tbuckley/cabot-search huggingface dataset:
XBP1 Is Essential for Survival under Hypoxic Conditions and Is Required for Tumor Growth
Authors: Lorenzo Romero-Ramirez, Hongbin Cao, Daniel Nelson, Ester Hammond, Ann-Hwee Lee, Hiderou Yoshida, Kazutoshi Mori, Laurie H. Glimcher, Nicholas C. Denko, Amato J. Giaccia, Quynh-Thu Le, Albert C. Koong
Journal: Cancer Research (2004)

Abstract Hypoxia within solid tumors is a major determinant of outcome after anticancer therapy. Analysis of gene expression changes during hypoxia indicated that unfolded protein response genes were one of the most robustly induced groups of genes. In this study, we investigated the hypoxic regulation of X-box binding protein (XBP1), a major transcriptional regulator of the unfolded protein response. Hypoxia induced XBP1 at the transcriptional level and activated splicing of its mRNA, resulting in increased levels of activated XBP1 protein. After exposure to hypoxia, apoptosis increased and clonogenic survival decreased in XBP1-deficient cells. Loss of XBP1 severely inhibited tumor growth due to a reduced capacity for these transplanted tumor cells to survive in a hypoxic microenvironment. Taken together, these studies directly implicate XBP1 as an essential survival factor for hypoxic stress and tumor growth.
Prognostic Factors in Renal Cell Carcinoma: Association of Preoperative Sodium Concentration with Survival
Authors: Naveen S. Vasudev, Janet E. Brown, Sarah R. Brown, Rumana Rafiq, Ruth Morgan, Poulam M. Patel, Dearbhaile O'Donnell, Patricia Harnden, Mark Rogers, Kim Cocks, Kirsty Anderson, Alan Paul, Ian Eardley, Peter J. Selby, Rosamonde E. Banks
Journal: Clinical Cancer Research (2008)

Conventional renal cell carcinoma (RCC) has a variable natural history, and determining individual prognosis is important to guide management. We have examined the prognostic significance of a large number of hematologic and biochemical variables, as well as traditional tumor-related factors in patients with RCC.Patients undergoing nephrectomy for newly diagnosed RCC between September 1998 and March 2005 were invited to participate. Clinical, pathologic, and laboratory data were recorded in each case, and immunophenotyping was carried out on a subset of patients. A planned subset analysis of patients presenting with N0M0 disease was done.Two hundred twelve patients with RCC formed the study population. In addition to tumor-related factors, multivariate analyses revealed preoperative serum sodium concentration to be independently and significantly associated with overall survival and disease-free survival when considered as both a continuous variable and when dichotomized to above and below the median value [139 mmol/L; reference range 135-145 mmol/L, hazard ratio 0.44, 95% confidence interval (95% CI) 0.22-0.88, P = 0.014]. Five-year overall survival estimates for patients above and below the median serum sodium were 67.6% (95% CI 54.2-80.9) and 44.3% (95% CI 32.8-55.8), respectively. These findings persisted in the N0M0 subgroup analysis.We have confirmed the prognostic value of traditional tumor-related factors but, to our knowledge, these are the first data to show that low preoperative sodium concentration may be an important factor associated with reduced survival in patients with RCC, suggesting that serum sodium should be considered with established prognostic variables in modeling survival in RCC.
An autosomal dominant major gene confers predisposition to pulmonary tuberculosis in adults
Authors: Jamila El Baghdadi, Marianna Orlova, Andrea Alter, Brigitte Ranque, Mohamed Chentoufi, Faouzia Lazrak, Moulay Idriss Archane, Jean-Laurent Casanova, Abdellah Benslimane, Erwin Schurr, Laurent Abel
Journal: The Journal of Experimental Medicine (2006)

The molecular basis of genetic predisposition to pulmonary tuberculosis in adults remains largely elusive. Few candidate genes have consistently been implicated in tuberculosis susceptibility, and no conclusive linkage was found in two previous genome-wide screens. We report here a genome-wide linkage study in a total sample of 96 Moroccan multiplex families, including 227 siblings with microbiologically and radiologically proven pulmonary tuberculosis. A genome-wide scan conducted in half the sample (48 families) identified five regions providing suggestive evidence (logarithm of the odds [LOD] score &amp;gt;1.17; P &amp;lt; 0.01) for linkage. These regions were then fine-mapped in the total sample of 96 families. A single region of chromosome 8q12-q13 was significantly linked to tuberculosis (LOD score = 3.49; P = 3 × 10−5), indicating the presence of a major tuberculosis susceptibility gene. Linkage was stronger (LOD score = 3.94; P = 10−5) in the subsample of 39 families in which one parent was also affected by tuberculosis, whereas it was much lower (LOD score = 0.79) in the 57 remaining families without affected parents, supporting a dominant mode of inheritance of the major susceptibility locus. These results provide direct molecular evidence that human pulmonary tuberculosis has a strong genetic basis, and indicate that the genetic component involves at least one major locus with a dominant susceptibility allele.
Weak and fragmented NHS commissioning threatens service improvement
Authors: A. O'Dowd
Journal: BMJ (2014)

Commissioning since last year’s NHS reorganisation took effect is too weak, fragmented, and overpopulated with bodies to the extent that it is threatening expected improvements in services, MPs have warned.

In a report published on 12 February by the parliamentary health select committee,1 MPs also warned that low pay rises for NHS staff, bureaucracy that was blocking service change, and an imbalance in funding between health and social care were all hampering improvements in the NHS.

The report says that the health and care system still needs major change before it can start to meet the needs of patients.

It cites the facts that 48% of NHS trusts in England are forecasting a deficit in the current financial …
HOW DOES LITHIUM WORK ON MANIC DEPRESSION? Clinical and Psychological Correlates of the Inositol Theory
Authors: R. H. Belmaker, M.D, Yuly Bersudsky, M.D, Galila Agam, M.D, Joseph Levine, M.D, Ora Kofman, M.D
Journal: Annual Review of Medicine (1996)

▪ Abstract How lithium works in manic-depressive illness is unknown. Recently, however, a powerful hypothesis has been gaining momentum. Distinguished by its testability and clinical implications, the inositol depletion hypothesis of lithium action is relevant to treatment of lithium side effects, to the development of new compounds with the clinical profile of lithium, and to new experimental treatment of depression.
Validation of Biomarkers That Complement CA19.9 in Detecting Early Pancreatic Cancer
Authors: Alison Chan, Ioannis Prassas, Apostolos Dimitromanolakis, Randall E. Brand, Stefano Serra, Eleftherios P. Diamandis, Ivan M. Blasutig
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer mortality. Carbohydrate antigen 19.9 (CA19.9), the only tumor marker available to detect and monitor PDAC, is not sufficiently sensitive and specific to consistently differentiate early cancer from benign disease. In this study, we aimed to validate recently discovered serum protein biomarkers for the early detection of PDAC and ultimately develop a biomarker panel that could discriminate PDAC from other benign disease better than the existing marker CA19.9. Patients and Methods: We performed a retrospective blinded evaluation of 400 serum samples collected from individuals recruited on a consecutive basis. The sample population consisted of 250 individuals with PDAC at various stages, 130 individuals with benign conditions and 20 healthy individuals. The serum levels of each biomarker were determined by ELISAs or automated immunoassay. Results: By randomly splitting matched samples into a training (n = 186) and validation (n = 214) set, we were able to develop and validate a biomarker panel consisting of CA19.9, CA125, and LAMC2 that significantly improved the performance of CA19.9 alone. Improved discrimination was observed in the validation set between all PDAC and benign conditions (AUCCA19.9 = 0.80 vs. AUCCA19.9+CA125+LAMC2 = 0.87; P &amp;lt; 0.005) as well as between early-stage PDAC and benign conditions (AUCCA19.9 = 0.69 vs. AUCCA19.9+CA125+LAMC2 = 0.76; P &amp;lt; 0.05) and between early-stage PDAC and chronic pancreatitis (CP; AUCCA19.9 = 0.59 vs. AUCCA19.9+CA125+LAMC2 = 0.74; P &amp;lt; 0.05). Conclusions: The data demonstrate that a serum protein biomarker panel consisting of CA125, CA19.9, and LAMC2 is able to significantly improve upon the performance of CA19.9 alone in detecting PDAC. Clin Cancer Res; 20(22); 5787–95. ©2014 AACR.
DETERMINATION OF THE QUANTITY OF SECRETING TISSUE IN THE LIVING KIDNEY
Authors: C. K. Watanabe, Jean Oliver, Thomas Addis
Journal: The Journal of Experimental Medicine (1918)

1. Under the strain induced by the administration of urea, it is possible to demonstrate the relation between the degree of anatomical damage in the kidney and the degree of defect in the urea-excreting capacity induced by uranium. 2. The closest correlation between structure and function was obtained when the ratio between the urea content of the urine and of the blood was used as the measure of function.
Effectiveness of skin protection measures in prevention of occupational hand eczema: results of a prospective randomized controlled trial over a follow-up period of 1 year
Authors: B. Kütting, T. Baumeister, W. Weistenhöfer, A. Pfahlberg, W. Uter, H. Drexler
Journal: British Journal of Dermatology (2009)

Journal Article Effectiveness of skin protection measures in prevention of occupational hand eczema: results of a prospective randomized controlled trial over a follow‐up period of 1 year Get access B. Kütting, B. Kütting Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, and Birgitta Kütting. E‐mail: birgitta.kuetting@ipasum.uni‐erlangen.de Search for other works by this author on: Oxford Academic Google Scholar T. Baumeister, T. Baumeister Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, and Search for other works by this author on: Oxford Academic Google Scholar W. Weistenhöfer, W. Weistenhöfer Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, and Search for other works by this author on: Oxford Academic Google Scholar A. Pfahlberg, A. Pfahlberg Department of Medical Informatics, Biometry and Epidemiology, Friedrich‐Alexander University of Erlangen‐Nuremberg, D‐91054 Erlangen, Germany Search for other works by this author on: Oxford Academic Google Scholar W. Uter, W. Uter Department of Medical Informatics, Biometry and Epidemiology, Friedrich‐Alexander University of Erlangen‐Nuremberg, D‐91054 Erlangen, Germany Search for other works by this author on: Oxford Academic Google Scholar H. Drexler H. Drexler Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, and Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 2, 1 February 2010, Pages 362–370, https://doi.org/10.1111/j.1365-2133.2009.09485.x Published: 01 February 2010
Sustained protection against distilled water provocation by a single dose of salmeterol in patients with asthma
Authors: GP Bootsma, PN Dekhuijzen, J Festen, JW Lammers, PG Mulder, CL van Herwaarden
Journal: European Respiratory Journal (1997)

The long-acting beta2-agonist salmeterol inhibits in vitro the release of inflammatory mediators up to 20 h. These mediators are involved in ultrasonically nebulized distilled water (UNDW)-induced bronchoconstriction. We investigated whether salmeterol provides prolonged protection against UNDW provocation and whether this effect was paralleled by its bronchodilator effects. Nineteen asthmatic patients (mean forced expiratory volume in one second (FEV1) 84.8% predicted, mean provocative concentration of histamine producing a 20% decrease in FEV1 0.65 mg x mL(-1)) participated in this randomized, double-blind, placebo-controlled crossover trial. After measuring baseline FEV1, patients inhaled 50 microg salmeterol or placebo by metered-dose inhaler. FEV1 was measured after 20 and 40 min, and UNDW provocations and FEV1 measurements were performed after 10, 20 and 34 h. Compared to placebo, salmeterol caused marked bronchodilatation from 20 min up to 20 h after inhalation. Salmeterol also provided more than 20 h of protection against UNDW provocation (still more than one doubling dose). Protection beyond the period of bronchodilatation did not occur. Eleven subjects had a significant reduction in provocative dose of UNDW causing a 20% fall in FEV1 (PD20,UNDW) values between 10 and 20 h, at a time when there was still persistent bronchodilation. No correlation existed between changes in FEV1 and changes in PD20,UNDW. From the equations of regression lines between FEV1 and corresponding PD20,UNDW values, it was calculated that only approximately 25% of the afforded protection was explained by bronchodilatation. In conclusion, a single dose of salmeterol induces both bronchodilatation and protection independently of this bronchodilation against a physiological bronchoconstrictor stimulus for more than 20 h.
Hierarchical and Spatially Explicit Clustering of DNA Sequences with BAPS Software
Authors: L. Cheng, T. R. Connor, J. Siren, D. M. Aanensen, J. Corander
Journal: Molecular Biology and Evolution (2013)

Phylogeographical analyses have become commonplace for a myriad of organisms with the advent of cheap DNA sequencing technologies. Bayesian model-based clustering is a powerful tool for detecting important patterns in such data and can be used to decipher even quite subtle signals of systematic differences in molecular variation. Here, we introduce two upgrades to the Bayesian Analysis of Population Structure (BAPS) software, which enable 1) spatially explicit modeling of variation in DNA sequences and 2) hierarchical clustering of DNA sequence data to reveal nested genetic population structures. We provide a direct interface to map the results from spatial clustering with Google Maps using the portal http://www.spatialepidemiology.net/ and illustrate this approach using sequence data from Borrelia burgdorferi. The usefulness of hierarchical clustering is demonstrated through an analysis of the metapopulation structure within a bacterial population experiencing a high level of local horizontal gene transfer. The tools that are introduced are freely available at http://www.helsinki.fi/bsg/software/BAPS/.
Outcomes of Angioplasty vs Thrombolysis by Hospital Angioplasty Volume—Reply
Authors: Aldo Mariotto
Journal: JAMA (2001)

concluded that pa-tients treated at hospitals that performed more than 16 pri-mary angioplasty procedures per year (93.5% of the proce-dures in the study) had lower in-hospital mortality rates withprimary angioplasty than with thrombolytic therapy. Severalother National Registry of Myocardial Infarction publicationshave also focused on primary angioplasty.
The novel proangiogenic effect of hydrogen sulfide is dependent on Akt phosphorylation
Authors: W CAI, M WANG, P MOORE, H JIN, T YAO, Y ZHU
Journal: Cardiovascular Research (2007)

Hydrogen sulfide (H(2)S) has been reported to be a gasotransmitter which regulates cardiovascular homeostasis. The present study aims to examine the hypothesis that hydrogen sulfide is able to promote angiogenesis.Angiogenesis was assessed using in vitro parameters (i.e. endothelial cell proliferation, adhesion, transwell migration assay, scratched wound healing and formation of tube-like structure) and in vivo by assessing neovascularization in mice. Phosphorylation of Akt was measured using Western blot analysis.Exogenously administered NaHS (H(2)S donor) concentration-dependently (10-20 micromol/l) increased cell growth, migration, scratched wound healing and tube-like structure formation in cultured endothelial cells. These effects of NaHS on endothelial wound healing and tube-like structure formation were prevented by either the phosphatidylinositol 3-kinase (PI3K) inhibitor LY 294002 (5 micromol/l) or transfection of a dominant-negative mutant of Akt. NaHS increased Akt phosphorylation and this effect was also blocked by either LY 294002 or wortmannin (25 nmol/l). NaHS did not significantly alter the levels of vascular endothelial growth factor, mRNA expression of fibroblast growth factor and angiopoietin-1, or nitric oxide metabolites. NaHS treatment (10 and 50 micromol kg(-1) day(-1)) significantly promoted neovascularization in vivo in mice.The present study reports a novel proangiogenic role of H(2)S which is dependent on activation of Akt.
Lymph Node Fibroblastic Reticular Cells Construct the Stromal Reticulum via Contact with Lymphocytes
Authors: Tomoya Katakai, Takahiro Hara, Manabu Sugai, Hiroyuki Gonda, Akira Shimizu
Journal: The Journal of Experimental Medicine (2004)

The sophisticated microarchitecture of the lymph node, which is largely supported by a reticular network of fibroblastic reticular cells (FRCs) and extracellular matrix, is essential for immune function. How FRCs form the elaborate network and remodel it in response to lymphocyte activation is not understood. In this work, we established ERTR7+gp38+VCAM-1+ FRC lines and examined the production of the ER-TR7 antigen. Multiple chemokines produced by FRCs induced T cell and dendritic cell chemotaxis and adhesion to the FRC surface. FRCs can secrete the ER-TR7 antigen as an extracellular matrix component to make a reticular meshwork in response to contact with lymphocytes. The formation of the meshwork is induced by stimulation with tumor necrosis factor-α or lymphotoxin-α in combination with agonistic antibody to lymphotoxin-β receptor in a nuclear factor-κB (RelA)–dependent manner. These findings suggest that signals from lymphocytes induce FRCs to form the network that supports the movement and interactions of immune effectors within the lymph node.
Screening for Testicular Cancer: An Evidence Review for the U.S. Preventive Services Task Force
Authors: Kenneth Lin, Ruta Sharangpani
Journal: Annals of Internal Medicine (2010)

Background: Testicular cancer is the most common type of cancer in men aged 15 to 34 years. Because treatment produces favorable outcomes even in advanced stages, the U.S. Preventive Services Task Force (USPSTF) concluded in 2004 that screening asymptomatic men for testicular cancer is unlikely to produce additional benefits over clinical detection. Purpose: To search for new evidence on the benefits and harms of screening for testicular cancer to assist the USPSTF in updating its 2004 recommendation. Data Sources: English-language articles indexed in PubMed and the Cochrane Library and published between 1 January 2001 and 11 November 2009. Study Selection: Randomized, controlled trials; meta-analyses; systematic reviews; cohort studies; and case–control studies were selected to determine the benefits of screening for testicular cancer. Randomized, controlled trials; meta-analyses; systematic reviews; cohort studies; case–control studies; and case series of large, multisite databases were selected to determine the harms of screening. Each author independently reviewed titles, abstracts, and full-text articles for possible inclusion. Data Extraction: One author abstracted information on the benefits and harms of screening for testicular cancer. Data Synthesis: No studies met the inclusion criteria. Three studies were considered for inclusion at the full-text stage of review. These inconclusive studies addressed testicular microlithiasis, XIST gene testing, and testis-sparing surgery. Limitation: The focused search strategy may have missed some smaller studies or studies published in languages other than English on the benefits or harms of testicular cancer screening. Conclusion: No new evidence was found on the benefits or harms of screening for testicular cancer that would affect the USPSTF's previous recommendation against screening. Primary Funding Source: Agency for Healthcare Research and Quality.
Researchers challenge findings of team that showed awareness in three patients in vegetative state
Authors: C. Dyer
Journal: BMJ (2013)

Questions have been raised about the findings of a study that hit the headlines two years ago claiming that electroencephalography had shown awareness in three patients who were in a vegetative state.

The 2011 study was carried out by the postdoctoral fellow Damian Cruse, the British neuroscientist Adrian Owen, and colleagues at the University of Western Ontario’s Centre for Brain and Mind in London, Ontario, in collaboration with Cambridge University and the University of Liege. It used electroencephalography to look at the brain images of 16 patients, thought to be in a vegetative state, after they were asked to undertake two tasks: making a fist and wriggling their toes.1

Owen, a neuroscientist who previously worked at Cambridge, moved in 2011 …
Transcriptional profiles in melanocytes from clinically unaffected skin distinguish the neoplastic growth pattern in patients with melanoma
Authors: C. Magnoni, E. Tenedini, F. Ferrari, L. Benassi, C. Bernardi, G. Gualdi, G. Bertazzoni, E. Roncaglia, L. Fantoni, R. Manfredini, S. Bicciato, S. Ferrari, A. Giannetti, E. Tagliafico
Journal: British Journal of Dermatology (2006)

It is generally accepted that sunlight may contribute to the development of melanoma.To analyse gene expression of melanocytes obtained from clinically unaffected skin of patients with melanoma and healthy controls before and after exposure to ultraviolet B radiation.Using GeneChip array technology, the gene expression of melanocytes obtained from the two donor groups was profiled, in order to identify transcriptional differences affecting susceptibility to melanoma.The data collected did not show any difference between the expression profiles of melanocytes purified from normal donors and from patients with melanoma that was able to give a statistically significant class separation. However, by means of unsupervised clustering our data could be divided into two main classes. The first class included the transcriptome profiles of melanocytes obtained from skin samples of patients with a vertical growth phase (VGP) melanoma, while the second class included the transcriptome profiles of melanocytes obtained from skin samples of patients with a radial growth phase (RGP) melanoma.These data suggest that melanocytes in patients with VGP and RGP melanomas show significant differences in gene expression profiles, which allow us to classify patients with melanoma also from clinically unaffected skin.