sigrid Mueller-Schotte, Tien Yin Wong, Yih Chung Tham, Ching-Yu Cheng, Allen T.C. Lee, Greta Rait, Bonnielin K. Swenor, Varshini Varadaraj, Willa D. Brenowitz, Felipe A. Medeiros, Virginie Naël, Kaavya Narasimhalu, Christopher L.H. Chen, Ecosse L. Lamoureux
Journal: Ophthalmology (2020)