tbuckley/cabot-search huggingface dataset:
Abstract 6371: Gaseous nitric oxide at high concentration is a powerful anti-tumor agent both in-vitro and in-vivo
Authors: Hila Confino, Steve Lisi, Rinat Kalaora, Matan Goldshtein, Amir Avniel
Journal: Cancer Research (2020)

Abstract Nitric Oxide (NO) acts as a signaling molecule in the body in different pathologic conditions, including cancer. Beyond Air is developing an innovative gaseous Nitric Oxide (gNO) based tumor ablation method. The highly diffusible nature of NO may ease its spreading inside the tumor, while its short half-life may limit its effect to the tumor site and not affect the surrounding area. According to our preliminary data, exposure of gNO at 10,000-50,000ppm for a very short time (in some cases one minute or less) efficiently eradicates breast, colon, lung and prostate cancers and shows a potent mouse tumor's destruction in-vivo. Methods: Mouse colon and breast cancer cell lines were exposed to gNO at 150-50,000 ppm for 10 seconds - 180 seconds. Cell viability was examined 24hrs later by XTT assay. Mouse colon tumors were treated by gNO at 10,000ppm - 50,000ppm intratumorally by hypodermic needles or local exposure of the tumor using a plastic box or tube. Results: To test if gNO at 150-50,000ppm can decrease cancer cell viability, cells were exposed (I) directly to NO in a 96 well plate or (II) in an acrylic glass box. Cell viability was tested 24hrs later by XTT. According to our findings, less than 3% of 4T1 cells remain viable when exposed to 10,000ppm NO for 3 minutes or 50,000ppm NO for 1 minute in a 96-well plate. ~1% of CT26 cells remain viable after exposure to 50,000ppm NO for 10 seconds in a 96 well plate; while less than 10% remain viable after 1 minute of exposure of 50,000ppm NO in a box. To test if gNO at 10,000-50,000ppm can destroy mouse colon cancer tumors in-vivo, tumors were exposed to gNO locally by hypodermic needles or a plastic cover. Air treated tumor bearing mice served as the control group. A complete tumor destruction was observed when the skin was removed from the tumor and the entire tumor was exposed to 10,000ppm gNO for 10 minutes. Conclusion: In the current work, gNO at high concentration showed a substantial cytotoxic effect on cancer cells in-vitro and in-vivo. The proposed project represents development of a novel treatment for cancer. Our innovative gNO based treatment may serve to treat solid tumors locally or be used as an adjunctive therapy for surgery and can be synergized with common anticancer therapies, such as chemotherapy and radiotherapy, to further enhance the effect. Citation Format: Hila Confino, Steve Lisi, Rinat Kalaora, Matan Goldshtein, Amir Avniel. Gaseous nitric oxide at high concentration is a powerful anti-tumor agent both in-vitro and in-vivo [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6371.
COVID-19 and Metabolic Syndrome: NF-κB Activation. Crossroads
Authors: Pablo Guisado-Vasco, Marta Cano-Megías, Margarita Rodríguez-López, Iris Mercedes de-Luna-Boquera, Daniel Carnevali-Ruiz
Journal: Trends in Endocrinology and Metabolism (2020)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in December 2019 as the cause of severe pneumonia in a cluster of patients in Wuhan, China. Subsequently, this viral pathogen was described as a novel RNA betacoronavirus [1]. As with other members of its group, SARS-CoV-2 is able to cause a severe acute respiratory syndrome, in this case named coronavirus disease 2019 (COVID-19).
Per-Oral Endoscopic Myotomy for Esophagogastric Junction Outflow Obstruction: A Multicenter Pilot Study
Authors: Chelsea C. Jacobs, Yaseen Perbtani, Dennis Yang, Mohammad A. Al-Haddad, Ite Obaitan, Mohamed Othman, Shawn Groth, Amrita Sethi, Emil Agarunov, Alessandro Repici, Roberta Maselli, Alessia Galtieri, Jacob Moremen, Haley N. Jenkins, Jason B. Samarasena, Kenneth J. Chang, Peter V. Draganov
Journal: Clinical Gastroenterology and Hepatology (2020)
Posttraumatic Stress Disorder and Electronically Measured Medication Adherence After Suspected Acute Coronary Syndromes
Authors: Ian M. Kronish, Talea Cornelius, Joseph E. Schwartz, Ari Shechter, Keith M. Diaz, Emily K. Romero, Donald Edmondson
Journal: Circulation (2020)

hypertension ◼ medication adherence ◼ posttraumatic stress disorder T he experience of a suspected acute coronary syndrome (ACS) can induce symptoms of posttraumatic stress disorder (PTSD), even among patients who rule out for ACS. 1 Patients who develop PTSD symptoms after ACS have twice the risk for recurrent cardiovascular events and mortality. 2Yet the reasons for this association between ACS-induced PTSD symptoms and adverse prognosis are poorly understood.A hallmark of PTSD is avoidance of reminders of traumatic events.Patients with ACS-induced PTSD report skipping cardiovascular medications because they serve as traumatic reminders. 3Self-reported adherence, however, is a poor indicator of true medication-taking behavior. 4This study is the first to test whether suspected ACS-induced PTSD symptoms are associated with electronically monitored medication nonadherence.From 2014 to 2017, we enrolled a cohort of patients with suspected ACS from the emergency department of Columbia University Irving Medical Center. 5Patients were included in this adherence substudy if they were prescribed a cardiovascular medication at discharge.Patients were excluded if they were non-English-or non-Spanish-speaking, cognitively impaired, in need of psychiatric intervention, terminally ill, or incapable of using an electronic pill bottle.The Columbia University Irving Medical Center institutional review board approved the protocol.All patients provided written informed consent.PTSD was evaluated by telephone 1 month after discharge using the 17-item PTSD Checklist for a specific stressor (PCL-S), cued to the ACS symptoms that brought patients to the emergency department.A PCL-S score of 30 has ≈80% sensitivity and specificity for PTSD diagnosis in primary care, and a score ≥44 is consistent with probable PTSD.Adherence to a single cardiovascular medication (typically aspirin) was assessed for up to 3 months after discharge using eCAPs (Information Mediary Corp, Ottawa, Canada).eCAPs resemble ordinary pill bottle caps but record the date and time when pill bottles are opened.Substudy participants transferred their monitored medication into an eCAP mailed to their address after hospital discharge and mailed back the eCAP after a follow-up phone call.Generalized estimating equations were used to model the percentage of adherent days per month (ie, days adherent/days monitored) from PTSD symptoms.Month was a repeated-measures factor.Covariates included age, sex, ethnicity, discharge diagnosis (ACS confirmed or ruled out), comorbidity (Charlson score), depression (8-item Patient Health Questionnaire), and dosing frequency of monitored medication.Of 783 eligible patients, 662 (84.5%) agreed to participate, 474 (60.5%) returned eCAPs, and 400 (51.1%) had complete data on covariates and were included in these analyses.Patients with greater PTSD symptoms were less likely to return eCAPs (P=0.03).
N0337: Phase II study of capecitabine in combination with vinorelbine and trastuzumab for the first or second treatment of HER2+ metastatic breast cancer
Authors: W. Tan, J. Allred, M. Salim, P. Flynn, J. W. Kugler, P. J. Stella, M. Wiesenfeld, A. M. Bernath, T. R. Fitch, E. A. Perez
Journal: Journal of Clinical Oncology (2009)

1020 Background: Trastuzumab-containing regimes have dramatically improved outcome of patients with HER2+ breast cancer. Efforts to improve efficacy and tolerability of combination regimens with this monoclonal antibody are important for patient care. Thus, we conducted a multi-institutional phase II study of a triplet combination in patients eligible to receive either first- or second-line treatment for HER2+ metastatic breast cancer (MBC). Methods: A phase II study designed to test that the true confirmed response rate (CRR) was at most 45% versus a true CRR of at least 65% was done (March 2005-June 2008). This design required that at least 25/45 confirmed responses in evaluable patients for the treatment to be considered promising. Patients received capecitabine 825 mg/m 2 po (days 1–14), vinorelbine intravenously (IV) 25 mg/m 2 days 1 and 8 every 3 weeks and trastuzumab IV 8mg/kg day 1, week 1, and then 6 mg/kg q 3 weeks. Tissue and blood have been collected for future studies on biomarkers. Results: 47 women were accrued, one patient cancelled participation prior to receiving any study drug, and another had a major protocol violation. 45 patients were evaluable and 30 (67%) achieved a confirmed response, (26 patients, 58% had a confirmed partial response and 4 patients, 9% had a confrimed complete response). Median progression free survival was 11.3 months (95% CI 8.4–23.2 months), median overall survival was 27.2 months (95% CI: 26.6-NA months), and among the 30 responders, the median duration of response time was 15.5 months (95% 7.7–26.1 months). The most common grade 3 events include neutropenia 61%, fatigue 13%, skin reaction-hand-foot 11%, and leukopenia 11%. Alopecia was not noted with this regimen. Conclusions: This triplet combination is effective, safe, and is promising in patients with HER2+ MBC. A phase III study should be conducted to compare the best doublet with this triplet combination whether this would lead to better clinical outcomes. [Table: see text]
Association of physical activity with risk of hepatobiliary diseases in China: a prospective cohort study of 0.5 million people
Authors: Yuanjie Pang, Jun Lv, Christiana Kartsonaki, Canqing Yu, Yu Guo, Huaidong Du, Derrick Bennett, Zheng Bian, Yiping Chen, Ling Yang, Iain Turnbull, Hao Wang, Hui Li, Michael V Holmes, Junshi Chen, Zhengming Chen, Liming Li
Journal: British Journal of Sports Medicine (2020)

Objective There is limited prospective evidence on the association of physical activity with hepatobiliary cancer subtypes and other major hepatobiliary diseases, especially in China. We aimed to quantify the associations with risk of these diseases. Methods The study population involved 460 937 participants of the prospective China Kadoorie Biobank aged 30–79 years from 10 diverse areas in China without history of cancer or hepatobiliary disease at baseline. Cox regression was used to estimate adjusted hazard ratios (HRs) for each disease associated with self-reported total and domain-specific physical activity (occupational and non-occupational, ie, leisure time, household and commuting). Results During ~10 years of follow-up, 22 012 incident cases of hepatobiliary diseases were recorded. The overall mean (SD) total physical activity was 21.2 (13.9) metabolic equivalent of task (MET)-hours/day, with 62% from occupational activity. Total physical activity was inversely associated with hospitalised non-alcoholic fatty liver disease (HR comparing top vs bottom quintile: 0.62, 95% confidence interval (CI) 0.53 to 0.72), viral hepatitis (0.73, 95% CI 0.62 to 0.87), cirrhosis (0.76, 95% CI 0.66 to 0.88) and liver cancer (0.81, 95% CI 0.71 to 0.93), as well as gallstone disease (0.86, 95% CI 0.81 to 0.90), gallbladder cancer (0.51, 95% CI 0.32 to 0.80) and biliary tract cancer (0.55, 95% CI 0.38 to 0.78). The associations for occupational physical activity were similar to those for total physical activity, but for non-occupational physical activity they differed by disease subtype. For leisure-time physical activity, there was an inverse association with liver cancer and an inverse trend for gallstone disease (HR comparing ≥7.5 MET-hours/day with none: 0.83, 95% CI 0.75 to 0.91 and 0.82, 95% CI 0.66 to 1.01). Conclusion Among Chinese adults, high total physical activity, particularly occupational physical activity, was inversely associated with risk of major hepatobiliary cancers and diseases, including non-alcoholic fatty liver disease, cirrhosis and certain types of cancer.
AB0024 Activities of purine metabolism enzymes and antioxidant system in rheumatoid arthritis patients
Authors: AB ZZborovsky, VF Martemyanov, MY Stazharov, SA Bedina, TP Chernykh, EE Mozgovaya
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The results of Antioxidant system researches of blood at Rheumatoid arthritis are inconsistent and not enough attention was given to Purine metabolism questions. <h3>Objectives</h3> The improvement of Rheumatoid arthritis diagnostics with use of the enzymatic tests. <h3>Methods</h3> 71 RA patients and 30 healthy controls were under observation. Adenosin deaminase (ADA), AMP-desaminase (AMPDA), Guanin desaminase (Guanase), Xanthine oxidase (XO), Xanthine dehydrogenase (XDG) activities were determined in blood serum; Glutation peroxidase (GP), Glutation reductase (GR), Superoxid dismutase (SOD) activities ? in plasma (pl.) and erythrocytes (er.). ADA, XDG, SOD isoenzymes were determined also. The enzymatic indices were defined in the process of treatment thrice and were analysed depending on clinical specificity of the disease. <h3>Results</h3> Increased ADA, Guanase, GRpl., GPer., XO, XDG, SOD activities, decreased AMPDA, GRer., GPpl. activities, increase ADA-2, XDG-2, SOD-1 isoenzymes were observed in RA patients (I degree of activity) in comparison with healthy controls. The increase of the pathological process activity was accompanied with the increase of Guanase, GRpl., XO, SODpl. activities, ADA-2, XDG-2, SOD-1 isoenzymes and the decrease of ADA, XDG, GRer. activities. RA patients with system defeats have more increased AMPDA, Guanase, XO activities, ADA-2, XDG-2 isoenzymes, but less ADA, XDG activities in comparison with patients, which had arthritis form of RA. The system defeates were characterised with the decrease of SOD, GPer. activities and the increase of GPpl. activity; patients with the arthritis form of RA had contrary changes. We observed more increase AMPDA, Guanase, XO, ADA-2 activities and less ADA activity in fast progressing RA in comparison with slow progressing. <h3>Conclusion</h3> The enzymatic indices essentially depended on clinical specificity of the disease and can be used as additional diagnostic criterions in RA.
Time Course of a Second Outbreak of COVID-19 in Beijing, China, June-July 2020
Authors: Zunyou Wu, Quanyi Wang, Jing Zhao, Peng Yang, Jennifer M. McGoogan, Zijian Feng, Chun Huang
Journal: JAMA (2020)

Clinical Characteristics of Patients With Novel Coronavirus (2019-nCoV) Infection Hospitalized in Beijing, China
Interim results of the phase I/II study of trabedersen (AP 12009) in patients with pancreatic carcinoma, malignant melanoma, or colorectal carcinoma
Authors: H. Oettle, A. Hilbig, T. Seufferlein, R. M. Schmid, T. Luger, G. von Wichert, S. Schmaus, H. Heinrichs, K. Schlingensiepen
Journal: Journal of Clinical Oncology (2009)

4619 Background: TGF-beta 2 is one of the most potent immunosuppressors and mediates escape from immunosurveillance. It also plays a crucial role in tumor progression by regulating metastasis, angiogenesis, and proliferation. Trabedersen, a TGF-beta 2-specific inhibitor has already shown a clear survival benefit in a randomized active-controlled phase II study in high-grade glioma patients, compared to standard chemotherapy. Methods: 33 patients with advanced pancreatic carcinoma (stage IVA/IVB) (N=23), malignant melanoma (stage III/IV) (N=5) or colorectal carcinoma (stage III/IV) (N=5) were treated with trabedersen as 2nd-4th-line treatment. Two treatment schedules (1st schedule:7d on, 7d off; 2nd schedule: 4d on, 10d off; up to 10 cycles) were evaluated in a cohort dose-escalation design. Primary study objective: maximum tolerated dose (MTD); secondary objectives: safety and tolerability, pharmacokinetics and antitumor activity. Results: Patient recruitment for both schedules is completed. Very good safety and tolerability of trabedersen was observed, with moderate thrombocytopenia as main adverse event. Max. grade 3 dose-limiting toxicities (2 thrombocytopenias, 1 exanthema) occurring with 240 mg/m2/d in the 1st schedule established the MTD at 160 mg/m2/d. MTD has not been reached in the 2nd schedule. Of the 5 melanoma patients one from the 1st schedule showed stable disease and lived for 13.8 months; 3 patients from the 2nd schedule are still alive. Median overall survival (mOS) for pancreatic carcinoma patients in the 1st schedule was 6.8 months. One pancreatic carcinoma patient showed a complete response and is alive 38 months after trabedersen therapy. Current mOS for pancreatic carcinoma patients in cohort 1 (N=5) of the 2nd schedule is 13.2 months; 2 of these patients are alive, one with stable disease 14.8 months after begin of trabedersen treatment. Conclusions: Trabedersen has a very good safety and tolerability profile. The survival data are very encouraging. The study will continue with one dose in at least 12 patients. A randomized, active-controlled phase II study compared to standard therapy in patients with pancreatic carcinoma is in preparation; another one in malignant melanoma is being planned. [Table: see text]
FRI0220 Stable anti-ro and anti-la serological profile in anti-ro and anti-la negative sialadenitis and sjÖgren’s syndrome patients as disease progresses
Authors: MM Zandbelt, LB Van de Putte, FH Van den Hoogen
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> It is generally considered that more weight should be put on objective signs in the classification criteria for Sjögren's syndrome SS). Such objective findings include the presence of anti-Ro- and anti-La-antibodies, as well as the sublabial gland histology expressed in focus-score (FS) and IgA containing plasmacells percentage (IgA%) score. So far, anti-Ro and/or anti-La autoantibodies in the patient?s serum have been the most sensitive (40–80%) and specific serological markers for Sjögren's syndrome. <h3>Objectives</h3> The aim of this study is to investigate whether sero-conversion from anti-Ro- and anti-La antibodies negative to positive occurs in our SS and focal sialadenitis patients after disease has progressed for a minimum of five years since diagnosis. <h3>Methods</h3> Blood samples were taken from 20 patients, and sera were measured for presence of anti-Ro- or anti-La antibodies using ELISA and counter immune electrophoresis (CIE). Twelve patients fulfilled the ESG criteria for Sjögren's syndrome. Five of them were diagnosed with primary SS and 7 were diagnosed with secondary SS. Histologic (FS &gt; 1, IgA% &lt; 70) underlined the diagnosis. The remainder 8 patients with sicca symptoms and FS &gt; 1 did not meet the ESG criteria and were therefore diagnosed as having focal sialadenitis. <h3>Results</h3> In the ELISA no anti-Ro or anti-La positive sera were detected. An initial CIE, performed as confirmation measurement technique, showed three possibly positive sera. However, in a second CIE these sera were identified as anti-RNP antibodies positive sera. <h3>Conclusion</h3> These results confirm other observations that the serological profile in patients with Sjögren's syndrome is stable as disease progresses. There appears to be no need for repeated measurements of anti-Ro- or anti-La antibodies presence in anti-Ro- and anti-La negative patients? sera. Further investigations should point out whether measurement for presence of these autoantibodies in exocrine tissue itself or in exocrine glands products such as saliva is preferable over serological analysis in terms of disease-sensitivity. These alternative methods might be necessary to increase accuracy of the diagnosis since at least 20% of SS patients show a sustained lack of anti-Ro and anti-La antibodies in their serum.
Resilience in older persons: A systematic review of the conceptual literature
Authors: M.J. Angevaare, J. Roberts, H.P.J. van Hout, K.J. Joling, M. Smalbrugge, L.J. Schoonmade, G. Windle, C.M.P.M. Hertogh
Journal: Ageing Research Reviews (2020)

Although ageing research increasingly incorporates resilience, a common notion on what resilience means is lacking. We aimed to give a comprehensive overview of the conceptual literature on resilience in older persons, identifying areas of consensus and variation/debate. A systematic search of eight databases from different disciplines led to the inclusion of 36 texts. Across the conceptual literature of resilience in older persons, three common features of descriptions of resilience were identified: a stressor, a response and a mechanism. Based on differences in their interpretation of how resilience is expressed we distinguished two perspectives. The first, classical and most widely applied perspective, describes the expression of resilience as a positive response to a high intensity stressor. The second, newer perspective, describes resilience in the context of responses relative to equilibrium, following low intensity stressors. Almost all descriptions across the two perspectives describe the resilience mechanism to be dynamic and emphasize the importance of the context in achieving resilience. This review provides clarity on the current conceptual status of resilience in older persons, an important step towards a higher level of consistency in the future use of resilience in ageing.
Biological activity of bevacizumab and erlotinib in patients with advanced hepatocellular carcinoma (HCC)
Authors: A. O. Kaseb, M. Iwasaki, M. Javle, G. Onicescu, E. Garrett-Mayer, J. L. Abbruzzese, M. B. Thomas
Journal: Journal of Clinical Oncology (2009)

4522 Purpose: HCC is the fifth most common solid tumor worldwide and the incidence is rising in western countries. Current standard of care for advanced HCC is sorafenib based on median survival (MS) of 10.7 months (mos), median time to progression 5.5 mos. HCC are highly vascular tumors, and due to the prevalence of vascular endothelial growth factor and epidermal growth factor receptors in HCC, a phase II single-arm open-label trial of B and E in patients (pts) with HCC has been completed. Patients and Methods: Eligibility criteria include biopsy-proven unresectable HCC, Child-Pugh class A or B cirrhosis, bilirubin ≤2.0 mg/dL, transaminase (TA) levels ≤5 times the upper limit of normal, platelets ≥50,000/μL and Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2. Prior allowed therapies are surgery, external radiotherapy, ablation, transarterial chemoembolization (TACE) and 1 systemic therapy. Pts received B 10 mg/kg every 14 days plus E 150 mg orally daily. Results: The primary endpoint was the percent of pts alive and progression-free after 16 weeks of therapy (PFS 16 ) based on historic median PFS of 3 to 5 mos. Response was evaluated by RECIST. 57 pts have been enrolled and were evaluable for analysis on an intent to treat basis. For all pts, the median age was 62.8 years (range 29–82), 44 (77%) male, 25 (43.9%) Caucasian; 25 (43.9%); ECOG PS of 0, 31 (54.4%) pts PS of 1. 14 pts (24.6%) had prior therapy (6 sorafenib). Of the 57 pts enrolled, 14 (28%) had confirmed partial responses, 31 (62%) had stable disease and 5 (10%) had progressive disease. PFS 16 , was 73% (95% CI 60%, 84%). The median PFS is 7.9 mos (95% CI 5.7, 9.5) and the OS is 12.8 mos, 95% CI (9.5, 17.9). 6 pts were removed for toxicity; there was one on-study death. The most common grade 1 or 2 toxicities are folliculitis, anorexia, diarrhea, dry skin, and epistaxis. Grade 3 or 4 toxicities were transaminase elevation, diarrhea, fatigue, hyperkalemia, hypertension, proteinuria, pulmonary embolus, leukoencephalopathy and gastrointestinal bleed. Conclusions: The combination of B and E appears to have significant clinically meaningful activity in HCC. A multi-institution randomized phase II trial is planned. [Table: see text]