tbuckley/cabot-search huggingface dataset:
Inhibition of the intrinsic coagulation pathway factor XI by antisense oligonucleotides: a novel antithrombotic strategy with lowered bleeding risk
Authors: Hong Zhang, Ester C. Löwenberg, Jeffrey R. Crosby, A. Robert MacLeod, Chenguang Zhao, Dacao Gao, Chris Black, Alexey S. Revenko, Joost C. M. Meijers, Erik S. Stroes, Marcel Levi, Brett P. Monia
Journal: Blood (2010)
Against taking linguistic diversity at “face value”
Authors: David Pesetsky
Journal: Behavioral and Brain Sciences (2009)

Abstract Evans &amp; Levinson (E&amp;L) advocate taking linguistic diversity at “face value.” Their argument consists of a list of diverse phenomena and the assertion that no non-vacuous theory could possibly uncover a meaningful unity underlying them. I argue, with evidence from Tlingit and Warlpiri, that E&amp;L's list itself should not be taken at face value – and that the actual research record already demonstrates unity amidst diversity.
Increased Risk of Acute Cardiovascular Events After Partner Bereavement
Authors: Iain M. Carey, Sunil M. Shah, Stephen DeWilde, Tess Harris, Christina R. Victor, Derek G. Cook
Journal: JAMA Internal Medicine (2014)

IMPORTANCE The period immediately after bereavement has been reported as a time of increased risk of cardiovascular events. However, this risk has not been well quantified, and few large population studies have examined partner bereavement. OBJECTIVE To compare the rate of cardiovascular events between older individuals whose partner dies with those of a matched control group of individuals whose partner was still alive on the same day. DESIGN, SETTING, AND PARTICIPANTS Matched cohort study using a UK primary care database containing availale data of 401 general practices from February 2005 through September 2012. In all, 30 447 individuals aged 60 to 89 years at study initiation who experienced partner bereavement during follow-up were matched by age, sex, and general practice with the nonbereaved control group (n = 83 588) at the time of bereavement. EXPOSURES Partner bereavement. MAIN OUTCOMES AND MEASURES The primary outcome was occurrence of a fatal or nonfatal myocardial infarction (MI) or stroke within 30 days of bereavement. Secondary outcomes were non-MI acute coronary syndrome and pulmonary embolism. All outcomes were compared between the groups during prespecified periods after bereavement (30, 90, and 365 days). Incidence rate ratios (IRRs) from a conditional Poisson model were adjusted for age, smoking status, deprivation, and history of cardiovascular disease. RESULTS Within 30 days of their partner's death, 50 of the bereaved group (0.16%) experienced an MI or a stroke compared with 67 of the matched nonbereaved controls (0.08%) during the same period (IRR, 2.20 [95% CI, 1.52-3.15]). The increased risk was seen in bereaved men and women and attenuated after 30 days. For individual outcomes, the increased risk was found separately for MI (IRR, 2.14 [95% CI, 1.20-3.81]) and stroke (2.40 [1.22-4.71]). Associations with rarer events were also seen after bereavement, including elevated risk of non-MI acute coronary syndrome (IRR, 2.20 [95% CI, 1.12-4.29]) and pulmonary embolism (2.37 [1.18-4.75]) in the first 90 days. CONCLUSIONS AND RELEVANCE This study provides further evidence that the death of a partner is associated with a range of major cardiovascular events in the immediate weeks and months after bereavement. Understanding psychosocial factors associated with acute cardiovascular events may provide opportunities for prevention and improved clinical care.
A Metastasis Modifier Locus on Human Chromosome 8p in Uveal Melanoma Identified by Integrative Genomic Analysis
Authors: Michael D. Onken, Lori A. Worley, J. William Harbour
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To identify genes that modify metastatic risk in uveal melanoma, a type of cancer that is valuable for studying metastasis because of its remarkably consistent metastatic pattern and well-characterized gene expression signature associated with metastasis. Experimental Design: We analyzed 53 primary uveal melanomas by gene expression profiling, array-based comparative genomic hybridization, array-based global DNA methylation profiling, and single nucleotide polymorphism–based detection of loss of heterozygosity to identify modifiers of metastatic risk. A candidate gene, leucine zipper tumor suppressor-1 (LZTS1), was examined for its effect on proliferation, migration, and motility in cultured uveal melanoma cells. Results: In metastasizing primary uveal melanomas, deletion of chromosome 8p12-22 and DNA hypermethylation of the corresponding region of the retained hemizygous 8p allele were associated with more rapid metastasis. Among the 11 genes located within the deleted region, LZTS1 was most strongly linked to rapid metastasis. LZTS1 was silenced in rapidly metastasizing and metastatic uveal melanomas but not in slowly metastasizing and nonmetastasizing uveal melanomas. Forced expression of LZTS1 in metastasizing uveal melanoma cells inhibited their motility and invasion, whereas depletion of LZTS1 increased their motility. Conclusions: We have described a metastatic modifier locus on chromosome 8p and identified LZTS1 as a potential metastasis suppressor within this region. This study shows the utility of integrative genomic methods for identifying modifiers of metastatic risk in human cancers and may suggest new therapeutic targets in metastasizing tumor cells.
Risk for hepatocellular carcinoma with respect to hepatitis B virus genotypes B/C, specific mutations of enhancer II/core promoter/precore regions and HBV DNA levels
Authors: M-F Yuen, Y Tanaka, N Shinkai, R T Poon, D Y.-K. But, D Y-T Fong, J Fung, D K.-H. Wong, J C.-H. Yuen, M Mizokami, C-L Lai
Journal: Gut (2007)

To examine the risks for hepatocellular carcinoma (HCC) with respect to hepatitis B virus (HBV) genotypes, specific viral mutations (MT), serum HBV DNA levels, and cirrhosis.HBV genotypes, 1653/1753/core promoter (CP)/precore MT and HBV DNA levels were determined in 248 HBV patients with HCC and 248 HBV controls.Genotype C, CP-MT, T1653, HBV DNA levels >or=4 log(10) copies/ml and cirrhosis had a higher risk for HCC compared to patients with genotype B (p = 0.001, OR 1.9), CP wild-type (WT) (p<0.001, OR 4.1), C1653 (p = 0.028, OR 2.4), HBV DNA <4 log(10) copies/ml (p = 0.003, OR 2.1) and without cirrhosis (p<0.001, OR 4.0) respectively. Multivariate analysis showed that CP-MT, T1653, HBV DNA >or=4 log(10) copies/ml and cirrhosis were independent factors for HCC (all p<0.05). A receiver operating characteristics curve showed no cut-off HBV DNA level associated with minimal chance of HCC. Patients with CP-MT and cirrhosis had a 22.2-fold increased risk of HCC compared to patients with CP-WT and without cirrhosis. Patients with CP-MT and HBV DNA levels >or=4 log(10) copies/ml had a 7.2-fold increased risk of HCC compared to patients with CP-WT and HBV DNA levels <4 log(10) copies/ml. Patients with CP-MT and T1653 had a 9.9-fold increased risk of HCC compared to patients with wild-type for both regions.CP-MT, T1653, HBV DNA levels >or=4 log(10) copies/ml and cirrhosis are independent factors for development of HCC. The risks increased substantially in patients having these factors in combination.
Work for the disabled.
Authors: M A Chamberlain
Journal: BMJ (1984)

courses of treatment and prophylaxis should be avoided.38Equally important is the early detection of resistant organisms and the prevention of cross infection by them.For the future, the strains ofH influenzae and N gonorrhoeae resistant to their previous antibiotics of choice are unlikely to disappear: they are too well established and resistance has not altered pathogenicity.The sensitivity of Str pneumoniae and N meningitidis to penicillins may be at risk, and the incidence of group A streptococci M types resistant to erythromycin may increase under selective pressure from this drug.The genetic event that transfers resistance to a common pathogen seems to be rare, but once resistance has occurred it may spread fast and far.In the Philippines penicillin became obsolete for gonorrhoea within months, and multiply resistant Staph aureus has progressed world wide.Constant vigilance and careful prescribing are necessary even to maintain the status quo.
Performance of 4 Clinical Decision Rules in the Diagnostic Management of Acute Pulmonary Embolism
Authors: Renée A. Douma
Journal: Annals of Internal Medicine (2011)

Background: Several clinical decision rules (CDRs) are available to exclude acute pulmonary embolism (PE), but they have not been directly compared. Objective: To directly compare the performance of 4 CDRs (Wells rule, revised Geneva score, simplified Wells rule, and simplified revised Geneva score) in combination with d-dimer testing to exclude PE. Design: Prospective cohort study. Setting: 7 hospitals in the Netherlands. Patients: 807 consecutive patients with suspected acute PE. Intervention: The clinical probability of PE was assessed by using a computer program that calculated all CDRs and indicated the next diagnostic step. Results of the CDRs and d-dimer tests guided clinical care. Measurements: Results of the CDRs were compared with the prevalence of PE identified by computed tomography or venous thromboembolism at 3-month follow-up. Results: Prevalence of PE was 23%. The proportion of patients categorized as PE-unlikely ranged from 62% (simplified Wells rule) to 72% (Wells rule). Combined with a normal d-dimer result, the CDRs excluded PE in 22% to 24% of patients. The total failure rates of the CDR and d-dimer combinations were similar (1 failure, 0.5% to 0.6% [upper-limit 95% CI, 2.9% to 3.1%]). Even though 30% of patients had discordant CDR outcomes, PE was not detected in any patient with discordant CDRs and a normal d-dimer result. Limitation: Management was based on a combination of decision rules and d-dimer testing rather than only 1 CDR combined with d-dimer testing. Conclusion: All 4 CDRs show similar performance for exclusion of acute PE in combination with a normal d-dimer result. This prospective validation indicates that the simplified scores may be used in clinical practice. Primary Funding Source: Academic Medical Center, VU University Medical Center, Rijnstate Hospital, Leiden University Medical Center, Maastricht University Medical Center, Erasmus Medical Center, and Maasstad Hospital.
An embodied theory of cognitive development: Within reach?
Authors: Jeffrey J. Lockman
Journal: Behavioral and Brain Sciences (2001)

Thelen et al. not only offer an important new theoretical account of the Stage 4 object permanence error but provide the foundation of a new theory of cognitive development that is grounded in action. The success of dynamic field theory as a more general account of cognitive functioning, however, will depend on the degree to which it can model more generative capacities that are not limited to simple choice situations. Imitation and problem solving are suggested as two capacities that might be productively modeled within their approach.
Genistein Prevents Nuclear Factor-Kappa B Activation and Acute Lung Injury Induced by Lipopolysaccharide
Authors: JIHEE L. KANG, HYE W. LEE, HUI S. LEE, IN S. PACK, YOUNGHAE CHONG, VINCENT CASTRANOVA, YOUNSUCK KOH
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Protein tyrosine kinase (PTK) inhibitors have been proposed to reduce lung injury and lethal toxicity. The mechanisms responsible for the effects of PTK inhibitors remain obscure. The purpose of the present study was to examine whether genistein, a specific inhibitor of PTK, inhibits nuclear factor-kappa B (NF- κ B) activation during acute lung injury induced by lipopolysaccharide (LPS) and, if so, to enumerate the effects of inhibition of NF- κ B activation on LPS-induced proinflammatory gene products, such as cytokine-inducible neutrophil chemoattractant (CINC) and matrix metalloproteinase-9 (MMP-9), as well as neutrophil influx into the lungs. Intratracheal treatment of rats with LPS (6 mg/kg) resulted in increases in total protein and lactate dehydrogenase activity in bronchoalveolar lavage fluid and activated DNA-binding activity of NF- κ B in alveolar macrophages and lung tissue. A 2-h pretreatment with genistein (50 mg/kg, intraperitoneally) inhibited the LPS-induced changes in lung injury parameters and the induction of NF- κ B activation. Furthermore, these inhibitory effects of genistein correlated with a depression of LPS-induced protein tyrosine phosphorylation (approximately molecular masses of 46, 48, and 54 kD) and phosphorylation of Jun N-terminal kinase (JNK) in lung tissue. Genistein also substantially reduced the LPS-induced CINC production and MMP-9 activity and suppressed neutrophil recruitment. These results suggest that genistein attenuates LPS-induced acute lung responses through inhibition of NF- κ B activation. In addition, NF- κ B activation appears to be an important mechanism mediating LPS-induced CINC production and MMP-9 activity and resulting neutrophil recruitment associated with acute lung inflammation and injury.
A Randomized Trial of Vertebroplasty for Painful Osteoporotic Vertebral Fractures
Authors: Rachelle Buchbinder, Richard Harry Osborne, Peter Robert Ebeling, John D Wark, Peter J Mitchell, Chris J Wriedt, Stephen E Graves, Margaret Staples, Bridie Murphy
Journal: New England Journal of Medicine (2009)

Vertebroplasty has become a common treatment for painful osteoporotic vertebral fractures, but there is limited evidence to support its use.We performed a multicenter, randomized, double-blind, placebo-controlled trial in which participants with one or two painful osteoporotic vertebral fractures that were of less than 12 months' duration and unhealed, as confirmed by magnetic resonance imaging, were randomly assigned to undergo vertebroplasty or a sham procedure. Participants were stratified according to treatment center, sex, and duration of symptoms (< 6 weeks or > or = 6 weeks). Outcomes were assessed at 1 week and at 1, 3, and 6 months. The primary outcome was overall pain (on a scale of 0 to 10, with 10 being the maximum imaginable pain) at 3 months.A total of 78 participants were enrolled, and 71 (35 of 38 in the vertebroplasty group and 36 of 40 in the placebo group) completed the 6-month follow-up (91%). Vertebroplasty did not result in a significant advantage in any measured outcome at any time point. There were significant reductions in overall pain in both study groups at each follow-up assessment. At 3 months, the mean (+/-SD) reductions in the score for pain in the vertebroplasty and control groups were 2.6+/-2.9 and 1.9+/-3.3, respectively (adjusted between-group difference, 0.6; 95% confidence interval, -0.7 to 1.8). Similar improvements were seen in both groups with respect to pain at night and at rest, physical functioning, quality of life, and perceived improvement. Seven incident vertebral fractures (three in the vertebroplasty group and four in the placebo group) occurred during the 6-month follow-up period.We found no beneficial effect of vertebroplasty as compared with a sham procedure in patients with painful osteoporotic vertebral fractures, at 1 week or at 1, 3, or 6 months after treatment. (Australian New Zealand Clinical Trials Registry number, ACTRN012605000079640.)
Ubiquitin-like Protein FAT10 Promotes the Invasion and Metastasis of Hepatocellular Carcinoma by Modifying β-Catenin Degradation
Authors: Rongfa Yuan, Kai Wang, Junwen Hu, Chen Yan, Ming Li, Xin Yu, Xiuxia Liu, Jun Lei, Wuhua Guo, Linquan Wu, Kui Hong, Jianghua Shao
Journal: Cancer Research (2014)

Abstract The ubiquitin-like protein FAT10 and the homeobox protein HOXB9 each promote metastatic progression in hepatocellular carcinoma (HCC). In this study, we investigated the clinicopathologic significance of FAT10 and HOXB9 in HCC and investigated a mechanistic role for FAT10 in HOXB9-mediated invasiveness and metastasis. Relative to adjacent normal tissues, FAT10 and HOXB9 were markedly overexpressed in HCC, where a positive correlation in their expression and associated malignant characteristics were found. RNAi-mediated silencing of FAT10 decreased HOXB9 expression and inhibited HCC invasion and metastasis in vitro and in vivo. The effects of FAT10 silencing were reversed by HOXB9 overexpression, whereas RNAi-mediated silencing of HOXB9 decreased HCC invasion and metastasis driven by FAT10 overexpression. Mechanistically, FAT10 regulated HOXB9 expression by modulating the β-catenin/TCF4 pathway, directly binding to β-catenin and preventing its ubiquitination and degradation. Together, our results identified a novel HCC regulatory circuit involving FAT10, β-catenin/TCF4, and HOXB9, the dysfunction of which drives invasive and metastatic character in HCC. Cancer Res; 74(18); 5287–300. ©2014 AACR.
Haem Biosynthesis in the Heart Muscle of Man and the Pig
Authors: D. A. L. Watt, A. C. Lochhead, A. Goldberg
Journal: Cardiovascular Research (1967)

Using radioisotopic techniques, haem synthesis has been studied in human and pig cardiac muscle. High levels of haemsynthetase and δ-aminolaevulic acid dehydrase have been demonstrated, and newly-formed haem has been traced to myoglobin. The effect of iron upon these enzymes has been studied, and the relevance of these findings to iron storage diseases is discussed.
Bilateral subdural effusion in a patient with neuro-Behcet's disease
Authors: N Suzuki
Journal: Annals of the Rheumatic Diseases (2003)

The central nervous system is sometimes affected in patients with Behcet’s disease.1 Meningoencephalitis and brainstem lesions are the most common problems. The appearance of subdural effusion has been rarely reported. Our patient, who had neuro-Behcet’s disease with massive bilateral subdural effusion, was successfully treated with steroid pulse therapy.

The patient (a 45 year old man) first developed polyarthralgia, fever, recurrent oral aphthosis, and headache in 1986. In 1987 he had a genital ulcer and positive pathergy test. Thus, he fulfilled the international criteria for the diagnosis of Behcet’s disease. He had two cycles of steroid pulse therapy, and his symptoms including headache subsided. In 1995 an episodic exacerbation of the neuro-Behcet’s disease occurred, accompanying parkinsonism and abnormal cerebral spinal …
Interactions between Prostaglandin E2, Liver Receptor Homologue-1, and Aromatase in Breast Cancer
Authors: Jiong Zhou, Takashi Suzuki, Agnes Kovacic, Ryoko Saito, Yasuhiro Miki, Takanori Ishida, Takuya Moriya, Evan R. Simpson, Hironobu Sasano, Colin D. Clyne
Journal: Cancer Research (2005)

Local synthesis of estrogens within breast adipose tissue by cytochrome P450 aromatase contributes to the growth of postmenopausal breast cancers. One of the major stimulators of aromatase expression in breast is prostaglandin E(2) (PGE(2)) derived from tumorous epithelium and/or infiltrating macrophages. Recently, the orphan nuclear receptor, liver receptor homologue-1 (LRH-1), has also been shown to regulate aromatase expression in breast adipose tissue. We therefore examined the expression of, and correlations between, aromatase and LRH-1 mRNA in a panel of breast carcinoma tissues and adjacent adipose tissue. LRH-1 mRNA expression was low in normal breast tissue but markedly elevated in both breast carcinoma tissue and adipose tissue surrounding the tumor invasion (thereby paralleling aromatase expression). Laser capture microdissection localized the site of LRH-1 expression to tumor epithelial cells but not to intratumoral stromal cells. A strong correlation between LRH-1 and aromatase mRNA levels was observed in tumor-containing adipose tissue but not in tumor tissue. Ectopic expression of LRH-1 in primary human adipose stromal cells strongly activated endogenous aromatase mRNA expression and enzyme activity. Finally, treatment of adipose stromal cells with PGE(2) induced expression of both LRH-1 and aromatase. We suggest that PGE(2) derived from breast tumor tissue may increase aromatase expression in the surrounding adipose stroma in part by inducing LRH-1 in these cells. The roles of LRH-1 in breast cancer proliferation merit further study.
Comprehensive Assessment of Genetic and Molecular Features Predicting Outcome in Patients With Chronic Lymphocytic Leukemia: Results From the US Intergroup Phase III Trial E2997
Authors: Michael R. Grever, David M. Lucas, Gordon W. Dewald, Donna S. Neuberg, John C. Reed, Shinichi Kitada, Ian W. Flinn, Martin S. Tallman, Frederick R. Appelbaum, Richard A. Larson, Elisabeth Paietta, Diane F. Jelinek, John G. Gribben, John C. Byrd
Journal: Journal of Clinical Oncology (2007)

Genomic features including unmutated immunoglobulin variable region heavy chain (IgVH) genes, del(11q22.3), del(17p13.1), and p53 mutations have been reported to predict the clinical course and overall survival of patients with chronic lymphocytic leukemia (CLL). In addition, ZAP-70 and Bcl-2 family proteins have been explored as predictors of outcome.We prospectively evaluated the prognostic significance of a comprehensive panel of laboratory factors on both response and progression-free survival (PFS) using samples and data from 235 patients enrolled onto a therapeutic trial. Patients received either fludarabine (FL; n = 113) or fludarabine plus cyclophosphamide (FC; n = 122) as part of a US Intergroup randomized trial for previously untreated CLL patients.Complete response (CR) rates were 24.6% for patients receiving FC and 5.3% for patients receiving FL (P = .00004). PFS was statistically significantly longer in patients receiving FC (median, 33.5 months for patients receiving FC and 19.9 months for patients receiving FL; P < .0001). The occurrence of del(17p13.1) (hazard ratio, 3.428; P = .0002) or del(11q22.3) (hazard ratio, 1.904; P = .006) was associated with reduced PFS. CR and overall response rates were not significantly different based on cytogenetics, IgVH mutational status, CD38 expression, or p53 mutational status. Expression of ZAP-70, Bcl-2, Bax, Mcl-1, XIAP, Caspase-3, and Traf-1 was not associated with either clinical response or PFS.These results support the use of interphase cytogenetic analysis, but not IgVH, CD38 expression, or ZAP-70 status, to predict outcome of FL-based chemotherapy. Patients with high-risk cytogenetic features should be considered for alternative therapies.
Early Insults to the Injured Brain
Authors: J. Douglas Miller
Journal: JAMA (1978)

Of 100 consecutive patients with severe head injury who arrived at a major trauma center, half of whom came direct from the accident site and half from another hospital, potentially serious systemic insults to the brain were present in 44 cases. Arterial hypotension (13 cases), anemia (12 cases), and hypercarbia (4 cases) were almost exclusively associated with multiple injuries, which were present in 57 patients and were caused usually by vehicular accidents. Hypoxia was seen in 30 patients, including several with brain injury alone. These systemic insults to the already injured brain were associated with an increase in mortality and morbidity. We believe that direct transfer to a trauma center that has full-time neurosurgical facilities for victims of automobile accidents and patients who have been rendered unconscious by a fall or blow on the head will increase survival. Care for the patient with head injuries should start at the roadside. (<i>JAMA</i>240:439-442, 1978)
Differences in Clinical Outcome in Patients with Common Variable Immunodeficiency Treated with Ig Replacement Therapy: Results from the ESID Database
Authors: G. Kindle, K. Warnatz, O. Paschenko, D. Kumararatne, S.S. Kilic, V. Thon, T. Witte, M. Helbert, T.W. Kuijpers, A. Exley, N. Mahlaoui, G. Notheis, H. Longhurst, U. Baumann, A. Jones, N. Kütükcüler, M. Borte, P. Wagström, C. Feighery, A. Szaflarska, H. Ritterbusch, S. Reda, T. Kononova, Z. Panahloo, B. Grimbacher
Journal: Journal of Allergy and Clinical Immunology (2011)