tbuckley/cabot-search huggingface dataset:
Relationship between hopelessness and ultimate suicide: a replication with psychiatric outpatients
Authors: A T Beck, G Brown, R J Berchick, B L Stewart, R A Steer
Journal: American Journal of Psychiatry (1990)

A prospective study of 1,958 outpatients found that hopelessness, as measured by the Beck Hopelessness Scale, was significantly related to eventual suicide. A scale cutoff score of 9 or above identified 16 (94.2%) of the 17 patients who eventually committed suicide, thus replicating a previous study with hospitalized patients. The high-risk group identified by this cutoff score was 11 times more likely to commit suicide than the rest of the outpatients. The Beck Hopelessness Scale thus may be used as a sensitive indicator of suicide potential.
Gonadal Steroid Action on the Brain: Neurochemistry and Neuropharmacology
Authors: B S McEwen, B Parsons
Journal: The Annual Review of Pharmacology and Toxicology (1982)

Steroid hormones of the gonads and adrenals influence the brain and alter the affective state as well as· overt behavior and neuroendocrine function. These actions are manifested in various ways and at various levels of obser­ vation and experimentation. For example, in female vertebrates of many species, estrogens prime the brain and pituitary gland and make possible the occurrence of ovulation and sexual receptivity. Androgens, On the other hand, facilitate male reproductive behavior including vocalizations (e.g. song in passerine birds, mate-calling in frogs), defense of territory and related aggressive displays, and copulatory behavior. At another level of analysis, estrogen treatment counteracts tardive diskinesia and L-DOPA­ induced diskinesia (1) and has antidepressant effects in women resistant to other kinds of antidepressant drug therapy (2). Moreover, changes in estro­ gen and progestin levels are often linked to the emotional lability associated with the premenstrual and postpartum periods (3, 4). Studies of the action of steroid honnones on the brain have progressed to a point where specific mechanisms and brain sites of action are now recognized. Especially important to the neurophannacologist are those aspects of mechanism which have begun to deal with hormonal modifica­ tion of properties and functions of synapses. Synaptic function and neuro­ transmission are indeed the common currency for the analysis of neuroendocrine events and honnone-regulated behaviors, as well as other aspects of brain function; and the study of drugs which modify neurotrans­ mission through blockade of synthesis, degradation, reuptake, and recep-
Phase I-II study of recombinant alpha-2 interferon against advanced leukemia and lymphoma in children.
Authors: J Ochs, M Abromowitch, S Rudnick, S B Murphy
Journal: Journal of Clinical Oncology (1986)

Alpha-2 interferon, produced in Escherichia coli using recombinant DNA techniques, was administered to 17 children with refractory acute lymphoblastic leukemia (ALL) in relapse, two children with TdT-positive, Philadelphia chromosome-positive chronic myelocytic leukemia (CML) in blast crisis, and one child with B cell (SIg+) non-Hodgkin's lymphoma (NHL) in a second extramedullary relapse. An initial 2-week intravenous (IV) phase of interferon was followed by a 3-month subcutaneous (SC) maintenance phase if patients had an objective response or disease stabilization without significant bleeding or infectious complications. When interferon dosages were escalated from 3 to 100 X 10(6) U/m2 in the first phase of therapy, there was rapid progression of disease in the first four patients treated, prompting a modification of the treatment plan. The last 16 patients enrolled received fixed dosages of interferon (ie, 10, 20, 30, and 50 X 10(6) U/m2 administered to four subjects each). One child with T cell ALL had an 11-month complete remission; the patient with lymphoma had a dramatic but brief response; three others (one CML and two ALL) showed disease stabilization for 3 to 6 months with a definite oncolytic effect in two of the three patients. The remaining 15 patients had progressive disease within 2 months and were removed from the study. Acute toxicity included a flu-like syndrome in all patients, increased serum transaminase levels in five, seizures in three (two cases temporally related to fever and one to a thrombocytopenic subarachnoid hemorrhage), and prolonged activated partial thromboplastin times in seven. This phase I-II trial of recombinant alpha-2 interferon demonstrated definite activity without dose-limiting toxicity.
Italian expert questions need for expanded vaccination schedule
Authors: Michael Day
Journal: BMJ (2015)

A vaccine expert who criticised plans to expand Italy’s national vaccination programme has been threatened with legal action by government medical officers.

Vittorio Demicheli, of the Cochrane Vaccines Field, has said that plans to introduce vaccines against human papillomavirus (HPV) for males, rotavirus for infants, and herpes zoster and pneumococcal polysaccharide for elderly people are too costly and sometimes ill advised, questioning the motives behind the new national programme.

Demicheli, who was previously director of public health for Italy’s Piedmont region, concluded in a letter to the daily newspaper Il Sole 24 Ore on 27 October1 that more scrutiny of the plans was needed “not …
Positive Selection Underlies Faster-Z Evolution of Gene Expression in Birds
Authors: Rebecca Dean, Peter W. Harrison, Alison E. Wright, Fabian Zimmer, Judith E. Mank
Journal: Molecular Biology and Evolution (2015)

The elevated rate of evolution for genes on sex chromosomes compared with autosomes (Fast-X or Fast-Z evolution) can result either from positive selection in the heterogametic sex or from nonadaptive consequences of reduced relative effective population size. Recent work in birds suggests that Fast-Z of coding sequence is primarily due to relaxed purifying selection resulting from reduced relative effective population size. However, gene sequence and gene expression are often subject to distinct evolutionary pressures; therefore, we tested for Fast-Z in gene expression using next-generation RNA-sequencing data from multiple avian species. Similar to studies of Fast-Z in coding sequence, we recover clear signatures of Fast-Z in gene expression; however, in contrast to coding sequence, our data indicate that Fast-Z in expression is due to positive selection acting primarily in females. In the soma, where gene expression is highly correlated between the sexes, we detected Fast-Z in both sexes, although at a higher rate in females, suggesting that many positively selected expression changes in females are also expressed in males. In the gonad, where intersexual correlations in expression are much lower, we detected Fast-Z for female gene expression, but crucially, not males. This suggests that a large amount of expression variation is sex-specific in its effects within the gonad. Taken together, our results indicate that Fast-Z evolution of gene expression is the product of positive selection acting on recessive beneficial alleles in the heterogametic sex. More broadly, our analysis suggests that the adaptive potential of Z chromosome gene expression may be much greater than that of gene sequence, results which have important implications for the role of sex chromosomes in speciation and sexual selection.
Regulation of Hepatic De Novo Lipogenesis in Humans
Authors: M K Hellerstein, J M Schwarz, R A Neese
Journal: Annual Review of Nutrition (1996)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More
Current evidence for therapeutic interventions and prognostic factors in polymyalgia rheumatica: a systematic literature review informing the 2015 European League Against Rheumatism/American College of Rheumatology recommendations for the management of polymyalgia rheumatica
Authors: Christian Dejaco, Yogesh P Singh, Pablo Perel, Andrew Hutchings, Dario Camellino, Sarah Mackie, Eric L Matteson, Bhaskar Dasgupta
Journal: Annals of the Rheumatic Diseases (2015)

To summarise evidence on therapeutic interventions and prognostic factors in polymyalgia rheumatica (PMR). A systematic literature review was conducted using Ovid Medline, Embase, PubMed, CINAHL, Web of Science and the Cochrane Library (1970 through April 2014). Quality of evidence (QoE) of identified studies was appraised by Grading of Recommendations Assessment, Development and Evaluation (GRADE) (interventions) and the Quality In Prognosis Studies (QUIPS) methodologies (prognostic factors). Out of 10 931 titles identified, 52 articles were finally selected. A single study indicated that an initial prednisone dose of 20 mg/day is associated with a lower short-term relapse rate than 10 mg/day but at the cost of a higher rate of adverse events. Another study suggested a comparable efficacy of intramuscular methylprednisolone and oral glucocorticoids (GCs) with lower cumulative GC doses and less weight gain in the former group. Moderate to high QoE (1–2 studies) indicated a benefit of methotrexate in remission rates and cumulative GC doses in early PMR. Anti-tumour necrosis factor α agents are ineffective for PMR treatment. Among prognostic factors, female sex, high erythrocyte sedimentation rate (ESR) and peripheral arthritis were associated in some studies with a higher relapse risk. Women and patients with high ESR also appeared to have a longer duration of treatment. Several studies of varying quality, however, failed to prove these associations. In PMR, evidence for initial GC doses and subsequent tapering regimens is limited. Intramuscular methylprednisolone and methotrexate may be effective GC sparing agents. Female sex, high ESR and peripheral arthritis at disease outset are potential risk factors for a worse prognosis.
Identification of the Ki-1 antigen (CD30) as a novel therapeutic target in systemic mastocytosis
Authors: Katharina Blatt, Sabine Cerny-Reiterer, Juliana Schwaab, Karl Sotlar, Gregor Eisenwort, Gabriele Stefanzl, Gregor Hoermann, Matthias Mayerhofer, Mathias Schneeweiss, Sylvia Knapp, Thomas Rülicke, Emir Hadzijusufovic, Karin Bauer, Dubravka Smiljkovic, Michael Willmann, Andreas Reiter, Hans-Peter Horny, Peter Valent
Journal: Blood (2015)
The Colony-Stimulating Factor 3 Receptor T640N Mutation Is Oncogenic, Sensitive to JAK Inhibition, and Mimics T618I
Authors: Julia E. Maxson, Samuel B. Luty, Jason D. MacManiman, Jason C. Paik, Jason Gotlib, Peter Greenberg, Swaleh Bahamadi, Samantha L. Savage, Melissa L. Abel, Christopher A. Eide, Marc M. Loriaux, Emily A. Stevens, Jeffrey W. Tyner
Journal: Clinical Cancer Research (2015)

Colony-stimulating factor 3 receptor (CSF3R) mutations have been identified in the majority of chronic neutrophilic leukemia (CNL) and a smaller percentage of atypical chronic myeloid leukemia (aCML) cases. Although CSF3R point mutations (e.g., T618I) are emerging as key players in CNL/aCML, the significance of rarer CSF3R mutations is unknown. In this study, we assess the importance of the CSF3R T640N mutation as a marker of CNL/aCML and potential therapeutic target.Sanger sequencing of leukemia samples was performed to identify CSF3R mutations in CNL and aCML. The oncogenicity of the CSF3R T640N mutation relative to the T618I mutation was assessed by cytokine independent growth assays and by mouse bone marrow transplant. Receptor dimerization and O-glycosylation of the mutants was assessed by Western blot, and JAK inhibitor sensitivity was assessed by colony assay.Here, we identify a CSF3R T640N mutation in two patients with CNL/aCML, one of whom was originally diagnosed with MDS and acquired the T640N mutation upon evolution of disease to aCML. The T640N mutation is oncogenic in cellular transformation assays and an in vivo mouse bone marrow transplantation model. It exhibits many similar phenotypic features to T618I, including ligand independence and altered patterns of O-glycosylation--despite the transmembrane location of T640 preventing access by GalNAc transferase enzymes. Cells transformed by the T640N mutation are sensitive to JAK kinase inhibition to a similar degree as cells transformed by CSF3R T618I.Because of its similarities to CSF3R T618I, the T640N mutation likely has diagnostic and therapeutic relevance in CNL/aCML.
Clinical, biophysical and immunohistochemical analysis of skin reactions to acute skin barrier disruption - a comparative trial between participants with sensitive skin and those with nonsensitive skin
Authors: R.J.H. Richters, N.E. Uzunbajakava, D. Falcone, J.C.M. Hendriks, E.J. Jaspers, P.C.M. van de Kerkhof, P.E.J. van Erp
Journal: British Journal of Dermatology (2015)
Long-term reduction in sperm count after chemotherapy with and without radiation therapy for non-Hodgkin's lymphomas.
Authors: R M Pryzant, M L Meistrich, G Wilson, B Brown, P McLaughlin
Journal: Journal of Clinical Oncology (1993)

PURPOSE Treatment of lymphomas with combination chemotherapy with or without radiation therapy (XRT) can result in long-term or permanent azoospermia. PATIENTS AND METHODS Semen analyses of lymphoma patients were performed before, during, and after treatment with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo) chemotherapy. Some of the patients also received other drugs or radiation therapy. RESULTS Although no patients were azoospermic before treatment, all were rendered azoospermic during treatment. Following the completion of treatment, the fraction of patients whose sperm counts recovered increased gradually over 5 years and plateaued by 7 years, with two thirds of the men achieving normospermic levels. Scattered gonadal radiation dose and cumulative cyclophosphamide dose were found to be independently significant determinants of recovery: the fraction of patients whose sperm counts recovered to 10 x 10(6)/mL were 83%, 47%, and 20% for those who received less than 9.5 g/m2 of cyclophosphamide, greater than 9.5 g/m2 of cyclophosphamide, and pelvic XRT, respectively. The inclusion of additional drugs and interferon alfa did not significantly affect the long-term recovery of spermatogenesis. CONCLUSION Pelvic XRT and cumulative cyclophosphamide dosages greater than 9.5 g/m2 are associated with a high risk of permanent sterility in lymphoma patients treated with the CHOP-Bleo regimen.
Persistence and evolution of allergen-specific IgE repertoires during subcutaneous specific immunotherapy
Authors: Mattias Levin, Jasmine J. King, Jacob Glanville, Katherine J.L. Jackson, Timothy J. Looney, Ramona A. Hoh, Adriano Mari, Morgan Andersson, Lennart Greiff, Andrew Z. Fire, Scott D. Boyd, Mats Ohlin
Journal: Journal of Allergy and Clinical Immunology (2015)

Specific immunotherapy (SIT) is the only treatment with proved long-term curative potential in patients with allergic disease. Allergen-specific IgE is the causative agent of allergic disease, and antibodies contribute to SIT, but the effects of SIT on aeroallergen-specific B-cell repertoires are not well understood.We sought to characterize the IgE sequences expressed by allergen-specific B cells and track the fate of these B-cell clones during SIT.We used high-throughput antibody gene sequencing and identification of allergen-specific IgE with combinatorial antibody fragment library technology to analyze immunoglobulin repertoires of blood and the nasal mucosa from aeroallergen-sensitized subjects before and during the first year of subcutaneous SIT.Of 52 distinct allergen-specific IgE heavy chains from 8 allergic donors, 37 were also detected by using high-throughput antibody gene sequencing of blood samples, nasal mucosal samples, or both. The allergen-specific clones had increased persistence, higher likelihood of belonging to clones expressing other switched isotypes, and possibly larger clone size than the rest of the IgE repertoire. Clone members in nasal tissue showed close mutational relationships.In the future, combining functional binding studies, deep antibody repertoire sequencing, and information on clinical outcomes in larger studies might aid assessment of SIT mechanisms and efficacy.
House dust mite sublingual immunotherapy is safe in patients with mild‐to‐moderate, persistent asthma: a clinical trial
Authors: P. Devillier, R. Fadel, O. de Beaumont
Journal: Allergy (2015)

Abstract Background The safety of allergen immunotherapy ( AIT ) in asthma has not always been sufficiently documented; accordingly, fear of asthma exacerbations has made physicians somewhat reluctant to prescribe AIT in this context. In a double‐blind, placebo‐controlled, randomized clinical trial, house dust mite ( HDM ) sublingual AIT was found to be efficacious in moderate, persistent asthma. The trial's safety results are now reported in detail. Methods Asthmatic adults were randomized 2 : 1 to twelve months of daily treatment with a sublingual solution of Dermatophagoides pteronyssinus and Dermatophagoides farinae extracts or a placebo. Adverse events ( AE s) at least possibly related to the investigational product were classified by the investigators as adverse drug reactions ( ADR s). Results Overall, the patients in the safety analysis set ( n = 484; active treatment: n = 322; placebo: n = 162) had mostly well‐controlled, persistent asthma [mild in 290 patients (59.9%), moderate in 183 (37.8%) and severe in 11 (2.3%)]. No treatment‐related serious AE s were reported. A total of 87.0% and 75.9% of the patients in the active and placebo groups, respectively, experienced at least one AE (mostly mild), and 78.9% and 48.1% experienced an ADR (mostly mild or moderate oral reactions). The incidence of asthma exacerbations (symptoms requiring a short course of oral corticosteroids) during the study was similar in the active treatment group (3.7%) and the placebo group (4.3%). There were no significant intergroup differences or intragroup changes over time in respiratory AE s, lung function or asthma‐related quality of life. Conclusions HDM sublingual AIT was safe and well tolerated in adult patients with mild‐to‐moderate, persistent asthma (ClinicalTrials.gov: NCT 00660452).
The Revised International Prognostic Index (R-IPI) Score Is Predictive Of Survival In Aggressive Transformed Lymphomas (TL) From Low Grade Non-Hodgkin Lymphomas In The Chemoimmunotherapy Era
Authors: Tsao Christina, Samir Dalia, Celeste M. Bello, Lubomir Sokol, Eduardo M. Sotomayor, Bijal D. Shah, Julio C Chavez
Journal: Blood (2013)
T-Cell Differentiation is Influenced by Thymic Microenvironments
Authors: W van Ewijk
Journal: Annual Review of Immunology (1991)

Intrathymic T-cell differentiation requires a symbiotic interaction between thymic microenvironments and developing T cells. This paper attempts to provide insight into lympho-stromal interaction and reviews the architecture of thymic microenvironments, the phenotype of thymic microenvironments, the in vitro culture of thymic microenvironments, and the supportive role of thymic microenvironments in T-cell differentiation. Moreover, we discuss experimental manipulation of thymic microenvironments in vivo and in vitro, using monoclonal antibodies directed to cell surface determinants on stromal cells or their ligands on lymphoid cells. Finally, new types of experimental mouse models are considered with special reference to the role of thymic microenvironments in positive and negative selection of the T-cell repertoire, and the potential influence of T cells on the development of thymic microenvironments.
A Review of: “Jonathan D. Moreno,<i>Is There an Ethicist in the House?: On the Cutting Edge of Bioethics</i>. Bloomington, IN: Indiana University Press, 2005. 274 pp. $29.95, hardcover.”
Authors: Felicia Cohn
Journal: The American Journal of Bioethics (2006)

"A Review of: “Jonathan D. Moreno, Is There an Ethicist in the House?: On the Cutting Edge of Bioethics. Bloomington, IN: Indiana University Press, 2005. 274 pp. $29.95, hardcover.”." , 6(6), pp. 72–73
Synaptic Integration of Adult-Born Hippocampal Neurons Is Locally Controlled by Astrocytes
Authors: Sébastien Sultan, Liyi Li, Jonathan Moss, Francesco Petrelli, Frédéric Cassé, Elias Gebara, Jan Lopatar, Frank W. Pfrieger, Paola Bezzi, Josef Bischofberger, Nicolas Toni
Journal: Neuron (2015)
Correlation of <i>BRAF</i> Mutation Status in Circulating-Free DNA and Tumor and Association with Clinical Outcome across Four BRAFi and MEKi Clinical Trials
Authors: Ademi Santiago-Walker, Robert Gagnon, Jolly Mazumdar, Michelle Casey, Georgina V. Long, Dirk Schadendorf, Keith Flaherty, Richard Kefford, Axel Hauschild, Patrick Hwu, Patricia Haney, Anne O'Hagan, Jennifer Carver, Vicki Goodman, Jeffrey Legos, Anne-Marie Martin
Journal: Clinical Cancer Research (2015)

Tumor-derived circulating cell-free DNA (cfDNA) is a potential alternative source from which to derive tumor mutation status. cfDNA data from four clinical studies of the BRAF inhibitor (BRAFi) dabrafenib or the MEK inhibitor (MEKi) trametinib were analyzed to determine the association between BRAF mutation status in cfDNA and tumor tissue, and the association of BRAF cfDNA mutation status with baseline factors and clinical outcome.Patients with BRAF V600 mutation-positive melanoma were enrolled in each study after central confirmation of BRAF status in tumor using a PCR-based assay. BRAF mutation status in cfDNA from patient plasma collected at baseline, 732 of 836 (88%) enrolled patients in total, was determined.BRAF mutations were detectable in cfDNA in 76% and 81% of patients with BRAF V600E/V600K-positive tumors, respectively. Patients negative for BRAF mutations in cfDNA had longer progression-free survival (PFS) and overall survival in each of the four studies, compared with patients with detectable cfDNA BRAF mutations. The presence of BRAF-mutant cfDNA was an independent prognostic factor for PFS after multivariate adjustment for baseline factors in three of four studies. Patients negative for BRAF mutation-positive cfDNA in plasma had higher response rates to dabrafenib and trametinib.BRAF mutations in cfDNA are detectable in >75% of late-stage melanoma patients with BRAF mutation-positive tumors. The lack of circulating, BRAF mutation-positive cfDNA is clinically significant for metastatic melanoma patients, and may be a prognostic marker for better disease outcome.