tbuckley/cabot-search huggingface dataset:
Evaluating the clinical impact of primary tumor location in pancreatic adenocarcinoma.
Authors: Randi Zukas Carhart, Ida Micaily, Roberto Stefan Fratamico, Constantine Daskalakis, Sophia Lam, Steven J. Cohen, Atrayee Basu Mallick
Journal: Journal of Clinical Oncology (2021)

428 Background: Pancreatic adenocarcinoma is the fourth most common cause of cancer-related death in the US. The location of the primary lesion has long been thought to influence survival due to differences in time to presentation and ability to undergo cancer directed surgery. We hypothesized that patients with tumors arising in the body or tail (distal) would have poorer survival than patients who presented with lesions in the head of the pancreas (proximal) and that this difference would be true regardless of stage at diagnosis due in part to other factors such as intrinsic differences in the biology of these tumor types. A retrospective chart review at a single center with a high volume of pancreatic cancer directed surgery was carried out to address this question. Methods: Institution database was queried to identify patients with the ICD9 diagnosis of pancreatic adenocarcinoma of the head, body, and tail between 2014-2017; the inclusion criteria were 18 years or older, biopsy proven adenocarcinoma and a single mass in the pancreas at presentation. A total of 907 entries were screened with 324 patients being analyzed (236 proximal and 88 distal). CDC National Death Index registry and obituary reports were utilized to determine official dates of death. Results: Overall median survival was statistically higher in the proximal group than the distal group 16.0 vs 11.2 months (p=0.015). However, there was no significant difference in survival by stage of the proximal group over the distal group with stage I/II in the proximal group surviving 21 months versus distal 25.7 months, p=0.436; stage III, proximal surviving 11.7 months versus distal 18.0 months, p=0.393; stage IV, proximal surviving 6.5 months versus distal 4.9 months, p=0.675. The distal group was more likely to be metastatic on diagnosis (59% versus 18%) and was less likely to undergo surgery (34% vs 50%). In the surgical group, there was similar survival of 24.6 months in the proximal group versus 19.4 distal (p=0.795). Conclusions: Patients in the proximal group had a higher overall survival than the distal group as expected. Overall, however, when broken down by stage or surgery, the difference in survival between the proximal and distal groups was minimal with Hazard Ratio 0.96 (95%, CI=0.7, 1.30). Therefore, early stage diagnosis or surgery strongly account for the survival benefit in the proximal population rather than other factors like an intrinsic difference in the nature of the tumors themselves.
Endosomal Escape: Amphiphilic Polyelectrolyte Graft Copolymers Enhance the Activity of Cyclic Dinucleotide STING Agonists (Adv. Healthcare Mater. 2/2021)
Authors: Dinh Chuong Nguyen, Daniel Shae, Hayden M. Pagendarm, Kyle W. Becker, Mohamed Wehbe, Kameron V. Kilchrist, Lucinda E. Pastora, Christian R. Palmer, Pedro Seber, Plamen P. Christov, Craig L. Duvall, John T. Wilson
Journal: Advanced Healthcare Materials (2021)

Endosomal escape is a rate limiting step for many promising therapeutics, including cyclic dinucleotide (CDN) agonists of the stimulator of interferon genes (STING) pathway. In article number 2001056, John T. Wilson and co-workers synthesize and screen a novel library of polymers with pH-responsive, membrane-destabilizing activity and evaluate their capacity to enhance cytosolic delivery of CDNs, resulting in identification of new drug carrier technologies for potent STING activation.
OP0079 Pain, psychological status, sleep disturbance, and serum concentration of 5-hydroxytryptamine in patients with primary fibromyalgia and chronic low back pain – a comparative study
Authors: PZ Hrycaj, B Hauns, K Ovenhausen, P Mennet, W Müller
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Several reports suggest that, in most cases, fibromyalgia syndrome (FS) begins as a localised pain syndrome which may precede for months or years the development of the full-blown disease. Thus, some patients who currently present with chronic low back pain (LBP) may in future develop FS. <h3>Objectives</h3> To study FS signs and symptoms and serum serotonin (5-hydroxytryptamine, 5-HT) in patients with chronic low back pain syndrome (LBP) in order to identify possible predictors of FS development. <h3>Methods</h3> Comparative and correlation analysis of clinical data (pain intensity, tender point count, average pain threshold, functional symptoms, levels of depression and anxiety, feeling of well-being, measures of sleep disturbance) and serum 5-HT in patients with FS (n = 34) and LBP (n = 46). <h3>Results</h3> FS patients had higher intensity of pain, higher tender point count, lower average pain threshold, more functional symptoms, higher scores on depression and anxiety scales, decreased feeling of well-being, and more sleep troubles than those with LBP (p &lt; 0.0001 for all comparisons). In both groups, there was a strong interrelationship between functional symptoms, depression, anxiety, feeling of well-being, and the sleep disturbance. Serum 5-HT was lower in FS group when compared to healthy sex- and age-matched controls (n = 26, p &lt; 0.03). Although low serum 5-HT was found in some patients with LBP, the median serum level of the monoamine did not differ significantly from that found in FS and controls. There was no relationship between serum 5-HT and the clinical characteristics in the LBP group. Women with LBP had higher count of tender points (p &lt; 0.0001), lower pain threshold (p &lt; 0.0001), higher median level of depression (p &lt; 0.005), and more disturbed sleep (p &lt; 0.05) than men. <h3>Conclusion</h3> As expected, striking differences in clinical characteristics were found between FS and LBP with greater disturbance seen with the FS group. Our study confirms earlier reports suggesting lowered serum 5-HT in FS and provide no support to the hypothesis that there may be a general 5-HT deficiency in LBP. Higher tender point count, decreased pain threshold, depression, and sleep disturbance are possible predictors of FS development in LBP and should be investigated in further prospective research.
Targeting of claudin-4 by Clostridium perfringens enterotoxin-conjugated polysialic acid nanoparticles for pancreatic cancer therapy
Authors: Man Kyu Shim, Jinhee Na, In Kyung Cho, Eun Hyang Jang, Jooho Park, Sangmin Lee, Jong-Ho Kim
Journal: Journal of Controlled Release (2021)
Persistence of Left Atrial Appendage Thrombus in Patients With Cardiac Amyloidosis
Authors: Edward A. El-Am, Martha Grogan, Ali Ahmad, Sri Harsha Patlolla, Kyle W. Klarich, Omar F. AbouEzzeddine, Rowlens M. Melduni, Joseph J. Maleszewski, Angela Dispenzieri, Vuyisile T. Nkomo
Journal: Journal of the American College of Cardiology (2021)
A systemically deliverable Vaccinia virus with increased capacity for intertumoral and intratumoral spread effectively treats pancreatic cancer
Authors: Giulia Marelli, Louisa S Chard Dunmall, Ming Yuan, Carmela Di Gioia, Jinxin Miao, Zhenguo Cheng, Zhongxian Zhang, Peng Liu, Jahangir Ahmed, Rathi Gangeswaran, Nicholas Lemoine, Yaohe Wang
Journal: Journal for ImmunoTherapy of Cancer (2021)

Pancreatic cancer remains one of the most lethal cancers and is refractory to immunotherapeutic interventions. Oncolytic viruses are a promising new treatment option, but current platforms demonstrate limited efficacy, especially for inaccessible and metastatic cancers that require systemically deliverable therapies. We recently described an oncolytic vaccinia virus (VV), VVLΔTKΔN1L, which has potent antitumor activity, and a regime to enhance intravenous delivery of VV by pharmacological inhibition of pharmacological inhibition of PI3 Kinase δ (PI3Kδ) to prevent virus uptake by macrophages. While these platforms improve the clinical prospects of VV, antitumor efficacy must be improved.VVLΔTKΔN1L was modified to improve viral spread within and between tumors via viral B5R protein modification, which enhanced production of the extracellular enveloped virus form of VV. Antitumor immunity evoked by viral treatment was improved by arming the virus with interleukin-21, creating VVL-21. Efficacy, functional activity and synergy with α-programmed cell death protein 1 (α-PD1) were assessed after systemic delivery to murine and Syrian hamster models of pancreatic cancer.VVL-21 could reach tumors after systemic delivery and demonstrated antitumor efficacy in subcutaneous, orthotopic and disseminated models of pancreatic cancer. The incorporation of modified B5R improved intratumoural accumulation of VV. VVL-21 treatment increased the numbers of effector CD8+ T cells within the tumor, increased circulating natural killer cells and was able to polarize macrophages to an M1 phenotype in vivo and in vitro. Importantly, treatment with VVL-21 sensitized tumors to the immune checkpoint inhibitor α-PD1.Intravenously administered VVL-21 successfully remodeled the suppressive tumor-microenvironment to promote antitumor immune responses and improve long-term survival in animal models of pancreatic cancer. Importantly, treatment with VVL-21 sensitized tumors to the immune checkpoint inhibitor α-PD1. Combination of PI3Kδ inhibition, VVL-21 and α-PD1 creates an effective platform for treatment of pancreatic cancer.
Abstract 11735: Subclinical Myocardial Injury and Cardiovascular Mortality: Racial Differences in Prevalence and Risk (From the Third National Health and Nutrition Examination Survey)
Authors: Stephen T Broughton, Jared W Magnani, Elsayed Z Soliman, Muhammad Ahmad
Journal: Circulation (2019)

Introduction: Subclinical myocardial injury (SCMI) determined from the electrocardiographic Cardiac Infarction/Injury Score (CIIS) is associated with increased risk of cardiovascular disease and mo...
A phase II, open-label pilot study evaluating the safety and activity of liposomal irinotecan (Nal-IRI) in combination with 5-FU and oxaliplatin (NALIRIFOX) in preoperative treatment of pancreatic adenocarcinoma (NEO-Nal-IRI Study).
Authors: Brian Hemendra Ramnaraign, Steven J. Hughes, Kathryn Hitchcock, Ji-Hyun Lee, Sherise C. Rogers, Z. Hugh Fan, Carmen Joseph Allegra, Jose Gilberto Trevino, Ahmad El-Far, Karen Bullock Russell, Anita Ahmed Turk, David L. DeRemer, Thomas J. George
Journal: Journal of Clinical Oncology (2021)

TPS446 Background: Neoadjuvant treatment for potentially curable pancreatic cancer (PDAC) is increasing in acceptability, but a standard regimen has yet to be established. Multiple studies have demonstrated feasibility and effectiveness of the FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen in the perioperative setting. However, FOLFIRINOX often requires dose modifications, delays and growth factor support due to excessive toxicity which can complicate care delivery when given neoadjuvantly. Liposomal irinotecan injection (Nal-IRI) is FDA approved with a well-tolerated safety profile in relapsed, refractory metastatic PDAC. The current study aims to substitute Nal-IRI for traditional irinotecan in the standard FOLFIRINOX regimen (NALIRIFOX) and to demonstrate safe and effective neoadjuvant delivery. Methods: This phase II, open-label, multicenter single-arm study focuses on patients (pts) with operable PDAC without metastatic disease. Other key eligibility criteria include age ≥18 years, resectability confirmed by multiD GI tumor board (resectable vs. borderline), adequate cardiac, renal, hepatic function and ECOG performance status of 0 to 1. Pts receive NALIRIFOX regimen as per the table below every 2 weeks for four months followed by disease reassessment. Pts who remain surgical candidates will undergo surgical resection within 4 to 8 weeks following last dose of therapy. The primary endpoint is to assess safety and feasibility of regimen in perioperative setting. Secondary endpoints include R0 resection rate, clinical, biochemical and radiological response rate and patient-reported quality of life during treatment as measured by the NCI validated FACT-G scale. Enrollment continues to a maximum of 28 evaluable pts to demonstrate a reduction in historical 30 day postoperative complication rate. Clinical trial information: NCT03483038. [Table: see text]
SAT0095 Comparative blood pressure effects of rofecoxib, celecoxib, and placebo in patients with osteoarthritis (oa): a randomised controlled trial
Authors: GP Geba, AB Polis, ME Dixon, TW Dobbins, JE Rush, MR Weir
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Dual inhibitors of cyclo-oxygenase (COX)-1 and COX-2 can potentially induce elevation of systolic and diastolic blood pressure in some patients. This is thought to be due to COX-2 mediated effects on the nephron, influencing natriuresis. We examined the relative effect of selective COX-2 inhibitors, rofecoxib and celecoxib on blood pressure (BP) during a 6-week, placebo controlled OA efficacy trial. <h3>Objectives</h3> <h3>Methods</h3> 1082 patients with OA of the knee or hip, after withdrawal of previous therapy for OA, were randomised to treatment with rofecoxib 25 mg (QD (N = 471), celecoxib 200 mg (QD (N = 460) or placebo (N = 151). Paracetamol was allowed as rescue during the trial. Treatment groups were similar in terms of age, race, gender, baseline OA severity, history of hypertension, and baseline BP. The mean age was 62 years, the majority were female. Greater than 40% in each group had a history of hypertension. BP (systolic, SBP and diastolic, DBP) was assessed at office visits at baseline, 2, 4, and 6 weeks in the sitting position after patients rested 10 min. Relative OA efficacy was determined by% patients with good or excellent response to therapy (%PGART) and WOMAC questionnaire at scheduled office visits over 6 weeks. <h3>Results</h3> The percent of patients with pre-defined changes in SBP (increase &gt; 20 mm Hg and SBP &gt;140) and DBP (increase &gt; 15 mm Hg and DBP &gt;90) was 9.6% for rofecoxib and 9.4% for celecoxib; 2.8% for rofecoxib and 2.0% for celecoxib, respectively compared to placebo (3.3% systolic change and 2.0% diastolic change). Differences between coxibs and placebo were significant for SBP (p = 0.015); rofecoxib and celecoxib did not differ significantly from one another in terms of either SBP or DBP. There was one discontinuation due to hypertension (overall incidence 0.2% for rofecoxib, 0% for celecoxib, and 0% for placebo). Mean changes from baseline in SBP were 1.9 mm Hg for rofecoxib. 0.2 mm Hg for celecoxib, and -4.3 mm Hg for placebo, and in DBP were 0.3 mm, -0.4 mm, and -2.6 mm Hg respectively. Relief of night pain and% PGART over six weeks were significantly greater for rofecoxib compared to celecoxib [night pain change from baseline: -36.2 mm for rofecoxib vs -32.7 mm for celecoxib (p = 0.023); PGART: 58.0% for rofecoxib vs 49.9% for celecoxib (p = 0.014)]. In addition, although not a prespecified endpoint, rofecoxib resulted in significantly greater improvement than celecoxib in scores for each of the WOMAC composite domains (pain, stiffness, and physical function: p &lt; 0.01). <h3>Conclusion</h3> Like dual COX-inhibiting NSAIDs, selective COX-2 inhibitors can induce elevations of systolic and diastolic blood pressure. Rofecoxib produced nearly identical small changes in SBP and DBP compared to celecoxib despite providing superior efficacy as determined by PGART and WOMAC.
Abstract 2484: Fragmented QRS on a 12-lead ECG is a Sign of Acute or Recent Myocardial Infarction
Authors: Mark A Michael, Mithilesh K Das
Journal: Circulation (2006)

Background: ST elevation and Q wave are highly specific signs of myocardial infarction (MI), but there is no specific ECG signs of non-Q wave MI. Fragmented QRS (fQRS) on a 12-lead ECG represents m...
Druggability modification strategies of the diarylpyrimidine‐type non‐nucleoside reverse transcriptase inhibitors
Authors: Li Ding, Chunlin Zhuang, Fener Chen
Journal: Medicinal Research Reviews (2021)

Abstract Drug discovery of human immunodeficiency virus (HIV) is a hot field in medicinal chemistry community for many years. The diarylpyrimidines (DAPYs) are the second‐generation non‐nucleoside reverse transcriptase inhibitors (NNRTIs) targeting reverse transcriptase, playing a great irreplaceable role in HIV transcriptional therapy. However, fast‐growing drug‐resistant mutations as nonnegligible challenge are still unpredictably appeared in the clinical practice, leading to deactivate or reduce the existing drugs. In the last 20 years, more and more novel DAPY derivatives have developed with the purpose to counter the mutants. Nevertheless, most of them have dissatisfactory pharmacokinetics (PK) or poor antiviral activity toward resistant mutant strains. In this article, we will analyze the NNRTI derivatives with promising druggability, and summarize a series of druggability modification strategies to improve the antiviral activity, reduce toxicity and improve the PK properties in recent years. The prospects of DAPYs and the directions for future efforts will be discussed.
Peptides in Postural Orthostatic Tachycardia Syndrome: Players or Epiphenomena?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: David G. Benditt, Lin Y. Chen
Journal: Journal of the American College of Cardiology (2012)
Abstract 12130: Age Stratified Analysis in Acute Myocardial Infarction Cardiogenic Shock. Insights From the National Cardiogenic Shock Initiative
Authors: Alejandro Lemor, Mir B Basir, Navin K Kapur, Kirit Patel, Murad A Salam, Theodore L Schreiber, Amir Kaki, Ivan D Hanson, Steve Almany, Steven Timmis, Simon R Dixon, Brian C Kolski, Josh Todd, Shaun Senter, Steven Marso, David Lasorda, Charles Wilkins, Thomas LaLonde, Antonious Attallah, Timothy Larkin, Allison Dupont, Jeffrey Marshall, Nainesh Patel, Tjuan Overly, Michael Green, Behnam Tehrani, Alexander G Truesdell, Rahul Sharma, Yasir Akhtar, Thomas McRaeIII, Brian P O’Neill, John Finley, Ayaz M Rahman, Malcolm Foster, Raza Askari, Andrew M Goldsweig, Scott Martin, Aditya Bharadwaj, Matheen Khuddus, Christopher Caputo, Denes Korpas, Ian M Cawich, Nimrod Blank, M Chadi M Alraies, Akshay Khandelwal, Khaldoon Alaswad, Tyrell Johnson, Michael Hacala, William O’Neill
Journal: Circulation (2019)

Background: The National Cardiogenic Shock Initiative (NCSI) is a single-arm, prospective, multicenter study to assess clinical outcomes associated with early mechanical circulatory support (MCS) i...
Balance where it really counts
Authors: Nicholas Epley, Leaf Van Boven, Eugene M. Caruso
Journal: Behavioral and Brain Sciences (2004)

A balanced approach that considers human strengths and weaknesses will lead to a more flattering set of empirical findings, but will distract researchers from focusing on the mental processes that produce such findings and will diminish the practical implications of their work. Psychologists ought to be doing research that is theoretically informative and practically relevant, exactly as they are doing.
Early tumor marker decrease to predict the efficacy of combination therapy with lenvatinib plus anti-PD-1 antibodies in unresectable hepatocellular carcinoma (uHCC).
Authors: Hui-Chuan Sun, Xiao-Dong Zhu, Cheng Huang, Ying-Hao Shen, Ning-Ling Ge, Jin-Jin Zhu, Bin Xu, Yi Chen, Mei-Ling Li, Jian Zhou, Jia Fan
Journal: Journal of Clinical Oncology (2021)

304 Background: Combination therapy with anti-angiogenic agents plus anti-PD-1 antibodies has shown high anti-tumor activity in uHCC. However, predicting the efficacy of this combination therapy remains a challenge. Methods: This study included consecutive patients with uHCC who received lenvatinib (8 mg/d regardless of body weight) and an anti-PD-1 antibody as first-line systemic therapy between Sep 2018 and July 2020, and had at least one imaging evaluation. Tumor response was assessed every 2 months (± 2 week) by the investigators using modified RECIST criteria. Patients were evaluated as having a radiological response (complete or partial response) or non-radiological response (stable disease or progressive disease) at the best overall response evaluation. Serum tumor markers for HCC, including alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), were evaluated at baseline and 2-3 weeks after therapy was initiated and their association with radiological response were assessed. Patients with baseline AFP or PIVKA-II between the upper limit of normal and the maximum measuring range of the kit were evaluable for AFP decrease or PIVKA-II decrease. Results: A total of 76 patients were eligible for this study. Baseline AFP ≥400 ng/mL or PIVKA-II ≥400 mAU/mL was not associated with radiological response (P = 0.167 and P = 0.916, respectively). At 2-3 weeks after the initiation of therapy, 51 patients were evaluable for AFP decrease; 78.4% experienced a &gt; 20% AFP decrease and 51.0% experienced a &gt; 50% AFP decrease. Patients with a &gt; 50% AFP decrease had a higher rate of radiological response than those with AFP increase or a ≤50% AFP decrease (73.1% vs 32.0%, P = 0.003). In 57 patients evaluable for PIVKA-II decrease, 50.9% and 35.1% experienced a &gt; 20% and &gt; 50% PIVKA-II decrease, respectively. Patients with a &gt; 50% PIVKA-II decrease had a higher rate of radiological response than those with PIVKA-II increase or a ≤50% PIVKA-II decrease (85.0% vs 29.7%, P &lt; 0.001). Both AFP decrease &gt; 50% and PIVKA-II decrease &gt; 50% predicted radiological response, with an area under receiver operating characteristic curve of 0.706 (95% CI, 0.560-0.852, P = 0.012) and 0.752 (95% CI, 0.621-0.883, P = 0.001), respectively. Furthermore, patients with a &gt; 20% AFP or PIVKA-II increase from baseline had a lower rate of radiological response (0% vs 57.4%, P = 0.043; and 21.7% vs 69.7%, P &lt; 0.001, respectively). Conclusions: A tumor marker decrease was seen in most patients as early as 2-3 weeks after the initiation of the combination therapy. Early on-treatment AFP or PIVKA-II decrease may serve as a predictor for objective response for patients with uHCC receiving combination anti-angiogenic and immune therapy.