tbuckley/cabot-search huggingface dataset:
Association of Plasma Phospholipid Long-Chain Omega-3 Fatty Acids With Incident Atrial Fibrillation in Older Adults
Authors: Jason H.Y. Wu, Rozenn N. Lemaitre, Irena B. King, Xiaoling Song, Frank M. Sacks, Eric B. Rimm, Susan R. Heckbert, David S. Siscovick, Dariush Mozaffarian
Journal: Circulation (2012)

Experimental studies suggest that long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) may reduce the risk of atrial fibrillation (AF). Prior studies evaluating fish or n-3 PUFA consumption from dietary questionnaires and incident AF have been conflicting. Circulating levels of n-3 PUFAs provide an objective measurement of exposure.Among 3326 US men and women ≥65 years of age and free of AF or heart failure at baseline, plasma phospholipid levels of eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid were measured at baseline by use of standardized methods. Incident AF (789 cases) was identified prospectively from hospital discharge records and study visit ECGs during 31 169 person-years of follow-up (1992-2006). In multivariable Cox models adjusted for other risk factors, the relative risk in the top versus lowest quartile of total n-3 PUFAs (eicosapentaenoic acid+docosapentaenoic acid+docosahexaenoic acid) levels was 0.71 (95% confidence interval, 0.57-0.89; P for trend=0.004) and of DHA levels was 0.77 (95% confidence interval, 0.62-0.96; P for trend=0.01). Eicosapentaenoic acid and docosapentaenoic acid levels were not significantly associated with incident AF. Evaluated nonparametrically, both total n-3 PUFAs and docosahexaenoic acid showed graded and linear inverse associations with incidence of AF. Adjustment for intervening events such as heart failure or myocardial infarction during follow-up did not appreciably alter results.In older adults, higher circulating total long-chain n-3 PUFA and docosahexaenoic acid levels were associated with lower risk of incident AF. These results highlight the need to evaluate whether increased dietary intake of these fatty acids could be effective for the primary prevention of AF.
Do the Dimensions of the Temperament and Character Inventory Map a Simple Genetic Architecture? Evidence From Molecular Genetics and Factor Analysis
Authors: Jeffrey H. Herbst, Alan B. Zonderman, Robert R. McCrae, Paul T. Costa
Journal: American Journal of Psychiatry (2000)

It has been reported that the human temperament dimensions of novelty seeking and harm avoidance are associated with polymorphisms in the D(4) dopamine receptor gene (D4DR) and the serotonin-transporter-linked promoter region (5-HTTLPR), respectively. Although these findings are consistent with Cloninger's hypothesized psychobiological model of temperament and character, many studies failed to replicate these findings. In the present study the authors tested whether the psychobiological model taps the genetic architecture of personality by exploring associations between these candidate genes and the dimensions of the Temperament and Character Inventory and by examining its phenotypic structure.Of the 946 male and female participants in the Baltimore Longitudinal Study of Aging to whom the Temperament and Character Inventory was administered, 587 were genotyped for a polymorphism with a 48-base-pair repeat in the D4DR gene and 425 were genotyped for a 44-base-pair insertion or deletion in the 5-HTTLPR polymorphism.There was no significant association between D4DR polymorphisms and novelty seeking. The authors also failed to find an association between 5-HTTLPR polymorphisms and harm avoidance. The factor structure of the Temperament and Character Inventory did not reveal the hypothesized phenotypic structure.This investigation produced no support for the temperament-character model at either the biological or psychological level.
Phase II Trial of Bicalutamide in Patients with Androgen Receptor–Positive, Estrogen Receptor–Negative Metastatic Breast Cancer
Authors: Ayca Gucalp, Sara Tolaney, Steven J. Isakoff, James N. Ingle, Minetta C. Liu, Lisa A. Carey, Kimberly Blackwell, Hope Rugo, Lisle Nabell, Andres Forero, Vered Stearns, Ashley S. Doane, Michael Danso, Mary Ellen Moynahan, Lamia F. Momen, Joseph M. Gonzalez, Arooj Akhtar, Dilip D. Giri, Sujata Patil, Kimberly N. Feigin, Clifford A. Hudis, Tiffany A. Traina
Journal: Clinical Cancer Research (2013)

Patients with hormone receptor-negative breast cancer generally do not benefit from endocrine-targeted therapies. However, a subset with androgen receptor (AR) expression is predicted to respond to antiandrogen therapies. This phase II study explored bicalutamide in AR-positive, estrogen receptor (ER), and progesterone receptor (PgR)-negative metastatic breast cancer.Tumors from patients with ER/PgR-negative advanced breast cancer were tested centrally for AR [immunohistochemistry (IHC) > 10% nuclear staining considered positive]. If either the primary or a metastatic site was positive, patients were eligible to receive the AR antagonist bicalutamide at a dose of 150 mg daily. Clinical benefit rate (CBR), the primary endpoint, was defined as the total number of patients who show a complete response (CR), partial response (PR), or stable disease (SD) > 6 months; secondary endpoints included progression-free survival (PFS) and toxicity. Correlative studies included measurement of circulating endocrine markers and IHC surrogates for basal-like breast cancer.Of 424 patients with ER/PgR-negative breast cancer, 12% tested AR-positive. The 6-month CBR was 19% [95% confidence interval (CI), 7%-39%] for bicalutamide. The median PFS was 12 weeks (95% CI, 11-22 weeks). Bicalutamide was well-tolerated with no grade 4/5 treatment-related adverse events observed.AR was expressed in 12% of patients with ER/PgR-negative breast cancer screened for this trial. The CBR of 19% observed with bicalutamide shows proof of principle for the efficacy of minimally toxic androgen blockade in a select group of patients with ER/PgR-negative, AR-positive breast cancer.
Cholestyramine in Type II Hyperlipoproteinemia
Authors: R. I. LEVY
Journal: Annals of Internal Medicine (1973)

The efficacy of cholestyramine (16 g/day) was compared with that of placebo in 47 outpatients with primary type II hyperlipoproteinemia (39 with type IIa) on isocaloric low-cholesterol diets over 14 weeks, by a random, crossover, double-blind design. Cholestyramine significantly (P < 0.005) lowered the plasma levels of cholesterol and of low-density lipoprotein cholesterol from means of 333 ± 54 mg/100 ml and 265 ± 49 mg/100 ml, respectively, to 264 ± 48 mg/100 ml and 193 ± 45 mg/100 ml; these were reductions of 20.6% and 27.3%. Cholestyramine had its greatest lipid-lowering effect during week 1 of therapy, although cholesterol levels continued to fall to week 4. With cholestyramine withdrawal, cholesterols returned to within 10% of base-line levels by week 1, but some effect persisted to week 4. Despite significant differences (P < 0.05) in base-line cholesterol levels between patients with and without xanthomas, between women and men, and between those above and those below 40 years of age, no significant differences were observed in lipid lowering. There was a direct relation (P < 0.05) between the initial cholesterol and low-density lipoprotein levels and the absolute cholesterol fall.
Smoking reduction with oral nicotine inhalers: double blind, randomised clinical trial of efficacy and safety
Authors: C. T Bolliger
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objectives:</b> To determine whether use of an oral nicotine inhaler can result in long term reduction in smoking and whether concomitant use of nicotine replacement and smoking is safe. <b>Design:</b> Double blind, randomised, placebo controlled trial. Four month trial with a two year follow up. <b>Setting:</b> Two university hospital pulmonary clinics in Switzerland. <b>Participants:</b> 400 healthy volunteers, recruited through newspaper advertisements, willing to reduce their smoking but unable or unwilling to stop smoking immediately. <b>Intervention:</b> Active or placebo inhaler as needed for up to 18 months, with participants encouraged to limit their smoking as much as possible. <b>Main outcome measures:</b> Number of cigarettes smoked per day from week six to end point. Decrease verified by a measurement of exhaled carbon monoxide at each time point compared with measurement at baseline. <b>Results:</b> At four months sustained reduction of smoking was achieved in 52 (26%) participants in the active group and 18 (9%) in the placebo group (P&lt;0.001; Fisher9s test). Corresponding figures after two years were 19 (9.5%) and 6 (3.0%) (P=0.012). <b>Conclusion:</b> Nicotine inhalers effectively and safely achieved sustained reduction in smoking over 24 months. Reduction with or without nicotine substitution may be a feasible first step towards smoking cessation in people not able or not willing to stop abruptly.
A radiosensitive T-lymphocyte associated with resistance of DBA/2 mice harboring Friend leukemia virus-dormant infections to transplantable Friend leukemia virus-erythroleukemia cells.
Authors: DiCicco Lm, Truitt Ga, Wheelock Ef
Journal: Cancer Research (1986)

The immunobiology of Friend erythroleukemia virus (FLV) has been the focal point of much research into immunological control of leukemia. We have been studying a murine model in which a rapidly fatal FLV infection of DBA/2 mice is suppressed to a dormant state by treatment with statolon, a double stranded RNA extract of Mycoplasma stoloniferum . We report here that mice with FLV-dormant infections resist the accumulation of transplanted FLV-transformed erythroleukemia cells (FLC-745) and that FLC-745 cells persist in the spleen for a prolonged period. Winn assays revealed that the spleen of FLV-dormant mice contain radiosensitive T-lymphocytes with anti-FLC-745 cell activity. Whole body irradiation of FLV-dormant mice abrogated their resistance to transplanted FLC-745 cells and confirmed the radiosensitivity of the protective immune response.
A unique pancreatic mitochondrial response to calcium and its role in apoptosis
Authors: W. Halangk, M. M Lerch
Journal: Gut (2009)

The exocrine pancreas synthesises more protein per gram of tissue than any other mammalian organ (with the exception of the lactating breast) and produces 6–20 g of digestive enzyme per day. This enormous metabolic activity requires an equally high energy supply for protein synthesis, transport and storage, as well as regulated secretion of active digestive enzymes and protease zymogens. Pancreatic acinar cells have therefore a high rate of mitochondrial energy metabolism. Pancreatic mitochondria effectively use nicotine adenine dinucleotide (NAD+)-dependent substrates to maintain the mitochondrial membrane potential (Δψm). Energy stored as Δψm is mainly used for two energy-requiring processes: ATP synthesis and Ca2+ accumulation. ATP is further needed for protein synthesis, signal transduction, intracellular ion homeostasis, vesicular transport to the apical pole of the acinar cell, and exocytosis of digestive enzymes into the duct lumen.

In pancreatic acinar cells a rise in intracellular free Ca2+ is the key signal transduction mechanism regulating stimulus–secretion coupling. Following exposure of the cell to cholecystokinin (CCK) or other hormones Ca2+ is released from intracellular stores via either Inositol triphosphate (IP3), nicotinic acid adenine dinucleotide phosphate (NAADP) or cyclic ADP ribose (cADPR) signalling pathways.1 2 The endoplasmatic reticulum (ER) operates as the main Ca2+ storing compartment, and this organelle is mostly located in the basal portion of the cell surrounding the nucleus.3 Additional Ca2+ storing organelles have been identified in the apical area of acinar cells and may be composed of ER protrusions into that region.2 3 Under physiological conditions hormonal stimulation results in an oscillating wave of free Ca2+ that is initiated in the apical portion of acinar cells and enables exocytosis of zymogen granule content from the luminal plasma membrane. Recently, …
Life jackets should be compulsory for all recreational boaters, say researchers
Authors: J. Wise
Journal: BMJ (2014)

<h3>Abstract</h3> <h3>Background</h3> Opioid signaling can occur through several downstream mediators and influence analgesia as well as reward mechanisms in the nervous system. K<sub>ATP</sub> channels are downstream targets of the μ opioid receptor and contribute to morphine-induced antinociception. <h3>Aims</h3> The aim of the present work was to assess the role of SUR1-subtype K<sub>ATP</sub> channels in antinocicpetion and hyperlocomotion of synthetic and semi-synthetic opioids. <h3>Methods</h3> Adult male and female mice wild-type (WT) and SUR1 deficient (KO) mice were assessed for mechanical and thermal antinociception after administration of either buprenorphine, fentanyl, or DAMGO. Potassium flux was assessed in the dorsal root ganglia and superficial dorsal horn cells in WT and KO mice. Hyperlocomotion was also assessed in WT and KO animals after buprenorphine, fentanyl, or DAMGO administration. <h3>Results</h3> SUR1 KO mice had attenuated mechanical antinociception after systemic administration of buprenorphine, fentanyl, and DAMGO. Potassium flux was also attenuated in the dorsal root ganglia and spinal cord cells after acute administration of buprenorphine and fentanyl. Hyperlocomotion after administration of morphine and buprenorphine was potentiated in SUR1 KO mice, but was not seen after administration of fentanyl or DAMGO. <h3>Conclusions</h3> These results suggest SUR1-subtype K<sub>ATP</sub> channels mediate the antinociceptive response of several classes of opioids (alkaloid and synthetic/semi-synthetic), but may not contribute to the “drug-seeking” behaviors of all classes of opioids.
Tetracycline for the treatment of pityriasis lichenoides
Authors: THADA PIAMPHONGSANT
Journal: British Journal of Dermatology (1974)

Thirteen cases of pityriasis lichenoides were treated with oral tetracycline. Five of them were completely cured, another seven had to continue to take 1 g/day. Addition of an antihistamine in one patient who did not respond to tetracycline gave a dramatic result. Throat swab cultures yielded coagulase positive staphylococci in four cases and other kinds of bacteria in many other cases. Based on the results of the treatment and histological findings, it is postulated that the pathogenesis of pityriasis lichenoides may be due to a hypersensitivity reaction to infectious agents.
Alterations in hepatic fructose metabolism in cirrhotic patients demonstrated by dynamic31phosphorus spectroscopy
Authors: Jean-François Dufour, Christopher Stoupis, François Lazeyras, Peter Vock, François Terrier, Jürg Reichen
Journal: Hepatology (1992)

ABSTRPlCT Quantitative liver function tests are based on the clearance concept and measure the plasma disappearance of a test compound such as galactose. Metabolism is inferred to be predominantly hepatic, and usually no knowledge is obtained of the true time course of metabolite formation. Dynamic 31 phosphorus magnetic resonance spectroscopy after intravenous administration of fructose directly measures hepatic sugar metabolism. To determine the feasability and the utility of 31 P magnetic resonance spectroscopy, we studied the responses of six healthy subjects and nine patients with nonalcoholic cirrhosis to a fructose load. Results were related to the impairment of hepatic function assessed by the galactose–elimination capacity test. Liver spectra were acquired in a 1.5 T whole–body nuclear magnetic resonance unit with a surface coil (9–cm diameter) placed ventrally on the liver; the one–dimensional chemical–shift imaging technique was used to obtain spectra from tissue slices parallel to the surface coil. After a basal spectrum had been obtained, fructose (250 mg/kg) was injected intravenously, and further spectra were collected sequentially every 6 min for 1 hr. Formation of monophosphate esters (9% ± 5% vs. 20% ± 8% of total area; p &lt; 0.01) and utilization of inorganic phosphate (5% ± 4% vs. 11% ± 3% of total area; p &lt; 0.005) were markedly decreased in cirrhotic patients. These measures correlated with the severity of the impairment of liver function measured by the galactose–elimination capacity (r = 0.53 to 0.69; p &lt; 0.05). We conclude that dynamic 31 P magnetic resonance spectroscopy is a safe, clinically feasible test that allows detailed insights into biochemical events in liver disease. (Hepatology 1992;15:835-842).
Identifying candidate allogeneic NK-cell donors for hematopoietic stem-cell transplantation based on functional phenotype
Authors: L V Hurton, R I Siddik, H Singh, S Olivares, B A Rabinovich, R Tian, D Mojsilovic, W Hildebrand, D A Lee, S S Kelly, R Champlin, E J Shpall, M Fernandez-Viña, L J N Cooper
Journal: Leukemia (2010)
FGFR3 has tumor suppressor properties in cells with epithelial phenotype
Authors: Marie Lafitte, Isabelle Moranvillier, Stéphane Garcia, Evelyne Peuchant, Juan Iovanna, Benoit Rousseau, Pierre Dubus, Véronique Guyonnet-Dupérat, Geneviève Belleannée, Jeanne Ramos, Aurélie Bedel, Hubert de Verneuil, François Moreau-Gaudry, Sandrine Dabernat
Journal: Molecular Cancer (2013)

Due to frequent mutations in certain cancers, FGFR3 gene is considered as an oncogene. However, in some normal tissues, FGFR3 can limit cell growth and promote cell differentiation. Thus, FGFR3 action appears paradoxical.FGFR3 expression was forced in pancreatic cell lines. The receptor exerted dual effects: it suppressed tumor growth in pancreatic epithelial-like cells and had oncogenic properties in pancreatic mesenchymal-like cells. Distinct exclusive pathways were activated, STATs in epithelial-like cells and MAP Kinases in mesenchymal-like cells. Both FGFR3 splice variants had similar effects and used the same intracellular signaling. In human pancreatic carcinoma tissues, levels of FGFR3 dropped in tumors.In tumors from epithelial origin, FGFR3 signal can limit tumor growth, explaining why the 4p16.3 locus bearing FGFR3 is frequently lost and why activating mutations of FGFR3 in benign or low grade tumors of epithelial origin are associated with good prognosis. The new hypothesis that FGFR3 can harbor both tumor suppressive and oncogenic properties is crucial in the context of targeted therapies involving specific tyrosine kinase inhibitors (TKIs). TKIs against FGFR3 might result in adverse effects if used in the wrong cell context.
IVT-seq reveals extreme bias in RNA sequencing
Authors: Nicholas F Lahens, Ibrahim Halil Kavakli, Ray Zhang, Katharina Hayer, Michael B Black, Hannah Dueck, Angel Pizarro, Junhyong Kim, Rafael Irizarry, Russell S Thomas, Gregory R Grant, John B Hogenesch
Journal: Genome biology (2014)

Abstract Background RNA-seq is a powerful technique for identifying and quantifying transcription and splicing events, both known and novel. However, given its recent development and the proliferation of library construction methods, understanding the bias it introduces is incomplete but critical to realizing its value. Results We present a method, in vitro transcription sequencing (IVT-seq), for identifying and assessing the technical biases in RNA-seq library generation and sequencing at scale. We created a pool of over 1,000 in vitro transcribed RNAs from a full-length human cDNA library and sequenced them with polyA and total RNA-seq, the most common protocols. Because each cDNA is full length, and we show in vitro transcription is incredibly processive, each base in each transcript should be equivalently represented. However, with common RNA-seq applications and platforms, we find 50% of transcripts have more than two-fold and 10% have more than 10-fold differences in within-transcript sequence coverage. We also find greater than 6% of transcripts have regions of dramatically unpredictable sequencing coverage between samples, confounding accurate determination of their expression. We use a combination of experimental and computational approaches to show rRNA depletion is responsible for the most significant variability in coverage, and several sequence determinants also strongly influence representation. Conclusions These results show the utility of IVT-seq for promoting better understanding of bias introduced by RNA-seq. We find rRNA depletion is responsible for substantial, unappreciated biases in coverage introduced during library preparation. These biases suggest exon-level expression analysis may be inadvisable, and we recommend caution when interpreting RNA-seq results.
Phase II Study of the AKT Inhibitor MK-2206 plus Erlotinib in Patients with Advanced Non–Small Cell Lung Cancer Who Previously Progressed on Erlotinib
Authors: Primo N. Lara, Jeff Longmate, Philip C. Mack, Karen Kelly, Mark A. Socinski, Ravi Salgia, Barbara Gitlitz, Tianhong Li, Mariana Koczywas, Karen L. Reckamp, David R. Gandara
Journal: Clinical Cancer Research (2015)

Preclinical modeling in non-small cell lung cancer (NSCLC) showed that stimulation with hepatocyte growth factor (HGF), the ligand for MET, could reverse the cytostatic and cytotoxic effects of the EGFR inhibitor erlotinib in erlotinib-sensitive cell lines. Inhibitors of AKT signaling mitigated this HGF-mediated resistance, partially restoring erlotinib activity. We conducted a phase II trial of erlotinib plus MK-2206, a highly selective inhibitor of AKT, in NSCLC patients.Eligible patients must have progressed following prior benefit from erlotinib, defined as response or stable disease > 12 weeks. Treatment consisted of erlotinib 150 mg orally every day + MK-2206 45 mg orally every alternate day on a 28-day cycle. Primary endpoints were RECIST response rate > 30% (stratum 1: EGFR mutant) and disease control rate (DCR) > 20% at 12 weeks (stratum 2: EGFR wild-type).Eighty patients were enrolled, 45 and 35 in stratum 1 and 2, respectively. Most common attributable adverse events (all grade 3) were rash, diarrhea, fatigue, and mucositis. Response and DCR were, respectively, 9% and 40% in stratum 1; 3% and 47% in stratum 2. Median progression-free survival was 4.4 months in stratum 1 and 4.6 months in stratum 2.Combination MK-2206 and erlotinib met its primary endpoint in erlotinib-pretreated patients with EGFR wild-type NSCLC. Although activity was seen in EGFR-mutated NSCLC, this did not exceed a priori estimates. AKT pathway inhibition merits further clinical evaluation in EGFR wild-type NSCLC.
Five-Year Risk of Colorectal Neoplasia after Negative Screening Colonoscopy
Authors: Thomas F. Imperiale, Elizabeth A. Glowinski, Ching Lin-Cooper, Gregory N. Larkin, James D. Rogge, David F. Ransohoff
Journal: New England Journal of Medicine (2008)

The appropriate interval for endoscopic rescreening after a negative colonoscopic examination is uncertain.