tbuckley/cabot-search huggingface dataset:
Alcohol consumption is not protective for systemic lupus erythematosus
Authors: J Wang, A B Kay, J Fletcher, M K Formica, T E McAlindon
Journal: Annals of the Rheumatic Diseases (2008)

Objective: Several studies have suggested that alcohol drinking is protective for the development and progression of systemic lupus erythematosus (SLE). However, a protopathic bias might also explain this apparent association. Our objective was to investigate the association between alcohol consumption and incidence of SLE in a data set that has information on both current and pre-diagnostic alcohol consumption. Methods: We performed an Internet-based case–control study of SLE. Cases were diagnosed within 5 years of the study and met ⩾4 American College of Rheumatology criteria for SLE. The control participants were tightly matched to cases on demographic and socio-economic characteristics using a propensity score. Participants completed an online exposure assessment. We used conditional logistic regression analyses to test the association of current and pre-diagnostic alcohol consumption with SLE. Results: The sample comprised 114 cases with SLE and 228 matched controls. Current drinking (&gt;2 days per week) was inversely associated with SLE (OR 0.35, 95% CI 0.13 to 0.98). Having more than two drinks per day was also inversely associated with SLE (OR 0.41, 95% CI 0.18 to 0.93). However, alcohol consumption before SLE diagnosis was not associated with the risk of SLE (p⩾0.4). Analysis of the change in drinking habits showed that people with lupus were more likely to quit drinking before (OR 2.25, 95% CI 0.96 to 5.28) or after (OR 2.38, 95% CI 0.88 to 6.49) being given the SLE diagnosis. Conclusions: Our results show that alcohol consumption before SLE diagnosis is not associated with the risk for SLE, and that individuals who develop SLE are more likely to quit.
Vascular endothelial growth factor-B-deficient mice show impaired development of hypoxic pulmonary hypertension
Authors: J Wanstall
Journal: Cardiovascular Research (2002)

Objective: To test the hypothesis that Vegf-B contributes to the pulmonary vascular remodelling, and the associated pulmonary hypertension, induced by exposure of mice to chronic hypoxia. Methods: Right ventricular systolic pressure, the ratio of right ventricle/[left ventricle+septum] (RV/[LV+S]) and the thickness of the media (relative to vessel diameter) of intralobar pulmonary arteries (o.d. 50–150 and 151–420 μm) were determined in Vegfb knockout mice (Vegfb−/−; n = 17) and corresponding wild-type mice (Vegfb+/+; n = 17) exposed to chronic hypoxia (10% oxygen) or housed in room air (normoxia) for 4 weeks. Results: In Vegfb+/+ mice hypoxia caused (i) pulmonary hypertension (a 70% increase in right ventricular systolic pressure compared with normoxic Vegfb+/+ mice; P<0.001), (ii) right ventricular hypertrophy (a 66% increase in RV/[LV+S]; P<0.001) and (iii) pulmonary vascular remodelling (a 27–36% increase in pulmonary arterial medial thickness; P<0.05). In contrast, in Vegfb−/− mice hypoxia did not cause any increase in either right ventricular systolic pressure or pulmonary arterial medial thickness; also right ventricular hypertrophy (41% increase in RV/[LV+S]; P<0.001) was less pronounced (P<0.05) than in Vegfb+/+ mice. Conclusion: Vegf-B may have a role in the development of chronic hypoxic pulmonary hypertension in mice by contributing to pulmonary vascular remodelling. If so, the effect of Vegf-B appears to be different from that of Vegf-A which is reported to protect against, rather than contribute to, hypoxia-induced pulmonary vascular remodelling.
Respiratory symptoms in arable farmworkers: role of storage mites.
Authors: A D Blainey, M D Topping, S Ollier, R J Davies
Journal: Thorax (1988)

Storage mites (acarid mites) are related to the house dust mite but are usually found in agricultural environments. They have been shown to cause allergic symptoms in Scottish farmworkers exposed to stored hay, but whether farmworkers who grow and store grain are also at risk is unknown. One hundred and one farmworkers on 22 Essex farms with grain storage facilities (88% of the available workforce) participated in a survey of respiratory symptoms, with skin tests and determination of serum levels of IgE specific for mite species, including storage mites. Of the 101 workers, 21 reported attacks of cough, wheeze, or breathlessness after exposure to stored grain and 15 reported nasal symptoms after grain exposure. Storage mite specific IgE was found in 59% of farmworkers with work related respiratory symptoms, in 60% with work related nasal symptoms, and in only 9% of symptomless farmworkers. Work related respiratory and nasal symptoms were also significantly associated with atopy, and with positive skin test responses and serum IgE specific for Dermatophagoides pteronyssinus. Storage mites were found in grain samples from 16 farms in which grain was sampled, whereas D pteronyssinus was not found in any. The close association between serum storage mite specific IgE and occupational respiratory symptoms suggests that storage mites may be responsible for respiratory symptoms in these Essex farmworkers exposed to grain.
Guiding the Optimal Translation of New Cancer Treatments From Canine to Human Cancer Patients
Authors: Chand Khanna, Cheryl London, David Vail, Christina Mazcko, Steven Hirschfeld
Journal: Clinical Cancer Research (2009)

On June 20, 2008, a meeting entitled "Translation of new cancer treatments from canine to human cancer patients," sponsored by the National Cancer Institute in Bethesda, Maryland, was convened to discuss the potential value, opportunity, risks, and rewards of an integrated and comparative drug development path for new cancer therapeutics that includes naturally occurring cancers in pet animals. A summary of this meeting and subsequent discussion are provided here to afford clarity on the conduct of these studies so as to optimize the opportunities provided by this novel drug development and modeling strategy.
Reduction of Behavioral Disturbances and Caregiver Distress by Galantamine in Patients With Alzheimer’s Disease
Authors: Jeffrey L. Cummings, Lon Schneider, Pierre N. Tariot, Paul R. Kershaw, Weiying Yuan
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Alzheimer's disease pathology includes both histologic changes and neurotransmitter deficits. The cholinergic deficit contributes to both cognitive and behavioral disturbances, and cholinesterase inhibitors may improve behavior in Alzheimer's disease patients. This analysis was conducted to assess the impact of galantamine, a cholinesterase inhibitor with nicotinic-receptor-modulating properties, on the pattern and evolution of behavioral disturbances in patients with Alzheimer's disease and on caregiver distress related to patients' behavior. METHOD: Data from 978 patients with mild to moderate Alzheimer's disease who were randomly assigned to placebo or galantamine (8, 16, or 24 mg/day) were analyzed. Behavioral changes were assessed with the Neuropsychiatric Inventory, and alterations in caregiver distress were measured by the Neuropsychiatric Inventory distress scale. Data collected at baseline and 12 and 21 weeks postbaseline were analyzed. RESULTS: Neuropsychiatric Inventory scores worsened with placebo, whereas patients treated with 16 or 24 mg/day of galantamine had no change in total Neurospcyhiatric Inventory scores. Treated patients, asymptomatic or symptomatic at baseline, had better Neuropsychiatric Inventory subscale scores than did patients receiving placebo. Behavioral improvement in patients symptomatic at baseline ranged from 29% to 48%. Changes were evident in patients receiving 16 or 24 mg/day of galantamine. High-dose galantamine was associated with a significant reduction in caregiver distress. CONCLUSIONS: Galantamine therapy was associated with reduced emergence of behavioral disturbances and improvement in existing behavioral problems in patients with mild to moderate Alzheimer's disease, with a concomitant reduction in reported caregiver distress.
Biphasic Stimulation of Aldosterone Secretion during Hemorrhage in Dogs
Authors: LOUIS F. FABRE, ROBERT W. FARMER, H. WINSTON DAVIS, GEORGE MCBEE, GORDON FARRELL
Journal: Circulation Research (1969)

The increase of aldosterone secretion in response to hemorrhage has been reevaluated with the aid of a newly developed micromethod using gas-liquid chromatography. Pentobarbital-anesthetized large male dogs were slowly exsanguinated through the lumboadrenal vein while sequential 15-minute samples of adrenal venous effluent were collected. Mean arterial blood pressure and blood loss were monitored. The response to hemorrhage was found to be biphasic; a significant increase in aldosterone secretion occurred before blood pressure changed significantly, the secretory rates then fell toward control, and rose again as the blood pressure fell to shock levels. Statistical evaluation of the data confirmed the quartic nature of the response and indicated a best-fit equation of y = 169.14x - 800.22x 2 + 1258.46x 3 - 619.24x 4 . These results demonstrate that control of aldosterone secretion is dependent on complex functions of blood volume and blood pressure. Volume receptor mechanisms as well as pressure receptor mechanisms would seem to be involved. Any investigation of the aldosterone response to hemorrhage, to be valid, must take these complex relationships into consideration.
Early recognition of hepatocellular carcinoma
Authors: Kunio Okuda
Journal: Hepatology (1986)

Primary liver cancer (PLC) is a malignant disease which is difficult to detect in its early stages and has very poor prognosis.Although relatively uncommon among Caucasians it is one of the major malignancies in many countries throughout the world, particularly in sub-Saharan Africa and the Far East.It accounts for 65.5% of all malignant disease in men and 31% of malignant tumors in women among Shangaan blacks in South Africa (1).It is the third major cause of cancer death in males and the fourth among females in China (2); it ranked third and fifth in these groups, respectively, in Japan in 1983 (3).Of PLC, hepatocellular carcinoma (HCC) is the major histological type followed in frequency by cholangiocellular carcinoma-the ratio of HCC to cholangiocellular carcinoma varies from 5:l to nearly 401 (4).In other words, the major malignant killer in the high PLC incidence areas is HCC.A close association of HCC with cirrhosis, particularly the posthepatitic or macronodular variety, has long been known (5-7).This interrelationship, an enigma in the past, now seems explainable in part by the hepatocarcinogenic properties of hepatitis B virus infection (8, 9).However, some epidemiological data speak against the theory that this virus is the sole etiologic factor in HCC (10,ll).Besides food contamination by aflatoxins in the tropical and subtropical regions, chronic non-A, non-B hepatitis is one recent etiologic candidate in Japan where HCC incidence has more than doubled in the past 15 years despite a concomitant increase in hepatitis B virus seronegative cases (12).A recent study in Tokyo shows that 40% of patients with HCC now have a history of past blood transfusion (13).Because of frustrations due to late diagnosis and bad therapeutic results, Japanese gastroenterologists have pioneered clinical programs for the early detection of HCC. MASS SCREENING FOR ASYMPTOMATIC HCCIn the early 1970's, when serum a-fetoprotein (AFP) was still under investigation for its diagnostic significance in HCC, an attempt was made by Masseyeff and his group (14) in Senegal to screen normal people for the detection of early HCC.They used the AFP Ouchterlony test and screened 9,000 male workers three times a year for 2 years.AFP-positive HCC was found in three apparently healthy males.Unfortunately, in only 1 of the
Words in the brain's language
Authors: Friedemann Pulverm&uuml;ller
Journal: Behavioral and Brain Sciences (1999)

If the cortex is an associative memory, strongly connected cell assemblies will form when neurons in different cortical areas are frequently active at the same time. The cortical distributions of these assemblies must be a consequence of where in the cortex correlated neuronal activity occurred during learning. An assembly can be considered a functional unit exhibiting activity states such as full activation ("ignition") after appropriate sensory stimulation (possibly related to perception) and continuous reverberation of excitation within the assembly (a putative memory process). This has implications for cortical topographies and activity dynamics of cell assemblies forming during language acquisition, in particular for those representing words. Cortical topographies of assemblies should be related to aspects of the meaning of the words they represent, and physiological signs of cell assembly ignition should be followed by possible indicators of reverberation. The following postulates are discussed in detail: (1) assemblies representing phonological word forms are strongly lateralized and distributed over perisylvian cortices; (2) assemblies representing highly abstract words such as grammatical function words are also strongly lateralized and restricted to these perisylvian regions; (3) assemblies representing concrete content words include additional neurons in both hemispheres; (4) assemblies representing words referring to visual stimuli include neurons in visual cortices; and (5) assemblies representing words referring to actions include neurons in motor cortices. Two main sources of evidence are used to evaluate these proposals: (a) imaging studies focusing on localizing word processing in the brain, based on stimulus-triggered event-related potentials (ERPs), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI), and (b) studies of the temporal dynamics of fast activity changes in the brain, as revealed by high-frequency responses recorded in the electroencephalogram (EEG) and magnetoencephalogram (MEG). These data provide evidence for processing differences between words and matched meaningless pseudowords, and between word classes, such as concrete content and abstract function words, and words evoking visual or motor associations. There is evidence for early word class-specific spreading of neuronal activity and for equally specific high-frequency responses occurring later. These results support a neurobiological model of language in the Hebbian tradition. Competing large-scale neuronal theories of language are discussed in light of the data summarized. Neurobiological perspectives on the problem of serial order of words in syntactic strings are considered in closing.
A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status
Authors: Sanjana Sood, Iain J. Gallagher, Katie Lunnon, Eric Rullman, Aoife Keohane, Hannah Crossland, Bethan E. Phillips, Tommy Cederholm, Thomas Jensen, Luc JC van Loon, Lars Lannfelt, William E. Kraus, Philip J. Atherton, Robert Howard, Thomas Gustafsson, Angela Hodges, James A. Timmons
Journal: Genome biology (2015)

Diagnostics of the human ageing process may help predict future healthcare needs or guide preventative measures for tackling diseases of older age. We take a transcriptomics approach to build the first reproducible multi-tissue RNA expression signature by gene-chip profiling tissue from sedentary normal subjects who reached 65 years of age in good health. One hundred and fifty probe-sets form an accurate classifier of young versus older muscle tissue and this healthy ageing RNA classifier performed consistently in independent cohorts of human muscle, skin and brain tissue (n = 594, AUC = 0.83–0.96) and thus represents a biomarker for biological age. Using the Uppsala Longitudinal Study of Adult Men birth-cohort (n = 108) we demonstrate that the RNA classifier is insensitive to confounding lifestyle biomarkers, while greater gene score at age 70 years is independently associated with better renal function at age 82 years and longevity. The gene score is 'up-regulated' in healthy human hippocampus with age, and when applied to blood RNA profiles from two large independent age-matched dementia case–control data sets (n = 717) the healthy controls have significantly greater gene scores than those with cognitive impairment. Alone, or when combined with our previously described prototype Alzheimer disease (AD) RNA 'disease signature', the healthy ageing RNA classifier is diagnostic for AD. We identify a novel and statistically robust multi-tissue RNA signature of human healthy ageing that can act as a diagnostic of future health, using only a peripheral blood sample. This RNA signature has great potential to assist research aimed at finding treatments for and/or management of AD and other ageing-related conditions.
Context, categories and modality: Challenges for the Rumelhart model
Authors: James A. Hampton
Journal: Behavioral and Brain Sciences (2008)

Abstract Three issues are raised in this commentary. First, the mapping of semantic information into the different layers could be done in a more realistic way by using the Context layer to represent situational contexts. Second, a way to differentiate category membership information from other property information needs to be considered. Finally, the issue of modal knowledge is raised.
Clinical and Pharmacologic Study of the Farnesyltransferase Inhibitor Tipifarnib in Cancer Patients With Normal or Mildly or Moderately Impaired Hepatic Function
Authors: Wandena S. Siegel-Lakhai, Mirjam Crul, Peter De Porre, Steven Zhang, Ilsung Chang, Henk Boot, Jos H. Beijnen, Jan H.M. Schellens
Journal: Journal of Clinical Oncology (2006)

Purpose This study explored the feasibility of treating patients with impaired hepatic function with tipifarnib. The safety profile, pharmacokinetics, and relationship between the pharmacokinetics and toxicities were evaluated. Patients and Methods Patients with mildly or moderately impaired hepatic function (Child-Pugh classification) were treated with tipifarnib bid on days 1 to 5 of cycle 1. Further dosing was based on the individual day 5 pharmacokinetic data and absolute neutrophil count. For patients with normal hepatic function, tipifarnib was dosed on days 1 to 14, followed by 1 week of rest. For all patients, in subsequent cycles, tipifarnib was administered for 21 consecutive days out of every 28 days. Results Twenty-eight patients were included in the normal (n = 16), mild (n = 9), and moderate (n = 3) impairment groups. The most important grade 3 to 4 hematologic toxicity was leukocytopenia/neutropenia, which was mostly observed in patients with moderate impairment. Common nonhematologic toxicities were fatigue, nausea, and vomiting. The pharmacokinetic data showed higher plasma concentrations of tipifarnib in patients with liver impairment compared with patients with normal hepatic function. Conclusion In patients with mildly impaired hepatic function, tipifarnib can be administered safely at a starting dose of 200 mg bid, but it is not safe to treat patients with moderate hepatic impairment.
ED-38 * AN UPDATED ANALYSIS OF PATIENT REGISTRY DATA ON NOVOTTF-100A ALTERNATING ELECTRIC FIELDS THERAPY FOR RECURRENT GLIOBLASTOMA
Authors: E. T. Wong, H. H. Engelhard, D. D. Tran, Y. Kew, M. M. Mrugala, R. Cavaliere, J. L. Villano, D. A. Bota, J. Rudnick, A. L. Sumrall, J. J. Zhu
Journal: Neuro-Oncology (2014)

The NovoTTF-100A System is an anticancer treatment that emits alternating electric fields, at an intensity of 1 V/cm and a frequency of 200 kHz, which mimic the cytotoxic effect of chemotherapy by disrupting charged cytoplasmic proteins involved in the tightly orchestrated process of mitosis. The pivotal phase III trial demonstrated equivalent efficacy when the device was compared to conventional cytotoxic chemotherapies and bevacizumab, but without their systemic side effects. After the initial approval, patients were prescribed the device at 91 oncology centers in the United States from October 2011 to November 2013 and they provided consent to their protected health information for the patient registry. We then retrospectively analyzed their outcome and treatment-related adverse events. There were 147 women and 310 men (n = 457) and their median age was 55 (range 18-26) years. Over 70% of them had a Karnofsky performance score (KPS) of 70 or higher. Sixty percent were in their first or second recurrence while 27% were in their third or greater recurrence. More than 55% of patients had prior treatment with bevacizumab. The overall Kaplan-Meier median overall survival (OS) was 9.6 (95% confidence interval [CI] 8.0 to 13.7) months and the median treatment duration was 4.1 (95% CI 3.5 to 4.8) months. Favorable prognostic factors include ≥75% treatment compliance (<0.0001), no prior bevacizumab usage (p = 0.0001), KPS of 90-100 (p = 0.0070) and first recurrence (0.0271). The most common device-related adverse events include skin reaction (24.3%), neurological disorders (10.4%), heat sensation (8.9%), electric sensation (7.7%) and headache (5.7%). Treatment with NovoTTF-100A System, as prescribed in the general clinical setting to patients with recurrent glioblastomas, offers favorable outcomes and no new unexpected toxicities. The data also indicate that treatment compliance, no prior bevacizumab usage, high KPS and application of the device at first recurrence are important prognostic factors.
Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data
Authors: Jack Cuzick, Ivana Sestak, Bernardo Bonanni, Joseph P Costantino, Steve Cummings, Andrea DeCensi, Mitch Dowsett, John F Forbes, Leslie Ford, Andrea Z LaCroix, John Mershon, Bruce H Mitlak, Trevor Powles, Umberto Veronesi, Victor Vogel, D Lawrence Wickerham
Journal: The Lancet (2013)
Role of Ubiquitin-Like Protein FAT10 in Epithelial Apoptosis in Renal Disease
Authors: Michael J. Ross, Matthew S. Wosnitzer, Michael D. Ross, Benedetta Granelli, G. Luca Gusella, Mohammad Husain, Lewis Kaufman, Matthew Vasievich, Vivette D. D’Agati, Patricia D. Wilson, Mary E. Klotman, Paul E. Klotman
Journal: Journal of the American Society of Nephrology (2006)

Dysregulated apoptosis of renal tubular epithelial cells (RTEC) is an important component of the pathogenesis of several renal diseases, including HIV-associated nephropathy (HIVAN), the most common cause of chronic kidney failure in HIV-infected patients. In HIVAN, RTEC become infected by HIV-1 in a focal distribution, and HIV-1 infection has been shown to induce apoptosis in vitro. In microarray studies that used a novel renal tubular epithelial cell line from a patient with HIVAN, it was found that the ubiquitin-like protein FAT10 is one of the most upregulated genes in HIV-infected cells. Previously, FAT10 was shown to induce apoptosis in murine fibroblasts. The expression of FAT10 in HIVAN and the ability of FAT10 to induce apoptosis in human RTEC therefore were studied. This study revealed that FAT10 expression is induced after infection of RTEC by HIV-1 and that expression of FAT10 induces apoptosis in RTEC in vitro. Moreover, it was found that inhibition of endogenous FAT10 expression abrogated HIV-induced apoptosis of RTEC. Immunohistochemical studies demonstrated increased FAT10 expression in a murine model of HIVAN, in HIVAN biopsy samples, and in autosomal dominant polycystic kidney disease, another renal disease that is characterized by cystic tubular enlargement and epithelial apoptosis. These results suggest a novel role for FAT10 in epithelial apoptosis, which is an important component of the pathogenesis of many renal diseases.