tbuckley/cabot-search huggingface dataset:
Understanding recent trends in incidence of invasive breast cancer in Norway: age-period-cohort analysis based on registry data on mammography screening and hormone treatment use
Authors: H. Weedon-Fekjaer, K. Bakken, L. J. Vatten, S. Tretli
Journal: BMJ (2012)

<b>Objective</b> To quantify the separate contributions of menopausal hormone treatment and mammography screening activities on trends in incidence of invasive breast cancer between 1987 and 2008. <b>Design</b> Population study using aggregated data analysed by an extended age-period-cohort model. <b>Setting</b> Norway. <b>Population</b> Norwegian women aged 30-90 between 1987 and 2008, including 50 102 newly diagnosed cases of invasive breast cancer. <b>Main outcomes measures</b> Attributable proportions of mammography screening and hormone treatment to recent incidence of invasive breast cancer, and the remaining variation in incidence after adjustment for mammography screening and hormone treatment. <b>Results</b> The incidence of invasive breast cancer in Norway increased steadily until 2002, levelled off, and then declined from 2006. All non-linear changes in incidence were explained by use of hormone treatment and mammography screening activities, with about similar contributions of each factor. In 2002, when the incidence among women aged 50-69 was highest, an estimated 23% of the cases in that age group could be attributed to mammography screening and 27% to use of hormone treatment. <b>Conclusions</b> Changes in incidence trends of invasive breast cancer since the early 1990s may be fully attributed to mammography screening and hormone treatment, with about similar contributions of each factor.
Microarray Analysis Reveals Glucocorticoid-Regulated Survival Genes That Are Associated With Inhibition of Apoptosis in Breast Epithelial Cells
Authors: Wei Wu, Shamita Chaudhuri, Deanna R. Brickley, Diana Pang, Theodore Karrison, Suzanne D. Conzen
Journal: Cancer Research (2004)

Activation of the glucocorticoid receptor (GR) results in diverse physiological effects depending on cell type. For example, glucocorticoids (GC) cause apoptosis in lymphocytes but can rescue mammary epithelial cells from growth factor withdrawal-induced death. However, the molecular mechanisms of GR-mediated survival remain poorly understood. In this study, a large-scale oligonucleotide screen of GR-regulated genes was performed. Several of the genes that were found to be induced 30 min after GR activation encode proteins that function in cell survival signaling pathways. We also demonstrate that dexamethasone pretreatment of breast cancer cell lines inhibits chemotherapy-induced apoptosis in a GR-dependent manner and is associated with the transcriptional induction of at least two genes identified in our screen, serum and GC-inducible protein kinase-1 (SGK-1) and mitogen-activated protein kinase phosphatase-1 (MKP-1). Furthermore, GC treatment alone or GC treatment followed by chemotherapy increases both SGK-1 and MKP-1 steady-state protein levels. In the absence of GC treatment, ectopic expression of SGK-1 or MKP-1 inhibits chemotherapy-induced apoptosis, suggesting a possible role for these proteins in GR-mediated survival. Moreover, specific inhibition of SGK-1 or MKP-1 induction by the introduction of SGK-1- or MKP-1-small interfering RNA reversed the anti-apoptotic effects of GC treatment. Taken together, these data suggest that GR activation in breast cancer cells regulates survival signaling through direct transactivation of genes that encode proteins that decrease susceptibility to apoptosis. Given the widespread clinical administration of dexamethasone before chemotherapy, understanding GR-induced survival mechanisms is essential for achieving optimal therapeutic responses.
Short-Term Changes in Ki-67 during Neoadjuvant Treatment of Primary Breast Cancer with Anastrozole or Tamoxifen Alone or Combined Correlate with Recurrence-Free Survival
Authors: Mitch Dowsett, Ian E. Smith, Steve R. Ebbs, J. Michael Dixon, Anthony Skene, Clive Griffith, Irene Boeddinghaus, Janine Salter, Simone Detre, Margaret Hills, Susan Ashley, Stephen Francis, Geraldine Walsh
Journal: Clinical Cancer Research (2005)

Neoadjuvant (preoperative) therapy for breast cancer may allow for the development of intermediate markers of treatment benefit, thereby circumventing the need for efficacy trials of adjuvant therapy, which require much larger patient numbers and longer follow-up. The aim of this study--as part of the Immediate Preoperative "Arimidex" (anastrozole), Tamoxifen, or Arimidex Combined with Tamoxifen (IMPACT) trial (n = 330)--was to test the hypotheses that changes in Ki-67 after 2 weeks and/or 12 weeks: (i) differed between treatments, (ii) predicted clinical tumor response, and/or (iii) may predict long-term outcome differences between treatments in adjuvant therapy.The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial compared these same agents in the adjuvant setting. Biomarkers were measured in biopsy specimens taken before and after 2 and 12 weeks of treatment.Suppression of the proliferation marker Ki-67 after 2 and 12 weeks was significantly greater with anastrozole than with tamoxifen (P = 0.004 and P < 0.001) but was similar between tamoxifen and the combination (P = 0.600 and P = 0.912). This result closely parallels that seen for the relative recurrence-free survival with the treatments after a median follow-up of 31 months in the ATAC trial in 9,366 patients. Against expectations, apoptosis was not increased in any of the treatment arms.The data indicate that short-term changes in proliferation in the neoadjuvant setting may be able to predict outcome during adjuvant use of the same treatments. If this can be confirmed, these findings could lead to a profound change in approaches to drug development in breast cancer. The data indicate that estrogen is not an important survival factor for human breast cancer cells.
Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study
Authors: I. M Stratton
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes. <b>Design:</b> Prospective observational study. <b>Setting:</b> 23 hospital based clinics in England, Scotland, and Northern Ireland. <b>Participants:</b> 4585 white, Asian Indian, and Afro-Caribbean UKPDS patients, whether randomised or not to treatment, were included in analyses of incidence; of these, 3642 were included in analyses of relative risk. <b>Outcome measures:</b> Primary predefined aggregate clinical outcomes: any end point or deaths related to diabetes and all cause mortality. Secondary aggregate outcomes: myocardial infarction, stroke, amputation (including death from peripheral vascular disease), and microvascular disease (predominantly retinal photo-coagulation). Single end points: non-fatal heart failure and cataract extraction. Risk reduction associated with a 1% reduction in updated mean HbA<sub>1c</sub> adjusted for possible confounders at diagnosis of diabetes. <b>Results:</b> The incidence of clinical complications was significantly associated with glycaemia. Each 1% reduction in updated mean HbA<sub>1c</sub> was associated with reductions in risk of 21% for any end point related to diabetes (95% confidence interval 17% to 24%, P&lt;0.0001), 21% for deaths related to diabetes (15% to 27%, P&lt;0.0001), 14% for myocardial infarction (8% to 21%, P&lt;0.0001), and 37% for microvascular complications (33% to 41%, P&lt;0.0001). No threshold of risk was observed for any end point. <b>Conclusions:</b> In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia. Any reduction in HbA<sub>1c</sub> is likely to reduce the risk of complications, with the lowest risk being in those with HbA<sub>1c</sub> values in the normal range (&lt;6.0%).
Physiological characteristics of high-frequency one-lung ventilation in thoracic surgery
Authors: Mikhail Kontorovich, Serghey Skornyakov, Igor Medvinsky, Dmytry Eremeev
Journal: European Respiratory Journal (2013)

INTRODUCTION. We believe no alternative use during operations in the light of high-frequency jet ventilation. HFJV provides excellent oxygenation of arterial blood in the lungs supports expanded position without the use of recruitment-maneuver, increases venous return and cardiac output, reducing intrapulmonary shunting.  MATERIALS AND METHODS. The two groups are comparable (in terms of volume of surgery, comorbidities, age) of 50 patients compared the parameters of gas exchange and hemodynamics in patients undergoing surgery for lung during one-lung convective (OCMV) and one-lung high-frequency (OHFJV) ventilation.  RESULTS. Results of the study demonstrated a reduction in OHFJV versus OCMV: PIP - to 26,5%; Pes - by 81.6%, PVR - by 41.7%; Qs/Qt - by 45.5% and the increase in PaO2 – 66. 1%, MI - by 91.0%; VA - by 47.8%, CVP - by 28.3% while maintaining the normal pH of 7.42 and PaCO2 = 34.5 mm Hg.  CONCLUSIONS. Under conditions of OHFJV, even a complete atelectasis of one lung does not go along with a considerable disorder of gas exchange in contrast to OCMV. This enabled a wider application of this kind of ventilation for lung surgeries on patients with distinct gas exchange and hemodynamics disorders.
HIV-1–specific CD4+ T lymphocyte turnover and activation increase upon viral rebound
Authors: Thomas J. Scriba, Hua-Tang Zhang, Helen L. Brown, Annette Oxenius, Norbert Tamm, Sarah Fidler, Julie Fox, Jonathan N. Weber, Paul Klenerman, Cheryl L. Day, Michaela Lucas, Rodney E. Phillips
Journal: Journal of Clinical Investigation (2005)

HIV-specific CD4+ T helper lymphocytes are preferred targets for infection. Although complete interruption of combination antiretroviral therapy (ART) can form part of therapeutic manipulations, there is grave concern that the resumption of viral replication might destroy, perhaps irreversibly, these T helper populations. High viremia blocks the proliferation capacity of HIV-specific helper cells. However, cytokine production assays imply that some antigen-specific effector function is retained. Despite this careful work, it remains unclear whether the return of HIV-1 replication physically destroys HIV-1–specific T helper cells in the peripheral blood. Difficulties in producing stable peptide-MHC class II complexes and the very low frequencies of antigen-specific CD4+ T cells have delayed the application of this powerful technique. Here we employ HLA class II tetramers and validate a sensitive, quantitative cell-enrichment technique to detect HIV-1 T helper cells. We studied patients with early-stage HIV infection who were given a short, fixed course of ART as part of a clinical study. We did not find significant deletion of these cells from the peripheral circulation when ART was stopped and unfettered HIV replication returned. The turnover of these virus-specific cells increased and they adopted an effector phenotype when viremia returned.
Adenosine-mediated cardioprotection in the aging myocardium
Authors: L WILLEMS, K ASHTON, J HEADRICK
Journal: Cardiovascular Research (2004)

With aging, it appears the heart's ability to withstand injury declines markedly. Unfortunately, the incidence of ischemic disorders increases dramatically with age. Though the genesis of the ischemia-intolerant phenotype is incompletely understood (and likely multi-factorial), it may involve changes in intrinsic cardioprotective responses. In this respect we and others have interrogated the role of the adenosine receptor (AR) system in dictating ischemic tolerance and the impact of age on AR-mediated cardioprotection. It is intriguing to note ARs impact on many processes implicated in myocardial ‘aging’: adenosine counters Ca2+ influx and oxidant injury, modifies substrate metabolism to improve tolerance, is pro-angiogenic, inhibits myocardial fibrosis, and can limit apoptosis. Thus, dysregulation of the AR system could contribute to many features of aged hearts (including ischemic intolerance). The latter is borne out by observations that AR-mediated protective responses decline with intrinsic tolerance and that transgenic manipulation of the AR system restores intrinsic tolerance and protective responses in aged hearts. Mechanisms underlying failure in adenosinergic protection remain undefined. Here we review data on the effects of aging on cardiovascular AR transcription and expression, generation of signal (adenosine formation), and protective signaling coupled to ARs.
Comparison of single-breath and tidal breathing exhaled nitric oxide levels in infants
Authors: P.J. Franklin, S.W. Turner, R.C. Mutch, S.M. Stick
Journal: European Respiratory Journal (2004)

The aim of this study was to compare two different methods, tidal breathing (TB) and single-breath (SB), for measuring fractional exhaled nitric oxide (FE NO ) in infants. FE NO was measured in 71 infants with either recurrent wheeze (n=32), recurrent cough (n=16) or no symptoms (healthy, n=23) using both methods. For TB measurements five breaths were collected into a gas sampling bag (off-line reservoir sampling). The SB method was modified from the raised volume rapid thoraco-abdominal technique. Agreement between the two methods was investigated and both methods were used to compare FE NO in infants with and without symptoms. Flow dependence of SB FE NO was demonstrated using two expiratory flows (11 and 40 mL·s −1 ). There was a moderate correlation (r=0.60) but poor agreement between levels using the TB and SB methods. A significant difference in FE NO between healthy children and children with wheeze was found using the SB but not the TB method. Due to lower expiratory flow and reduced nasal nitric oxide contamination the single-breath technique may be more sensitive than the tidal breathing method for detecting differences in exhaled nitric oxide between infants with and without respiratory symptoms.
A6.15 Refractory Chronic Erythema Nodosum and Treatment with Anti TNF: Abstract A6.15 Table 1
Authors: J Uceda, R Hernández, L Mayordomo, JL Marenco
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Introduction</h3> Erythema nodosum septal panniculitis without vasculitis, characterised by acute episodes of inflammatory and painful subcutaneous nodules affecting, in most cases, the lower extremities. Remission of lesions occurs within 1–6 weeks without scarring or residual atrophy. There are, however, some cases which become chronic or reoccur. In 50% of cases we find an underlying cause. Treatment of acute outbreak involves rest and NSAIDs. The chronic or recurrent cases are treated with oral potassium iodide, cortic osteroids, colchicine, hydroxychloroquine or immunosuppressive agents. <h3>Objectives</h3> Description of the cases of refractory chronic erythema nodosum and review of the literature. <h3>Methods</h3> Selection of patients with refractory chronic erythema nodosum undergoing treatment with anti TNF in the Rheumatology unit from 2000 to 2010. Literature search using PubMed with keywords erythema nodosum and Adalimumab, Etanercept, Infliximab. <h3>Results</h3> See table 1. <h3>Conclusions</h3> In our sample, all cases have responded favourably to treatment with anti TNF. No adverse events were observed, except the occurrence of cutaneous psoriasis in one patients after infliximab treatment. In reviewing the literature we find that anti TNF paradoxically brings about an immediate response in erythema nodosum patients, however provokes erythema nodosum and others skin manifestations in patients with either rheumatic pathology or inflammatory bowel disease. [1, 2] <h3>Bibliography</h3> Clayton TH <i>et al</i>, Treatment of chronic erythema nodosum with infliximab. <i>Clin Exp Dermatol</i>. 2006 Nov; 31(6):823–4. Ortego-Centeno N <i>et al</i>, Refractory chronic erythema nodosum successfully treated with adalimumab. <i>J Eur Acad Dermatol Venereol</i>. 2007 Mar; 21(3):408–10.
Control of Macrophage Activation and Function by PPARs
Authors: Ajay Chawla
Journal: Circulation Research (2010)

Abstract: Macrophages, a key component of the innate defense against pathogens, participate in the initiation and resolution of inflammation, and in the maintenance of tissues. These diverse and at times antithetical functions of macrophages are executed via distinct activation states, ranging from classical to alternative to deactivation. Because the dysregulation of macrophage activation is pathogenically linked to various metabolic, inflammatory and immune disorders, regulatory proteins controlling macrophage activation have emerged as important new therapeutic targets. Here, the mechanisms by which peroxisome proliferator-activated receptors (PPARs) transcriptionally regulate macrophage activation in health and disease states, including obesity, insulin resistance and cardiovascular disease, are reviewed.
Dosage Thresholds for AAV2 and AAV8 Photoreceptor Gene Therapy in Monkey
Authors: Luk H. Vandenberghe, Peter Bell, Albert M. Maguire, Cassia N. Cearley, Ru Xiao, Roberto Calcedo, Lili Wang, Michael J. Castle, Alexandra C. Maguire, Rebecca Grant, John H. Wolfe, James M. Wilson, Jean Bennett
Journal: Science Translational Medicine (2011)

AAV2 and AAV8 viral vectors administered subretinally transduce retinal pigment epithelium and photoreceptors in monkey.
A computational approach for genome-wide mapping of splicing factor binding sites
Authors: Martin Akerman, Hilda David-Eden, Ron Y Pinter, Yael Mandel-Gutfreund
Journal: Genome biology (2009)

Alternative splicing is regulated by splicing factors that serve as positive or negative effectors, interacting with regulatory elements along exons and introns. Here we present a novel computational method for genome-wide mapping of splicing factor binding sites that considers both the genomic environment and the evolutionary conservation of the regulatory elements. The method was applied to study the regulation of different alternative splicing events, uncovering an interesting network of interactions among splicing factors.
Local warming and insertion of peripheral venous cannulas: single blinded prospective randomised controlled trial and single blinded randomised crossover trial
Authors: Rainer Lenhardt, Tanja Seybold, Oliver Kimberger, Brigitte Stoiser, Daniel I Sessler
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To determine whether local warming of the lower arm and hand facilitates peripheral venous cannulation. <b>Design:</b> Single blinded prospective randomised controlled trial and single blinded randomised crossover trial. <b>Setting:</b> Neurosurgical unit and haematology ward of university hospital. <b>Participants:</b> 100 neurosurgical patients and 40 patients with leukaemia who required chemotherapy. <b>Interventions:</b> Neurosurgical patients9 hands and forearms were covered for 15 minutes with a carbon fibre heating mitt. Patients were assigned randomly to active warming at 52°C or passive insulation (heater not activated). The same warming system was used for 10 minutes in patients with leukaemia. They were assigned randomly to active warming or passive insulation on day 1 and given alternative treatment during the subsequent visit. <b>Main outcome measures:</b> Primary: success rate for insertion of 18 gauge cannula into vein on back of hand. Secondary: time required for successful cannulation. <b>Results:</b> In neurosurgical patients, it took 36 seconds (95% confidence interval 31 to 40 seconds) to insert a cannula in the active warming group and 62 (50 to 74) seconds in the passive insulation group (P=0.002). Three (6%) first attempts failed in the active warming group compared with 14 (28%) in the passive insulation group (P=0.008). The crossover study in patients with leukaemia showed that insertion time was reduced by 20 seconds (8 to 32, P=0.013) with active warming and that failure rates at first attempt were 6% with warming and 30% with passive insulation (P&lt;0.001). <b>Conclusions:</b> Local warming facilitates the insertion of peripheral venous cannulas, reducing both time and number of attempts required. This may decrease the time staff spend inserting cannulas, reduce supply costs, and improve patient satisfaction.
Yellow Fever: 100 Years of Discovery
Authors: J. Erin Staples
Journal: JAMA (2008)

The article describes a series of experiments conducted to explore how yellow fever is propagated from individual to individual and how the contagium is spread within households.The study was conducted in an experimental sanitary station in Cuba, where exposures and movements could be completely controlled.During the investigation, 12 nonimmune persons underwent different exposures, including mosquitoes that had fed on yellow fever patients, blood from infected patients, and fomites belonging to infected patients.
Pincer nail deformity and pseudo-Kaposi's sarcoma: complications of an artificial arteriovenous fistula for haemodialysis
Authors: S.M. Hwang, S.H. Lee, S.K. Ahn
Journal: British Journal of Dermatology (1999)

Journal Article Pincer nail deformity and pseudo‐Kaposi's sarcoma: complications of an artificial arteriovenous fistula for haemodialysis Get access S.M. Hwang, S.M. Hwang Department of Dermatology, Yonsei University Wonju College of Medicine, 162 Ilsan‐Dong, Wonju, Kangwon‐Do 220‐701, South Korea Search for other works by this author on: Oxford Academic Google Scholar S.H. Lee, S.H. Lee Department of Dermatology, Yonsei University Wonju College of Medicine, 162 Ilsan‐Dong, Wonju, Kangwon‐Do 220‐701, South Korea Search for other works by this author on: Oxford Academic Google Scholar S.K. Ahn S.K. Ahn Department of Dermatology, Yonsei University Wonju College of Medicine, 162 Ilsan‐Dong, Wonju, Kangwon‐Do 220‐701, South Korea Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 141, Issue 6, 1 December 1999, Pages 1129–1132, https://doi.org/10.1046/j.1365-2133.1999.03219.x Published: 01 December 1999