tbuckley/cabot-search huggingface dataset:
Rapid identification of CBFB-MYH11–positive acute myeloid leukemia (AML) cases by one single MYH11 real-time RT-PCR
Authors: Bert A. van der Reijden, Marion Massop, Evelyn Tönnissen, Louis van de Locht, Petra Muus, Theo de Witte, Joop H. Jansen
Journal: Blood (2003)
Time course of response to prednisolone in chronic airflow obstruction.
Authors: J Webb, T J Clark, C Chilvers
Journal: Thorax (1981)

Nineteen patients with chronic airflow obstruction measured their morning and evening peak expiratory flow (PEF) daily for 28 days. A placebo was taken for the first week and prednisolone 20 mg twice daily was taken for the last three weeks. The mean PEF in 13 patients who responded to prednisolone reached a maximum after eight days9 treatment. The majority of the 19 patients had asthma and were thought to represent a typical cross section of patients who would be considered for a trial of oral corticosteroids. Most responsive patients will achieve a maximum response within eight days.
The pulmonary physician in critical care middle dot 8: Ventilatory management of ALI/ARDS
Authors: J J Cordingley
Journal: Thorax (2002)

Abstract Current data relating to ventilation in ARDS are reviewed. Recent studies suggest that reduced mortality may be achieved by using a strategy which aims at preventing overdistension of lungs. acute respiratory distress syndromeacute lung injuryventilationcritical care
Mechanisms of Endothelial Dysfunction, Injury, and Death
Authors: Jordan S. Pober, Wang Min, John R. Bradley
Journal: Annual Review of Pathology Mechanisms of Disease (2008)

Vascular endothelial cells normally perform several key homeostatic functions such as keeping blood fluid, regulating blood flow, regulating macromolecule and fluid exchange with the tissues, preventing leukocyte activation, and aiding in immune surveillance for pathogens. Injury or cell death impairs or prevents conduct of these activities, resulting in dysfunction. Most endothelial cell death is apoptotic, involving activation of caspases, but nonapoptotic death responses also have been described. Stimuli that can cause endothelial injury or death include environmental stresses such as oxidative stress, endoplasmic reticulum stress, metabolic stress, and genotoxic stress, as well as pathways of injury mediated by the innate and adaptive immune systems. Pathways of immune-mediated death include those activated by death receptors as well as those activated by cytolytic granules and reactive oxygen species. The biochemical pathways activated by these injurious stimuli are described herein and will serve as a basis for future development of endothelial protective therapies.
Global expression changes resulting from loss of telomeric DNA in fission yeast.
Authors: Jeffrey G Mandell, Jürg Bähler, Thomas A Volpe, Robert A Martienssen, Thomas R Cech
Journal: Genome biology (2004)

Abstract Background Schizosaccharomyces pombe cells lacking the catalytic subunit of telomerase (encoded by trt1 + ) lose telomeric DNA and enter crisis, but rare survivors arise with either circular or linear chromosomes. Survivors with linear chromosomes have normal growth rates and morphology, but those with circular chromosomes have growth defects and are enlarged. We report the global gene-expression response of S. pombe to loss of trt1 + . Results Survivors with linear chromosomes had expression profiles similar to cells with native telomeres, whereas survivors with circular chromosomes showed continued upregulation of core environmental stress response (CESR) genes. In addition, survivors with circular chromosomes had altered expression of 51 genes compared to survivors with linear chromosomes, providing an expression signature. S. pombe progressing through crisis displayed two waves of altered gene expression. One coincided with crisis and consisted of around 110 genes, 44% of which overlapped with the CESR. The second was synchronized with the emergence of survivors and consisted of a single class of open reading frames (ORFs) with homology both to RecQ helicases and to dh repeats at centromeres targeted for heterochromatin formation via an RNA interference (RNAi) mechanism. Accumulation of transcript from the ORF was found not only in trt1 - cells, but also in dcr1 - and ago1 - RNAi mutants, suggesting that RNAi may control its expression. Conclusions These results demonstrate a correlation between a state of cellular stress, short telomeres and growth defects in cells with circular chromosomes. A putative new RecQ helicase was expressed as survivors emerged and appears to be transcriptionally regulated by RNAi, suggesting that this mechanism operates at telomeres.
Results of a multicenter randomized study to evaluate the safety and efficacy of combined immunotherapy with interleukin-2, interferon-α2b and histamine dihydrochloride versus dacarbazine in patients with stage IV melanoma
Authors: M. Middleton, A. Hauschild, D. Thomson, R. Anderson, S. Burdette-Radoux, K. Gehlsen, K. Hellstrand, P. Naredi
Journal: Annals of Oncology (2007)
Survey of medical oncology fellows' burnout, communication skills, and perceived competencies
Authors: J. L. Armstrong, J. Holland
Journal: Journal of Clinical Oncology (2004)

8132 Background: We sought to investigate the degree of burnout, perceived competencies in communication skills, and the delivery of psychosocial care among Medical Oncology fellows at our institution. Methods: A written survey was distributed to fellows who attended a workshop in communication skills training at the beginning of the academic year. The survey included demographic questions, the Maslach Burnout Inventory, and a Likert scale on the experience of discussing end of life, informed consent, and error disclosure. Results: Sixteen of the 18 fellows completed the baseline survey: 8 first year, 4 second year, and 4 third year fellows; 13 women, 3 men; mixed ethnic and religious backgrounds; median age of 32.5 years. Moderate to high emotional exhaustion and sense of diminished empathy were reported in 69%; moderate to high sense of personal accomplishment was reported in 63%. Fellows were most confident discussing informed consent and end of life issues but were less confident in breaking bad news and error disclosure. Fellows frequently thought there was not enough time to give patients needed emotional attention. While the average fellow saw patients who were distressed and/or depressed nearly everyday, they referred a patient to social work or psychiatry once a week or less. Conclusions: Fellows shared high rates of emotional exhaustion and diminished empathy, which are cardinal burnout symptoms. However, they reported moderately high sense of personal accomplishment. They reported thinking they did not have enough time to give patients needed emotional attention, and may be under-utilizing supportive services for distressed and depressed patients. No significant financial relationships to disclose.
Acute and Fractionated Irradiation Differentially Modulate Glioma Stem Cell Division Kinetics
Authors: Xuefeng Gao, J. Tyson McDonald, Lynn Hlatky, Heiko Enderling
Journal: Cancer Research (2012)

Abstract Glioblastoma multiforme (GBM) is one of the most aggressive human malignancies with a poor patient prognosis. Ionizing radiation either alone or adjuvant after surgery is part of standard treatment for GBM but remains primarily noncurative. The mechanisms underlying tumor radioresistance are manifold and, in part, accredited to a special subpopulation of tumorigenic cells. The so-called glioma stem cells (GSC) are bestowed with the exclusive ability to self-renew and repopulate the tumor and have been reported to be less sensitive to radiation-induced damage through preferential activation of DNA damage checkpoint responses and increased capacity for DNA damage repair. During each fraction of radiation, non–stem cancer cells (CC) die and GSCs become enriched and potentially increase in number, which may lead to accelerated repopulation. We propose a cellular Potts model that simulates the kinetics of GSCs and CCs in glioblastoma growth and radiation response. We parameterize and validate this model with experimental data of the U87-MG human glioblastoma cell line. Simulations are conducted to estimate GSC symmetric and asymmetric division rates and explore potential mechanisms for increased GSC fractions after irradiation. Simulations reveal that in addition to their higher radioresistance, a shift from asymmetric to symmetric division or a fast cycle of GSCs following fractionated radiation treatment is required to yield results that match experimental observations. We hypothesize a constitutive activation of stem cell division kinetics signaling pathways during fractionated treatment, which contributes to the frequently observed accelerated repopulation after therapeutic irradiation. Cancer Res; 73(5); 1481–90. ©2012 AACR.
Impact of PCB and <i>p</i> , <i>p</i> ′-DDE Contaminants on Human Sperm Y:X Chromosome Ratio: Studies in Three European Populations and the Inuit Population in Greenland
Authors: Tarmo Tiido, Anna Rignell-Hydbom, Bo A.G. Jönsson, Yvonne Lundberg Giwercman, Henning S. Pedersen, Bogdan Wojtyniak, Jan K. Ludwicki, Vladimir Lesovoy, Valentyna Zvyezday, Marcello Spano, Gian-Carlo Manicardi, Davide Bizzaro, Eva C. Bonefeld-Jørgensen, Gunnar Toft, Jens Peter Bonde, Lars Rylander, Lars Hagmar, Aleksander Giwercman
Journal: Environmental Health Perspectives (2005)

Recent studies indicate that persistent organohalogen pollutants (POPs) may contribute to sex ratio changes in offspring of exposed populations. Our aim in the present study was to investigate whether exposure to 2,2 ,4,4 ,5,5 -hexachlorobiphenyl (PCB-153) and dichlorodiphenyldichloroethene (p,p -DDE) affects sperm Y:X chromosome distribution.We obtained semen and blood for analysis of PCB-153 and p,p -DDE levels from 547 men from Sweden, Greenland, Poland (Warsaw), and Ukraine (Kharkiv), with regionally different levels of POP exposure. The proportion of Y- and X-chromosome-bearing sperm in the semen samples was determined by two-color fluorescence in situ hybridization analysis.Swedish and Greenlandic men had on average significantly higher proportions of Y sperm (in both cohorts, 51.2%) and correspondingly higher lipid-adjusted concentrations of PCB-153 (260 ng/g and 350 ng/g, respectively) compared with men from Warsaw (50.3% and 22 ng/g) and Kharkiv (50.7% and 54 ng/g). In the Swedish cohort, log-transformed PCB-153 and log-transformed p,p -DDE variables were significantly positively associated with Y-chromosome fractions (p-values 0.04 and <0.001, respectively). On the contrary, in the Polish cohort PCB-153 correlated negatively with the proportion of Y-bearing fraction of spermatozoa (p=0.008).The present study indicates that POP exposure might be involved in changing the proportion of ejaculated Y-bearing spermatozoa in human populations. Intercountry differences, with different exposure situations and doses, may contribute to varying Y:X chromosome ratios.
Noninvasive Versus Conventional Mechanical Ventilation
Authors: ANNALISA CARLUCCI, JEAN-CHRISTOPHE RICHARD, MARC WYSOCKI, ERIC LEPAGE, LAURENT BROCHARD
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

A prospective survey was performed over a period of 3 wk among 42 intensive care units to assess the incidence of use and effectiveness of noninvasive mechanical ventilation (NIV) in clinical practice. All patients requiring ventilatory support for acute respiratory failure (ARF), either with endotracheal intubation (ETI) or NIV, were included. Ventilatory support was required in 689 patients, 581 with ETI and 108 (16%) with NIV (35% of patients not intubated on admission). Reasons for mechanical ventilation were coma (30%), cardiogenic pulmonary edema (7%), and hypoxemic (48%) and hypercapnic ARF (15%). NIV was never used for patients in coma (who were excluded from further analysis), but was used in 14% of patients with hypoxemic ARF, in 27% of those with pulmonary edema, and in 50% of those with hypercapnic ARF. NIV was followed by ETI in 40% of cases. The incidence of both nosocomial pneumonia (10% versus 19%, p = 0.03), and mortality (22% versus 41%, p < 0.001) was lower in NIV patients than in those with ETI. After adjusting for differences at baseline, Simplified Acute Physiology Score (SAPS) II (odds ratio [OR] = 1.05 per point; confidence interval [CI]: 1.04 to 1.06), McCabe/Jackson score (OR = 2.18; CI: 1.57 to 3.03), and hypoxemic ARF (OR = 2.30; CI: 1.33 to 4.01) were identified as risk factors explaining mortality; success of NIV was associated with a lower risk of pneumonia (OR = 0.06; CI: 0.01 to 0.45) and of death (OR = 0.16; CI: 0.05 to 0.54). In NIV patients, SAPS II and a poor clinical tolerance predicted secondary ETI. Failure of NIV was associated with a longer length of stay. In conclusion, NIV can be successful in selected patients, and is associated with a lower risk of pneumonia and death than is ETI.
Stoichiometric Relationships Between Endothelial Tetrahydrobiopterin, Endothelial NO Synthase (eNOS) Activity, and eNOS Coupling in Vivo
Authors: Jennifer K. Bendall, Nicholas J. Alp, Nicholas Warrick, Shijie Cai, David Adlam, Kirk Rockett, Mitsuhiro Yokoyama, Seinosuke Kawashima, Keith M. Channon
Journal: Circulation Research (2005)

Endothelial dysfunction in vascular disease states is associated with reduced NO bioactivity and increased superoxide (O 2 ·− ) production. Some data suggest that an important mechanism underlying endothelial dysfunction is endothelial NO synthase (eNOS) uncoupling, whereby eNOS generates O 2 ·− rather than NO, possibly because of a mismatch between eNOS protein and its cofactor tetrahydrobiopterin (BH4). However, the mechanistic relationship between BH4 availability and eNOS coupling in vivo remains undefined because no studies have investigated the regulation of eNOS by BH4 in the absence of vascular disease states that cause pathological oxidative stress through multiple mechanisms. We investigated the stoichiometry of BH4–eNOS interactions in vivo by crossing endothelial-targeted eNOS transgenic (eNOS-Tg) mice with mice overexpressing endothelial GTP cyclohydrolase 1 (GCH-Tg), the rate-limiting enzyme in BH4 synthesis. eNOS protein was increased 8-fold in eNOS-Tg and eNOS/GCH-Tg mice compared with wild type. The ratio of eNOS dimer:monomer was significantly reduced in aortas from eNOS-Tg mice compared with wild-type mice but restored to normal in eNOS/GCH-Tg mice. NO synthesis was elevated by 2-fold in GCH-Tg and eNOS-Tg mice but by 4-fold in eNOS/GCH-Tg mice compared with wild type. Aortic BH4 levels were elevated in GCH-Tg and maintained in eNOS/GCH-Tg mice but depleted in eNOS-Tg mice compared with wild type. Aortic and cardiac O 2 ·− production was significantly increased in eNOS-Tg mice compared with wild type but was normalized after NOS inhibition with N ω-nitro- l -arginine methyl ester hydrochloride (L-NAME), suggesting O 2 ·− production by uncoupled eNOS. In contrast, in eNOS/GCH-Tg mice, O 2 ·− production was similar to wild type, and L-NAME had no effect, indicating preserved eNOS coupling. These data indicate that eNOS coupling is directly related to eNOS–BH4 stoichiometry even in the absence of a vascular disease state. Endothelial BH4 availability is a pivotal regulator of eNOS activity and enzymatic coupling in vivo.
Galectin-Binding O-Glycosylations as Regulators of Malignancy
Authors: Charles J. Dimitroff
Journal: Cancer Research (2015)

Cancer cells commonly display aberrant surface glycans and related glycoconjugate scaffolds. Compared with their normal counterparts, cancer cell glycans are variably produced and often structurally distinct, serving as biomarkers of cancer progression or as functional entities to malignancy. The glycan signature of a cancer cell is created by the collaborative activities of glycosyltransferases, glycosidases, nucleotide-sugar transporters, sulfotransferases, and glycan-bearing protein/lipid scaffolds. In a coordinated fashion, these factors regulate the synthesis of cancer cell glycans and thus are considered correlates of cancer cell behavior. Functionally, cancer cell glycans can serve as binding targets for endogenous lectin effectors, such as C-type selectins and S-type galectins. There has been a recent surge of important observations of the role of glycosytransferases, specifically α2,6 sialyltransferases, in regulating the length and lectin-binding features of serine/threonine (O)-glycans found on cancer cells. The capping activity of O-glycan-specific α2,6 sialyltransferases, in particular, has been found to regulate cancer growth and metastasis in a galectin-dependent manner. These findings highlight the functional importance of cancer cell O-glycans and related galectin-binding features in the virulent activity of cancer and raise the prospect of targeting cancer cell glycans as effective anticancer therapeutics.
ED-28 * EFFECT OF VALPROIC ACID EXPOSURE ON SURVIVAL IN LOW-GRADE GLIOMA PATIENTS: A RETROSPECTIVE ANALYSIS
Authors: W. Sayeed, G. Musto, M. Pitz
Journal: Neuro-Oncology (2014)

BACKGROUND: Recent years have seen growing interest in histone deacetylase inhibitors (HDACi) in the treatment of various cancers, including gliomas. Valproic acid (VPA), a well-known anticonvulsant, is an HDACi and has been shown to increase sensitivity of tumour cells to multiple agents in vitro and in vivo. Retrospective work in glioblastoma has suggested an overall survival (OS) benefit for patients taking VPA. We performed a retrospective analysis of low-grade glioma (LGG) diagnoses in Manitoba, Canada and prescription histories to determine whether VPA improved survival. METHODS: The Manitoba Cancer Registry was searched for all cases of glioma diagnosis dating back to 1996. We included all patients with LGG aged 18 or older. Patients were considered to have LGG if they had histological confirmation, or had neuroimaging >1 year prior to the first surgery date with a higher grade histology. Date of diagnosis was set as the date of first neuroimaging. The Drug Program Information Network database was searched for anticonvulsant prescriptions received by patients identified. Variables tested were use of VPA (with or without other anticonvulsants), use of anticonvulsants excluding VPA, and no use of any anticonvulsants. RESULTS: We identified 321 patients, 37 (12%) of whom were on VPA, 138 (43%) of whom were on other anticonvulsants excluding VPA, and 146 (45%) of whom were without anticonvulsants. Preliminary analysis reveals a 6.9 years median OS for patients taking VPA, compared to 3.1 years for those taking other anticonvulsants and 0.6 years for those taking no anticonvulsants. CONCLUSIONS: This retrospective analysis suggests that VPA lengthens OS in patients with LGG. Multivariable analysis will further evaluate this potential difference. One limitation is the inclusion of rapidly progressive lesions in the median OS analysis, despite their known poor prognosis. Further prospective work is warranted to study the utility of VPA in improving OS.
Statin therapy is associated with reduced incidence of hypoxic hepatitis in critically ill patients
Authors: Andreas Drolz, Thomas Horvatits, Barbara Michl, Kevin Roedl, Peter Schellongowski, Ulrike Holzinger, Christian Zauner, Gottfried Heinz, Christian Madl, Michael Trauner, Valentin Fuhrmann
Journal: Journal of Hepatology (2014)
Effect of screening on incidence of and mortality from cancer of cervix in England: evaluation based on routinely collected statistics
Authors: M. Quinn, P. Babb, J. Jones, E. Allen
Journal: BMJ (1999)

# Effect of screening on incidence of and mortality from cancer of cervix in England: evaluation based on routinely collected statistics {#article-title-2} Objective: To assess the impact of screening on the incidence of and mortality from cervical cancer. Design: Comparison of age specific incidence and mortality before and after the introduction of the national call and recall system in 1988. Setting: England. Subjects: Women aged over 19 years. Results: From the mid-1960s, the number of smears taken rose continuously to 4.5 million at the end of the 1980s. Between 1988 and 1994, coverage of the target group doubled to around 85%. Registrations of in situ disease increased broadly in parallel with the numbers of smears taken. The overall incidence of invasive disease remained stable up to the end of the 1980s, although there were strong cohort effects; from 1990 incidence fell continuously and in 1995 was 35% lower than in the 1980s. The fall in overall mortality since 1950 accelerated at the end of the 1980s; there were strong cohort effects. Mortality in women under 55 was much lower in the 1990s than would have been expected. Conclusions: The national call and recall system and incentive payments to general practitioners increased coverage to around 85%. This resulted in falls in incidence of invasive disease in all regions of England and in all age groups from 30 to 74. The falls in mortality in older women were largely unrelated to screening, but without screening there might have been 800 more deaths from cervical cancer in women under 55 in 1997.
The effects of pressurization rate on breathing pattern, work of breathing, gas exchange and patient comfort in pressure support ventilation
Authors: D. Chiumello, P. Pelosi, M. Croci, L.M. Bigatello, L. Gattinoni
Journal: European Respiratory Journal (2001)

The aim of this study was to investigate the effects of different pressurization rates during pressure support ventilation on breathing pattern, work of breathing, gas exchange and patient comfort in patients with acute lung injury. The pressurization rate modifies the initial pressure ramp by changing the initial peak flow rate: the increase in pressurization rate is associated with a decrease in the time to reach the level of pressure support ventilation by increasing the peak flow rate. Ten intubated patients (age 64±17 yrs, body mass index 24±17 Kg·m −2 , arterial oxygen tension/inspired oxygen fraction 214±59) were studied in random order varying the pressurization rate at 5 and 15 cmH 2 O of pressure support ventilation. Breathing comfort was evaluated by a visual analogue scale. Increasing the pressurization rate caused an increase of peak flow rate from 473±141 mL·s −1 to 758±302 mL·s −1 at pressure support ventilation 5 (p&lt;0.05) and from 481±126 mL·s −1 to 1,121±175 mL·s −1 at pressure support ventilation 15 (p&lt;0.05). At the lowest pressurization rate the tidal volume was the lowest, the respiratory rate and the work of breathing were the highest (p&lt;0.05) compared with other pressurization rates. Excluding the lowest pressurization rate, in all the other pressurization rates tested the breathing pattern and the work of breathing did not change. The lowest and the highest pressurization rates caused the worst patient comfort (p&lt;0.05). The gas exchange was stable throughout the study. The presented results suggest: 1) the lowest pressurization rate caused the lowest tidal volume, highest respiratory rate and highest work of breathing; 2) at the other pressurization rates no differences in breathing pattern and work of breathing were observed; and 3) the patient's comfort was worse at the lowest and highest pressurization rates.