tbuckley/cabot-search huggingface dataset:
Association of tumor necrosis factor-alpha promoter variants with risk of HPV-associated oral squamous cell carcinoma
Authors: Lei Jin, Erich M Sturgis, Yang Zhang, Zhigang Huang, Xicheng Song, Chao Li, Qingyi Wei, Guojun Li
Journal: Molecular Cancer (2013)

Tumor necrosis factor alpha (TNF-α) plays an important role in inflammation, immunity, and defense against infection and clearance of human papillomavirus (HPV). Thus, genetic variants may modulate individual susceptibility to HPV-associated oral squamous cell carcinoma (OSCC).In this study we genotyped four common single nucleotide polymorphisms (SNPs) in the TNF-α promoter [ -308G > A(rs1800629), -857C > T (rs1799724), -863C > A (rs1800630), and -1031T > C (rs1799964)] and determined HPV16 serology in 325 OSCC cases and 335 matched controls and tumor HPV status in 176 squamous cell carcinomas of the oropharynx (SCCOP) patients. Univariate and multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).We found that HPV16 seropositivity alone was associated with an increased risk of OSCC (OR, 3.1; 95% CI, 2.1-4.6), and such risk of HPV16-associated OSCC was modified by each SNP. Patients with both HPV16 seropositivity and variant genotypes for each SNP had the highest risk when using patients with HPV16 seronegativity and a wild-type genotype as a comparison group. Moreover, similar results were observed for the combined risk genotypes of four variants and all such significant associations were more pronounced in several subgroups, particularly in SCCOP patients and never smokers. Notably, the combined risk genotypes of four variants were also significantly associated with tumor HPV-positive SCCOP.Taken together, these results suggest that TNF-α SNPs may individually or, more likely, jointly affect individual susceptibility to HPV16-associated OSCC, particularly SCCOP and never smokers. Validation of our findings is warranted.
Comparison between pathogen directed antibiotic treatment and empirical broad spectrum antibiotic treatment in patients with community acquired pneumonia: a prospective randomised study
Authors: M M van der Eerden
Journal: Thorax (2005)

<b>Background:</b> There is much controversy about the ideal approach to the management of community acquired pneumonia (CAP). Recommendations differ from a pathogen directed approach to an empirical strategy with broad spectrum antibiotics. <b>Methods:</b> In a prospective randomised open study performed between 1998 and 2000, a pathogen directed treatment (PDT) approach was compared with an empirical broad spectrum antibiotic treatment (EAT) strategy according to the ATS guidelines of 1993 in 262 hospitalised patients with CAP. Clinical efficacy was primarily determined by the length of hospital stay (LOS). Secondary outcome parameters for clinical efficacy were assessment of therapeutic failure on antibiotics, 30 day mortality, duration of antibiotic treatment, resolution of fever, side effects, and quality of life. <b>Results:</b> Three hundred and three patients were enrolled in the study; 41 were excluded, leaving 262 with results available for analysis. No significant differences were found between the two treatment groups in LOS, 30 day mortality, clinical failure, or resolution of fever. Side effects, although they did not have a significant influence on the outcome parameters, occurred more frequently in patients in the EAT group than in those in the PDT group (60% <i>v</i> 17%, 95% CI −0.5 to −0.3; p&lt;0.001). <b>Conclusions:</b> An EAT strategy with broad spectrum antibiotics for the management of hospitalised patients with CAP has comparable clinical efficacy to a PDT approach.
Radiologist Interpretive Volume and Breast Cancer Screening Accuracy in a Canadian Organized Screening Program
Authors: Isabelle Théberge, Sue-Ling Chang, Nathalie Vandal, Jean-Marc Daigle, Marie-Hélène Guertin, Éric Pelletier, Jacques Brisson
Journal: JNCI Journal of the National Cancer Institute (2014)

To strengthen evidence on which radiologist mammography interpretive volume requirements can be based, we assessed the relation of volume to accuracy in the Quebec Breast Cancer Screening Program. Annual interpretive volume (total, screening, and diagnostic) for all 340 radiologists who interpreted 1315327 screening examinations in the period from 2000 to 2006 was obtained using provincial databases. The association of volume to sensitivity, false-positive rate, and accuracy (sensitivity/false-positive rate) was assessed by multivariable Poisson regression with robust error variance. All statistical tests were two-sided. Radiologists consistently interpreting less than 500 mammograms annually experienced a 58% reduction in accuracy (adjusted accuracy ratio = 0.42; 95% confidence interval [CI] = 0.24 to 0.74) compared with those who consistently interpreted at least 500 mammograms annually. Moreover, accuracy increased progressively as total annual volume increased (Ptrend = .0005). Radiologists interpreting at least 4000 mammograms annually experienced a 32% increase in accuracy (adjusted accuracy ratio = 1.32; 95% CI = 1.13 to 1.54) compared with those interpreting 500 to 999 mammograms annually. This increase in accuracy is attributable to a reduction in false-positive rate as total volume increased (Ptrend = .001). Sensitivity changed little with total volume (Ptrend = .68). Gains in accuracy were greater up to approximately 3000 mammograms interpreted annually. The minimum annual volume of 500 mammograms required in North America is justified; radiologist accuracy may be compromised if interpretive volume is consistently less than this requirement. Raising interpretive volume may help to reduce the frequency of false positives without loss of sensitivity. Possible gains in accuracy may be greater with increases in volume of up to approximately 3000 mammograms interpreted annually.
Osteopontin Is Involved in the Initiation of Cutaneous Contact Hypersensitivity by Inducing Langerhans and Dendritic Cell Migration to Lymph Nodes
Authors: J.M. Weiss, A.C. Renkl, C.S. Maier, M. Kimmig, L. Liaw, T. Ahrens, S. Kon, M. Maeda, H. Hotta, T. Uede, J.C. Simon
Journal: The Journal of Experimental Medicine (2001)

Osteopontin (OPN) is a chemotactic protein that attracts immune cells, to inflammatory sites. The sensitization phase of allergic cutaneous contact hypersensitivity (CHS) requires the migration of Langerhans cells/dendritic cells (LCs/DCs) from skin to draining lymph nodes. Characterizing OPN function for LC/DC migration we found upregulated OPN expression in hapten sensitized skin and draining lymph nodes. OPN induces chemotactic LC/DC migration, initiates their emigration from the epidermis, and attracts LCs/DCs to draining lymph nodes by interacting with CD44 and αv integrin. Furthermore, OPN-deficient mice have a significantly reduced CHS response that correlates with an impaired ability of OPN-deficient mice to attract LCs/DCs to draining lymph nodes. In conclusion, OPN is an important factor in the initiation of CHS by guiding LCs/DCs from skin into lymphatic organs.
MEF2 negatively regulates learning-induced structural plasticity and memory formation
Authors: Christina J. Cole, Valentina Mercaldo, Leonardo Restivo, Adelaide P. Yiu, Melanie J. Sekeres, Jin Hee Han, Gisella Vetere, Tetyana Pekar, P. Joel Ross, Rachael L. Neve, Paul W. Frankland, Sheena A. Josselyn
Journal: Nature Neuroscience (2012)
Non-specific interstitial pneumonia as pulmonary involvement of systemic sclerosis
Authors: J Fujita
Journal: Annals of the Rheumatic Diseases (2001)

The pathological features of lung disease in nine patients with systemic sclerosis (SSc) were evaluated. The patients comprised one man and eight women, with a median age of 58 years. SSc was diagnosed according to the criteria of the American Rheumatism Association. In all patients, high resolution computed radiographic scanning of the lungs (HRCT) was performed, and apparent honeycomb formation was seen in four patients. Pathologically, four patients were diagnosed with usual interstitial pneumonia (UIP), three with non-specific interstitial pneumonia (NSIP) group II, one NSIP group II–III, and one NSIP group II with diffuse alveolar damage. HRCT showed no apparent honeycomb formations in patients diagnosed with NSIP. This is the first report describing NSIP as a pulmonary complication of SSc.
Primary chemotherapy in operable breast carcinoma comparing CMF (cyclophosphamide, methotrexate, 5-fluorouracil) with an anthracycline-containing regimen: short-term responses translated into long-term outcomes
Authors: G. Cocconi, B. Di Blasio, C. Boni, G. Bisagni, E. Rondini, M.A. Bella, F. Leonardi, L. Savoldi, C. Vallisneri, R. Camisa, P. Bruzzi
Journal: Annals of Oncology (2005)
The value of synovial fluid assays in the diagnosis of joint disease: a literature survey
Authors: A Swan
Journal: Annals of the Rheumatic Diseases (2002)

To carry out a critical appraisal of the literature in an attempt to assess the current value of synovial fluid (SF) analysis in the diagnosis of joint disease.A literature search was undertaken using the Medline, Biomed, Bids, Pubmed, and Embase electronic databases using the keywords: synovial fluid (SF) analysis, SF crystals, joint sepsis, acute arthritis, and SF cell counts, cytology, biomarkers, and microbiology.Publications fell into three main categories. Firstly, reports assessing the value of the three traditional assays (microbiology, white blood cell counts, and microscopy for pathogenic crystals). For these quality control evidence was found to be sparse, and tests for sensitivity, specificity, and reliability showed worrying variations. These poor standards in SF analysis may be due to lack of inclusion of some tests within routine pathology services. Secondly, claims for the usefulness of "new" assays (cytology and biochemical markers). For cytology, the supporting evidence was mainly anecdotal and there were no reports on specificity, sensitivity, and reliability. Interpretation difficulties are a major hindrance to the clinical use of biochemical assays, which remain primarily research tools. Finally, work on the diagnostic value of SF analysis in general. The appraisal confirmed that SF analysis remains of major diagnostic value in acute arthritis, where septic arthritis or crystal arthropathy is suspected, and in intercritical gout.Given the importance of SF tests, rationalisation of their use, together with improved quality control, should be immediate priorities. Further investigation is recommended into the contribution of SF inspection and white cell counts to diagnosis, as well as of the specificity and sensitivity of SF microbiological assays, crystal identification, and cytology.
Adjuvants That Improve the Ratio of Antigen-Specific Effector to Regulatory T Cells Enhance Tumor Immunity
Authors: Rachel Perret, Sophie R. Sierro, Natalia K. Botelho, Stéphanie Corgnac, Alena Donda, Pedro Romero
Journal: Cancer Research (2013)

Abstract Antitumor immunity is strongly influenced by the balance of tumor antigen-specific effector T cells (Teff) and regulatory T cells (Treg). However, the impact that vaccine adjuvants have in regulating the balance of antigen-specific T-cell populations is not well understood. We found that antigen-specific Tregs were induced following subcutaneous vaccination with either OVA or melanoma-derived peptides, with a restricted expansion of Teffs. Addition of the adjuvants CpG-ODN or Poly(I:C) preferentially amplified Teffs over Tregs, dramatically increasing the antigen-specific Teff:Treg ratios and inducing polyfunctional effector cells. In contrast, two other adjuvants, imiquimod and Quil A saponin, favored an expansion of antigen-specific Tregs and failed to increase Teff:Treg ratios. Following therapeutic vaccination of tumor-bearing mice, high ratios of tumor-specific Teffs:Tregs in draining lymph nodes were associated with enhanced CD8+ T-cell infiltration at the tumor site and a durable rejection of tumors. Vaccine formulations of peptide+CpG-ODN or Poly(I:C) induced selective production of proinflammatory type I cytokines early after vaccination. This environment promoted CD8+ and CD4+ Teff expansion over that of antigen-specific Tregs, tipping the Teff to Treg balance to favor effector cells. Our findings advance understanding of the influence of different adjuvants on T-cell populations, facilitating the rational design of more effective cancer vaccines. Cancer Res; 73(22); 6597–608. ©2013 AACR.
Upper airway obstruction and raised intracranial pressure in children with craniosynostosis
Authors: S Gonsalez, R Hayward, B Jones, R Lane
Journal: European Respiratory Journal (1997)

In children with craniosynostosis, raised intracranial pressure (ICP) and upper airway obstruction (UAO) are both common features. However, potential interactions between UAO and ICP during sleep are poorly understood. The aim of the present study was to compare the levels of ICP during sleep between a group of patients with syndromic craniosynostosis (with facial involvement and consequent UAO) and a group of control patients with isolated unicoronal synostosis (with no facial involvement and normal upper airways). Polygraphic cardiorespiratory sleep studies with continuous monitoring of ICP were performed during unsedated sleep in 13 children with syndromic craniosynostosis and 7 control patients with isolated unicoronal synostosis only. In the syndromic group, UAO was present in 11 out of 13 patients, with 8 out of 13 having frank obstructive sleep apnoea. In contrast, none of the control patients showed signs of UAO during sleep. There was no evidence of central apnoeas in any of the patients studied. Clinical histories taken from parents tended to underestimate the severity of the respiratory problems. Elevated ICP was seen in 10 of the 13 syndromic patients, with borderline raised ICP in the remaining three cases. In contrast, raised ICP was seen in only 3 of the 7 control patients, with borderline raised levels in 2 of the 7. For both patient groups, ICP was higher during active sleep compared to quiet sleep. Multiple regression analysis showed that ICP during active sleep was dependent upon disease severity (unicoronal/ multiple synostosis) and to the baseline ICP level during quiet sleep. Both raised ICP and airway obstruction were more apparent during active sleep. There was a significant correlation between severity of UAO and increased ICP in active sleep. We conclude that obstructive respiratory problems are frequent in the syndromic patients, and can be severe in a large proportion of cases; intracranial hypertension is also frequent in this group. Further studies are required to investigate the possibility of a causal relationship between upper airway obstruction and raised intracranial pressure.
Prenatal and childhood infections: implications for the development and treatment of childhood asthma
Authors: Oliver Fuchs, Erika von Mutius
Journal: The Lancet Respiratory Medicine (2013)

Bacterial and viral infections occur early and recurrently in life and thereby impose a substantial disease burden. Besides causing clinical symptoms, a potential role of infection in the development of the asthma syndrome later in life has also been suggested. However, whether bacterial and viral infections unmask host factors in children at risk of asthma or whether they directly cause asthma remains unclear; both viewpoints could be justified, but the underlying mechanisms are complex and poorly understood. Recently, the role of the bacterial microbiome has been emphasised. But data are still sparse and future studies are needed for definitive conclusions to be made. In this Review, we discuss present knowledge of viruses and bacteria that infect and colonise the respiratory tract and mucosal surfaces, including their timepoint of action, host factors related to infection, and their effect on childhood asthma. Childhood asthma could be the result of a combination of altered host susceptibility and infectious agents.
Growth Factors in Breast Cancer
Authors: ROBERT B. DICKSON, MARC E. LIPPMAN
Journal: Endocrine Reviews (1995)

A. Hormonal control of mammary development, proliferation, and lactational defferentation DEVELOPMENT of the normal breast, carcinogenesis of its epithelium breast, and progression of breast cancer are regulated by hormonal factors. The best defined of these factors are the endocrine steroids, peptides, and other molecules produced by the secretory cells of the ovaries, pituitary, endocrine pancreas, thyroid, and adrenal cortex. After their initial interaction with either nuclear or cell surface receptors, these hormones regulate cellular function. In addition, normal and malignant mammary tissues are able to synthesize locally acting hormone-like substances. One class of these factors is known as the paracrine hormones, factors released by one cell type which then modulate the function of neighboring cells of the same or different mammary cell type. A recently described variation on this theme is the class of juxtacrine factors. These factors are growth-regulatory molecules that remain exposed on a cell surface and modulate adjacent cells by contact. A third general class of local factors is that of the autocrine (or intracrine) hormones, soluble molecules synthesized by one cell type that act back on the same cell type through surface or intracellular receptors. It is of considerable interest that after their synthesis, polypeptide factors may be routed either to a cell surface receptor or to a nuclear site.
Calcium, Phosphate, and Parathyroid Hormone Levels in Combination and as a Function of Dialysis Duration Predict Mortality
Authors: Lesley A. Stevens, Ognjenka Djurdjev, Savannah Cardew, E. C. Cameron, Adeera Levin
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Current literature suggests associations between abnormal mineral metabolism (MM) to cardiovascular disease in dialysis populations, with conflicting results. MM physiology is complex; therefore, it was hypothesized that constellations of MM parameters, reflecting this complexity, would be predictive of mortality and that this effect would be modified by dialysis duration (DD). Prevalent dialysis patients in British Columbia, Canada, who had measurements of calcium (Ca), phosphate (Pi), and parathyroid hormone (iPTH) between January and March 2000 were followed prospectively until December 2002. Statistical analysis included Cox proportional hazard models with Ca, Pi, and iPTH alone and in combination as explanatory variables; analyses were stratified by DD. The 515 patients included in this analysis represent British Columbia and Canadian dialysis populations: 69% were on hemodialysis, mean age was 60 ± 17 yr, 40% were female, and 34% had diabetes. Mean Ca and Pi values were 2.32 ± 0.22 mmol/L and 1.68 ± 0.59 mmol/L, respectively, and median iPTH was 15.8 pmol/L (25th to 75th percentile: 6.9 to 37.3 pmol/L). Serum Pi, after adjusting for demographic, dialysis type and adequacy, hemoglobin, and albumin, independently predicted mortality (risk ratio [RR], 1.56 per 1 mmol/L; 95% confidence interval [CI], 1.15 to 2.12; P = 0.004). When combinations of parameters were modeled (overall P = 0.003), the combinations of high serum Pi and Ca with high iPTH (RR, 3.71; 95% CI, 1.53 to 9.03; P = 0.004) and low iPTH (RR, 4.30; 95% CI, 2.01 to 9.22; P < 0.001) had highest risks for mortality as compared with the combination of high iPTH with normal serum Ca and Pi that had the lowest mortality and was used as index category. These effects varied across different strata of DD. This analysis demonstrates the importance of examining combinations of MM parameters as opposed to single variables alone and the effect of DD. In so doing, the complex interaction of time and MM can begin to be understand. Further exploration is required.
MECHANISMS INVOLVED IN GASTRIC MUCOSAL RESISTANCE TO INJURY
Authors: D Fromm
Journal: Annual Review of Medicine (1987)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Direct evidence that the greater contractility of resistance vessels in spontaneously hypertensive rats is associated with a narrowed lumen, a thickened media, and an increased number of smooth muscle cell layers.
Authors: M J Mulvany, O K Hansen, C Aalkjaer
Journal: Circulation Research (1978)

The mechanical and morphological properties of segments of certain precisely defined resistance vessels (approximately 150 micrometer lumen diameter) in the mesenteric bed of spontaneously hypertensive (SHR) and normotensive (WKY) rats have been compared in vitro under carefully controlled conditions and also after fixation. At a given transmural pressure, the relaxed SHR vessels (compared with the WKY vessels) would have had a 16% smaller lumen diameter (P less than 0.01) and a 49% thicker media (P less than 0.005), so that the media volume per unit segment length was 31% greater (P less than 0.05). The smooth muscle cells were arranged circumferentially in about four layers in the SHR vessels and in about three layers in the WKY vessels. The SHR active wall tension in response to potassium was 53% greater (P less than 0.02) and to norepinephrine was 50% greater (P less than 0.01) than for WKY. However, the ED50 values for the norepinephrine dose-response curves were similar (approximately 5 micrometer). Activation with potassium plus norepinephrine gave greater responses in both vessel types, than with either agent alone, but the SHR responses were on average only 19% greater than the WKY (P less than 0.10). However, under these conditions, the SHR vessels would have been able to contract against 45% greater transmural pressures (P less than 0.001) because of their smaller lumen. On maximal activation, the mean force developed by each cell (approximately 3.85 micro N) was the same in both vessel types, even though on average (P = 0.10) the SHR cells had a 21% greater cross-sectional area. The results support the Folkow hypothesis that in genetic hypertension the increased peripheral resistance is associated with structural changes in the resistance vessels.
Combining Microbubbles and Ultrasound for Drug Delivery to Brain Tumors: Current Progress and Overview
Authors: Hao-Li Liu, Ching-Hsiang Fan, Chien-Yu Ting, Chih-Kuang Yeh
Journal: Theranostics (2014)

Malignant glioma is one of the most challenging central nervous system (CNS) diseases, which is typically associated with high rates of recurrence and mortality.Current surgical debulking combined with radiation or chemotherapy has failed to control tumor progression or improve glioma patient survival.Microbubbles (MBs) originally serve as contrast agents in diagnostic ultrasound but have recently attracted considerable attention for therapeutic application in enhancing blood-tissue permeability for drug delivery.MB-facilitated focused ultrasound (FUS) has already been confirmed to enhance CNS-blood permeability by temporally opening the blood-brain barrier (BBB), thus has potential to enhance delivery of various kinds of therapeutic agents into brain tumors.Here we review the current preclinical studies which demonstrate the reports by using FUS with MB-facilitated drug delivery technology in brain tumor treatment.In addition, we review newly developed multifunctional theranostic MBs for FUS-induced BBB opening for brain tumor therapy.
The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients
Authors: A. Fariña-Sarasqueta, G. van Lijnschoten, E. Moerland, G.-J. Creemers, V.E.P.P. Lemmens, H.J.T. Rutten, A.J.C. van den Brule
Journal: Annals of Oncology (2010)