tbuckley/cabot-search huggingface dataset:
Reducing Cardiovascular Disparities Through Community-Engaged Implementation Research
Authors: George A. Mensah, Richard S. Cooper, Anna Maria Siega-Riz, Lisa A. Cooper, Justin D. Smith, C. Hendricks Brown, John M. Westfall, Elizabeth O. Ofili, LeShawndra N. Price, Sonia Arteaga, Melissa C. Green Parker, Cheryl R. Nelson, Bradley J. Newsome, Nicole Redmond, Rebecca A. Roper, Bettina M. Beech, Jada L. Brooks, Debra Furr-Holden, Samson Y. Gebreab, Wayne H. Giles, Regina Smith James, Tené T. Lewis, Ali H. Mokdad, Kari D. Moore, Joseph E. Ravenell, Al Richmond, Nancy E. Schoenberg, Mario Sims, Gopal K. Singh, Anne E. Sumner, Roberto P. Treviño, Karriem S. Watson, M. Larissa Avilés-Santa, Jared P. Reis, Charlotte A. Pratt, Michael M. Engelgau, David C. Goff, Eliseo J. Pérez-Stable
Journal: Circulation Research (2018)

Cardiovascular disparities remain pervasive in the United States. Unequal disease burden is evident among population groups based on sex, race, ethnicity, socioeconomic status, educational attainment, nativity, or geography. Despite the significant declines in cardiovascular disease mortality rates in all demographic groups during the last 50 years, large disparities remain by sex, race, ethnicity, and geography. Recent data from modeling studies, linked micromap plots, and small-area analyses also demonstrate prominent variation in cardiovascular disease mortality rates across states and counties, with an especially high disease burden in the southeastern United States and Appalachia. Despite these continued disparities, few large-scale intervention studies have been conducted in these high-burden populations to examine the feasibility of reducing or eliminating cardiovascular disparities. To address this challenge, on June 22 and 23, 2017, the National Heart, Lung, and Blood Institute convened experts from a broad range of biomedical, behavioral, environmental, implementation, and social science backgrounds to summarize the current state of knowledge of cardiovascular disease disparities and propose intervention strategies aligned with the National Heart, Lung, and Blood Institute mission. This report presents the themes, challenges, opportunities, available resources, and recommended actions discussed at the workshop.
Estudio descriptivo de evolución ponderal, metabólica, hormonal y radiológica de los pacientes sometidos a gastroplastia vertical endoscópica (Método Apollo®) y balón intragástrico de 1 año como tratamiento de la obesidad. Resultados preliminares (BECA 2016)
Authors: E Espinet Coll, C Vila Lolo, JA Gómez Valero, S Bacchiddu, D Irigoyen, C Quintana, P Díaz Galán, C Segura, A Juan-Creix Comamala
Journal: Endoscopy (2017)

En los últimos años, están apareciendo novedosas estrategias endoscópicas para el tratamiento del paciente obeso. Aunque parecen ofrecer buenos resultados de seguridad y ponderales a corto y medio plazo, los cambios metabólicos, hormonales y radiológicos que presentan estos pacientes no están bien establecidos, así como tampoco la durabilidad a largo plazo de los mismos.
Veliparib (ABT-888) extended-release formulations: A phase 1 study on safety, pharmacokinetics (PK), and bioavailability in patients with advanced solid tumors.
Authors: Theresa Louise Werner, Jasgit C. Sachdev, Elizabeth M. Swisher, Martin Gutierrez, Muaiad Kittaneh, Mark N. Stein, Hao Xiong, Martin Dunbar, Danielle Marie Sullivan, Peter J Ansell, Robert Hetman, Philip Komarnitsky, Mark D. McKee, Antoinette R. Tan
Journal: Journal of Clinical Oncology (2016)

2579 Background: Veliparib is a potent oral PARP1/2 inhibitor. Monotherapy trials with immediate release formulation veliparib (IR-v) showed antitumor activity in BRCA+ cancers. An extended release formulation (ER-v) may lower the peak-to-trough concentration ratio while maintaining exposure and improving tolerability, providing a rationale to conduct a phase 1 study (NCT01853306) of ER-v in pts with advanced tumors. Methods: Eligible pts had metastatic BRCA+ cancer, BRCA± high-grade serous ovarian/primary peritoneal/fallopian tube cancer (OC), (part 1/2), or BRCA+ breast cancer (BC), or OC (part 3). Part 1 – PK assessment: pts received ER-v (3 different ER-vs tested) or IR-v 200 mg in fed/fasted state on days 1/3/5 (3-group, single-sequence crossover). Part 2 – 3+3 dose escalation: pts received ER-v daily (QD or BID) starting at 200 mg. Part 3 – safety expansion: ER-v was administered continuously at the RP2D. Primary objectives were to determine the bioavailability and food effect of ER-v vs IR-v, the MTD, and the RP2D/schedule of ER-v. ER-v and IR-v safety were also assessed. Results: As of 16 December 2014, 71 pts (96% female, 75% OC) received veliparib (part 1/2/3, n = 24/35/12). Pts were heavily pretreated and included platinum-refractory OC pts. ER-v had a longer Tmax (3.5 vs 1.7 h) and lower Cmax (629 vs 1471 ng/mL) than IR-v; AUC∞ was similar. The ER-v peak-to-trough concentration ratio was low, and food intake moderately increased Cmax and Tmax. Three pts experienced DLTs: 2/5 pts treated at 600 mg BID ER-v (G2 asthenia and G3 N&V) and 1/3 pts treated at 800 mg QD ER-v (G3 seizure). The ER-v RP2D was determined to be 400 mg BID. G 3/4 TEAEs (part 1/2/3) occurred in 25/20/17% of pts; most common were thrombocytopenia (8/6/0%), small intestinal obstruction (4/0/8%), nausea (0/3/8%), and vomiting (0/3/8%). Gastrointestinal TEAEs were in line with historic IR-v data. Confirmed and unconfirmed responses were observed in pts with BC (6/16, 38%) and OC (8/44, 18%). Conclusions: ER-v was well tolerated in pts with advanced tumors and led to a reduced peak-to-trough ratio and more sustained exposure compared to IR-v. ER-v demonstrated single-agent antitumor activity. Clinical trial information: NCT01853306.
Risk factors for gastric cancer: is it time to discard PPIs?
Authors: Lucrezia Laterza, Franco Scaldaferri, Antonio Gasbarrini
Journal: Gut (2018)

We read with great interest the paper by Cheung et al recently published in your journal.1 The extensive worldwide use of proton pump inhibitors (PPIs) makes the debate about a related risk of gastric cancer a very popular and current topic.2 Potentially, the PPI-induced reduction of acid content in the stomach may contribute to gastric cancer pathogenesis, possibly by increasing gastrin secretion, with a resultant constant trophic stimulus on the gastric mucosa, similar to Helicobacter pylori -related chronic atrophic gastritis.3 These conditions may both feasibly share a similar alteration of the gastric microbiota.4 

However, evidence on this topic is not definitive: two meta-analyses of randomised controlled trials found no correlation between gastric cancer and long-term PPI use,5 6 whereas a meta-analysis of observational …
Early Assessment of Lung Cancer Immunotherapy Response via Circulating Tumor DNA
Authors: Sarah B. Goldberg, Azeet Narayan, Adam J. Kole, Roy H. Decker, Jimmitti Teysir, Nicholas J. Carriero, Angela Lee, Roxanne Nemati, Sameer K. Nath, Shrikant M. Mane, Yanhong Deng, Nitin Sukumar, Daniel Zelterman, Daniel J. Boffa, Katerina Politi, Scott N. Gettinger, Lynn D. Wilson, Roy S. Herbst, Abhijit A. Patel
Journal: Clinical Cancer Research (2018)

Purpose: Decisions to continue or suspend therapy with immune checkpoint inhibitors are commonly guided by tumor dynamics seen on serial imaging. However, immunotherapy responses are uniquely challenging to interpret because tumors often shrink slowly or can appear transiently enlarged due to inflammation. We hypothesized that monitoring tumor cell death in real time by quantifying changes in circulating tumor DNA (ctDNA) levels could enable early assessment of immunotherapy efficacy.Experimental Design: We compared longitudinal changes in ctDNA levels with changes in radiographic tumor size and with survival outcomes in 28 patients with metastatic non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitor therapy. CtDNA was quantified by determining the allele fraction of cancer-associated somatic mutations in plasma using a multigene next-generation sequencing assay. We defined a ctDNA response as a >50% decrease in mutant allele fraction from baseline, with a second confirmatory measurement.Results: Strong agreement was observed between ctDNA response and radiographic response (Cohen's kappa, 0.753). Median time to initial response among patients who achieved responses in both categories was 24.5 days by ctDNA versus 72.5 days by imaging. Time on treatment was significantly longer for ctDNA responders versus nonresponders (median, 205.5 vs. 69 days; P < 0.001). A ctDNA response was associated with superior progression-free survival [hazard ratio (HR), 0.29; 95% CI, 0.09-0.89; P = 0.03], and superior overall survival (HR, 0.17; 95% CI, 0.05-0.62; P = 0.007).Conclusions: A drop in ctDNA level is an early marker of therapeutic efficacy and predicts prolonged survival in patients treated with immune checkpoint inhibitors for NSCLC. Clin Cancer Res; 24(8); 1872-80. ©2018 AACR.
Abstract 18996: Exosomes Derived From Cortical Bone Stem Cells Are a Novel Cardioprotective Therapy < Myocardial Injury
Authors: Sadia Mohsin, Constantine D Troupes, Deborah M Eaton, Mohsin Khan, Xiaoxuan Fan, Jaslyn Johnson, Eric A Feldsott, Yijun Yang, Tao Wang, Hajime Kubo, Remus M Berretta, Steven R Houser
Journal: Circulation (2016)

Rationale:  Cortical bone derived stem cells (CBSCs) have gained prominence recently due to their incredible growth kinetics and myocardial repair properties that outperform known stem cell types used for cardiac repair. Salutary effects of CBSCs in large are mediated by paracrine secretion. Since exosomes represent active component of released factors whether CBSC derived exosomes (CBSCs-Exo) are a viable therapy for heart repair after injury is presently unknown.   Objective:  Determine the therapeutic value of CBSC exosomes and their contents for myocardial repair.   Methods and Results:  Exosomes isolated from murine CBSCs by ultracentrifugation showed typical exosome size (30-100nm) validated by electron microscopy and dynamic light scattering. To determine cardiac therapeutic value, CBSC exosomes (60μg) injected mice after myocardial infarction (MI) demonstrated reduced infarct size and increased myocyte protection after acute MI injury. Interestingly, serum levels of pro-inflammatory cytokines were significantly reduced along with decreased expression of CD68+ cells in animals receiving CBSCs-Exo versus control animals. Long term analysis of CBSC-Exo animals showed improved cardiac function and contractility compared to saline treated animals concurrent with enhanced angiogenesis 6 weeks after MI. Salutary effects of CBSC-Exo were confirmed in vitro and showed increased cardiac protection in NRVMs after hypoxic challenge and enhanced tube formation in HUVECs. Simultaneously, treatment of bone marrow-derived macrophages stimulated with lipopolysaccharide (LPS) and treated with CBSCs-Exo showed increased polarization towards M2 phenotype demonstrating immunomodulation capacity of CBSC-Exo. The underlying mechanism for beneficial effects was tied to increased packaging of cardioprotective miRs in CBSCs-Exo confirmed by MiRNA array analysis.   Conclusion:  Exosomes derived from CBSCs provide a cell free system using reparative power of CBSC to augment cardiac function after myocardial injury recapitulating earlier findings with CBSCs. Increased packaging of cardioprotective and immune-modulatory miRs highlight a potential new insight into the salutary effects of exosome therapy.
Angioedema in patients with chronic spontaneous urticaria: assessment of disease severity and response to treatment
Authors: João Paulo de Assis, Gabriella Melo Fontes Silva Dias, Claudia Castilho Mouco, Andressa Zanandréa, Raisa Borges Castro, Jorge Kalil, Antonio Abilio Motta, Rosana C. Agondi
Journal: Journal of Allergy and Clinical Immunology (2018)
Comparative phase II study of intraperitoneal (IP) versus intravenous (IV) carboplatin administration with IV paclitaxel in patients with bulky residual disease after primary debulking surgery for epithelial ovarian or primary peritoneal cancer: A Sankai Gynecology Study Group (SGSG) study
Authors: K. Fujiwara, S. Nagao, J. Kigawa, J. Noma, N. Akamatsu, Y. Miyagi, F. Numa, M. Okada, E. Aotani, N. Terakawa
Journal: Journal of Clinical Oncology (2007)

5584 Background: To assess the anti-tumor effect and safety of IP carboplatin (C) administration comparing with IV C administration in combination with IV infusion of paclitaxel (P). Methods: This is a non-randomized comparative phase II trial. Eligible patients were those with histologically confirmed epithelial ovarian or primary peritoneal cancer who received initial surgery and ended up with residual disease &gt;= 2 cm. They must have reasonable hematological, hepatic, renal function before receiving chemotherapy. The patients received either of the following treatment arms; IP Arm: IV P 175 mg/m 2 over 3h followed by IP C AUC6, IV Arm: IV P 175 mg/m 2 over 3h followed by IV C AUC6. The treatments were scheduled to repeat 6–8 cycles. Interval debulking surgery was allowed after 3 to 5 cycle of treatment. Each participating institution had to declare, before the study was opened, which of the treatment arms the patients from the institution would be entered. Primary endpoint was a response. Secondary endpoints were toxicity and progression-free survival (PFS) and overall survival (OS). Target accrual was 30 patients in each arm. Results: Total accrual was 26 patients for IP arm and 30 patients for IV arm between 2001 and 2005. The study was closed early, because of the conflict of protocols for IP treatment. Eligible patients were 24 in IP Arm and 25 for IV arm. Median number of treatment cycle was 6 for both arms. Although the difference was not statistically significant, response rate was better in the IP Arm. Response rates were 83.3% (95%CI: 62.6%-95.3%) for IP Arm and 60.0% (95%CI: 38.7%-78.9%) for IV Arm. As of median followup of 31 months, median PFS is 25 months for IP Arm and 21 months for IV Arm,. Median OS is not reached for IP Arm, and 52 months for IV arm. Incidences of hematological and non-hematological toxicities were essentially the same on both arms. Conclusions: IP administration of C may be a better treatment strategy for epithelial ovarian and primary peritoneal cancer patients. A randomized phase III trial including bulky residual disease for comparison of IP and IV carboplatin treatment. No significant financial relationships to disclose.
The unique carcinogenic factor Tipα in cancer microenvironment of H. pylori infection
Authors: Masami Suganuma, Miki Kurusu, Takashi Kuzuhara, Kensei Yamaguchi, Hirota Fujiki
Journal: Cancer Research (2007)

5662  To investigate the carcinogenic process of H. pylori infection in the stomach, we first identified TNF-α inducing protein gene (Tipα), which is cloned from genomic DNA of H. pylori strain 26695. Tipα protein is a potent inducer of TNF-α gene expression and tumor promoting activity in Bhas 42 (v-H-ras transfected BALB3T3) cells. Furthermore, we found that Tipα strongly induced expression of chemokine genes, such as Ccl2, Ccl7, Ccl20, Cxcl1, Cxcl5, Cxcl10 and Cxcl12, as determined by comprehensive DNA microarray analysis and quantitative real-time RT-PCR. Thus, Tipα released from H. pylori is a potent inducer of chemokines as well as cytokines. Next, we determined the amounts of Tipα in culture mediums secreted from various H. pylori strains isolated from patients with gastritis and gastric cancer, by Western blotting using anti-Tipα antibody. It is of interest to note that the H. pylori clinical isolates obtained from gastric cancer patients released Tipα significantly more than did those from patients with gastritis, suggesting that Tipα is an important factor in cancer development during the process of H. pylori infection in the human stomach. To clarify precisely how Tipα induces NF-κB activation in the gastric epithelial cells, we studied whether Tipα would bind to a receptor of stomach cancer cells, MGT-40, using fluorescently labeled Tipα: We found that fluorescent-Tipα specifically bound to the cells and then entered the cells, in a dose- and temperature-dependent manner, whereas, an inactive mutant del-Tipα neither bound to, nor entered the cells, indicating the presence of a specific receptor for Tipα. Immunoprecipitation of Tipα after labeling of cell surface proteins with biotin indicated that Tipα bound to 160 kDa biotin-labeled proteins, but that inactive del-Tipα did not, suggesting that 160 kDa protein is the receptor of Tipα. All the results showed that Tipα induces NF-κB activation, and that gene expression of TNF-α and chemokines - mediated through a receptor, 160 kDa membrane protein in the gastric epithelial cells - causes inflammation and cancer in the stomach. Tipα is a unique carcinogenic factor of H. pylori, and its mechanism of action is completely different from that of CagA.
The Hippo Pathway Component TAZ Promotes Immune Evasion in Human Cancer through PD-L1
Authors: Helena J. Janse van Rensburg, Taha Azad, Min Ling, Yawei Hao, Brooke Snetsinger, Prem Khanal, Lori M. Minassian, Charles H. Graham, Michael J. Rauh, Xiaolong Yang
Journal: Cancer Research (2018)

The Hippo pathway component WW domain-containing transcription regulator 1 (TAZ) is a transcriptional coactivator and an oncogene in breast and lung cancer. Transcriptional targets of TAZ that modulate immune cell function in the tumor microenvironment are poorly understood. Here, we perform a comprehensive screen for immune-related genes regulated by TAZ and its paralog YAP using NanoString gene expression profiling. We identify the immune checkpoint molecule PD-L1 as a target of Hippo signaling. The upstream kinases of the Hippo pathway, mammalian STE20-like kinase 1 and 2 (MST1/2), and large tumor suppressor 1 and 2 (LATS1/2), suppress PD-L1 expression while TAZ and YAP enhance PD-L1 levels in breast and lung cancer cell lines. PD-L1 expression in cancer cell lines is determined by TAZ activity and TAZ/YAP/TEAD increase PD-L1 promoter activity. Critically, TAZ-induced PD-L1 upregulation in human cancer cells is sufficient to inhibit T-cell function. The relationship between TAZ and PD-L1 is not conserved in multiple mouse cell lines, likely due to differences between the human and mouse PD-L1 promoters. To explore the extent of divergence in TAZ immune-related targets between human and mouse cells, we performed a second NanoString screen using mouse cell lines. We show that many targets of TAZ may be differentially regulated between these species. These findings highlight the role of Hippo signaling in modifying human/murine physiologic/pathologic immune responses and provide evidence implicating TAZ in human cancer immune evasion.Significance: Human-specific activation of PD-L1 by a novel Hippo signaling pathway in cancer immune evasion may have a significant impact on research in immunotherapy. Cancer Res; 78(6); 1457-70. ©2018 AACR.
Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response
Authors: Giuseppe Faraco, David Brea, Lidia Garcia-Bonilla, Gang Wang, Gianfranco Racchumi, Haejoo Chang, Izaskun Buendia, Monica M. Santisteban, Steven G. Segarra, Kenzo Koizumi, Yukio Sugiyama, Michelle Murphy, Henning Voss, Joseph Anrather, Costantino Iadecola
Journal: Nature Neuroscience (2018)
The Leukotriene E 4 Receptor, CysLT 3 r Regulates Airway Chemosensory Brush Cell Expansion
Authors: Lora Georgieva Bankova, Eri Yoshimoto, Matthew P. Giannetti, Yoshihide Kanaoka, K. Frank Austen, Nora A. Barrett
Journal: Journal of Allergy and Clinical Immunology (2018)
Prediction of late seizures after ischaemic stroke with a novel prognostic model (the SeLECT score): a multivariable prediction model development and validation study
Authors: Marian Galovic, Nico Döhler, Barbara Erdélyi-Canavese, Ansgar Felbecker, Philip Siebel, Julian Conrad, Stefan Evers, Michael Winklehner, Tim J von Oertzen, Hans-Peter Haring, Anna Serafini, Giorgia Gregoraci, Mariarosaria Valente, Francesco Janes, Gian Luigi Gigli, Mark R Keezer, John S Duncan, Josemir W Sander, Matthias J Koepp, Barbara Tettenborn
Journal: The Lancet Neurology (2018)
Abstract 13064: The Long-term Cardiac Rehabilitation Improves the Prognosis of Patients With Cardiovascular Disease: The Large Cohort Study of Cardiac Rehabilitation in Tokyo (CART Study)
Authors: Atsuko Nakayama, Masatoshi Nagayama, Issei Komuro, Hitonobu Tomoike
Journal: Circulation (2016)

Introduction: The effects of comprehensive cardiac rehabilitation (CR) were already reported, but the most of the rehabilitation programs are consisted of short periods and the studies of continuous exercise training in a long time are not sufficient. Otherwise, many patients with cardiovascular disease clinically need sustained CR. Propose: The aim of this study is to prove the effects of the long-term CR and find the suitable candidates to be recommended participating in a rehabilitation program in the maintenance phase. Methods: We conducted a prospective cohort study on 10,275 patients receiving CR without dropout the CR program in Sakakibara Heart Institute in Tokyo from January 2003 to August 2015. The patients who had CR in the acute phase were classified into Phase l group who needs hospitalization and the patients after acute phase who had CR more than once a week for less than 150 days were classified into Phase ll group. The patients who had CR more than once a week for more than 150 days were classified into Phase lll group. Phase ll and lll groups underwent cardiopulmonary exercise testing (CPX) at intervals of 3 months. The rate of major adverse cardiac events (MACE: composite of cardiac death, acute coronary syndrome and cerebral infarction), the rate of mortality and the result of CPX in the three groups were compared. The sub-analysis was performed on each disease which composed of stable angina pectoris, acute coronary syndrome, heart failure, post CABG, post heart valve surgery, and large vessel disease. Results: The average age of patients was 66±14 years and the average follow-up period was 5.1±3.0 years. The patients were divided into three groups (Phase l: n=5178, Phase ll: n=3902, and Phase lll: n=1195). The average rehabilitation period of Phase lll group was 1.8±2.0 years. The risks of MACE and death were extremely lower in Phase lll group compared to that in Phase ll group, especially in patients with heart failure (MACE: HR0.59, p=0.022, and death: HR0.83, p=0.023). The improved peak VÒ 2 of Phase lll group with heart failure significantly paralleled till 4.4 years by multilevel modeling. Conclusions: The long-term cardiac rehabilitation for patients with cardiovascular disease improves the MACE, mortality and peak VÒ 2 .