tbuckley/cabot-search huggingface dataset:
Assessment of Psychopathology
Authors: Barbara Pavlova, Rudolf Uher
Journal: JAMA Psychiatry (2020)

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URINARY MARKER OF RNA OXIDATIVE DAMAGE AS A POTENTIAL BIOMARKER OF FRAILTY FOR ELDERLY PATIENTS WITH CARDIOVASCULAR DISEASE
Authors: Yaodan Liang, Qian Liu, Minghui Du, Simin Yao, Peipei Zheng, Yuhao Wan, Ning Sun, Jiefu Yang, Jianping Cai, Hua Wang
Journal: Journal of the American College of Cardiology (2020)
The αC helix of TIRAP holds therapeutic potential in TLR-mediated autoimmune diseases
Authors: Masaud Shah, Gi-Young Kim, Asma Achek, Eun-Young Cho, Wook-Young Baek, Yang Seon Choi, Wang Hee Lee, Dong-Jin Kim, Sang Ho Lee, Wook Kim, Soon Sun Kim, Jae Youn Cheong, Chang-Hee Suh, Sangdun Choi
Journal: Biomaterials (2020)

Despite being crucial for combating microbes, paradoxical Toll-like receptors (TLRs) signaling have been associated with the aggravation of multiple immune disorders such as systemic lupus erythematosus, psoriasis, rheumatoid arthritis, and nonalcoholic steatohepatitis. The stoichiometry and precise arrangement of the interaction of adapters (via their Toll/interleukin-1 receptor [TIR] domains) are indispensable for the activation of TLRs and of downstream signaling cascades. Among adapters, plasma membrane–anchored MyD88 adaptor–like (MAL) has the potential for BB-loop–mediated self-oligomerization and interacts with other TIR domain–containing adaptors through αC and αD helices. Here, we used information on the MAL–αC interface to exploit its pharmacophores and to design a decoy peptide (MIP2) with broad-range TLR-inhibitory abilities. MIP2 abrogated MyD88- and TRIF-dependent lipopolysaccharide (LPS)-induced TLR4 signaling in murine and human cell lines and manifested a therapeutic potential in models of psoriasis, systemic lupus erythematosus, nonalcoholic steatohepatitis, and sepsis. Levels of hallmark serological and histological biomarkers were significantly restored and the disease symptoms were substantially ameliorated by MIP2 treatment of the animals. Collectively, our biophysical, in vitro, and in vivo findings suggest that MIP2 has broad specificity for TLRs and may be effective in modulating autoimmune complications caused by microbial or environmental factors.
A phase III trial of virulizin plus gemcitabine vs. gemcitabine alone in advanced pancreatic cancer: Results of subgroup analysis
Authors: J. A. Wright, J. Osterlee, S. Fekete, Y. Lee, A. H. Young
Journal: Journal of Clinical Oncology (2006)

4116 Background: Virulizin (V) is a novel antitumor immune modulator that improves survival in pancreatic cancer patients (pts) as monotherapy. A double-blind, multicenter, randomized, phase III study was conducted to evaluate the survival benefits and safety of V in combination with gemcitabine (G) in pts with advanced pancreatic cancer. Methods: Chemo-naive pts with locally advanced or metastatic pancreatic cancer with ECOG Performance Status (PS) of 0, 1 or 2 were enrolled. Pts were randomized to receive intramuscular injections of either V or placebo (P) 3 times weekly + G (1,000 mg/m 2 weekly ×7 with 1 week rest, then weekly ×3 q4w). Randomization was stratified according to ECOG PS (0 or 1, and 2) and extent of disease (locally advanced and metastatic). Pts who showed no clinical benefit or were intolerant to G entered 2nd-line therapy (stage 3), in which pts continued to receive either V or P alone or with 5-FU, or best supportive care. The primary endpoint was survival, defined as time from baseline/treatment day 1 to time of death from any cause. Results: The intent to treat (ITT) population comprised 434 pts, of which 377 were efficacy evaluable (EE). Median overall survival for V + G was 6.3 months for the ITT population (6.8 months for EE pts) and 6 months for P + G for both ITT and EE pts. While differences in survival times were not statistically significant, exploratory analysis showed encouraging results in specific subgroups treated with V + G ( table ). Importantly, a significant difference was found in stage 3 pts who received V in a salvage setting compared to pts who received P. Conclusions: Pancreatic cancer pts with either low ECOG PS or metastatic cancer showed a survival benefit when treated with V + G, which was significant in pts who continued to receive V as a salvage therapy. Further studies in these targeted patient populations are being considered. [Table: see text] No significant financial relationships to disclose.
POST-OPERATIVE ATRIAL FIBRILLATION AND FLUTTER AFTER LUNG TRANSPLANTATION IS ASSOCIATED WITH INCREASED HOSPITAL LENGTH OF STAY, ICU LENGTH OF STAY, AND RISK OF RE-INTUBATION
Authors: Dan Nguyen, Andrew Harris, Erika D. Lease, Robert Rho, Bhrigu Parmar, Michael Mulligan, Kent Koprowicz, Kelley Branch
Journal: Journal of the American College of Cardiology (2020)
Induction gefitinib followed by concurrent chemoradiotherapy in patients with unresectable stage IIIA/b lung adenocarcinoma harboring mutations of epidermal growth factor receptor: Three case reports.
Authors: Yoshitsugu Horio, Chiaki Kondo, Jangchul Park, Junichi Shimizu, Kimihide Yoshida, Toyoaki Hida
Journal: Journal of Clinical Oncology (2012)

e17510 Background: Gefitinib has shown good activity in lung cancer harboring mutations in the epidermal growth factor receptor (EGFR) gene. However, how to integrate gefitinib into concurrent chemoradiotherapy for unresectable locally advanced non-small cell lung cancer (NSCLC) with EGFR mutations is uncertain. Methods: We present three cases of locally advanced lung adenocarcinoma with EGFR mutation, which were treated with gefitinib followed by weekly paclitaxel and carboplatin concurrent with radiation. Three female patients (median age, 73 years; range, 61–77 years) received induction gefitinib 150 mg daily for 1-2 months followed by weekly paclitaxel 40 mg/m2 weekly over 1 hour; carboplatin at AUC (area under the curve) of 2 weekly over 1 hour; and radiation therapy of 60 Gy in 30 fractions. Results: Gefitinib induced very rapid response within the first month without pulmonary toxicity. Subsequent concurrent chemoradiotherapy was performed with safety. One patient recurred as hematogenous lung metastases at 5 months after treatment. The remaining two patients are well doing without adverse events. Conclusions: The very quick response to induction gefitinib and sequential chemoradiotherapy may be an effective treatment with good tolerance. We believe that this treatment strategy deserves further evaluation in unresectable locally advanced NSCLC with EGFR mutations.
MYOCARDITIS COMPLICATING INFLAMMATORY BOWEL DISEASE: A COMPARISON BETWEEN ULCERATIVE COLITIS AND CROHN'S DISEASE FROM THE NATIONAL INPATIENT SAMPLE
Authors: Shivaraj Patil, Karthik Gonuguntla, Manish Kumar, Chaitanya Rojulpote, Amreet Aujla, Abhishek Achunair, Kai Chen
Journal: Journal of the American College of Cardiology (2020)
CASE SERIES: A SINGLE-CENTER EXPERIENCE IN THREE-DIMENSIONAL PRINTING FOR PRE-OPERATIVE PLANNING: APPLICATIONS IN THE REPAIR OF CONGENITAL HEART DISEASE, AIRWAY STENOSIS, VASCULAR ANOMALIES, AND THE RESECTION OF SOLID ORGAN TUMOR
Authors: Natasha Gonzalez, Brian M. Wall, Jennifer Maldonado, Ravi Ashwath
Journal: Journal of the American College of Cardiology (2020)
Comparison of the effects of subcutaneous APF530, intravenous granisetron, moxifloxacin, and placebo on the QT interval in humans.
Authors: Jay Mason, Thomas E Moon, Erin O'Boyle, Albert J Dietz
Journal: Journal of Clinical Oncology (2013)

e20539 Background: This study evaluated effects of subcutaneous (SC) APF530 (sustained-release granisetron) and intravenous (IV) granisetron on placebo-adjusted change from baseline in QT corrected with the Fridericia method (QTcF) over 48 h (ddQTcF), using moxifloxacin as an active control. The FDA recently required a label warning regarding risk of QT prolongation by granisetron and other 5-HT 3 antagonists for chemotherapy-induced nausea and vomiting on the basis of anecdotal reporting. Methods: Normal healthy subjects received 1 of 4 treatments in a 4-period crossover: APF530 1 g SC (20 mg granisetron; 2 x therapeutic dose), IV granisetron 50 µg/kg (5 x therapeutic dose), oral (PO) moxifloxacin 400 mg, or placebo. Drugs were given at the start of each 10-day period. 12-lead ECGs and blood samples for pharmacokinetic evaluations were taken at prespecified times. Results: 51 subjects completed the study. APF530 had no clinically significant effect on QTcF. Maximum adjusted mean change (ddQTcF) was 3.75 ms for APF530 1 g at 3 h (Table). While CI excluded 0 at 3 and 12 h, upper boundaries of 6.89 and 6.70 ms were well below the level of FDA concern (10 ms). Mean APF530 C max was 35.8 ng/mL, twice that observed in patients receiving the standard dose. IV granisetron also had minimal effect on ddQTcF, while moxifloxacin produced the expected large change. Pharmacokinetic and pharmacodynamic modeling revealed a very small granistetron-ddQTcF gradient; the linear model predicted a ddQTcF value of 1.37 ms at the highest concentration observed in patients (97.8 ng/mL). Conclusions: No clinically significant QT prolongation occurred with SC APF530 up to 1 g, despite achievement of mean C max greater than that in previous studies. APF530 was well tolerated. Clinical trial information: NCT01416259. [Table: see text]
RISK OF EARLY HOSPITAL DISCHARGE AFTER ACUTE CORONARY SYNDROMES: INSIGHTS FROM SECURE-PCI TRIAL AND ACCEPT REGISTRY
Authors: Pedro Gabriel Melo De Barros E Silva, Otavio Berwanger, Renato Nakagawa, Thiago Macedo, Oscar Dutra, Dalton Precoma, John H. Alexander, Christopher B. Granger, Renato Lopes
Journal: Journal of the American College of Cardiology (2020)
Sunitinb in advanced renal cell carcinoma (RCC): Is effectiveness good enough in real life practice?
Authors: Marta Paulina Trojniak, Silvia Imbevaro, Angelo Claudio Palozzo, Antonio Jirillo
Journal: Journal of Clinical Oncology (2012)

e15072 Background: The sunitnib approval trials have established this multi-targeted TKI as a standard treatment in patients with metastatic RCC. However, even RCTs may fail to show relevant clinical benefit in wider population, as certain patient subtypes are under-represented, notably those with poorer prognostic factors and pretreated. The purpose of the study was to evaluate effectiveness of sunitinb in unselected RCC patients in real life practice in Italy. Methods: The data were collected through national registry on oncology drugs as part of mandatory surveillance program, which allows prospective investigations of effectiveness. RCC patients receiving sunitinb once daily, on schedule 4/2, between 2007 and 2011, had been included. All patients were checked prospectively for toxicity, clinical outcomes and length of treatment using registry inputs. Retrospective analysis of previous and following treatments and mortality data was performed based on clinical records and hospital databases. Results: A total of 106 patients (median age 64 years, M 70/F 36) were reviewed, 77% had prior nephrectomy and 74% were treatment-naïve. At first evaluation we found 28% partial responses, 25% stable diseases, 46% progressions and one discontinuation due to toxicity. The median TTP and OS were 7 and 11.3 months, respectively. Among 102 RCC patients (pts) with metastases (mets) at first diagnosis, 65% had lung mets, 19% pts had liver mets, 25% had bone mets and 8% had brain mets. The Cox regression model showed in subgroups analysis significantly worse survival prognosis in males, brain and liver mets, ECOG PS&gt;1, non-clear cell histology and non prior nephrectomy. Sorafenib treatment after progression on sunitinib (33% pts) did not improved OS. Grade 3 thrombocytopenia, neutropenia, mucositis and HFS caused dosage reductions. Conclusions: The results on examined RCC study population show that sunitinib clinical benefit was gained in selected responders, but in overall the effectiveness was nearly half of that reported in the approval RCTs. Post-marketing studies in real life practice are required in order to verify both effectiveness and safety in general population, testing for external validity of randomized trials.
Abstract 18671: The Response of Saturated Non-Esterified Fatty Acids to a Glucose Challenge is Distinct From Unsaturated, and Altered in Insulin Resistance
Authors: Rachel E Walker, Jennifer L Ford, Michael H Green, Gregory C Shearer
Journal: Circulation (2016)

Introduction: Insulin suppresses intracellular lipolysis in adipocytes, and poor suppression of non-esterified fatty acid (NEFA) release is directly related to adipocyte insulin resistance (IR). It...
THE IMPACT OF BASELINE MITRAL REGURGITATION ON THE DEGREE OF LEFT ATRIAL REMODELING AFTER TRANSCATHETER AORTIC VALVE IMPLANTATION
Authors: Abdalla Hassan, Ashraf Abugroun, Shafaq Mahmoud, Amartya Kundu, Nikolaos Kakouros, Gerard P. Aurigemma
Journal: Journal of the American College of Cardiology (2020)
NATIONAL GENDER-BASED IN-HOSPITAL MORTALITY AND OUTCOME IN PATIENTS WITH LEFT VENTRICULAR ASSIST DEVICE: 2008-2014 NATIONAL INPATIENT SAMPLE TREND ANALYSIS
Authors: Neelkumar Patel, Dhrubajyoti Bandyopadhyay, Sandipan Chakraborty, Birendra Amgai, Aneeta Kumari, Zeel Patel, Soniya Koirala, Wilbert Aronow, Mazin Khalid, Ahmed Bakhit
Journal: Journal of the American College of Cardiology (2020)
BRD4 Levels Determine the Response of Human Lung Cancer Cells to BET Degraders That Potently Induce Apoptosis through Suppression of Mcl-1
Authors: Dan Zong, Jiajia Gu, Giovanna C. Cavalcante, Weilong Yao, Guojing Zhang, Shaomeng Wang, Taofeek K. Owonikoko, Xia He, Shi-Yong Sun
Journal: Cancer Research (2020)

Abstract Lung cancer consists of approximately 80% non–small cell lung cancer (NSCLC) and 20% small cell lung cancer (SCLC) and remains the leading cause of cancer-related deaths worldwide despite advances in early diagnosis, targeted therapy, and immunotherapy. Thus, novel therapies are still urgently needed. Bromodomain and extraterminal (BET) proteins, primarily comprised of BRD2, BRD3, and BRD4 proteins, function as epigenetic readers and master transcription coactivators and are now recognized cancer therapeutic targets. BET degraders such as ZBC260 and dBET represent a novel class of BET inhibitors that act by inducing BET degradation. The current study demonstrates the therapeutic efficacies of BET degraders, particularly ZBC260, against lung cancer, as well as understanding the underlying mechanisms and identifying molecular markers that determine cell sensitivity to BET degraders. A panel of NSCLC cell lines possessed similar response patterns to ZBC260 and dBET but different responses to BET inhibitor JQ-1. BRD levels, particularly BRD4, correlated positively with high sensitivity to BET degraders but not to JQ-1. BET degraders potently induced apoptosis in sensitive NSCLC cells and were accompanied by reduction of Mcl-1 and c-FLIP levels, which are critical for mediating induction of apoptosis and enhancement of TRAIL-induced apoptosis. Accordingly, ZBC260 exerted more potent activity than JQ-1 in vivo against the growth of NSCLC xenografts and patient-derived xenografts. These findings warrant future clinical validation of the efficacy of BET degraders in NSCLC, particularly those with high levels of BRD proteins, especially BRD4. Significance: The current study demonstrates the potential of novel BET degraders in the treatment of lung cancer and warrants clinical validation of BET degraders in lung cancer with high levels of BRD4.
Phase II study of carboplatin, paclitaxel and bevacizumab as first line chemotherapy and consolidation for advanced müllerian tumors
Authors: R. T. Penson, S. A. Cannistra, M. V. Seiden, C. N. Krasner, U. A. Matulonis, N. S. Horowitz, S. Berlin, D. S. Dizon, H. Lee, S. M. Campos
Journal: Journal of Clinical Oncology (2006)

5020 Background: Vascular endothelial growth factor (VEGF) is a major promoter of tumor angiogenesis. Bevacizumab is a recombinant humanized monoclonal antibody that neutralizes VEGF and is active in several tumor types, including epithelial ovarian cancer. Methods: We are conducting a phase II trial of carboplatin, paclitaxel and bevacizumab (CPB) in newly diagnosed patients with chemotherapy naïve, stage ≥ IC, epithelial ovarian, fallopian, primary peritoneal, or uterine papillary serous (UPSC) tumors. Patients receive carboplatin AUC of 5 IV, paclitaxel 175 mg/m 2 IV, and bevacizumab 15 mg/kg IV for 6–8 cycles on a 21-day cycle. Bevacizumab is omitted in the first cycle, and continued for one year’s consolidation. Principle endpoints include response rate and progression free survival. Results: Since 3/05, 35 patients have been enrolled. Of the 30 evaluable patients, 24 have ovarian, 4 peritoneal, 1 fallopian tube cancer, and 1 UPSC (1 stage IIB, 22 stage III, and 7 stage IV), and median age is 57 (range 18–77). 133 cycles of chemotherapy have been administered with acceptable toxicity. Grade IV neutropenia has been seen in 3 cycles with 1 episode of febrile neutropenia. Grade I, II, and III HTN was observed in 1, 3, and 4 cycles, and grade I (42% hematuria 45% epistaxis) and II bleeding observed in 36 and 1 cycle(s), respectively. There has been 1 nasal perforation, 2 delayed wound healing, and no bowel perforation. 1 woman withdrew consent (for PMH diverticulitis), and 3 women have been removed for toxicity (1 autonomic neurotoxicity, 1 HTN, and 1 PE). To date, 13 patients have completed the chemotherapy phase of treatment, and only one patient has come off study for progression on consolidation bevacizumab. Conclusion: First line CBP is a highly active regimen that has been well tolerated thus far. Updated toxicity and response data will be available in the spring of 2006. [Table: see text]
Venetoclax in combination with cytarabine with or without idarubicin in children with relapsed or refractory acute myeloid leukaemia: a phase 1, dose-escalation study
Authors: Seth E Karol, Thomas B Alexander, Amit Budhraja, Stanley B Pounds, Kristin Canavera, Lei Wang, Joshua Wolf, Jeffery M Klco, Paul E Mead, Soumyasri Das Gupta, Su Y Kim, Ahmed Hamed Salem, Tammy Palenski, Norman J Lacayo, Ching-Hon Pui, Joseph T Opferman, Jeffrey E Rubnitz
Journal: The Lancet Oncology (2020)
In uncontrolled asthma, adding a LAMA to ICS plus LABA improved lung function at 6 mo and reduced exacerbations at 1 y
Authors: Matthew B. Stanbrook
Journal: Annals of Internal Medicine (2020)

Source Citation Virchow JC, Kuna P, Paggiaro P, et al. Single inhaler extrafine triple therapy in uncontrolled asthma (TRIMARAN and TRIGGER): two double-blind, parallel-group, randomised, controlled phase 3 trials. Lancet. 2019;394:1737-49. 31582314
Association of Functional, Cognitive, and Psychological Measures With 1-Year Mortality in Patients Undergoing Major Surgery
Authors: Victoria L. Tang, Bocheng Jing, John Boscardin, Sarah Ngo, Molly Silvestrini, Emily Finlayson, Kenneth E. Covinsky
Journal: JAMA Surgery (2020)

More older adults are undergoing major surgery despite the greater risk of postoperative mortality. Although measures, such as functional, cognitive, and psychological status, are known to be crucial components of health in older persons, they are not often used in assessing the risk of adverse postoperative outcomes in older adults.
Achieving quality: Comparing recommendations for cancer care between NCCN and ESMO.
Authors: Jennifer Gao, Geoffrey Calkins, Michael J. Birrer, Don S. Dizon
Journal: Journal of Clinical Oncology (2013)

6579 Background: Guidelines for the treatment of cancer are in place in both the United States and Europe. However, specific recommendations that can be utilized as measures of quality care have not been evaluated in either guideline set, nor have they have been compared against one another. Our aim was to delineate the number of concrete treatment recommendations made using the PICO model for evidence-based medicine. Methods: Three authors (JG, GC, DD) independently reviewed treatment guidelines of the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO) for three common cancers: 1) breast cancer; 2) colon cancer; 3) non-Hodgkin lymphoma (specifically diffuse large B-cell lymphoma and follicular lymphoma). The primary objective was to differentiate the concordant versus discordant recommendations. Recommendations were identified by first identifying all category 1 and 2 guidelines in ESMO, then finding the equivalent NCCN recommendations, and finally assessing their fulfillment of the PICO model (Patient/Problem – Intervention – Comparison – Outcome). Each recommendation was separately analyzed by the three aforementioned authors of this abstract. The results reflect the unanimous agreement of all three reporters. Results: Using PICO criteria, we identified a total of 46 recommendations (10 colon cancer, 22 breast cancer, and 14 in NHL). Concordance between NCCN and ESMO was 80, 86, and 100 percent, respectively. Discordance between NCCN and ESMO were noted in first line chemotherapy regimens in localized colon cancer and fluoropyridine as maintenance therapy in unresectable colon cancer; patients who should receive partial breast irradiation and chemotherapy regimens in the elderly with breast cancer. Conclusions: The number of actual recommendations that meet the PICO evidence-based medicine criteria is relatively small. However, comparing NCCN and ESMO, there is a high rate of agreement between guidelines reviewed regarding treatment recommendations. Our data suggest that it may be possible to identify specific measures of quality treatment as defined by evidence based medicine criteria.
JOINT SUBCLAVIAN ARTERY AND RIGHT INTERNAL JUGULAR VEIN INFLOW CANNULATION FOR VENO-ARTERIAL/VENOUS EXTRACORPOREAL MEMBRANE OXYGENATION
Authors: Ali Ebrahimi, Peter Marogil, Tamer Amer, Zaw Win Tun, Mena Yacoub, Ali Abdul Jabbar, Greg Von Merring, Mustafa Ahmed
Journal: Journal of the American College of Cardiology (2020)
23P Novel ERα degrader, 3,20(R)-dihydroxy-19-norpregnatriene, inhibits MCF-7 cell growth through p21/CDK2/CDK4 pathway
Authors: A.M. Scherbakov, I.S. Levina, Y. Kuznetsov, M. Tserfas, I. Zavarzin
Journal: Annals of Oncology (2020)