tbuckley/cabot-search huggingface dataset:
Specific immune responses against hepatocellular carcinoma induced by dendritic cell- HepG2 fusion cells derived- exosomes
Authors: H. Zhang, L. W. Zhang, W. C. Liu
Journal: Journal of Clinical Oncology (2007)

13511 Background: To assess the properties of exosomes secreted by fusion cells of hepatoma patient-derived dendritic cells(DCs)and hepatoma cell line (HepG2) and to evaluate the function of these exosomes to trigger efficient T cell responses against HepG2 cells in vitro. Methods: Peripheral blood mononuclear cells (PBMC) from hepatoma patients were isolated and in the presence of GM-CSF and IL-4, PBMC were cultured in vitro for one week to induce dendritic cells (DC). Fusion cells of DC with HepG2 cells (DC- HepG2) were achieved by PEG and were isolated by magnetic device with HLA Class II Dynabeads. Exosomes were then prepared from the supernatants of the fusion cells by ultra filtration centrifugation and sucrose gradient ultracentrifugation. T lymphocytes were pulsed with exosomes directly in the presence of IL-2. After co-cultured with target cells, the stimulated lymphocytes were tested by IFN-? release assay and cytotoxicity capacity assay. Results: After fusion, DC-HepG2 expressed expressed high level of DC surface molecules, including CD83 87.4%, CD80 94.9%, CD86 90.13% and HLA-DR 98.62%. Application of the isolation procedure to fusion cells also revealed exosome vesicles by transmission electron microscopy. Protein analysis by FCM was performed and revealed that the costimulatory molecule CD86 and AFP protein was detectable. The fusion cell- derived exosomes could directly activate T lymphocytes which lysed HepG2 target cells much more effectively than T cells alone did (P&lt;0.05). To determine whether the lysis was HepG2 tumor cell-specific, SMMC7721 and K562 cells were used as target cells and nearly no lysis of these cells was observed. Furthermore, IFN-? in the culture supernatants of exosomes- activated T cells was significantly higher than that in normal control T cells (P&lt;0.05). Conclusions: Exosomes could be purified from the supernatants of fusion cells. These exosomes could activate T cells directly and could induce effective HepG2 secific CTL responses. DC- HepG2 fusion cells-derived exosomes may represent as a promising approach of immunotherapy for HCC. No significant financial relationships to disclose.
Randomized trial of a left ventricular assist device as destination therapy versus guideline‐directed medical therapy in patients with advanced heart failure. Rationale and design of the SWEdish evaluation of left Ventricular Assist Device (SweVAD) trial
Authors: Kristjan Karason, Lars H. Lund, Magnus Dalén, Erik Björklund, Karl Grinnemo, Oscar Braun, Johan Nilsson, Henriette van der Wal, Jonas Holm, Laila Hübbert, Krister Lindmark, Barna Szabo, Erik Holmberg, Göran Dellgren
Journal: European Journal of Heart Failure (2020)
Phase I study of bi-weekly pemetrexed (P) plus cisplatin (C) in patients with advanced cancer
Authors: A. Lopez-Martin, L. Paz-Ares, E. Calvo, D. Castellano, C. Valverde, S. Neciosup, E. Vilar, B. San Antonio, I. Garcia-Ribas, H. Cortes-Funes, J. Bellmunt
Journal: Journal of Clinical Oncology (2007)

2580 Background: Cisplatin and pemetrexed have demonstrated clinical activity in several malignant tumors including mesothelioma and non small cell lung cancer. There is preclinical evidence of synergism between both agents as well as clinical non-overlapping toxicities, thus providing the rationale for their evaluation in combination. Our aim was to develop a well-tolerated combination of bi-weekly CP able to deliver higher dose intensity than the every 3-week standard. Methods: Escalating doses of P from a starting dose level of 300 mg/m 2 , with a fixed-dose of C 50 mg/m 2 , both biweekly on 28-day cycles, were administered to patients with refractory advanced solid malignancies and calculated creatinine clearance = 45 mL/min. Results: Twenty one patients (5 female/16 male); median age 61 (39–76); ECOG 0 (16), 1 (5); lung cancer (9); soft-tissue sarcoma (3); unknown primary, bladder, breast, rectum, esophagus, melanoma, mesothelioma, prostate, and tonsil (1, each) have received a total of 48 courses (median 2, range 0–5), at P dose levels of 300 mg/m 2 [8 pts, Dose level 1 (DL1)], 400 mg/m 2 (7 pts, DL2), and 500 mg/m 2 (6 pts, DL3), with full doses of C. Four patients were non-evaluable (2 at DL1, 1 at DL2 and 1 at DL3) because of early PD (2) and non-drug related serious adverse event (2 pt). Dose Limiting Toxicities (DLT) were G4 neutropenia (1 pt) at 300 mg/m 2 ; and prolonged G 1/2 thrombocytopenia (1 pt) at 500 mg/m 2 . There were also 2 pts with non-DLT G4 neutropenia at DL3. The rest of toxicities were mild to moderate being the most frequent asthenia, nausea, anorexia, stomatatis, and sensory neuropathy. DL3 was considered the Maximum Tolerated Dose (MTD) and the previous level with P at 400 mg/m 2 was declared the recommended phase II dose. Three additional patients were treated at DL2 for dose confirmation. A PR has been observed in 2 pts with NSCLC, 1 pt with breast, and 1 with esophagus cancer. Conclusions: Biweekly administration of pemetrexed (400 mg/m 2 ) plus cisplatin (50 mg/m 2 ) is clinically well tolerated and can be used safely. The regimen delivers higher dose intensity of P and equal of C as the standard. This regimen is currently being studied in a phase 2 trial in patients with locally advanced, non resectable or metastatic urothelial cancer. No significant financial relationships to disclose.
Purine and pyrimidine transporters of pathogenic protozoa – conduits for therapeutic agents
Authors: Gustavo D. Campagnaro, Harry P. de Koning
Journal: Medicinal Research Reviews (2020)

Purines and pyrimidines are essential nutrients for any cell. Most organisms are able to synthesize their own purines and pyrimidines, but this ability was lost in protozoans that adapted to parasitism, leading to a great diversification in transporter activities in these organisms, especially for the acquisition of amino acids and nucleosides from their hosts throughout their life cycles. Many of these transporters have been shown to have sufficiently different substrate affinities from mammalian transporters, making them good carriers for therapeutic agents. In this review, we summarize the knowledge obtained on purine and pyrimidine activities identified in protozoan parasites to date and discuss their importance for the survival of these parasites and as drug carriers, as well as the perspectives of developments in the field.
Abstract P269: Physical Activity Relative Intensity is Inversely Associated With Mortality in Older Women
Authors: Michael J LaMonte, John BELLETTIERE, Chongzhi Di, Andrea Z LACROIX
Journal: Circulation (2020)

Background: Aerobic capacity and efficiency of movement reduce with aging, and do so at an accelerated rate. Consequently, the relative intensity (effort) of a defined physical activity (PA) task is higher at older compared with younger ages. The magnitude of association for PA relative intensity with health outcomes in older adults is unknown, and is a research priority identified in the 2018 PA Guidelines for Americans. Methods and Results: We followed 5,756 women, ages 63-99 years, for all-cause mortality (369 deaths) during a median of 4.3 years. Self-rated relative intensity during usual daily PA was determined using the Borg 0-10 point scale at baseline. PA relative intensity categories were “nothing to very weak” (Borg 0-2; n=1052; referent group), “weak” (Borg 3; n=2854), “moderate to maximal” (Borg ≥4; n=1850), over which numbers of deaths and crude mortality rates (per 1000 person-years) were 118 (25.7), 170 (13.0), 81 (9.5), respectively. In Cox regression analysis controlling for age, race-ethnicity, education, smoking, alcohol, use of assistive walking device, sleep duration, self-rated health status, number of comorbidities and BMI, hazard ratios (95% CI) across the above exposure categories were 1.00 (ref), 0.69 (0.54, 0.89), and 0.72 (0.53, 0.98), trend P=.03. The significant inverse association was evident in older women ≥80 years (HR: 1.00, 0.60, 0.68, trend P=.01) but not in women &lt;80 years (HR: 1.00, 1.26, 0.99, trend P=.88; interaction P=.58). Conclusions: Self-rated PA relative intensity is inversely associated with mortality in older ambulatory women, and may provide a simple approach in epidemiologic studies to characterizing the relevance that age-related changes in aerobic fitness and energetics of movement have on health outcomes.
Abnormal Glucose Regulation in Chinese Patients with Coronary Artery Disease: A Gender Analysis
Authors: Chaugai Sandip, Harish Jevallee, Juan Liu, Qiong-li Zheng, Wen-cai Zhang, Shao-Fang Nie, Ting-ting Tang, Ni Xia, Yu-hua Liao, Xiang Cheng
Journal: Metabolism (2020)
Gut microbiota and human NAFLD: disentangling microbial signatures from metabolic disorders
Authors: Judith Aron-Wisnewsky, Chloé Vigliotti, Julia Witjes, Phuong Le, Adriaan G. Holleboom, Joanne Verheij, Max Nieuwdorp, Karine Clément
Journal: Nature Reviews Gastroenterology & Hepatology (2020)
Wasteful Health Care Spending in the United States
Authors: Edward W. Martin, John B. Murphy, Richard W. Besdine
Journal: JAMA (2020)

To the Editor Dr Shrank and colleagues reported on “the sources of waste in health care spending” in the United States.1 Although we agree with the authors that an understanding of wasteful spending and overtreatment is important, we are concerned about their use of the term end-of-life care.
Abstract P103: Tobacco-21 Policy Implementation In A Texas Community: Utilizing Interorganizational Network Analysis To Evaluate Tobacco Coalition Dynamics
Authors: Sonya Panjwani, Whitney R Garney, Kristen Garcia
Journal: Circulation (2020)

Introduction: In El Paso County, TX, a local tobacco coalition is working in partnership with the American Heart Association’s (AHA) Heart Racial and Ethnic Approaches to Community Health (REACH) program to focus efforts on aligning local activities with the new, statewide Tobacco-21 policy. As coalitions have been on the forefront of spearheading policy implementation efforts, understanding and quantifying coalition dynamics is necessary to increase collaboration and leverage resources. The purpose of this study is to highlight the findings of a baseline Interorganizational Network (ION) analysis of a tobacco coalition in El Paso County, TX in order to determine current levels of collaboration between organizations and strength of relationships. Hypothesis: We assessed the hypothesis that by using ION analysis, we can characterize relationships between organizations, identify organizations that are working in silos, and leverage ties between organizations to implement new, tobacco control initiatives that support the Tobacco-21 policy. Methods: Evaluators from Texas A&amp;M University worked in conjunction with the AHA to conduct an ION survey that assessed information sharing and joint planning of organizations involved in the tobacco coalition (n=18). Using UCINET© network analysis software, density and centrality scores at the network-level were calculated. Network diagrams were then developed to depict relationships among partners using Gephi© visualization software. Results: Network collaboration related to information sharing had a network density score of 0.340 (SD=0.474) while joint planning had a network density score of 0.297 (SD=0.457). The centralization index for information sharing was 0.055 and 0.0729 for joint planning with the coalition as the most central for both domains. Conclusion: This study shows how determination of organizational relationships within a coalition can be leveraged for strategic planning. Density measures were useful to understand the connectedness of the network, and centrality measures at the network-level were helpful in determining network structure. In conclusion, results from this study informed program implementers on how to better foster collaboration among organizations. Subsequent iterations of the survey will allow for documentation of changes in the strength of relationships over the project period.
Gamma knife radiosurgery for melanoma/renal cell carcinoma brain metastases 1 -10 lesions with optimized margin dose: Improved tumor control and survival
Authors: A. O. Fregene, P. Mobit, L. Zamorano, F. Diaz, M. Guthikonda, M. Syrian, J. Rakowski
Journal: Journal of Clinical Oncology (2007)

8581 Background: Radioresistant brain metastases melanoma/renal cell carcinoma cause significant morbidity and mortality: response to whole brain external beam radiotherapy (WBXRT) is minimal, chemotherapy role is investigative, and surgery has its indications and limitations. Reports of survival with Gamma Knife Radiosurgery (GK) is mixed. Reports indicate that 80 to 90% of tumor failure following GK is in the margin: recent multivariate analyses indicate tumor control dependence on margin dose. This study evaluates the impact of better control of brain lesions and consequent reduction of CNS death on overall survival. Methods: Between 10/2002 and 12/2005, 24 consecutive patients with melanoma and renal cell carcinoma male/female radio 14/10, 20 melanoma and 4 renal cell were treated by WBXRT followed by GK radiosurgery utilizing optimized margin dose. Dose was (16 - 20 Gy) to the 50% line with adequate margin to reduce systematic and other associated errors. This was achieved by combining the separate errors associated with the procedure; extent of tumor infiltration beyond gross tumor margin; GK/procedure mechanical precision limitations; MRI image transfer spatial limitations and beam profile margin dose sensitivity. Karnofsky Performance status was 70 - 90%. Follow-up period was 52 months. Results: The mean survival period for the 24 patients with 1 - 10 lesions was 14.11 months: median survival by Kaplan-Meier was 12.0 months. This result is a significant improvement on the 5.5 months reported earlier from this institution for 1 - 5 lesions treated with non-optimized GK dosage; and data by Lavin, et al, at 8 months for predominantly solitary lesions. Conclusions: Melanoma and renal cell carcinoma brain metastases respond very well to GK radiosurgery with optimized margin dose: mean survival for these patients with 1 -3 and 4 - 10 lesions is 14.11 months and comparable to the survival of patients with brain metastases from lung and breast patients: More studies along this line are called for. Patients with multiple metastatic brain lesions from melanoma and renal cell cancers stand to benefit. No significant financial relationships to disclose.
Epitranscriptomic 5-Methylcytosine Profile in PM<b>2.5</b>-Induced Mouse Pulmonary Fibrosis
Authors: Xiao Han, Hanchen Liu, Zezhong Zhang, Wenlan Yang, Chunyan Wu, Xueying Liu, Fang Zhang, Baofa Sun, Yongliang Zhao, Guibin Jiang, Yun-Gui Yang, Wenjun Ding
Journal: Genomics Proteomics & Bioinformatics (2020)

Abstract Exposure of airborne particulate matter (PM) with an aerodynamic diameter less than 2.5 μm (PM2.5) is epidemiologically associated with lung dysfunction and respiratory symptoms, including pulmonary fibrosis. However, whether epigenetic mechanisms are involved in PM2.5-induced pulmonary fibrosis is currently poorly understood. Herein, using a PM2.5-induced pulmonary fibrosis mouse model, we found that PM2.5 exposure leads to aberrant mRNA 5-methylcytosine (m5C) gain and loss in fibrotic lung tissues. Moreover, we showed the m5C-mediated regulatory map of gene functions in pulmonary fibrosis after PM2.5 exposure. Several genes act as m5C gain-upregulated factors, probably critical for the development of PM2.5-induced fibrosis in mouse lungs. These genes, including Lcn2, Mmp9, Chi3l1, Adipoq, Atp5j2, Atp5l, Atpif1, Ndufb6, Fgr, Slc11a1, and Tyrobp, are highly related to oxidative stress response, inflammatory responses, and immune system processes. Our study illustrates the first epitranscriptomic RNA m5C profile in PM2.5-induced pulmonary fibrosis and will be valuable in identifying biomarkers for PM2.5 exposure-related lung pathogenesis with translational potential.
A phase II study of the feasibility of sequential carboplatin (C) followed by paclitaxel (P) and gemcitabine (G) as first-line chemotherapy for stage Ic-IV ovarian (OC), fallopian tube (FTC), and primary peritoneal carcinoma (PPC)
Authors: R. Agarwal, J. Paul, K. Carty, T. Perren, N. Reed, C. Gourley, D. Parkin, M. Gore, S. Kaye
Journal: Journal of Clinical Oncology (2007)

5578 Background: We previously explored the feasibility of adding G to C + P in a phase II study, in which 4 cycles of C followed by 4 cycles of concurrent weekly P and G were given (BJC (2004) 91:627–32). Although highly active (med PFS 19.5m), the feasibility of this 1st-line regimen was limited by dyspnea during the weekly P+G phase. The current trial assessed whether the dyspnoea could be ameliorated by altering the schedule. Methods: Untreated FIGO stage Ic-IV OC, FTC and PPC patients (pts) were eligible. Chemotherapy (CTX) consisted of 4 cycles of C (AUC 7) q21 days, followed by 4 cycles of concurrent P (175 mg/m 2 ) d1 and G (1,000 mg/m 2 ) d1 and d8 q21 days. The primary endpoint of the study was the percentage of pts completing the planned 8 cycles of CTX. The planned sample size was 54 pts, based on a one stage single arm study design with 95% power to reject the null hypothesis (completion rate less than 60%), assuming a true completion rate of 80% using one-sided alpha=0.05. Results: All 54 pts were recruited between June 05 and June 06. Details for 44 pts are currently available for the C phase. 38% of these pts had one or more dose reduction (DR), and 68% had dose delays (DD). The commonest reason for DR and DD was neutropenia. Details for 33 pts are currently available for the P+G phase. 27% of these pts had a DR of P and 51% had a DR of G. 71% of pts omitted G on D8, and 64% had a DD. The commonest reasons for DR and DD were neutropenia and thrombocytopenia. Overall, the KM estimate of the percentage completing 8 cycles is 75% (95% CI 61%-89%) based on the current data. Dyspnoea (Grade 2 only) was observed in 4.5% and 3% pts during the C and P+G phases respectively. No significant treatment related CXR changes were observed. The overall response rate was 68% (95% CI 45–86%; 36% CR, 32%PR, 14% SD, 5%PD, 14% NE; n=22). The median follow-up is 7.5 months and the PFS at 8 months is 92% (95% CI 77–97%). Conclusion: This schedule appears to ameliorate the previously observed dyspnoea, while retaining comparable efficacy. The feasibility of this regimen is limited by myelosuppression which could potentially be overcome by: a) reducing the dose of gemcitabine to 750 mg/m 2 , or b) using prophylactic Peg-GCSF. [Table: see text]
Outcome of patients with locally advanced breast cancer (LABC) followed at the University of Cincinnati (UC)
Authors: R. S. Komrokji, Z. Nahleh, S. Dhaliwal, D. Sivasubramaniam
Journal: Journal of Clinical Oncology (2007)

21160 Background: LABC poses a difficult clinical challenge . The correlation of complete clinical (cCR) and pathological response rates (pCR) based on molecular tumor characteristics with outcome is of great clinical interest. Methods: We conducted a retrospective chart review on consecutive patients diagnosed with LABC who completed NC between 2001–2006 at UC. Pathological response was classified as pCR (no invasive tumor in breast and axillary lymph nodes), RDLN (disease in lymph nodes), RDB( disease in breast), and RDBLN (disease in both). Overall survival (OS)and event free survival (EFS) were calculated using Kaplan-Meier analysis. Result: We included 45 patients. Median age 51, 40% (n=18) white and 60% (n=27) African American, Stage IIB 9%, IIIA 29%, IIIB 51 % and IIIC 11%. 75 % invasive ductal, 9% invasive lobular and 16% inflammatory breast cancer (IBC). ER+/or PR+ in 47% (18% ER + / PR +, 27% ER +/PR -, 2% ER-/PR+), and 53% ER -/PR-. HER2 neu + ( IHC 3 + or FISH ratio &gt; 2.2) was identified in 27% of patients. NC regimens included: doxorubicin or epirubicine plus taxane (paclitaxel or docetaxel) 80 %, anthracycline only 10%, single agent taxane 4%, and 6% other regimens (2 CMF, 1 capecitabine). One patient received NC with trastuzumab. Response to NC was as follows: Clinically, 55% (n=25) achieved cCR, 38% partial clinical response, 4% stable disease and 2% progressive disease. Pathpogically, pCR was achieved in 22% (n=10) of all patients, 7% pPRLN, 24% pPRB and 47% RDBLN . None of the patients with IBC had pCR. Among ER+ and or PR + tumors , 19% achieved pCR compared to pCR of 25% among ER-/PR-. Among HER2 neu +, 17% achieved pCR compared to 25% in HER2 neu -. Among all patients who achieved cCR, only 36% actually had pCR. For patients who did not achieve pCR, OS and EFS were 5.7 years and 19 months respectively compared to both not yet reached for those with pCR. Conclusion: LABC has poor prognosis overall using standard chemotherapy. Clinical response followingNC was not well predictive of pathological response. ER-/PR - tumors respond better to neoadjuvant chemotherapy compared to ER+/orPR+ tumors. Less than 20% of HER2 neu + tumors achieve pCR before trastuzumab's routine use. More research is urgently needed to optimize treatment strategies and improve outcome of LABC and IBC. No significant financial relationships to disclose.
Application programming interfaces for knowledge transfer and generation in the life sciences and healthcare
Authors: Stephen K Woody, David Burdick, Hilmar Lapp, Erich S. Huang
Journal: npj Digital Medicine (2020)

Storing very large amounts of data and delivering them to researchers in an efficient, verifiable, and compliant manner, is one of the major challenges faced by health care providers and researchers in the life sciences. The electronic health record (EHR) at a hospital or clinic currently functions as a silo, and although EHRs contain rich and abundant information that could be used to understand, improve, and learn from care as part learning health system access to these data is difficult, and the technical, legal, ethical, and social barriers are significant. If we create a microservice ecosystem where data can be accessed through APIs, these challenges become easier to overcome: a service-driven design decouples data from clients. This decoupling provides flexibility: different users can write in their preferred language and use different clients depending on their needs. APIs can be written for iOS apps, web apps, or an R library, and this flexibility highlights the potential ecosystem-building power of APIs. In this article, we use two case studies to illustrate what it means to participate in and contribute to interconnected ecosystems that powers APIs in a healthcare systems.