tbuckley/cabot-search huggingface dataset:
Correlation between WT1 Levels and Chimeric Transcripts in Core Binding Factor AML: Discrepancies Are Not Uncommon AML1-ETO Leukemias.
Authors: Adriana Lasa, Maite Carricondo, Daniela Cilloni, Salut Brunet, Anna M. Aventin, Jorge Sierra, Josep F. Nomdedeu
Journal: Blood (2006)
Intravital evaluation of time-course efficacy of anticancer drugs on colorectal liver metastases in the same living mice using two-photon laser scanning microscopy.
Authors: K. Tanaka, Y. Morimoto, Y. Toiyama, S. Saigusa, Y. Okugawa, Y. Inoue, K. Uchida, K. Matsushita, M. Kawamura, A. Mizoguchi, M. Kusunoki
Journal: Journal of Clinical Oncology (2011)

10621 Background: There is a significant site-specific variation in response to chemotherapy for human solid tumors. Whether subcutaneous non-metastatic xenograft models are representative of clinically metastatic disease remains an unanswered question. Metastatic xenograft models may be ideal and practical for preclinical anti-cancer drug evaluation. We evaluated intravitally the time-course efficacy of anti-cancer drugs at the metastatic site in the same living mice using two-photon laser scanning microscopy (TPLSM). Methods: Red fluorescent protein expressing human colorectal cancer cell line (HT29) was inoculated to the spleen of green fluorescent protein expressing mice for experimental liver metastasis models. 5-fluorouracil (50 mg/kg) or irinotecan (20 mg/kg) was administered intraperitoneally three times a week for three weeks after the confirmation of macroscopic liver metastases. TPLSM was used for intravital visualization of treatment efficacy at a magnification of over 600×. Intravital TPLSM was performed by exteriorizing and fixing the liver lobe of living mice. This procedure was repeated several times for the time-course imaging of treatment efficacy on liver metastases in the same mice. Results: Approximately eight weeks later, HT29 cells formed macroscopic liver metastases. Under the first TPLSM, micrometastatic nodules consisting of viable cancer cells (red) and surrounding stroma with tumor vessels (green) were visualized in the living liver of living mice. After anti-cancer drug treatment, morphologic change of micrometastatic nodules was observed in the same mouse under the second TPLSM. The fragmentation of cancer cells surrounding residual metastatic colonies was visualized three-dimentionally. There was no apparant morphological difference in tumor responsiveness on liver metastases between 5-fluorouracil and irinotecan. Conclusions: Intravital time-course visualization of treatment efficacy in the same mouse using metastatic xenograft model under TLPSM could be ideal and practical for screening and evaluating new anti-cancer drugs with less interindividual variability.
Megalin Blockade with Cilastatin Suppresses Drug-Induced Nephrotoxicity
Authors: Yoshihisa Hori, Nobumasa Aoki, Shoji Kuwahara, Michihiro Hosojima, Ryohei Kaseda, Sawako Goto, Tomomichi Iida, Shankhajit De, Hideyuki Kabasawa, Reika Kaneko, Hiroyuki Aoki, Yoshinari Tanabe, Hiroshi Kagamu, Ichiei Narita, Toshiaki Kikuchi, Akihiko Saito
Journal: Journal of the American Society of Nephrology (2017)

Nephrotoxicity induced by antimicrobial or anticancer drugs is a serious clinical problem. Megalin, an endocytic receptor expressed at the apical membranes of proximal tubules, mediates the nephrotoxicity of aminoglycosides and colistin, key antimicrobials for multidrug-resistant organisms. The mechanisms underlying the nephrotoxicity induced by vancomycin, an antimicrobial for methicillin-resistant Staphylococcus aureus, and cisplatin, an important anticancer drug, are unknown, although the nephrotoxicity of these drugs and gentamicin, an aminoglycoside, is suppressed experimentally with cilastatin. In the clinical setting, cilastatin has been used safely to suppress dehydropeptidase-I-mediated renal metabolism of imipenem, a carbapenem antimicrobial, and thereby limit tubular injury. Here, we tested the hypothesis that cilastatin also blocks megalin-mediated uptake of vancomycin, cisplatin, colistin, and aminoglycosides, thereby limiting the nephrotoxicity of these drugs. Quartz crystal microbalance analysis showed that megalin also binds vancomycin and cisplatin and that cilastatin competes with megalin for binding to gentamicin, colistin, vancomycin, and cisplatin. In kidney-specific mosaic megalin knockout mice treated with colistin, vancomycin, or cisplatin, the megalin-replete proximal tubule epithelial cells exhibited signs of injury, whereas the megalin-deficient cells did not. Furthermore, concomitant cilastatin administration suppressed colistin-induced nephrotoxicity in C57BL/6J mice. Notably, cilastatin did not inhibit the antibacterial activity of gentamicin, colistin, or vancomycin in vitro, just as cilastatin did not affect the anticancer activity of cisplatin in previous studies. In conclusion, megalin blockade with cilastatin efficiently suppresses the nephrotoxicity induced by gentamicin, colistin, vancomycin, or cisplatin. Cilastatin may be a promising agent for inhibiting various forms of drug-induced nephrotoxicity mediated via megalin in the clinical setting.
P2.05-025 9-Year Experience: Prophylactic Cranial Irradiation in Extensive Disease Small-Cell Lung Cancer
Authors: Denise Bernhardt, Sebastian Adeberg, Farastuk Bozorgmehr, Juliane Hoerner-Rieber, Jutta Kappes, Michael Thomas, Helge Bischoff, Felix Jf Herth, Claus Heussel, Jürgen Debus, Martin Steins, Stefan Rieken
Journal: Journal of Thoracic Oncology (2017)
High Aldehyde Dehydrogenase Activity (ALDH) Is a General Marker for Normal Hematopoietic Stem Cells but Not Leukemic Stem Cells in Acute Myeloid Leukemia (AML). .
Authors: Linda Smit, Lisa A Min, Monique Terwijn, Angele Kelder, Alexander N Snel, Gert J Ossenkoppele, Gerrit J. Schuurhuis
Journal: Blood (2009)
S5 Vitamin d for the management of asthma: cochrane systematic review and meta-analysis
Authors: AR Martineau, CJ Cates, M Urashima, M Jensen, AP Griffiths, U Nurmatov, A Sheikh, CJ Griffiths
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> Several clinical trials of vitamin D to prevent asthma exacerbation and improve asthma control have been conducted in children and adults, but a meta-analysis restricted to double-blind randomised placebo-controlled trials of this intervention is lacking. We conducted a Cochrane systematic review and meta-analysis to evaluate the efficacy of administration of vitamin D in reducing asthma exacerbations treated with systemic corticosteroids (primary outcome) and improving asthma symptom control. <h3>Methods</h3> Standard Cochrane collaboration procedures were followed. Double-blind randomised placebo-controlled trials of vitamin D in children and adults with asthma evaluating exacerbation risk and/or asthma symptom control were included. <h3>Results</h3> Seven trials involving a total of 435 children and two trials involving a total of 658 adults were included in the primary analysis. Administration of vitamin D reduced the rate of exacerbations requiring systemic corticosteroids (Rate Ratio 0.63, 95% CI: 0.45 to 0.88; 680 participants; 3 studies; high quality evidence), and decreased the risk of having at least one exacerbation requiring an emergency department visit and/or hospitalisation (Odds Ratio [OR] 0.39, 95% CI: 0.19 to 0.78; number needed to treat for one additional person to experience a beneficial outcome (NNTB), 27; 963 participants; 7 studies; high quality evidence). There was no effect of vitamin D on % predicted forced expiratory volume in one second (Mean Difference [MD] 0.48, 95% CI: −0.93 to 1.89; 387 participants; 4 studies; high quality evidence) or Asthma Control Test scores (MD −0.08, 95% CI: −0.70 to 0.54; participants = 713; studies = 3; high quality evidence). Administration of vitamin D did not influence the risk of serious adverse events (OR 1.01, 95% CI: 0.54 to 1.89; 879 participants; 5 studies; moderate quality evidence). No participant in any included trial suffered a fatal asthma exacerbation. <h3>Conclusions</h3> Meta-analysis of a modest number of trials in patients with predominantly mild to moderate asthma suggests that vitamin D is likely to reduce the risk of severe asthma exacerbation and reduce health care use.
MA01.06 Long-Term Follow-Up of Small Pulmonary Ground-Glass Nodules Stable for 3 Years: Proper Follow-Up Period and Risk Factors for Subsequent Growth
Authors: Jaeyoung Cho, Eun Sun Kim, Se Joong Kim, Yeon Joo Lee, Jong Sun Park, Young-Jae Cho, Ho Il Yoon, Jae Ho Lee, Choon-Taek Lee
Journal: Journal of Thoracic Oncology (2017)
Treatment of Zebrafish Models of Ribosomopathies (Diamond Blackfan Anemia (DBA) and 5q- Syndrome) with L-Leucine Results In An Improvement of Anemia and Developmental Defects: Evidence for a Common Pathway?
Authors: Maria Virgilio, Elspeth Payne, Anupama Narla, Hong Sun, Barry Paw, A. Thomas Look, Benjamin L. Ebert, Nancy Berliner, Arati Khanna-Gupta
Journal: Blood (2010)
P1.05-056 Increased Risk of Postoperative Recurrence in EGFR-Positive Stage IA to IB Invasive Lung Adenocarcinoma
Authors: Masaoki Ito, Yoshihiro Miyata, Kei Kushitani, Tomoharu Yoshiya, Yasuhiro Tsutani, Kazuo Konishi, Yukio Takeshima, Morihito Okada
Journal: Journal of Thoracic Oncology (2017)
‘Tagging’ along memories in aging: Synaptic tagging and capture mechanisms in the aged hippocampus
Authors: Mahesh Shivarama Shetty, Sreedharan Sajikumar
Journal: Ageing Research Reviews (2017)

Aging is accompanied by a general decline in the physiological functions of the body with the deteriorating organ systems. Brain is no exception to this and deficits in cognitive functions are quite common in advanced aging. Though a variety of age-related alterations are observed in the structure and function throughout the brain, certain regions show selective vulnerability. Medial temporal lobe, especially the hippocampus, is one such preferentially vulnerable region and is a crucial structure involved in the learning and long-term memory functions. Hippocampal synaptic plasticity, such as long-term potentiation (LTP) and depression (LTD), are candidate cellular correlates of learning and memory and alterations in these properties have been well documented in aging. A related phenomenon called synaptic tagging and capture (STC) has been proposed as a mechanism for cellular memory consolidation and to account for temporal association of memories. Mounting evidences from behavioral settings suggest that STC could be a physiological phenomenon. In this article, we review the recent data concerning STC and provide a framework for how alterations in STC-related mechanisms could contribute to the age-associated memory impairments. The enormity of impairment in learning and memory functions demands an understanding of age-associated memory deficits at the fundamental level given its impact in the everyday tasks, thereby in the quality of life. Such an understanding is also crucial for designing interventions and preventive measures for successful brain aging.
MA14.01 Updated Dataset Assessing Tumor Mutation Burden (TMB) as a Biomarker for Response to PD-1/PD-L1 Targeted Therapies in Lung Cancer (LC)
Authors: Alexa Schrock, Neelesh Sharma, Nir Peled, Jose Bufill, Gordan Srkalovic, David Spigel, David Fabrizio, Garrett Frampton, Caitlin Connelly, Mary Beth Lipka, Anna Belilovski, Jun Lo, Yali Li, James Sun, Kyle Gowen, Gregory Kalemkerian, Luis Raez, Sai-Hong Ou, Jeffrey Ross, Philip Stephens, Siraj Ali, Vincent Miller
Journal: Journal of Thoracic Oncology (2017)
Cytoreductive Therapeutic Approach in the Essential Thrombocythemia (ET) Patients of the Registro Italiano Trombocitemia (RIT): Preliminary Data
Authors: Luigi Gugliotta, Alessia Tieghi, Anna Candoni, Monia Lunghi, Gianluca Gaidano, Francesco Passamonti, Elisa Rumi, Alfredo Dragani, Franca Radaelli, Alessandra Iurlo, Giorgina Specchia, Paola Carluccio, Potito Rosario Scalzulli, Lorella Melillo, Vincenzo Martinelli, Rosanna Ciancia, Maria Luigia Randi, Alessandro Vannucchi, Elisabetta Antonioli, Ercole De Biasi, Fausto Palmieri, Roberto Latagliata, Cristina Santoro, Anna Marina Liberati, Marta Gubbiotti, Serena Rupoli, Anna Rita Scortechini, Maria Rosaria Villa, Rossella R Cacciola, Emma Cacciola, Ivana Pierri, Marzia Salvucci, Claudio Cristofalo, Daniela Cilloni, Nicola Vianelli, Augusto B. Federici, Anna Falanga, Marco Ruggeri
Journal: Blood (2008)
P2.01-004 The Methylation Profiling of Multiple Tumor Suppressor Genes in Plasma Cell-Free DNA of Patients with NSCLC vs Benign Tumors
Authors: Mateusz Florczuk, Adam Szpechcinski, Monika Gos, Renata Langfort, Michal Komorowski, Aleksandra Landowska, Dorota Giedronowicz, Wlodzimierz Kupis, Piotr Rudzinski, Jolanta Zaleska, Tadeusz Orlowski, Kazimierz Roszkowski-Sliz, Joanna Chorostowska-Wynimko
Journal: Journal of Thoracic Oncology (2017)
Defective γδ T-Cell Function and Granzyme B Gene Polymorphism in Newly Diagnosed Breast Care Patients. Expansion with Zoledronic Acid Partially Compensates for This Deficiency.
Authors: Ameera Gaafar, Abdulla Al-Sulaiman, Alia Iqniebi, Adher Al-Sayed, Entezam Sahovic, Naeem A. Chaudhri, Fahad Al-Mohareb, Dahish Ajarim, Abdelghani Tbakhi, Kkaled Al-Hussein, Mahmoud Aljurf
Journal: Blood (2006)
Neutrophils from Cystic Fibrosis Patients Are Defective in Killing of Phagocytosed Pseudomonas aeruginosa.
Authors: Guoshun Wang, Vincent G. Valentine, Nicholas A. Lanson, Kevin Leidal, Qiang Zhang, Gisele Lombard, Connie Thompson, Anand Viswanathan, William M. Nauseef, Guangdi Wang, Richard G. Painter
Journal: Blood (2006)
Evaluation of MAPK and PI3K/AKT Signaling Pathways In Adult Acute Lymphoblastic Leukemia
Authors: Gustavo Loureiro, Daniella Bahia Kerbauy, Maria de Lourdes, L. F. Chauffaille, Maria Lucia M. Lee, Franciele B. M. Candido, Marçal C.A Silva, Eliza Y. S. Kimura, Fabio P. Guirao, Denise C. Rezende, Mihoko Yamamoto
Journal: Blood (2010)
Molecular Characterization in Two Families Bearing Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD) IN Rosario, Argentina.
Authors: Irma del Luján, Susana Mabel SMP Pérez, Sabrina SB Botta, Virginia VR Rescia, Mauro MD Davoli, Angela Cristina ACM Milani
Journal: Blood (2009)
A Generative Angular Model of Protein Structure Evolution
Authors: Michael Golden, Eduardo García-Portugués, Michael Sørensen, Kanti V. Mardia, Thomas Hamelryck, Jotun Hein
Journal: Molecular Biology and Evolution (2017)

Recently described stochastic models of protein evolution have demonstrated that the inclusion of structural information in addition to amino acid sequences leads to a more reliable estimation of evolutionary parameters. We present a generative, evolutionary model of protein structure and sequence that is valid on a local length scale. The model concerns the local dependencies between sequence and structure evolution in a pair of homologous proteins. The evolutionary trajectory between the two structures in the protein pair is treated as a random walk in dihedral angle space, which is modelled using a novel angular diffusion process on the two-dimensional torus. Coupling sequence and structure evolution in our model allows for modelling both "smooth" conformational changes and "catastrophic" conformational jumps, conditioned on the amino acid changes. The model has interpretable parameters and is comparatively more realistic than previous stochastic models, providing new insights into the relationship between sequence and structure evolution. For example, using the trained model we were able to identify an apparent sequence-structure evolutionary motif present in a large number of homologous protein pairs. The generative nature of our model enables us to evaluate its validity and its ability to simulate aspects of protein evolution conditioned on an amino acid sequence, a related amino acid sequence, a related structure or any combination thereof.
P178 Childhood asthma management in primary care: implementation of nitric oxide and spirometry (champions) study. preliminary findings
Authors: DKH Lo, A Wilson, B Gaillard, D Rowland, C Beardsmore, E Gaillard
Journal: Thorax (2016)

<h3>Introduction</h3> Despite the common nature of asthma there is no gold standard test for diagnosis. Both under- and over-diagnosis of childhood asthma in primary care have been reported but there is no UK data.<sup>1,2</sup> Diagnostic algorithms including objective tests have been proposed but not implemented following a recent NICE consultation. Concerns regarding efficacy and additional resources needed in primary care to provide these tests have delayed implementation. <h3>Aims</h3> Evaluate practice based barriers to spirometry and exhaled nitric oxide (eNO) testing in children aged 5–16 years Examine how training impacts on the utilisation of objective tests on asthma diagnosis <h3>Methods</h3> Currently 3 GP surgeries of different sizes and demographics participate in this 2-year project. Initial face-to-face (F2F) meetings and questionnaires are conducted at each practice to identify barriers to implementation. Paediatric spirometry and eNO training is provided to practice staff (F2F theory session plus practical supervision). All children on the practice asthma register AND those who received asthma medications within the last 12 months (but not on register) are invited for review. Data collection (medications, exacerbations, asthma diagnosis etc.) and quality of life questionnaires are conducted at baseline and then again at 6 months by post and repeat review of electronic records <h3>Results</h3> Recruitment commenced on 01/06/2016. To date, nursing staff at two practices have received training and 10 children (5–15 years) have been recruited (11 eligible) in the course of 3 asthma review clinics. Spirometry and eNO were successful in 8 of these children. Practice staff have expressed concerns regarding funding, additional clinic time and staff training as the main barriers against implementation. <h3>Conclusions</h3> Our early data suggests that providing spirometry and eNO for children in general practice is achievable with our training package. Both the training package and clinic structure are being refined to improve time and cost-efficiency. This study (which when complete will contain a health economic analysis) will provide important evidence to inform NHS decision makers and primary care stakeholders on the usefulness of objective testing in children diagnosed and/or under investigation for asthma in general practice. <h3>References</h3> <i>Br J Gen Pract</i> 2016;<b>66</b>(644):e152–7. <i>BMJ</i> 1998;<b>316</b>:118–124.
P252 Accurate measurement of lung function in the workplace and potential effects of underestimation
Authors: JE Sumner, E Robinson, A Codling, L Lewis, RE Wiggans, LM Bradshaw, CM Barber, N Warren, S Forman, D Fishwick
Journal: Thorax (2016)

<h3>Introduction</h3> Accurate workplace spirometry measurement is key to giving workers the best clinical assessment of their respiratory health. We were interested in the underestimation of spirometry that occurs if best practice is not adhered to and the significance of this on assessment of health at work. <h3>Methods</h3> 667 stone, brick and foundry workers (with varying spirometry experience), carried out lung function testing as part of a larger cross sectional workplace study. Each performed a minimum of 3 forced expirations. Testing continued until each worker had met the ATS/ERS guidance. The final FEV<sub>1</sub> and FVC recorded was the maximum value attained from 3 technically acceptable blows, and that the two highest FEV<sub>1</sub> and FVC values were within 150 mls. Using the final FEV<sub>1</sub> and FVC for each worker, it was then possible to calculate the underestimate of both measures, had only the first blow, or the maximum of the first two blows, been used for interpretation. <h3>Results</h3> 613 of the 669 (91.6%) attained the ATS/ERS criteria based on FEV<sub>1</sub>. Analysis of the first actual blow, regardless of technical quality, showed an FEV<sub>1</sub> mean underestimate of 250 mls (median = 80 mls, IQR = 210 mls). If only the first technically acceptable blow had been carried out, the FEV<sub>1</sub> would have been underestimated by a mean of 114 mls (60 mls, 150 mls). If only two technically acceptable blows had been carried out, and the maximum of these used, the FEV<sub>1</sub> would have been underestimated by a mean of 36 mls (0 mls, 50 mls). Similarly, the FVC would have been underestimated by a mean of 131 mls (75 mls, 180 mls) if only the first technically acceptable blow had been used for interpretation. If only two technically acceptable blows were carried out, the FVC would have been underestimated by a mean of 43 mls (0 mls, 50 mls). <h3>Conclusion</h3> Non adherence to ATS/ERS lung function testing guidance at work can cause the FEV<sub>1</sub> and FVC to be underestimated by clinically significant amounts.
A bloody bronchoscopy
Authors: Karthi Srikanthan, Husain Shabeeh, Anthony De Souza, Pallav Shah
Journal: Thorax (2017)

A 42-year-old male non-smoker presented to the emergency department with a 1-month history of fever.He had no medical history.He was treated with oral antibiotics for a presumed chest infection.Initial chest radiograph (CXR) is shown in figure 1A.Two weeks later, he was seen in outpatients with fever, progressive dyspnoea and haemoptysis.Repeat CXR (figure 1B) was performed in addition to a chest CT (figure 1C).He underwent urgent bronchoscopy and bronchoalveolar lavage (BAL).After the procedure, he was admitted due to persistent hypoxia.Bedside observations: temperature 36.4°C,oxygen saturation 95% with Fio 2 0.35, blood pressure 125/45 mm Hg, heart rate 105 bpm and respiratory rate 25 breaths per minute.Chest auscultation revealed bilateral fine inspiratory crackles.Examination of the heart sounds, jugular venous pressure and peripheries were unremarkable.Blood tests: haemoglobin 10.5 g/dL, white cell count 7.3×10 9 /L, creatinine 100 mmol/L, alanine transaminase 48 IU/L, c-reactive protein 118 mg/L, Chest clinic
Murine systemic thrombophilia and hemolytic uremic syndrome from a factor H point mutation
Authors: Yoshiyasu Ueda, Imran Mohammed, Delu Song, Damodar Gullipalli, Lin Zhou, Sayaka Sato, Yuan Wang, Shuchi Gupta, Zhongjian Cheng, Hong Wang, Jialing Bao, Yingying Mao, Lawrence Brass, X. Long Zheng, Takashi Miwa, Matthew Palmer, Joshua Dunaief, Wen-Chao Song
Journal: Blood (2017)
Early Invasive versus Selectively Invasive Management for Acute Coronary Syndromes
Authors: Robbert J. de Winter, Fons Windhausen, Jan Hein Cornel, Peter H.J.M. Dunselman, Charles L. Janus, Peter E.F. Bendermacher, H. Rolf Michels, Gerard T. Sanders, Jan G.P. Tijssen, Freek W.A. Verheugt
Journal: New England Journal of Medicine (2005)

Current guidelines recommend an early invasive strategy for patients who have acute coronary syndromes without ST-segment elevation and with an elevated cardiac troponin T level. However, randomized trials have not shown an overall reduction in mortality, and the reduction in the rate of myocardial infarction in previous trials has varied depending on the definition of myocardial infarction.