tbuckley/cabot-search huggingface dataset:
Phase II study of weekly paclitaxel with trastuzumab and pertuzumab in patients with HER2-overexpressing metastatic breast cancer (MBC): Updated progression-free survival with overall survival result.
Authors: Lillian Mary Smyth, Neil M. Iyengar, Sarat Chandarlapaty, Steven Sugarman, Elizabeth Anne Comen, Pamela Drullinsky, Nancy T. Sklarin, Tiffany A. Traina, Tiffany A. Troso-Sandoval, Sujata Patil, Carolyn Wasserheit-Lieblich, Daniel Fontes Santos De Teive E Argolo, Jose Baselga, Larry Norton, Clifford A. Hudis, Chau T. Dang
Journal: Journal of Clinical Oncology (2015)

607 Background: We previously reported results of the phase II breast cancer (BC) trial of weekly paclitaxel (T), trastuzumab (H) and pertuzumab (P) with its primary endpoint of 6-month (mo) progression-free survival (PFS) of 86% (95% CI, 75% to 92%) in patients (pts) with HER2+ metastatic (M) BC treated in first- and second-line settings. At a median (med) follow-up (FU) of 21 mo, med PFS was 19.5 mo overall. Updated PFS and OS analysis from this fully accrued study is presented here. Methods: Pts with HER2+ MBC with 0-1 prior treatment (Rx) were eligible. Rx was weekly (w) T (80mg/m2), q3w H (loading dose 8mg/kg → 6mg/kg) and q3w P (loading dose 840mg → 420mg), all given intravenously. Primary endpoint was 6 mo-PFS. Secondary endpoints included 6-mo and median OS. Evaluable pts received at least one full dose of Rx. Results: From January 2011 to December 2013, 69 pts were enrolled: 51 (74%) and 18 (26%) treated in first- and second-line metastatic settings, respectively. 67 were evaluable for efficacy. As of 12-01-14, 26/67 pts (39%) remain progression-free (6 CR, 13 PR and 7 SD); 34 pts have progressed and there are 51 survivors. At a med FU of 23 mo (range, 3-40 mo), 6-mo PFS was 85% (95% CI, 74%-92%). Med PFS was 21.4 mo (95% CI, 13.8-NR) overall and 26.1 mo (95% CI, 17.0-NR) and 16.4 mo (95% CI, 8.5-NR) for pts with 0-1 prior Rx, respectively. 6-mo OS was 98% (95% CI, 90%-100%) and med OS was 37.5 mo (95% CI 31-NR). Median duration of ChemoRx was 30 weeks. Rx was well-tolerated; there were no febrile neutropenia and no symptomatic left ventricular systolic dysfunction. Conclusions: Updated analysis demonstrates that weekly paclitaxel, when added to H and P, is associated with prolonged PFS and OS and a favourable toxicity profile and should be considered as a therapeutic option in this patient population Clinical trial information: NCT01276041.
The influence of naturopathic doctors on supplement use within a network of oncology hospitals.
Authors: Edra Spevack, Sharon Wesley Dev Sahadevan, Navneet Dhillon, Tanya Lawson, Giuseppe Del Priore
Journal: Journal of Clinical Oncology (2015)

e17556 Background: A growing body of evidence supports the use of natural compounds in oncology care. The majority of cancer patients use supplements (supps); however, most rely on questionable sources. Naturopathic Doctors (NDs) are licensed doctoral-level healthcare providers who facilitate the safe use of natural compounds and provide evidence-based treatment regimens. We sought to explore the influence of naturopathic physicians on supp use within a tertiary hospital setting. Methods: A two month retrospective chart review using a convenient sample of all new patients seen by NDs working within the hospital clinic. Results: 242 patients were identified; 98 had gynecological malignancies, 51 colon, 47 lung, 18 breast, 28 prostate and others. The average age was 55 (32-79); 61% Caucasians, 33% African American, 6% Hispanic and others. Prior to seeing an ND, 25% of patients were taking an average of 4 supps (median 3, range [1-15]). Of these, 44% had an average of 3 supps removed (median 2, range [1-8]) by the ND on their initial visit. The most commonly removed supps represented herbal combinations containing multiple ingredients that were judged by the ND to pose a potential safety risk. NDs prescribed an average of 4 (median 3, range [1-10]) additional supps to 98% of new patients during the initial visit. The most commonly recommended supp was vitamin D. Concurrent serum analysis revealed 60% as vitamin D deficient according to standard ranges (<30 mmol). There was no statistically significant correlation between MD Anderson Symptom Inventory scores, BMI, age, or race and the number of supps recommended or removed by the NDs. NDs were able to completely stop all supp use by patients prior to surgery. Post-op, patients resumed supps as directed by the NDs. Conclusions: Changes in every patient’s supplement regimen demonstrate that NDs play a prominent role in the supp use of cancer patients in a tertiary oncology hospital setting. Based on these findings, more research is warranted to define the influences on supplement use, including the role of NDs.
Concomitant characterization of androgen receptor (AC) and immune checkpoints (ICs) in cell-free (cf) DNA and RNA from patients with metastatic castration resistant prostate cancer (mCRPC).
Authors: Sumanta K. Pal, Christopher Szeto, Sandeep K. Reddy, Roberto Nussenzveig, Richard Y. Lam, Mark C. Scholz, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2019)

286 Background: Immunotherapy (IO) appears to benefit a subset of patients (pt) with mCPRC, with recent data showing disease control &gt; 6 mo in 11% of patients (De Bono et al ASCO 2018). We interrogate cfDNA/cfRNA from pt with mCRPC to ascertain relationships between AR and IC markers, and offer preliminary correlation with response to IC inhibitors (ICIs). Methods: Pt in this series were on active therapy for mCRPC and received cfDNA/cfRNA assessment for 26 analytes using the CLIA-certified NantHealth LiquidGPS platform during the course of routine clinical care. For this assay, 10 mL of blood were separately collected in DNA and RNA stabilizing solutions, respectively. DNA was amplified via mutant allele-specific blocker or allele-specific PCR assays. Wild type (WT) DNA was PCR amplified in an area where mutations had not been detected, and allele fractions were determined by the ratio of mutant to WT alleles. RNA was reverse transcribed to cDNA using random hexamer primers and amplified via gene specific assays relative to a stably expressed housekeeping gene, beta actin. Results: 103 pt were tested, median age 74y (range, 51-95). Expression was elevated for AR in 41%, and for AR-V7 in 3% pt. cfRNA detected expression for PD-L1, CTLA4, LAG-3 and TIM-3 in 60%, 52%, 72%, and 81% pt respectively. There was no strong association between AR and PD-L1 expression (Rho = 0.03, P = 0.77), or coincidence of detectable levels (OR = 1.4, p = 0.43). AR expression weakly inversely correlated with expression of CTLA4, LAG-3 and TIM-3. In 2 pts responding to ICI therapy, markedly increased PD-L1 and CTLA4 expression was noted. Multiple additional pts are receiving ICIs and correlation between expression of AR/IC markers and response will be presented. Conclusions: Unlike within the tumor microenvironment,expression ofcirculating AR and IC markers are independent biomarkers offering potentially more specific insights into combination versus sequential strategies for AR-directed tx and IO. Our preliminary observation of elevated circulating IC makers in the context of ICI response in mCRPC will be assessed in a larger series.
A comparative evaluation of hybrid error correction methods for error-prone long reads
Authors: Shuhua Fu, Anqi Wang, Kin Fai Au
Journal: Genome biology (2019)

Third-generation sequencing technologies have advanced the progress of the biological research by generating reads that are substantially longer than second-generation sequencing technologies. However, their notorious high error rate impedes straightforward data analysis and limits their application. A handful of error correction methods for these error-prone long reads have been developed to date. The output data quality is very important for downstream analysis, whereas computing resources could limit the utility of some computing-intense tools. There is a lack of standardized assessments for these long-read error-correction methods. Here, we present a comparative performance assessment of ten state-of-the-art error-correction methods for long reads. We established a common set of benchmarks for performance assessment, including sensitivity, accuracy, output rate, alignment rate, output read length, run time, and memory usage, as well as the effects of error correction on two downstream applications of long reads: de novo assembly and resolving haplotype sequences. Taking into account all of these metrics, we provide a suggestive guideline for method choice based on available data size, computing resources, and individual research goals.
Abstract P027: Perceived Discrimination and Trajectory of High-Sensitivity C-Reactive Protein: The Jackson Heart Study
Authors: Kendra D Sims, Mario Sims, LáShauntá Glover, Ellen Smit, Michelle C Odden
Journal: Circulation (2019)

Introduction: Perceiving discriminatory treatment against oneself may induce a stress response, and over time contribute to cardiovascular pathophysiology. The study evaluated the association of self-reported discrimination and changes in high-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation predictive of incident cardiovascular disease. Hypothesis: We assessed the following hypotheses: 1) higher levels of perceived discrimination are associated with higher serum hs-CRP at baseline, 2) over 13 years of follow-up, greater mean increases in hs-CRP are observed among those with higher levels of baseline discrimination than those with lower levels of discrimination, and 3) body composition mediates the longitudinal trajectory. Methods: The sample included 5145 African American participants, aged 21-92, in the Jackson Heart Study. Multiple imputation addressed missingness in baseline sociodemographic (e.g, age, sex, education), behavioral (e.g., AHA smoking and physical activity categorizations) and clinical covariates (e.g, estimated glomerular filtration rate, diastolic blood pressure, hemoglobin A1c) as well as in hs-CRP taken at all three study examinations. Everyday, lifetime, and burden from perceived discrimination -attributed to reasons including race, gender, age, or weight- comprised primary predictors in three sets of multivariable linear regression models of baseline (2000-2004) discrimination and ln(hs-CRP). Linear mixed models (LMMs) were fitted to assess mean changes in ln(hs-CRP) between three study examinations (2000-2013).Mediation was quantified by percent changes in estimates adjusted for the adiposity measures BMI, waist circumference, or waist-to-height ratio. Results: In the cross-sectional analyses, those in the highest tertile of lifetime discrimination had adjusted ln(hs-CRP) levels 0.08 ln(mg/dL) lower than those in the lowest tertile (95% CI= -0.16, -0.01). However, the ln(hs-CRP) increases among those reporting more frequent everyday discrimination were 0.07 ln(mg/dL) higher per examination than those reporting no everyday discrimination (95% CI=0.01, 0.12) A similar trend emerged for lifetime discrimination and changes in ln(hs-CRP) (adjusted mean increase per visit: 0.04 ln(mg/dL), CI=0.01, 0.08). BMI, waist circumference, or waist-to-height ratio did not mediate the longitudinal associations between any discrimination measure and hs-CRP. In sensitivity analyses, the magnitude of these estimates did not change before or after multiple imputation. Conclusion: Everyday and lifetime discrimination were associated with significant hs-CRP increases over 13 years of follow-up. These conclusions build upon the existing research that indicates the physiological response to discrimination may lead to systemic inflammation and in turn cardiovascular disease.
Olaparib and α-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: a dose-escalation and dose-expansion phase 1b trial
Authors: Panagiotis A Konstantinopoulos, William T Barry, Michael Birrer, Shannon N Westin, Karen A Cadoo, Geoffrey I Shapiro, Erica L Mayer, Roisin E O'Cearbhaill, Robert L Coleman, Bose Kochupurakkal, Christin Whalen, Jennifer Curtis, Sarah Farooq, Weixiu Luo, Julia Eismann, Mary K Buss, Carol Aghajanian, Gordon B Mills, Sangeetha Palakurthi, Paul Kirschmeier, Joyce Liu, Lewis C Cantley, Scott H Kaufmann, Elizabeth M Swisher, Alan D D'Andrea, Eric Winer, Gerburg M Wulf, Ursula A Matulonis
Journal: The Lancet Oncology (2019)
Fumarate hydratase expression in localized, radically-resected clear cell renal cell carcinoma and its association with clinical outcomes.
Authors: Giovanni FucÃ, Claudio Vernieri, Simona Massa, Alessia Bertolotti, Giovanna Garzone, Amir Hosseini, Elena Verzoni, Raffaele Ratta, Giancarlo Pruneri, Saverio Minucci, Filippo G. De Braud, Maurizio Colecchia, Giuseppe Procopio
Journal: Journal of Clinical Oncology (2019)

620 Background: Prognostic stratification of localized clear cell renal cell carcinoma (lccRCC) mainly relies on clinical characteristics and TNM staging system, while biological biomarkers are currently lacking. We previously showed that reduced expression of the tricarboxylic acid cycle enzyme fumarate hydratase (FH) was associated with better clinical outcomes in patients (pts) with metastatic ccRCC. In the present study we aimed at assessing the association between intratumor FH expression and clinical outcomes in pts with radically-resected lccRCC. Methods: Pts with radically-resected lccRCC and available formalin-fixed, paraffin-embedded (FFPE) primary (renal) tumor tissue were included. FH protein expression was assessed by means of immunohistochemistry (IHC) and defined as normal (comparably to non-neoplastic tubular cells) or low (lower than in non-neoplastic tubular cells). Results: Out of 50 pts included, we found a normal FH expression in 20 cases (40%) and a low FH expression in 30 cases (60%). Median age was 57 years (interquartile range 49-68) and 48 pts (96%) had pN0 disease, while 2 pts (4%) had pN1 disease. Low FH expression was associated with pT ( P= .003) but not with sex, age, Fuhrman grade or pN. After a median follow-up of 76.9 months, low FH expression was associated with a lower relapse rate (13% vs 50%; odds ratio for relapse 0.16; 95% confidence interval [CI] 0.04-0.62; P= .005), longer relapse-free survival (RFS) (5-years RFS rate 90% vs 50%; HR 0.20; 95% CI 0.06-0.63; P= .006) and a trend toward a better overall survival (OS) (5-years OS rate 100% vs 77.3%; HR 0.14; 95% CI 0.02-1.23; P= .07) when compared with normal FH expression. In the multivariable model including other characteristics associated with RFS, low FH expression confirmed an independent association with RFS (adjusted HR 0.25; 95% CI 0.06-0.91; P= .03). Conclusions: In our study, low intratumor FH, as detected by IHC, was associated with lower relapse rate, better RFS and a trend toward a better OS in patients with lccRCC when compared with normal FH levels. The role of FH expression as a prognostic biomarker in this setting warrants further investigation.
Abstract P342: Life’s Simple 7 Among Statin Users and Non-Users at High Cardiovascular Risk. The Polish Norwegian Study-PONS
Authors: Georgeta Vaidean, Marta Manczuk, Sandeep Vansal
Journal: Circulation (2019)

Introduction: Cardiovascular risk reduction requires the pharmacological treatment of hyperlipidemia to be accompanied by the adoption of healthy behaviors. Whether statin users do so, is not clear and both, false reassurance and healthy adherer-phenomena have been theorized. Our objectives were: 1) to compare AHA Life’s Simple 7 (LS7) prevalence in statin users vs. non- users among statin candidates at high cardiovascular risk and 2) to assess LS7 among potential statin users candidates for Ethyl eicosapentaenoic acid (EPA) treatment. Methods: We used cross-sectional, baseline data of 12754 participants, age 45 to 64 years in a community-based cohort study (PONS). Data were collected through structured questionnaires and fasting blood samples. LS7 were defined based on AHA criteria. Statin use was recorded by trained nurses. We defined as high risk those with clinical ASCVD or diabetes, and those with LDL higher than 190 mg/dL. Statin users potential candidates for EPA therapy were defined based on the REDUCE-IT trial entry criteria. Results: There were 2722 (21.3%) individuals at high risk, of which 791 (29.1%) were using statins. Compared to non-users, statin users were older, mean age (SD) 59 (4) vs. 57 (5), more men (37.4% vs. 32.7%), had lower TC, 185.3 (43) vs. 224.7 (48), lower LDL, 105.6 mg/dL (39) vs. 141.5 (46) , more obesity, 46.1% vs.39.6%, less controlled blood pressure 5.5 % vs. 5.6%, less optimal plasma glucose, 48.3 % vs. 53.2% and more AHA poor diet, 40.1% vs. 32.7% (all p-val. less than 0.05). More statin users than non-users (90.6% vs 73.6%) had poor cardiovascular health, with an age- and sex-adjusted OR (95% CI) of 3.2 (2.4-4.2). The prevalence of potential statin users EPA candidates in the full, community-based sample was low (73 individuals, 0.6%); these individuals had poor glucose control (42.5%), high prevalence of obesity (64.4%) and poor AHA diet (32.4%). Conclusion: Statin users had a worse LS7 profile than non-users, with most unhealthy behaviors being poor diet and obesity. In the context of efficacious pharmacological agents, behavioral cardiovascular health remains an unfulfilled target.
Treatment of multiple esophageal diverticula by peroral endoscopic myotomy
Authors: Li-Hua Ren, Ya-Dong Feng, Rui-Hua Shi
Journal: Endoscopy (2019)

A 55-year-old man with persistent dysphagia and chest pain for 5 years was referred to our medical team. Gastroscopy (Olympus, Tokyo, Japan) revealed two distinct diverticula: one mid-esophageal diverticulum located 33 cm from the incisors and another "kissing" epiphrenic diverticula 43 cm from the incisors ([Fig. 1], preoperation). Barium swallow showed the size of the esophageal diverticula to be 4 mm, 19 mm and 22 mm, respectively ([Fig. 2], preoperation). Esophageal manometry showed no findings of a primary motility disorder ([Fig. 3]).
Abstract 16722: Impact of the Continued Positive Airway Pressure Breathing on Ablation-outcome in Atrial Fibrillation Patients With Obstructive Sleep Apnea and/or Metabolic Syndrome at Long-term Follow-up: A Single-center Experience
Authors: Sanghamitra Mohanty, Chintan Trivedi, Domenico G Della Rocca, Carola Gianni, John D Burkhardt, Javier Sanchez, Rodney Horton, G J Gallinghouse, Amin Al-Ahmad, Luigi Di Biase, Andrea Natale
Journal: Circulation (2017)

Introduction: Metabolic syndrome (MS) and obstructive sleep apnea (OSA) are well-known independent risk factors for AF recurrence. Several studies have demonstrated an increasing association of MS ...
Abstract P185: Alcohol Consumption and Cardiovascular Disease Mortality in Adults With Hypertension Following the 2017 Blood Pressure Guidelines
Authors: Angelique G Brellenthin, Duck-chul Lee, Xuemei Sui, Steven N Blair
Journal: Circulation (2019)

Introduction: Approximately half of adults have hypertension (HTN) under the 2017 blood pressure (BP) guidelines. The guidelines recommend lifestyle factors, such as limiting alcohol consumption, to manage BP, although safe levels of alcohol consumption have not been investigated for this new population with HTN. Objective: To examine the dose-response associations of alcohol consumption and cardiovascular disease (CVD) mortality in 29,499 adults (45±10 years) with HTN defined as systolic/diastolic BP ≥130/80 mmHg or physician diagnosis. Methods: Participants received a preventive medical examination during 1974-2003 and were without CVD, cancer, or abnormal electrocardiogram at baseline. Participants self-reported the number of standard alcoholic beverages they consumed per week on a medical history questionnaire. Participants were classified into 5 groups: non-drinkers and sex-stratified quartiles of weekly drinks based on no significant interaction by sex. Non-drinkers with a previous history of alcohol use problems were excluded to minimize a potential selection bias. Mortality follow-up was through 2003 using the National Death Index. Cox regression models included baseline age, sex, examination year, smoking status, body mass index, meeting the aerobic physical activity guidelines, and parental CVD. Models were further adjusted for cardiorespiratory fitness (CRF; in METs). Results: During a mean follow-up of 14.5 years, 672 CVD deaths occurred. Quartiles of alcohol consumption were 1-3, 4-7, 8-14, ≥15 drinks per week for men and 1-2, 3-4, 5-9, ≥10 drinks per week for women. Compared with non-drinkers (23%; 6,756 of 29,499), the hazard ratios (95% confidence intervals) for CVD mortality among quartiles of drinking were 0.71 (0.54-0.92), 0.73 (0.58-0.92), 0.76 (0.60-0.98), and 0.84 (0.67-1.05) after adjusting for potential confounders. After additional adjustment for CRF, the HRs were 0.75 (0.58-0.98), 0.79 (0.62-0.996), 0.82 (0.65-1.05) and 0.90 (0.72-1.13) for CVD mortality compared with non-drinkers. We found similar trends for CVD mortality after adjusting for fasting glucose, resting systolic and diastolic BP, total cholesterol, diabetes, and hyperlipidemia. We also found similar results in subgroups of men and women, young (&lt;60 years) and old (≥60 years), and normal weight (&lt;25 kg/m 2 ) and overweight/obese (≥25 kg/m 2 ) individuals. Similar trends were observed for all-cause mortality, although the associations were attenuated in all quartiles of drinking both before and after adjusting for CRF. Conclusions: The risk of CVD mortality was lower in light-to-moderate (quartiles 1-3) alcohol drinking in adults with HTN although these associations became weaker after adjusting for CRF. These results suggest a potential confounding effect of CRF on the association between alcohol consumption and CVD mortality that should be considered for future studies.
Effect of Continuous Positive Airway Pressure on Blood Pressure in Obstructive Sleep Apnea with Cardiovascular Disease
Authors: Emer Van Ryswyk, Craig S. Anderson, Ferran Barbe, Kelly A. Loffler, Geraldo Lorenzi-Filho, Yuanming Luo, Weiwei Quan, Jiguang Wang, Danni Zheng, R. Doug McEvoy
Journal: American Journal of Respiratory and Critical Care Medicine (2019)
The repertoire of maternal anti-viral antibodies in human newborns
Authors: Christian Pou, Dieudonné Nkulikiyimfura, Ewa Henckel, Axel Olin, Tadepally Lakshmikanth, Jaromir Mikes, Jun Wang, Yang Chen, Anna Karin Bernhardsson, Anna Gustafsson, Kajsa Bohlin, Petter Brodin
Journal: Nature Medicine (2019)
Nonclassical GH Insensitivity: Characterization of Mild Abnormalities of GH Action
Authors: Helen L Storr, Sumana Chatterjee, Louise A Metherell, Corinne Foley, Ron G Rosenfeld, Philippe F Backeljauw, Andrew Dauber, Martin O Savage, Vivian Hwa
Journal: Endocrine Reviews (2018)

Abstract GH insensitivity (GHI) presents in childhood with growth failure and in its severe form is associated with extreme short stature and dysmorphic and metabolic abnormalities. In recent years, the clinical, biochemical, and genetic characteristics of GHI and other overlapping short stature syndromes have rapidly expanded. This can be attributed to advancing genetic techniques and a greater awareness of this group of disorders. We review this important spectrum of defects, which present with phenotypes at the milder end of the GHI continuum. We discuss their clinical, biochemical, and genetic characteristics. The objective of this review is to clarify the definition, identification, and investigation of this clinically relevant group of growth defects. We also review the therapeutic challenges of mild GHI.