tbuckley/cabot-search huggingface dataset:
A First-in-Man, Randomized, Placebo-Controlled Study to Evaluate the Safety and Feasibility of Autologous Delipidated High-Density Lipoprotein Plasma Infusions in Patients With Acute Coronary Syndrome
Authors: Ron Waksman, Rebecca Torguson, Kenneth M. Kent, Augusto D. Pichard, William O. Suddath, Lowell F. Satler, Brenda D. Martin, Timothy J. Perlman, Jo-Ann B. Maltais, Neil J. Weissman, Peter J. Fitzgerald, H. Bryan Brewer
Journal: Journal of the American College of Cardiology (2010)

This study aimed to determine whether serial autologous infusions of selective high-density lipoprotein (HDL) delipidated plasma are feasible and well tolerated in patients with acute coronary syndrome (ACS). Low HDL is associated with increased risk of cardiovascular disease. Plasma selective delipidation converts αHDL to preβ-like HDL, the most effective form of HDL for lipid removal from arterial plaques. ACS patients undergoing cardiac catheterization with ≥1 nonobstructive native coronary artery atheroma were randomized to either 7 weekly HDL selective delipidated or control plasma apheresis/reinfusions. Patients underwent intravascular ultrasound (IVUS) evaluation of the target vessel during the catheterization for ACS and up to 14 days following the final apheresis/reinfusion session. 2-D gel electrophoresis of delipidated plasmas established successful conversion of αHDL to preβ-like HDL. The trial was complete with 28 patients randomized. All reinfusion sessions were tolerated well by all patients. The levels of preβ-like HDL and αHDL in the delipidated plasma converted from 5.6% to 79.1% and 92.8% to 20.9%, respectively. The IVUS data demonstrated a numeric trend toward regression in the total atheroma volume of −12.18 ± 36.75 mm3in the delipidated group versus an increase of total atheroma volume of 2.80 ± 21.25 mm3in the control group (p = 0.268). In ACS patients, serial autologous infusions of selective HDL delipidated plasma are clinically feasible and well tolerated. This therapy may offer a novel adjunct treatment for patients presenting with ACS. Further study will be needed to determine its ability to reduce clinical cardiovascular events.
Safety and Efficacy of Drug-Eluting and Bare Metal Stents
Authors: Ajay J. Kirtane, Anuj Gupta, Srinivas Iyengar, Jeffrey W. Moses, Martin B. Leon, Robert Applegate, Bruce Brodie, Edward Hannan, Kishore Harjai, Lisette Okkels Jensen, Seung-Jung Park, Raphael Perry, Michael Racz, Francesco Saia, Jack V. Tu, Ron Waksman, Alexandra J. Lansky, Roxana Mehran, Gregg W. Stone
Journal: Circulation (2009)

The safety and efficacy of drug-eluting stents (DES) among more generalized "real-world" patients than those enrolled in pivotal randomized controlled trials (RCTs) are controversial. We sought to perform a meta-analysis of DES studies to estimate the relative impact of DES versus bare metal stents (BMS) on safety and efficacy end points, particularly for non-Food and Drug Administration-labeled indications.Comparative DES versus BMS studies published or presented through February 2008 with > or =100 total patients and reporting mortality data with cumulative follow-up of > or =1 year were identified. Data were abstracted from studies comparing DES with BMS; original source data were used when available. Data from 9470 patients in 22 RCTs and from 182 901 patients in 34 observational studies were included. RCT and observational data were analyzed separately. In RCTs, DES (compared with BMS) were associated with no detectable differences in overall mortality (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.81 to 1.15; P=0.72) or myocardial infarction (HR, 0.95; 95% CI, 0.79 to 1.13; P=0.54), with a significant 55% reduction in target vessel revascularization (HR, 0.45; 95% CI, 0.37 to 0.54; P<0.0001); point estimates were slightly lower in off-label compared with on-label analyses. In observational studies, DES were associated with significant reductions in mortality (HR, 0.78; 95% CI, 0.71 to 0.86), myocardial infarction (HR, 0.87; 95% CI, 0.78 to 0.97), and target vessel revascularization (HR, 0.54; 95% CI, 0.48 to 0.61) compared with BMS.In RCTs, no significant differences were observed in the long-term rates of death or myocardial infarction after DES or BMS use for either off-label or on-label indications. In real-world nonrandomized observational studies with greater numbers of patients but the admitted potential for selection bias and residual confounding, DES use was associated with reduced death and myocardial infarction. Both RCTs and observational studies demonstrated marked and comparable reductions in target vessel revascularization with DES compared with BMS. These data in aggregate suggest that DES are safe and efficacious in both on-label and off-label use but highlight differences between RCT and observational data comparing DES and BMS.
Dignity-Conserving Care—A New Model for Palliative Care
Authors: Harvey Max Chochinov
Journal: JAMA (2002)

The basic tenets of palliative care may be summarized as the goal of helping patients to die with dignity. The term "dignity" provides an overarching framework that may guide the physician, patient, and family in defining the objectives and therapeutic considerations fundamental to end-of-life care. Dignity-conserving care is care that may conserve or bolster the dignity of dying patients. Using segments of interviews with a patient with advanced lung cancer, his wife, and his palliative care physician, this article illustrates and explores various aspects of dignity-conserving care and the model on which it is based. Dignity-conserving care offers an approach that clinicians can use to explicitly target the maintenance of dignity as a therapeutic objective and as a principle of bedside care for patients nearing death.
Immunologic Therapy of Multiple Sclerosis
Authors: Barry G. W. Arnason, MD
Journal: Annual Review of Medicine (1999)

Three interferon β preparations (Betaseron ® , Avonex ® , and Rebif ® ) have shown efficacy in the treatment of relapsing-remitting multiple sclerosis (MS). Attack frequency is reduced by 30% and major attacks to an even greater extent. Accumulating disease burden as measured by annual T2-weighted magnetic resonance imaging is markedly lessened, and disease activity as measured by serial gadolinium-enhanced MRI scanning is reduced by over 80%. A fourth preparation, Copaxone ® , a basic copolymer of four amino acids, lessens MS attack frequency by 30% and also lessens disease activity as measured by gadolinium-enhanced MRI. Betaseron ® lessens accumulation of disability in MS patients with secondary progressive disease regardless of the severity of disability at the time treatment is commenced. MS is now a treatable disease.
Novel Therapies for Hepatitis C: Insights from the Structure of the Virus
Authors: Dahlene N. Fusco, Raymond T. Chung
Journal: Annual Review of Medicine (2011)

For the first time since the discovery of the hepatitis C virus (HCV), therapeutic options for hepatitis C have expanded. Several agents directly effective against HCV are now in development, including both direct-acting antiviral agents (DAAs) and host cofactor inhibitors. DAAs have been developed to inhibit several HCV proteins, including the NS3/4A serine protease, the NS5B RNA polymerase, NS5A, and NS4B. Host cofactor inhibitors include, but are not limited to, cyclophilin inhibitors, miR122 antagonists, and statins. Development of these agents represents a major advance in HCV therapeutics. This review provides a guide to HCV drugs in various stages of development, including an introduction to their mechanism of action, state of clinical development, efficacy, and side effects.
RNA Interference Suppression of MUC1 Reduces the Growth Rate and Metastatic Phenotype of Human Pancreatic Cancer Cells
Authors: Hideaki Tsutsumida, Benjamin J. Swanson, Pankaj K. Singh, Thomas C. Caffrey, Shinichi Kitajima, Masamichi Goto, Suguru Yonezawa, Michael A. Hollingsworth
Journal: Clinical Cancer Research (2006)

Abstract MUC1 is a highly glycosylated, type I transmembrane protein expressed by normal ductal epithelial cells of the pancreas, breast, lung, and gastrointestinal tract, and overexpressed in many cases of adenocarcinoma. We down-regulated MUC1 expression by RNA interference and investigated the effects on malignant and metastatic potential of a human pancreatic cancer cell line, S2-013. MUC1-suppressed clones, S2-013.MTII.C1 and S2-013.MTII.C2, were established by targeting a sequence 3,151 bp from the initiation codon and characterized in vitro for proliferation, invasion, and adhesion. We evaluated the effects of MUC1 suppression in vivo on tumor growth and metastatic properties following implantation into the cecum or pancreas of athymic mice. MUC1-suppressed clones showed significantly decreased proliferation in vitro and in vivo. Global gene expression was evaluated by oligonucleotide microarray analysis. Surprisingly, genes predicted to increase doubling times (cyclin B1 and cyclin D3) were overexpressed in MUC1-suppressed clones. There were alterations in expression of several genes that may affect the malignant properties of pancreatic cancer. Adhesion of MUC1-suppressed cells in vitro to type IV collagen and fibronectin was slightly increased, and adhesion was slightly decreased to type I collagen and laminin. Results of implantation to cecum and pancreas showed significant reduction of metastasis to lymph nodes, lung, or peritoneal sites compared with S2-013.gfp-neo control cells. These results support the hypothesis that MUC1 contributes significantly to growth and metastasis, and that down-regulation of MUC1 protein expression decreases the metastatic potential of pancreatic adenocarcinoma.
RE: Serum Lipids, Lipoproteins, and Risk of Breast Cancer: A Nested Case-Control Study Using Multiple Time Points
Authors: Lisa J. Martin, Ella Huszti, Philip W. Connelly, Cary V. Greenberg, Salomon Minkin, Norman F. Boyd
Journal: JNCI Journal of the National Cancer Institute (2016)

BACKGROUND There is strong evidence that breast cancer risk is influenced by environmental factors. Blood lipid and lipoprotein levels are also influenced by environmental factors and are associated with some breast cancer risk factors. We examined whether serial measures of serum lipids and lipoproteins were associated with breast cancer risk. METHODS We carried out a nested case-control study within a randomized long-term dietary intervention trial with 4690 women with extensive mammographic density followed for an average of 10 years for breast cancer incidence. We measured lipids in an average of 4.2 blood samples for 279 invasive breast cancer case subjects and 558 matched control subjects. We calculated subaverages of lipids for each subject based on menopausal status and use of hormone replacement therapy (HRT) at blood collection and analyzed their association with breast cancer using generalized estimating equations. All statistical tests were two-sided. RESULTS High-density lipoprotein-cholesterol (HDL-C) (P = .05) and apoA1 (P = .02) levels were positively associated with breast cancer risk (75(th) vs 25(th) percentile: HDL-C, 23% higher; apoA1, 28% higher) and non-HDL-C (P = .03) and apoB (P = .01) levels were negatively associated (75(th) vs 25(th) percentile: non-HDL-C, 19% lower; apoB, 22% lower). These associations were observed only when lipids were measured when HRT was not used. Total cholesterol and triglyceride levels were not statistically significantly associated with breast cancer risk. CONCLUSIONS These results demonstrate that serum lipids are associated with breast cancer risk in women with extensive mammographic density. The possibility that interventions for heart disease prevention, which aim to reduce non-HDL-C or raise HDL-C, may have effects on breast cancer risk merits examination.
Molecular abnormality of a unique japanese glucose‐6‐phosphate dehydrogenase variant (G6PD Kobe) with a greatly increased affinity for galactose‐6‐phosphate
Authors: Akira Hirono, Shiro Nakayama, Hisaichi Fujii, Shiro Miwa
Journal: American Journal of Hematology (1994)

Abstract Systematic molecular analysis of a Japanese class 1 glucose‐6‐phosphate dehydrogenase (GGPD) variant (G6PD Kobe) cONA revealed a unique nucleotide substitution (1318 C to T) in exon 11, which predicts a substitution of leucine for phenylalanine at residue 440. This substitution is located in a region surrounding the putative structural NADP‐binding domain. The markedly abnormal kinetics of glucose‐6‐phosphate (GGP) of GGPD Kobe suggest the interaction between both NADP and G6P binding sites. © 1994 Wiley‐Liss, Inc.
Online Medical Professionalism: Patient and Public Relationships: Policy Statement From the American College of Physicians and the Federation of State Medical Boards
Authors: Jeanne M. Farnan
Journal: Annals of Internal Medicine (2013)

User-created content and communications on Web-based applications, such as networking sites, media sharing sites, or blog platforms, have dramatically increased in popularity over the past several years, but there has been little policy or guidance on the best practices to inform standards for the professional conduct of physicians in the digital environment. Areas of specific concern include the use of such media for nonclinical purposes, implications for confidentiality, the use of social media in patient education, and how all of this affects the public's trust in physicians as patient–physician interactions extend into the digital environment. Opportunities afforded by online applications represent a new frontier in medicine as physicians and patients become more connected. This position paper from the American College of Physicians and the Federation of State Medical Boards examines and provides recommendations about the influence of social media on the patient–physician relationship, the role of these media in public perception of physician behaviors, and strategies for physician–physician communication that preserve confidentiality while best using these technologies.
The angiotensin-I-converting enzyme inhibitor enalapril and aspirin delay progression of pancreatic intraepithelial neoplasia and cancer formation in a genetically engineered mouse model of pancreatic cancer
Authors: V. Fendrich, N. M. Chen, M. Neef, J. Waldmann, M. Buchholz, G. Feldmann, E. P. Slater, A. Maitra, D. K. Bartsch
Journal: Gut (2009)

<h3>Background and aims</h3> There are no chemopreventive strategies for pancreatic cancer or its precursor lesions, pancreatic intraepithelial neoplasia (PanINs). Recent evidence suggests that aspirin and inhibitors of angiotensin-I converting enzyme (ACE inhibitors) have potential chemopreventive properties. In this study, we used a genetically engineered mouse model of pancreatic cancer to evaluate the chemopreventive potential of these drugs. <h3>Methods</h3> Drug treatment was initiated at the age of 5 weeks. <i>LsL-Kras<sup>G12D</sup>; Pdx1-Cre</i> or <i>LsL-Kras<sup>G12D</sup>; LsL-Trp53<sup>R172H</sup>; Pdx1-Cre</i> transgenic mice were randomly assigned to receive either mock treatment, aspirin, enalapril, or a combination of both. After 3 and 5 months, animals were killed. The effect of aspirin and enalapril was evaluated by histopathological analyses, immunostaining, and real-time PCR. <h3>Results</h3> After 3 and 5 months of treatment, enalapril and aspirin were able to significantly delay progression of mPanINs in <i>LsL-Kras<sup>G12D</sup></i>; <i>Pdx1-Cre</i> mice. Furthermore, development of invasive pancreatic cancer in <i>LsL-Kras<sup>G12D</sup>; LsL-Trp53<sup>R172H</sup></i>; <i>Pdx1-Cre</i> transgenic mice was partially inhibited by enalapril and aspirin. Invasive pancreatic cancer was identified in 15 of 25 (60%) <i>LsL-Kras<sup>G12D</sup>; LsL-Trp53<sup>R172H</sup></i>; <i>Pdx1-Cre</i> untreated control mice, but in only three of 17 (17.6%, p=0.01) mice treated with aspirin, in four of 17 (23.5%, p=0.03) in mice treated with enalapril alone, and in five of 16 (31.2%, p=0.11) mice treated with a combination of both drugs. Using real-time PCR we found a significant downregulation of the target genes VEGF and RelA demonstrating our ability to achieve effective pharmacological levels of aspirin and enalapril during pancreatic cancer formation in vivo. <h3>Conclusion</h3> Using a transgenic mouse model that imitates human pancreatic cancer, this study provides first evidence that aspirin and enalapril are effective chemopreventive agents by delaying the progression of PanINs and partially inhibiting the formation of murine pancreatic cancer. This study together supports the hypothesis that aspirin and ACE inhibitors might be a valid chemopreventive strategy.
HIV prevalence and testing practices among tuberculosis cases in London: a missed opportunity for HIV diagnosis?
Authors: A J Rodger, A Story, Z Fox, A Hayward
Journal: Thorax (2009)

<h3>Background:</h3> Universal testing for HIV in patients with tuberculosis (TB) has been advocated for over a decade. The aim of this study was to describe the prevalence and testing practices of HIV in TB centres in London. <h3>Methods:</h3> A cohort study was undertaken of all patients with TB in Greater London in 2003–4 (n = 1941). Logistic regression was used to assess factors affecting being offered and accepting testing and having a positive HIV result. <h3>Results:</h3> The overall known prevalence of HIV was 9.9% (193/1941). In those with a test result (including those diagnosed previously) it was 25.6%. Overall, 50.8% of patients aged ⩾20 years without previous testing were offered HIV testing and, of these, 73% accepted. In multivariable analysis, factors associated with being HIV positive were age 20–49 years, black ethnicity and being born overseas. Those with smear-negative disease and with a poor understanding of English were significantly less likely to be offered HIV testing. Factors associated with refusal of an offered test were female gender or age &gt;49 years. HIV status was not associated with smear status, drug resistance or death, but was associated with CNS disease (OR 1.8, 95% CI 1.0 to 3.0, p = 0.003). <h3>Conclusions:</h3> Nearly half the patients with TB in London in 2003–4 were not offered HIV testing. In those offered testing, uptake was high. Patients in higher risk groups were more likely to be offered testing but, even within the highest risk groups, testing was not universally offered. This represents a missed opportunity for diagnosing HIV in patients with TB in London.
Predicting the Future With Stem Cells
Authors: Sadia Mohsin, Joseph C. Wu, Mark A. Sussman
Journal: Circulation (2013)

The best way to predict future is to invent it.-Alan Kay T he efficacy of bypass surgery in patients with ischemic car- diomyopathy remains impossible to forecast accurately.In particular, individual variability in factors such as disease comorbidities, genetic background, aging, disease progression, lifestyle, and medications makes the prediction of the outcome of bypass surgery 1 a herculean task.Identifying readily available patient-specific information to prognosticate the likelihood of benefit with highly invasive procedures such as bypass surgery not only could minimize patient suffering but also could significantly reduce the cost and resource burdens on a healthcare system that is already stretched to the limit.
Fast and systematic genome-wide discovery of conserved regulatory elements using a non-alignment based approach.
Authors: Olivier Elemento, Saeed Tavazoie
Journal: Genome biology (2005)

Abstract We describe a powerful new approach for discovering globally conserved regulatory elements between two genomes. The method is fast, simple and comprehensive, without requiring alignments. Its application to pairs of yeasts, worms, flies and mammals yields a large number of known and novel putative regulatory elements. Many of these are validated by independent biological observations, have spatial and/or orientation biases, are co-conserved with other elements and show surprising conservation across large phylogenetic distances.
Meta-analysis: Travel and Risk for Venous Thromboembolism
Authors: Divay Chandra
Journal: Annals of Internal Medicine (2009)

Background: The potential risk for travel-related venous thromboembolism (VTE) has become an important public health concern because of rapid increases in long-distance travel; however, previous studies on this relationship are surprisingly contradictory. Purpose: To estimate the risk for VTE in travelers, determine whether a dose–response relationship exists, and identify reasons for the contradictory results of previous studies. Data Sources: MEDLINE, EMBASE, BIOSIS, CINAHL, grey-literature sources, contact with investigators, and reference lists of studies, without language restrictions. Study Selection: Reports were selected if they investigated the association between travel and VTE for persons who used any mode of transportation and if nontraveling persons were included for comparison. Data Extraction: Data on study and patient characteristics, risk estimates, and quality were independently extracted by 2 investigators. Pooled effect estimates were obtained by using random-effect meta-analysis. Data Synthesis: Of 1560 identified abstracts, 14 studies (11 case–control, 2 cohort, and 1 case–crossover) met inclusion criteria, including 4055 cases of VTE. Compared with nontravelers, the overall pooled relative risk for VTE in travelers was 2.0 (95% CI, 1.5 to 2.7). Significant heterogeneity was present because of the method for selecting control participants (P = 0.008): whether the studies used control participants who had been referred for VTE evaluation or nonreferred control participants. When the studies that used referred control participants were excluded, the pooled relative risk for VTE in travelers was 2.8 (CI, 2.2 to 3.7), without significant heterogeneity. A dose–response relationship was identified, with an 18% higher risk for VTE for each 2-hour increase in duration of travel by any mode (P = 0.010) and a 26% higher risk for every 2 hours of air travel (P = 0.005). Limitation: All available studies were from Western countries; generalizability to non-Western populations is expected but needs confirmation. Conclusion: Travel is associated with a nearly 3-fold higher risk for VTE, with a dose–response relationship of 18% higher risk for each 2-hour increase in travel duration. Heterogeneity in results of previous studies was due to selection bias toward the null from use of referred control participants.