tbuckley/cabot-search huggingface dataset:
Suicide and Serious Suicide Attempts in Youth: A Multiple-Group Comparison Study
Authors: Annette L. Beautrais
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: This study compared risk factors for suicide and medically serious nonfatal suicide attempts among youth under 25 years of age. METHOD: Three groups were examined: individuals who committed suicide (N=60), individuals who made serious suicide attempts (N=125), and nonsuicidal community comparison subjects (N=151). Suicidal and nonsuicidal subjects were compared in terms of sociodemographic, childhood, family, psychosocial, and psychiatric factors. RESULTS: Suicides were characterized by male gender, lack of educational qualifications, mood disorder, history of mental health care, and stressful life events. Except for gender, similar risk factors were associated with serious suicide attempts. Suicides and serious suicide attempts were discriminated by gender and mood disorder. Gender differences between suicides and nonfatal suicide attempts were explained by gender differences in methods. CONCLUSIONS: The same risk factors (mood disorder, history of psychiatric care, educational disadvantage, stressful circumstances) play a similar role in suicide and serious suicide attempts. Suicide and suicide attempts are discriminated by mood disorder and gender differences in methods.
MGMT promoter methylation is predictive of response to radiotherapy and prognostic in the absence of adjuvant alkylating chemotherapy for glioblastoma
Authors: A. L. Rivera, C. E. Pelloski, M. R. Gilbert, H. Colman, C. De La Cruz, E. P. Sulman, B. N. Bekele, K. D. Aldape
Journal: Neuro-Oncology (2009)

Hypermethylation of the O6-methylguanine-DNA-methyltransferase (MGMT) gene has been shown to be associated with improved outcome in glioblastoma (GBM) and may be a predictive marker of sensitivity to alkylating agents. However, the predictive utility of this marker has not been rigorously tested with regard to sensitivity to other therapies, namely radiation. To address this issue, we assessed MGMT methylation status in a cohort of patients with GBM who underwent radiation treatment but did not receive chemotherapy as a component of adjuvant treatment. Formalin-fixed, paraffin-embedded tumor samples from 225 patients with newly diagnosed GBM were analyzed via methylation-specific, quantitative real-time polymerase chain reaction following bisulfite treatment on isolated DNA to assess MGMT promoter methylation status. In patients who received radiotherapy alone following resection, methylation of the MGMT promoter correlated with an improved response to radiotherapy. Unmethylated tumors were twice as likely to progress during radiation treatment. The median time interval between resection and tumor progression of unmethylated tumors was also nearly half that of methylated tumors. Promoter methylation was also found to confer improved overall survival in patients who did not receive adjuvant alkylating chemotherapy. Multivariable analysis demonstrated that methylation status was independent of age, Karnofsky performance score, and extent of resection as a predictor of time to progression and overall survival. Our data suggest that MGMT promoter methylation appears to be a predictive biomarker of radiation response. Since this biomarker has also been shown to predict response to alkylating agents, perhaps MGMT promoter methylation represents a general, favorable prognostic factor in GBM.
H6D Polymorphism in Macrophage-Inhibitory Cytokine-1 Gene Associated With Prostate Cancer
Authors: F. Lindmark, S. L. Zheng, F. Wiklund, J. Bensen, K. A. Balter, B. Chang, M. Hedelin, J. Clark, P. Stattin, D. A. Meyers, H.-O. Adami, W. Isaacs, H. Gronberg, J. Xu
Journal: JNCI Journal of the National Cancer Institute (2004)

Accumulating epidemiologic and molecular evidence suggest that inflammation is an important component in the etiology of prostate cancer. Macrophage-inhibitory cytokine-1 (MIC-1), a member of the transforming growth factor beta superfamily, is thought to play an important role in inflammation by regulating macrophage activity. We examined whether sequence variants in the MIC-1 gene are associated with the risk of prostate cancer.The study population, a population-based case-control study in Sweden, consisted of 1383 prostate cancer case patients and 780 control subjects. From 94 of the control subjects, we constructed gene-specific haplotypes of MIC-1 and identified four haplotype-tagging single-nucleotide polymorphisms (SNPs): Exon1+25 (V9L), Exon1+142 (S48T), IVS1+1809, and Exon2+2423 (H6D). All study subjects were genotyped for the four SNPs, and conditional logistic regression analysis was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs).A statistically significant difference (P =.006) in genotype frequency was observed for the nonsynonymous change H6D (histidine to aspartic acid at position 6) between prostate cancer patients and control subjects. Carriers of the GC genotype, which results in the H6D change, experienced a lower risk of sporadic prostate cancer (OR = 0.80, 95% CI = 0.66 to 0.97) and of familial prostate cancer (OR = 0.61, 95% CI = 0.42 to 0.89) than the CC genotype carriers. In the study population, the proportion of prostate cancer cases attributable to the CC genotype was 7.2% for sporadic cancer and 19.2% for familial cancer. None of the other SNPs or haplotypes was associated with prostate cancer.This study shows an association between a nonsynonymous change (H6D) in the MIC-1 gene and prostate cancer. This finding supports the hypothesis that genetic variation in the inflammatory process contributes to prostate cancer susceptibility.
Critical Role for Cd8 in T Cell Receptor Binding and Activation by Peptide/Major Histocompatibility Complex Multimers
Authors: Mark A. Daniels, Stephen C. Jameson
Journal: The Journal of Experimental Medicine (2000)

Recent data using MHC/peptide tetramers and dimers suggests that the T cell coreceptors, CD4 and CD8, although important for T cell activation, do not play a direct role in facilitating T cell receptor (TCR) binding to multivalent MHC/peptide ligands. Instead, a current model proposes that coreceptors are recruited only after a stable TCR–MHC/peptide complex has already formed and signaled. In contrast, we show using multimeric class I MHC/peptide ligands that CD8 plays a critical (in some cases obligatory) role in antigen-specific TCR binding. T cell activation, measured by calcium mobilization, was induced by multimeric but not monomeric ligands and also showed CD8 dependency. Our analysis using anti-CD8 antibodies revealed that binding to different epitopes of CD8 can either block or augment TCR–MHC/peptide interaction. These effects on TCR binding to high-affinity agonist ligands were even more pronounced when binding to multimeric low-affinity ligands, including TCR antagonists, was studied. Our data have important implications for the role of CD8 in TCR binding to MHC/peptide ligands and in T cell activation. In addition, our results argue against the view that multimeric MHC/peptide ligands bind directly and solely to the TCR; rather, our data highlight a pivotal contribution of CD8 for this association.
A revised view of cardiac sodium channel “blockade” in the long-QT syndrome
Authors: Nicholas G. Kambouris, H. Bradley Nuss, David C. Johns, Eduardo Marbán, Gordon F. Tomaselli, Jeffrey R. Balser
Journal: Journal of Clinical Investigation (2000)

Mutations in SCN5A, encoding the cardiac sodium (Na) channel, are linked to a form of the congenital long-QT syndrome (LQT3) that provokes lethal ventricular arrhythmias. These autosomal dominant mutations disrupt Na channel function, inhibiting channel inactivation, thereby causing a sustained ionic current that delays cardiac repolarization. Sodium channel–blocking antiarrhythmics, such as lidocaine, potently inhibit this pathologic Na current (INa) and are being evaluated in patients with LQT3. The mechanism underlying this effect is unknown, although high-affinity "block" of the open Na channel pore has been proposed. Here we report that a recently identified LQT3 mutation (R1623Q) imparts unusual lidocaine sensitivity to the Na channel that is attributable to its altered functional behavior. Studies of lidocaine on individual R1623Q single-channel openings indicate that the open-time distribution is not changed, indicating the drug does not block the open pore as proposed previously. Rather, the mutant channels have a propensity to inactivate without ever opening ("closed-state inactivation"), and lidocaine augments this gating behavior. An allosteric gating model incorporating closed-state inactivation recapitulates the effects of lidocaine on pathologic INa. These findings explain the unusual drug sensitivity of R1623Q and provide a general and unanticipated mechanism for understanding how Na channel–blocking agents may suppress the pathologic, sustained Na current induced by LQT3 mutations.
Comparison of HER-2 status between primary breast cancer and corresponding distant metastatic sites
Authors: D. Gancberg, A. Di Leo, F. Cardoso, G. Rouas, M. Pedrocchi, M. Paesmans, A. Verhest, C. Bernard-Marty, M.J. Piccart, D. Larsimont
Journal: Annals of Oncology (2002)
The July Phenomenon Revisited
Authors: Gary E. Rosenthal, Mary Vaughan-Sarrazin
Journal: Circulation (2013)

E ach July, teaching hospitals experience an influx of new residents and fellows who recently have graduated from medical school or completed residency training programs.During this period, teaching hospitals also assign new positions of responsibility to existing residents and fellows.Medical education is a core mission of teaching hospitals, and, in these hospitals, interns, residents, and fellows play major roles in patient care.This recurrent cycle in which care is delivered by less experienced physicians in the initial month of the academic year has led to the often expressed conventional wisdom of "not to get sick in July.
Prediction of carcinoma in acquired cystic disease as a function of kidney weight.
Authors: M L MacDougall, L W Welling, T B Wiegmann
Journal: Journal of the American Society of Nephrology (1990)

Acquired renal cystic disease occurs in up to 80% of patients on chronic dialysis and is complicated by renal adenocarcinoma in about 6% of cases. This report suggests that acquired cystic kidneys weighing more than 150 g are six times more likely to contain carcinoma than are kidneys of smaller size. This relationship is true whether or not the large kidney contains a radiologically detectable tumor. Therefore, even in the absence of demonstrable tumor mass, strong consideration should be given to the removal of large acquired cystic kidneys.
Osteo-Arthritis of the Hip-Joint Treated by Vaccines
Authors: H. W. Crowe
Journal: BMJ (1926)

case of rlheumatoid artlhritis (Still's disease) as a clinical elntity witlh very definite signs, and he was not inclined to allow any chemical investigations to interfere, one way or the other, with his opinion.He was not prepared to accept Mr. Irwin's explanation of the fact that displacement of the head of the femur did not occur in the youinger children.He thoulght the buffer-like action of the thick epipllyseal cartilage might be responsible, since in the femur, as in other bones, the displacement of the epiplysis
One-year change in health status and subsequent outcomes in COPD
Authors: Sarah Wilke, Paul W Jones, H Müllerova, Jørgen Vestbo, Ruth Tal-Singer, Frits ME Franssen, Alvar Agusti, Per Bakke, Peter M Calverley, Harvey O Coxson, Courtney Crim, Lisa D Edwards, David A Lomas, William MacNee, Stephen I Rennard, Julie C Yates, Emiel FM Wouters, Martijn A Spruit
Journal: Thorax (2015)

<h3>Background</h3> Poor health status has been associated with morbidity and mortality in patients with COPD. To date, the impact of changes in health status on these outcomes remains unknown. <h3>Aims</h3> To explore the relationship of clinically relevant changes in health status with exacerbation, hospitalisation or death in patients with COPD. <h3>Methods</h3> Characteristics and health status (St George9s Respiratory Questionnaire, SGRQ) were assessed over a period of 3 years in 2138 patients with COPD enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study: a longitudinal, prospective, observational study. Associations between change in health status (=4 units in SGRQ score) during year 1 and time to first exacerbation, hospitalisation and death during 2-year follow-up were assessed using Kaplan–Meier plots and log-rank test. <h3>Results</h3> 1832 (85.7%) patients (age 63.4±7.0 years, 65.4% male, FEV<sub>1</sub> 48.7±15.6% predicted) underwent assessment at baseline and 1 year. Compared with those who deteriorated, patients with improved or stable health status in year 1 have a lower likelihood of exacerbation (HR 0.78 (95% CI 0.67 to 0.89), p&lt;0.001 and 0.84 (0.73 to 0.97), p=0.016, respectively), hospitalisation (0.72 (0.58 to 0.90), p=0.004 and 0.77 (0.62 to 0.96), p=0.023, respectively) or dying (0.61 (0.39 to 0.95), p=0.027 and 0.58 (0.37 to 0.92), p=0.019, respectively) during 2-year follow-up. This effect persisted after stratification for age and the number of exacerbations and hospitalisations during the first year of the study. <h3>Conclusions</h3> Patients with stable or improved health status during year 1 of ECLIPSE had a lower likelihood of exacerbation, hospitalisation or dying during 2-year follow-up. Interventions that stabilise and improve health status may also improve outcomes in patients with COPD. <h3>Trial registration number</h3> NCT00292552, registered at ClinicalTrials.gov.
All that glitters is not gold
Authors: R P Mookerjee
Journal: Gut (2002)

Addition of vasoactive drug therapy improved the effectiveness of injection sclerosis or band ligation for acute variceal bleeding but failed to produce a significant reduction in mortality

Initial presentation with variceal bleeding is associated with a 20–30% risk of mortality within the first two weeks. Early control of bleeding is paramount and traditionally has taken the form of endoscopic therapy to mechanically reduce variceal blood flow, or vasoactive drugs that decrease splanchnic and/or azygous blood flow. Although sclerotherapy has been shown to reduce bleeding compared with placebo,1 it results in more frequent adverse events than medical interventions2 and has largely been superseded by variceal band ligation. Indeed ligation has been shown to reduce rebleeding and mortality compared with sclerotherapy and is the current gold standard for acute bleeding and secondary prophylaxis.3 A recent evaluation combining the two endoscopic modalities demonstrated no benefit over ligation alone in preventing rebleeding or mortality.4

The systematic review by Banares et al suggests a potential benefit from combining vasoactive drugs with endoscopic therapy with improved initial endoscopic control of bleeding and five day haemostasis, albeit with no reduction in mortality. This is a high quality systematic review with assessment of the quality of all included …
Extensive glycosylation of ACPA-IgG variable domains modulates binding to citrullinated antigens in rheumatoid arthritis
Authors: Yoann Rombouts, Annemiek Willemze, Joyce J B C van Beers, Jing Shi, Priscilla F Kerkman, Linda van Toorn, George M C Janssen, Arnaud Zaldumbide, Rob C Hoeben, Ger J M Pruijn, André M Deelder, Gertjan Wolbink, Theo Rispens, Peter A van Veelen, Tom W J Huizinga, Manfred Wuhrer, Leendert A Trouw, Hans U Scherer, René E M Toes
Journal: Annals of the Rheumatic Diseases (2015)

Objectives To understand the molecular features distinguishing anti-citrullinated protein antibodies (ACPA) from ‘conventional’ antibodies in rheumatoid arthritis (RA). Methods Serum of ACPA-positive RA patients was fractionated by size exclusion chromatography and analysed for the presence of ACPA-IgG by ELISA. ACPA-IgG and non-citrulline-specific IgG were affinity purified from serum, plasma and/or synovial fluid and analysed by gel electrophoresis. Electrophoresis bands were excised, enzymatically digested and analysed by mass spectrometry. Binding affinity to citrullinated antigens was measured by ELISA and imaging surface plasmon resonance using recombinant monoclonal ACPA with molecular modifications. Results In all donor samples studied (n=24), ACPA-IgG exhibited a 10–20 kDa higher molecular weight compared with non-autoreactive IgG. This feature also distinguished ACPA-IgG from antibodies against recall antigens or other disease-specific autoantibodies. Structural analysis revealed that a high frequency of N-glycans in the (hyper)variable domains of ACPA is responsible for this observation. In line with their localisation, these N-glycans were found to modulate binding avidity of ACPA to citrullinated antigens. Conclusions The vast majority of ACPA-IgG harbour N-glycans in their variable domains. As N-linked glycosylation requires glycosylation consensus sites in the protein sequence and as these are lacking in the ‘germline-counterparts’ of identified variable domains, our data indicate that the N-glycosylation sites in ACPA variable domains have been introduced by somatic hypermutation. This finding also suggests that ACPA-hyperglycosylation confers a selective advantage to ACPA-producing B cells. This unique and completely novel feature of the citrulline-specific immune response in RA elucidates our understanding of the underlying B cell response.
Morphologic and molecular genetic aspects of oligodendroglial neoplasms
Authors: Sandra H. Bigner, B.K. Ahmed Rasheed, Rodney Wiltshire, Roger E. McLendon
Journal: Neuro-Oncology (1999)

Morphologic criteria for diagnosing oligodendrogliomas and for classifying them as well-differentiated (World Health Organization grade II) and anaplastic (World Health Organization grade III) are well recognized. Nevertheless, applying these guidelines to specific cases often reveals discrepancies among different observers. In addition, whether a given tumor also contains an astrocytic component may be debatable. Loss of heterozygosity studies have demonstrated that oligodendroglial neoplasms have a high incidence of loss of the 1p and 19q chromosomal arms. Although loss of heterozygosity for portions of 19q are sometimes seen in astrocytic neoplasms, these tumors seldom show complete loss of 19q accompanied by loss of 1p. Loss of 9p or homozygous deletion of the CDKN2 gene or both are associated with anaplastic oligodendrogliomas, whereas loss of 17p or TP53 gene mutations or both are frequent in astrocytomas, but rare in oligodendrogliomas. These observations suggest that molecular genetic parameters could provide an objective, reproducible framework for classifying oligodendroglial neoplasms.
THE PHRENOTROPIC ACTION OF RITALIN AS EVALUATED BY AN IBM RATING SCALE
Authors: VERONICA M. PENNINGTON
Journal: American Journal of Psychiatry (1958)

The use of a universal measuring stick, the International Business Machine rating scale, makes the findings before and after phrenotropic drug trials comparable and intelligible to all workers in the field of neuropsychiatry. Ritalin is a useful phrenotropic drug in many neuropsychiatric cases showing lethargy, retardation, confusion, inertia and depression, constitutional or drug induced.
Mesalazine and thymoquinone attenuate intestinal tumour development in Msh2<sup>loxP/loxP</sup>Villin-Cre mice
Authors: Benedikt Kortüm, Christoph Campregher, Michaela Lang, Vineeta Khare, Matthias Pinter, Rayko Evstatiev, Gerald Schmid, Martina Mittlböck, Theresa Scharl, Melanie H Kucherlapati, Winfried Edelmann, Christoph Gasche
Journal: Gut (2014)

<h3>Objective</h3> Lynch syndrome is caused by germline mutations in DNA mismatch repair genes leading to microsatellite instability (MSI) and colorectal cancer. Mesalazine, commonly used for the treatment of UC, reduces MSI in vitro. Here, we tested natural compounds for such activity and applied mesalazine and thymoquinone in a Msh2<sup>loxP/loxP</sup> Villin-Cre mouse model for Lynch syndrome. <h3>Design</h3> Flow cytometry was used for quantitation of mutation rates at a CA<sub>13</sub> microsatellite in human colon cancer (HCT116) cells that had been stably transfected with pIREShyg2-enhanced green fluorescent protein/CA13, a reporter for frameshift mutations. Mice were treated for 43 weeks with mesalazine, thymoquinone or control chow. Intestines were analysed for tumour incidence, tumour multiplicity and size. MSI testing was performed from microdissected normal intestinal or tumour tissue, compared with mouse tails and quantified by the number of mutations per marker (NMPM). <h3>Results</h3> Besides mesalazine, thymoquinone significantly improved replication fidelity at 1.25 and 2.5 µM in HCT116 cells. In Msh2<sup>loxP/loxP</sup> Villin-Cre mice, tumour incidence was reduced by mesalazine from 94% to 69% (p=0.04) and to 56% (p=0.003) by thymoquinone. The mean number of tumours was reduced from 3.1 to 1.4 by mesalazine (p=0.004) and to 1.1 by thymoquinone (p&lt;0.001). Interestingly, MSI was reduced in normal intestinal tissue from 1.5 to 1.2 NMPM (p=0.006) and to 1.1 NMPM (p=0.01) by mesalazine and thymoquinone, respectively. Thymoquinone, but not mesalazine, reduced MSI in tumours. <h3>Conclusions</h3> Mesalazine and thymoquinone reduce tumour incidence and multiplicity in Msh2<sup>loxP/loxP</sup> Villin-Cre mice by reduction of MSI independent of a functional mismatch repair system. Both substances are candidate compounds for chemoprevention in Lynch syndrome mutation carriers.
In vitro regulation of IgA subclass synthesis. I. Discordance between plasma cell production and antibody secretion.
Authors: M E Conley, W J Koopman
Journal: The Journal of Experimental Medicine (1982)

To investigate the in vitro regulation of IgA subclass synthesis, peripheral blood lymphocytes from healthy adults were cultured with the polyclonal B cell activator, pokeweed mitogen. Although 50% of the IgA plasma cells from a 7-d culture were positive for cytoplasmic IgA1 and 50% were positive for IgA2, less than 10% of the IgA released into the culture supernatant was IgA2. This discrepancy could not be explained by failure of the assay to detect in vitro synthesized IgA2, selective loss or destruction of IgA2 in culture media, delayed release of IgA2, or failure of IgA2 plasma cells to produce J chain. The results suggest that additional signals may be required for the differentiation of plasma cells into immunoglobulin-secreting cells.
Empathy: Each is in the right – hopefully, not all in the wrong
Authors: Stephanie D. Preston, Frans B. M. de Waal
Journal: Behavioral and Brain Sciences (2002)

Only a broad theory that looks across levels of analysis can encompass the many perspectives on the phenomenon of empathy. We address the major points of our commentators by emphasizing that the basic perception-action process, while automatic, is subject to control and modulation, and is greatly affected by experience and context because of the role of representations. The model can explain why empathy seems phenomenologically more effortful than reflexive, and why there are different levels of empathy across individuals, ages, and species.