tbuckley/cabot-search huggingface dataset:
A Prototype Approach to Personality Disorder Diagnosis
Authors: Drew Westen, Jonathan Shedler, Rebekah Bradley
Journal: American Journal of Psychiatry (2006)

Virtually no research has tested alternatives to the diagnostic method used since DSM-III, which requires decisions about the presence/absence of individual diagnostic criteria, followed by counting symptoms and applying cutoffs (the count/cutoff method). This study tested an alternative, prototype matching procedure designed to simplify diagnosis. The procedure was applied to personality disorders.A random national sample of psychiatrists and clinical psychologists (N=291) described a randomly selected patient in their care. Clinician-provided diagnostic data were used to generate categorical and dimensional DSM-IV diagnoses (number of symptoms present per disorder). Clinicians also used one of two prototype matching systems to provide a diagnosis for the selected patient.Prototype diagnosis led to reduced comorbidity relative to DSM-IV diagnosis, yielded similar estimates of validity in predicting criterion variables (adaptive functioning, treatment response, and etiology), and outperformed DSM-IV diagnosis in ratings of clinical utility and ease of use. Adding a personality health prototype further increased prediction.A simple prototype matching procedure provides a viable alternative for improving diagnosis of personality disorders in clinical practice. Prototype diagnosis has multiple advantages, including ease of use, minimization of artifactual comorbidity, compatibility with naturally occurring cognitive processes, and ready translation into both categorical and dimensional diagnosis.
MB-11 * IMPACT OF MOLECULAR SUB-TYPE AND CRANIOSPINAL IRRADIATION (CSI) DOSE ON RELAPSE OF MEDULLOBLASTOMA
Authors: A. Wang, S. Partap, K. Yeom, M. Martinez, H. Vogel, S. Donaldson, P. Fisher, S. Perreault, Y.-J. Cho, I. Gibbs
Journal: Neuro-Oncology (2015)

PURPOSE: To evaluate the impact of craniospinal irradiation (CSI) dose and molecular sub-type on medulloblastoma relapse rates. METHODS: 115 medulloblastoma patients were treated with 18- ≥ 36 Gy CSI. Molecular subtyping data was done by nanostring assay [WNT, SHH, and Group 3/4 non-WNT/non-SHH (NWNS)]. A CSI dose schema based on prognostic implications of molecular subtype was devised: ≥36 Gy for M+ or Group 3; ≤18 Gy for non-disseminated WNT; 23.4 Gy all others. Relapse rates were assessed and correlated with CSI dose. RESULTS: After excluding patients with incomplete data, the final cohort included 36 subjects with median age 8.7 years (range 3.3–16.9) and median follow-up 4.1 years (0.2-3.7). Molecular subtypes were as follows: 2-WNT, 6-SHH, 28-NWNS. CSI dose was 18 Gy(11 cases), 23.4 Gy(9), and ≥36 Gy(16). CSI dose was divergent from the proposed schema in 18 cases (14-lower, 4-higher). There were 14 relapses (by molecular subtype: 0-WNT, 1-SHH, 13-NWNS; by histology: 8-classic, 5-LC/A, 1-EN), with median time to relapse 18.5 months (0.43-62). Seven of 14 tumors treated to a lower dose relapsed (1 SHH; 6 NWNS); only 1 (NWNS) of 4 patients with higher divergent dose relapsed. Six of 18 patients treated to similar dose relapsed; all were NWNS, and 4/6 had M3 disease. Eleven of 14 patients who relapsed died. CONCLUSION: Molecular subtyping may help avoid under-treating some NWNS tumors but innovative strategies for metastatic NWNS are needed. We confirm that histological subtypes may hold some predictive value as 5/7 LC/A relapsed and no desmoplastic tumors relapsed. In this small sample, no WNT relapse occurred and only 1 SHH relapsed, suggesting that dose de-escalation can be cautiously explored for these subtypes. Future research directions include applying an MRI image-based algorithm to subtype the entire cohort, and combining molecular data with other institutions to examine relapse patterns by subtype.
Validation of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis: slight improvement over the 1987 ACR criteria
Authors: K. Britsemmer, J. Ursum, M. Gerritsen, L. van Tuyl, D. van Schaardenburg
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Recently, an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) collaboration developed new classification criteria for rheumatoid arthritis (RA). <h3>Objective</h3> To evaluate the diagnostic and discriminative ability of these new criteria compared with the 1987 ACR criteria and the Visser decision rule. <h3>Methods</h3> 455 patients with early arthritis were studied. The diagnostic performance of the criteria was evaluated using methotrexate treatment within 1 year, expert opinion RA and erosive disease as 'gold standards'. Erosive disease was defined as a 0–3 year change in radiographic score of ≥5. <h3>Results</h3> The discriminative ability of the three criteria sets (2010 ACR/EULAR, 1987 ACR criteria and Visser algorithm) was similar with areas under the curve of 0.71–0.78 ('gold standard' methotrexate), 0.74–0.80 (gold standard expert opinion RA) and 0.63–0.67 (gold standard erosive disease after 3 years). The sensitivity of the 2010 ACR/EULAR criteria was highest with 0.85 (gold standard methotrexate). 86% of patients with RA and 51% of 'non-RA' patients according to the new criteria used methotrexate. <h3>Conclusion</h3> The 2010 ACR/EULAR criteria were slightly more sensitive, but otherwise performed similarly to the older criteria. A high percentage of 'non-RA' patients used methotrexate, the gold standard for RA. The ability of the new criteria to identify patients with erosive disease was low, possibly owing to the effect of intensive treatment.
Does ‘altitude training’ increase exercise performance in elite athletes?
Authors: Carsten Lundby, Gregoire P Millet, Jose A Calbet, Peter Bärtsch, Andrew W Subudhi
Journal: British Journal of Sports Medicine (2012)

The general practice of altitude training is widely accepted as a means to enhance sport performance despite a lack of rigorous scientific studies. For example, the scientific gold-standard design of a double-blind, placebo-controlled, cross-over trial has never been conducted on altitude training. Given that few studies have utilised appropriate controls, there should be more scepticism concerning the effects of altitude training methodologies. In this brief review we aim to point out weaknesses in theories and methodologies of the various altitude training paradigms and to highlight the few well-designed studies to give athletes, coaches and sports medicine professionals the current scientific state of knowledge on common forms of altitude training. Another aim is to encourage investigators to design well-controlled studies that will enhance our understanding of the mechanisms and potential benefits of altitude training.
P140 BPIFB1/LPLUNC1 is a novel marker for the bronchiolised epithelium in IPF
Authors: CD Bingle, B Araujo, WA Wallace, HM Marriott, N Hirani, L Bingle
Journal: Thorax (2013)

<h3></h3> Idiopathic pulmonary fibrosis (IPF) is an irreversible and progressive lung disease with limited life expectancy after diagnosis. Histopathological studies of IPF lungs reveal the typical “Usual Interstitial Pneumonia” (UIP) pattern, with epithelial hyperplasia, areas of scarring with fibroblast foci and characteristic morphological abnormalities, including bronchiolization of alveolar ducts and honeycomb cysts. Although it seems likely that bronchiolar abnormalities are caused by changes in epithelial cell differentiation, specific markers of this process remain elusive. By analysis of published array data sets from IPF patients, we identified BPIFB1/LPLUNC1 as a potential candidate marker for the disease. Indeed, in the largest published study the gene was the most differentially expressed transcript. This putative innate defence protein is normally expressed in the airway submucosal glands and in a population of MUC5A/C positive goblet cells in the upper airways. Analysis of lung tissue from UIP revealed strong staining of BPIFB1/LPLUNC1 within the bronchiolized epithelium lining the honeycomb cysts as well as in the mucosubstance filling these regions. MUC5B was localized to the same cells as BPIFB1/LPLUNC1 wheras the related protein, BPIFA1/SPLUNC1, was not co-expressed. This pattern of staining was not seen in other chronic lung diseases, suggesting a degree of specificity for IPF. To shed light on a temporal association of expression of these markers with fibrosis development we studied mice exposed to the pro-fibrotic agent bleomycin (Bleo). MUC5B and LPLUNC1 were co-expressed in a population of goblet cells in the airways of mice within 3–7 days of Bleo exposure, prior to the onset of fibrosis. Continued expression was seen during the development of fibrosis between 14–21 days post treatment. In contrast, in mice treated with PBS neither protein was seen (due to mouse airways being essentially free of goblet cells). Staining was absent from the fibrotic regions and the lung parenchyma, as is the case in IPF. Our data show that the ectopic expression seen in human IPF, is mirrored by that seen in the fibrotic mouse model. Furthermore it suggests that BPIFB1/LPLUNC1 may be worthy of further study as potential marker for the disease.
Parkinson's disease brain mitochondria have impaired respirasome assembly, age-related increases in distribution of oxidative damage to mtDNA and no differences in heteroplasmic mtDNA mutation abundance
Authors: Charles R Arthur, Stephanie L Morton, Lisa D Dunham, Paula M Keeney, James P Bennett
Journal: Molecular Neurodegeneration (2009)

Sporadic Parkinson's disease (sPD) is a nervous system-wide disease that presents with a bradykinetic movement disorder and is frequently complicated by depression and cognitive impairment. sPD likely has multiple interacting causes that include increased oxidative stress damage to mitochondrial components and reduced mitochondrial bioenergetic capacity. We analyzed mitochondria from postmortem sPD and CTL brains for evidence of oxidative damage to mitochondrial DNA (mtDNA), heteroplasmic mtDNA point mutations and levels of electron transport chain proteins. We sought to determine if sPD brains possess any mtDNA genotype-respiratory phenotype relationships.Treatment of sPD brain mtDNA with the mitochondrial base-excision repair enzyme 8-oxyguanosine glycosylase-1 (hOGG1) inhibited, in an age-dependent manner, qPCR amplification of overlapping ~2 kbase products; amplification of CTL brain mtDNA showed moderate sensitivity to hOGG1 not dependent on donor age. hOGG1 mRNA expression was not different between sPD and CTL brains. Heteroplasmy analysis of brain mtDNA using Surveyor nuclease(R) showed asymmetric distributions and levels of heteroplasmic mutations across mtDNA but no patterns that statistically distinguished sPD from CTL. sPD brain mitochondria displayed reductions of nine respirasome proteins (respiratory complexes I-V). Reduced levels of sPD brain mitochondrial complex II, III and V, but not complex I or IV proteins, correlated closely with rates of NADH-driven electron flow. mtDNA levels and PGC-1alpha expression did not differ between sPD and CTL brains.PD brain mitochondria have reduced mitochondrial respiratory protein levels in complexes I-V, implying a generalized defect in respirasome assembly. These deficiencies do not appear to arise from altered point mutational burden in mtDNA or reduction of nuclear signaling for mitochondrial biogenesis, implying downstream etiologies. The origin of age-related increases in distribution of oxidative mtDNA damage in sPD but not CTL brains is not clear, tracks with but does not determine the sPD phenotype, and may indicate a unique consequence of aging present in sPD that could contribute to mtDNA deletion generation in addition to mtDNA replication, transcription and sequencing errors. sPD frontal cortex experiences a generalized bioenergetic deficiency above and beyond aging that could contribute to mood disorders and cognitive impairments.
Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus
Authors: Veronique Chauvet, Xin Tian, Herve Husson, David H. Grimm, Tong Wang, Thomas Hieseberger, Peter Igarashi, Anton M. Bennett, Oxana Ibraghimov-Beskrovnaya, Stefan Somlo, Michael J. Caplan
Journal: Journal of Clinical Investigation (2004)

Polycystin-1, which is encoded by a gene that is mutated in autosomal dominant polycystic kidney disease (ADPKD), is involved in cell-matrix interactions as well as in ciliary signaling. The precise mechanisms by which it functions, however, remain unclear. Here we find that polycystin-1 undergoes a proteolytic cleavage that releases its C-terminal tail (CTT), which enters the nucleus and initiates signaling processes. The cleavage occurs in vivo in association with alterations in mechanical stimuli. Polycystin-2, the product of the second gene mutated in ADPKD, modulates the signaling properties of the polycystin-1 CTT. These data reveal a novel pathway by which polycystin-1 transmits messages directly to the nucleus.
Cranking the Immunologic Engine with Chemotherapy: Using Context to Drive Tumor Antigen Cross-Presentation towards Useful Antitumor Immunity
Authors: Robbert G. van der Most, Andrew Currie, Bruce W.S. Robinson, Richard A. Lake
Journal: Cancer Research (2006)

Abstract This review shows how tumor antigen cross-presentation is affected by the major therapeutic modalities including chemotherapy, radiotherapy, and surgery. We argue that this process could affect the way that a tumor works as its own cellular vaccine, and that it is differentially modulated by the choice of treatment. (Cancer Res 2006; 66(2): 601-4)
730 PEGBELIVER STUDY: HBSAG DECLINE AT WEEK 24 OF EXTENDED PEGINTERFERON ALFA-2A (PEG-IFNα-2A) THERAPY IS SIGNIFICANTLY ASSOCIATED WITH POST-TREATMENT RESPONSE IN HBEAG-NEGATIVE GENOTYPE D PATIENTS
Authors: P. Lampertico, M. Viganò, A. Galeota Lanza, E. Sagnelli, M. Fasano, V. Di Marco, S. Bininsegna, P. Farci, S. Fargion, T. Giuberti, C. Iannacone, B. Massetto, E.B. Martins, M. Colombo
Journal: Journal of Hepatology (2011)
Nonfatal Acute Myocardial Infarction in Costa Rica
Authors: Edmond K. Kabagambe, Ana Baylin, Hannia Campos
Journal: Circulation (2007)

Background— Cardiovascular disease, including myocardial infarction (MI), is increasing in developing countries. Knowledge of risk factors and their impact on the population could offer insights into primary prevention. Methods and Results— We estimated the population-attributable risk (PAR) for major MI risk factors among Costa Ricans without a history of diabetes, hypertension, or regular use of medication (889 MI cases, 1167 population-based controls). Lifestyle and dietary variables were measured with validated questionnaires. In multivariate analyses, abdominal obesity (PAR, 29.3%), smoking (PAR, 25.6%), nonuse of alcohol (PAR, 14.8%), caffeine intake (PAR, 12.8%), physical inactivity (PAR, 9.6%), and poor diet (PAR, 6.0%) were the most important MI risk factors. Subjects in the favorable categories of the above 6 risk factors showed a lower risk of MI (odds ratio, 0.09; 95% CI, 0.03 to 0.33) than those in the unfavorable categories. Compared with women, men were more likely to smoke (31% versus 10%) but less likely to have waist circumferences greater than Adult Treatment Panel III cutoffs (9% versus 35%). Many subjects did not meet the American Heart Association or World Health Organization/Food and Agriculture Organization dietary guidelines. For instance, 95% obtained ≥7% of energy from saturated fat, 25% had ≤5% of energy from polyunsaturated fat, 63% had ≥1% energy from trans fat, and 53% had low fiber intake (&lt;25 g/d). Conclusions— These findings confirm the benefit of a healthy diet, physical activity, moderate alcohol, and cessation of smoking as approaches for the primary prevention of MI. Obesity and smoking were the 2 most important risk factors for nonfatal MI in Costa Rica.
Catecholamines restore myocardial contractility in dilated cardiomyopathy at the expense of increased coronary blood flow and myocardial oxygen consumption (MvO<sub>2</sub> cost of catecholamines in heart failure)
Authors: Lazaros A. Nikolaidis, Dennis Trumble, Teresa Hentosz, Aaron Doverspike, Rhonda Huerbin, Michael A. Mathier, You‐Tang Shen, Richard P. Shannon
Journal: European Journal of Heart Failure (2004)
Selection Fine-Tunes the Expression of MicroRNA Target Genes in Arabidopsis thaliana
Authors: S. Takuno, H. Innan
Journal: Molecular Biology and Evolution (2011)

MicroRNAs (miRNAs) are involved in posttranscriptional gene regulation by repressing the expression of their target genes through inhibition of translation and/or cleavage of mRNAs. In plants, the target genes of miRNAs usually belong to large gene families, and miRNA regulation is gained for individual genes throughout gene family evolution. To explore the selective effect of miRNA regulation on their target genes, we investigated the pattern of polymorphism and interspecific divergence in 11 multigene families that include target genes of ancient miRNAs in Arabidopsis thaliana. We found that the levels of polymorphism and divergence in target genes are significantly reduced, whereas those for nontarget genes are very similar to the genomic averages. This pattern is particularly clear at synonymous sites; we found that the reduction of synonymous variation is caused by selection for optimal codons, which increase the efficiency and accuracy of translation. Based on these results, we conclude that tuning via miRNA regulation has a strong impact on the evolution of target genes through which highly sophisticated regulation systems have been established.miRNA system, gene duplication, codon usage bias.
Tuberculosis in Elderly Persons
Authors: W W Stead, A K Dutt
Journal: Annual Review of Medicine (1991)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
Metabolic activation stimulates acid secretion and expression of matrix degrading proteases in human osteoblasts
Authors: M George
Journal: Annals of the Rheumatic Diseases (2003)

<b>Background:</b> Both cellular and matrix components of healthy bone are permanently renewed in a balanced homoeostasis. Osteoclastic bone resorption involves the expression of vacuolar-type ATPase proton pumps (vATPase) on the outer cell membrane and the secretion of matrix degrading proteases. Osteoblasts modulate the deposition of bone mineral components and secrete extracellular matrix proteins. <b>Objectives:</b> To investigate the ability of osteoblasts and osteosarcoma to secrete acid and express matrix degrading proteases upon metabolic activation. To examine also the potential contribution of vATPases to proton secretion expressed on osteoblasts. <b>Methods:</b> Osteoblasts were isolated from trabecular bone and characterised by reverse transcriptase-polymerase chain reaction and immunohistochemistry. Proton secretion was analysed by a cytosensor microphysiometer. <b>Results:</b> Osteoblasts not only express matrix degrading proteases upon stimulation with tumour necrosis factor or with phorbol ester but they also secrete protons upon activation. Proton secretion by osteoblasts is associated partially with proton pump ATPases. <b>Conclusion:</b> These data suggest that, in addition to monocyte derived osteoclasts, cytokine activated mesenchymal osteoblasts and osteosarcoma cells may contribute to the acidic milieu required for bone degradation.
Guidelines for time-to-event end point definitions in breast cancer trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)
Authors: S. Gourgou-Bourgade, D. Cameron, P. Poortmans, B. Asselain, D. Azria, F. Cardoso, R. A'Hern, J. Bliss, J. Bogaerts, H. Bonnefoi, E. Brain, M.J. Cardoso, B. Chibaudel, R. Coleman, T. Cufer, L. Dal Lago, F. Dalenc, E. De Azambuja, M. Debled, S. Delaloge, T. Filleron, J. Gligorov, M. Gutowski, W. Jacot, C. Kirkove, G. MacGrogan, S. Michiels, I. Negreiros, B.V. Offersen, F. Penault Llorca, G. Pruneri, H. Roche, N.S. Russell, F. Schmitt, V. Servent, B. Thürlimann, M. Untch, J.A. van der Hage, G. van Tienhoven, H. Wildiers, J. Yarnold, F. Bonnetain, S. Mathoulin-Pélissier, C. Bellera, T.S. Dabakuyo-Yonli
Journal: Annals of Oncology (2015)
Comparison of agents producing a neutrophilic leukocytosis in man. Hydrocortisone, prednisone, endotoxin, and etiocholanolone.
Authors: D C Dale, A S Fauci, I V Guerry D, S M Wolff
Journal: Journal of Clinical Investigation (1975)

To study the potential application of glucocorticosteroid administration for the measurement of the bone marrow neutrophil reserve response, blood neutrophil count changes were measured in normal subjects after the administration of intravenous hydrocortisone (25, 50, 100, 200, and 400 mg) and oral prednisone (5, 10, 20, 40, and 80 mg). The upper three doses of both steroids increased the blood neutrophil count by approximately 4,000 cells/mm3. The neutrophilia occurring after hydrocortisone (200 mg) and/or prednisone (40 mg) was compared with that observed after endotoxin (0.8 ng/kg) and etiocholanolone (0.1 mg/kg) in 14 normal subjects, 7 patients with Wegener's granulomatosis on cyclophosphamide therapy and 10 patients with chronic idiopathic neutropenia. The normal responses (mean increase of blood neutrophils/mm3 above base line +/- 1 SEM) were: hydrocortisone 4,220 +/- 320, prednisone 4,610 +/- 360, endotoxin 6,060 +/- 880, and etiocholanolone 3,780 +/- 440. In the patient studies, etiocholanolone gave the smallest mean responses, but, in general, the results were similar for all agents. These data indicate that these glucocorticosteroids can be used as equivalent agents to endotoxin and etiocholanolone for measuring the neutrophil reserve response.
Targeted Overexpression of the Sarcoplasmic Reticulum Ca <sup>2+</sup> -ATPase Increases Cardiac Contractility in Transgenic Mouse Hearts
Authors: Debra L. Baker, Katsuji Hashimoto, Ingrid L. Grupp, Yong Ji, Thomas Reed, Evgenij Loukianov, Gunter Grupp, Ajit Bhagwhat, Brian Hoit, Richard Walsh, Eduardo Marban, Muthu Periasamy
Journal: Circulation Research (1998)

Cardiac hypertrophy and heart failure are known to be associated with a reduction in Ca2+-ATPase pump levels of the sarcoplasmic reticulum (SR). To determine whether, and to what extent, alterations in Ca2+ pump numbers can affect contraction and relaxation parameters of the heart, we have overexpressed the cardiac SR Ca2+-ATPase specifically in the mouse heart using the alpha-myosin heavy chain promoter. Analysis of 2 independent transgenic lines demonstrated that sarco(endo)plasmic reticulum Ca2+-ATPase isoform (SERCA2a) mRNA levels were increased 3.88+/-0. 4-fold and 7.90+/-0.2-fold over those of the control mice. SERCA2a protein levels were increased by 1.31+/-0.05-fold and 1.54+/-0. 05-fold in these lines despite high levels of mRNA, suggesting that complex regulatory mechanisms may determine the SERCA2a pump levels. The maximum velocity of Ca2+ uptake (Vmax) was increased by 37%, demonstrating that increased pump levels result in increased SR Ca2+ uptake function. However, the apparent affinity of the SR Ca2+-ATPase for Ca2+ remains unchanged in transgenic hearts. To evaluate the effects of overexpression of the SR Ca2+ pump on cardiac contractility, we used the isolated perfused work-performing heart model. The transgenic hearts showed significantly higher myocardial contractile function, as indicated by increased maximal rates of pressure development for contraction (+dP/dt) and relaxation (-dP/dt), together with shortening of the normalized time to peak pressure and time to half relaxation. Measurements of intracellular free calcium concentration and contractile force in trabeculae revealed a doubling of Ca2+ transient amplitude, with a concomitant boost in contractility. The present study demonstrates that increases in SERCA2a pump levels can directly enhance contractile function of the heart by increasing SR Ca2+ transport.