tbuckley/cabot-search huggingface dataset:
Liver cirrhosis as a risk factor for mortality in a national cohort of patients with bacteremia
Authors: Cheol-In Kang, Jae-Hoon Song, Doo Ryeon Chung, Kyong Ran Peck, Joon-Sup Yeom, Hyun Kyun Ki, Jun Seong Son, Jin Seo Lee, Yeon-Sook Kim, Sook-In Jung, Shin-Woo Kim, Hyun-Ha Chang, Seong Yeol Ryu, Ki Tae Kwon, Hyuck Lee, Dong Sik Jung, Chisook Moon, Sang Taek Heo, Eu Suk Kim, Ji-Young Rhee
Journal: Journal of Infection (2011)
Association of a CYP4A11 Variant and Blood Pressure in Black Men
Authors: James V. Gainer, Michael S. Lipkowitz, Chang Yu, Michael R. Waterman, Elliott P. Dawson, Jorge H. Capdevila, Nancy J. Brown
Journal: Journal of the American Society of Nephrology (2008)

CYP4A11 arachidonic acid monooxygenase oxidizes endogenous arachidonic acid to 20-hydroxyeicosatetraenoic acid, a renal vasoconstrictor and natriuretic. Cyp4a deficiency causes hypertension in male mice, and a loss-of-function variant (T8590C) of CYP4A11 is associated with hypertension in white individuals. Hypertension and hypertensive renal disease are more common among black than white individuals, but the relationship between genetic variation at CYP4A11 and hypertension in black individuals is not known. This study tested the hypothesis that the CYP4A11 T8590C polymorphism is associated with higher BP or clinical outcomes in 732 black Americans with hypertensive renal disease participating in the African American Study of Kidney Disease (AASK). Men with the 8590CC genotype had significantly higher systolic BP (CC 156.5 +/- 22.6 versus 148.4 +/- 24.3 mmHg in CT and TT combined; P = 0.04) and pulse pressure (P = 0.04) at baseline; this association was not observed among women. In addition, this genotype was associated with higher systolic and diastolic BP at 36-mo follow-up among those randomly assigned to the lower BP arm of the AASK. Among all participants (or men but not women) with proteinuria, the 8590CC genotype was associated with an increased cumulative incidence of ESRD or death, controlling for randomization and clinical characteristics. In summary, the CYP4A11 8590CC genotype is associated with increased BP in black men with hypertensive nephrosclerosis and is associated with adverse clinical outcomes in those with baseline proteinuria. These data support a role for renal monooxygenases and 20-hydroxyeicosatetraenoic acid in the regulation of BP and renal function in men.
Genome-wide Profiling of Chromatin Signatures Reveals Epigenetic Regulation of MicroRNA Genes in Colorectal Cancer
Authors: Hiromu Suzuki, Shintaro Takatsuka, Hirofumi Akashi, Eiichiro Yamamoto, Masanori Nojima, Reo Maruyama, Masahiro Kai, Hiro-o Yamano, Yasushi Sasaki, Takashi Tokino, Yasuhisa Shinomura, Kohzoh Imai, Minoru Toyota
Journal: Cancer Research (2011)

Altered expression of microRNAs (miRNA) occurs commonly in human cancer, but the mechanisms are generally poorly understood. In this study, we examined the contribution of epigenetic mechanisms to miRNA dysregulation in colorectal cancer by carrying out high-resolution ChIP-seq. Specifically, we conducted genome-wide profiling of trimethylated histone H3 lysine 4 (H3K4me3), trimethylated histone H3 lysine 27 (H3K27me3), and dimethylated histone H3 lysine 79 (H3K79me2) in colorectal cancer cell lines. Combining miRNA expression profiles with chromatin signatures enabled us to predict the active promoters of 233 miRNAs encoded in 174 putative primary transcription units. By then comparing miRNA expression and histone modification before and after DNA demethylation, we identified 47 miRNAs encoded in 37 primary transcription units as potential targets of epigenetic silencing. The promoters of 22 transcription units were associated with CpG islands (CGI), all of which were hypermethylated in colorectal cancer cells. DNA demethylation led to increased H3K4me3 marking at silenced miRNA genes, whereas no restoration of H3K79me2 was detected in CGI-methylated miRNA genes. DNA demethylation also led to upregulation of H3K4me3 and H3K27me3 in a number of CGI-methylated miRNA genes. Among the miRNAs we found to be dysregulated, many of which are implicated in human cancer, miR-1-1 was methylated frequently in early and advanced colorectal cancer in which it may act as a tumor suppressor. Our findings offer insight into the association between chromatin signatures and miRNA dysregulation in cancer, and they also suggest that miRNA reexpression may contribute to the effects of epigenetic therapy.
On Cases of Pleuritic Effusion
Authors: E. M. Skerritt
Journal: BMJ (1878)

that the evidence thus furnished is inadequate-that we are not justified in extending to all contagia what has been proved to be true of some only; but, until evidence of the same order and of equal weight has been brought forward on the other side-and I am not aware that this has yet been done-we are surely entitled, at any rate provisionally, to accept the conclusion in question.Again, the statement that the infective principle is probably non- volatile, is not, as the reader of Dr. Notter's remarks might fairly suppose, a mere hypothesis or inference.It rests on experimental evidence obtained in the case of small-pox, ovine variola, and cattle- plague. (A brief account of the experiments is given on page 219 of my Report.)In short, the assertion that the contagia of certain commu- nicable diseases are neither soluble, diffusible, nor volatile, is grounded on a substantial basis of observed facts; it is not what Magendie was so fond of stigmatising as a " vuc de 'esprit".All this, however, only goes to show that contagium is particulate; it does not show that it consists of living "germs".It is quite com- patible with the belief that the virus of infective inflammation is "simply fibrinous exudation, which, after coagulation, has acquired poisonous properties".Whatever may have been my opinion on the subject of " germs", I was careful to keep it well apart from my investigation.This brings me to the very point to which I wish to draw attention.So far from making the above-mentioned facts-which Dr. Notter terms my "questionable premisses"-the starting-point of my inquiry, I took great pains to show that the method of research which I ventured to advocate for the determination of the relative value of disinfectant agents differed from those previously followed, in yielding results wholly independent of any theory concerning the intimate nature of the con- tagia.In this complete independence I conceived its special value to consist.Conclusions arrived at in accordance with the principles laid down in my Report, would lose none of their force were the "chemical" theory, which Dr. Notter is inclined to favour, universally accepted as the true one.The essential nature of the i;fective principle is a problem of vast importance and corresponding difficulty.Were it necessary to solve it before trying to ascertain the value of our disinfectant measures, our hands might remain tied for a long time.I did my best to show that the obstacle might be turned, as it could not be surmounted.
Defining the risk of toxicity in phase I oncology trials of novel molecularly targeted agents: a single centre experience
Authors: L.R. Molife, S. Alam, D. Olmos, M. Puglisi, K. Shah, R. Fehrmann, L. Trani, A. Tjokrowidjaja, J.S. de Bono, U. Banerji, S.B. Kaye
Journal: Annals of Oncology (2012)
Late Cardiac Morbidity and Mortality in Early-Stage Breast Cancer Patients After Breast-Conservation Treatment
Authors: Gabor Gyenes
Journal: Journal of Clinical Oncology (2007)

TO THE EDITOR: Harris et al have to be commended for their efforts in analyzing the medical records of 961 patients who received radiation therapy (RT) for early breast cancer. They found an increased risk of morbidity for ischemic heart disease after RT for leftsided cancer compared with right-sided RT, especially after more than 10 years post-treatment. There was a trend for increased mortality but their study must have been underpowered to detect a significant mortality difference. Their findings are consistent with some, although, not all previous trials, and I agree with Recht who points out in his editorial that it is difficult to know which patients should really worry about this problem. Can anything be done about this potentially life-threatening complication other than optimizing RT techniques and waiting for 10 years to find out whether or not we were right? Advising patients to quit smoking and to have their blood pressure and lipids treated makes perfect sense, but I would recommend a more structured approach. Framingham risk score (FRS) calculations can give a reliable assessment of the patients’ 10-year cardiovascular risks and it defines their lipid targets. Based on the aforementioned studies and on the study by Harris et al, it would be reasonable to assume that left-sided chest wall RT is a nonmodifiable risk factor that increases the risk by a factor of 1.5 to 2. Thus, the FRS could be multiplied by this factor and the patients’ modifiable cardiac risk factors could be treated accordingly. Alternatively, this may be the right time to initiate a multicenter open-label trial for such patients who could be randomly assigned for an FRS-based approach, including aggressive statin therapy versus usual care.
The Role of Serum Immunoglobulin Free Light Chain in Response and Progression in Waldenstrom Macroglobulinemia
Authors: Xavier Leleu, Wanling Xie, Meghan Bagshaw, Ranjit Banwait, Renee Leduc, Nitin Roper, Edie Weller, Irene M. Ghobrial
Journal: Clinical Cancer Research (2011)

Abstract Introduction: The serum free light chain (sFLC) has been widely used in the assessment of response in patients with multiple myeloma and other plasma cell dyscrasias. However, its use in Waldenstrom macroglobulinemia (WM) has not been previously assessed. We sought to examine the role of sFLC in response and progression of patients with WM. Methods: This study was conducted in a cohort of 48 patients with a diagnosis of WM, untreated (n = 20) or relapsed/refractory (n = 28), prospectively treated on a bortezomib and rituximab trial. Results: Involved FLC (iFLC) response occurred in 79% patients versus 60% by M-spike protocol criteria. The median time to response was shorter with iFLC than per protocol (2.1 and 3.7 months; P = 0.05). Progression defined using iFLC also correlated well to progression in the protocol (κ = 0.63). However, the median time to progression (TTP) was more rapid by iFLC than per protocol (13.7 and 18.9 months). We also confirmed that a flare in iFLC in post–rituximab therapy did not correlate with lack of response or shorter TTP. Conclusion: Involved sFLC may be a useful marker of tumor measurement, showing earlier response and progression compared with IgM or M-spike measurements. Clin Cancer Res; 17(9); 3013–8. ©2011 AACR.
A new use for an old Holter monitor: an ambulatory cough meter
Authors: AB Chang, RG Newman, PD Phelan, CF Robertson
Journal: European Respiratory Journal (1997)

Cough is commonly used as an outcome measure in clinical studies, although the subjective reporting of cough is unreliable when compared to objective measures. We describe an inexpensive new ambulatory cough meter that is based on a disused Holter monitor. The cough meter consists of a Holter monitor and a cough processor, designed on a computer to select the most appropriate filters. The cough meter was then validated against the overnight tape recorder on 21 occasions in 18 children (aged 6-15 yrs). The agreement between the cough meter and the tape recorder was good (mean difference of -0.3 coughs x h(-1); limits of agreement -2.2 to 1.7 coughs x h(-1)). We conclude that our newly described ambulatory cough meter provides a valid and inexpensive method of objectively monitoring cough for up to 24 h.
Mortality risk attributable to high and low ambient temperature: a multicountry observational study
Authors: Antonio Gasparrini, Yuming Guo, Masahiro Hashizume, Eric Lavigne, Antonella Zanobetti, Joel Schwartz, Aurelio Tobias, Shilu Tong, Joacim Rocklöv, Bertil Forsberg, Michela Leone, Manuela De Sario, Michelle L Bell, Yue-Liang Leon Guo, Chang-fu Wu, Haidong Kan, Seung-Muk Yi, Micheline de Sousa Zanotti Stagliorio Coelho, Paulo Hilario Nascimento Saldiva, Yasushi Honda, Ho Kim, Ben Armstrong
Journal: The Lancet (2015)

BackgroundAlthough studies have provided estimates of premature deaths attributable to either heat or cold in selected countries, none has so far offered a systematic assessment across the whole temperature range in populations exposed to different climates. We aimed to quantify the total mortality burden attributable to non-optimum ambient temperature, and the relative contributions from heat and cold and from moderate and extreme temperatures.MethodsWe collected data for 384 locations in Australia, Brazil, Canada, China, Italy, Japan, South Korea, Spain, Sweden, Taiwan, Thailand, UK, and USA. We fitted a standard time-series Poisson model for each location, controlling for trends and day of the week. We estimated temperature–mortality associations with a distributed lag non-linear model with 21 days of lag, and then pooled them in a multivariate metaregression that included country indicators and temperature average and range. We calculated attributable deaths for heat and cold, defined as temperatures above and below the optimum temperature, which corresponded to the point of minimum mortality, and for moderate and extreme temperatures, defined using cutoffs at the 2·5th and 97·5th temperature percentiles.FindingsWe analysed 74 225 200 deaths in various periods between 1985 and 2012. In total, 7·71% (95% empirical CI 7·43–7·91) of mortality was attributable to non-optimum temperature in the selected countries within the study period, with substantial differences between countries, ranging from 3·37% (3·06 to 3·63) in Thailand to 11·00% (9·29 to 12·47) in China. The temperature percentile of minimum mortality varied from roughly the 60th percentile in tropical areas to about the 80–90th percentile in temperate regions. More temperature-attributable deaths were caused by cold (7·29%, 7·02–7·49) than by heat (0·42%, 0·39–0·44). Extreme cold and hot temperatures were responsible for 0·86% (0·84–0·87) of total mortality.InterpretationMost of the temperature-related mortality burden was attributable to the contribution of cold. The effect of days of extreme temperature was substantially less than that attributable to milder but non-optimum weather. This evidence has important implications for the planning of public-health interventions to minimise the health consequences of adverse temperatures, and for predictions of future effect in climate-change scenarios.FundingUK Medical Research Council.
McMinn’s colour atlas of human anatomy
Authors: R Highet
Journal: British Journal of Sports Medicine (2005)

Edited by P H Abrahams, S C Marks Jr, R T Hutchings. London: Mosby, £38.99, pp 378, softcover. ISBN 0723432120

Back in the late 70s, when Gray’s and Grant’s anatomy atlases ruled supreme for my vintage going through medical school, this text would have been a hit on the medical bookshop shelves: over 350 pages of layered real photo images of cadavers beautifully numbered, indexed, and with useful undergraduate level clinical text at the end of each chapter.

For students of medicine and other undergraduate areas, this is a whole atlas of …
Increase in prostanoid formation in rat liver macrophages (Kupffer cells) by human anaphylatoxin C3a
Authors: Gerhard P. Püschel, Ursula Hespeling, Martin Oppermann, Peter Dieter
Journal: Hepatology (1993)

Human anaphylatoxin C3a increases glycogenolysis in perfused rat liver. This action is inhibited by prostanoid synthesis inhibitors and prostanoid antagonists. Because prostanoids but not anaphylatoxin C3a can increase glycogenolysis in hepatocytes, it has been proposed that prostanoid formation in nonparenchymal cells represents an important step in the C3a-dependent increase in hepatic glycogenolysis. This study shows that (a) human anaphylatoxin C3a (0.1 to 10 micrograms/ml) dose-dependently increased prostaglandin D2, thromboxane B2 and prostaglandin F2 alpha formation in rat liver macrophages (Kupffer cells); (b) the C3a-mediated increase in prostanoid formation was maximal after 2 min and showed tachyphylaxis; and (c) the C3a-elicited prostanoid formation could be inhibited specifically by preincubation of C3a with carboxypeptidase B to remove the essential C-terminal arginine or by preincubation of C3a with Fab fragments of a neutralizing monoclonal antibody. These data support the hypothesis that the C3a-dependent activation of hepatic glycogenolysis is mediated by way of a C3a-induced prostanoid production in Kupffer cells.
Efficacy and Safety of Emtricitabine vs Stavudine in Combination Therapy in Antiretroviral-Naive Patients&lt;SUBTITLE&gt;A Randomized Trial&lt;/SUBTITLE&gt;
Authors: Michael S Saag, Pedro Cahn, François Raffi, Marcelo Wolff, Daniel Pearce, Jean-Michel Molina, William Powderly, Audrey L Shaw, Elsa Mondou, John Hinkle, Katyna Borroto-Esoda, Joseph B Quinn, David W Barry, Franck Rousseau
Journal: JAMA (2004)

Emtricitabine is a new, once-daily nucleoside reverse transcriptase inhibitor (NRTI) with potent activity against human immunodeficiency virus (HIV).To assess the efficacy and safety of emtricitabine as compared with stavudine when used with a background regimen of didanosine and efavirenz.Randomized, double-blind, double-dummy study conducted at 101 research clinics in North America, Latin America, and Europe. The first patient was enrolled on August 21, 2000; no investigator or patient was unblinded until the last patient randomized completed the week 48 visit on October 24, 2002. Analyses were based on data collected in a double-blind setting with a median follow-up of 60 weeks. Patients were 571 antiretroviral-naive, HIV-1-infected adults aged 18 years or older with viral load levels greater than or equal to 5000 copies/mL.Receipt of either 200 mg of emtricitabine once daily (plus stavudine placebo twice daily) (n = 286) or stavudine at standard doses twice daily (plus emtricitabine placebo once daily) (n = 285) plus open-label didanosine and efavirenz, once daily.Persistent virological response, defined as achieving and maintaining viral load at or below the limit of assay quantification (< or =400 or 50 copies/mL).At the interim analysis on June 14, 2002, when the last patient randomized completed 24 weeks of double-blind treatment (median follow-up time of 42 weeks), patients in the emtricitabine group had a higher probability of a persistent virological response < or =50 copies/mL vs the stavudine group (85% vs 76%, P =.005). This was associated with a higher mean CD4 cell count change from baseline for the emtricitabine group (156 cells/ microL vs 119 cells/microL, P =.01 [of note, there was no statistical difference at 48 weeks [P =.15], although a sensitivity analysis, using an intent-to-treat population with the last CD4 cell count observation carried forward to week 48 showed a difference [P =.02]]). The independent data and safety monitoring board recommended offering open-label emtricitabine based on the interim analysis. The probability of persistent virological response < or =50 copies/mL through week 60 was 76% for the emtricitabine group vs 54% for the stavudine group (P<.001). The probability of virological failure through week 60 was 4% in the emtricitabine group and 12% in the stavudine group (P<.001). Patients in the stavudine group had a greater probability of an adverse event that led to study drug discontinuation through week 60 than did those in the emtricitabine group (15% vs 7%, P =.005).Once-daily emtricitabine appeared to demonstrate greater virological efficacy, durability of response, and tolerability compared with twice-daily stavudine when used with once-daily didanosine and efavirenz.
Choline transport in rat liver basolateral plasma membrane vesicles
Authors: R H Moseley, H Takeda, L J Zugger
Journal: Hepatology (1996)

Previous studies have demonstrated several pathways for the sinusoidal uptake of endogenous and exogenous organic cations, including two distinct organic cation:H+ exchanges and a separate carrier–mediated system driven by the inside–negative membrane potential. In this study, the driving force(s) for the uptake of the endogenous quaternary amine, choline, were determined in rat liver basolateral plasma membrane (blLPM) vesicles. Choline uptake into an osmotically sensitive space was not stimulated by an outwardly directed H+ or inwardly directed Na+ gradient. Instead, an inside–negative K+ diffusion potential stimulated choline uptake, suggesting the presence of a conductive pathway for choline uptake in bILPM vesicles. Conductive choline uptake was confirmed by inducing variable changes in the transmembrane potential with anions of different membrane permeability. Choline uptake in blLPM vesicles exhibitied (1) temperature dependency; (2) trans –stimulation; and (3) saturability, with an approximate Michaelis constant (Km) of 0.34 mmol/L and maximum velocity (Vmax) of 0.45 nmol/mg protein/15 s. Choline uptake in blLPM vesicles was cis–inhibited by the structurally similar derivative, hemicholinium–3 and acetylcholine, but not by substrates for other organic cation transport processes identified in blLPM vesicles, including thiamine, tetraethylammonium (TEA), tri– n –butyl–methylammonium (TBuMA), and N ′–methylnicotinamide (NMN). These findings demonstrate an electrogenic pathway on the sinusoidal membrane for the uptake of this essential nutrient and support the existence of multiple pathways for the sinusoidal uptake of endogenous and exogenous organic cations.
Effective Control of Epstein-Barr Virus–Related Hemophagocytic Lymphohistiocytosis With Immunochemotherapy
Authors: Shinsaku Imashuku, Shigeyoshi Hibi, Toshio Ohara, Asayuki Iwai, Masahiro Sako, Masahiko Kato, Hirokazu Arakawa, Manabu Sotomatsu, Satoshi Kataoka, Keiko Asami, Daijiro Hasegawa, Yoshiyuki Kosaka, Kimihiko Sano, Noboru Igarashi, Keiko Maruhashi, Ryouji Ichimi, Hajime Kawasaki, Naoko Maeda, Akihiko Tanizawa, Koji Arai, Takanori Abe, Hiroaki Hisakawa, Hidemasa Miyashita, Jan-Inge Henter
Journal: Blood (1999)
Genetic Predisposition to Central Obesity and Risk of Type 2 Diabetes: Two Independent Cohort Studies
Authors: Tao Huang, Qibin Qi, Yan Zheng, Sylvia H. Ley, JoAnn E. Manson, Frank B. Hu, Lu Qi
Journal: Diabetes Care (2015)

OBJECTIVE Abdominal obesity is a major risk factor for type 2 diabetes (T2D). We aimed to examine the association between the genetic predisposition to central obesity, assessed by the waist-to-hip ratio (WHR) genetic score, and T2D risk. RESEARCH DESIGN AND METHODS The current study included 2,591 participants with T2D and 3,052 participants without T2D of European ancestry from the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). Genetic predisposition to central obesity was estimated using a genetic score based on 14 established loci for the WHR. RESULTS We found that the central obesity genetic score was linearly related to higher T2D risk. Results were similar in the NHS (women) and HPFS (men). In combined results, each point of the central obesity genetic score was associated with an odds ratio (OR) of 1.04 (95% CI 1.01–1.07) for developing T2D, and the OR was 1.24 (1.03–1.45) when comparing extreme quartiles of the genetic score after multivariate adjustment. CONCLUSIONS The data indicate that genetic predisposition to central obesity is associated with higher T2D risk. This association is mediated by central obesity.