tbuckley/cabot-search huggingface dataset:
Abstract 001: Proteomic Signatures of Cardiovascular Risk Factors: A Cross-sectional Analysis of the Plasma Proteome in the Framingham Heart Study
Authors: Laura Corlin, Chunyu Liu, Martin G Larson, Ramachandran S Vasan
Journal: Circulation (2019)

Introduction: Proteomic biomarkers related to cardiovascular disease (CVD) risk factors may offer insights into the pathogenesis of subclinical and clinical CVD. Hypothesis: We hypothesized that 1) CVD risk factors may have distinctive proteomic signatures; and 2) select proteins are associated with multiple CVD risk factors indicating a central (pleiotropic) role in disease pathogenesis. Methods: We measured 1317 circulating plasma proteomic biomarkers (SomaScan; using the SomaLogic platform) in up to 897 Framingham Heart Study Generation 3 participants (mean age 46 years; 56% women) without hypertension, diabetes mellitus, or clinical CVD at the second examination (2008-2011). We used linear regression (or logistic for binary outcomes) to relate levels of each inverse-log transformed proteomic biomarker to age, sex, body mass index (BMI), waist circumference, systolic and diastolic blood pressure, blood lipid fractions, fasting blood sugar and insulin, coronary artery calcium (by computed tomography), left ventricular mass (by echocardiography), pre-hypertension, pre-diabetes, dyslipidemia, overweight, obesity, alcohol consumption, physical activity (by accelerometer), and smoking. All models adjusted for age, sex, and BMI. A Bonferroni-adjusted p-value &lt;2.7E-5 indicated statistical significance. Results: Forty-one proteins were associated with ≥8 CVD risk factors and 13 proteins (Apo E, C5a, GHR, IGFBP-2, leptin, NG36, Notch-3, QORL1, RGMB, SHBG, TIG2, XTP3A, tPA) were associated with ≥10 risk factors. Illustrative volcano plots for proteomic signatures of smoking and physical activity show high representation of proteins related to tumor suppression, immunologic function, and cellular communication (Figure). Conclusions: Our cross-sectional data from a relatively healthy community-based sample elucidated distinctive proteomic signatures of CVD risk factors. A small group of proteins were associated with multiple risk factors, suggesting their potential pleiotropic role in CVD.
Epidemiology of male seminomatous (SGCT) and non-seminomatous germ cell tumours (NSGCT) and response to first line chemotherapy (CT) from a tertiary cancer centre in India.
Authors: Saurabh shyamsunder Zanwar, Amit Joshi, Vanita Noronha, Vijay Maruti Patil, Nishitha Shetty, Kumar Prabhash
Journal: Journal of Clinical Oncology (2015)

e15553 Background: Unlike the developed countries, there is lack of good epidemiologic data for testicular GCTs in India. The epidemiology tends to differ from that of developed countries with a fair proportion presenting in advanced stage. As a result, outcomes with 1st line CT are likely to differ. This study aims to elaborate on the epidemiology of testicular GCTs and response to standard 1st line CT. Methods: GCTs treated at our centre from January 2013 to August 2014 were retrospectively analysed. Patients underwent orchidectomy either outside or at our hospital. Based on stage and risk group, standard CT (BEP/EP/Carboplatin AUC7) and radiotherapy (RT) was given as appropriate. Response was calculated based on RECIST. Statistical analysis was performed using SPSS 18. Results: 49 of NSGCT and 39 of SGCT cases were studied. The mean age was 28 years (17-70) for NSGCT and 36 years (22-65) for SGCT. 6% of NSGCT and 13% of SGCT had cryptorchidism. 31%, 45%, 63% of NSGCT and 10%, 31%, 21% of SGCT had N2, N3 and M1 disease respectively. The mean nodal size was 5.3cm (0-19) in NSGCT and 2.75cm (0-11) in SGCT. As per the IGCCCG classification 33% NSGCT were good, 35% intermediate and 32% were poor risk whereas 82% of SGCT were good and 18% were intermediate risk. 22% of NSGCT and 13% of SGCT had scrotal violation outside. Following CT amongst NSGCT, 5% and 64% had radiologic CR and PR respectively and 43% had residual nodal disease requiring RPLND. Amongst SGCT, 31% and 56% had radiologic CR and PR respectively and 6% required RPLND. 18% NSGCT and 6% SGCT were unamenable for surgical resection post CT. 20%, 52%, 11% of NSGCT and 16%, 32%, 28% of SGCT developed febrile neutropenia, grade 3/4 haematological and non-haematological toxicity respectively after standard CT. 10% of both NSGCT and SGCT patients defaulted after CT. Conclusions: GCTs in India present with large nodal and high risk disease wherein the standard first line CT may not be adequate as curative therapy, however significant chemotoxicity is also a hinderance.
Moderately hypofractionated radiotherapy for localized prostate cancer: Long-term outcomes for 854 consecutive patients treated over 10 years (70 Gy in 2.5 Gy/fraction).
Authors: Omar Y. Mian, Ibrahim Abu-Gheida, Rupesh Kotecha, Michael A. Weller, Chandana A. Reddy, Patrick Kupelian, Moshe Chaim Ornstein, Timothy D. Gilligan, Jorge A. Garcia, Brian I. Rini, Andrew J. Stephenson, Eric A. Klein, Chirag Shah, Jay P. Ciezki, Kevin L. Stephans, Rahul D. Tendulkar
Journal: Journal of Clinical Oncology (2019)

78 Background: Moderately hypofractionated radiotherapy has been increasingly adopted in the management of localized prostate cancer (PCa). We report 10-year outcomes for patients treated with intensity modulation radiation therapy (IMRT) for localized PCa with 70 Gy in 28 fractions at 2.5 Gy/fraction. Methods: This retrospective study included 854 consecutive patients with localized PCa treated with image-guided moderately hypofractionated IMRT at a single institution between 1998 and 2012. Patients with a single intermediate-risk factor were considered to have favorable intermediate-risk (FIR) disease; multiple intermediate-risk factors were considered unfavorable (UIR). Biochemical relapse free survival (bRFS), clinical relapse free survival (cRFS), overall survival (OS) and PCa specific mortality (PCSM) were analyzed used Kaplan-Meier analysis. Grade ≥3 genitourinary (GU) and gastrointestinal (GI) toxicities were recorded (CTCAE v4.03). Results: The median follow-up was 11.3 years (Max. 19 years). For patients with low-risk (LR, 31%), FIR (28%), UIR (12.5%), and high-risk (HR, 28.5%) disease the 10 year bRFS rates were 88%, 78%, 71% and 42%, respectively (p &lt; 0.0001). The number of patients receiving no ADT, 1-6 months, or &gt; 6 months of ADT were 39%, 50%, and 11%, respectively, reflecting practice patterns during this treatment period. The 10-year cRFS were 95%, 91%, 85% and 72% for patients with LR, FIR, UIR, and HR, respectively (p &lt; 0.0001). The 10-year actuarial OS rate was 69% (95% CI 66-73%) and the 10-year PCSM was 6.8% (95% CI 5.1-8.6%) overall. For patients with LR, FIR, UIR and HR disease, the 10 year PCSM rates were 2%, 5%, 5% and 15%. 10-year cumulative incidence of grade ≥3 GU and GI toxicity was 2% and 1%, respectively. Multivariate analysis identified associations between clinical variables (ADT use, PSA nadir &lt; 0.5ng/ml, and ISUP Grade Group) and bRFS, cRFS, and PCSM. Conclusions: Moderately hypofractionated IMRT with daily image guidance for localized PCa demonstrates favorable 10-year oncologic outcomes with a low incidence of toxicity for patients across all risk groups.
Neutrophil-to-lymphocyte ratio as a prognostic biomarker for overall survival in men with advanced prostate cancer treated with platinum chemotherapy.
Authors: Panagiotis J. Vlachostergios, Aileen Lee, Charlene Thomas, Amy Hackett, Ana M. Molina, David M. Nanus, Himisha Beltran, Scott T. Tagawa
Journal: Journal of Clinical Oncology (2019)

266 Background: Platinum compounds are active in pts with metNEPC/CRPC. The neutrophil-to-lymphocyte ratio (NLR) is a simple clinical metric of systemic inflammation with prognostic and predictive value in advanced PC treated with FDA-approved therapies (doc, abi, enza, cabaz, mitox). We hypothesized that pretreatment NLR may be associated with clinical outcomes of platinum-treated pts. Methods: Records were reviewed from NEPC/CRPC platinum-treated pts with available information to enable pretreatment NLR calculation. Kaplan Meier curves, Cox regression analyses were used to predict PSA-PFS, radiographic PFS and OS after platinum initiation. For NLR, a cutoff of ≤5 was used as previously described (Leibowitz-Amit et al. 2014). Results: 108 men, median age 64 yrs (range 46-80), were studied. 28 pts (26%) were NEPC based on histological features. 54 had visceral mets (39 liver, 31 lung, 8 brain). 100 received carboplatin, 17 received cisplatin (9 received both sequentially, with initial platinum used for this analysis). Most received platinum in combination with other drugs, most commonly paclitaxel (N = 71) and etoposide (N = 20). 51 (47.2%) had low NLR ≤5 and 57 (52.7%) had high NLR &gt; 5. Median PSA-PFS was 5 months in the low NLR group versus 3 months in the high NLR group (log-rank P = 0.07). Median rPFS did not differ between the two NLR groups (log-rank P = 0.36). Median OS of pts with NLR ≤5 was 15 months vs only 9 months in the high NLR ( &gt; 5) subgroup (log-rank P = 0.06). There was no significant difference in NLR or OS status between NEPC and CRPC pts. On multivariate analysis (adjusted for age at platinum, Gleason, PSA, ALP, LDH, Hb, measurable disease, visceral mets, ECOG PS, use of opioids), NLR emerged as an independent prognostic factor for OS (HR 5.39, 95% CI 1.25-23.33, P = 0.02), together with PSA (P = 0.03) and visceral mets (P = 0.02). Conclusions: NLR is associated with shorter OS in men with advanced PC who receive platinum-based chemotherapy. It may serve as a useful clinical indicator of systemic inflammatory response and is more prognostic than standard NEPC vs adenocarcinoma histology. Prospective validation studies in such pts are needed to confirm these findings.
Alterations of DNA damage response (DDR) genes correlate with favorable response and overall survival (OS) in anti-PD-1/PD-L1-treated advanced urothelial cancer (UC).
Authors: Monika Joshi, Petros Grivas, Amir Mortazavi, Paul Monk, Steven K. Clinton, Michele Sue-Ann Woo, Sheldon L. Holder, Joseph J. Drabick, Ming Yin
Journal: Journal of Clinical Oncology (2019)

438 Background: DDR gene alterations may contribute to higher tumor mutational burden (TMB) via genomic instability in addition to APOBEC mutagenesis. We previously showed that ATM mutations correlated with shorter OS in UC, while Teo et al. showed patients (pts) with DDR alterations benefited from PD-1/PD-L1 blockade in advanced UC. Here, we aimed to validate those findings and further explore the prognostic role of ATM mutations in advanced UC treated with anti-PD-1/PD-L1 agents. Methods: The study included 53 pts who had FoundationOne tumor tissue genomic sequencing and anti-PD-1/PD-L1 therapy. Fisher exact test was used to test difference in objective response rate (ORR). OS was measured from time of initial UC diagnosis and Cox proportional hazard regression analysis was performed to calculate the hazard ratio (HR) and 95% confidence interval (CI). Results: The cohort had a median age of 66 (range 21–81) with 34% females and 64.2% platinum-based chemotherapy. DDR alterations (including ATM) were present in 49.1% pts (26/53) and favored a higher ORR (37.5% vs. 23.1%, p = 0.26). Compared with those without DDR alterations, pts with DDR alterations (excluding ATM) seemed to have longer OS, although significance was not reached likely due to a short follow-up time (HR = 0.53, 95% CI 0.20–1.38, p = 0.19). ATM alterations seemed to favor higher response rate to PD-1/PD-L1 blockade (ORR, 40% vs. 28.9%, p = 0.6), but was associated with significantly shorter OS (HR = 5.7, 95% CI 1.65–19.74, p = 0.006) in overall pts and in subgroups with/without platinum-based chemotherapy (data not shown). Pts with ≥ 3 DDR alterations (including ATM) had substantial higher TMB (13.9–72.2 perMb, median 22.6) and benefited the most from PD-1/PD-L1 blockade with 80% ORR vs. 24.4% ORR in pts with &lt; 3 DDR alterations. Conclusions: Our study supported that DDR alterations are associated with higher response rate and prolonged OS in advanced UC pts receiving anti-PD-1/PD-L1 agents, likely from impact on TMB. However, ATM alterations correlated with poor prognosis also in those pts. Further studies are needed to assess the clinical utility of DDR alterations in directing therapies in UC.
Lessons on managing pulmonary nodules from NELSON: we have come a long way
Authors: Carolyn Horst, Arjun Nair, Sam M Janes
Journal: Thorax (2019)

The results of the Dutch-Belgian low-dose CT (LDCT) screening trial (NELSON) have been eagerly awaited since the US National Lung Screening Trial (NLST), published in 2011, demonstrated annual LDCT screening of the chest led to a 20% decrease in lung cancer mortality compared with chest X-ray screening.1 While the US Preventative Service Task Force approved lung cancer screening in 2014,2 Europe and the rest of the globe have been paralysed by fear of implementation costs and the feasibility of introducing national LDCT screening programmes. The consensus from healthcare payers outside of the USA has been that we should wait for the results of the NELSON trial which, while smaller in size, would give us the confidence of a second randomised controlled trial and proof of effect in a population outside of the US healthcare system. Indeed, a recent Health Technology Assessment of LDCT screening in the UK specifically named the NELSON trial as an important source of future information and explicitly stated the results were required in order to make a decision about its efficacy and cost-effectiveness.3 It was on this background of hope and perhaps, dare we say it, healthcare payer fear that the NELSON trial preliminary results were released at the World Conference on Lung Cancer in Toronto in October.

Despite NELSON being smaller in size than NLST and having a preponderance of male participants, the results were clear: LDCT screening compared with no screening leads to a statistically significant lung cancer mortality reduction of 26% for men and numbers hint that the benefit could be even greater in women (between 40% and 60%). With this new data the UK, and indeed the world outside of the USA, now needs to cast aside concerns over efficacy, as well as procrastination over implementation, and concentrate more …
What's in a model? Network models as tools instead of representations of what psychiatric disorders really are
Authors: Hanna M. van Loo, Jan-Willem Romeijn
Journal: Behavioral and Brain Sciences (2019)

Abstract Network models block reductionism about psychiatric disorders only if models are interpreted in a realist manner – that is, taken to represent “what psychiatric disorders really are.” A flexible and more instrumentalist view of models is needed to improve our understanding of the heterogeneity and multifactorial character of psychiatric disorders.
Mechanisms of Venetoclax Resistance in Chronic Lymphocytic Leukemia
Authors: Lukas P. Frenzel, Carmen D. Herling, Nima Abedpour, Jonathan Weiss, Petra Mayer, Maria Cartolano, Valeska Berg, Nadine Kutsch, Paula Cramer, Clemens-Martin Wendtner, Thorsten Persigehl, Andreas Saleh, Janine Altmüller, Peter Nürnberg, Christian Pallasch, Viktor Achter, Ulrich Lang, Barbara F. Eichhorst, Roberta Castiglione, Stephan C. Schaefer, Reinhard Buettner, Karl-Anton Kreuzer, Hans Christian Reinhardt, Michael J. Hallek, Martin Peifer
Journal: Blood (2017)
Effects of Icosapent Ethyl on Total Ischemic Events
Authors: Deepak L. Bhatt, Ph. Gabriel Steg, Michael Miller, Eliot A. Brinton, Terry A. Jacobson, Steven B. Ketchum, Ralph T. Doyle, Rebecca A. Juliano, Lixia Jiao, Craig Granowitz, Jean-Claude Tardif, John Gregson, Stuart J. Pocock, Christie M. Ballantyne
Journal: Journal of the American College of Cardiology (2019)

In time-to-first-event analyses, icosapent ethyl significantly reduced the risk of ischemic events, including cardiovascular death, among patients with elevated triglycerides receiving statins. These patients are at risk for not only first but also subsequent ischemic events.Pre-specified analyses determined the extent to which icosapent ethyl reduced total ischemic events.REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) randomized 8,179 statin-treated patients with triglycerides ≥135 and <500 mg/dl (median baseline of 216 mg/dl) and low-density lipoprotein cholesterol >40 and ≤100 mg/dl (median baseline of 75 mg/dl), and a history of atherosclerosis (71% patients) or diabetes (29% patients) to icosapent ethyl 4 g/day or placebo. The main outcomes were total (first and subsequent) primary composite endpoint events (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina) and total key secondary composite endpoint events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke). As a pre-specified statistical method, we determined differences in total events using negative binomial regression. We also determined differences in total events using other statistical models, including Andersen-Gill, Wei-Lin-Weissfeld (Li and Lagakos modification), both pre-specified, and a post hoc joint frailty analysis.In 8,179 patients, followed for a median of 4.9 years, 1,606 (55.2%) first primary endpoint events and 1,303 (44.8%) subsequent primary endpoint events occurred (which included 762 second events, and 541 third or more events). Overall, icosapent ethyl reduced total primary endpoint events (61 vs. 89 per 1,000 patient-years for icosapent ethyl versus placebo, respectively; rate ratio: 0.70; 95% confidence interval: 0.62 to 0.78; p < 0.0001). Icosapent ethyl also reduced totals for each component of the primary composite endpoint, as well as the total key secondary endpoint events (32 vs. 44 per 1,000 patient-years for icosapent ethyl versus placebo, respectively; rate ratio: 0.72; 95% confidence interval: 0.63 to 0.82; p < 0.0001).Among statin-treated patients with elevated triglycerides and cardiovascular disease or diabetes, multiple statistical models demonstrate that icosapent ethyl substantially reduces the burden of first, subsequent, and total ischemic events. (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial [REDUCE-IT]; NCT01492361).
Level of Evidence and Ethical Considerations for Locoregional Treatments in Metastatic Cervical Cancer—In Reply
Authors: Yuefeng Wang, Noam VanderWalde, Matthew T. Ballo
Journal: JAMA Oncology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Multi-center, randomized, controlled, open-label effectiveness study of primary tumor resection or not in asymptomatic colorectal cancer with unresectable metastatic disease.
Authors: Gong Chen, Rong-xin Zhang, Yu-hong Li, Jun-Zhong Lin, Ling-Heng Kong, Zhiqiang Wang, Pei-Rong Ding, Desen Wan, Zhi-zhong Pan, Yanhong Deng, Hui Wang, Jianjun Peng, Meng Qiu, Chang Wang, Jun Zhang, Wenliang Li, Ying Yuan, Wei Wang
Journal: Journal of Clinical Oncology (2015)

TPS3628 Background: It is still unclear whether asymptomatic colorectal cancer patients with unresectable metastatic disease can benefit from palliative resection of primary tumor. Retrospective studies showed a controversial result that some patients who received the resection of the primary tumor would prolong their overall survival time for 6 months. We plan to initiate the first randomized study to evaluate the efficacy of the resection of primary tumor in asymptomatic metastatic colorectal cancer patients who respond to initial chemotherapy. Methods: This is a multi-center, randomized, controlled, open label, phase III study. The primary endpoint of the study was overall survival (OS) based on independent assessment. Secondary end-points include progress free survival (PFS), health-related quality of life (HRQoL) and toxicity profiles. The study was designed to have 80% power to detect a 0.71 HR of OS in surgery arm (from 15 month to 21 month). Results from a one-sided log rank test at 0.025 significance level will be presented. Based on these assumptions, a total of 480 patients are needed to observe 320 events. All asymptomatic colorectal cancer patients with unresectable metastatic disease who agree to join this study will receive screening chemotherapy (any useful first line chemotherapy can be used here, except -becacizumab-which may affect the safety of surgery) for 6 months. Those who respond to chemotherapy or stable will be randomly assigned (1:1) to receive surgical resection of the primary tumor or continue chemotherapy. The patients in surgery group will receive chemotherapy after recover from surgery. Recruitment will begin in March 2015. The duration of the trial will be 72 months (36 months recruitment and 36 months follow-up). Clinical trial information: NCT02149784.
Networks, intentionality and multiple realizability: Not enough to block reductionism
Authors: Markus I. Eronen, Laura F. Bringmann
Journal: Behavioral and Brain Sciences (2019)

Abstract Borsboom et al. propose that the network approach blocks reductionism in psychopathology. We argue that the two main arguments, intentionality and multiple realizability of mental disorders, are not sufficient to establish that mental disorders are not brain disorders, and that the specific role of networks in these arguments is unclear.
The Paraventricular Hypothalamus Regulates Satiety and Prevents Obesity via Two Genetically Distinct Circuits
Authors: Monica M. Li, Joseph C. Madara, Jennifer S. Steger, Michael J. Krashes, Nina Balthasar, John N. Campbell, Jon M. Resch, Nicholas J. Conley, Alastair S. Garfield, Bradford B. Lowell
Journal: Neuron (2019)