tbuckley/cabot-search huggingface dataset:
The Consequences of Base Pair Composition Biases for Regulatory Network Organization in Prokaryotes
Authors: Otto X. Cordero, Paulien Hogeweg
Journal: Molecular Biology and Evolution (2009)

Given the dramatic variation in guanine-cytosine (GC) content observed in prokaryotes, from approximately 20% to approximately 75% GC, one wonders if these extreme biases in base pair composition affect the evolution of transcription factor-binding sites (BS). This letter shows that, along the wide range of GC content variation in bacteria, bacterial BS keep a high frequency of AT bases, roughly independently of the background (BG) base pair composition of intergenic regions. As a result, the equilibrium base pair frequencies of BS depart the most from those of BS DNA in GC-rich genomes. This not only implies a higher specificity but also a higher coding barrier for BS in GC-rich genomes. In accordance, we observe that the average percentage of divergently transcribed regions increases with the GC content of the genome, suggesting the use of a more efficient coding strategy.
EFFECTS OF LARGE INFUSIONS OF HETEROLOGOUS SERUM PROTEINS ON THE SERUM PROTEIN METABOLISM OF RABBITS
Authors: Frank J. Dixon, Paul H. Maurer
Journal: The Journal of Experimental Medicine (1955)

Infusions of heterologous serum proteins large enough to replace the entire normal catabolic loss of the corresponding autologous proteins in the recipient rabbits caused increased rates of plasma protein catabolism, an increase in the size of the plasma protein pool and normal or even slightly increased rates of plasma protein synthesis. The principal proteins in these infusions were catabolized at rates similar to those for corresponding homologous proteins. The most marked hyperproteinemias which developed were caused principally by increases in the host's own globulin and to a lesser extent by the presence of foreign protein in the circulation.
A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function
Authors: Sonia A Melo, Santiago Ropero, Catia Moutinho, Lauri A Aaltonen, Hiroyuki Yamamoto, George A Calin, Simona Rossi, Agustin F Fernandez, Fatima Carneiro, Carla Oliveira, Bibiana Ferreira, Chang-Gong Liu, Alberto Villanueva, Gabriel Capella, Simo Schwartz Jr, Ramin Shiekhattar, Manel Esteller
Journal: Nature Genetics (2009)
Methotrexate Therapy and Pulmonary Disease
Authors: I. Robert Schwartz
Journal: JAMA (1969)

To the Editor:—  We have seen two cases we believe to be the pulmonary disease complicating intermittent therapy with methotrexate as described by Clarysse et al in the Sept 22, 1969, issue ofThe Journal. 1 In both these patients, we have treated this complication with prednisone which resulted in prompt recovery.  Report of Cases.—Case 1.—  The diagnosis of acute lymphoblastic leukemia was made in a 13-year-old girl on Dec 27, 1967. A complete remission was induced within four weeks with orally administered prednisone, 40 mg/sq m daily, and vincristine, 2 mg/sq m weekly, was administered intravenously. This was followed by maintenance therapy with methotrexate, given orally twice weekly and adjusted to a maximally tolerated dose (25 mg twice weekly). On July 10, 1968, approximately 150 days after initiation of methotrexate therapy, the patient was rehospitalized with headaches, cough, high fever, severe dyspnea, tachypnea, and cyanosis. There were
UK regulators deny claims that their access to oseltamivir trial data was insufficient
Authors: A. O'Dowd
Journal: BMJ (2013)

The main regulators of drugs in the United Kingdom have denied that they had insufficient access to clinical trial data on the antiviral oseltamivir from its manufacturer, despite concerns about missing data.

Witnesses appearing before the parliamentary Public Accounts Committee said, however, that the current system allowed drug companies to withhold some trial data.

MPs on the committee held an evidence session on 17 June as part of their inquiry into clinical trials and Tamiflu, Roche’s branded form of oseltamivir, which had been used to treat pandemic flu.

The inquiry was prompted by a report published last month by the National Audit Office, which looked at drug regulators’ access to all the clinical trial evidence when licensing oseltamivir and whether the Department of Health for England stockpiled the drug on the basis of clinical evidence.1

Between 2006-07 and 2012-13 the department bought nearly 40 million units of oseltamivir, costing £424m (€495m; $665m). But only 2.4 million units were consumed, mostly during the flu pandemic in 2009-10, and over the same period …
Circulating endothelial progenitor cells do not contribute to regeneration of endothelium after murine arterial injury
Authors: Mette K. Hagensen, Merete K. Raarup, Martin B. Mortensen, Troels Thim, Jens R. Nyengaard, Erling Falk, Jacob F. Bentzon
Journal: Cardiovascular Research (2011)

AimsEndothelial regeneration after vascular injury, including percutaneous coronary intervention, is essential for vascular homeostasis and inhibition of neointima formation. Circulating endothelial progenitor cells (EPCs) have been implicated to contribute by homing and differentiating into endothelial cells (ECs). We tested this theory in a murine arterial injury model using carotid artery transplants and fluorescent reporter mice.
Clinical Findings, Pathology, and Outcomes of C3GN after Kidney Transplantation
Authors: Ladan Zand, Elizabeth C. Lorenz, Fernando G. Cosio, Fernando C. Fervenza, Samih H. Nasr, Manish J. Gandhi, Richard J. H. Smith, Sanjeev Sethi
Journal: Journal of the American Society of Nephrology (2013)

C3 glomerulonephritis (C3GN) results from abnormalities in the alternative pathway of complement, and it is characterized by deposition of C3 with absent or scant Ig deposition. In many patients, C3GN progresses to ESRD. The clinical features, pathology, and outcomes of patients with C3GN receiving kidney transplantation are unknown. Between 1996 and 2010, we identified 21 patients at our institution who received a kidney transplant because of ESRD from C3GN. The median age at the time of initial diagnosis of C3GN at kidney biopsy was 20.8 years. The median time from native kidney biopsy to dialysis or transplantation was 42.3 months. Of 21 patients, 14 (66.7%) patients developed recurrent C3GN in the allograft. The median time to recurrence of disease was 28 months. Graft failure occurred in 50% of patients with recurrent C3GN, with a median time of 77 months to graft failure post-transplantation. The remaining 50% of patients had functioning grafts, with a median follow-up of 73.9 months. The majority of patients had hematuria and proteinuria at time of recurrence. Three (21%) patients were positive for monoclonal gammopathy and had a faster rate of recurrence and graft loss. Kidney biopsy at the time of recurrence showed mesangial proliferative GN in eight patients and membranoproliferative GN in six patients. All allograft kidney biopsies showed bright C3 staining (2-3+), with six biopsies also showing trace/1+ staining for IgM and/or IgG. To summarize, C3GN recurs in 66.7% of patients, and one half of the patients experience graft failure caused by recurrence.
Associations between HLA and antibodies to collagen in rheumatoid arthritis.
Authors: M J Rowley, B Tait, T Doran, P Emery, I R Mackay
Journal: Annals of the Rheumatic Diseases (1990)

Associations between HLA types and serum antibodies to native and denatured type II collagen were sought in 105 patients with rheumatoid arthritis (RA). Antibodies were measured using a solid phase radioimmunoassay. There were no significant associations between any HLA antigen (A, B, or DR) and a high antibody titre to native collagen. There were significant associations, however, between HLA antigens and high antibody titres to denatured collagen. Although DR4 did not show an association, the phenotype A2+DR4+ did; this was not related to A2 as A2+DR- was not associated with a high antibody titre. No single B locus antigen showed an association, but several B locus antigens, B12, B15, and B40, were included in phenotypes with A2 and DR4 which were associated with a high antibody titre to denatured collagen. These HLA associations with anticollagen type II are best explained by a gene other than DR4 (but in linkage with it) which may regulate the antibody response to denatured collagen. If so, this would represent an HLA gene in addition to DR4 that is active in RA.
Pediatric Radiation Oncology
Authors: M. WHARAM
Journal: JNCI Journal of the National Cancer Institute (1990)

Pediatric Radiation Oncology Get access Edward C. Halperin , Larry E. kun , Louis S. constine , Nancy J. Tarbell . New York : Raven Press , 1989 , 434 pp. $98. MOODY WHARAM MOODY WHARAM Division of Radiation Oncology, The Johns Hopkins Oncology center600 N. Wolfe St. Baltimore, MD 21205 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 8, 18 April 1990, Pages 709–710, https://doi.org/10.1093/jnci/82.8.709 Published: 18 April 1990
Long-Term Therapy With Low-Dose Isotretinoin for Prevention of Basal Cell Carcinoma: A Multicenter Clinical Trial
Authors: J. A. Tangrea, B. K. Edwards, P. R. Taylor, A. M. Hartman, G. L. Peck, S. J. Salasche, P. A. Menon, P. M. Benson, J.R. Mellette, M. A. Guill, J. K. Robinson, J. D. Guin, H. L. Stoll, W. J. Grabski, G. B. Winton
Journal: JNCI Journal of the National Cancer Institute (1992)

Background : High-dose isotretinoin has been reported to have a prophylactic effect on nonmelanoma skin cancer, although it is associated with significant toxicity. Purpose : To test the effectiveness of the long-term administration of low-dose isotretinoin in reducing the occurrence of basal cell carcinoma at a new site in patients with previously treated basal cell carcinomas and to measure the toxicity associated with this regimen, we conducted a clinical trial at eight cancer centers. Methods : Nine hundred and eighty-one patients with two or more previously confirmed basal cell carcinomas were randomly assigned to receive either 10 mg of isotretinoin or a placebo daily. Patients were followed for 36 months and monitored at 6-month intervals for skin cancer and toxic effects. Results: After 36 months of treatment, no statistically significant difference in either the cumulative percent of patients with an occurrence of basal cell carcinoma at a new site or the annual rate of basal cell carcinoma formation existed between patients receiving isotretinoin and those receiving the placebo. Elevated serum triglycerides, hyperos-totic axial skeletal changes, and mucocutaneous reactions were more frequent in the group receiving isotretinoin than in the control group, and these differences were all statistically significant (P<.001). Conclusion : This low-dose regimen of isotretinoin not only is ineffective in reducing the occurrence of basal cell carcinoma at new sites in patients with two or more previously treated basal cell carcinomas but also is associated with significant adverse systemic effects. Implication : The toxicity associated with the long-term administration of isotretinoin, even at the low dose used in this trial, must be weighed in planning future prevention trials. [J Natl Cancer Inst 84: 328–332, 1992]
“适度”体外授精与“强化选择”等效
Authors: 朱丽琳（译）
Journal: BMJ (2007)

体外授精是一种治疗不孕症的有效措施，但也有一些缺点，比如“强化选择”（过度用药）、感觉不适、价格昂贵，且可造成多胎妊娠。荷兰的学者提出了一种“适度”的方法，即减少对卵巢的刺激程度，仅用一个而非两个胚胎进行移植。此方法效果较好。在第一项随机试验中，接受“适度”体外授精的妇女与接受更多“强化选择”的妇女得到活产婴儿的几率是相似的（分别为43％和45％），并且前者更不易发生多胎妊娠（几率分别为0．5％和13％）。两组报告的不适和焦虑程度相似，且前者价格要比后者低2000欧元（1350英镑；2640美元）。
Facilitation of Th1-mediated immune response by prostaglandin E receptor EP1
Authors: Miyako Nagamachi, Daiji Sakata, Kenji Kabashima, Tomoyuki Furuyashiki, Takahiko Murata, Eri Segi-Nishida, Kitipong Soontrapa, Toshiyuki Matsuoka, Yoshiki Miyachi, Shuh Narumiya
Journal: The Journal of Experimental Medicine (2007)

Prostaglandin E2 (PGE2) exerts its actions via four subtypes of the PGE receptor, EP1–4. We show that mice deficient in EP1 exhibited significantly attenuated Th1 response in contact hypersensitivity induced by dinitrofluorobenzene (DNFB). This phenotype was recapitulated in wild-type mice by administration of an EP1-selective antagonist during the sensitization phase, and by adoptive transfer of T cells from sensitized EP1−/− mice. Conversely, an EP1-selective agonist facilitated Th1 differentiation of naive T cells in vitro. Finally, CD11c+ cells containing the inducible form of PGE synthase increased in number in the draining lymph nodes after DNFB application. These results suggest that PGE2 produced by dendritic cells in the lymph nodes acts on EP1 in naive T cells to promote Th1 differentiation.
Genetic Variation in Native Americans, Inferred from Latino SNP and Resequencing Data
Authors: J. D. Wall, R. Jiang, C. Gignoux, G. K. Chen, C. Eng, S. Huntsman, P. Marjoram
Journal: Molecular Biology and Evolution (2011)

Analyses of genetic polymorphism data have the potential to be highly informative about the demographic history of Native American populations, but due to a combination of historical and political factors, there are essentially no autosomal sequence polymorphism data from any Native American group.However, there are many resequencing studies involving Latinos, whose genomes contain segments inherited from their Native American ancestors.In this study, we introduce a new method for estimating local ancestry across the genomes of admixed individuals and show how this method, along with dense genotyping and targeted resequencing, can be used to assay genetic variation in ancestral Native American groups.We analyze roughly 6 Mb of resequencing data from 22 Mexican Americans to provide the first largescale view of sequence level variation in Native Americans.We observe low levels of diversity and high levels of linkage disequilibrium in the Native American-derived sequences, consistent with a recent severe population bottleneck associated with the initial peopling of the Americas.Using two different computational approaches, one novel, we estimate that this bottleneck occurred roughly 12.5 Kya; when uncertainty in the estimation process is taken into account, our results are consistent with archeological estimates for the colonization of the Americas.
The pleura: the outer space of pulmonary medicine
Authors: H Hamm, RW Light
Journal: European Respiratory Journal (1997)

In this issue of the Journal, MISEROCCHI [1] starts our series of articles on the pleura with a review of the physiology and the pathophysiology of the pleural space. In forthcoming months this series will cover a wide range of issues on pleural diseases. We have seen much progress in basic research as well as changing standards in the diagnosis and management of pleural disorders in recent years. The aim of this series is to supply the readership of the Journal with a concise and up-to-date overview on these developments, bringing some of the important information from the outer  of research down to the earth of everyday clinical practice. The understanding of the physiology of the pleural space has come a long way since the pioneering work by scientists, such as STARLING [2, 3] at the end of the last century and VON NEERGARD [4] in the 1920s, who developed pressure control models of pleural fluid turnover. The relevant pressures were identified as the pleural liquid pressure (resulting from the expanding force of the thoracic cage versus the recoil force of the lung), the capillary and oncotic pressures in both the visceral and parietal membranes, and the oncotic pressure of the pleural fluid itself. The early models initially suggested a pressure-driven fluid flow from the parietal side across the pleural space to the visceral pleura and subsequently, into the pulmonary interstitium. Such models were derived from studies of animals with a thin visceral membrane, in which the blood supply originates from branches of the pulmonary arteries (with low capillary pressures). Later, it was found that in some other mammals, including man, the visceral pleura is considerably thicker and the blood supply is from the systemic circulation (with higher capillary pressures). This means that once the fluid enters the pleural space, there is no clear local pressure gradient to explain its further distribution. Thus, pressure models in man fall short in explaining the existence of a constant physiological amount of fluid in the pleural cavity and also, they do not give a clue as to the further fate of the fluid. In other words, volume control mechanisms need to be
Serum concentrations and peripheral secretion of the beta chemokines monocyte chemoattractant protein 1 and macrophage inflammatory protein 1α in alcoholic liver disease
Authors: N C Fisher, D A H Neil, A Williams, D H Adams
Journal: Gut (1999)

BACKGROUND Alcoholic liver disease is associated with increased hepatic expression of monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1α (MIP-1α). AIMS To determine whether concentrations of chemokines in the peripheral circulation reflect disease activity, and whether chemokine secretion is restricted to the liver or is part of a systemic inflammatory response in alcoholic liver disease. PATIENTS Fifty one patients with alcoholic liver disease and 12 healthy controls. METHODS Peripheral vein (and hepatic vein in patients undergoing transjugular liver biopsy) chemokine concentrations were measured by ELISA. Chemokine secretion and transcription in isolated peripheral mononuclear cells were assessed using ELISA and in situ hybridisation in patients with severe alcoholic hepatitis. RESULTS Serum MCP-1 concentrations were higher in alcoholic hepatitis compared with cirrhosis or healthy controls. MIP-1α concentrations were below the assay sensitivity in most patients. Serum MCP-1 concentrations correlated significantly with serum aspartate aminotransferase and creatinine. In severe alcoholic hepatitis, MCP-1 concentrations were higher in hepatic compared with peripheral veins; in mild alcoholic hepatitis there was no difference. Mononuclear cell secretion of both MCP-1 and MIP-1α was higher in severe alcoholic hepatitis compared with healthy controls, and chemokine mRNA was identified in monocytes. CONCLUSIONS Serum MCP-1 concentrations are raised in alcoholic liver disease and reflect severity of hepatic inflammation. Monocyte secretion of both MCP-1 and MIP-1α is increased in severe alcoholic hepatitis. Both intrahepatic sources and peripheral mononuclear cells contribute to the raised serum MCP-1 concentrations.
Comprehensive Genomic Analysis Identifies Novel Subtypes and Targets of Triple-Negative Breast Cancer
Authors: Matthew D. Burstein, Anna Tsimelzon, Graham M. Poage, Kyle R. Covington, Alejandro Contreras, Suzanne A.W. Fuqua, Michelle I Savage, C. Kent Osborne, Susan G. Hilsenbeck, Jenny C. Chang, Gordon B. Mills, Ching C. Lau, Powel H. Brown
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Genomic profiling studies suggest that triple-negative breast cancer (TNBC) is a heterogeneous disease. In this study, we sought to define TNBC subtypes and identify subtype-specific markers and targets. Experimental Design: RNA and DNA profiling analyses were conducted on 198 TNBC tumors [estrogen receptor (ER) negativity defined as Allred scale value ≤ 2] with &amp;gt;50% cellularity (discovery set: n = 84; validation set: n = 114) collected at Baylor College of Medicine (Houston, TX). An external dataset of seven publically accessible TNBC studies was used to confirm results. DNA copy number, disease-free survival (DFS), and disease-specific survival (DSS) were analyzed independently using these datasets. Results: We identified and confirmed four distinct TNBC subtypes: (i) luminal androgen receptor (AR; LAR), (ii) mesenchymal (MES), (iii) basal-like immunosuppressed (BLIS), and (iv) basal-like immune-activated (BLIA). Of these, prognosis is worst for BLIS tumors and best for BLIA tumors for both DFS (log-rank test: P = 0.042 and 0.041, respectively) and DSS (log-rank test: P = 0.039 and 0.029, respectively). DNA copy number analysis produced two major groups (LAR and MES/BLIS/BLIA) and suggested that gene amplification drives gene expression in some cases [FGFR2 (BLIS)]. Putative subtype-specific targets were identified: (i) LAR: androgen receptor and the cell surface mucin MUC1, (ii) MES: growth factor receptors [platelet-derived growth factor (PDGF) receptor A; c-Kit], (iii) BLIS: an immunosuppressing molecule (VTCN1), and (iv) BLIA: Stat signal transduction molecules and cytokines. Conclusion: There are four stable TNBC subtypes characterized by the expression of distinct molecular profiles that have distinct prognoses. These studies identify novel subtype-specific targets that can be targeted in the future for the effective treatment of TNBCs. Clin Cancer Res; 21(7); 1688–98. ©2014 AACR. See related commentary by Vidula and Rugo, p. 1511
Increased risk of chronic obstructive pulmonary diseases in coke oven workers: interaction between occupational exposure and smoking
Authors: Yunping Hu, Bo Chen, Zhengyu Yin, Lin Jia, Yuanfen Zhou, Taiyi Jin
Journal: Thorax (2006)

<b>Background:</b> Coke oven workers are regularly exposed to coke oven emissions (COE) and may be at risk of developing lung diseases. There is limited evidence for the link between exposure to COE and chronic obstructive pulmonary diseases (COPD). The aim of this study was to explore the dose-response relationship between COE exposure and COPD and to assess the interaction with cigarette smoking. <b>Methods:</b> Seven hundred and twelve coke oven workers and 211 controls were investigated in southern China. Benzene soluble fraction (BSF) concentrations as a surrogate of COE were measured in representative personal samples and the individual cumulative COE exposure level was quantitatively estimated. Detailed information on smoking habits and respiratory symptoms was collected and spirometric tests were performed. <b>Results:</b> The mean BSF levels at the top of two coking plants were 743.8 and 190.5 μg/m<sup>3</sup>, respectively, which exceed the OSHA standard (150 μg/m<sup>3</sup>). After adjusting for cigarette smoking and other risk factors, there was a significant dose-dependent reduction in lung function and increased risks of chronic cough/phlegm and COPD in coke oven workers. The odds ratio for COPD was 5.80 (95% confidence interval 3.13 to 10.76) for high level cumulative COE exposure (⩾1714.0 μg/m<sup>3</sup>-years) compared with controls. The interaction between COE exposure and smoking in COPD was significant. The risk of COPD in those with the highest cumulative exposure to COE and cigarette smoking was 58-fold compared with non-smokers not exposed to COE. <b>Conclusion:</b> Long term exposure to COE increases the risk of an interaction between COPD and cigarette smoking.