tbuckley/cabot-search huggingface dataset:
Abstract P315: The Impact Of Neighborhood Factors On Hospital Readmission Among Depressed Patients With Systolic Heart Failure.
Authors: Emily Guhl, Julia P Holber, Kwonho Jeong, Kaleab Z Abebe, Amy Anderson, Jared W Magnani, Bruce L Rollman
Journal: Circulation (2020)

Introduction: Neighborhood factors such as walkability and proximity to stores, parks, and public transportation have been associated with obesity, diabetes, and physical activity level as well as hospital readmission rates. Among individuals with systolic heart failure (HF), reducing hospital readmissions is challenging, but little is known on the role of neighborhood factors on hospital readmissions in this population. Hypothesis: We hypothesized that better walk scores and less deprivation would be associated with a lower readmissions in HF patients. Methods: We screened hospitalized patients with systolic HF (EF≤45%) and NYHA class II-IV symptoms for depression at 8 Pittsburgh-area hospitals as part of the Hopeful Heart Study (R01 HL114016) and included patients who screened positive for depression and remained depressed when re-contacted by telephone 2 weeks after discharge. We classified neighborhoods using the validated neighborhood Walk Score®and Area Deprivation Index for each patient’s address at study entry (both 0-100 scales), and assessed readmissions for 12 months following each patient’s enrollment. We then compared the ADI and Walk Score of individuals who were readmitted vs. those who were not. Results: Final analysis included 629 depressed patients with systolic HF (43% female, 75% white, 86% HTN, 52% DM). Overall, 73.1% of individuals were readmitted at least once, and readmitted and not readmitted patients had similar walk scores (34.1±25.2 vs. 32.2±27.0, p = 0.40) and ADI (66.6±23.1 vs. 64.2±22.7, p=0.50) as those who were not readmitted. Table 1. Conclusions: Among depressed patients with systolic HF, Walk Score and ADI were associated with not associated with readmission rates. Further research is warranted to determine how neighborhood factors adversely impact individual with co-morbid depression and systolic HF. Further analyses are ongoing to determine if individual components of the Walk Score and ADI contribute to differences in readmission.
Final report of a phase II trial of nimotuzumab in the treatment of refractory and relapsed high-grade gliomas in children and adolescents
Authors: U. Bode, S. Buchen, M. Warmuth-Metz, T. Pietsch, F. Bach, G. Fleischhack
Journal: Journal of Clinical Oncology (2007)

2006 Background: Despite multimodal therapy most children with high grade gliomas (HGG), including glioblastoma multiforme (GM), anaplastic astrocytoma (AA) and intrinsic pontine glioma (PG) have an infaust prognosis if they relapse or are refractory to the primary treatment. Recently novel therapeutic approaches are investigated in order to improve the survival of these patients while preserving a good quality of life. This multicentre phase II trial was designed to explore the feasibility and efficacy of the h-R3 monoclonal anti-EGFR antibody (nimotuzumab) in the treatment of these patients. Patients and Methods: Pediatric patients with GM, AA or PG with radiologically proven progressive disease following primary or relapse treatment and a life expectancy of less than 4 weeks were eligible to the study. The treatment consisted of an induction therapy including a weekly short infusion of 150 mg/m 2 nimotuzumab for six weeks, and in case of non-PD a consolidation therapy of 4 infusions in a 3 week interval. The response was documented by MRI in week 8 and 21 and only clinically in rapidly progresssive disease. Results: Between June 2004 and April 2006 47 patients aged 4 to 17 years (median 11 years) were enrolled in this study. 46 patients were evaluable for response. According to RECIST 14 out of 46 patients showed objective responses (PR n=4, SD n=10) in the MRI as the best response with a median change in the largest diameter of the index lesion of -11% (-50% to +16%). The PR/SD were seen in 2/13 patients with GM, 2/11 with AA and 10/22 with PG. Thirteen patients continued with the consolidation therapy and showed 4 PR, 3 SD and 6 PD in week 21. The median overall survival was 4.4 months (0.3–25.4 months) and was significantly better for repsonders (median 10 months) than for nonresponders (median 4.0 months). No severe side effects related to the study medication were observed. Conclusions: These data suggest that the repeated application of nimotuzumab is well tolerated and safe. Nimotuzumab has cytotoxic efficacy in heavily pre- treated relapsed HGG. Based on this data a phase III trial with nimotuzumab in newly diagnosed diffuse intrinsic pontine gliomas concomittent with radiotherapy was introduced in first quarter 2006. No significant financial relationships to disclose.
Automated CT biomarkers for opportunistic prediction of future cardiovascular events and mortality in an asymptomatic screening population: a retrospective cohort study
Authors: Perry J Pickhardt, Peter M Graffy, Ryan Zea, Scott J Lee, Jiamin Liu, Veit Sandfort, Ronald M Summers
Journal: The Lancet Digital Health (2020)

Body CT scans are frequently performed for a wide variety of clinical indications, but potentially valuable biometric information typically goes unused. We investigated the prognostic ability of automated CT-based body composition biomarkers derived from previously-developed deep-learning and feature-based algorithms for predicting major cardiovascular events and overall survival in an adult screening cohort, compared with clinical parameters.Mature and fully-automated CT-based algorithms with pre-defined metrics for quantifying aortic calcification, muscle density, visceral/subcutaneous fat, liver fat, and bone mineral density (BMD) were applied to a generally-healthy asymptomatic outpatient cohort of 9223 adults (mean age, 57.1 years; 5152 women) undergoing abdominal CT for routine colorectal cancer screening. Longitudinal clinical follow-up (median, 8.8 years; IQR, 5.1-11.6 years) documented subsequent major cardiovascular events or death in 19.7% (n=1831). Predictive ability of CT-based biomarkers was compared against the Framingham Risk Score (FRS) and body mass index (BMI).Significant differences were observed for all five automated CT-based body composition measures according to adverse events (p<0.001). Univariate 5-year AUROC (with 95% CI) for automated CT-based aortic calcification, muscle density, visceral/subcutaneous fat ratio, liver density, and vertebral density for predicting death were 0.743(0.705-0.780)/0.721(0.683-0.759)/0.661(0.625-0.697)/0.619 (0.582-0.656)/0.646(0.603-0.688), respectively, compared with 0.499(0.454-0.544) for BMI and 0.688(0.650-0.727) for FRS (p<0.05 for aortic calcification vs. FRS and BMI); all trends were similar for 2-year and 10-year ROC analyses. Univariate hazard ratios (with 95% CIs) for highest-risk quartile versus others for these same CT measures were 4.53(3.82-5.37) /3.58(3.02-4.23)/2.28(1.92-2.71)/1.82(1.52-2.17)/2.73(2.31-3.23), compared with 1.36(1.13-1.64) and 2.82(2.36-3.37) for BMI and FRS, respectively. Similar significant trends were observed for cardiovascular events. Multivariate combinations of CT biomarkers further improved prediction over clinical parameters (p<0.05 for AUROCs). For example, by combining aortic calcification, muscle density, and liver density, the 2-year AUROC for predicting overall survival was 0.811 (0.761-0.860).Fully-automated quantitative tissue biomarkers derived from CT scans can outperform established clinical parameters for pre-symptomatic risk stratification for future serious adverse events, and add opportunistic value to CT scans performed for other indications.
Abstract 11929: Lipoprotein(a) and Family History of Coronary Heart Disease Are Additive for Predicting Long-Term Cardiovascular Risk: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Anurag Mehta, Salim S Virani, Colby R Ayers, Wensheng Sun, Ron C Hoogeveen, Anand Rohatgi, Jarett D Berry, Parag H Joshi, Christie M Ballantyne, Amit Khera
Journal: Circulation (2018)

Introduction: Elevated lipoprotein(a) [Lp(a)] levels and family history of coronary heart disease (FHx) are associated with an increased risk of cardiovascular events. Whether elevated Lp(a) and FH...
Evaluating the efficacy of multiple myeloma cell lines as models for patient tumors via transcriptomic correlation analysis
Authors: Vishesh Sarin, Katharine Yu, Ian D. Ferguson, Olivia Gugliemini, Matthew A. Nix, Byron Hann, Marina Sirota, Arun P. Wiita
Journal: Leukemia (2020)

Abstract Multiple myeloma (MM) cell lines are routinely used to model the disease. However, a long-standing question is how well these cell lines truly represent tumor cells in patients. Here, we employ a recently described method of transcriptional correlation profiling to compare similarity of 66 MM cell lines to 779 newly diagnosed MM patient tumors. We found that individual MM lines differ significantly with respect to patient tumor representation, with median R ranging from 0.35 to 0.54. ANBL-6 was the “best” line, markedly exceeding all others ( p &lt; 2.2e−16). Notably, some widely used cell lines (RPMI-8226, U-266) scored poorly in our patient similarity ranking (48 and 52 of 66, respectively). Lines cultured with interleukin-6 showed significantly improved correlations with patient tumor ( p = 9.5e−4). When common MM genomic features were matched between cell lines and patients, only t (4;14) and t (14;16) led to increased transcriptional correlation. To demonstrate the utility of our top-ranked line for preclinical studies, we showed that intravenously implanted ANBL-6 proliferates in hematopoietic organs in immunocompromised mice. Overall, our large-scale quantitative correlation analysis, utilizing emerging datasets, provides a resource informing the MM community of cell lines that may be most reliable for modeling patient disease while also elucidating biological differences between cell lines and tumors.
Immunohistochemical Profile and 47-Gene Next-Generation Sequencing (NGS) Solid Tumor Panel Analysis of a Series of 13 Strumal Carcinoids
Authors: S. Theurer, M. Ingenwerth, T. Herold, K. Herrmann, K. W. Schmid
Journal: Endocrine Pathology (2020)

Abstract Strumal carcinoid is an extraordinary rare tumor of the ovary consisting of thyroid tissue intermixed with neuroendocrine tumor component. The cellular origin of strumal carcinoids has been an area of debate. There is also little data on detailed immunohistochemical and molecular characteristics of these neoplasms. For this reason, this series investigated the characteristics of a series of 13 strumal carcinoids using immunohistochemical markers and a 47-gene next-generation sequencing (NGS) solid tumor panel analysis. Both cellular components showed thyroglobulin expression in all tumors. TTF-1 expression was noted in both cellular components of 11 cases. Chromogranin A was positive in both components of most tumors ( n = 12, 92.3% in the neuroendocrine component and n = 10, 76.9% in the thyroid follicular component). Synaptophysin stained the neuroendocrine component of all cases, and it was also identified in the follicular thyroid component of a single case. All tumors were negative for CDX2 and calcitonin. ISLET1 was positive in the neuroendocrine component of 8 cases (6.5%). With the exception of one case, all tumors were positive for SSTR2a. The tumors were associated with a low Ki67 labeling index. All cases were microsatellite stable and no pathogenic mutations were identified using a 47-gene NGS solid tumor analysis. This series underscored that strumal carcinoids are distinct neuroendocrine tumors. The synchronous expression for thyroid follicular epithelial and neuroendocrine differentiation biomarkers may suggest a precursor cell origin displaying mixed-amphicrine differentiation. While strumal carcinoids can be diagnosed by their typical morphology and immunohistochemical profile, frequent SSTR expression may serve as a potential theranostic biomarker in the management of affected patients. In addition, the absence of common driver mutations in the NGS solid tumor panel may suggest that these neoplasms seem to be genetically unrelated to follicular epithelial–derived thyroid tumors and potentially different than other commonly identified well-differentiated neuroendocrine neoplasms. Therefore, further studies focusing on molecular characteristics of this entity are still needed.
Abstract P240: Discrimination Mediates the Adverse Effect of Neighborhood Problems on Cardiometabolic Risk Among Latino/a Adults
Authors: Maryam Hussain
Journal: Circulation (2020)

Introduction: Latino/as in the US on average present with low high-density lipoprotein (HDL) cholesterol and high body-mass index (BMI), putting them at higher risk for future cardiometabolic disease. Neighborhoods have been implicated, directly and indirectly, in poorer cardiometabolic health among ethnic minorities. US Latino/as often live in neighborhoods where they may not have access to engage in positive health behaviors, such as proper diet and physical activity. However, the mediating role of discrimination experienced in these neighborhoods has hardly been examined within the context of Latino/a cardiometabolic health. Methods: We analyzed data from the Texas City Stress and Health Study. Participants were self-identified Latino/a/Hispanic ( N = 500, 61.8% female, M age = 49.08, SD age = 15.80) who reported on their perceived experience of discrimination (higher scores reflecting more discrimination) and their perception of their neighborhood (higher scores reflecting more positive environment) validated survey measures. A trained phlebotomist drew blood in a clinic or in the participant’s home between 8 and 11 AM after fasting for HDL (mg/dL). Blood samples were centrifuged to obtain plasma, which was stored at –70°C until testing. All specimen were batch analyzed and read blind-coded. Additionally, they took clinical measures of participant’s height and weight, to calculate BMI (adjusted for sex). To estimate the mediating effect of discrimination through perception of neighborhood on cardiometabolic risk, path analysis with bootstrapped linear regression models were conducted. We conducted analyses unadjusted and adjusted for age, sex, education, and nativity. All analyses were conducted in the PROCESS macro in SPSS. Results: Participants on average had high HDL levels ( M mg/dL = 51.00, SD = 15.59). Males on average were overweight ( M BMI = 29.78, SD = 5.49) and females ( M BMI = 31.42, SD = 7.27) on average were obese. Bootstrapped estimates showed that perception of neighborhood fully mediated the effect of discrimination on HDL (b = -.43, SE = .18 p = .015) and BMI (b = .02, SE = .01, p = .023), unadjusted for covariates. Although the fully mediated model for BMI withstood adjustment for covariates, the model for HDL did not withstand adjustment. Conclusion: Discrimination accounts for the negative impact that neighborhood problems have on poor cardiometabolic health among adult Latino/as. Future research should examine how positive neighborhood interactions (e.g., walking clubs or playgroups) can mitigate the adverse effects on cardiometabolic health among this at-risk population.
Recent advances in the surgical treatment for esophageal cancer in Japan: An experience of 1000 cases who underwent an esophagectomy at a single institute
Authors: M. Morita, R. Yoshida, K. Ikeda, T. Honboh, M. Ohta, A. Egashira, E. Oki, N. Sadanaga, Y. Kakeji, Y. Maehara
Journal: Journal of Clinical Oncology (2007)

15011 Background: Most cases of esophageal cancer are squamous cell carcinoma in Japan and the prognosis of such patients tends to be poor. However, the clinical results after an esophagectomy have recently been reported to improve. Methods: The mortality and morbidity as well as the patients’ prognosis were evaluated in 1000 cases of esophageal cancer who all underwent an esophagectomy in the Department of Surgery and Science (Department of Surgery II), Kyushu University, Japan from 1964 to 2006. The incidence of squamous cell carcinoma was 94 %. The patients were divided into three groups according to the operation period: Group I (n=197), Group II (n=432), and Group III (n=371) underwent an esophagectomy during the periods of ‘64-’80, ’81-’93, and ’93-’06, respectively. The incidences of TNM Stage 0 or I gradually increased (4, 19 and 24 %, respectively), while those of Stage IV decreased (28, 19 and 14 %). Results: The 5-yr overall survival rates (OSR) and cause-specific survival rate (CSR) after an esophagectomy for all 1000 cases were 30 and 37 %, respectively. The 5-yr OSRs of Groups I, II and III were 14, 27 and 46 %, while the 5-yr CSRs were 18, 36, and 52 %, respectively (P&lt;0.01 between each group). When the prognoses were compared for each TNM stage, an improvement in the prognosis was observed at every tumor stage. A multivariate analysis (Cox proportional hazard model) revealed not only the age, depth of invasion, node metastasis, curability (each P&lt;0.001) and extent of a lymphadenectomy (P&lt;0.05) but also the operation period (P&lt;0.001) to be independent prognostic factors. The morbidity rates of Groups I, II and III were 62, 38, and 33 %, and the incidences of pulmonary complications were 42, 13 and 14 %, respectively (P&lt;0.01, Group I vs. II and I vs. III). The 30-day mortality rates were 8.1, 2.1 and 0 %, respectively (P&lt;0.01 between each group). Conclusions: An analysis of a total of 1000 cases with esophageal cancer revealed that an esophagectomy has generally been safely performed without any critical pulmonary complications, while an increasingly favorable prognosis has been achieved due to recent advances in surgical techniques and treatment modalities. No significant financial relationships to disclose.
Prospective phase II trial of a combination of gemcitabine, cisplatin and UFT as first-line treatment in patients with advanced, unresectable, non-small cell lung carcinoma
Authors: S. S. Jin, Y. Min, H. Kim, J. Ahn, Y. Jegal, K. Seo, C. Park, J. Shin, H. Cha, W. Kwon, J. Park
Journal: Journal of Clinical Oncology (2007)

18109 Background: Most patients with advanced non-small cell lung cancer (NSCLC) receive either single agents or doublet chemotherapy. For non-elderly patients in good performance status, platinum-based double combinations represent the standard treatment. And oral UFT had the survival advantage in adjuvant setting. Therefore we performed a phase II study using the combination of gemcitabine, cisplatin and UFT as a first line therapy in patients with advanced NSCLC. Methods: Eligible patients had histologically or cytologically confirmed stage IIIB or IV NSCLC with good performance status and were chemotherapy-naive. This study was two-stage design and planned number of patients was forty-seven. Gemcitabine (1,250 mg/m 2 , 10 mg/kg/min on days 1 and 8) and cisplatin (75 mg/m 2 on day 1) were injected intravenously and UFT (400 mg/day) was administered orally on day 1–14. Treatment repeated every 3 weeks. Primary end point was overall response rate and secondary end points were overall survival, time to progression and toxicity. Results: Thirty seven patients with advanced NSCLC were enrolled. The median age of the patients was 60 years (range: 44 to 72). The performance status (WHO) was 0 in 4, 1 in 30 and 2 in 3 patients. Twenty three patients completed six cycles. Complete response was achieved in 1 (3%) patient, partial response in 22 (59%) patients, stable disease in 9 (24%) patients. Overall response rate was 62% on intent to treat basis. Among patients who response evaluation was possible (33 patients), response rate was 70%. The median survival time was 14.5 months (95% CI 6.9, 22.3) and the 1 year survival was 35% and then median time to progression was 3.4 months(95% CI 3, 3.9). Toxicities were moderate and mostly hematological adverse events. Grade 3/4 neutropenia occurred in 37%, 5 patients with febrile neutropenia. Grade 3/4 anemia and thrombocypenia was occurred in 37% and 5%. Nonhematologic toxicities were mild. Conclusion: The combination therapy consisted of gemcitabine, cisplatin and UFT is active and well tolerable first line regimen for NSCLC patients. No significant financial relationships to disclose.
Lysine 4 of histone H3.3 is required for embryonic stem cell differentiation, histone enrichment at regulatory regions and transcription accuracy
Authors: Maja Gehre, Daria Bunina, Simone Sidoli, Marlena J. Lübke, Nichole Diaz, Matteo Trovato, Benjamin A. Garcia, Judith B. Zaugg, Kyung-Min Noh
Journal: Nature Genetics (2020)
Prepare for a pandemic
Authors: Richard Hurley
Journal: BMJ (2020)

A covid-19 pandemic is highly likely, warns our editorialist, the epidemiologist John Watkins (doi:10.1136/bmj.m810), and we need to plan now how to reconfigure care services to cope with the looming escalation in demand. “We should plan on the assumption that most of the population may contract the virus with few or no long term effects,” he writes, “while harnessing vital secondary healthcare resources to treat the small percentage of people who become seriously ill.”

As at Tuesday 3 March the UK had confirmed 51 cases of infection (doi:10.1136/bmj.m854). England’s chief medical officer, Chris Witty, said at the launch of …
Grafting of 3D Bioprinting to In Vitro Drug Screening: A Review
Authors: Jing Nie, Qing Gao, Jianzhong Fu, Yong He
Journal: Advanced Healthcare Materials (2020)

Abstract The inadequacy of conventional cell‐monolayer planar cultures and animal experiments in predicting the toxicity and clinical efficacy of drug candidates has led to an imminent need for in vitro methods with the ability to better represent in vivo conditions and facilitate the systematic investigation of drug candidates. Recent advances in 3D bioprinting have prompted the precise manipulation of cells and biomaterials, rendering it a promising technology for the construction of in vitro tissue/organ models and drug screening devices. This review presents state‐of‐the‐art in vitro methods used for preclinical drug screening and discusses the limitations of these methods. In particular, the significance of constructing 3D in vitro tissue/organ models and microfluidic analysis devices for drug screening is emphasized, and a focus is placed on the grafting process of 3D bioprinting technology to the construction of such models and devices. The in vitro methods for drug screening are generalized into three types: mini‐tissue, organ‐on‐a‐chip, and tissue/organ construct. The revolutionary process of the in vitro methods is demonstrated in detail, and relevant studies are listed as examples. Specifically, the tumor model is adopted as a precedent to illustrate the possible grafting of 3D bioprinting to antitumor drug screening.