tbuckley/cabot-search huggingface dataset:
Chronic myelomonocytic leukemia: 2016 update on diagnosis, risk stratification, and management
Authors: Mrinal M. Patnaik, Ayalew Tefferi
Journal: American Journal of Hematology (2016)

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder characterized by overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms. Diagnosis is based on the presence of persistent (&gt;3 months) peripheral blood monocytosis (&gt;1 × 10 9 /L), along with bone marrow dysplasia. Clonal cytogenetic abnormalities occur in ∼20–30% of patients, while &gt;90% have gene mutations. Mutations involving TET2 (∼60%), SRSF2 (∼50%), ASXL1 (∼40%), and RAS (∼30%) are frequent; with only ASXL1 mutations negatively impacting overall survival. Two molecularly integrated, CMML‐specific prognostic models include; the Groupe Français des Myélodysplasies (GFM) and the Molecular Mayo Model (MMM). The GFM model segregates patients into 3 groups based on: age &gt;65 years, WBC &gt;15 × 10 9 /L, anemia, platelets &lt;100 × 10 9 /L, and ASXL1 mutation status, with respective median survivals of 56 (low), 27.4 (intermediate), and 9.2 (high) months. The MMM is based on ASXL1 mutational status, absolute monocyte count &gt;10 × 10 9 /L, hemoglobin &lt;10 g/dL, platelets &lt;100 × 109/L and circulating immature myeloid cells. This model stratifies patients into four groups; high (≥3 risk factors), intermediate‐2 (2 risk factors), intermediate‐1 (1 risk factor) and low (no risk factors), with median survivals of 16, 31, 59, and 97 months, respectively. Hypomethylating agents such as 5‐azacitidine and decitabine are commonly used, with overall response rates of ∼30–40% and complete remission rates of ∼7–17%. Allogeneic stem cell transplant is the only potentially curative option, but is associated with significant morbidity and mortality. Individualized therapy, including epigenetic modifiers and small molecule inhibitors, are exciting prospects. Am. J. Hematol. 91:632–642, 2016. © 2016 Wiley Periodicals, Inc.
Mammalian Chromosomes &lt;italic&gt;In Vitro&lt;/italic&gt;. X. Heteroploid Transformation in Neoplastic cells&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: T. C. Hsu, Oleta Klatt
Journal: JNCI Journal of the National Cancer Institute (1959)

Three tissue-culture strains were successfully established from Novikoff hepatoma cells originally carried intraperitoneally in Sprague-Dawley rats. The populations in vivo consisted roughly of 60 percent s (s = 2n-3 = 39) and 40 percent 2s (2s = 4n-6 = 78) elements. The populations in vitro at first showed a decrease in the number of s cells and an increase in 2s cells. Later, the proportion of the 2s group also decreased, and many cells with chromosome numbers in the 60's or low 70's appeared (the stage of spread of chromosome spectrum). After the stage of “spread,” the chromosome numbers narrowed and the populations may be represented by a modal chromosome number or by a small group of connecting numbers. Strain N-1 was characterized by possessing 67 or 68 chromosomes; strain N-3, 59 to 61 chromosomes; and strain N-4, 74 or 75 chromosomes. If we consider the s cells “diploid” and the 2s cells “tetraploid,” the route of “heteroploid transformation” in vitro taken by Novikoff hepatoma cells may serve as a model for the transformation of normal tissues. Prolonged residence in vitro seemed to cause the cells to lose their transplantability and perhaps also malignancy. The cell strains finally failed to produce tumors when reintroduced into hosts. These hosts developed a certain degree of immunity against subsequent challenges of tumor cells in vivo. Cultivating tumor cells in vitro thus appeared to attenuate the virulence of the cells without causing them to lose their antigenicity.
HER2 gene amplification (HER2) and hormone receptor expression (ER/PR) in early (EBC) and metastatic breast cancer (MBC) in the same patients
Authors: U. Wilking, L. Skoog, G. Elmberger, N. Wilking, J. Bergh
Journal: Journal of Clinical Oncology (2007)

1023 Background: HER2 and ER/PR expression are used as predictors of response to trastuzumab and hormonal treatments, respectively. In most institutions these markers are only analyzed in EBC and any later treatment decisions are based these analyses. At our institution, it has been the routine to verify the breast cancer diagnosis, as well as HER2 and ER/PR status in MBC, if ever possible. We focus this report on data obtained for double testing during the time period 2000–2005. Methods: HER2 and ER/PR in MBC (metastatic site = 43% cutaneous or lymph node; 17% liver; 29% bone, 3% CNS and 8% GI tract) were compared to EBC results. Any result with IHC 3+/FISH amplification was regarded as HER2 +. Any ER/PR expression was regarded as ER/PR +. Results: HER2 testing: We identified sixty one (61) patients who had their tumor analyzed for HER2 in both EBC and MBC. Thirty-seven (61%) of these tumors were negative in both EBC and MBC. One (2%) had a positive EBC and negative MBC; 20 patients (32%) had both positive EBC and MBC testing and 3 patients (5%) had negative EBC testing and positive MBC testing. ER/PR testing: One hundred and four (104) patients underwent both EBC and MBC testing for ER/PR. Forty nine (47%) remained ER/PR +, 7 (7%) had EBC- and MBC+ test; 22 patients (21%) had ER/PR EBC+ test and MBC- test; 26 patients (25%) remained negative from EBC to MBC. Conclusions: Breast cancer tumor characteristics are not constant as the disease progresses. In this study we found that 7% have a change in their HER2 expression and 28% had a change in their ER/PR expression based on analyses of both primary and metastatic disease. It is therefore important that, whenever possible, not only to morphologically verify MBC, but also to analyze HER2 and hormone receptors (ER/PR) to be able to offer the best possible treatment to all patients. [Table: see text]
The Use of Propensity Score Methods in Psychotherapy Research
Authors: Anna Bartak, Marieke D. Spreeuwenberg, Helene Andrea, Jan J.V. Busschbach, Marcel A. Croon, Roel Verheul, Paul M.G. Emmelkamp, Theo Stijnen
Journal: Psychotherapy and Psychosomatics (2008)

Randomized controlled trials are considered the best scientific proof of effectiveness. There is increasing concern, though, about their feasibility in psychotherapy research. We discuss a quasi-experimental study design for situations in which a randomized controlled trial is not feasible. Here, as an alternative strategy, the propensity score (PS) method is used to correct for selection bias.We used data from a Dutch research project, SCEPTRE (Study on Cost-Effectiveness of Personality Disorder Treatment). The sample consisted of 749 psychotherapy patients with personality pathology. We tested whether the PS method was useful and applicable. We examined differences between 2 treatment groups (short vs. long treatment duration) in pretreatment characteristics before and after PS correction. This revealed the impact of the PS on outcome differences.The PS offered statistical control over observed pretreatment differences between patients in a non-randomized study.When a randomized controlled trial is not possible, this quasi-experimental design using the PS could be a feasible alternative. Its advantages and limitations are discussed. Implemented carefully, this method is promising for future effectiveness research.
Early Exposure to Traffic-Related Air Pollution, Respiratory Symptoms at 4 Years of Age, and Potential Effect Modification by Parental Allergy, Stressful Family Events, and Sex: A Prospective Follow-up Study of the PARIS Birth Cohort
Authors: Fanny Rancière, Nicolas Bougas, Malika Viola, Isabelle Momas
Journal: Environmental Health Perspectives (2016)

The relation between traffic-related air pollution (TRAP) exposure and the incidence of asthma/allergy in preschool children has been widely studied, but results remain heterogeneous, possibly due to differences in methodology and susceptibility to TRAP.We aimed to study the relation of early TRAP exposure with the development of respiratory/allergic symptoms and asthma during preschool years, and to investigate parental allergy, "stressful" family events, and sex as possible effect modifiers.We examined data of 2,015 children from the PARIS birth cohort followed up with repeated questionnaires completed by parents until age 4 years. TRAP exposure in each child's first year of life was estimated by nitrogen oxides (NOx) air dispersion modeling, taking into account both home and day care locations. Association between TRAP exposure and patterns of wheezing, dry night cough, and rhinitis symptoms was studied using multinomial logistic regression models adjusted for potential confounders. Effect modification by parental history of allergy, stressful family events, and sex was investigated.An interquartile range (26 μg/m3) increase in NOx levels was associated with an increased odds ratio (OR) of persistent wheezing at 4 years (adjusted OR = 1.27; 95% confidence interval: 1.09, 1.47). TRAP exposure was positively associated with persistent wheeze, dry cough, and rhinitis symptoms among children with a parental allergy, those experiencing stressful family events, and boys, but not in children whose parents did not have allergies or experience stressful events, or in girls (all interaction p-values < 0.2).This study supports the hypothesis that not all preschool children are equal regarding TRAP health effects. Parental history of allergy, stressful family events, and male sex may increase their susceptibility to adverse respiratory effects of early TRAP exposure.
Humoral and intestinal immunity induced by new schedules of bivalent oral poliovirus vaccine and one or two doses of inactivated poliovirus vaccine in Latin American infants: an open-label randomised controlled trial
Authors: Edwin J Asturias, Ananda S Bandyopadhyay, Steve Self, Luis Rivera, Xavier Saez-Llorens, Eduardo Lopez, Mario Melgar, James T Gaensbauer, William C Weldon, M Steven Oberste, Bhavesh R Borate, Chris Gast, Ralf Clemens, Walter Orenstein, Miguel O'Ryan G, José Jimeno, Sue Ann Costa Clemens, Joel Ward, Ricardo Rüttimann
Journal: The Lancet (2016)
Allogeneic bone marrow transplantation after high-dose busulfan and cyclophosphamide in patients with acute nonlymphocytic leukemia
Authors: RB Geller, R Saral, S Piantadosi, M Zahurak, GB Vogelsang, JR Wingard, RF Ambinder, WB Beschorner, HG Braine, WH Burns
Journal: Blood (1989)
Postcardiotomy delirium: conclusions after 25 years?
Authors: L W Smith, J E Dimsdale
Journal: American Journal of Psychiatry (1989)

Although postcardiotomy delirium has been studied widely, there are few data about the current prevalence, compared to that reported in the late 1960s. There have been few efforts to replicate early observations. The authors review the literature using meta-analysis to combine the results of 44 studies. They examined the relationships between postcardiotomy delirium and 28 hypothesized risk variables. The prevalence of postcardiotomy delirium has remained fairly constant over time at 32%. There was no difference in the total prevalence of postcardiotomy delirium reported in studies that used interviews versus chart reviews. Sex, previous psychiatric illness, intelligence, and time on bypass failed to correlate with postcardiotomy delirium, and age correlated with it only slightly. Correlation coefficients of more than 0.30 were found only for noncongenital heart disease and postoperative EEG abnormality. Preoperative psychiatric intervention had the highest correlation with postcardiotomy delirium (r = -0.60).
Non-Producing Multiple Myeloma (MM) Is a Distinct Subset Of Non-Secretory MM Characterized By High Cyclin D1 Expression and Decreased Progression Free Survival
Authors: Xenofon Papanikolaou, Qing Zhang, Christoph Heuck, Sarah Waheed, Shebli Atrash, Zeba N Singh, Daisy V. Alapat, Frits van Rhee, Shweta S. Chavan, Joshua Epstein, Bart Barlogie
Journal: Blood (2013)
Abstract P5-06-05: MED12 exon 2 mutations in phyllodes tumors of the breast
Authors: S Nagasawa, T Ohta, K Tsugawa
Journal: Cancer Research (2016)

Abstract Exon 2 of MED12, a subunit of the transcriptional mediator complex, has been frequently mutated in uterine leiomyomas and breast fibroadenomas; however, it has been rarely mutated in other tumors. Although the mutations were also found in uterine leiomyosarcomas, the frequency was significantly lower than in uterine leiomyomas. Here, we examined the MED12 mutation in phyllodes tumors, another biphasic tumor with epithelial and stromal components related to breast fibroadenomas. Mutations in MED12 exon 2 were analyzed in nine fibroadenomas and eleven phyllodes tumors via Sanger sequencing. A panel of cancer- and sarcoma-related genes was also analyzed using Ion Torrent next-generation sequencing. Six mutations in fibroadenomas, including those previously reported (6/9, 67%), and five mutations in phyllodes tumors (5/11, 45%) were observed. Three mutations in the phyllodes tumors were missense mutations at Gly44, which is common in uterine leiomyomas and breast fibroadenomas. In addition, two deletion mutations (in-frame c.133_144del12 and loss of splice acceptor c.100-68_137del106) were observed in the phyllodes tumors. No other recurrent mutation was observed with next-generation sequencing. Frequent mutations in MED12 exon 2 in the phyllodes tumors suggest that it may share genetic etiology with uterine leiomyoma, a subgroup of uterine leiomyosarcomas and breast fibroadenoma. Citation Format: Nagasawa S, Ohta T, Tsugawa K. MED12 exon 2 mutations in phyllodes tumors of the breast. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-06-05.
Overcoming barriers to develop a broad access data sharing platform.
Authors: Charles Hugh-Jones, Robin Jenkins, Joel Beetsch, Kald Abdallah, Michael Curnyn, Fang Liz Zhou, Mace L. Rothenberg, Gregory A. Curt, John Dornan, Martin J. Murphy
Journal: Journal of Clinical Oncology (2015)

e17690 Background: Analysis of Phase 3 clinical trial data is uncommon beyond the pre-defined protocol. Project Data Sphere, LLC (PDS), an independent initiative of the non-profit CEO Roundtable on Cancer, provides a single platform to share, integrate, and analyze historical comparator-arm cancer trial data sets from Phase 3 trials together with protocols, CRFs, and data descriptors, online at www.ProjectDataSphere.org. Methods: The commitment to develop broad access to an oncology clinical trial data sharing platform was made by the CEO Roundtable on Cancer in 2011. Numerous barriers existed that historically impeded broad data sharing including privacy, errant reanalysis, intellectual property, IT, resource concerns and ability to maintain data utility. PDS engaged experts worldwide through a network of collaboration to develop approaches to address these concerns. Results: A team of data de-identification experts, representatives from academia, industry, government and advocacy groups, were engaged to review privacy and errant reanalysis concerns. Collaboration resulted in an approach to effectively mitigate risk while maintaining data integrity for secondary research. Approaches included providers adhering to customized and rigorous patient de-identification methodologies with a goal of initially sharing comparator-arm data only. To develop a legal framework, representatives from PDS, providers and legal counsel from Hogan Lovell’s developed uniform legal agreements for provision and use of data. To develop a technical platform for sharing, integration and analytics, a team of experts from the SAS Institute, data providers, other data platform experts collaborated to develop a state of the art platform that also minimizes resource requirements for providers. Conclusions: The launch of PDS in April 2014 demonstrates that the historical barriers to data sharing can be overcome. Data is now available from 7 providers and over 300 users are registered in the first eight months. In November 2014 the first public presentation of PDS derived research was made at the 21st Annual PCF Scientific Retreat 2014.
Royal colleges welcome junior contract agreement
Authors: Abi Rimmer
Journal: BMJ (2016)

Medical royal colleges have welcomed the agreement that has been reached on a new contract for junior doctors in England.

On 18 May the arbitration body Acas (the Advisory, Conciliation and Arbitration Service) announced that an agreement had been reached on a new contract for junior doctors in England, after 10 days of talks between the BMA and the government.1 BMA junior doctor members will be balloted on acceptance …
Indochinese versions of the Hopkins Symptom Checklist-25: a screening instrument for the psychiatric care of refugees
Authors: R F Mollica, G Wyshak, D de Marneffe, F Khuon, J Lavelle
Journal: American Journal of Psychiatry (1987)

The United States is accepting the largest number of displaced persons since World War II. Over 70% are Southeast Asians; many have suffered serious war trauma and torture. Cultural differences in health-seeking behavior and lack of specialized mental health services make the recognition of psychiatric distress in Southeast Asia refugees difficult for American health care providers. The authors describe the development and validation of Cambodian, Laotian, and Vietnamese versions of the Hopkins Symptom Checklist-25. This brief, simple, and reliable instrument is well received by refugee patients, offers an effective screening method for the psychiatric symptoms of anxiety and depression, and is especially helpful for evaluating trauma victims.
Abstract A09: The long noncoding RNA SPRIGHTLY regulates cell proliferation in primary human melanocytes
Authors: Wei Zhao, Joseph Mazar, Bongyong Lee, Junko Sawada, Jian-Liang Li, John Shelley, Subramaniam Govindarajan, Dwight Towler, John S. Mattick, Masanobu Komatsu, Marcel E. Dinger, Ranjan J. Perera
Journal: Cancer Research (2016)

Abstract The long non-coding RNA (lncRNA) SPRIGHTLY (formerly SPRY4-IT1), which lies within the intronic region of the SPRY4 gene is upregulated in human melanoma cells compared to melanocytes. SPRIGHTLY regulates a number of cancer hallmarks including proliferation, motility, and apoptosis. To better understand its oncogenic role, SPRIGHTLY was stably transfected into human melanocytes, which resulted in increased cellular proliferation, invasion, and development of a multinucleated dendritic-like phenotype. RNA sequencing and mass spectrometric analysis of SPRIGHTLY-expressing cells revealed changes in the expression of genes involved in cell proliferation, apoptosis, chromosome organization, regulation of DNA damage responses, and cell cycle. The proliferation marker Ki67, minichromosome maintenance genes (MCM2-5), and the anti-apoptotic genes X-linked inhibitor of apoptosis (XIAP) and baculoviral IAP repeat-containing 7 (livin) were upregulated in SPRIGHTLY-expressing melanocytes, while the pro-apoptotic tumor suppressor gene DPPIV/CD26 was downregulated. Since downregulation of DPPIV is known to be associated with malignant transformation in melanocytes, SPRIGHTLY-mediated DPPIV downregulation may play an important role in melanoma pathobiology. These findings provide novel insights into how SPRIGHTLY regulates proliferation, and apoptosis in primary human melanocytes. Citation Format: Wei Zhao, Joseph Mazar, Bongyong Lee, Junko Sawada, Jian-Liang Li, John Shelley, Subramaniam Govindarajan, Dwight Towler, John S. Mattick, Masanobu Komatsu, Marcel E. Dinger, Ranjan J. Perera. The long noncoding RNA SPRIGHTLY regulates cell proliferation in primary human melanocytes. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr A09.
Effect of Early Prophylactic High-Dose Recombinant Human Erythropoietin in Very Preterm Infants on Neurodevelopmental Outcome at 2 Years
Authors: Giancarlo Natalucci, Beatrice Latal, Brigitte Koller, Christoph Rüegger, Beate Sick, Leonhard Held, Hans Ulrich Bucher, Jean-Claude Fauchère
Journal: JAMA (2016)

<h3>Importance</h3> Very preterm infants are at risk of developing encephalopathy of prematurity and long-term neurodevelopmental delay. Erythropoietin treatment is neuroprotective in animal experimental and human clinical studies. <h3>Objective</h3> To determine whether prophylactic early high-dose recombinant human erythropoietin (rhEPO) in preterm infants improves neurodevelopmental outcome at 2 years' corrected age. <h3>Design, Setting, and Participants</h3> Preterm infants born between 26 weeks 0 days' and 31 weeks 6 days' gestation were enrolled in a randomized, double-blind, placebo-controlled, multicenter trial in Switzerland between 2005 and 2012. Neurodevelopmental assessments at age 2 years were completed in 2014. <h3>Interventions</h3> Participants were randomly assigned to receive either rhEPO (3000 IU/kg) or placebo (isotonic saline, 0.9%) intravenously within 3 hours, at 12 to 18 hours, and at 36 to 42 hours after birth. <h3>Main Outcomes and Measures</h3> Primary outcome was cognitive development assessed with the Mental Development Index (MDI; norm, 100 [SD, 15]; higher values indicate better function) of the Bayley Scales of Infant Development, second edition (BSID-II) at 2 years corrected age. The minimal clinically important difference between groups was 5 points (0.3 SD). Secondary outcomes were motor development (assessed with the Psychomotor Development Index), cerebral palsy, hearing or visual impairment, and anthropometric growth parameters. <h3>Results</h3> Among 448 preterm infants randomized (mean gestational age, 29.0 [range, 26.0-30.9] weeks; 264 [59%] female; mean birth weight, 1210 [range, 490-2290] g), 228 were randomized to rhEPO and 220 to placebo. Neurodevelopmental outcome data were available for 365 (81%) at a mean age of 23.6 months. In an intention-to-treat analysis, mean MDI was not statistically significantly different between the rhEPO group (93.5 [SD, 16.0] [95% CI, 91.2 to 95.8]) and the placebo group (94.5 [SD, 17.8] [95% CI, 90.8 to 98.5]) (difference, −1.0 [95% CI, −4.5 to 2.5];<i>P</i> = .56). No differences were found between groups in the secondary outcomes. <h3>Conclusions and Relevance</h3> Among very preterm infants who received prophylactic early high-dose rhEPO for neuroprotection, compared with infants who received placebo, there were no statistically significant differences in neurodevelopmental outcomes at 2 years. Follow-up for cognitive and physical problems that may not become evident until later in life is required. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT00413946
The elective within the required psychiatric clerkship
Authors: M D Plutzer
Journal: American Journal of Psychiatry (1979)

Two important goals of a successful psychiatric clerkship are to maximize students' responsibility and flexibility and to provide knowledge and skills relevant to their future careers. The author describes an elective program within the required medical school psychiatric clerkship that meets these criteria. On the basis of feedback from both students and staff, the author concludes that the advantages of the elective program to students, patients, faculty, and the department far outweigh the disadvantages.