tbuckley/cabot-search huggingface dataset:
Abstract 19212: Racial Differences in Clinical Outcomes and Resource Utilization Associated With Heart Failure Hospitalizations in the United States: A Nationwide Analysis From 2011-2012
Authors: Nilay Kumar, Rohan Khera, Neetika Garg
Journal: Circulation (2015)

Background and objectives: Heart failure (HF) incidence is higher among Blacks compared to Whites. There is a paucity of recent data on racial differences in in-hospital mortality and resource utilization in a nationally representative, multiracial cohort of HF hospitalizations. Hypothesis: There are significant racial-ethnic differences in HF hospitalization outcomes. Methods: We used the 2011-2012 Nationwide/National Inpatient Sample to identify hospitalizations with a primary diagnosis of HF using relevant ICD-9 codes. Outcomes of interest were in-hospital mortality, length of stay (LOS) and mean inflation adjusted charges. The effect of race on outcomes was ascertained using logistic or linear regression. Results: 375,740 primary HF hospitalizations representing 1.8 million hospitalizations nationwide were included. Mean age was 72.6 (SD 14.6) years and 50.1% were females. After adjusting for age, sex, hypertension, diabetes, APR-DRG mortality risk and socioeconomic status, in-hospital mortality was significantly lower for Blacks (OR 0.69, 95% CI 0.64 - 0.74; p&lt;0.001), Hispanics (OR 0.82, 95% CI 0.75 - 0.91; p&lt;0.001) and Asians or Pacific Islanders (OR 0.85, 95% CI 0.73 - 0.99; p=0.04) compared to Whites. Average inflation adjusted charges were significantly higher for all minorities compared to Whites except for Native Americans for whom charges were significantly lower than Whites (p&lt;0.05 for Black, Hispanic, Asian, NA or Others vs. Whites). LOS was modestly higher for Blacks or Other races vs. Whites (p=0.01 B vs. W and Others vs. W) and lower for Native Americans vs. Whites (p&lt;0.001). Conclusions: Blacks, Hispanics and Asians hospitalized for HF are significantly less likely to die in the hospital compared to Whites. Hospital charges for racial-ethnic minorities are significantly higher compared to Whites. The reasons for racial differences in HF hospitalization outcomes require further investigation.
<i>Artemisia</i> pollen allergy in China: Component‐resolved diagnosis reveals allergic asthma patients have significant multiple allergen sensitization
Authors: Zhongshan Gao, Wan‐Yi Fu, Yuemei Sun, Biyuan Gao, Hui‐Ying Wang, Meiling Liu, Fang‐Mei Luo, Xiang Zhou, Jing Jin, Lan Zhao, Shandong Wu, Yi Liu, Lingying Wu, Xuefeng Wang, Ning‐Bo Tang, Bao‐Hua Guo, Yan Feng, Jian Ying Zhou, Gabriele Gadermaier, Fatima Ferreira, Serge A. Versteeg, Ronald van Ree
Journal: Allergy (2018)

Artemisia pollen allergy is a major cause of asthma in Northern China. Possible associations between IgE responses to Artemisia allergen components and clinical phenotypes have not yet been evaluated. This study was to establish sensitization patterns of four Artemisia allergens and possible associations with demographic characteristics and clinical phenotypes in three areas of China.Two hundred and forty patients allergic to Artemisia pollen were examined, 178 from Shanxi and 30 from Shandong Provinces in Northern China, and 32 from Yunnan Province in Southwestern China. Allergic asthma, rhinitis, conjunctivitis, and eczema symptoms were diagnosed. All patients' sera were tested by ImmunoCAP with mugwort pollen extract and the natural components nArt v 1, nArt ar 2, nArt v 3, and nArt an 7.The frequency of sensitization and the IgE levels of the four components in Artemisia allergic patients from Southwestern China were significantly lower than in those from the North. Art v 1 and Art an 7 were the most frequently recognized allergens (84% and 87%, respectively), followed by Art v 3 (66%) and Art ar 2 (48%). Patients from Northern China were more likely to have allergic asthma (50%) than patients from Southwestern China (3%), and being sensitized to more than two allergens increased the risk of allergic asthma, in which co-sensitization to three major allergens Art v 1, Art v 3, and Art an 7 is prominent.Component-resolved diagnosis of Chinese Artemisia pollen-allergic patients helps assess the potential risk of mugwort-associated allergic asthma.
Consecutive Day HSP90 Inhibitor Administration Improves Efficacy in Murine Models of KIT-Driven Malignancies and Canine Mast Cell Tumors
Authors: Cheryl A. London, Jaime Acquaviva, Donald L. Smith, Manuel Sequeira, Luisa Shin Ogawa, Heather L. Gardner, Louis Feo Bernabe, Misty D. Bear, Sandra A. Bechtel, David A. Proia
Journal: Clinical Cancer Research (2018)

STA-1474, prodrug of the heat shock protein 90 inhibitor (HSP90i) ganetespib, previously demonstrated activity in canine preclinical models of cancer; interestingly, prolonged infusions were associated with improved biologic activity. The purpose of this study was to identify the ideal treatment schedule for HSP90i in preclinical models of KIT-driven malignancies and in dogs with spontaneous mast cell tumors (MCT), where KIT is a known driver.In vitro and murine xenograft experiments and clinical studies in dogs with MCTs were used to define the effects of HSP90i-dosing regimen on client protein downregulation and antitumor activity.Continuous HSP90 inhibition led to durable destabilization of client proteins in vitro; however, transient exposure required >10× drug for comparable effects. In vivo, KIT was rapidly degraded following a single dose of HSP90i but returned to baseline levels within a day. HSP90 levels increased and stabilized 16 hours after HSP90i and were not elevated following a subsequent near-term exposure, providing a functional pool of chaperone to stabilize proteins and a means for greater therapeutic activity upon HSP90i reexposure. HSP90i administered on days 1 and 2 (D1/D2) demonstrated increased biologic activity compared with D1 treatment in KIT or EGFR-driven murine tumor models. In a trial of dogs with MCT, D1/D2 dosing of HSP90i was associated with sustained KIT downregulation, 50% objective response rate and 100% clinical benefit rate compared with D1 and D1/D4 schedules.These data provide further evidence that prolonged HSP90i exposure improves biologic activity through sustained downregulation of client proteins.
Progress in the application of CRISPR: From gene to base editing
Authors: Wenyi Wu, Yanhui Yang, Hetian Lei
Journal: Medicinal Research Reviews (2018)

Abstract The system of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR‐associated endonucleases (Cas) has been utilized for genome editing with great accuracy and high efficiency in generating gene knockout, knockin, and point mutations in eukaryotic genomes. However, traditional CRISPR/Cas9 technology introduces double‐stranded DNA breaks (DSBs) at a target locus as the first step to make gene corrections, which easily results in undesired mutations. Thus, it is necessary to develop new methods for correcting the unwanted mutations. In this review, we summarize the recent developments and a new approach to genome and base editing by using CRISPR/Cas9. This methodology renders a conversion of one target base into another, for example, C to T (or G to A), and A to G (or T to C) without producing DSBs, requiring a donor DNA template, or generating excessive insertions and deletions. Furthermore, CRISPR/Cas9‐derived base editing also improves efficiency in repairing point mutations in the genome.
Recurrence of Extramedullary Plasmacytomas Involving Lymph Nodes and Pancreas Revealed by 68Ga-DOTATATE and 18F-FDG PET/CT
Authors: Qingqing Pan, Yaping Luo, Jian Li, Shu Zhang, Fang Li
Journal: Clinical Nuclear Medicine (2018)

A 40-year-old man with history of extramedullary plasmacytoma in nasal cavity presented with right submandibular mass for 3 months. F-FDG PET/CT demonstrated mild radioactivity in the right submandibular mass, pancreatic mass, and lymph nodes in the abdomen and left hilum of the lung. To differentiate from pancreatic neuroendocrine tumor, Ga-DOTATATE PET/CT was performed. The above lesions were TATE avid, and additional lesions with intense radioactivity were also detected in the right internal mammary node and intrapericardial node. Finally, biopsy of the right submandibular mass confirmed recurrence of extramedullary plasmacytoma.
Abstract 15339: Balloon Angioplasty Alone versus Stent Implantation in Chronic Total Occlusion Patients With Small Vessel Disease (<2.5mm)
Authors: Hu Li, Seung Woon Rha, Byoung Geol Choi, Jae Kyeong Byun, Se Yeon Choi, Jun Hyuk Kang, Woo Hyeun Kim, Ja Yeon Choi, Eun Jin Park, Sung Hun Park, Sunki Lee, Jin Oh Na, Cheol Ung Choi, Jin Won Kim, Hong Euy Lim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh
Journal: Circulation (2016)

Background: Chronic total occlusion (CTO) intervention has a lower initial success rate than non-CTO lesions, but has many clinical benefit. Current meta-analysis reported that successful percutane...
Proton Pump Inhibitors and Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B or C
Authors: Wei‐Yu Kao, Chien‐Wei Su, Elise Chia‐Hui Tan, Pei‐Chang Lee, Ping‐Hsien Chen, Jui‐Hsiang Tang, Yi‐Hsiang Huang, Teh‐Ia Huo, Chun‐Chao Chang, Ming‐Chih Hou, Han‐Chieh Lin, Jaw‐Ching Wu
Journal: Hepatology (2018)

Researchers have hypothesized that the long‐term use of proton pump inhibitors (PPIs) can increase the risk of developing cancer. However, the association between PPI use and hepatocellular carcinoma (HCC) risk is unclear. Using data from the Taiwan National Health Insurance Research Database for the period between 2003 and 2013, we identified 35,356 patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. One‐to‐one propensity score matching by gender, age, cohort entry year, comorbidity, and medication resulted in the inclusion of 7,492 pairs of patients (PPI users and non‐PPI users) for analyses. We performed multivariate and stratified analysis using the Kaplan‐Meier method and Cox proportional hazards models in order to estimate the association between PPI use and the risk of developing HCC. In the HBV cohort, 237 patients developed HCC during a median follow‐up of 53 months. However, PPI use was not associated with an increased risk of developing HCC (adjusted hazard ratio [aHR], 1.25; 95% confidence interval [CI], 0.90‐1.73; P = 0.18). In the HCV cohort, 211 patients developed HCC; but again, PPI use was not associated with an increase in the risk of developing HCC (aHR, 1.19; 95% CI, 0.88‐1.61; P = 0.25). We observed no relationship between a dose‐dependent effect of PPI use and HCC risk. Subgroup analysis also confirmed that PPI use was not correlated to an increased HCC risk. Conclusion: Based on a retrospective population‐based cohort study throughout Taiwan, where the prescription of PPI is tightly regulated, PPI use is not associated with the risk of developing HCC among patients with chronic HBV or HCV infections.
Abstract 18106: Interaction Between Exercise Capacity and CHA2DS2-VASC Score in Predicting Ischemic Stroke in Patients With Atrial Fibrillation: The Henry Ford Exercise Testing (FIT) Project
Authors: Muhammad Ajlan, Benjamin Wessler, Sherif Sakr, Michael Blaha, Clinton A Brawner, Jonathan K Ehrman, Steven Keteyian, Robin Ruthazer, David Kent, Amjad Ahmed, Waqas Qureshi, Mouaz H Al-Mallah
Journal: Circulation (2017)

Background: Current guidelines recommend the CHA2DS2-VASc score to aid decision making regarding anticoagulation in patients with atrial fibrillation (AF). However, the interaction between exercise...
Abstract 12358: Epidemiology of Acute Myocardial infarction in Systemic Sclerosis: Incidence and Outcomes
Authors: Rohan Khera, Snigdha Jain, Nilay Kumar, Namrata Singh, Chris T Derk, Saket Girotra
Journal: Circulation (2015)

Introduction: Risk of acute myocardial infarction (AMI) in inflammatory arthritides like rheumatoid arthritis (RA) is elevated. However, in autoimmune disorders with microvascular dysfunction, like systemic sclerosis (SS), the risk of AMI and its outcomes are not known. Methods: In the National Inpatient Sample (2003-2012), we used ICD9 codes to identify patients (≥18 years) with a primary diagnosis of AMI and a concurrent diagnosis of SS. We estimated population of SS at risk for AMI during each year by multiplying the previously reported stable SS prevalence of 276/million by the US adult population for the corresponding year. We used survey-analysis to generate national estimates for incident AMI and calculated incidence of AMI among SS patients by dividing the number of AMI patients during each year by the at-risk SS population. Characteristics and outcomes of AMI in SS were compared to those with RA and those without rheumatologic disease. Results: During 2003-2012, there were 4570 admissions for AMI in patients with SS in the US for an average of 63,121 at-risk SS patients each year. The incidence of AMI in patients with SS was 721/100,000 at-risk SS patients, which is 3-fold higher compared to incidence of AMI in the general population and remained elevated during 2003-12 (Figure). AMI patients with SS were younger, more likely to be female but were less likely to present as STEMI compared to RA or those with no rheumatologic disease (Table). They were also less likely to undergo PCI than either group. In-hospital AMI mortality in SS was higher than RA or those without rheumatologic disease (risk-adjusted odds ratio 1.65, 95%CI 1.28, 2.11, Table). Conclusions: There is a three-fold increase in risk of AMI in SS compared to the general population. Among AMI patients, in-hospital mortality is significantly higher in SS patients, compared to patients with RA or without rheumatologic disease. Further investigation is warranted to further assess measures to mitigate this risk.
Abstract 11184: Effects of Supervised Exercise on Select Outcomes for Patients With Heart Failure
Authors: Kirsten Roberts
Journal: Circulation (2016)

EFFECTS OF SUPERVISED EXERCISE ON SELECT OUTCOMES FOR PATIENTS WITH HEART FAILURE Background: There is an urgent need to implement strategies to improve outcomes for heart failure (HF) patients. Supervised exercise programs are a Class A recommendation for a multitude of cardiac conditions and are reimbursable by Medicare and most insurance carriers. Stating lack of evidence of improved patient outcomes, the Centers for Medicare and Medicaid Services deny/limit HF as a reimbursable diagnosis for such programs. Hypothesis: To determine the impact of a supervised exercise program for HF patients on the functional capacity, quality of life, level of depression, and rate of hospital readmission. Methods: A before-after cohort study of HF patients who participated in an outpatient phase II cardiac rehabilitation program was done. HF patients (n = 70) with stable New York Heart Association class II-IV diastolic or systolic heart failure were enrolled during an outpatient nurse navigation contact or referral by cardiologists. Surveys to assess quality of life and level of depression (the Kansas City Cardiomyopathy Questionnaire (KCCQ) and Patient Health Questionnaire-9 (PHQ-9)) were used. Functional level was measured using the 6 Minute Walk Distance (6MWD) test. Readmission data were collected from medical records. Results: Depression (PHQ-9) scores dropped (t = 5.86, p &lt; .01). Quality of life scores (KCCQ) improved with for all KCCQ subsets (except system stability) including physical limitation (t = -7.86, p &lt; .01), system frequency (t = -5.91, p &lt; .01), system burden (t = -5.95, p &lt; .01), total system (t = -6.62, p &lt; .01), self-efficacy (t = -5.04, p &lt; .01), quality of life (t = -7.35, p &lt; .01), social limitation (t = -5.66, p &lt; .01), overall summary (t value = -7.73, p &lt; .01), and clinical summary (t value = -7.67, p &lt; .01). Functional status improved with increase in 6MWD (t = -8.55, p &lt; .01). Readmission rates improved with admission encounters dropping (t = 6.07, p &lt; .01) and fewer number of days hospitalized (t = 4.96, p &lt; .01). Conclusions: Participation in a supervised exercise program resulted in clinically and statistically significant positive changes in depression scores, quality of life scores, functional status, and rates of readmission.
Association between age, gender, residential region, and prevalence of subependymal giant cell astrocytoma among patients with tuberous sclerosis complex: A U.S. Healthcare Claims Database study.
Authors: Michael Kohrman, Peter Sun, Zhimei Liu, Darcy Kruger
Journal: Journal of Clinical Oncology (2012)

1609 Background: Subependymal giant-cell astrocytomas (SEGA) are slow growing non-cancerous tumors that can occur in patients with tuberous sclerosis complex (TSC). The objectives of this study were to examine SEGA prevalence among TSC patients in a real world setting, and to ascertain the relationships between SEGA prevalence and age groups, genders, or residential regions. Methods: We conducted a retrospective cohort study based on a large US commercial healthcare claims database. Patients with a TSC claim between 2000 and 2009 and with 12-month continuous enrollment after their first TSC claim were included into the study. SEGA was identified based on ICD-9CM codes in inpatient or outpatient claims. Patients’ genders, residential regions and ages of their first TSC claim and /or their first SEGA claim (if they had SEGA) were extracted from enrollment files respectively. SEGA prevalence was assessed with subgroup analyses of genders, age groups of first TSC claim, and residential regions. Two-sample t tests and Chi-square tests were used to explore the relationships between SEGA prevalence and age groups, genders, or residential regions. Results: The study had 2,767 patients with a mean age of 28.5 years on their first observed TSC claim, and 55.3% were female. Among these TSC patients, 7.7% had SEGA with variations by age groups of their first TSC claim (5.9% for age&lt;1 year, 12.6% for age 1-5 years, 11.0% for age 6-10 years, 11.0% for age 11-18 years, 7.6% for age 19-25 years, and 5.1% for age 26 years or more), by genders (8.7% for males vs. 6.9% for females), and by residential regions (6.0%-11.0%). The associations between SEGA prevalence and age groups, genders or residential regions were all statistically significant with p&lt;0.05. Conclusions: In a real world setting, and by the end of the first post-TSC year, 7.7% TSC patients had an observed SEGA diagnosis. This prevalence varied by age groups, genders, residential regions. Further research is needed to explore the factors that results into these variations.
Abstract 12341: Combined Assessment of Urinary Liver-Type Fatty-Acid Binding Protein and Serum N-Terminal Pro-B-Type Natriuretic Peptide Levels Improves Prediction of Acute Kidney Injury in Patients Hospitalized to Coronary Care Units
Authors: Hiroyuki Naruse, Junnichi Ishii, Taketo Nishimura, Hideki Kawai, Takashi Muramatsu, Masahide Harada, Akira Yamada, Shigeru Matsui, Sadako Motoyama, Mutsuharu Hayashi, Masayoshi Sarai, Eiichi Watanabe, Hideo Izawa, Yukio Ozaki
Journal: Circulation (2017)

Background: Urinary concentration of liver-type fatty-acid binding protein (L-FABP) reflects tubulointerstitial injury. We prospectively investigated the predictive value of urinary L-FABP, both in...
Spatially Resolved Transcriptomics Enables Dissection of Genetic Heterogeneity in Stage III Cutaneous Malignant Melanoma
Authors: Kim Thrane, Hanna Eriksson, Jonas Maaskola, Johan Hansson, Joakim Lundeberg
Journal: Cancer Research (2018)

Cutaneous malignant melanoma (melanoma) is characterized by a high mutational load, extensive intertumoral and intratumoral genetic heterogeneity, and complex tumor microenvironment (TME) interactions. Further insights into the mechanisms underlying melanoma are crucial for understanding tumor progression and responses to treatment. Here we adapted the technology of spatial transcriptomics (ST) to melanoma lymph node biopsies and successfully sequenced the transcriptomes of over 2,200 tissue domains. Deconvolution combined with traditional approaches for dimensional reduction of transcriptome-wide data enabled us to both visualize the transcriptional landscape within the tissue and identify gene expression profiles linked to specific histologic entities. Our unsupervised analysis revealed a complex spatial intratumoral composition of melanoma metastases that was not evident through morphologic annotation. Each biopsy showed distinct gene expression profiles and included examples of the coexistence of multiple melanoma signatures within a single tumor region as well as shared profiles for lymphoid tissue characterized according to their spatial location and gene expression profiles. The lymphoid area in close proximity to the tumor region displayed a specific expression pattern, which may reflect the TME, a key component to fully understanding tumor progression. In conclusion, using the ST technology to generate gene expression profiles reveals a detailed landscape of melanoma metastases. This should inspire researchers to integrate spatial information into analyses aiming to identify the factors underlying tumor progression and therapy outcome.Significance: Applying ST technology to gene expression profiling in melanoma lymph node metastases reveals a complex transcriptional landscape in a spatial context, which is essential for understanding the multiple components of tumor progression and therapy outcome. Cancer Res; 78(20); 5970-9. ©2018 AACR.
Simulation of AML clonality in patient-derived xenografts.
Authors: Zdeňka Herudková, Martin Čulen, Ivana Ježíšková, Adam Folta, Veronika Janečková, Jana Černá, Tomáš Loja, Nikola Tom, Lukáš Semerád, Zuzana Šustková, Dana Dvořáková, Jiří Mayer, Zdeněk Ráčil
Journal: Blood (2017)
Impact of Biomarker-based Design Strategies on the Risk of False-Positive Findings in Targeted Therapy Evaluation
Authors: Tat-Thang Vo, Alexandre Vivot, Raphaël Porcher
Journal: Clinical Cancer Research (2018)

Abstract Purpose: When there is more than one potentially predictive biomarker for a new drug, the drug is often evaluated in different subpopulations defined by different biomarkers. We aim to (i) estimate the risk of false-positive findings with this approach and (ii) evaluate the cross-validated adaptive signature design (CVASD) as a potential alternative. Experimental Design: By using numerically simulated data, we compare the current approach and the CVASD across different settings and scenarios. We consider three strategies for CVASD. The first two CVASD strategies are different in terms of the partitioning of the overall significance level (between the population test and the subgroup test). In the third CVASD strategy, the order of the two tests is reversed, that is, the population test is realized when the prioritized subgroup test is not statistically significant. Results: The current approach results in a high risk of false-positive findings, whereas this risk is close to the nominal level of 5% once applying the CVASD, regardless of the strategy. When the treatment is equally effective to all patients, only the CVASD strategies could specify correctly the absence of a sensitive subgroup. When the treatment is only effective for some sensitive responders, the third CVASD strategy stands out by its ability to correctly identify the predictive biomarker(s). Conclusions: The drug–biomarker coevaluation based on a series of independent enrichment trials can result in a high risk of false-positive findings. CVASD with some appropriate adjustments can be a good alternative to overcome this multiplicity issue.
Cervical Cancer Presenting as an Omental Cake
Authors: Fevziye Canbaz, Handan Celik, Mehmet Kefeli, Migraci Tosun
Journal: Clinical Nuclear Medicine (2018)

In women, peritoneal carcinomatosis usually originates from primary ovarian cancer. We report a case of omental cake as the initial presentation of a cervical cancer, which is extremely rare for this disease. F-FDG PET/CT imaging demonstrated diffuse hypermetabolic abdominopelvic peritoneal carcinomatosis originating from cervical cancer that was confirmed by histopathologically.