tbuckley/cabot-search huggingface dataset:
Genomic insights into the overlap between psychiatric disorders: implications for research and clinical practice
Authors: Joanne L Doherty, Michael J Owen
Journal: Genome Medicine (2014)

Psychiatric disorders such as schizophrenia, bipolar disorder, major depressive disorder, attention-deficit/hyperactivity disorder and autism spectrum disorder are common and result in significant morbidity and mortality. Although currently classified into distinct disorder categories, they show clinical overlap and familial co-aggregation, and share genetic risk factors. Recent advances in psychiatric genomics have provided insight into the potential mechanisms underlying the overlap between these disorders, implicating genes involved in neurodevelopment, synaptic plasticity, learning and memory. Furthermore, evidence from copy number variant, exome sequencing and genome-wide association studies supports a gradient of neurodevelopmental psychopathology indexed by mutational load or mutational severity, and cognitive impairment. These findings have important implications for psychiatric research, highlighting the need for new approaches to stratifying patients for research. They also point the way for work aiming to advance our understanding of the pathways from genotype to clinical phenotype, which will be required in order to inform new classification systems and to develop novel therapeutic strategies.
A Meta-Analytic Review of Eating Disorder Prevention Programs: Encouraging Findings
Authors: Eric Stice, Heather Shaw, C. Nathan Marti
Journal: Annual Review of Clinical Psychology (2006)

This meta-analytic review found that 51% of eating disorder prevention programs reduced eating disorder risk factors and 29% reduced current or future eating pathology. Larger effects occurred for programs that were selected (versus universal), interactive (versus didactic), multisession (versus single session), solely offered to females (versus both sexes), offered to participants over 15 years of age (versus younger ones), and delivered by professional interventionists (versus endogenous providers). Programs with body acceptance and dissonance-induction content and without psychoeducational content and programs evaluated in trials using validated measures and a shorter follow-up period also produced larger effects. Results identify promising programs and delineate sample, format, and design features associated with larger effects, which may inform the design of more effective prevention programs in the future.
BCL6 repression of EP300 in human diffuse large B cell lymphoma cells provides a basis for rational combinatorial therapy
Authors: Leandro C. Cerchietti, Katerina Hatzi, Eloisi Caldas-Lopes, Shao Ning Yang, Maria E. Figueroa, Ryan D. Morin, Martin Hirst, Lourdes Mendez, Rita Shaknovich, Philip A. Cole, Kapil Bhalla, Randy D. Gascoyne, Marco Marra, Gabriela Chiosis, Ari Melnick
Journal: Journal of Clinical Investigation (2010)

B cell lymphoma 6 (BCL6), which encodes a transcriptional repressor, is a critical oncogene in diffuse large B cell lymphomas (DLBCLs). Although a retro-inverted BCL6 peptide inhibitor (RI-BPI) was recently shown to potently kill DLBCL cells, the underlying mechanisms remain unclear. Here, we show that RI-BPI induces a particular gene expression signature in human DLBCL cell lines that included genes associated with the actions of histone deacetylase (HDAC) and Hsp90 inhibitors. BCL6 directly repressed the expression of p300 lysine acetyltransferase (EP300) and its cofactor HLA-B-associated transcript 3 (BAT3). RI-BPI induced expression of p300 and BAT3, resulting in acetylation of p300 targets including p53 and Hsp90. Induction of p300 and BAT3 was required for the antilymphoma effects of RI-BPI, since specific blockade of either protein rescued human DLBCL cell lines from the BCL6 inhibitor. Consistent with this, combination of RI-BPI with either an HDAC inhibitor (HDI) or an Hsp90 inhibitor potently suppressed or even eradicated established human DLBCL xenografts in mice. Furthermore, HDAC and Hsp90 inhibitors independently enhanced RI-BPI killing of primary human DLBCL cells in vitro. We also show that p300-inactivating mutations occur naturally in human DLBCL patients and may confer resistance to BCL6 inhibitors. Thus, BCL6 repression of EP300 provides a basis for rational targeted combinatorial therapy for patients with DLBCL.
Cigarette smoking significantly increases basal metabolic rate in patients with rheumatoid arthritis
Authors: G S Metsios, A Stavropoulos-Kalinoglou, A M Nevill, K M J Douglas, Y Koutedakis, G D Kitas
Journal: Annals of the Rheumatic Diseases (2007)

Basal metabolic rate (BMR) is the most important indicator of human metabolism and its abnormalities have been linked to undesirable health outcomes. Cigarette smoking associates with increased BMR in healthy individuals; it is also related with worse disease outcomes in patients with rheumatoid arthritis(RA), in whom BMR is high due to hypercatabolism caused by systemic inflammation. We aimed to investigate whether smokers with RA demonstrated higher BMR levels than their non-smoking counterparts.A total of 53 patients with RA (36 female, 17 male, 20 current smokers) were assessed for: BMR(indirect calorimetry), anthropometrical data, fat-free mass (bioelectrical impedance), physical function (health assessment questionnaire; HAQ) and disease activity(disease activity score DAS28 and C reactive protein).RA smokers and non-smokers were not significantly different for age, height, weight, body mass index and fat-free mass. Compared to non-smokers,smokers with RA demonstrated significantly higher BMR (mean (SD) 1513.9 (263.3) vs 1718.1 (209.2) kcal/day; p,0.001) and worse HAQ (1.0 (0.8) vs 1.7 (0.8); p=0.01). The BMR difference was significantly predicted by the interaction smoking/gender (p=0.04). BMR was incrementally higher in light, moderate and heavy smokers (p=0.018), and correlated with the daily number of cigarettes smoked (r=0.68, p=0.04).Current cigarette smoking further increases BMR in patients with RA and has a negative impact on patients self-reported functional status. Education regarding smoking cessation is needed for the RA population.
Tryptophan-Induced Eosinophilia–Myalgia Syndrome
Authors: Thomas A. Medsger
Journal: New England Journal of Medicine (1990)

Beginning in the late spring of 1989, large numbers of patients became ill with a disorder first recognized the following October and termed the eosinophilia—myalgia syndrome.1 , 2 Almost all the people affected had taken dietary supplements of tryptophan, a naturally occurring amino acid publicized as useful for the treatment of insomnia, depression, and premenstrual symptoms. The median dose ingested was 1.5 g per day — twice the usual dietary intake. The duration of ingestion varied from a few weeks to several years, and a few patients had stopped taking the tryptophan before their symptoms appeared.As of February 9, 1990, the . . .
INTRA-STOMACHAL AND INTRA-INTESTINAL INOCULATIONS OF TRYPANOSOME VIRUS WITH TESTS FOR IMMUNITY
Authors: B. T. Terry
Journal: The Journal of Experimental Medicine (1911)

In nearly 50 per cent. of the cases, virulent trypanosome virus inoculated directly through the stomach wall of rats failed to infect these animals. The percentage of infections after inoculation of this kind seemed to vary with the virus. Surra of India proved to be the most virulent, and caderas the least. Nagana and dourine occupied intermediate positions. The rats that escaped infection showed no trace of immunity when tested with small quantities of the same virus between the twelfth and the twenty-eighth days after the intra-stomachal inoculations. The majority of the rats tested for immunity with surra of India and nagana seemed to have acquired, instead of an immunity, a certain hypersensitiveness to infection. Five of the seven nagana rats died before their controls. The results of testing the vitality of the trypanosomes of caderas, dourine, and nagana introduced directly into the stomachs and intestines of living rats seem to show that both motility and virulence are usually lost in less than two hours. Surra of India proved exceptionally resistant to the harmful influences of the stomach, for in one case, surra trypanosomes introduced into the intestines were found to be sluggishly motile in the stomach one hour and fifty-five minutes later, and in another instance, surra parasites injected into the stomach were found, when removed from that organ two hours later, to be actively motile and infectious.
Impact of Pretransplantation Minimal Residual Disease, As Detected by Multiparametric Flow Cytometry, on Outcome of Myeloablative Hematopoietic Cell Transplantation for Acute Myeloid Leukemia
Authors: Roland B. Walter, Ted A. Gooley, Brent L. Wood, Filippo Milano, Min Fang, Mohamed L. Sorror, Elihu H. Estey, Alexander I. Salter, Emily Lansverk, Jason W. Chien, Ajay K. Gopal, Frederick R. Appelbaum, John M. Pagel
Journal: Journal of Clinical Oncology (2011)

Allogeneic hematopoietic cell transplantation (HCT) benefits many patients with acute myeloid leukemia (AML) in first remission. Hitherto, little attention has been given to the prognostic impact of pretransplantation minimal residual disease (MRD).We retrospectively studied 99 consecutive patients receiving myeloablative HCT for AML in first morphologic remission. Ten-color multiparametric flow cytometry (MFC) was performed on bone marrow aspirates before HCT. MRD was identified as a cell population showing deviation from normal antigen expression patterns compared with normal or regenerating marrow. Any level of residual disease was considered MRD positive.Before HCT, 88 patients met morphologic criteria for complete remission (CR), whereas 11 had CR with incomplete blood count recovery (CRi). Twenty-four had MRD before HCT as determined by MFC. Two-year estimates of overall survival were 30.2% (range, 13.1% to 49.3%) and 76.6% (range, 64.4% to 85.1%) for MRD-positive and MRD-negative patients; 2-year estimates of relapse were 64.9% (range, 42.0% to 80.6%) and 17.6% (range, 9.5% to 27.9%). After adjustment for all or a subset of cytogenetic risk, secondary disease, incomplete blood count recovery, and abnormal karyotype pre-HCT, MRD-positive HCT was associated with increased overall mortality (hazard ratio [HR], 4.05; 95% CI, 1.90 to 8.62; P < .001) and relapse (HR, 8.49; 95% CI, 3.67 to 19.65; P < .001) relative to MRD-negative HCT.These data suggest that pre-HCT MRD is associated with increased risk of relapse and death after myeloablative HCT for AML in first morphologic CR, even after controlling for other risk factors.
Down-Regulation of S100C Is Associated with Bladder Cancer Progression and Poor Survival
Authors: Ashfaque Ahmed Memon, Boe Sandahl Sorensen, Peter Meldgaard, Lars Fokdal, Thomas Thykjaer, Ebba Nexo
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The goal of this study was to identify proteins down-regulated during bladder cancer progression. Experimental design: By using comparative proteome analysis and measurement of mRNA, we found a significant down-regulation of S100C, a member of the S100 family of proteins, in T24 (grade 3) as compared with RT4 (grade 1) bladder cancer cell lines. Moreover, quantification of the mRNA level revealed that decreased expression of the protein reflects a low level of transcription of the S100C gene. Based on this observation, we quantified the S100C mRNA expression level with real-time PCR in bladder cancer biopsy samples obtained from 88 patients followed for a median of 23 months (range, 1-97 months). Results: We found a significantly lower mRNA expression of S100C in connective tissue invasive tumors (T1, P = 0.0030) and muscle invasive tumors [(T2-T4), P &amp;lt; 0.0001] compared with superficial tumors (Ta). A negative correlation between S100C and histopathologic grade (P = 0.0003) was also observed. Furthermore, the papillary type showed higher expression of S100C than did the solid type of the tumor (P &amp;lt; 0.0001). Importantly, we found that loss of S100C was associated with survival in bladder cancer patients (P = 0.0006). Conclusions: Our results show that low expression of S100C is associated with poor survival in patients with bladder cancer. Furthermore, loss of S100C in T1 as compared with Ta stage tumors emphasize that S100C expression is suppressed early during bladder cancer development.
Administration of oral vitamin D induces cathelicidin production in atopic individuals
Authors: Tissa R. Hata, Paul Kotol, Michelle Jackson, Meggie Nguyen, Aimee Paik, Don Udall, Kimi Kanada, Kenshi Yamasaki, Doru Alexandrescu, Richard L. Gallo
Journal: Journal of Allergy and Clinical Immunology (2008)
Mean Platelet Volume on Admission Predicts Impaired Reperfusion and Long-Term Mortality in Acute Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention
Authors: Zenon Huczek, Janusz Kochman, Krzysztof J. Filipiak, Grzegorz J. Horszczaruk, Marcin Grabowski, Radoslaw Piatkowski, Joanna Wilczynska, Andrzej Zielinski, Bernhard Meier, Grzegorz Opolski
Journal: Journal of the American College of Cardiology (2005)
The selfish goal meets the selfish gene
Authors: Steven L. Neuberg, Mark Schaller
Journal: Behavioral and Brain Sciences (2014)

Abstract The connection between selfish genes and selfish goals is not merely metaphorical. Many goals that shape contemporary cognition and behavior are psychological products of evolutionarily fundamental motivational systems and thus are phenotypic manifestations of genes. An evolutionary perspective can add depth and nuance to our understanding of “selfish goals” and their implications for human cognition and behavior.
Galectin-1, an Endogenous Lectin Produced by Thymic Epithelial Cells, Induces Apoptosis of Human Thymocytes
Authors: Nancy L. Perillo, Christel H. Uittenbogaart, Julie T. Nguyen, Linda G. Baum
Journal: The Journal of Experimental Medicine (1997)

Galectin-1, a β-galactoside binding protein, is produced by thymic epithelial cells and binds to human thymocytes. We have previously reported that galectin-1 induces the apoptosis of activated T lymphocytes. Because the majority of thymocytes die via apoptosis while still within the thymus, we tested whether galectin-1 could induce the apoptosis of these cells. We now report that in vitro exposure to galectin-1 induced apoptosis of two subsets of CD4lo CD8lo thymocytes. The phenotypes of susceptible thymocytes were consistent with that of both negatively selected and nonselected cells. Galectin-1–induced apoptosis was enhanced by preexposure of thymocytes to antibody to CD3, suggesting that galectin-1 may be a participant in T-cell– receptor mediated apoptosis. In contrast, pretreatment of thymocytes with dexamethasone had no effect on galectin-1 susceptibility. We noted that 71% of the cells undergoing apoptosis after galectin-1 treatment had a DNA content greater than 2N, indicating that proliferating thymocytes were most sensitive to galectin-1. We propose that galectin-1 plays a role in the apoptosis of both negatively selected and nonselected thymocytes, and that the susceptibility of thymocytes to galectin-1 is regulated, in part, by entry or exit from the cell cycle.
Podoplanin: A Novel Marker for Oral Cancer Risk in Patients With Oral Premalignancy
Authors: Hidetoshi Kawaguchi, Adel K. El-Naggar, Vali Papadimitrakopoulou, Hening Ren, You-Hong Fan, Lei Feng, J. Jack Lee, Edward Kim, Waun Ki Hong, Scott M. Lippman, Li Mao
Journal: Journal of Clinical Oncology (2008)

Oral leukoplakia (OPL) is a heterogeneous oral lesion with an increased oral cancer risk. Current clinical parameters cannot predict the potential of malignant transformation in patients with OPL. We have shown that podoplanin, a lymphatic endothelial marker, is highly expressed in oral cancer and some oral premalignancies. The purpose of this study is to determine a role of podoplanin in predicting oral cancer development in patients with OPL.Podoplanin expression was determined in 150 OPL patients with long-term follow-up using immunohistochemistry. Association between the protein expression patterns and clinicopathologic parameters including oral cancer development during the follow-up were analyzed.Fifty-six (37%) of the 150 OPL patients exhibited podoplanin expression in the basal and suprabasal layers and were classified as podoplanin positive. Podoplanin positivity was more frequent in older patients (P = .016), females (P = .020), and dysplastic lesions (P = .040). Patients with OPL that was podoplanin positive had significantly higher incidence of oral cancer than did those whose OPL was podoplanin negative (P = .0002). In the multivariate analysis using histology and podoplanin as cofactors, podoplanin was the only independent factor for oral cancer development (hazard ratio = 3.087; 95% CI, 1.530 to 6.231; P = .002). Importantly, oral cancer risk can be further stratified by considering both histology and podoplanin information.Podoplanin is frequently expressed in OPL. Together with histology, podoplanin may serve as a powerful biomarker to predict the risk for oral cancer development in patients with OPL.
A novel subset of human lymphocytes with a T cell receptor-gamma complex.
Authors: S Jitsukawa, F Faure, M Lipinski, F Triebel, T Hercend
Journal: The Journal of Experimental Medicine (1987)

We have previously characterized a CD3+ T cell receptor (TCR) alpha/beta- human fetal cloned cell line, termed F6C7, which surface-expresses a CD3-associated gamma chain identified by anti-NKFi, an mAb with a restricted clonotypic reactivity. Here, we have produced an additional antibody, anti-Ti-gamma A, which recognizes a public epitope of the gamma molecule defined by anti-NKFi. Ti-gamma A is present on approximately 3% of circulating lymphocytes with a wide range (1-15%) among 30 healthy individuals tested. Two-color immunofluorescence experiments performed with anti-Ti-gamma A and BMA 031 mAb (a reagent specific for the TCR-alpha/beta receptor) showed that surface expression of Ti-alpha/beta and Ti-gamma A is mutually exclusive. Moreover, it was found that most Ti-gamma A+ cells are CD2+, CD3+, CD4-, CD5+, NKH1-, HLA class II-negative. In contrast, the expression of the CD8 molecule on these T lymphocytes appears to be variable from one individual to another. Finally, we found that Ti-gamma A+ cells represent a majority of peripheral lymphocytes that express CD3 proteins but not the TCR-alpha/beta heterodimer. The delineation of this unique lymphocyte subset should help further studies on the biology of cells with a CD3-associated gamma complex.
Impaired survival and long-term neurological problems in benign meningioma
Authors: Hanna van Alkemade, Michelle de Leau, Edith M.T. Dieleman, Jan W.P.F. Kardaun, Rob van Os, W. Peter Vandertop, Wouter R. van Furth, Lukas J.A. Stalpers
Journal: Neuro-Oncology (2012)

Purpose: To assess long-term functional outcome and survival among patients with meningioma World Health Organization (WHO) grade I. Methods: Retrospective analysis of 205 patients after resection of WHO grade I intracranial meningioma from 1985 through 2003. Expected age- and sex-specific survival was calculated by applying Dutch life-table statistics to each patient for the individual duration of follow-up. Long-term functional outcome was assessed using a mailed questionnaire to the general practitioner. Results: The mean duration of follow-up was 11.5 years. Survival at 5, 10, 15, and 20 years was 92%, 81%, 63%, and 53%, respectively, which is significantly lower than the expected survival (94%, 86%, 78%, and 66%, respectively). Survival was worse with higher age (P < .001). Survival among patients younger than 45 years and older than 65 years was comparable to the expected survival but significantly worse among patients aged 45–65 years. Analysis of the cause of death suggests an excess mortality associated with both brain tumor death and stroke (P = .07). Recurrence rates at 5, 10, and 15 years were 18%, 26%, and 32%, respectively. Higher Simpson grade (P < .001) and lower age (P = .02) were associated with a higher recurrence rate. In 29 patients (14%) receiving radiotherapy, the 5-year recurrence rate was 18% and the 5-year survival was only 58%. Long-term functioning (≥5 years after last treatment) could be assessed in 89 long-term survivors: 29 patients (33%) showed no deficits, and 60 (67%) showed at least 1 neurological symptom, of whom 24 (27%) were unable to perform normal daily activities. Conclusion: Long-term survival in WHO grade I meningioma is challenged in patients more than45 years of age. Excess mortality seems to be associated with both tumor recurrence and stroke. The majority of patients have long-term neurological problems.
Multivariable analysis of prognostic factors for toxicity and survival for patients enrolled in phase I clinical trials
Authors: T. Bachelot, I. Ray-Coquard, G. Catimel, C. Ardiet, J.P. Guastalla, A. Dumortier, F. Chauvin, J.P. Droz, T. Philip, M. Clavel
Journal: Annals of Oncology (2000)
Psychological Defense Styles in Women Who Report Childhood Sexual Abuse: A Controlled Community Study
Authors: Sarah E. Romans, Judy L. Martin, Eleanor Morris, G. Peter Herbison
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: The psychological defense styles of women who reported childhood sexual abuse were assessed and compared to those of women without childhood sexual abuse. METHOD: Subjects in a random community sample (N=354) of New Zealand women were interviewed and completed two relevant questionnaires, the Defense Style Questionnaire and the Dissociative Experiences Scale. RESULTS: Women reporting childhood sexual abuse showed more immature defense styles, and those who experienced the most severe childhood sexual abuse showed the most immature styles. Dissociation, however, as measured on the Dissociative Experiences Scale, was not linked to childhood sexual abuse. CONCLUSIONS: Reporting childhood sexual abuse was associated with more immature coping styles, although not dissociation, in this community sample of women. Coping styles are likely to be a major mechanism through which childhood sexual abuse increases rates of later psychological problems.
Hypofractionated Stereotactic Radiotherapy (HypoFXSRT) for Stage I Non-small Cell Lung Cancer: Updated Results of 257 Patients in a Japanese Multi-institutional Study
Authors: Hiroshi Onishi, Hiroki Shirato, Yasushi Nagata, Masahiro Hiraoka, Masaharu Fujino, Kotaro Gomi, Yuzuru Niibe, Katsuyuki Karasawa, Kazushige Hayakawa, Yoshihiro Takai, Tomoki Kimura, Atsuya Takeda, Atsushi Ouchi, Masato Hareyama, Masaki Kokubo, Ryusuke Hara, Jun Itami, Kazunari Yamada, Tsutomu Araki
Journal: Journal of Thoracic Oncology (2007)
Usefulness of serum procalcitonin levels in pulmonary tuberculosis
Authors: M. Ugajin, S. Miwa, M. Shirai, H. Ohba, T. Eifuku, H. Nakamura, T. Suda, H. Hayakawa, K. Chida
Journal: European Respiratory Journal (2010)

There are very few data on serum procalcitonin (PCT) levels in pulmonary tuberculosis (PTB) patients who are negative for HIV. We assessed serum PCT in consecutive patients diagnosed with pulmonary tuberculosis or community-acquired pneumonia (CAP) on admission to discriminate between PTB and CAP, and examined the value of prognostic factors in PTB. 102 PTB patients, 62 CAP patients, and 34 healthy volunteers were enrolled. Serum PCT in PTB patients was significantly lower than in CAP patients (mean ± sd 0.21 ± 0.49 versus 4.10 ± 8.68 ng·mL⁻¹; p < 0.0001). By receiver-operating characteristic curve analysis, serum PCT was an appropriate discrimination marker for PTB and CAP (area under the curve 0.866). PTB patients with ≥ 0.5 ng·mL⁻¹ (normal cut-off) had significantly shorter survival than those with < 0.5 ng·mL⁻¹ (p < 0.0001). Serum PCT is not habitually elevated in HIV-negative PTB patients and is a useful biomarker for discriminating between PTB and CAP; however, when serum PCT is outside the normal range, it is a poor prognostic marker.