tbuckley/cabot-search huggingface dataset:
Prospective web-based collection of sarcoma cases diagnosed and treated in France: Experience of the NetSarc network of the French Sarcoma Tumor Boards.
Authors: Francoise Ducimetiere, Jean-Yves Blay, Axel Le Cesne, Binh Bui Nguyen, Nicolas Penel, Emmanuelle Bompas, Francois Gouin, Florence Duffaud, Jean-Michel Coindre, Maria Rios, Christine Chevreau, Jean-Emmanuel Kurtz, Nicolas Isambert, Philippe Anract, Sophie Piperno-Neumann, François Bertucci, Pierre Kerbrat, Cecile Guillemet, Celeste Lebbe, Isabelle Ray-Coquard
Journal: Journal of Clinical Oncology (2012)

10056 Background: The management of sarcomas, as for all rare tumors, is hampered by the limited dissemination of medical knowledge. Management within a specialized multidisciplinary sarcoma tumor board (STB) improves compliance to clinical practice guidelines. Since 2010, a national network with a dedicated system for referral, gathering the 26 regional STBs, is supported by the French NCI. Its objectives are to monitor the management of sarcomas and give equal access to expertise and innovative treatments to all patients with sarcoma. We report here the first experience of a web-based data collection from these STBs. Methods: The expected incidence of sarcoma in France is 6.1/10 5 /year, ie 4000 new cases per year. A website collecting all files discussed in the 26 STBs was generated from Jan 2010 ( www.netsarc.org ). The prospective collection of clinical data, STB decision and patient follow-up was implemented in the national database (40 items). Results: 7472 patients were accrued during 2 years, 6202 (83%) had sarcoma, 2860 (46%) were new cases, representing 36% of expected incident cases. The number of new cases discussed in STB increased between 2010 and 2011 (+38%). Patients were referred to the STB (2010-2011; % of cases) prior 1) to biopsy (9%-15%), 2) to first surgery (34%-39%), 3) to adjuvant treatment (35%-34%), after treatment (14%-8%) and at time of relapse (8%-4%). 15% had a metastases at initial diagnosis. The R0+R1 resection rates for primary surgery were 55% vs 42% within vs outside the STB centers of NetSarc. 8% of declared patients were proposed to inclusion into a clinical trial. Conclusions: This web-based tool enabled the description of the activity of the STB at the national level. Clinical practices improved between 2010 and 2011, but 64% of new cases of sarcoma were not discussed in the referent STB prior to surgery. The yearly follow-up of the database will help to monitor evolution of clinical practices.
Single-dimension CT measurements with RECIST 1.1 to evaluate liver metastases in GIST patients on imatinib.
Authors: Gaia Schiavon, Alessandro Ruggiero, Stefan Sleijfer, Dave J. Bekers, Bronno van der Holt, Jacqueline S.L. Kloth, Gabriel P. Krestin, Patrick Schoffski, Jaap Verweij, Ron H.J. Mathijssen
Journal: Journal of Clinical Oncology (2012)

10091 Background: Tumor response assessment to therapy is crucial in oncology, both in daily practice and research.We analyzed the morphology of liver metastases (LM) in gastrointestinal stromal tumors (GIST). Aims were to 1) determine whether uni-dimensional measurements of tumor lesions (according to RECIST 1.1) are accurate reflections of their volumes and 2) estimate eventual bias in volume change calculations, as introduced by using only the longest diameter. Methods: 78 GIST patients with LM were evaluated at baseline (n=139 lesions), 3 (n=129), 6 (n=128), and 12 months (n=108) after imatinib therapy. LM were segmented semi-automatically on standard CT scans. All measurements at baseline were obtained by 2 independent investigators and agreement between observers was assessed with Bland-Altman plots. Values for segmented volume (Vs; mL), maximum transaxial diameter (MTD; mm), and elongation value (EV, defined as 1 - [width/length], where EV of 1 = fully ellipsoidal and 0 = fully spherical) were reported for each lesion at several time-points. A calculated volume (Vc) of each LM was also generated using the MTD, with the hypothesis that metastases were fully spherical. Results: At baseline, 44% (61/139) of the LM was spherical and 56% (78/139) was ellipsoidal. Their EV ranged from 0.08 to 0.94 (mean, 0.53±0.17). During treatment, overall 42% of the lesions kept their morphology (spherical or ellipsoidal) and the other half changed from spherical to ellipsoidal or vice versa. At baseline, there was strong inter-observer agreement in the determination of Vs, with mean inter-observer variability of 1.5% (95% CI, -14.5% to 17.5%). The difference between Vs and Vc was highly significant (P&lt;0.0001). Vc overestimates the actual volume of 35% (95% CI, -26% to 95%). Conclusions: LM are not always spherical and can change their morphology during imatinib therapy. Therefore, a lesion's single largest trans-axial dimension, as used in RECIST 1.1, is not an accurate surrogate of its actual volume. Further studies are warranted to fully understand the clinical impact of these findings and to assess whether we should apply different criteria for response assessment to therapies in solid tumors.
Rituximab Maintenance Failure in Mantle Cell Lymphoma Is Associated with High Risk of Death: Analysis of the Czech Lymphoma Study Group (CLSG)
Authors: Aleš Obr, Vit Prochazka, Tomas Papajik, Pavel Klener, Andrea Janikova, David Salek, David Belada, Robert Pytlik, Alice Sýkorová, Heidi Mocikova, Martin Simkovic, Vit Campr, Jitka Dlouha, Tomas Fuerst, Marek Trněný
Journal: Blood (2017)
A novel noninvasive method for remote heart failure monitoring: the EuleriAn video Magnification apPLications In heart Failure studY (AMPLIFY)
Authors: Freddy Abnousi, Guson Kang, John Giacomini, Alan Yeung, Shirin Zarafshar, Nicholas Vesom, Euan Ashley, Robert Harrington, Celina Yong
Journal: npj Digital Medicine (2019)

Current remote monitoring devices for heart failure have been shown to reduce hospitalizations but are invasive and costly; accurate non-invasive options remain limited. The EuleriAn Video Magnification ApPLications In Heart Failure StudY (AMPLIFY) pilot aimed to evaluate the accuracy of a novel noninvasive method that uses Eulerian video magnification. Video recordings were performed on the neck veins of 50 patients who were scheduled for right heart catheterization at the Palo Alto VA Medical Center. The recorded jugular venous pulsations were then enhanced by applying Eulerian phase-based motion magnification. Assessment of jugular venous pressure was compared across three categories: (1) physicians who performed bedside exams, (2) physicians who reviewed both the amplified and unamplified videos, and (3) direct invasive measurement of right atrial pressure from right heart catheterization. Motion magnification reduced inaccuracy of the clinician assessment of central venous pressure compared to the gold standard of right heart catheterization (mean discrepancy of -0.80 cm H2O; 95% CI -2.189 to 0.612, p = 0.27) when compared to both unamplified video (-1.84 cm H2O; 95% CI -3.22 to -0.46, p = 0.0096) and the bedside exam (-2.90 cm H2O; 95% CI -4.33 to 1.40, p = 0.0002). Major categorical disagreements with right heart catheterization were significantly reduced with motion magnification (12%) when compared to unamplified video (25%) or the bedside exam (27%). This novel method of assessing jugular venous pressure improves the accuracy of the clinical exam and may enable accurate remote monitoring of heart failure patients with minimal patient risk.
High Glucose Intake Exacerbates Autoimmunity through Reactive-Oxygen-Species-Mediated TGF-β Cytokine Activation
Authors: Dunfang Zhang, Wenwen Jin, Ruiqing Wu, Jia Li, Sang-A Park, Eric Tu, Peter Zanvit, Junji Xu, Ousheng Liu, Alexander Cain, WanJun Chen
Journal: Immunity (2019)
Purinostat Mesylate Is a Uniquely Potent and Selective Inhibitor of HDACs for the Treatment of <i>BCR-ABL</i>–Induced B-Cell Acute Lymphoblastic Leukemia
Authors: Linyu Yang, Qiang Qiu, Minghai Tang, Fang Wang, Yuyao Yi, Dongni Yi, Zhuang Yang, Zejiang Zhu, Shoujun Zheng, Jianhong Yang, Heying Pei, Li Zheng, Yong Chen, Liping Gou, Liya Luo, Xing Deng, Haoyu Ye, Yiguo Hu, Ting Niu, Lijuan Chen
Journal: Clinical Cancer Research (2019)

This study was to perform preclinical evaluation of a novel class I and IIb HDAC-selective inhibitor, purinostat mesylate, for the treatment of Ph+ B-cell acute lymphoblastic leukemia (B-ALL).Biochemical assays were used to test enzymatic activity inhibition of purinostat mesylate. Ph+ leukemic cell lines and patient cells were used to evaluate purinostat mesylate activity in vitro. BL-2 secondary transplantation Ph+ B-ALL mouse model was used to validate its efficacy, mechanism, and pharmacokinetics properties in vivo. BCR-ABL(T315I)-induced primary B-ALL mouse model and PDX mouse model derived from relapsed Ph+ B-ALL patient post TKI treatment were used to determine the antitumor effect of purinostat mesylate for refractory or relapsed Ph+ B-ALL. Long-term toxicity and hERG blockade assays were used to safety evaluation of purinostat mesylate.Purinostat mesylate, a class I and IIb HDAC highly selective inhibitor, exhibited robust antitumor activity in hematologic cancers. Purinostat mesylate at low nanomolar concentration induced apoptosis, and downregulated BCR-ABL and c-MYC expression in Ph+ leukemia cell lines and primary Ph+ B-ALL cells from relapsed patients. Purinostat mesylate efficiently attenuated Ph+ B-ALL progression and significantly prolonged the survival both in BL-2 secondary transplantation model with clinical patient symptoms of Ph+ B-ALL, BCR-ABL(T315I)-induced primary B-ALL mouse model, and PDX model derived from patients with relapsed Ph+ B-ALL post TKI treatment. In addition, purinostat mesylate possesses favorable pharmacokinetics and low toxicity properties.Purinostat mesylate provides a new therapeutic strategy for patients with Ph+ B-ALL, including those who relapse after TKI treatment.
Steps to better understanding resistant behaviours in hospitalised patients with dementia
Authors: Rob Cook, Tara Lamont, Rosie Martin
Journal: BMJ (2019)

The study Featherstone K, Northcott A, Harden J, et al. Refusal and resistance to care by people living with dementia being cared for within acute hospital wards: an ethnographic study. Health Serv Deliv Res 2019;7. This study was funded by the National Institute for Health Research Health Services and Delivery Research Programme (project number 13/10/80). To read the full NIHR Signal, go to https://discover.dc.nihr.ac.uk/content/signal-000779/understanding-dementia-care-in-hospitals
Delta beta thalassemia
Authors: Barbara J. Bain
Journal: American Journal of Hematology (2019)

A 19-year-old woman of Lebanese ethnic origin was referred for investigation of microcytosis. Her blood count showed: red cell count 5.32 × 1012/L, hemoglobin concentration 116 g/L, mean cell volume 70 fL, mean cell hemoglobin 21.8 pg and mean cell hemoglobin concentration 312 g/L. Her blood film showed microcytosis, mild hypochromia and poikilocytosis. The poikilocytes included elliptocytes (left Image) and small numbers of irregularly contracted cells (right Image). There were only occasional target cells. Thalassemia trait was suspected and high performance liquid chromatography (HPLC) was performed. Hemoglobin A2 was normal at 2.8%, but hemoglobin F, as quantified by the Bio-Rad Variant II instrument (unmodified hemoglobin F), was increased to 11.8%; the total hemoglobin F was about 14% if acetylated F, which is not integrated by the instrument, was included. The likely diagnosis now became δβ thalassemia. This diagnosis was confirmed by Gap-PCR which showed heterozygosity for the Sicilian δβ thalassemia deletion mutation. The diagnosis of δβ thalassemia is important, particularly in a patient in the reproductive age range, since homozygosity or compound heterozygosity with β thalassemia can lead to thalassemia intermedia. It might be expected that the hemoglobin A2 would be reduced since one δ gene has been deleted but in fact it is often normal. Hemoglobin F is usually between 5 and 20%. Nothing to report.
Improved precision of epigenetic clock estimates across tissues and its implication for biological ageing
Authors: Qian Zhang, Costanza L. Vallerga, Rosie M. Walker, Tian Lin, Anjali K. Henders, Grant W. Montgomery, Ji He, Dongsheng Fan, Javed Fowdar, Martin Kennedy, Toni Pitcher, John Pearson, Glenda Halliday, John B. Kwok, Ian Hickie, Simon Lewis, Tim Anderson, Peter A. Silburn, George D. Mellick, Sarah E. Harris, Paul Redmond, Alison D. Murray, David J. Porteous, Christopher S. Haley, Kathryn L. Evans, Andrew M. McIntosh, Jian Yang, Jacob Gratten, Riccardo E. Marioni, Naomi R. Wray, Ian J. Deary, Allan F. McRae, Peter M. Visscher
Journal: Genome Medicine (2019)

DNA methylation changes with age. Chronological age predictors built from DNA methylation are termed ‘epigenetic clocks’. The deviation of predicted age from the actual age (‘age acceleration residual’, AAR) has been reported to be associated with death. However, it is currently unclear how a better prediction of chronological age affects such association. In this study, we build multiple predictors based on training DNA methylation samples selected from 13,661 samples (13,402 from blood and 259 from saliva). We use the Lothian Birth Cohorts of 1921 (LBC1921) and 1936 (LBC1936) to examine whether the association between AAR (from these predictors) and death is affected by (1) improving prediction accuracy of an age predictor as its training sample size increases (from 335 to 12,710) and (2) additionally correcting for confounders (i.e., cellular compositions). In addition, we investigated the performance of our predictor in non-blood tissues. We found that in principle, a near-perfect age predictor could be developed when the training sample size is sufficiently large. The association between AAR and mortality attenuates as prediction accuracy increases. AAR from our best predictor (based on Elastic Net, https://github.com/qzhang314/DNAm-based-age-predictor ) exhibits no association with mortality in both LBC1921 (hazard ratio = 1.08, 95% CI 0.91–1.27) and LBC1936 (hazard ratio = 1.00, 95% CI 0.79–1.28). Predictors based on small sample size are prone to confounding by cellular compositions relative to those from large sample size. We observed comparable performance of our predictor in non-blood tissues with a multi-tissue-based predictor. This study indicates that the epigenetic clock can be improved by increasing the training sample size and that its association with mortality attenuates with increased prediction of chronological age.
Association between plasma GFAP concentrations and MRI abnormalities in patients with CT-negative traumatic brain injury in the TRACK-TBI cohort: a prospective multicentre study
Authors: John K Yue, Esther L Yuh, Frederick K Korley, Ethan A Winkler, Xiaoying Sun, Ross C Puffer, Hansen Deng, Winward Choy, Ankush Chandra, Sabrina R Taylor, Adam R Ferguson, J Russell Huie, Miri Rabinowitz, Ava M Puccio, Pratik Mukherjee, Mary J Vassar, Kevin K W Wang, Ramon Diaz-Arrastia, David O Okonkwo, Sonia Jain, Geoffrey T Manley, Opeolu M Adeoye, Neeraj Badjatia, Kim Boase, Yelena G Bodien, Malcom R Bullock, Randall M Chesnut, John D Corrigan, Karen Crawford, Sureyya S Dikmen, Ann-Christine Duhaime, Richard G Ellenbogen, Venkata Feeser, Brandon Foreman, Raquel C Gardner, Etienne Gaudette, Joseph T Giacino, Dana P Goldman, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J C Hemphill, Gillian Hotz, Joel H Kramer, Natalie P Kreitzer, Harvey S Levin, Christopher J Lindsell, Joan Machamer, Christopher J Madden, Alastair J Martin, Thomas W McAllister, Michael McCrea, Randall Merchant, Lindsay D Nelson, Florence Noel, Eva M Palacios, Daniel P Perl, Ava M Puccio, Miri Rabinowitz, Claudia S Robertson, Jonathan Rosand, Angelle M Sander, Gabriela G Satris, David M Schnyer, Seth A Seabury, Mark Sherer, Murray B Stein, Nancy R Temkin, Arthur W Toga, Alex B Valadka, Mary J Vassar, Paul M Vespa, Esther L Yuh, Ross Zafonte
Journal: The Lancet Neurology (2019)
Medium and long-term risks of specific cardiovascular diseases in survivors of 20 adult cancers: a population-based cohort study using multiple linked UK electronic health records databases
Authors: Helen Strongman, Sarah Gadd, Anthony Matthews, Kathryn E Mansfield, Susannah Stanway, Alexander R Lyon, Isabel dos-Santos-Silva, Liam Smeeth, Krishnan Bhaskaran
Journal: The Lancet (2019)

The past few decades have seen substantial improvements in cancer survival, but concerns exist about long-term cardiovascular disease risk in survivors. Evidence is scarce on the risks of specific cardiovascular diseases in survivors of a wide range of cancers to inform prevention and management. In this study, we used large-scale electronic health records data from multiple linked UK databases to address these evidence gaps.
Treatment of multidrug-resistant tuberculosis using therapeutic drug monitoring: first experiences with sub-300 mg linezolid dosages using in-house made capsules
Authors: Mathieu S. Bolhuis, Tjip S. van der Werf, Huib A.M. Kerstjens, Wiel C.M. de Lange, Jan-Willem C. Alffenaar, Onno W. Akkerman
Journal: European Respiratory Journal (2019)

<b>Therapeutic drug monitoring allows for sub-300 mg linezolid dosages once daily to successfully achieve PK/PD targets. Let9s confirm these retrospective data in a prospective study using dried blood spots.</b>http://bit.ly/2H9fDSc
Per- and Polyfluoroalkyl Substance Plasma Concentrations and Bone Mineral Density in Midchildhood: A Cross-Sectional Study (Project Viva, United States)
Authors: Rachel Cluett, Shravanthi M. Seshasayee, Lisa B. Rokoff, Sheryl L. Rifas-Shiman, Xiaoyun Ye, Antonia M. Calafat, Diane R. Gold, Brent Coull, Catherine M. Gordon, Clifford J. Rosen, Emily Oken, Sharon K. Sagiv, Abby F. Fleisch
Journal: Environmental Health Perspectives (2019)

Background: Identifying factors that impair bone accrual during childhood is a critical step toward osteoporosis prevention. Exposure to per- and polyfluoroalkyl substances (PFASs) has been associated with lower bone mineral density, but data are limited, particularly in children. Methods: We studied 576 children in Project Viva, a Boston-area cohort of mother/child pairs recruited prenatally from 1999 to 2002. We quantified plasma concentrations of several PFASs and measured areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) in midchildhood. We used linear regression to examine associations between plasma concentrations of individual PFASs and aBMD z-score. We used weighted quantile sum (WQS) regression to examine the association of the PFAS mixture with aBMD z-score. All models were adjusted for maternal age, education, annual household income, census tract median household income, and child age, sex, race/ethnicity, dairy intake, physical activity, and year of blood draw. Results: Children were [mean±standard deviation (SD)] 7.9±0.8years of age. The highest PFAS plasma concentrations were of perfluorooctanesulfonic acid (PFOS) {median [interquartile range (IQR)]: 6.4 (5.6) ng/mL} and perfluorooctanoic acid (PFOA) [median (IQR): 4.4 (3.2) ng/mL]. Using linear regression, children with higher plasma concentrations of PFOA, PFOS, and perfluorodecanoate (PFDA) had lower aBMD z-scores [e.g., β: −0.16; 95% confidence interval (CI): −0.25, −0.06 per doubling of PFOA]. The PFAS mixture was negatively associated with aBMD z-score (β: −0.16; 95% CI: −0.28, −0.04 per IQR increment of the mixture index). Conclusions: PFAS exposure may impair bone accrual in childhood and peak bone mass, an important determinant of lifelong skeletal health. https://doi.org/10.1289/EHP4918
Abuse of medical students
Authors: Richard J. Meli
Journal: JAMA (1990)

<h3>To the Editor.—</h3> I found the two recent articles on medical student abuse<sup>1,2</sup>to be of particular concern. With my thirdyear rotations beginning in July, I am approaching the point at which, according to the findings, the putative mistreatment tends to burgeon. Although I am by no means surprised by the data, I believe the articles are important in their provision of concrete information regarding an issue that, in the past, seemed to receive mostly verbal attention. This information should serve to prepare students who have yet to commence their clinical years for an environment that, in addition to offering crucial and exciting medical experience, may seem hostile toward them. First, we students should remind ourselves that such abusive behavior is not exclusive to medical training, or to the medical profession itself; in every profession there will be ugly confrontations. Although they are inexcusable, physical, sexual, and verbal mistreatments
A study to investigate the pharmacokinetics of carboplatin and etoposide in infants with neuroblastoma
Authors: Gareth J. Veal, Julie Errington, Caroline Ellershaw, Andrew Pearson, Alan Boddy
Journal: Cancer Research (2005)

2953  Instructions for dosing in infants and young children frequently differ between tumour types and protocols without scientific rationale. Given the toxicity observed with many chemotherapeutic drugs commonly used in infants and young children, it is appropriate to establish a pharmacological basis for such dose adjustments. The pharmacokinetics of carboplatin and etoposide were determined in infant neuroblastoma patients (less than one year of age) treated on the European Infant Neuroblastoma Study (INES) protocol. Carboplatin was administered as a single intravenous dose of 6.6 mg/kg, with a 1h infusion time, etoposide as a 2h intravenous infusion of 5.0 mg/kg, each on three consecutive days of treatment. 17 children were studied at 6 UK clinical centres, with pharmacokinetic sampling at 0, 30, 60 and 120 min for carboplatin and 0, 1, 2 and 4 h following etoposide administration. Carboplatin concentrations in plasma ultrafiltrate samples were determined by atomic absorption spectrometry (AAS) and drug clearance and exposure (AUC) calculated using a two-compartment model with Bayesian estimation. Plasma etoposide concentrations were quantified using liquid chromatography-mass spectrometry (LC-MS). The mean exposure (AUC) of carboplatin was 1.9 mg/ml.min on each of days 1, 2 and 3 of treatment, with a range of 1.1 - 2.8 mg/ml.min on day 1. Limited intra-patient variation in carboplatin AUC values was seen over the 3 days of treatment. Etoposide peak plasma concentrations of 10.9 - 38.9 μg/ml were observed 1-2 hrs after the start of administration. As seen with carboplatin, there was limited intra-patient variation over the 3 days of etoposide treatment. When carboplatin AUC values previously obtained from older children are normalized to an equivalent dose of 6.6 mg/kg/day, these data show a comparable mean AUC value, indicating that carboplatin pharmacokinetics are similar in infant patients and older children. However, when carboplatin exposure is normalized to body weight, a greater degree of inter-patient variation in exposure is observed in patients