tbuckley/cabot-search huggingface dataset:
Tumor immune microenvironment and nivolumab efficacy in EGFR mutation-positive non-small-cell lung cancer based on T790M status after disease progression during EGFR-TKI treatment
Authors: K. Haratani, H. Hayashi, T. Tanaka, H. Kaneda, Y. Togashi, K. Sakai, K. Hayashi, S. Tomida, Y. Chiba, K. Yonesaka, Y. Nonagase, T. Takahama, J. Tanizaki, K. Tanaka, T. Yoshida, K. Tanimura, M. Takeda, H. Yoshioka, T. Ishida, T. Mitsudomi, K. Nishio, K. Nakagawa
Journal: Annals of Oncology (2017)
Enhancing Insights into Pulmonary Vascular Disease through a Precision Medicine Approach. A Joint NHLBI–Cardiovascular Medical Research and Education Fund Workshop Report
Authors: John H. Newman, Stuart Rich, Steven H. Abman, John H. Alexander, John Barnard, Gerald J. Beck, Raymond L. Benza, Todd M. Bull, Stephen Y. Chan, Hyung J. Chun, Declan Doogan, Jocelyn Dupuis, Serpil C. Erzurum, Robert P. Frantz, Mark Geraci, Hunter Gillies, Mark Gladwin, Michael P. Gray, Anna R. Hemnes, Roy S. Herbst, Adrian F. Hernandez, Nicholas S. Hill, Evelyn M. Horn, Kendall Hunter, Zhi-Cheng Jing, Roger Johns, Sanjay Kaul, Steven M. Kawut, Tim Lahm, Jane A. Leopold, Greg D. Lewis, Stephen C. Mathai, Vallerie V. McLaughlin, Evangelos D. Michelakis, Steven D. Nathan, William Nichols, Grier Page, Marlene Rabinovitch, Jonathan Rich, Franz Rischard, Sharon Rounds, Sanjiv J. Shah, Victor F. Tapson, Naomi Lowy, Norman Stockbridge, Gail Weinmann, Lei Xiao
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Section:ChooseTop of pageAbstract <<Inadequacies of Therapy o...Why a Precision Medicine ...PVDOMICS, Linking Phenoty...The Role of Large Data An...Considerations in the Con...Considerations in the Des...The ChallengesSummary of Recommendation...ReferencesCITING ARTICLES
Symptom burden and survival outcome: 3 cycles versus 6 cycles of chemotherapy in advanced NSCLC
Authors: X. S. Wang, C. Lu, Q. Shi, D. Fariclough, G. Mobley, L. Palos, T. Mendoza, C. Cleeland
Journal: Journal of Clinical Oncology (2007)

17054 Background: Improving survival and quality of life is the primary treatment goal for patient with advanced NSCLC receiving palliative chemotherapy. The optimal treatment duration remains to be determined, and there are few studies that examine longitudinal symptom burden in this population. Methods: We prospectively collected self-reported symptom data from advanced stage NSCLC patients receiving chemotherapy. Symptom data was collected weekly utilizing the MD Anderson Symptom Inventory (15 symptoms) pre chemotherapy until therapy discontinuation or up to 26 weeks. Principal components analysis of symptoms measures with a Varimax rotation were used to identify symptom clusters. A piecewise linear mixed-effect regression model was used to estimate the changes over time in symptom severity, and Cox modeling was used for data analysis. Results: Data from 102 subjects were available for analysis. Chemotherapy was primarily discontinued because of tumor progression or a decline in the patient's functional status. Seventy patients received only 2 cycles of chemotherapy, while 46 and 29 patients received 4 and 6 cycles of chemotherapy, respectively. Four clusters of symptoms were identified prior to therapy, including: general symptoms (such as pain, fatigue, sleeping disturbance), GI distress (nausea, vomiting, lack of appetite &amp; constipation), affective symptoms (sadness &amp; distress) and specific disease related symptoms (coughing &amp; shortness of breath). In patients who received = 3 cycles of chemotherapy, a rapid increased in symptom severity was observed, compared to those who received &gt; 3 cycles (P&lt;.05). Patients who received =3 cycles of chemotherapy demonstrated shorter survival compared to those who received &gt; 3 of chemotherapy (HR=9.9, CI=4–22.7, P&lt;.001). Conclusion: Patients with advanced NSCLC who received more than 3 cycles of chemotherapy demonstrated more stable symptom burden and longer survival compared to those who received = 3 cycles of chemotherapy. No significant financial relationships to disclose.
Abstract P288: ATP Signaling Stimulates Fibroblast Activation: The Role of Pannexin1 Channels in Fibrosis
Authors: Heather S Duffy, Elena Dolmatova, Jennifer Baum, Kimberly Keith, Daniella Boassa, Gina Sosinsky, Maria I Kontaridis
Journal: Circulation Research (2011)

BACKGROUND-We have shown that Pannexin1 (Panx1), a novel ATP channel, is found in ventricular cardiac myocytes and upregulated on myocyte sarcolemmal membranes during acute ischemia. We hypothesize that the channel is part of a protein complex that plays a role in downstream cell signaling post myocardial infarction (MI). METHODS-Using a canine model of MI, where the left anterior descending coronary artery is occluded (CO) we examined epicardial tissue from hearts subjected to 0–3 hrs of CO. Immunoprecipitation (IP) with subsequent silver stain studies revealed novel binding partners for Panx1. Co-immunoprecipitation studies (Co-IP) were performed to confirm Panx1 binding partners. In vitro dye uptake studies and ATP assays were used to determine the function of Panx1 channels under hypoxic conditions. RESULTS-IP followed by silver staining revealed multiple potential binding partners for Panx1 in the heart. Following 3 hrs CO some interactions increased while others decreased. Co-immunoprecipitation identified one of these partners for Panx1 as the MAGUK scaffolding protein SAP97, an interaction that is significantly increased following 3 hr CO (n=3, p&lt;0.05). Immunostaining showed that CO increased trafficking and stabilization of Panx1 channels at the cell membranes. In vitro dye uptake studies show that cells increase dye uptake following hypoxia, an event that is blocked by the Panx1 channel blocker, Probenecid. Hypoxia also causes increased ATP release likely due to opening of Panx1 channels. ATP release activated fibroblasts and stimulated early fibrosis signaling. CONCLUSIONS-Our data show the presence of a Panx1 protein complex in cardiac myocytes that is scaffolded at the cell membranes by SAP97. Under cellular stress Panx1 channels release ATP to induce early fibrotic events. We We conclude that Panx1 plays a key functional role in ATP signaling and formation of fibrosis in the post-MI heart.
Dose-Adjusted EPOCH Chemotherapy for Untreated Peripheral T-Cell Lymphomas: Multicenter Phase II Trial of West-Jhog PTCL0707
Authors: Yoshinobu Maeda, Hisakazu Nishimori, Yasushi Hiramatsu, Isao Yoshida, Masatoshi Uno, Yasufumi Masaki, Kazutaka Sunami, Taro Masunari, Yuichiro Nawa, Hiroshi Gomyo, Hiromichi Yamane, Tsutomu Takahashi, Tomofumi Yano, Hidetaka Takimoto, Keitaro Matsuo, Tadashi Yoshino, Mitsune Tanimoto
Journal: Blood (2016)
INTRINSIC AND EXTRINSIC INJURY RISK FACTORS OF ELITE WINTER SPORTS ATHLETE IN TRAINING
Authors: Victor Wang, Frank Mayer, Klaus Bonaventura, Maria Wippert
Journal: British Journal of Sports Medicine (2017)

Background Multi-factorial sport injury related models are well accepted for sport medicine scientists and experts. However, injury risk factors research involved with winter sport athletes seems not well documented due to its complicated, interactive intrinsic and extrinsic factors. Objective To exam the significant difference and correlation relationships between injury outcomes and winter sport elite athletes' intrinsic and extrinsic risk factors. Design and Setting A cross-section and retrospective risk of injury questionnaire (Risk-IQ) designed for elite athlete in training period was employed. Currently active and retired national delegation athletes of Olympic winter sports were recruited. Participants 34 winter Olympic sport elite athletes (f/m 13/21 age=28.9+-7.7) were recruited from national sport training centres, sport federations and universities fron both Germany and Taiwan. Assessment of Risk Factors Potential risk for athletic accumulated injuries were assessed through 6 intrinsic (age, gender, experience, stress, cardiovascular problems and importance of risk screening) and 6 extrinsic (nation, sport type, training environment, periodic health examination(PHE)/preparticipation evaluation (PPE), physical complains, medical care support) factors. Kruskal-Wallis test, Mann-Whitney U test and Spearmann correlation test were used. Main Outcome Measurements The total sport training related injury incidences were planned as outcome measurements. The adapted intrinsic and extrinsic injury related risk factors were tested for significance difference and correlations. Results Significant results were found in intrinsic factors: age (10 body-part p&lt;0.01; back &amp; chest p&lt;0.01; shoulder &amp; arm p&lt;0.01, elbow &amp; hand p&lt;0.01; hip &amp; thigh p&lt;0.01; knee p&lt;0.05), stress level (knee r=0.348 p&lt;0.05, foot &amp; toe r=0.404 p&lt;0.05); in extrinsic factors: nation (p&lt;0.01), sport type(Olympic), PHE screen(back p&lt;0.05, physical complain on knee(r=0.355, p&lt;0.05l leg &amp; ankle r=0.487 p&lt;0.01) and foot (elbow &amp; hand r=0.386, p&lt;0.05). Conclusions Some factors showed their significant results with body-part specificity (only some body-parts but not others) which deserved further detailed investigation with greater subject population.
Analysis of a neoadjuvant regimen with a fixed dose of doxorubicin followed by a 10-day course of 27 Gy radiation in the treatment of soft tissue sarcoma (STS) of the extremity/trunk.
Authors: John Mathews, Gerhard Maale, Donald E. Schwarz, James Fredric Strauss, Mark Feldman, Juan G. Posada, Ashwini Bhat
Journal: Journal of Clinical Oncology (2012)

10037 Background: Local tumor control and preservation of limb function are major goals of treatment of STS. With current standard of combining limb-sparing surgery and 5-6 weeks of neoadjuvant or adjuvant 50-65 Gy radiation, reducing local recurrence has been a challenge with rates of 15-30%. Eilber et al. (Cancer Treatment Symposia 1985; 3:49-57) used a fixed daily dose of doxorubicin for three days with radiation of 35Gy. This yielded a 5% local recurrence, while wound complication rate was 35 %. We reduced the radiation dose to lower the wound complications rate. We report a cohort of patients treated in this manner at our institution. Methods: After a baseline echocardiogram, patients received a radiosensitizing dose of intravenous doxorubicin (30mg/day) for 3 consecutive days, then radiation with 2.7 Gy in 10 fractions, followed by limb sparing surgery. After IRB approval, we retrospectively analyzed records of 191 patients during the treatment period from 1991 to 2010. Data extracted included local tumor recurrences and wound complications defined as non-healed wound at 1 month, number of limb salvage surgeries and involvement of surgical margins. Results: Of the 191 patients, median age was 53 (range, 13-89). Stages at presentation included I, II, III and IV, with 2%, 33%, 61%, 4% respectively. The median follow up was 5 years. Of the 24 types of sarcomas treated, pleomorphic sarcoma was the most common at 21%. The local recurrence rate was 5% (95% CI, 2.7-8.6%) and local wound complications were 21% (95% CI, 15-28%). Most (172 or 90%) of patients were able to undergo limb salvage surgery while 19 (10%) required amputation. Of the 172 patients that had limb salvage, 97% (95% CI, 93-98%) had wide surgical margins, three had &lt; 2 cm margins and two had involved margins. Conclusions: To our knowledge, this is the largest study showing that this short two week course of chemoradiation is effective in achieving high rate of local control, acceptable wound complication rate, wide surgical margins and limb salvage in the treatment of STS. Randomized trials are warranted to confirm results.
Low-dose ionizing radiation induces therapeutic neovascularization in a pre-clinical model of hindlimb ischemia
Authors: Augusto Ministro, Paula de Oliveira, Raquel J. Nunes, André dos Santos Rocha, Adriana Correia, Tânia Carvalho, José Rino, Pedro Faísca, Jorg D. Becker, João Goyri-O’Neill, Filomena Pina, Esmeralda Poli, Bruno Silva-Santos, Fausto Pinto, Marc Mareel, Karine Serre, Susana Constantino Rosa Santos
Journal: Cardiovascular Research (2017)

We have previously shown that low-dose ionizing radiation (LDIR) induces angiogenesis but there is no evidence that it induces neovascularization in the setting of peripheral arterial disease. Here, we investigated the use of LDIR as an innovative and non-invasive strategy to stimulate therapeutic neovascularization using a model of experimentally induced hindlimb ischemia (HLI).After surgical induction of unilateral HLI, both hindlimbs of female C57BL/6 mice were sham-irradiated or irradiated with four daily fractions of 0.3 Gy, in consecutive days and allowed to recover. We demonstrate that LDIR, significantly improved blood perfusion in the murine ischemic limb by stimulating neovascularization, as assessed by laser Doppler flow, capillary density, and collateral vessel formation. LDIR significantly increased the circulating levels of VEGF, PlGF, and G-CSF, as well as the number of circulating endothelial progenitor cells (EPCs) mediating their incorporation to ischemic muscles. These effects were dependent upon LDIR exposition on the ischemic niche (thigh and shank regions). In irradiated ischemic muscles, these effects were independent of the recruitment of monocytes and macrophages. Importantly, LDIR induced a durable and simultaneous up-regulation of a repertoire of pro-angiogenic factors and their receptors in endothelial cells (ECs), as evident in ECs isolated from the irradiated gastrocnemius muscles by laser capture microdissection. This specific mechanism was mediated via vascular endothelial growth factor (VEGF) receptor signaling, since VEGF receptor inhibition abrogated the LDIR-mediated gene up-regulation and impeded the increase in capillary density. Finally, the vasculature in an irradiated non-ischemic bed was not affected and after 52 week of LDIR exposure no differences in the incidence of morbidity and mortality were seen.These findings disclose an innovative, non-invasive strategy to induce therapeutic neovascularization in a mouse model of HLI, emerging as a novel approach in the treatment of critical limb ischemia patients.
Risankizumab versus Ustekinumab for Moderate-to-Severe Plaque Psoriasis
Authors: Kim A. Papp, Andrew Blauvelt, Michael Bukhalo, Melinda Gooderham, James G. Krueger, Jean-Philippe Lacour, Alan Menter, Sandra Philipp, Howard Sofen, Stephen Tyring, Beate R. Berner, Sudha Visvanathan, Chandrasena Pamulapati, Nathan Bennett, Mary Flack, Paul Scholl, Steven J. Padula
Journal: New England Journal of Medicine (2017)

Interleukin-23 is thought to be critical to the pathogenesis of psoriasis. We compared risankizumab (BI 655066), a humanized IgG1 monoclonal antibody that inhibits interleukin-23 by specifically targeting the p19 subunit and thus prevents interleukin-23 signaling, and ustekinumab, an interleukin-12 and interleukin-23 inhibitor, in patients with moderate-to-severe plaque psoriasis.We randomly assigned a total of 166 patients to receive subcutaneous injections of risankizumab (a single 18-mg dose at week 0 or 90-mg or 180-mg doses at weeks 0, 4, and 16) or ustekinumab (45 or 90 mg, according to body weight, at weeks 0, 4, and 16). The primary end point was a 90% or greater reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 12.At week 12, the percentage of patients with a 90% or greater reduction in the PASI score was 77% (64 of 83 patients) for risankizumab (90-mg and 180-mg groups, pooled), as compared with 40% (16 of 40 patients) for ustekinumab (P<0.001); the percentage of patients with a 100% reduction in the PASI score was 45% in the pooled 90-mg and 180-mg risankizumab groups, as compared with 18% in the ustekinumab group. Efficacy was generally maintained up to 20 weeks after the final dose of 90 or 180 mg of risankizumab. In the 18-mg and 90-mg risankizumab groups and the ustekinumab group, 5 patients (12%), 6 patients (15%), and 3 patients (8%), respectively, had serious adverse events, including two basal-cell carcinomas and one major cardiovascular adverse event; there were no serious adverse events in the 180-mg risankizumab group.In this phase 2 trial, selective blockade of interleukin-23 with risankizumab was associated with clinical responses superior to those associated with ustekinumab. This trial was not large enough or of long enough duration to draw conclusions about safety. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number, NCT02054481 ).
Which personal qualities do cancer patients value the most in their clinical oncologists?
Authors: Ernesto Gil Deza, Gaston Martin Reinas, Daniela Gercovich, Eduardo L. Morgenfeld, Flavio Tognelli, Monica Montiel, Carlos Fernando Garcia Gerardi, Edgardo G. J. Rivarola, Felipe G. Gercovich
Journal: Journal of Clinical Oncology (2013)

e20636 Background: In the History of medicine, the most desired qualities in a doctor have changed over time. The objective of the following paper is to analyze which qualities do our patients (Pt) consider most important in their doctors. Methods: Between Oct 15 th and Nov 15 th , 2012, 1003 out of 3,795 Pt who were assisted at the IOHM were given the option to partake in an anonymous survey which evaluated the qualities they valued the most in their doctor, such as: knowledge, experience, honesty, sympathy, availability, humility, humanity or other. Each Pt was asked to pick the three they thought most important. Answers were gathered and analyzed according to frequency distribution. Results: A total of 845 out of 1003 (84%) Pt elected to participate. Population characteristics: Sex: fem: 332, male: 207, left blank (LB): 306. Mean age 58y (range 18 – 94). Married: 355, unmarried: 211, LB: 279. Children: Yes 460 No/LB: 385. Highest educational level achieved: primary studies:186, high school: 348, university: 216. LB: 98. Employed: 382, retired: 240, unemployed: 112, LB 111. The following results are expressed as a percentage of 845 Pt. The most valued qualities in a doctor were: knowledge (51%), honesty (44%), humanity (43%), availability (32%), experience (31%), humility (19%), sympathy (18%), others (3%). Although the most important quality was always knowledge, there was a marked difference between sexes: women valued humanity more than honesty (Chi square p=0.001) while men believed honesty (Chi square p=0.001) and experience (Chi square= 0.01) were more important than humanity. Conclusions: These results showed that there is no set of qualities that is valued above all others. Even though knowledge was always the most important, the value of the other six characteristics depends in great measure from the individual condition of the patients (such as sex, age and stage of the disease). However as the Pt usually do not have the skills to evaluate the Dr’s knowledge, honesty and humanity remains the most valued personal conditions.
Guideline: In type 2 diabetes, ACP recommends metformin monotherapy if drugs are needed for glycemic control
Authors: René Rodriguez-Gutierrez, Victor M. Montori
Journal: Annals of Internal Medicine (2017)

Source Citation Qaseem A, Barry MJ, Humphrey LL, Forciea MA, Clinical Guidelines Committee of the American College of Physicians. Oral pharmacologic treatment of type 2 diabetes mellitus: a clinical practice guideline update from the American College of Physicians. Ann Intern Med. 2017;166:279-90. 28055075
Immune Cell Recruitment: Mechanically Enhanced Hierarchically Porous Scaffold Composed of Mesoporous Silica for Host Immune Cell Recruitment (Adv. Healthcare Mater. 8/2017)
Authors: Youngjin Choi, Ji Hoon Jeong, Jaeyun Kim
Journal: Advanced Healthcare Materials (2017)

Recruiting immune cells (green) to subcutaneously-implanted hierarchical macroporous and mesoporous silica scaffold is described by Jaeyun Kim and co-workers in article number 1601160. The magnification of scaffold indicates that the scaffold is composed of mesoporous silica microparticles, which is releasing pro-inflammatory signals (red dot) to recruit host immune cells.
Adhesion-induced eosinophil cytolysis requires the receptor-interacting protein kinase 3 (RIPK3)–mixed lineage kinase-like (MLKL) signaling pathway, which is counterregulated by autophagy
Authors: Susanne Radonjic-Hoesli, Xiaoliang Wang, Elisabeth de Graauw, Christina Stoeckle, Beata Styp-Rekowska, Ruslan Hlushchuk, Dagmar Simon, Peter J. Spaeth, Shida Yousefi, Hans-Uwe Simon
Journal: Journal of Allergy and Clinical Immunology (2017)
Efficacy of Human Fibrinogen Concentrate for on-Demand Treatment of Acute Bleeding and to Prevent Bleeding during and after Surgery in Subjects with Congenital Fibrinogen Deficiency
Authors: Bruce A. Schwartz, Cecil Ross, Bella Madan, Toshko Jelev Lissitchkov, Mehran Karimi, Sigurd Knaub, Flora Peyvandi
Journal: Blood (2016)
Randomized Trial Comparing a Web-Mediated Follow-up With Routine Surveillance in Lung Cancer Patients
Authors: Fabrice Denis, Claire Lethrosne, Nicolas Pourel, Olivier Molinier, Yoann Pointreau, Julien Domont, Hugues Bourgeois, Hélène Senellart, Pierre Trémolières, Thibaut Lizée, Jaafar Bennouna, Thierry Urban, Claude El Khouri, Alexandre Charron, Anne-Lise Septans, Magali Balavoine, Sébastien Landry, Philippe Solal-Céligny, Christophe Letellier
Journal: JNCI Journal of the National Cancer Institute (2017)

The use of web-based monitoring for lung cancer patients is growing in interest because of promising recent results suggesting improvement in cancer and resource utilization outcomes. It remains an open question whether the overall survival (OS) in these patients could be improved by using a web-mediated follow-up rather than classical scheduled follow-up and imaging.Advanced-stage lung cancer patients without evidence of disease progression after or during initial treatment were randomly assigned in a multicenter phase III trial to compare a web-mediated follow-up algorithm (experimental arm), based on weekly self-scored patient symptoms, with routine follow-up with CT scans scheduled every three to six months according to the disease stage (control arm). In the experimental arm, an alert email was automatically sent to the oncologist when self-scored symptoms matched predefined criteria. The primary outcome was OS.From June 2014 to January 2016, 133 patients were enrolled and 121 were retained in the intent-to-treat analysis; 12 deemed ineligible after random assignment were not subsequently followed. Most of the patients (95.1%) had stage III or IV disease. The median follow-up was nine months. The median OS was 19.0 months (95% confidence interval [CI] = 12.5 to noncalculable) in the experimental and 12.0 months (95% CI = 8.6 to 16.4) in the control arm (one-sided P = .001) (hazard ratio = 0.32, 95% CI = 0.15 to 0.67, one-sided P = .002). The performance status at first detected relapse was 0 to 1 for 75.9% of the patients in the experimental arm and for 32.5% of those in the control arm (two-sided P < .001). Optimal treatment was initiated in 72.4% of the patients in the experimental arm and in 32.5% of those in the control arm (two-sided P < .001).A web-mediated follow-up algorithm based on self-reported symptoms improved OS due to early relapse detection and better performance status at relapse.