tbuckley/cabot-search huggingface dataset:
Adolescent Psychiatry, vol 1: Developmental and Clinical Studies
Authors: Marjorie C. Meehan
Journal: JAMA (1971)

<b>Teaching and Learning Adolescent Psychiatry</b>edited by Daniel Offer and James F. Masterson (conference University of Chicago, Nov 1969), 157 pp, $9.50, Springfield, Ill: Charles C Thomas, Publisher, 1971. Psychiatrists, like the rest of the community, recently have become more aware of teenagers. In the early 1950s there were few psychiatric facilities for treating adolescents and probably no psychiatrists considered themselves specialists in this field. Since then clinics and inpatient services have sprung up, books and articles have multiplied. In 1958, the Society for Adolescent Psychiatry of New York was established. Similar organizations formed in other cities, and in 1967 these were confederated in the American Society for Adolescent Psychiatry, which had over 900 members by 1970. This organization is sponsoring a series of books, of which<i>Adolescent Psychiatry: Development and Clinical Studies</i>is the first. The same organization sponsored a conference in 1969, the proceedings of which are now
Alternative Overexpression of NRF2 or MYC Defines a Subgroup of Poor Prognosis Acute Myeloid Leukemia and Suggests a Novel Therapeutic Strategy By Combined Bromodomain Inhibition and Forced NRF2 Pathway Activation
Authors: Giorgia Simonetti, Samantha Bruno, Carmine Onofrillo, Cristina Papayannidis, Giovanni Marconi, Michele Cavo, Lorenzo Montanaro, Giovanni Martinelli
Journal: Blood (2018)
History of Psychopharmacology
Authors: Joel T. Braslow, Stephen R. Marder
Journal: Annual Review of Clinical Psychology (2019)

We live in an age of psychopharmacology. One in six persons currently takes a psychotropic drug. These drugs have profoundly shaped our scientific and cultural understanding of psychiatric disease. By way of a historical review, we try to make sense of psychiatry's dependency on psychiatric drugs in the care of patients. Modern psychopharmacology began in 1950 with the synthesis of chlorpromazine. Over the course of the next 50 years, the psychiatric understanding and treatment of mental illness radically changed. Psychotropic drugs played a major part in these changes as state hospitals closed and psychotherapy gave way to drug prescriptions. Our review suggests that the success of psychopharmacology was not the consequence of increasingly more effective drugs for discrete psychiatric diseases. Instead, a complex mix of political economic realities, pharmaceutical marketing, basic science advances, and changes in the mental health-care system have led to our current infatuation with psychopharmacology.
Severity and Variability of Depression Symptoms Predicting Suicide Attempt in High-Risk Individuals
Authors: Nadine M. Melhem, Giovanna Porta, Maria A. Oquendo, Jamie Zelazny, John G. Keilp, Satish Iyengar, Ainsley Burke, Boris Birmaher, Barbara Stanley, J. John Mann, David A. Brent
Journal: JAMA Psychiatry (2019)

Predicting suicidal behavior continues to be among the most challenging tasks in psychiatry.To examine the trajectories of clinical predictors of suicide attempt (specifically, depression symptoms, hopelessness, impulsivity, aggression, impulsive aggression, and irritability) for their ability to predict suicide attempt and to compute a risk score for suicide attempts.This is a longitudinal study of the offspring of parents (or probands) with mood disorders who were recruited from inpatient units at Western Psychiatric Institute and Clinic (Pittsburgh) and New York State Psychiatric Institute. Participants were recruited from July 15, 1997, to September 6, 2005, and were followed up through January 21, 2014. Probands and offspring (n = 663) were interviewed at baseline and at yearly follow-ups for 12 years. Lifetime and current psychiatric disorders were assessed, and self-reported questionnaires were administered. Model evaluation used 10-fold cross-validation, which split the entire data set into 10 equal parts, fit the model to 90% of the data (training set), and assessed it on the remaining 10% (test set) and repeated that process 10 times. Preliminary analyses were performed from July 20, 2015, to October 5, 2016. Additional analyses were conducted from July 26, 2017, to July 24, 2018.The broad definition of suicide attempt included actual, interrupted, and aborted attempts as well as suicidal ideation that prompted emergency referrals during the study. The narrow definition referred to actual attempt only.The sample of offspring (n = 663) was almost equally distributed by sex (316 female [47.7%]) and had a mean (SD) age of 23.8 (8.5) years at the time of censored observations. Among the 663 offspring, 71 (10.7%) had suicide attempts over the course of the study. The trajectory of depression symptoms with the highest mean scores and variability over time was the only trajectory to predict suicide attempt (odds ratio [OR], 4.72; 95% CI, 1.47-15.21; P = .01). In addition, we identified the following predictors: younger age (OR, 0.82; 95% CI, 0.74-0.90; P < .001), lifetime history of unipolar disorder (OR, 4.71; 95% CI, 1.63-13.58; P = .004), lifetime history of bipolar disorder (OR, 3.4; 95% CI, 0.96-12.04; P = .06), history of childhood abuse (OR, 2.98; 95% CI, 1.40-6.38; P = .01), and proband actual attempt (OR, 2.24; 95% CI, 1.06-4.75; P = .04). Endorsing a score of 3 or higher on the risk score tool resulted in high sensitivity (87.3%) and moderate specificity (63%; area under the curve = 0.80).The specific predictors of suicide attempt identified are those that clinicians already assess during routine psychiatric evaluations; monitoring and treating depression symptoms to reduce their severity and fluctuation may attenuate the risk for suicidal behavior.
Voters and Health Care in the 1996 Election
Authors: R J Blendon, J M Benson, M Brodie, D E Altman, D Rowland, P Neuman, M James
Journal: JAMA (1997)

OVER THE past decade, health care has emerged as an important issue for voters in national elections. 1,2 As a result, political leaders from both parties have been shown to pay increasing attention to the views of voters when selecting their health care priorities and positions for the next administration and Congress. 3,4 What message about health care policy should our elected officials, the health care community, and the American people take from the 1996 presidential and congressional elections? What, from the voters' perspective, should be the health care agenda for the next Congress?  This article uses the results of a postelection survey of self-described voters, combined with secondary analysis of 2 Election Day exit polls of voters and 3 national opinion surveys, to examine these questions. The voting public's responses tell us a great deal about the role of health care in the 1996 election and in the agenda
ASH 2009 meeting report—Top 10 clinically oriented abstracts in coagulation medicine and platelet disorders
Authors: Rajiv K. Pruthi
Journal: American Journal of Hematology (2010)

The 2009 American Society of Hematology annual meeting took place December 5-8, in New Orleans, Louisiana, USA.Official sources indicate over 20,000 people attended the meeting and more than 4,000 scientific abstracts were presented.Among the latter, close to 100 were in the category of BCR-ABL1-negative myeloproliferative neoplasms (MPN), including polycythemia vera, essential thrombocythemia and primary myelofibrosis.Here, I summarize and discuss the top 10 MPN abstracts, which I believe contain information that is immediately relevant to clinical practice.All 10 abstracts are published in full in the November 20, 2009 issue of Blood (volume 114, No. 22) and are identified here by their abstract numbers.
Prevalence, Characteristics, and Risk Factors of Moderate or High Hyperopia among Multiethnic Children 6 to 72 Months of Age
Authors: Xuejuan Jiang, Kristina Tarczy-Hornoch, Douglas Stram, Joanne Katz, David S. Friedman, James M. Tielsch, Saiko Matsumura, Seang-Mei Saw, Paul Mitchell, Kathryn A. Rose, Susan A. Cotter, Rohit Varma
Journal: Ophthalmology (2019)
Electroconvulsive therapy: lack of studies is not the same as lack of effect
Authors: Keith Dudleston
Journal: BMJ (2019)

Read and Cunliffe argue against electroconvulsive therapy (ECT).1 Attitudes to ECT can be formed early in a career. As a young doctor, I witnessed the double blind, placebo controlled trial of the short term efficacy of ECT for inpatients with depression that was conducted at Mapperley Hospital, Nottingham, in the early 1980s.2 After the …
Mutational analysis of protein tyrosine phosphatase, receptor type, T (PTPRT) in esophageal adenocarcinoma
Authors: Takatsugu Kan, Jing Yin, Andreea Olaru, Yuriko Mori, Fumiaki Sato, Kun Cai, Anca Sterian, Suna Wang, Agnes Berki, James Hamilton, Bogdan C. Paun, John M. Abraham, Stephen J. Meltzer
Journal: Cancer Research (2005)

1908  Tyrosine phosphorylation is important in signaling pathways underlying tumorigenesis. Protein tyrosine phosphatase, receptor type, T (PTPRT) is a protein tyrosine phosphatase that plays a suppressive role in tumorigenesis. Mutational analysis of the PTPRT gene has been performed in several types of cancers, including colorectal, breast, ovarian, gastric, and pancreatic cancers, but not in tumors of the esophagus.   48 esophageal adenocarcinoma (EAC) patients were enrolled in this study. All patients underwent surgical resection at the Baltimore VA Hospital with informed consent. Each exon was amplified by PCR using published primer sets (Science, Vol. 304, p.1164-66, 2004) from cancer genomic DNA and directly sequenced with dye terminator chemistry (DYEnamic ET dye terminator kit, and MegaBACE 1000, Amersham Biosciences, Buckinghamshire, UK). Analysis of the sequences was performed by sequence analysis software (Sequence Analyser ver.3.0, Amersham Biosciences, Mutation Surveyor ver.2.41, Soft Genetics Inc., State College, PA) Whenever a presumptive mutation was identified, it was examined with reverse sequence primers to confirm any sequence alterations. We also examined genomic DNA sequence from white blood cells of each identical patient to determine whether the mutation was acquired somatically or not. We discovered 14 germline sequence alterations in 9/48 (18.8%) patients and 2 somatic mutations in 2/48 (4.2%) patients: at mRNA nucleotide positions G2642del (homozygous) and C3765T (heterozygous). 12 of these 14 germline sequence alterations were synonymous. T1059C, which had been previously reported as a synonymous polymorphism, was detected in 3 patients. We also discovered T2580C (heterozygous) in 3 patients and C1305T (homozygous) in 2 patients, both of which synonymous and not reported.   Two somatic mutations of PTPRT were detected in EACs. Furthemore, a number of novel and known germline sequence alterations of PTPRT gene were discovered in EACs. Although some of these sequence alterations may correspond to polymorphisms, some may represent true germline mutations associated with an increased risk of EAC development. Family studies are required to investigate this possibility.
P171 Hsp90 in axial spondyloarthritis, psoriatic arthritis and rheumatoid arthritis
Authors: H Storkanova, K Bubova, S Oreska, M Spiritovic, B Hermankova, M Gregorova, K Mintalova, J Horinkova, K Pavelka, J Vencovsky, J Stolfa, M Husakova, S Forejtova, L Senolt, M Tomcik
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD. <h3>Introduction</h3> Hsp90 is a highly conserved molecular chaperone that regulates activation of innate immunity, antigen presentation, and the induction of proinflammatory cytokines and chemokines. These properties predispose Hsp90 to its potential role in the pathogenesis of autoimmune inflammatory rheumatic diseases. <h3>Objectives</h3> The aim of this study was to assess plasma Hsp90 in patients with axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), rheumatoid arthritis (RA) and healthy controls (HC) and to determine its potential association with disease activity and clinical features. <h3>Methods</h3> A total of 136 patients, that were divided into groups according to the type of a rheumatic disease (SpA, RA, PsA), and age-/sex- matched healthy individuals were included. Plasma Hsp90 levels were measured by ELISA (eBioscience, Vienna, Austria). Data are presented as median (IQR). <h3>Results</h3> Plasma Hsp90 levels were significantly increased in axSpA and in RA patients compared to HC. The increased plasma levels of Hsp90 in PsA compared to HC did not reach statistical significance. Hsp90 concentrations were higher in RA patients with an altered serum lipid profile: low-density lipoprotein (LDL: r=0.352, p=0.048), high-density lipoprotein (HDL: r=−0.349, p=0.046) and atherogenic index (calculated as log (triglycerides/HDL)) (AI: r=0.454, p=0.009). Furthermore, Hsp90 levels in r-axSpA patients positively correlated with the MRI presence of active inflammatory lesions in sacroiliac joints (SPARCC MRI score for SI joints: r=0.594, p=0.020). Increased Hsp90 levels in PsA patients were associated with the count of joint deformities (r=0.526, p=0.025). No further statistically significant associations were found between Hsp90 plasma levels and RA-, axSpA- or PsA-specific clinical features. <h3>Conclusions</h3> We demonstrated elevated plasma concentrations of Hsp90 in RA and in axSpA patients compared to healthy controls. Hsp90 could be associated with early alterations of serum lipids and development of atherosclerosis in RA. Furthermore, in r-axSpA, Hsp90 may represent an independent marker of SI joint inflammation, whereas in PsA, plasma Hsp90 correlates with joint deformities. These data suggest that Hsp90 could become a potential biomarker of structural changes in SpA. <h3>Reference</h3> None. <h3>Acknowledgements</h3> Supported by AZV-16–33542A and MHCR 023728. <h3>Disclosure of Interest</h3> None declared.
P012 Patients with cancer and preexisting autoimmune and inflammatory diseases treated by anti-programmed death 1 (PD-1) antibodies at gustave roussy cancer center
Authors: F-X Danlos, M Najean, A-L Voisin, A Marabelle, M Texier, O Lambotte
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD. <h3>Introduction</h3> Immune checkpoint inhibitors anti PD-1 are monoclonal antibodies used in cancers.<sup>1</sup> PD-1 ligand/PD-1 pathway antagonism between cancer cells and antitumoral cytotoxic CD8 T cells increase antitumoral immunity but is involved in autoimmune diseases (AID). <h3>Objectives</h3> Evaluate tolerance and efficacy of anti PD-1 in AID patients. <h3>Methods</h3> Patients had been included in REISAMIC registry (Registry of Severe Adverse Events of Immunomodulating Monoclonal Antibodies in Oncology) between June 1st, 2014, and December 31st, 2017. Patients were treated with anti-PD-1. Exclusion criteria were malignant hematologic disease, second advanced cancer or chronic viral infection. AID subtypes were defined for sensitivity analyses: diseases of clinical interest (DCI), prognostic interest (DPI) and vitiligo. One patient with pre-existing AID were matched on age, sex and cancer type with 3 patients without preexisting AID (controls). Analyses were adjusted for OMS status, corticosteroid, cerebral metastasis, LDH, albuminemia and neutrophil/lymphocyte ratio &gt;3. Endpoints were grade ≥2 irAE free survival and overall survival (OS). Objective response rates (ORR) were described. <h3>Results</h3> 641 patients were included in REISAMIC. Among them, 69 patients were excluded. 572 patients had been included: 63 with AID and 509 controls. Among AID patients, we observed 38% DCI, 38% DPI and 24% vitiligo. DCI were Sjögren syndrome (n=4), rheumatoid arthritis (n=4), polymyalgia rheumatica/giant cell arteritis (n=2) and others. DPI were psoriasis (n=11), thyroiditis (n=8) and others. We matched 55 AID patients with 165 controls. Cancer type, TNM or AJCC grade, age and sex were similar between AID patients and controls. Overall survival (HR 0,67, IC95% [0,42–1,08], p=0,098) and irAE free survival (HR 1,27, IC95% [0,84–1,90], p=0,25) were not different between AID patients and controls. After vitiligo exclusion in sensitivity analyses, irAE free survival was shorter for AID patients than controls (HR 1,69, IC05% [1- 2,87], p=0,05) and more for DCI patients only (HR 2,66, IC95% [1,01–7], p=0,049). ORR were 35,5% and 28,5% for AID patients and controls respectively. <h3>Conclusions</h3> Preexisting AID should not be a contraindication for anti PD-1. We suspect that mechanisms involved in AID are important in irAE mechanism and antitumoral response. CD4 T cells and Th17 cells should be study in these situations. <h3>Reference</h3> Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. <i>Science</i> 2018 Mar 23;359(6382):1350–5. <h3>Disclosure of Interest</h3> None declared.
CBIO-06. IDH1 MUTATIONS TRIGGER ENHANCEMENT OF ENDOCYTOSIS VIA Rac1
Authors: Chunzhang Yang, Yang Liu
Journal: Neuro-Oncology (2016)

Mutations in isocitrate dehydrogenase (IDH1/2) are common early genetic abnormalities in low grade diffusive/anaplastic astrocytomas and oligodendrogliomas. Despite the influence of these IDH mutations on tricarboxylic acid cycle, little is known about the impact of IDH mutations on the adaptive changes in cellular biology and tumor characteristics such as migration. In the present study, we report that IDH1 mutations result in fundamental changes in endocytosis and cellular motility, through the activation of a small GTPase Rac1. We established a series of U251 cell lines with stable expression of IDH1 Wildtype, R132C or R132H variant. Endocytosis were analyzed through electron microscopy, optical imaging and uptake assays. Changes in molecular signaling were further analyzed by quantitative PCR, western blot, immunostaining and GTPase activation assay. Introduction of IDH1 mutations led to robust changes in the plasma membrane, which is demonstrated by increased membrane ruffling, lamellipodia formation, enhancement in endocytosis (>27x increase endocytosis index) and cellular migration (>2x increase in travel distance). Up-regulation of endocytosis/endosomal markers further demonstrated that varies endocytosis mechanisms were activated, such as caveolin, clathrin, Rab5 and EEA1 (over 1.9x, 14x, 5.0x and 4.3x increase, respectively). In addition, the endocytosis is related to the activation of Rac1, as Rac1 phosphorylation increased by 1.5x in mutant cells. Inhibition on Rac1 pathway extensively limited endocytosis (>89% reduction as endocytosis index) in IDH1 mutant cells. Our findings highlight a novel molecular mechanism that is possibly involved in IDH1-associated oncogenesis. The observed enhancement of endocytosis and cellular motility suggests this as a potential mechanism related to a more infiltrative and possibly more aggressive phenotype during cancer progression. The unexpected finding of Rac1 activation suggests the potential for a novel therapeutic target for glioma treatment.
Infectious Complications in the Outpatient and Inpatient Autologous Stem Cell Transplantation Setting for Patients with Multiple Myeloma. Princess Margaret Cancer Center Experience
Authors: Anna Nikonova, Christina Zeglinski, Shahid Husain, Miranda So, Eshetu G Atenafu, Donna E Reece, Suzanne Trudel, Vishal Kukreti, Rodger E. Tiedemann, Anca Prica, Norman Anthony Franke, Jane Huynh, Leeping Tao, Christine I Chen
Journal: Blood (2018)
Increased HLA-E Expression Correlates with Early Relapse in Multiple Myeloma
Authors: Alessandro Lagana, Dan Fu Ruan, David Melnekoff, Violetta Leshchenko, Deepak Perumal, Adeeb Rahman, Seunghee Kim-Schultze, Ying Song, Jonathan J Keats, Jennifer Yesil, Daniel Auclair, Deepu Madduri, Joshua Richter, Ajai Chari, Hearn Jay Cho, Bart Barlogie, Sundar Jagannath, Joel Dudley, Amir Horowitz, Samir Parekh
Journal: Blood (2018)
I welcomed the inane chatter during a procedure
Authors: Rhiannon De Wreede
Journal: BMJ (2019)

I welcomed the inane chatter during a procedureRhiannon De Wreede recalls the importance of inane chatter and encouragement while going through an uncomfortable procedure Rhiannon De WreedeI have just had my coil changed.The first one was fitted five years ago and because of a routine smear the "mystery of the missing threads" was discovered.After several attempts from healthcare professionals to find them and some ultrasound scans the problem was still unresolved.So, I booked an appointment at a sexual health clinic to have the coil removed.I was nervous and didn't know what to expect.
Long-Term Follow-up of Myeloablative Haploidentical (HID) Peripheral Blood Stem Cell Transplantation and Post-Transplant Cyclophosphamide (PTCy) Following Fludarabine and Total Body Irradiation (TBI)
Authors: Scott R Solomon, Xu Zhang, Melhem Solh, Lawrence E Morris, H. Kent Holland, Asad Bashey
Journal: Blood (2018)
Prognostic Value of Nodal Response After Preoperative Treatment of Gastric Adenocarcinoma
Authors: Yvonne H. Sada, Brandon G. Smaglo, Joy C. Tan, Hop S. Tran Cao, Benjamin L. Musher, Nader N. Massarweh
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Pathologically positive lymph nodes (ypN+) after preoperative chemotherapy are associated with poor survival in patients with gastric cancer. Little is known about the association between response to preoperative therapy and the benefit of postoperative therapy. Methods: This retrospective cohort study of the National Cancer Database included patients with clinically node-positive (cN+) gastric cancer treated with preoperative therapy followed by surgery (2006–2014). Preoperative treatment modality was categorized as the inclusion of radiation therapy (RT) or chemotherapy alone. Pretreatment clinical and pathologic stages were used to determine pathologic treatment response rates. The association between overall risk of death and preoperative treatment, disease response, and adjuvant therapy use was evaluated using multivariable Cox regression. Results: Preoperative RT was used in 53.6% of 1,976 patients with cN+ gastric cancer, (74.3% cardia and 10.1% noncardia). The nodal response rate was 38.9% and was higher with RT than with chemotherapy alone (cardia, 46.0% vs 29.1%; P &lt;.001; noncardia, 43.8% vs 31.9%; P =.06). Preoperative RT was associated with an approximate 2-fold increase in the odds of pathologic response compared with chemotherapy. Overall, use of adjuvant therapy was not associated with a decreased risk of death. A primary tumor response with residual nodal disease was not associated with survival (hazard ratio [HR], 1.03; 95% CI, 0.66–1.60). However, a nodal response with residual primary disease was significantly associated with survival (HR, 0.54; 95% CI, 0.44–0.65). Conclusions: More than one-third of node-positive gastric cancers showed pathologic nodal response with preoperative treatment. RT is associated with a higher response than chemotherapy. Patients with ypN+ disease have worse survival, regardless of whether they receive postoperative therapy. Future gastric cancer trials should evaluate the role of preoperative RT and individualize postoperative therapy use.
Viral, immunologic, and clinical features of primary effusion lymphoma
Authors: Kathryn Lurain, Mark N. Polizzotto, Karen Aleman, Manisha Bhutani, Kathleen M. Wyvill, Priscila H. Gonçalves, Ramya Ramaswami, Vickie Ann Marshall, Wendell Miley, Seth M. Steinberg, Richard F. Little, Wyndham Wilson, Armando C. Filie, Stefania Pittaluga, Elaine S. Jaffe, Denise Whitby, Robert Yarchoan, Thomas S. Uldrick
Journal: Blood (2019)