tbuckley/cabot-search huggingface dataset:
Meta-Analysis: Apolipoprotein E Genotypes and Risk for Coronary Heart Disease
Authors: Yiqing Song, Meir J. Stampfer, Simin Liu
Journal: Annals of Internal Medicine (2004)

Apolipoprotein E (apoE) genotypes play critical roles in lipid metabolism and are believed to influence risk for coronary heart disease (CHD). Despite many population studies, however, the impact of apoE polymorphism on risk for CHD remains uncertain.To qualitatively and quantitatively assess the evidence regarding the relation of apoE polymorphism to CHD risk.All relevant reports and references from original and review papers published from 1966 to January 2004.Predefined criteria were used to identify 48 relevant studies.A summary database that contained variables of study design, study sample and ethnicity, sex, apoE genotypes, CHD end points, plasma lipid levels, and other CHD risk factors was developed.The authors qualitatively evaluated many potential sources of heterogeneity. To quantify the extent of heterogeneity and assess the consistency of apoE-CHD associations, stratified analyses were conducted using the classic random-effects model. To further incorporate uncertainty due to between-study variation, the pooled odds ratios (ORs) and 95% credible intervals (CrIs) were estimated by using a Bayesian hierarchical model. Finally, the robustness of the pooled estimates was tested in multiple sensitivity analyses. Compared with individuals with the epsilon3/3 genotype, carriers of the apoE epsilon4 allele had a 42% higher risk for CHD (OR, 1.42 [95% CrI, 1.26 to 1.61]). The epsilon2 allele had no significant association with CHD risk (OR, 0.98 [CrI, 0.66 to 1.46]).This meta-analysis did not include unpublished data or studies published in languages other than English.Inadequate statistical power, differences in geographic and ethnic background, allele frequency, sex, CHD phenotypes, study design, and potential gene-environment interactions may have contributed to the conflicting results of previous studies. The apoE epsilon4 allele is a significant risk factor for CHD.
Intravenous Calcium and Magnesium for Oxaliplatin-Induced Sensory Neurotoxicity in Adjuvant Colon Cancer: NCCTG N04C7
Authors: Axel Grothey, Daniel A. Nikcevich, Jeff A. Sloan, John W. Kugler, Peter T. Silberstein, Todor Dentchev, Donald B. Wender, Paul J. Novotny, Umesh Chitaley, Steven R. Alberts, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2010)

Purpose Cumulative sensory neurotoxicity (sNT) is the dose-limiting toxicity of oxaliplatin, which commonly leads to early discontinuation of oxaliplatin-based therapy in the palliative and adjuvant settings. In a nonrandomized, retrospective study, intravenous (IV) calcium/magnesium (Ca/Mg) was associated with reduced oxaliplatin-induced sNT. Methods Patients with colon cancer undergoing adjuvant therapy with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) were randomly assigned to Ca/Mg (1g calcium gluconate plus 1g magnesium sulfate pre- and post-oxaliplatin) or placebo, in a double-blinded manner. The primary end point was the percentage of patients with grade 2 or greater sNT at any time during or after oxaliplatin-based therapy by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; version 3) criteria. An oxaliplatin-specific sNT scale and patient questionnaires were also used to assess sNT. After 104 of 300 planned patients were enrolled, the study was closed. This was due to preliminary reports from another trial that suggested that Ca/Mg decreased treatment efficacy; these data were subsequently found to be incorrect. Results Overall, 102 patients were available for analysis. Ca/Mg decreased the incidence of chronic, cumulative, grade 2 or greater sNT, as measured by NCI CTCAE (P = .038) and also by the oxaliplatin-specific sNT scale (P = .018). In addition, acute muscle spasms associated with oxaliplatin were significantly reduced (P = .01) No effect on acute, cold-induced sNT was found. No substantial differences in adverse effects were noted between Ca/Mg and placebo. Conclusion Despite early termination and decreased statistical power, this study supports IV Ca/Mg as an effective neuroprotectant against oxaliplatin-induced cumulative sNT in adjuvant colon cancer.
Patients' Decision-Making Process Regarding Participation in Phase I Oncology Research
Authors: Manish Agrawal, Christine Grady, Diane L. Fairclough, Neal J. Meropol, Kim Maynard, Ezekiel J. Emanuel
Journal: Journal of Clinical Oncology (2006)

This study assesses the decision-making process of patients enrolling in phase I oncology studies.Participants were eligible if they had consented to participate in a phase I cancer study at one of five cancer centers, understood English, and were older than 18 years. Trained interviewers conducted structured in-person interviews.Of the 163 participants, 88% were white, 96% had health insurance, and 51% were college graduates or post graduates. Overall, 81% were aware of hospice, but only 6% had seriously considered hospice for themselves; 84% were aware of palliative care and 10% seriously considered it for themselves; and 7% considered getting no treatment at all. Overall, 75% reported moderate or a lot of pressure to participate in the phase I study because their cancer was growing, whereas 7% reported such pressure from the study investigators and 9% felt such pressure from their families. For 63% of patients, the most important information for decision making was that the phase I drug killed cancer cells; only 12% reported that the adverse effects of the drug(s) was the most useful information. More than 90% of patients said they would still participate in the study even if the experimental drug caused serious adverse effects, including a 10% chance of dying.Patients are aware of many alternatives to phase I studies, but do not seriously consider them. Very few experience pressure from family or researchers to participate in research. Their main goal is to fight their cancer, and almost no adverse effect, including death, would dissuade them from enrolling.
CELL BIOLOGY OF ANTIGEN PROCESSING IN VITRO AND IN VIVO
Authors: E. Sergio Trombetta, Ira Mellman
Journal: Annual Review of Immunology (2005)

The conversion of exogenous and endogenous proteins into immunogenic peptides recognized by T lymphocytes involves a series of proteolytic and other enzymatic events culminating in the formation of peptides bound to MHC class I or class II molecules. Although the biochemistry of these events has been studied in detail, only in the past few years has similar information begun to emerge describing the cellular context in which these events take place. This review thus concentrates on the properties of antigen-presenting cells, especially those aspects of their overall organization, regulation, and intracellular transport that both facilitate and modulate the processing of protein antigens. Emphasis is placed on dendritic cells and the specializations that help account for their marked efficiency at antigen processing and presentation both in vitro and, importantly, in vivo. How dendritic cells handle antigens is likely to be as important a determinant of immunogenicity and tolerance as is the nature of the antigens themselves.
EGb761 ameliorates the formation of foam cells by regulating the expression of SR-A and ABCA1: role of haem oxygenase-1
Authors: Jin-Yi Tsai, Kuo-Hui Su, Song-Kun Shyue, Yu Ru Kou, Yuan-Bin Yu, Sheng-Huang Hsiao, An-Na Chiang, Yuh-Lin Wu, Li-Chieh Ching, Tzong-Shyuan Lee
Journal: Cardiovascular Research (2010)

Accumulation of foam cells in the intima is a hallmark of early-stage atherosclerotic lesions. Ginkgo biloba extract (EGb761) has been reported to exert anti-oxidative and anti-inflammatory properties in atherosclerosis, yet the significance and the molecular mechanisms of action of EGb761 in the formation of macrophage foam cells are not fully understood.Treatment with EGb761 resulted in a dose-dependent decrease in oxidized low-density lipoprotein (oxLDL)-mediated cholesterol accumulation in macrophages, a consequence that was due to a decrease in cholesterol uptake and an increase in cholesterol efflux. Additionally, EGb761 significantly down-regulated the mRNA and protein expression of class A scavenger receptor (SR-A) by decreasing expression of activator protein 1 (AP-1); however, EGb761 increased the protein stability of ATP-binding cassette transporter A1 (ABCA1) by reducing calpain activity without affecting ABCA1 mRNA expression. Small interfering RNA (siRNA) targeting haem oxygenase-1 (HO-1) abolished the EGb761-induced protective effects on the expression of AP-1, SR-A, ABCA1, and calpain activity. Accordingly, EGb761-mediated suppression of lipid accumulation in foam cells was also abrogated by HO-1 siRNA. Moreover, the lesion size of atherosclerosis was smaller in EGb761-treated, apolipoprotein E-deficient mice compared with the vehicle-treated mice, and the expression of HO-1, SR-A, and ABCA1 in aortas was modulated similar to that observed in macrophages.These findings suggest that EGb761 confers a protection from the formation of foam cells by a novel HO-1-dependent regulation of cholesterol homeostasis in macrophages.
Differential anti-hepatitis B virus activity in vitro of three potent of inosine monophosphate dehydrogenase inhibitors: mycophenolic acid (MPA), 5-ethynyl-1-β-d-ribofuranosyli-midazole-4-carboxamide (EICAR) and ribavirin
Authors: Z.J. Gong, S. De Meyer, C. Clarysse, J.F. van Pelt, T. Coopmans, J. Neyts, E. De Clerq, S.H. Yap
Journal: Journal of Hepatology (1998)
Common Structural and Epigenetic Changes in the Genome of Castration-Resistant Prostate Cancer
Authors: Terence W. Friedlander, Ritu Roy, Scott A. Tomlins, Vy T. Ngo, Yasuko Kobayashi, Aruna Azameera, Mark A. Rubin, Kenneth J. Pienta, Arul Chinnaiyan, Michael M. Ittmann, Charles J. Ryan, Pamela L. Paris
Journal: Cancer Research (2011)

Abstract Progression of primary prostate cancer to castration-resistant prostate cancer (CRPC) is associated with numerous genetic and epigenetic alterations that are thought to promote survival at metastatic sites. In this study, we investigated gene copy number and CpG methylation status in CRPC to gain insight into specific pathophysiologic pathways that are active in this advanced form of prostate cancer. Our analysis defined and validated 495 genes exhibiting significant differences in CRPC in gene copy number, including gains in androgen receptor (AR) and losses of PTEN and retinoblastoma 1 (RB1). Significant copy number differences existed between tumors with or without AR gene amplification, including a common loss of AR repressors in AR-unamplified tumors. Simultaneous gene methylation and allelic deletion occurred frequently in RB1 and HSD17B2, the latter of which is involved in testosterone metabolism. Lastly, genomic DNA from most CRPC was hypermethylated compared with benign prostate tissue. Our findings establish a comprehensive methylation signature that couples epigenomic and structural analyses, thereby offering insights into the genomic alterations in CRPC that are associated with a circumvention of hormonal therapy. Genes identified in this integrated genomic study point to new drug targets in CRPC, an incurable disease state which remains the chief therapeutic challenge. Cancer Res; 72(3); 616–25. ©2011 AACR.
Adjuvant Androgen Deprivation for High-Risk Prostate Cancer After Radical Prostatectomy: SWOG S9921 Study
Authors: Tanya B. Dorff, Thomas W. Flaig, Catherine M. Tangen, Maha H.A. Hussain, Gregory P. Swanson, David P. Wood, Wael A. Sakr, Nancy A. Dawson, Naomi B. Haas, E. David Crawford, Nicholas J. Vogelzang, Ian M. Thompson, L. Michael Glode
Journal: Journal of Clinical Oncology (2011)

Purpose Men with high-risk features (extraprostatic extension or high Gleason grade) face a high risk of prostate cancer recurrence after radical prostatectomy. Clinical trials of adjuvant systemic therapy for such patients have been limited. Patients and Methods The SWOG (Southwest Oncology Group) S9921 study randomly assigned 983 men with high-risk features at prostatectomy to receive adjuvant therapy with androgen deprivation (ADT) alone or in combination with mitoxantrone chemotherapy. ADT consisted of goserelin and bicalutamide for 2 years. Results Although the final primary treatment comparison results are not ready for publication, this article reports results in the ADT-alone control arm with a median follow-up of 4.4 years. For these 481 men, the estimated 5-year biochemical failure-free survival is 92.5% (95% CI, 90 to 95), and 5-year overall survival is 95.9% (95% CI, 93.9 to 97.9). Conclusion The results of this trial, taken in context, make a compelling argument for counseling all high-risk patients with prostate cancer about adjuvant ADT. This article discusses the challenges in the design and implementation of clinical trials to take the next step forward in adjuvant therapy for prostate cancer because of the excellent survival achieved with currently available therapies and highlights the need for better molecular markers to personalize care.
A NATIONAL STRATEGY FOR RESEARCH AND DEVELOPMENT:Lessons from England
Authors: Nick Black
Journal: Annual Review of Public Health (1997)

▪ Abstract Increasing concern about the state of basic and clinical research in England during the 1980s led to an influential parliamentary review. Surprisingly, the review recommended the strengthening of public health and health services research through the establishment of a research and development (R&amp;D) program for the National Health Service (NHS). The program that started in 1991 was unique in that it was fully integrated into the management structure of the NHS. No country had ever attempted such an ambitious approach. While a review of the first five years of the program reveals many achievements, it also raises several concerns: Debate about the philosophy and aims of the program continues; the need to maintain political support requires constant attention; policy changes in other areas need to be accommodated; central control of a national, coordinated R&amp;D program has to be guarded; methods of priority setting need to be enhanced; insufficient human resources to run the program have to be contended with; and the program needs to be rigorously evaluated. Other countries with a unified health system could learn much from the English experience. Countries with pluralist systems might benefit from specific parts of the experience.
Are we Willing to Fight for our Research?
Authors: David H. Hubel
Journal: Annual Review of Neuroscience (1991)

In June of 1989 The Johns Hopkins Medical School celebrated its hun­ dredth anniversary. In the half-dozen speeches at the opening ceremonies, given by major figures at Hopkins, plus the Secretary of Health, the Postmaster General, and the chief executive officer of one of the country's leading pharmaceutical houses, all the important problems confront­ ing modern medicine were addressed, from AIDS to our legal system­ with one exception. Not one speaker mentioned the animal activists. After the convocation I asked my host, one of the world's leading neurophysiologists, how he could account for this. His answer: David, they're scared to death. On February 8, 1990, the Dean of the Knoxville Tennessee School of Veterinary Medicine was murdered. He was found in the driveway of his home with eight bullets in his chest. Less than two weeks later the Boston Herald reported that animal-rights extremists had threatened to kill one veterinary-college dean each month for twelve months, as a protest against research involving the use of animals. At present these rumors remain unconfirmed, and there seems to be no shred of evidence that the murder had anything to do with the animal activists. What is significant is the immediate and instinctive reaction of those of us who use animals in our research, to have it even cross our minds that the murder might represent some new wave of fanaticism on the part of the animal-rights activists. No one who uses animals in medical research can doubt that these activists pose a most serious threat to our field and to society. I am not a scholar of the animal-activist movement and do not count myself an expert in its history or philosophy. My involvement comes partly from the fact
The Fish Odor Syndrome
Authors: E. Dorinda Shelley
Journal: JAMA (1984)

TOO OFTEN the patient with generalized body odor of inapparent origin presents only a history of the problem to a skeptical physician. Like hives, the odor may be episodic and not present at the time of an office visit. The odor also may be apparent only to an hyperosmic patient, such as one with cystic fibrosis.<sup>1</sup>The physician himself may be hyposmic, or the odor lost in the efficient ventilation of the office setting, as happened with an occupationally induced tellurium odor.<sup>2</sup>Unable to confirm the complaint, the physician may begin to entertain a diagnosis of schizophrenia or consider a computed tomographic scan of the brain to search for a tumor. Finally, both the physician and the patient may be disbelieving when the odor is noticed only by others, as has occurred with the use of topical benzoyl peroxide.<sup>3</sup> However, some body odors overwhelm and call for
Groin pain associated with ultrasound finding of inguinal canal posterior wall deficiency in Australian Rules footballers.
Authors: J W Orchard, J W Read, J Neophyton, D Garlick
Journal: British Journal of Sports Medicine (1998)

OBJECTIVES: To investigate the prevalence of inguinal canal posterior wall deficiency (sports hernia) in professional Australian Rules footballers using an ultrasound technique and correlate the results with the clinical symptom of groin pain. METHODS: Thirty five professional Australian footballers with and without groin pain were investigated blind with a dynamic high resolution ultrasound technique for presence of posterior wall deficiency. RESULTS: Fourteen players had a history of significant recent groin pain and ten of these were found to have bilateral inguinal canal posterior wall deficiency (p &lt; 0.01). The relative risk for a history of groin pain with bilateral deficiency was 8.0 (95% confidence interval 1.73 to 37.1). Groin pain was also found to be associated with increasing age (p &lt; 0.01) which was an independent risk factor. Surgical, clinical, and ultrasound follow up for players who underwent hernia repair confirmed the validity of ultrasound as a diagnostic tool. CONCLUSIONS: Dynamic ultrasound examination is able to detect inguinal canal posterior wall deficiency in young males with no clinical signs of hernia. This condition is very prevalent in professional Australian Rules footballers, including some who are asymptomatic. There was a correlation between bilateral deficiency and groin pain, although the temporal relationship between the clinical and ultrasound findings is not established by the current study. Ultrasound shows promise as a diagnostic tool in athletes with chronic groin pain who are considered possible candidates for hernia repair.
Effect of sport-related concussion on clinically measured simple reaction time
Authors: James T Eckner, Jeffrey S Kutcher, Steven P Broglio, James K Richardson
Journal: British Journal of Sports Medicine (2013)

Reaction time (RT) is a valuable component of the sport concussion assessment battery. RT is typically measured using computers running specialised software, which limits its applicability in some athletic settings and populations. To address this, we developed a simple clinical test of RT (RTclin) that involves grasping a falling measuring stick.To determine the effect of concussion on RTclin and its sensitivity and specificity for concussion.Concussed athletes (n=28) and non-concussed control team-mates (n=28) completed RTclin assessments at baseline and within 48 h of injury. Repeated measures analysis of variance compared mean baseline and follow-up RTclin values between groups. Sensitivity and specificity were calculated over a range of reliable change confidence levels.RTclin differed significantly between groups (p<0.001): there was significant prolongation from baseline to postinjury in the concussed group (p=0.003), with a trend towards improvement in the control group (p=0.058). Sensitivity and specificity were maximised when a critical change value of 0 ms was applied (ie, any increase in RTclin from baseline was interpreted as abnormal), which corresponded to a sensitivity of 75%, specificity of 68% and a 65% reliable change confidence level.RTclin appears sensitive to the effects of concussion and distinguished concussed and non-concussed athletes with similar sensitivity and specificity to other commonly used concussion assessment tools. Given its simplicity, low cost and minimal time requirement, RTclin should be considered a viable component of the sports medicine provider's multifaceted concussion assessment battery.
Effect of inhaled heparin on lung function and coagulation in healthy volunteers
Authors: K.E. Bendstrup, J. Gram, J.I. Jensen
Journal: European Respiratory Journal (2002)

The aim of the present study was to investigate the safety of increasing doses of a well-defined lower respiratory tract (LRT) dose of inhaled heparin with regard to pulmonary function and coagulation. Ten volunteers inhaled heparin from Sidestream jet nebulizers loaded with 100,000, 200,000, 300,000 or 400,000 International Units (IU) of heparin. Lung function, antifactor (anti)-Xa, activated partial thromboplastin time (APTT), tissue factor pathway inhibitor (TFPI), whole blood clotting time, platelets, von Willebrand factor, and C‐reactive protein were determined before and 1, 3, 6, and 24 h after inhalation. The highest LRT dose was 32,000 IU heparin. Inhaled heparin did not affect pulmonary function. The area under the curve of the anti-Xa activity increased with increasing doses of heparin (p=0.005), but remained unchanged for all other variables. Peak anti-Xa activity was 0.113 IU·mL −1 6 h after inhalation of 400,000 IU heparin. When compared to baseline values: anti-Xa increased after 200,000 (p=0.03), 300,000 (p=0.004), and 400,000 IU (p=0.002) heparin; APTT increased to a maximum of 1.03 6 h after inhalation of 400,000 IU heparin (p=0.05); TFPI increased after 100,000 (p=0.01), 200,000 (p=0.01), 300,000 (p=0.006) and 400,000 IU (p&lt;0.001). Inhaled heparin delivery of 32,000 International Units to the lower respiratory tract can safely be inhaled for clinical or research purposes.
Induction chemotherapy followed by concurrent chemotherapy and definitive high-dose radiotherapy for patients with locally advanced non-small-cell lung cancer (stages IIIa/IIIb):a pilot phase I/II trial
Authors: C. Pöttgen, W. Eberhardt, S. Bildat, G. Stüben, G. Stamatis, L. Hillejan, S. Sohrab, H. Teschler, S. Seeber, H. Sack, M. Stuschke
Journal: Annals of Oncology (2002)