tbuckley/cabot-search huggingface dataset:
Modulation of Attention During Visual Masking in Schizophrenia
Authors: Yuri Rassovsky, Michael F Green, Keith H Nuechterlein, Bruno Breitmeyer, Jim Mintz
Journal: American Journal of Psychiatry (2005)

Schizophrenia patients consistently demonstrate performance deficits on visual masking procedures. The present study examined whether attentional manipulation would improve subjects' performance on visual masking.A metacontrast task was administered to 105 schizophrenia patients and 52 healthy comparison subjects. Attention was manipulated by associating selected trials of the task with monetary reward.Schizophrenia patients exhibited poorer performance than the comparison subjects across conditions. Patients demonstrated modest, but statistically significant, improvement in performance with the attentional manipulation. This improvement was not significant for the comparison subjects.These findings suggest that early visual processes in schizophrenia are responsive to attentional manipulation but that the degree of improvement is relatively small, suggesting that these processes are not easily altered.
Slope and curvature of the relationship between ventilation and tidal volume in COPD patients
Authors: Bente Frisk, Jon Andrew Hardie, Birgitte Espehaug, Tomas Mikal Eagan, Liv Inger Strand, Rolf Moe-Nilssen, Per Bakke, Einar Thorsen
Journal: European Respiratory Journal (2013)

BACKGROUND:  Ventilatory capacity is reduced in COPD patients. Tidal volume (V T ) is lower and breathing frequency higher at a given ventilation (V E ) compared to healthy subjects. The relationship between V E  and V T  during incremental exercise is curvilinear and can be described by a quadratic model in healthy subjects.   AIMS:  To examine whether the V E  – V T  relationship in COPD patients can be described by a quadratic model, and whether the curve parameters are related to spirometric variables.   METHODS:  An incremental treadmill exercise test was performed in 60 COPD patients (35 men), aged 65 years (48-79 years) with a mean forced expiratory volume in one second (FEV 1 ) of 48 % of predicted (SD=15 %). Data were averaged over 20 sec. The V E  – V T  relationship was described by the quadratic equation V T =a+bV E +cV E  2  for each subject. The relationships between the curve parameters b and c, and spirometric variables were analysed by multivariate linear regression.   RESULTS:  The V E  – V T  relationship could be described by a quadratic model in 55 subjects with median R 2  of 0.91 (0.40-0.98). The 1. degree coefficient (b) was negatively (p=0.001) and the 2. degree coefficient (c) positively ( 1 . Forced vital capacity, sex, height, weight, age and difference in inspiratory capacity from start to end of exercise, were not associated with the curve parameters after adjusting for FEV 1 .   CONCLUSION:  The V E  – V T  relationship can be satisfactorily described by a quadratic model in most COPD patients. The curve parameters are both related to FEV 1 . With a lower FEV 1  maximal V T  is lower and achieved at a lower V E . This information can be helpful in interpreting cardiopulmonary exercise tests.
Histone H3 Phosphorylation in GBM: a New Rational to Guide the Use of Kinase Inhibitors in anti-GBM Therapy
Authors: Romain Pacaud, Mathilde Cheray, Arulraj Nadaradjane, François M. Vallette, Pierre-François Cartron
Journal: Theranostics (2014)

Histones post-translational modifications (PTMs) are crucial components of diverse processes that modulate chromatin. Among the histones PTMs, the histones phosphorylation appears such crucial since it plays a significant role into DNA repair structure, transcription and chromatin compaction during cell division and apoptosis. However, little is known about the prognostic value of the histone phosphorylation in human cancer. This point could be considerate such as an important gap in anti-cancer therapy since the use of adequate kinase inhibitors could remedy to the aberrant histone phosphorylation associated with a poor prognosis factor. To remedy at this situation, we analyzed the phosphorylation level of histone H3 at the residues T3, T6, S10, S28, Y41 and T45 in a collection of 42 glioblastoma multiformes (GBM). Our data indicated that the high level of pH3T6, pH3S10 and pH3Y41 are signatures associated with a poor prognosis of overall survival (OS) of GBM treated with the "temozolomide and irradiation standard" treatment of GBM (named TMZ+Irad treatment). Our data also showed that these signatures are correlated with the high activity of kinases already described as writers of the pH3T6, pH3S10 and pH3Y41 i.e. the PKC, Aurora-B and JAK2, respectively. Finally, our analysis revealed that the use of Enzastaurin, AZD1152, and AZD1480 abrogated the high level of pH3T6, pH3S10 and pH3Y41 while increasing the sensitivity to the "temozolomide and irradiation"-induced cell death. To conclude, it appears that this work provides biomarkers for patient stratification for a therapy including kinase inhibitors.
Adjuvant chemotherapy for osteosarcoma: a randomized prospective trial.
Authors: F Eilber, A Giuliano, J Eckardt, K Patterson, S Moseley, J Goodnight
Journal: Journal of Clinical Oncology (1987)

To determine the role of chemotherapy in the multidisciplinary treatment of patients with osteosarcoma, a randomized prospective trial of postoperative adjuvant chemotherapy was begun in 1981. Fifty-nine patients with nonmetastatic classic intramedullary osteosarcoma were randomized; 32 received postoperative adjuvant chemotherapy consisting of high-dose methotrexate, Adriamycin (Adria Laboratories, Columbus, OH), and BCD (bleomycin, cytoxan, actinomycin D), and 27 patients received no adjuvant chemotherapy. At a median follow-up of 2 years, there was a statistically significant improvement in both disease-free and overall survival in those who received adjuvant chemotherapy. In addition, there was no difference in the less than 20% disease-free or overall survival of patients treated in the 1970s who did not receive chemotherapy, as compared with the concurrent nontreatment controls. Therefore, with identical staging procedures, uniform surgical management, and standard pathologic evaluation, postoperative adjuvant chemotherapy definitely improves disease-free and overall survival in patients with osteosarcoma.
FK506 promotes melanocyte and melanoblast growth and creates a favourable milieu for cell migration via keratinocytes: possible mechanisms of how tacrolimus ointment induces repigmentation in patients with vitiligo
Authors: C-C.E. Lan, G-S. Chen, M-H. Chiou, C-S. Wu, C-H. Chang, H-S. Yu
Journal: British Journal of Dermatology (2005)

Vitiligo is an acquired pigmentary disorder characterized by depigmentation of skin and hair. As the pathogenesis of this disease is still obscure, the treatment of vitiligo has generally been unsatisfactory and often disappointing. Topical tacrolimus (FK506) ointment has recently been added to the armamentarium against this pigmentary disorder. Despite its clinical efficacy, the underlying mechanisms of how topical tacrolimus induces repigmentation in vitiligo have rarely been investigated. As tacrolimus ointment is applied directly to the skin, its impact on keratinocytes (KCs) requires thorough investigation.To investigate the effects of FK506 on melanocyte (MC) and melanoblast (MB) growth via KCs.Cultured MCs and MBs were treated with supernatant of KC cultures conditioned with various concentrations of FK506. The impact of supernatant on MCs and MBs was assessed in terms of its effect on MC/MB proliferation, melanin formation and cell migration. The activities of matrix metalloproteinase (MMP)-2 and MMP-9, known for their influence on cell migration, were evaluated. The concentrations of MC/MB growth factors in the KC supernatant were also determined.Results demonstrated that proliferation of both MCs and MBs was significantly enhanced by FK506-treated KC supernatant. In addition, the concentration of stem cell factor in KC supernatant increased dose-dependently with FK506 treatment. The supernatant from FK506-treated KC culture showed a significant increase in MMP-9 activity.Our study provides in vitro evidence demonstrating that direct interaction between FK506 and KCs creates a favourable milieu for MC growth and migration. Furthermore, our findings provide a possible mechanism explaining how tacrolimus ointment induces repigmentation in patients with vitiligo.
Lipoprotein(a), Ethnicity, and Cardiovascular Risk
Authors: Paul M Ridker
Journal: Circulation (2011)

F or Ͼ20 years, textbooks of medicine and guidelines for cardiovascular risk screening have suggested that elevated levels of lipoprotein(a) [Lp(a)] are a risk marker for coronary heart disease in white populations, but not among blacks.This observation, included in the Adult Treatment Panel III guidelines in 2002, 1 has long been puzzling, because blacks have both higher Lp(a) levels and higher absolute cardiovascular event rates than age-and sex-matched whites.Many explanations for this assumed ethnicity-based Lp(a) paradox have been described in the cardiovascular literature, including effect modification on the basis of diverse environmental and social influences, as well as genetic differences related to variation in kringle IV type 2 copy number.In retrospect, however, this embedded piece of preventive cardiology wisdom may prove to be a faux clinical pearl that entered the literature because of little more than poor statistical power.
Consequences of partial and subtotal colectomy in the rat.
Authors: P C Masesa, J M Forrester
Journal: Gut (1977)

Rats were subjects to right hemicolectomy (including removal of the caecum), left hemicolectomy or subtotal colectomy. Body weight resumed and maintained a rate of increase very similar to that in control rats. After hemicolectomy, food intake showed no change. Faecal weight increased by about one-third after right hemicolectomy, but did not increase after left hemicolectomy. After right hemicolectomy, the remaining--that is, downstream--portion of the colon showed increase in weight, and so did the (upstream) small intestine, in which the increase involved all three-thirds of its length and was predominantly mucosal. No such changes in the remaining colon or in small intestine were found after left hemicolectomy. After subtotal hemicolectomy, rats ate 30-40% more food than control rats, and faecal weight increased 60% at three months after operation. Study of energy intake and output indicated diminished absorption. All three-thirds of the small intestine showed increase in weight, predominantly mucosal in the upper two-thirds and predominantly seromuscular in the lowest third; villi were taller at all levels. Evidence suggests that the increase in food intake is not due to cessation of coprophagy, and that the small intestine changes are not due solely to increased food intake and occur when the colon is bypassed but not removed.
Selective distribution of protein kinase A regulatory subunit RIIα in rodent gliomas
Authors: Carla Mucignat-Caretta, Andrea Cavaggioni, Marco Redaelli, Manuela Malatesta, Carlo Zancanaro, Antonio Caretta
Journal: Neuro-Oncology (2008)

Differential diagnosis of brain tumor types is mainly based on cell morphology and could benefit from additional markers. The cAMP second-messenger system is involved in regulating cell proliferation and differentiation and is conceivably modulated during cancer transformation. The cAMP second-messenger system mainly activates protein kinases, which are in part docked to cytoskeleton, membranes, or organelles by anchoring proteins, forming protein aggregates that are detergent insoluble and not freely diffusible and that are characteristic for each cell type. The intracellular distribution of the detergent-insoluble regulatory subunits (R) of the cAMP-dependent protein kinase has been examined in mouse and rat glioma cells both in vitro and in vivo by immunohistochemistry. In normal rodent brains, the RIIα regulatory subunit is detergent insoluble only in ependymal cells, while in the rest of the brain it is present in soluble form. Immunohistochemistry shows that in both mouse and rat glioma cell lines, RIIα is mainly detergent insoluble. RIIα is localized close to the nucleus, associated with smooth vesicles in the trans-Golgi network area. Both paclitaxel and vinblastine cause a redistribution of RIIα within the cell. Under conditions that increased intracellular cAMP, apoptosis of glioma cells was observed, and it was accompanied by RIIα redistribution. Also in vivo, detergent-insoluble RIIα can be observed in mouse and rat gliomas, where it delineates the border between normal brain tissue and glioma. Therefore, intracellular distribution of detergent-insoluble RIIα can assist in detecting tumor cells within the brain, thus making the histologic diagnosis of brain tumors more accurate, and may represent an additional target for therapy.
Hidden Biases in an Observational Study of Bevacizumab Beyond Progression
Authors: Scott Kopetz, James L. Abbruzzese
Journal: Journal of Clinical Oncology (2009)

TO THE EDITOR: Grothey et al 1 recently reported a prospective observational study that monitored oncologists’ use of bevacizumab after patients experienced disease progression while receiving a prior bevacizumab-containing regimen. The conclusion formed on the basis of this study was that there was a suggested survival benefit from continuing bevacizumab after failure of a first-line bevacizumabcontaining regimen, with a hazard ratio (HR) of 0.46 on multivariate analysis. Generally, observational studies can provide important data on toxicities and practice patterns, but these types of studies have significant limitations when they are used to answer comparative questions of efficacy. Grothey et al 1 clearly acknowledge the potential bias with this study design and attempt to adjust for several factors. Unfortunately, it is impossible to quantify the extent to which this bias formed or altered the outcome of the trial. Several important sources of bias cannot be controlled for in the absence of randomization to treatment in this study, as will undoubtedly be delineated in this space by other readers of this journal. As a result, factors that are correlated with survival also affect the oncologist’s decision to continue bevacizumab. Several poor prognosis factors that may decrease an oncologist’s enthusiasm to continue bevacizumab include poor performance status at progression, higher vascular comorbidities, rapid tumor growth while receiving the prior bevacizumab-containing regimen, or peritoneal disease. Each of these factors would generally have predicted shorter survival in patients in whom bevacizumab was discontinued. However, in lieu of enumerating the number and reasoning for such biases in greater detail, we conducted similar analyses that may help to highlight the extent to which the conclusions in this observational trial may have been formed by these unseen biases. Since the US Food and Drug Administration’s approval of bevacizumab in 2004, most previously untreated metastatic colorectal patients at our institution have been treated with a bevacizumab-containing regimen. We chose to retrospectively examine these sequential patients to determine if patients treated again with bevacizumab as part of a later-line regimen had improved outcomes than those who did not receive a later-line bevacizumab-containing regimen. Indeed, we were able to demonstrate a similar HR of 0.62 (P .01) in favor of patients receiving bevacizumab after failing a prior bevacizumab-containing regimen.
Csf3r mutations in mice confer a strong clonal HSC advantage via activation of Stat5
Authors: Fulu Liu, Ghada Kunter, Maxwell M. Krem, William C. Eades, Jennifer A. Cain, Michael H. Tomasson, Lothar Hennighausen, Daniel C. Link
Journal: Journal of Clinical Investigation (2008)

A fundamental property of leukemic stem cells is clonal dominance of the bone marrow microenvironment. Truncation mutations of CSF3R, which encodes the G-CSF receptor (G-CSFR), are implicated in leukemic progression in patients with severe congenital neutropenia. Here we show that expression of a truncated mutant Csf3r in mice confers a strong clonal advantage at the HSC level that is dependent upon exogenous G-CSF. G-CSF–induced proliferation, phosphorylation of Stat5, and transcription of Stat5 target genes were increased in HSCs isolated from mice expressing the mutant Csf3r. Conversely, the proliferative advantage conferred by the mutant Csf3r was abrogated in myeloid progenitors lacking both Stat5A and Stat5B, and HSC function was reduced in mice expressing a truncated mutant Csf3r engineered to have impaired Stat5 activation. These data indicate that in mice, inappropriate Stat5 activation plays a key role in establishing clonal dominance by stem cells expressing mutant Csf3r.
Metronomic low-dose oral cyclophosphamide and methotrexate plus or minus thalidomide in metastatic breast cancer: antitumor activity and biological effects
Authors: M. Colleoni, L. Orlando, G. Sanna, A. Rocca, P. Maisonneuve, G. Peruzzotti, R. Ghisini, M.T. Sandri, L. Zorzino, F. Nolè, G. Viale, A. Goldhirsch
Journal: Annals of Oncology (2005)
Human colorectal tumour infiltrating lymphocytes express activation markers and the CD45RO molecule, showing a primed population of lymphocytes in the tumour area.
Authors: B Ostenstad, T Lea, E Schlichting, M Harboe
Journal: Gut (1994)

This study investigated the phenotype of freshly isolated human tumour infiltrating lymphocytes (TIL) from 14 patients with colorectal tumours, and compared them with lymphocytes derived from the lamina propria of the unaffected mucosa and with lymphocytes derived from peripheral blood of the same patients. It was found that TIL expressed the activation markers CD25 and HLA-DR to a higher extent than the peripheral blood lymphocytes (p = 0.01), and that both lamina propria lymphocytes and TIL preferentially expressed the CD45RO + phenotype, associated with memory cells, in contrast with peripheral blood lymphocytes [corrected]. Both lamina propria lymphocytes and TIL contained few natural killer (NK) cells (CD3-CD56+) compared with peripheral blood lymphocytes (p = 0.001), and this was reflected in the cytotoxicity assays. After 1 to 2 weeks in culture with interleukin-2 100 U/ml, lymphocytes from all three compartments had a high cytolytic activity against all targets tested, consistent with the lymphokine activated killer cell phenomenon. No increase in the number of NK cells was noted after culture, but 20-30% of the T cells now coexpressed the CD56 molecule. This was most prominent in the CD8+ subset, but lymphokine activated killer cell activity was found in both CD4+ and CD8+ subsets. Possible tumour escape mechanisms are discussed.
The bronchitic phenotype is related to morbidity and mortality - report from the OLIN COPD study
Authors: Anne Lindberg, Linnea Hedman, Sami Sawalha, Eva Rönmark, Bo Lundbäck
Journal: European Respiratory Journal (2013)

Background: The bronchitic phenotype in COPD may be related to a worse general health status and exacerbations. It is probably under-diagnosed and there is a lack of knowledge about the impact of long term outcome.

Aim. To estimate the prevalence of bronchitic phenotype in COPD and the relation to respiratory events (RE) and mortality in a population based study.

Method: In 2002-04 subjects from four population based cohorts within the OLIN-studies were invited to a re-examination. From the participants all subjects with COPD according to the GOLD spirometric criteria, FEV1/FVC<0.7, were identified (n=993) together with gender- and age matched subjects without COPD (n=993). The COPD cohort and the control sample have been invited to yearly examinations since 2005. Baseline characteristics were used to identify subjects with chronic productive cough (CPC). Mortality data were collected until the end of 2011.

Results: CPC and RE during the last 12 months were more common in COPD compared to in non-COPD (42.8 vs. 23.5 %, p<0.001 and 21.0 vs. 9.1 %, p<0.001). Subjects with CPC had higher mortality compared to those without, in both COPD (29.2 vs. 18.8, p<0.001) and non-COPD (23.2 vs. 15.9, p=0.011). The risk for RE was higher in non-COPD with CPC, COPD without CPC and COPD with CPC compared to in non-COPD without CPC also when adjusted for gender, age, smoking status and heart disease (OR 4.21, 95%CI 2.67-6.64, OR 2.86, 95%CI 1.93-4.24 and OR 9.23, 95%CI 6.22-13.7). COPD with CPC was a significant risk factor for death (OR 1.45, 95% CI 1.02-2.05) in a similar model.

Conclusion: The bronchitic phenotype is related to increased morbidity and mortality in COPD.
The Murray collection of pre-antibiotic era Enterobacteriacae: a unique research resource
Authors: Kate S Baker, Edward Burnett, Hannah McGregor, Ana Deheer-Graham, Christine Boinett, Gemma C Langridge, Alexander M Wailan, Amy K Cain, Nicholas R Thomson, Julie E Russell, Julian Parkhill
Journal: Genome Medicine (2015)

Studies of historical isolates inform on the evolution and emergence of important pathogens and phenotypes, including antimicrobial resistance. Crucial to studying antimicrobial resistance are isolates that predate the widespread clinical use of antimicrobials. The Murray collection of several hundred bacterial strains of pre-antibiotic era Enterobacteriaceae is an invaluable resource of historical strains from important pathogen groups. Studies performed on the Collection to date merely exemplify its potential, which will only be realised through the continued effort of many scientific groups. To enable that aim, we announce the public availability of the Murray collection through the National Collection of Type Cultures, and present associated metadata with whole genome sequence data for over half of the strains. Using this information we verify the metadata for the collection with regard to subgroup designations, equivalence groupings and plasmid content. We also present genomic analyses of population structure and determinants of mobilisable antimicrobial resistance to aid strain selection in future studies. This represents an invaluable public resource for the study of these important pathogen groups and the emergence and evolution of antimicrobial resistance.
Factors controlling colonic motility: Colonic pressures and transit after meals in patients with total gastrectomy, pernicious anaemia, or duodenal ulcer
Authors: D. J. Holdstock, J. J. Misiewicz
Journal: Gut (1970)

The motor responses of the proximal colon, sigmoid, and rectum to the ingestion of a standard meal have been compared in patients with total gastrectomy, pernicious anaemia, or duodenal ulcer. Colonic pressure activity increased during and after food in all the patients, but this was only once associated with propulsive activity. The results suggest that the postprandial pressure activity in the sigmoid colon is greater after total gastrectomy than in the other two groups. It is concluded that entry of food into the upper small intestine is the most important factor in initiating the colonic pressure response to food, since this response does not require the presence of the stomach, acid, antral gastrin, or of vagal innervation.
Xpert MTB/RIF assay for diagnosis of pulmonary tuberculosis in children: A prospective, multi-centre evaluation
Authors: Klaus Reither, Christina Manyama, Petra Clowes, Andrea Rachow, Daniel Mapamba, Andreas Steiner, Amanda Ross, Elirehema Mfinanga, Mohamed Sasamalo, Martin Nsubuga, Francesco Aloi, Daniela Cirillo, Levan Jugheli, Fred Lwilla
Journal: Journal of Infection (2014)