tbuckley/cabot-search huggingface dataset:
Impact of subsequent post-discontinuation immunotherapy on overall survival in patients with unresectable, stage III NSCLC from PACIFIC
Authors: M. Ouwens, A. Darilay, Y. Zhang, P. Mukhopadhyay, H. Mann, J. Ryan, P.A. Dennis
Journal: Annals of Oncology (2019)

Background: In cancer trials, pts often receive subsequent lines of anticancer Tx following progression, which, in standard ITT analyses, can lead to bias and underestimation of OS Tx effect. In the phase 3 PACIFIC trial of durvalumab vs. placebo in Stage III NSCLC pts without progression after CRT, both primary endpoints PFS and OS were met, significantly improved with durvalumab. However, after discontinuation, many pts received further anticancer Tx (41% and 54% in the durvalumab and placebo groups), including immunotherapies (IMTs), which may have influenced OS. Using the Rank Preserving Structural Failure Time (RPSFT) model, we quantified the specific impact of subsequent IMT on OS in PACIFIC. Methods: RPSFT modeling is commonly used for analysis of trials with crossover. By assuming a similar effect for Tx in different sequences, RPSFT is capable to pinpoint the most likely effect size based on observed data. Here, we adapted RPSFT to isolate the likely effect of subsequent IMT by assuming similar mortality risk reduction for nivolumab, pembrolizumab, and durvalumab. RPSFT analyses were applied to quantify health outcomes for two hypothetical scenarios: (1) no subsequent IMT was received by pts in either arm, and (2) among placebo pts who received subsequent Tx (54%), all received IMT as first subsequent Tx, and durvalumab pts received no subsequent IMT, to test if delaying IMT was detrimental. Results: Among pts randomized to durvalumab and placebo, 8% (38/476) and 22% (53/237), respectively, received subsequent IMT. Within the ITT population, the HR for OS with durvalumab vs. placebo was 0.68 (95% CI, 0.53–0.87), with respective median OS not reached (NR) and 28.7 months. For scenario 1, there was minimal change in OS, with an estimated HR of 0.67 (95% CI, 0.52–0.86) and identical median OS estimates. For scenario 2, the estimated HR was 0.79 (95% CI: 0.62–1.00), with median OS NR and 32.2 months, respectively. Conclusions: After removing the effects of subsequent IMT, the OS benefit with durvalumab was still evident compared with the ITT analysis. In addition, early Tx with durvalumab after CRT appeared to be associated with improved OS compared with starting IMT after progression. Clinical trial identification: NCT02125461. Editorial acknowledgement: Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Hashem Dbouk, PhD, of Cirrus Communications, an Ashfield company, and was funded by AstraZeneca. Legal entity responsible for the study: AstraZeneca. Funding: AstraZeneca. Disclosure: M. Ouwens, Y. Zhang, P. Mukhopadhyay: Employment, stock options: AstraZeneca, outside the conduct of the study. A. Darilay, J. Ryan: Employment, stock: AstraZeneca, outside the conduct of the study. H. Mann: Employment: AstraZeneca, outside conduct of the study. P.A. Dennis: Employment, stocks: AstraZeneca, outside the submitted work.
Abstract 16797: Mechanisms That Repress BMP2 in Mesenchymal Cells
Authors: Melissa Rogers, Anastasios Fotinos, Tapan Shah
Journal: Circulation (2014)

BMP2 is an essential protein. A short burst of BMP2 promotes repair after vascular injury. However, excessive BMP2 levels in the vasculature and heart valves promote pathological calcification. A sequence within the 3’UTR of the mRNA termed the “ultra-conserved sequence” (UCS) has been largely unchanged since fishes and mammals diverged. Cre-lox mediated deletion of the UCS in a mouse reporter transgene revealed that one role of the UCS is to repress BMP2 synthesis in heart valves and vascular cells. We are now testing the hypothesis that normal heart morphology requires UCS-mediated restraint of BMP2 synthesis. We used homologous recombination to generate a Bmp2 allele with the endogenous Bmp2 UCS flanked by loxP sites. We bred this strain to strains that express Cre-recombinase thus deleting the UCS. The survival of pups with homozygous loss of the UCS was significantly reduced. We are now assessing embryonic heart morphology in these strains. We also postulate that the regulatory proteins and microRNAs that mediate UCS-mediated repression may be exploited to pharmacologically reawaken BMP2 repression in tissues undergoing pathological pathologies. Specific miRNAs inhibit UCS-bearing reporters and mutations of miRNA binding sites activate these reporters. Interestingly, an A+U rich element (ARE) known to bind HuR (generally an activator) and AUF1 (a repressor) is embedded in a conserved miRNA binding site. Selective mutations of the ARE and the miRNA seed indicate that repressive molecules bind this site in mesenchymal cells where the UCS functions as a repressor.
SAT-336-lLver stiffness measurement: An alternative practical predictor for early kidney dysfunction in patients with non-alcoholic fatty liver disease
Authors: DQ Sun, Fang-Zhou Ye, HALUK TARIK Kani, Chen-Fei Zheng, Pei-Wu Zhu, Hong-Lei Ma, Wen-Yue Liu, Hao-Yang Zhang, Xiao-Dong Wang, Wei-Jie Yuan, Yong-Ping Chen, Yusuf Yilmaz, Ming-Hua Zheng
Journal: Journal of Hepatology (2019)
Abstract 17545: Among Young Adults With MI, Women Have a Higher Rate of 1-Year Cardiac Readmission
Authors: Amber Fatima, Avinainder Singh, Bradley Collins, Arman Qamar, David Biery, Mary Cawley, Monica Eng, Roxanna Rajabi, Ankur Gupta, Viviany R Taqueti, Khurram Nasir, Marcelo F Di Carli, Deepak L Bhatt, Ron Blankstein
Journal: Circulation (2017)

Introduction: Hospital readmissions lead to increased health-care expenditure in patients with myocardial infarction (MI). However, the prevalence, determinants and prognostic implications in young...
TCTAP A-038 Evaluation of EPICOR Score for Predicting Two-year Outcomes in Patients with Acute Coronary Syndrome After Percutaneous Coronary Intervention
Authors: Yue Liu, Sida Jia, Yi Yao, Xiao-Fang Tang, Na Xu, Ping Jiang, Xueyan Zhao, Jue Chen, Yuejin Yang, Runlin Gao, Bo Xu, Jinqing Yuan
Journal: Journal of the American College of Cardiology (2019)
Can Network Meta-analysis Substitute for Direct Comparisons in Psychotherapy Trials?
Authors: Holly A. Swartz, Jay Fournier
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
TCTAP A-064 The Impact of Plaque Type on Strut Embedment/Protrusion and Shear Stress Distribution in Bioresorbable Scaffold
Authors: Erhan Tenekecioglu, Yuki Katagiri, Ryo Torii, Yoshinobu Onuma, Kerem Pekkan, Robert Van Geuns, Christos V. Bourantas, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (2019)
GS-18-Preventive administration of ursodeoxycholic acid after liver transplantation for primary biliary cholangitis prevents disease recurrence and prolongs graft survival
Authors: Christophe Corpechot, Olivier Chazouillères, Aldo Montano-Loza, Andrew L. Mason, Maryam Ebadi, Dennis Eurich, Sascha Chopra, Dietmar Jacob, Christoph Schramm, Martina Sterneck, Tony Bruns, Philipp Reuken, Falk Rauchfuss, Bettina Hansen, Davide Roccarina, THORBURN Douglas, Palak Trivedi, Gideon Hirschfield, Patrick McDowell, Olivier Boillot, Alexie Bosch, Emiliano Giostra, CONTI Filomena, Raoul Poupon, Albert Parés, Anna Reig, Annarosa Floreani, Francesco Paolo Russo, Jorn Goet, Maren Harms, Henk Van Buuren, Natalie Van den Ende, Frederik Nevens, Verhelst Xavier, Maria Francesca Donato, Federica Malinverno, Pierre Belnou, Fabrice Carrat, Jérôme Dumortier
Journal: Journal of Hepatology (2019)
Association of Maternal Cigarette Smoking and Smoking Cessation With Preterm Birth
Authors: Samir Soneji, Hiram Beltrán-Sánchez
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Cigarette smoking during pregnancy increases the risk of preterm birth, low birth weight, and infant mortality. <h3>Objective</h3> To assess the probability of preterm birth among expectant mothers who smoked cigarettes before pregnancy and quit smoking at the start or during pregnancy. <h3>Design, Setting, and Participants</h3> This cross-sectional study analyzed information provided on live birth certificates from 2011 through 2017 that were obtained from US states that implemented the 2003 revision of the US live birth certificate. In total, 25 233 503 expectant mothers who delivered live neonates and had known prepregnancy and trimester-specific cigarette smoking frequency were included in the analyses. <h3>Exposures</h3> Cigarette smoking frequency (1-9, 10-19, and ≥20 cigarettes per day) 3 months prior to pregnancy and for each trimester during pregnancy. <h3>Main Outcomes and Measures</h3> Cigarette smoking cessation throughout pregnancy, after the first trimester, after the second trimester, and during the third trimester irrespective of first and second trimester smoking. Probability of preterm birth (&lt;37 weeks’ gestation). <h3>Results</h3> Of 25 233 503 expectant mothers who delivered live neonates between 2011 and 2017, the modal age at delivery was 25 to 29 years; 52.9% were non-Hispanic white, 23.6% were Hispanic, and 14.2% were non-Hispanic black women; 22 600 196 mothers did not smoke during the 3 months prior to pregnancy, and 2 633 307 smoked during the 3 months prior to pregnancy. The proportion of prepregnancy smokers who quit throughout pregnancy was 24.3% in 2011 and 24.6% in 2017. The proportion of prepregnancy smokers who quit during the third trimester was 39.5% in 2011 and 39.7% in 2017. High-frequency cigarette smoking often occurred among expectant mothers who smoked during pregnancy (eg, 46.9% of third-trimester smokers smoked ≥10 cigarettes per day in 2017). The probability of preterm birth decreased more the earlier smoking cessation occurred in pregnancy. For example, the probability of preterm birth was 9.8% (95% CI, 9.7%-10.0%) among 25- to 29-year-old, non-Hispanic white, primigravida and primiparous expectant mothers (ie, pregnant for the first time and not yet delivered) who smoked 1 to 9 cigarettes per day prior to pregnancy and maintained this frequency throughout their pregnancy. The probability of preterm birth was 9.0% (95% CI, 8.8%-9.1%) if smoking cessation occurred at the start of the second trimester (an 8.9% relative decrease), and 7.8% (95% CI, 7.7%-8.0%) if cessation occurred at the start of pregnancy (a 20.3% relative decrease). <h3>Conclusions and Relevance</h3> Quitting smoking—and quitting early in pregnancy—was associated with reduced risk of preterm birth even for high-frequency cigarette smokers.
Obesity has an impact on the efficacy of EGFR-TKI in NSCLC patients harbouring EGFR mutation: A real-world study
Authors: Z.-Y. Ding, Y.-Y. Chen, Y. Hong, Y. Fu, L.-P. Tong, Q. Li, P.-P. Lin
Journal: Annals of Oncology (2019)

Background: EGFR-TKI has become the standard-of-care therapy for advanced NSCLC harbouring EGFR mutation. However, the efficacy varies widely, suggestive of other confounding factors. Obesity is related to the etiology, morbidity, and mortality of cancer. However, its impact on the efficacy of EGFR-TKI remains unknown. Methods: This was a multi-center, real-world study conducted in 3 tertiary referring medical centers. Treatment-naive metastatic NSCLC patients harbouring EGFR mutation who were prescribed with TKI (gefitinib, erlotinib, or icotinib) were enrolled. Body Mass Index (BMI) was proposed as the indicator of obesity. The PFS of all patients were collected and analyzed. Results: The training cohort (n = 321) consisted consecutive patients in West China Hospital from Sept 2010 to Jul 2018. The total PFS was 12.1m (95%CI: 11.2-13.0m). Those with a high BMI (>22.8) achieved a longer PFS than their counterparts (10.9 and 13.8 m, HR 0.68, 95% CI: 0.54-0.86, P = 0.001). Although the cut-off value was set-up by ROC analysis, the superiority was irrespective of the artificially-defined cut-off value (median 22.9, quadrant value 22.5 or 25). Additionally, the difference was confirmed in an independent validation cohort (n = 108) in 3 tertiary referring medical centers. The PFS was 11.3 and 13.7 m (HR 0.74, 95% CI: 0.61-0.91, P = 0.004). Interestingly, the influence of obesity was restricted in men (HR 0.45, 95% CI: 0.31-0.65, P<0.0001), while not in women (HR 0.89, 95% CI: 0.66-1.2, P = 0.47). Conclusions: High BMI is associated with improved outcomes in advanced NSCLC, primarily in men. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
ERS statement on respiratory muscle testing at rest and during exercise
Authors: Pierantonio Laveneziana, Andre Albuquerque, Andrea Aliverti, Tony Babb, Esther Barreiro, Martin Dres, Bruno-Pierre Dubé, Brigitte Fauroux, Joaquim Gea, Jordan A. Guenette, Anna L. Hudson, Hans-Joachim Kabitz, Franco Laghi, Daniel Langer, Yuan-Ming Luo, J. Alberto Neder, Denis O'Donnell, Michael I. Polkey, Roberto A. Rabinovich, Andrea Rossi, Frédéric Series, Thomas Similowski, Christina M. Spengler, Ioannis Vogiatzis, Samuel Verges
Journal: European Respiratory Journal (2019)

Assessing respiratory mechanics and muscle function is critical for both clinical practice and research purposes. Several methodological developments over the past two decades have enhanced our understanding of respiratory muscle function and responses to interventions across the spectrum of health and disease. They are especially useful in diagnosing, phenotyping and assessing treatment efficacy in patients with respiratory symptoms and neuromuscular diseases. Considerable research has been undertaken over the past 17 years, since the publication of the previous American Thoracic Society (ATS)/European Respiratory Society (ERS) statement on respiratory muscle testing in 2002. Key advances have been made in the field of mechanics of breathing, respiratory muscle neurophysiology (electromyography, electroencephalography and transcranial magnetic stimulation) and on respiratory muscle imaging (ultrasound, optoelectronic plethysmography and structured light plethysmography). Accordingly, this ERS task force reviewed the field of respiratory muscle testing in health and disease, with particular reference to data obtained since the previous ATS/ERS statement. It summarises the most recent scientific and methodological developments regarding respiratory mechanics and respiratory muscle assessment by addressing the validity, precision, reproducibility, prognostic value and responsiveness to interventions of various methods. A particular emphasis is placed on assessment during exercise, which is a useful condition to stress the respiratory system.
PD-L1 confers primary resistance to EGFR-TKI in EGFR mutant non-small cell lung cancer via inducing EMT phenotype
Authors: Y. Zhang, T. Liu, Y. Zeng, J. Zhu, W. Du, Z. Liu, J.-A. Huang
Journal: Annals of Oncology (2019)

Background: There were approximately 30% of patients with epidermal growth factor receptor (EGFR)-activating mutations do not respond to EGFR- tyrosine kinase inhibitors (TKIs) (primary resistance). However, little is known about the molecular mechanism involved in primary resistance to EGFR-TKIs in EGFR-mutant non-small-cell lung cancer (NSCLC). Programmed death ligand-1 (PD-L1) (B7-H1, CD274) is an important immune co-signaling molecule from the B7/CD28 family, it not only negatively regulates T cell functions through its PD-1 and CD80 interactions, but also plays important regulatory roles in intracellular functions and leads to acquired resistance to EGFR-TKIs in NSCLC. Here, we investigated that mechanistic role of PD-L1 in primary resistance to EGFR-TKIs in EGFR-mutant NSCLC. Methods: The mRNA expression level of PD-L1 was detected using real-time quantitative reverse transcriptase PCR. Molecular manipulations (overexpression or silencing) were performed to investigate the effect of PD-L1 expression on sensitivity to gefitinib in vitro, and a xenograft mouse model was used for in vivo confirmation. Migration and invasion assay were used to determine EMT phenotype. Results: The mRNA expression level of PD-L1 was consistent with IC50 value for gefitinib in H1975, HCC827 and PC-9 cell line. Overexpression of PD-L1 decreased the sensibility to gefitinib, in addition, knockdown of PD-L1 increased the sensibility to gefitinib in vitro. Furthermore, Overexpression of PD-L1 attenuated sensitivity to gefitinib in a xenograft mouse model. Overexpression of PD-L1 leaded to primary resistance to gefitinib through inducing EMT phenotype. Conclusions: PD-L1 contributes to primary resistance to EGFR-TKI in EGFR mutant non-small-cell lung cancer, which may be mediated by inducing EMT phenotype. Legal entity responsible for the study: The First Affiliated Hospital of Soochow University. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Decision Support and Alerts of Apps for Self-management of Blood Glucose for Type 2 Diabetes
Authors: Elaine Lum, Geronimo Jimenez, Zhilian Huang, Linh Thai, Monika Semwal, Bernhard O. Boehm, Josip Car
Journal: JAMA (2019)

This study characterizes the proportion of apps available in 2018 for self-management of type 2 diabetes that included goal-setting features, reminders to measure blood glucose, hypoglycemia and hyperglycemia alerts, and action prompts.
Accuracy of Patient Health Questionnaire-9 (PHQ-9) for screening to detect major depression: individual participant data meta-analysis
Authors: Brooke Levis, Andrea Benedetti, Brett D Thombs
Journal: BMJ (2019)

Abstract Objective To determine the accuracy of the Patient Health Questionnaire-9 (PHQ-9) for screening to detect major depression. Design Individual participant data meta-analysis. Data sources Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, and Web of Science (January 2000-February 2015). Inclusion criteria Eligible studies compared PHQ-9 scores with major depression diagnoses from validated diagnostic interviews. Primary study data and study level data extracted from primary reports were synthesized. For PHQ-9 cut-off scores 5-15, bivariate random effects meta-analysis was used to estimate pooled sensitivity and specificity, separately, among studies that used semistructured diagnostic interviews, which are designed for administration by clinicians; fully structured interviews, which are designed for lay administration; and the Mini International Neuropsychiatric (MINI) diagnostic interviews, a brief fully structured interview. Sensitivity and specificity were examined among participant subgroups and, separately, using meta-regression, considering all subgroup variables in a single model. Results Data were obtained for 58 of 72 eligible studies (total n=17 357; major depression cases n=2312). Combined sensitivity and specificity was maximized at a cut-off score of 10 or above among studies using a semistructured interview (29 studies, 6725 participants; sensitivity 0.88, 95% confidence interval 0.83 to 0.92; specificity 0.85, 0.82 to 0.88). Across cut-off scores 5-15, sensitivity with semistructured interviews was 5-22% higher than for fully structured interviews (MINI excluded; 14 studies, 7680 participants) and 2-15% higher than for the MINI (15 studies, 2952 participants). Specificity was similar across diagnostic interviews. The PHQ-9 seems to be similarly sensitive but may be less specific for younger patients than for older patients; a cut-off score of 10 or above can be used regardless of age.. Conclusions PHQ-9 sensitivity compared with semistructured diagnostic interviews was greater than in previous conventional meta-analyses that combined reference standards. A cut-off score of 10 or above maximized combined sensitivity and specificity overall and for subgroups. Registration PROSPERO CRD42014010673.
Endothelial cell derived micro-vesicular proteins to induce breast cancer cell migration.
Authors: Martin Buess, Daniela A. Ferraro, Ryan Goosen, Francesca Patella, Sara Zanivan, Gerhard Christofori
Journal: Journal of Clinical Oncology (2015)

e22014 Background: The microenvironment is a central regulator of tumor biology. While the contribution of fibroblasts has been largely studied, the role of endothelial cells as regulators of cancer cell behavior is still poorly understood. As in a diverse spectrum of physiological processes in normal tissues, endothelial cells may exert a similar regulatory control in malignant cancer progression and metastasis, not only contributing to vessel formation but also through endothelial cell specific signaling. Methods: To characterize the functional effects of endothelial-cancer interaction we focused on an in vitro model of SKBR3 breast cancer cells and human endothelial cells. Results: SKBR3 cells treated with HUVEC derived supernatant show significantly increased migratory potential, an elongated phenotype and expression of mesenchymal markers (up-regulation of FN1, Stress Fibers and Focal Adhesion formation) without any parallel increase in proliferation. The pro-migratory effect is significantly more pronounced when the supernatant is obtained from a sparse and highly proliferative endothelial cell culture than from confluent and resting endothelial cells. To better understand the differential regulation on cancer cell migration, we analyzed the supernatant of sparse or dense endothelial cells by quantitative MS proteomics (SILAC analysis). Interestingly, extracellular matrix proteins were enriched in supernatant from dense endothelium. Amongst them, Biglycan reduced the pro-migratory effect of treatment with supernatant from sparse endothelium, suggesting a potential role of resting endothelium as an inhibitor of cancer cell migration. The proteomic analysis of sparse endothelial cell supernatant revealed an enrichment in proteins belonging to the micro-vesicular compartment. Knocking down these proteins significantly reduced the pro-migratory effect of the endothelial supernatant on cancer cells, demonstrating that the microvesicular compartment can play a role in the modulation of tumor aggressiveness. Conclusions: We suggest that identification of the endothelial cell's role in cancer progression independent from vessel formation could reveal targets for novel therapeutic strategies.