tbuckley/cabot-search huggingface dataset:
Health-Related Quality of Life in Stable, Long-Term Survivors of Low-Grade Glioma
Authors: Florien W. Boele, Linda Douw, Jaap C. Reijneveld, Rianne Robben, Martin J.B. Taphoorn, Neil K. Aaronson, Jan J. Heimans, Martin Klein
Journal: Journal of Clinical Oncology (2015)

Purpose Patients with low-grade glioma (LGG) often experience long periods of stable disease, emphasizing the importance of maintaining good health-related quality of life (HRQOL). We assessed the changes in HRQOL in long-term survivors of WHO grade I or II astrocytoma, oligodendroglioma, or oligoastrocytoma with clinically and radiologically stable disease. Patients and Methods Patients completed self-report measures of generic HRQOL (Short Form-36 [SF-36]) and disease-specific HRQOL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Brain Cancer Module). Assessments took place at midterm and long-term follow-up, on average 6 and 12 years after histologic diagnosis and initial treatment, respectively. Comparisons between patients with LGG and individually matched healthy controls were made, and change within the patients with LGG was calculated, as was minimal detectable change. Results Although no statistically significant differences between patients with LGG and healthy matched controls were found at midterm follow-up, patients with LGG had worse physical role functioning (P = .004) and general health perceptions (P = .004) than controls at long-term follow-up. Within patients with stable LGG (n = 65), physical HRQOL (the SF-36 physical component summary and the physical functioning subscale) was significantly worse at long-term than at midterm follow-up (both P &lt; .001). Although 48% of patients improved or remained stable on all HRQOL scales, 38.5% of patients experienced detectable decline on one or more scales. Conclusion Although HRQOL remains mostly preserved in the majority of patients with LGG, a subset of patients experience detectable decline on one or more HRQOL scales despite long-term stable disease. For this subgroup, further research is recommended to better aid patients in dealing with the consequences of LGG.
Glycogen Synthase Kinase 3β Regulates Cell Death Induced by Synthetic Triterpenoids
Authors: Roberta Venè, Patrizia Larghero, Giuseppe Arena, Michael B. Sporn, Adriana Albini, Francesca Tosetti
Journal: Cancer Research (2008)

Abstract The induction of programmed cell death in premalignant or malignant cancer cells by chemopreventive agents could be a valuable tool to control prostate cancer initiation and progression. In this work, we present evidence that the C-28 methyl ester of the synthetic oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO-Me) induces cell death in androgen-responsive and unresponsive human prostate cancer cell lines at nanomolar and low micromolar concentrations. CDDO-Me induced caspase-3, caspase-8, and caspase-9 activation; poly(ADP-ribose) polymerase cleavage; internucleosomal DNA fragmentation; and loss of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction in PC3 and DU145 cells. However, caspase-3 and caspase-8 inhibition by Z-DEVD-fmk and Z-IETD-fmk, respectively, or general caspase inhibition by BOC-D-fmk or Z-VAD-fmk did not rescue loss of cell viability induced by CDDO-Me, suggesting the activation of additional caspase-independent mechanisms. Interestingly, CDDO-Me induced inactivating phosphorylation at Ser9 of glycogen synthase kinase 3β (GSK3β), a multifunctional kinase that mediates essential events promoting prostate cancer development and acquisition of androgen independence. The GSK3 inhibitor lithium chloride and, more effectively, GSK3 gene silencing sensitized PC3 and DU145 prostate cancer cells to CDDO-Me cytotoxicity. These data suggest that modulation of GSK3β activation is involved in the cell death pathway engaged by CDDO-Me in prostate cancer cells. [Cancer Res 2008;68(17):6987–96]
High Efficacy of Panobinostat Towards Human Gastrointestinal Stromal Tumors in a Xenograft Mouse Model
Authors: Giuseppe Floris, Maria Debiec-Rychter, Raf Sciot, Cristiana Stefan, Steffen Fieuws, Kathleen Machiels, Peter Atadja, Agnieszka Wozniak, Gavino Faa, Patrick Schöffski
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Histone deacetylase inhibitors have emerged as potent anticancer compounds. Using a nude-mouse xenograft model, for the first time we evaluated the response of human gastrointestinal stromal tumors (GIST) carrying different oncogenic KIT mutations to panobinostat (LBH589), administered single or in combination with imatinib. Experimental Design: We grafted the human GIST882 cell line with KIT exon 13 mutation and two biopsies from patients radiologically progressing under imatinib showing KIT exon11 and KIT exon9 mutations, respectively. Our study included 4 groups: A (n = 9; control), B (n = 10; panobinostat 10 mg/kg daily, i.p.), C (n = 9; imatinib 150 mg/kg bidaily, p.o), and D (n = 8; combination panobinostat-imatinib, same dose/schedule as above). Treatment lasted 12 days. Tumor size was measured regularly using standard variables. Histopathological assessment was by H&amp;E, and immunohistochemically with KIT, cleaved caspase-3, Ki-67, and histone acetylation staining. Results: Overall, GIST xenografts responded rapidly to panobinostat as indicated by tumor regression, necrosis, hemorrhages, fibrosis, and/or myxoid degeneration, remarkable apoptosis, and substantial decline of cell proliferation. H3 and H4 acetylation increased significantly from control level in all treated groups. The combination of panobinostat and imatinib further enhanced most of the assessed parameters. Conclusions: We show for the first time potential therapeutic activity of panobinostat in human GISTs, in vivo. Our results warrant further exploration of histone deacetylase inhibitors for the treatment of advanced GISTs. Our study is also the first one on human GIST mouse xenografts established using patient biopsies.
Neuropilin-2 Regulates the Development of Select Cranial and Sensory Nerves and Hippocampal Mossy Fiber Projections
Authors: Hang Chen, Anil Bagri, Joel A Zupicich, Yimin Zou, Esther Stoeckli, Samuel J Pleasure, Daniel H Lowenstein, William C Skarnes, Alain Chédotal, Marc Tessier-Lavigne
Journal: Neuron (2000)
A contrast agent recognizing activated platelets reveals murine cerebral malaria pathology undetectable by conventional MRI
Authors: Constantin von zur Muhlen, Nicola R. Sibson, Karlheinz Peter, Sandra J. Campbell, Panop Wilainam, Georges E. Grau, Christoph Bode, Robin P. Choudhury, Daniel C. Anthony
Journal: Journal of Clinical Investigation (2008)

Human and murine cerebral malaria are associated with elevated levels of cytokines in the brain and adherence of platelets to the microvasculature. Here we demonstrated that the accumulation of platelets in the brain microvasculature can be detected with MRI, using what we believe to be a novel contrast agent, at a time when the pathology is undetectable by conventional MRI. Ligand-induced binding sites (LIBS) on activated platelet glycoprotein IIb/IIIa receptors were detected in the brains of malaria-infected mice 6 days after inoculation with Plasmodium berghei using microparticles of iron oxide (MPIOs) conjugated to a single-chain antibody specific for the LIBS (LIBS-MPIO). No binding of the LIBS-MPIO contrast agent was detected in uninfected animals. A combination of LIBS-MPIO MRI, confocal microscopy, and transmission electron microscopy revealed that the proinflammatory cytokine TNF-α, but not IL-1β or lymphotoxin-α (LT-α), induced adherence of platelets to cerebrovascular endothelium. Peak platelet adhesion was found 12 h after TNF-α injection and was readily detected with LIBS-MPIO contrast-enhanced MRI. Temporal studies revealed that the level of MPIO-induced contrast was proportional to the number of platelets bound. Thus, the LIBS-MPIO contrast agent enabled noninvasive detection of otherwise undetectable cerebral pathology by in vivo MRI before the appearance of clinical disease, highlighting the potential of targeted contrast agents for diagnostic, mechanistic, and therapeutic studies.
Difficult bacteria, antibiotic resistance and transmissibility in cystic fibrosis
Authors: J S Elborn
Journal: Thorax (2004)

<h3>Objectives &amp; Background</h3> Emergency Medicine (EM) is facing a worsening recruitment and retention crisis in Ireland. We sought to document the numbers of doctors applying to, resigning from, and completing Core Specialist Training in EM (CSTEM), as well as applying to and resigning from Advanced Specialist Training in EM (ASTEM). <h3>Methods</h3> Records of CSTEM and ASTEM data were interrogated by hand search following approval from the Irish Committee for Emergency Medicine Training (ICEMT) for the time periods from 2011 to 2015 for CSTEM and 2007 to 2015 for ASTEM. <h3>Results</h3> Following a peak in 2013, the numbers of CSTEM applicants decreased by 28% by 2015 (75 to 54). The percentage of CSTEM trainees who resigned during their 3-year Training Programme increased from 4% in 2011 to 15% in 2014. Only 1–2 CSTEM trainees out of up to 26 who started first year applied to ASTEM on completion of CSTEM each year. Following an increase between 2007 and 2009, the number of doctors applying to ASTEM decreased by 66% between 2009 and 2015 (29 to 10 trainees). The number of doctors accepted to ASTEM decreased by 70% from its peak of 10 in 2012 to 3 in 2015. A total of 7 trainees who completed CSTEM since it was established have been accepted for ASTEM. There has been no attrition from ASTEM in recent years. <h3>Conclusion</h3> ICEMT data demonstrates a dramatic decrease in the number of doctors applying to both CSTEM and ASTEM in Ireland, coupled with an increase in the number of trainees resigning from CSTEM. Significant improvement in terms and working conditions must be implemented if we are to recruit and retain trainees, and make EM a more attractive and sustainable specialty in Ireland.
The Human Response to Acute Enteral and Parenteral Phosphate Loads
Authors: Roberto Scanni, Matthias vonRotz, Sigrid Jehle, Henry N. Hulter, Reto Krapf
Journal: Journal of the American Society of Nephrology (2014)

The human response to acute phosphate (PO4) loading is poorly characterized, and it is unknown whether an intestinal phosphate sensor mechanism exists. Here, we characterized the human mineral and endocrine response to parenteral and duodenal acute phosphate loads. Healthy human participants underwent 36 hours of intravenous (IV; 1.15 [low dose] and 2.30 [high dose] mmol of PO4/kg per 24 hours) or duodenal (1.53 mmol of PO4/kg per 24 hours) neutral sodium PO4 loading. Control experiments used equimolar NaCl loads. Maximum PO4 urinary excretory responses occurred between 12 and 24 hours and were similar for low-dose IV and duodenal infusion. Hyperphosphatemic responses were also temporally and quantitatively similar for low-dose IV and duodenal PO4 infusion. Fractional renal PO4 clearance increased approximately 6-fold (high-dose IV group) and 4-fold (low-dose IV and duodenal groups), and significant reductions in plasma PO4 concentrations relative to peak values occurred by 36 hours, despite persistent PO4 loading. After cessation of loading, frank hypophosphatemia occurred. The earliest phosphaturic response occurred after plasma PO4 and parathyroid hormone concentrations increased. Plasma fibroblast growth factor-23 concentration increased after the onset of phosphaturia, followed by a decrease in plasma 1,25(OH)2D levels; α-Klotho levels did not change. Contrary to results in rodents, we found no evidence for intestinal-specific phosphaturic control mechanisms in humans. Complete urinary phosphate recovery in the IV loading groups provides evidence against any important extrarenal response to acute PO4 loads.
Simplified versions of the original disease activity score: validation in the BeSt trial
Authors: R. Koevoets, N. Klarenbeek, M. Guler-Yuksel, M. van Oosterhout, M. van Krugten, P. Kerstens, T. Huizinga, B. Dijkmans, D. van der Heijde, C. Allaart
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> To evaluate three disease activity score (DAS) alternatives without the Ritchie articular index (RAI). To compare the use of patient global assessment (PGA) of disease activity versus global assessment of health (GH) in DAS, DAS alternatives and DAS28. <h3>Methods</h3> Data from the BeSt study were used, a treatment strategy trial in early rheumatoid arthritis patients aiming at a DAS ≤2.4. DAS alternatives were DAS 0–1, with the RAI (0–3) reduced to a no–yes (0–1) score, DAS tender joint count 53 (DAS TJC53), with a 0–1 TJC in 53 separate joints and DAS TJC44 in 44 joints. Correlation patterns, mean difference from original DAS, classification differences in disease activity level and patient percentages with radiological damage progression per level were determined for all scores. <h3>Results</h3> In the majority of patients the scores were equal and correlation was high. Mean difference with the DAS at year 1 was −0.03 for DAS 0–1, 0.18 for DAS TJC53 and 0.11 for DAS TJC44. Classification agreement between scores was high (κ year 1 0.76–0.98). Patient percentages with joint damage progression were similar for all scores. DAS, DAS alternative and DAS28 perform similarly using either PGA or GH. <h3>Conclusion</h3> DAS without the RAI perform comparably to the original DAS and may be chosen as alternatives. PGA can replace GH in the DAS, the alternatives and DAS28.
The Physiological and Clinical Results of Division of the Vas Deferens
Authors: A. C. Morson
Journal: BMJ (1933)

culture in our case was negative.Nevertheless, as suppurative changes are unknown in Hodgkin's disease, apart from secondary infection, the osteomyelitic nature of the infection taking part in the extensive erosion of the vertebral bodies and development of the abscess may be regarded as the correct explanation.The case here reported is further proof of the extra- ordinary difficulties that may have to be overcome in order to arrive at the correct diagnosis of Hodgkin's disease.
Tolerance of Infections
Authors: Janelle S. Ayres, David S. Schneider
Journal: Annual Review of Immunology (2012)

A host has two methods to defend against pathogens: It can clear the pathogens or reduce their impact on health in other ways. The first, resistance, is well studied. Study of the second, which ecologists call tolerance, is in its infancy. Tolerance measures the dose response curve of a host's health in reaction to a pathogen and can be studied in a simple quantitative manner. Such studies hold promise because they point to methods of treating infections that put evolutionary pressures on microbes different from antibiotics and vaccines. Studies of tolerance will provide an improved foundation to describe our interactions with all microbes: pathogenic, commensal, and mutualistic. One obvious mechanism affecting tolerance is the intensity of an immune response; an overly exuberant immune response can cause collateral damage through immune effectors and because of the energy allocated away from other physiological functions. There are potentially many other tolerance mechanisms, and here we systematically describe tolerance using a variety of animal systems.
A Novel Dual-targeted Lentiviral Vector Leads to Specific Transduction of Prostate Cancer Bone Metastases In Vivo After Systemic Administration
Authors: Nonia Pariente, Kouki Morizono, Mandeep S Virk, Frank A Petrigliano, Robert E Reiter, Jay R Lieberman, Irvin SY Chen
Journal: Molecular Therapy (2007)

Targeted gene transduction to organs and tissues of interest is the ultimate goal of therapeutic gene delivery. Lentiviral vectors (LVs) are powerful tools for stable gene delivery but their integration into undesired cell types poses a serious safety concern for their use in the clinic. Here we report the development of a new dual-targeted LV that can preferentially home to and express in prostate cancer bone metastases in vivo after systemic delivery. Transductional targeting is mediated by a modified Sindbis virus envelope that interacts with the prostate stem cell antigen (PSCA) expressed by prostate cancer cells, and transcriptional targeting is mediated by a prostate cell specific promoter. Homing to prostate tumors was achieved in 70% of the animals. Importantly, tumors could be detected in some cases by molecular imaging prior to X-ray detection. The dual-targeted vector presents enhanced specificity with respect to individual transcriptional or transductional targeted vectors. Transgene expression in the liver was 190 times lower than the expression associated with solely transductionally targeted vectors, and there was 12 times less vector DNA than the amount present with solely transcriptionally targeted vectors. The LV presented here is a powerful tool for obtaining stable and site-specific gene expression and can be easily modified for its use in other diseases.
Metabolic changes at the margin of the spreading psoriatic lesion
Authors: P.C.M. KERKHOF, HELGA RENNES, RUFI GROOD, F.W. BAUER, P.D. MIER
Journal: British Journal of Dermatology (1983)

Keratotome slices were cut across the margins of rapidly-spreading psoriatic plaques. Each slice was divided into eight sections and in each section we measured the percentage cells in S phase and the levels of glucose-6-phosphate dehydrogenase (both related to epidermal proliferation), acid phosphatase (associated with keratinization) and alkaline phosphatase (a marker for dermal capillaries). Disturbances in the epidermis extended only 2 to 4 mm into the 'uninvolved' skin, whereas the capillaries were metabolically abnormal for a distance of about 2 cm ahead of the advancing edge of the plaque. This implies that changes in the capillary may precede those in the epidermis during the spread of the psoriatic lesion.
Validation of the STOP-BANG questionnaire as a screening tool for sleep apnoea in patients undergoing ablation for paroxysmal atrial fibrillation
Authors: Marcus Pittman, Martina Mason, Danielle Packer, Rebecca Chadwick, Timothy Quinnell
Journal: European Respiratory Journal (2013)

Background 

Patients with treated obstructive sleep apnoea have greater success compared to those untreated, when undergoing ablation for atrial fibrillation (AF) (Patel Circ Arrhythm Electrophysiol 2010: 445-51). The STOP-BANG questionnaire has not been validated in AF patients. We present preliminary results from a study examining its predictive value in this group.

Methods 

Patients with paroxysmal (P)AF due for ablation were recruited, completed the STOP-BANG and underwent overnight oximetry. Sleep apnoea was defined as a 4% oxygen desaturation index of >5/hr. A sleep physician assessed subjects to determine the likely nature of any apnoeas present and the need for continuous positive airway pressure (CPAP).

Results 

Of 40 patients, 15 (37.5%) had sleep apnoea and 5 (12.5%) required CPAP. One participant had oximetry consistent with central apnoea, later confirmed on a respiratory study.

View this table:

Characteristics of the participants





The STOP-BANG questionnaire had a sensitivity of 100% and specificity of 60% for detecting sleep apnoea in this group. STOP questions alone had a sensitivity of 67% and specificity of 68%. For predicting sleep apnoea requiring CPAP their sensitivity was 100% and specificity 63%.

Conclusion 

Undiagnosed sleep apnoea is highly prevalent in patients with PAF. The STOP-BANG questionnaire is highly sensitive for detecting sleep apnoea in this group. The STOP questions appear to be a useful screening tool for sleep apnoea requiring CPAP in PAF patients.
Association between variants in the gene encoding myosin light chain kinase (MLCK) and asthma and atopy*1
Authors: M. Munoz, A. Zambelli-Weiner, A. Grant, M. Lorenzo, E. Ehrlich, M. Burki, L. Gao, S. Ye, T.H. Beaty, J.G. Garcia, K.C. Barnes
Journal: Journal of Allergy and Clinical Immunology (2004)
B cells solicit their own help from T cells.
Authors: B Stockinger, T Zal, A Zal, D Gray
Journal: The Journal of Experimental Medicine (1996)

We have made use of T cell receptor (TCR)-transgenic mice with CD4+ T cells expressing a receptor specific for the self-antigen C5 (fifth component of complement) to study the role of different antigen-presenting cells in the determination of CD4+ T cell effector type. Contact of T cells from C5 TCR-transgenic mice with C5 protein or C5 peptide in vivo or in vitro induces biased T helper cell (Th) 1 type responses resulting in exclusive production of high levels of interferon gamma and interleukin (IL) 2. Transgenic mice, in contrast to nontransgenic littermates, do not generate an antibody response to C5. We show in this paper that B cell presentation in vitro induces a switch to the Th2 subset indicated by production of IL-4, and targetting C5 to B cells in vivo results in the generation of C5-specific antibodies.
A randomized comparison of nativeEscherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: a Children's Cancer Group study
Authors: Vassilios I. Avramis, Susan Sencer, Antonia P. Periclou, Harland Sather, Bruce C. Bostrom, Lewis J. Cohen, Alice G. Ettinger, Lawrence J. Ettinger, Janet Franklin, Paul S. Gaynon, Joanne M. Hilden, Beverly Lange, Fataneh Majlessipour, Pracad Mathew, Michael Needle, Joseph Neglia, Gregory Reaman, John S. Holcenberg
Journal: Blood (2002)
Commentary on "Anabolic androgenic steroids induce micronuclei in buccal mucosa cells of bodybuilders"
Authors: Saleha B Vuyyuri
Journal: British Journal of Sports Medicine (2007)

Empirical evidence from the literature documents that the size effect has gradually diminished since the early 1980s. In this article, the authors examine the stability of this anomaly between 1926 and 2014. The evidence they document indicates a substantial presence of the size effect across various calendar anomalies. The anomalies considered are the January effect, the Halloween effect, the Mark Twain effect, the other January effect, the seasonal affective disorder effect, and the turn-of-the-month, day-of-the-week, and week-of-the-year effects. Their findings hold true for different sample periods, various modeling specifications, and types of returns and may provide investment professionals such as portfolio managers, investment officers, analysts, and other market participants with a practical tool for their daily decision-making. <b>TOPIC:</b>Factor-based models
Alefacept therapy produces remission for patients with chronic plaque psoriasis
Authors: G.G. Krueger, C.N. Ellis
Journal: British Journal of Dermatology (2003)

Summary Background Alefacept, human LFA-3/IgG1 fusion protein, is a novel biological agent currently being developed for the treatment of chronic plaque psoriasis. Alefacept selectively reduces the memory-effector T cells that have been implicated in the pathogenesis of the disease; as a result, alefacept is classified as a therapy that induces remission (so-called 'remittive' therapy). In a previously published randomized, placebo-controlled phase II study of intravenous alefacept in 229 patients with chronic plaque psoriasis, clinical improvement was observed during dosing as well as in the postdosing follow-up period. Objectives To assess the remission period following alefacept therapy. Methods The time before re-treatment was required was measured in patients who were 'clear' or 'almost clear' of disease according to a physician global assessment at the end of the follow-up phase. Results In these patients, responses were sustained for a median of 10 months, and for up to 18 months. No patient reported disease rebound after cessation of alefacept. Conclusions Alefacept is a biological agent for the treatment of chronic plaque psoriasis that provides disease-free intervals and time off drug therapy.