tbuckley/cabot-search huggingface dataset:
NTCT-07ANTI-GLIOMA ALKYLATING AGENTS SHOW DIFFERENT CHEMOSENSITIVITY AGAINST HUMAN NEURAL PROGENITOR CELLS FROM NEURAL TISSUES AND THOSE FROM iPS CELLS
Authors: Yonehiro Kanemura, Tomoko Shofuda, Yukako Handa, Atsuyo Yamamoto, Daisuke Kanematsu, Hayato Fukusumi
Journal: Neuro-Oncology (2015)

Anti-glioma alkylating agents, like temozolomide (TMZ) or nimustine (ACNU), show in vitro and in vivo cytotoxicity against various glioma cells. Conventional neurotoxicity assays have been carried out using animal-derived primary neuronal cells or human-derived cell lines to examine cytotoxicity of anti-glioma agents against normal neural cells. However, these assays are not necessarily optimal evaluation system to predict neurotoxicity, and especially cytotoxicity against human-derived normal neuronal cells has not been fully examined. Human neural tissue-derived primary cells are ethically and practically less accessible materials, and those are also very difficult to obtain enough cells for high throughput in vitro screening assays. Recently, it was demonstrated that neural cells can be differentiated from human induced pluripotent stem cells (hiPSCs), and those are adaptable, powerful alternatives for tissue-derived primary cells in neurotoxicological assays. In this study, we generated hiPS-derived neural progenitor cells (hiPS-NPCs), expanded as free-floating spheroids (neurospheres) with self-renewal potential and differentiation capacity restricted to neural lineage (neurons and astrocytes), and examined cytotoxicity of anti-glioma alkylating agents against hiPS-NPCs in comparison with human neural tissue derived NPCs (hN-NPCs). The hiPS-NPCs were almost identical in phenotype to hN-NPCs, in both cell-surface marker expression and their ability to differentiate into neuronal cells, although gene expression profiles showed that the hiPS-NPCs had higher neural and lower glial gene expression, along with mid-hindbrain-like regional specificity. Cytotoxicity assays revealed both hN-NPCs and hiPS-NPCs showed different sensitivity against ACNU and TMZ, and gene expression pattern of O-6-methylguanine-DNA methyltransferase (MGMT) and mismatch repair (MMR)-related genes have been different between two human NPCs. These results suggest that human-derived normal neuronal cells show different chemosensitivity against anti-glioma alkylating agents, and MGMT and/or MMR-related genes might be involved with these properties. Our present findings will provide useful information for understanding of neurotoxicity of anti-glioma agents.
Parathyroid Hormone Directs Bone Marrow Mesenchymal Cell Fate
Authors: Yi Fan, Jun-ichi Hanai, Phuong T. Le, Ruiye Bi, David Maridas, Victoria DeMambro, Carolina A. Figueroa, Serkan Kir, Xuedong Zhou, Michael Mannstadt, Roland Baron, Roderick T. Bronson, Mark C. Horowitz, Joy Y. Wu, John P. Bilezikian, David W. Dempster, Clifford J. Rosen, Beate Lanske
Journal: Cell Metabolism (2017)
15-year survival after radical prostatectomy (RP): Which prognostic factors are available for patient counseling?
Authors: Sophie D. Fossa, Haakon Waehre, Milada Cvancarova, Haavard E Danielsen
Journal: Journal of Clinical Oncology (2013)

181 Background: Studies on 15-year Post-RP survival including data on PSA relapse (PSA-Rel) are rare. We established the 15-year post-RP prostate cancer specific mortality (PCSM), to explore the time to PSA-Rel and PCSM thereafter, and to identify clinically available prognostic factors. Methods: In men prostatectomized from 1987-2004 slightly modified D`Amico risk groups were identified (T1: No palpable tumor ;”T2 unilateral”/”T2 bilateral” according to tumor palpability in one or both lobes). PSA –Rel was defined as PSA ≥4 µg/l before 2000, and thereafter as PSA &gt;0.2 µg/l. Delay of RP was defined as RP performance 3-12 months after diagnosis. Competing risk modeling was performed with a significance level of &lt;0.05. Results: After a median observation time of 12 years (range: 0-22), of 309 men (median age:62 years [range:40-74]) 40 have died from prostate cancer ( PCa) and 68 due to other causes (15-year PCSM: 15% [95%CI: 10-19%). No difference of PCSM was found between the low (N: 12) and the intermediate group (N: 121), the “conventional” high risk group ( N: 121) displaying a 24% PCSM rate (95% CI:16-32%) with particularly poor prognosis for men who presented with two high risk factors ( N. 32 ; PCSM: 33% [95% CI:20-46%]). The median time to PSA relapse (N: 152) was 5 years (range: 0-17), the median overall survival time after PSA- Rel being 7 years (range: 0-17). PCSM continued to increase after 10 years. Delay of RP had no impact on PCSM. Conclusions: After a median observation time of 12 years approximately 1 of 7 men with localized PCa, most of them diagnosed before the PSA- era, have died of prostate cancer. The “conventional” high-risk group is prognostically heterogeneous: Men with two high risk criteria have a particularly poor prognosis. PSA-Rel 10 years after RP is no rare event followed by survival times of &gt;10 years. Delay of RP for up to one year had no impact on PCSM.
ADAMTS13 Gene Deletion Aggravates Ischemic Brain Damage
Authors: Kenji Nishio, Masayuki Fujioka, Kazuhide Hayakawa, Kenichi Mishima, Michihiro Fujiwara, Fumiaki Banno, Koichi Kokame, Toshiyuki Miyata, Yasuaki Shida, Mitsuhiko Sugimoto, Hidetada Fukushima, Kazuo Okuchi
Journal: Blood (2008)
Erratum: Corrigendum: Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts
Authors: Emma M Jenkinson, Mathieu P Rodero, Paul R Kasher, Carolina Uggenti, Anthony Oojageer, Laurence C Goosey, Yoann Rose, Christopher J Kershaw, Jill E Urquhart, Simon G Williams, Sanjeev S Bhaskar, James O'Sullivan, Gabriela M Baerlocher, Monika Haubitz, Geraldine Aubert, Kristin W Barañano, Angela J Barnicoat, Roberta Battini, Andrea Berger, Edward M Blair, Janice E Brunstrom-Hernandez, Johannes A Buckard, David M Cassiman, Rosaline Caumes, Duccio M Cordelli, Liesbeth M De Waele, Alexander J Fay, Patrick Ferreira, Nicholas A Fletcher, Alan E Fryer, Himanshu Goel, Cheryl A Hemingway, Marco Henneke, Imelda Hughes, Rosalind J Jefferson, Ram Kumar, Lieven Lagae, Pierre G Landrieu, Charles M Lourenço, Timothy J Malpas, Sarju G Mehta, Imke Metz, Sakkubai Naidu, Katrin Õunap, Axel Panzer, Prab Prabhakar, Gerardine Quaghebeur, Raphael Schiffmann, Elliott H Sherr, Kanaga R Sinnathuray, Calvin Soh, Helen S Stewart, John Stone, Hilde Van Esch, Christine E G Van Mol, Adeline Vanderver, Emma L Wakeling, Andrea Whitney, Graham D Pavitt, Sam Griffiths-Jones, Gillian I Rice, Patrick Revy, Marjo S van der Knaap, John H Livingston, Raymond T O'Keefe, Yanick J Crow
Journal: Nature Genetics (2017)
National Trends in Atrial Fibrillation Hospitalization, Readmission, and Mortality for Medicare Beneficiaries, 1999–2013
Authors: James V. Freeman, Yun Wang, Joseph Akar, Nihar Desai, Harlan Krumholz
Journal: Circulation (2017)

Data are lacking on national trends for atrial fibrillation (AF) hospitalization, particularly with regard to long-term outcomes including readmission and mortality.We studied all Medicare fee-for-service beneficiaries between 1999 and 2013, and we evaluated rates of hospitalization for AF, in-hospital mortality, length of stay, and hospital payments. We then evaluated rates of long-term outcomes, including 30-day readmission, 30-day mortality, and 1-year mortality. To evaluate changes in rates of AF hospitalization and mortality, we used mixed-effects models, adjusting for age, sex, race, and comorbidity. To assess changes in rates of 30-day readmission, we constructed a Cox proportional hazards model adjusting for age, sex, race, and comorbidity.Adjusted rates of hospitalization for AF increased by ≈1% per year between 1999 and 2013, and although geographic variation was present, this trend was consistent nationwide. Median hospital length of stay remained unchanged at 3.0 (interquartile range 2.0-5.0) days, but median Medicare inpatient expenditure per beneficiary increased from $2932 (interquartile range $2232-$3870) to $4719 (interquartile range $3124-$7209) per stay. During the same period, the rate of inpatient mortality during AF hospitalization decreased by 4% per year, and the rate of 30-day readmission decreased by 1% per year. The rates of 30-day and 1-year mortality decreased more modestly by 0.4% and 0.26% per year, respectively.Between 1999 and 2013, among Medicare fee-for-service beneficiaries, patients were hospitalized more frequently and treated with more costly inpatient therapies such as AF catheter ablation, but this finding was associated with improved outcomes, including lower rates of in-hospital mortality, 30-day readmission, 30-day mortality, and 1-year mortality.
Vaccine Reponses Following Unmodified or T Cell Depleted Unrelated and Mismatched Related HCT.
Authors: Trudy N. Small, Esperanza B. Papadopoulos, Farid Boulad, Nancy A. Kernan, Ruth Ford, Joanne Taylor, Anne Casson, Joann Torok-Castanza, Bernadette Cuello, James W. Young, Ann Jakubowksi, Hugo Castro-Malaspina, Miguel Perales, Richard J. O’Reilly
Journal: Blood (2004)
Overcoming therapeutic resistance in glioblastoma: the way forward
Authors: Satoru Osuka, Erwin G. Van Meir
Journal: Journal of Clinical Investigation (2017)

Glioblastoma is the most common and lethal primary malignant brain tumor in adults. Patients die from recurrent tumors that have become resistant to therapy. New strategies are needed to design future therapies that target resistant cells. Recent genomic studies have unveiled the complexity of tumor heterogeneity in glioblastoma and provide new insights into the genomic landscape of tumor cells that survive and initiate tumor recurrence. Resistant cells also co-opt developmental pathways and display stem-like properties; hence we propose to name them recurrence-initiating stem-like cancer (RISC) cells. Genetic alterations and genomic reprogramming underlie the innate and adaptive resistance of RISC cells, and both need to be targeted to prevent glioblastoma recurrence.
OPTIMISING ORAL HEALTH AMONG DUTCH ELITE ATHLETES FOR RIO 2016
Authors: Eppo Wolvius, Lea Kragt, Cees-Rein van den Hoogenband, Maarten Moen
Journal: British Journal of Sports Medicine (2017)

Background Elite athletes are at high risk for poor oral health. A screening program to monitor oral health and create dental awareness can improve oral health among elite athletes. Objective Prior to RIO2016, a national dental screening program was conducted in elite athletes of the Nederlands Olympisch Committee*Nederlandse Sport Federatie (NOC*NSF). Design Cross-sectional study. Setting questionnairres via online surveys; intraoral screening at 5 dental offices througout the Netherlands by dentist trained specifically for this purpose. Participants 800 Dutch athletes eligible for the Olympic and Paralympic Games in Rio de Janeiro 2016 were invited to a costless an voluntary intraoral examination. Interventions (or Assessment of Risk Factors) Questionnaires and dental screening program. Main Outcome Measurements the decayed, missing and filled teeth-index (DMFT), the basic erosive wear examination (BEWE) and the Dutch Periodontal Screening-score (DPSI-score) were used to evaluate athletes oral health. Information on sociodemographic variables and sport performance were collected in questionnaires, which included also questions on Oral Health-Related Quality of Life (OHRQOL). Results In total, 116 Dutch elite athletes were included in the study. The median (90%-range) dmft-score was 3.0 (0.0–16.0), the median BEWE-score was 2.0 (0.0–10.0) and the mean±SD DPSI-score was 2.0±0.73. Also OHRQOL was generally high, although only 28.2% of the athletes reported never having problems with their dentition or mouth. In 43% of the athletes clinical findings were reported which needed a direct referral to the general dentist. Conclusions Oral health in Dutch elite athletes seems not worse than in the general population. Still, almost half of them needed dental treatment. Regular screening of oral health incorporated into the general preventive health care of elite athletes is necessary to ensure athletes are fully healthy during competitions like the Olympic and Paralympic Games.
Treatment with Bortezomib (Bor) Based Therapy Followed By Autologous Stem Cell Transplantation (SCT) Improves Outcomes in Light Chain Amyloidosis (AL)
Authors: Tania Jain, Shu Ting Kung, Vishal Shah, Amylou Constance Dueck, Heidi E. Kosiorek, Joseph Mikhael, P. Leif Bergsagel, Craig B. Reeder, Pierre Noel, Roberta H. Adams, Susan Luft, Angela Mayo, A. Keith Stewart, Rafael Fonseca
Journal: Blood (2016)
Heading football is related to concussion symptoms, study finds
Authors: Jacqui Wise
Journal: BMJ (2017)

Football players who head the ball a lot are three times more likely to have concussion symptoms than those who head it less often, a study published in Neurology suggests.

The study,1 funded by the US National Institutes for Health, also found that players whose heads were hit in a collision twice or more in a two week period were six times more likely to have concussion symptoms than players who had no unintentional head trauma.

Researchers studied 222 amateur US soccer players who played for at least six months of the year at clubs in the New York City …
The aging clock: circadian rhythms and later life
Authors: Suzanne Hood, Shimon Amir
Journal: Journal of Clinical Investigation (2017)

Circadian rhythms play an influential role in nearly all aspects of physiology and behavior in the vast majority of species on Earth. The biological clockwork that regulates these rhythms is dynamic over the lifespan: rhythmic activities such as sleep/wake patterns change markedly as we age, and in many cases they become increasingly fragmented. Given that prolonged disruptions of normal rhythms are highly detrimental to health, deeper knowledge of how our biological clocks change with age may create valuable opportunities to improve health and longevity for an aging global population. In this Review, we synthesize key findings from the study of circadian rhythms in later life, identify patterns of change documented to date, and review potential physiological mechanisms that may underlie these changes.
A global phase II, single-arm, open-label study to determine the efficacy of midostaurin in patients with aggressive systemic mastocytosis (ASM) or mast cell leukemia (MCL) with or without an associated hematologic clonal nonmast cell lineage disease (AHNMD).
Authors: J. R. Gotlib, H. Kluin-Nelemans, M. J. Mauro, O. Hermine, E. O. Hexner, J. H. Lipton, F. T. Awan, Z. G. Nikolova, S. H. Gross, C. Dutreix, B. Dharan, T. George, P. Horny, C. Akin, K. Hartmann, P. Valent, A. Reiter
Journal: Journal of Clinical Oncology (2011)

TPS200 Background: ASM and MCL are rare diseases with high unmet need and poor prognosis. The D816V KIT mutation occurs in up to 90% of patients (pts) with advanced SM, and exhibits resistance to imatinib. Midostaurin is an oral multi-targeted kinase inhibitor, that blocks D816V KIT-transformed cell growth at an IC50 of 30-40nM. In a US phase II study (N=26) of ASM, MCL or SM + AHNMD pts, midostaurin 100 mg BID demonstrated an overall response rate (ORR) of 69%, including 38% major responses (MRs). All pts achieving an MR exhibited D816V KIT. These data support further evaluation of midostaurin in advanced SM. Methods: This global, multi-center phase II study (NCT00782067) evaluates the efficacy and safety of midostaurin in adult pts with World Health Organization-defined ASM or MCL +/- AHNMD with at least 1 measurable C-Finding (e.g. cytopenia(s), liver dysfunction, hypoalbuminemia, and/or weight loss >10% over 6 months prior to entry). KIT mutation status is collected prospectively. Midostaurin 100 mg BID is administered continuously (28 days/cycle) until progressive disease, intolerability, or withdrawal. The primary endpoint is ORR by Valent criteria at 6 cycles of treatment. Secondary objectives include duration of response, progression-free and overall survival, safety/tolerability, and changes in marrow mast cell burden and serum tryptase. Modified Cheson/IWG criteria for MDS (Blood 2006) are utilized to evaluate pts with pre-existing RBC or platelet transfusion dependence. Histopathology and response are determined by central review/committee. The expected response rates are ≤ 30% and ≥ 50% for the null and alternative hypothesis, respectively. Using an adapted Fleming two-stage design with a nominal alpha of 0.025 and power of 84%, the null hypothesis will be rejected at the end of the first stage if ≥ 19/40 pts enrolled in the primary efficacy population are responders, and if ≥ 27/60 pts enrolled at the end of the second stage are responders. 80 pts will be enrolled in both stages and an extension phase. Enrollment began in January 2009 and will complete by December 2011.
Co-Treatment with a Novel Heat Shock Protein (hsp) 90 Inhibitor IPI504 and the Histone Deacetylase Inhibitor (HDI) Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA): A Highly Active Combination Against Wild Type or Mutant Bcr-Abl-T315I or FLT-3-ITD-Containing Human Leukemia Cells.
Authors: Warren Fiskus, Purva Bali, Michael Pranpat, Maria Balasis, Sandhya Kumaraswamy, Sandhya Boyapalle, Kathy Rocha, Jeffery Tong, Victoria Richon, Emmanuel Normant, Kapil Bhalla
Journal: Blood (2005)
Effect of Rituximab and/or High-Dose Therapy with Autotransplant at Time of Relapse in Patients with Follicular Lymphoma.
Authors: Bertrand Coiffier, Pauline Brice, Richard Delarue, Corinne Haioun, Bertrand Souleau, Nicolas Mounier, Pierre Feugier, Hervé Tilly, Catherine Sebban
Journal: Blood (2007)
Assessing Frequency and Risk of Weight Entry Errors in Pediatrics
Authors: Philip A. Hagedorn, Eric S. Kirkendall, Michal Kouril, Judith W. Dexheimer, Joshua Courter, Thomas Minich, S. Andrew Spooner
Journal: JAMA Pediatrics (2017)

Assessing Frequency and Risk of Weight Entry Errors in PediatricsPediatric patient weights are commonly used by electronic health records to calculate weight-based medication doses.Patient weights, which are frequently user entered, are susceptible to data entry errors, such as digit omission, addition, or transposition or entry of the right data into the wrong patient's medical record. 1 This means that errant weight entries can lead to errors in medication calculation, which has been previously reported. 2,3Outside of case reports, to our knowledge, there is little published regarding the frequency of or the risk associated with these errors.Methods | The Institutional Review Board of Cincinnati Children's Hospital Medical Center judged this work to be nonhuman subjects research and provided a waiver of informed consent.We set out to characterize the frequency of and the risk associated with weight entry errors at our institution.To accomplish this, we developed an electronic trigger tool that was applied to all new weights entered into our electronic health record during the study period to notify members of the study team if a newly entered patient weight varied more than 50% from that patient's last recorded weight, provided the previous entry was within 30 days of the new weight entry.This temporal restriction served 2 purposes.First, it reduced falsepositive alerts by eliminating patients with long gaps between weight measurements who we could reasonably expect would grow more than 50% between weights.Second, this time limit targeted the population we hypothesized to be at highest risk: hospitalized patients who were more likely to have frequent weights entered into our system.Receipt of this alert then prompted a medical record review of the flagged patient, including past weights, growth chart, medical diagnoses, clinical notes, and other context of the new weight entry in question, followed by determination of the hypothetical cause of the deviant weight entry.Standard causes investigated included common errors, such as digit or unit transposition.Medical records in which more common errors appeared implausible to the reviewer were investigated for other possible sources of the weight entry, such as vital signs or patient equipment noted in proximity to the weight entry.If these values matched or closely matched the entered
CSIG-10IMMUNIHISTOCHEMICAL STUDY OF THE EXPRESSION LEVELS OF NF-kB AND ITS REGULATORS ING-4, AEG-1 IN GLIOMAS
Authors: George Klironomos, Alireza Mansouri, Lior Gonen, Sofia Papanikolaou, Eleni Papadaki, Gelareh Zadeh
Journal: Neuro-Oncology (2015)

BACKROUND: Nuclear factor-kappa B (NF-kB is implicating in many cellular processes and its aberrant levels have been detected in many malignancies. Inhibitor of growth-4 (ING-4) and astrocytes elevated genes (AEG-1) are important regulators of NF-kB activity. This study aimed to evaluate the expression levels of p65, p50 subunits of NF-kB as well as its regulators ING-4 and AEG-1 in human gliomas tissues. METHODS: We examined formalin-fixed, paraffin-embedded tumor samples from 101 gliomas patients with immunohistochemical technique using primary antibodies for p50, p65, ING-4, AEG-1. The mean age of the patients was 56 yo. The tissues were categorized to four grade according to the World Health Organization criteria: 11(10.8%) low grade gliomas, 18(17.8%) grade III gliomas and 72(71.3%) glioblastomas. We used as a control normal brain cortex from 15 autopsy cases. RESULTS: Nuclear, cytoplasmic and total immunoreaction for p65 was significantly higher in grade IV comparing to grade III as well as in grade III comparing to LGG (p = 0.01 for nuclear, p = 0.003 for cytoplasmic, p = 0.001 for total expression). Strong correlations were observed in immunoreactivity for p50 subunit with grades with higher expression in high grade comparing to LGG (P= 0.09). Normal brain tissues didn't display any expression of NF-kB subunits. The expression levels of ING-4 was reversely correlated to tumor grade and was higher in LGG comparing to high grade (p = 0.07) and the normal brain tissue expressed high levels of ING-4. The expression levels of AEG-1 was higher in high grade gliomas comparing with lower grade (0.016) and minimal in normal brain. No correlation noted between age groups and genders and expression levels of all molecules. CONCLUSIONS: The expression of NF-kB and its regulating factors seems to be important role in gliomas behavior. More studies are required in order to evaluate the role of these molecules to gliomagenesis and glioma progression.