tbuckley/cabot-search huggingface dataset:
Abstract B03: Loss of the Polycomb mark at bivalent promoters leads to activation of intestinal stem cell genes in colorectal cancer
Authors: Maria A. Hahn, Arthur X. Li, Xiwei Wu, Daniel W. Rosenberg, Gerd P. Pfeifer
Journal: Cancer Research (2013)

Abstract During tumor formation, transcription of many genes becomes deregulated. In order to elucidate epigenetic mechanisms responsible for this phenomenon, we analyzed genome-wide patterns of several histone marks, 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in human stage II colorectal cancer and matching normal tissue samples. By using liquid chromatography—mass spectrometry (LC-MS/MS), we determined that colon tumors have strongly reduced global levels of 5hmC. However, Tet-assisted bisulfite sequencing showed that site-specific loss of 5hmC in tumors is not associated with localized aberrant CpG island hypermethylation. We observed that DNA hypermethylation is generally targeted to bivalent promoters, which loose H3K27me3 and the associated genes are repressed effectively. Importantly, loss of H3K27me3 at bivalent promoters is not always coupled with gain of 5mC. Instead, H3K27me3 loss is also frequently associated with activation of intestinal stem cell markers and stem cell regulators including LGR5, SOX9, CDX1, CDX2, KLF5, and SALL4 as well as activation of many genes linked to colorectal cancer progression such as MET, CLDN1, PTGS2 (COX-2) and CCND1 (cyclin D1). Activation of these genes correlates with accumulation of the active chromatin mark H3K4me3 at their promoters. Our study demonstrates two distinct features of H3K27me3 loss in cancer. Loss of H3K27me3 at bivalent genes can be accompanied by either gain of 5mC and strong repression or by persistence or gain of H3K4me3 and gene activation. We propose that instability of H3K27me3 coupled with selection for tumor-promoting events plays a major role in colorectal cancer progression most notably by causing activation of cancer driving genes including factors involved in stem cell maintenance. Citation Format: Maria A. Hahn, Arthur X. Li, Xiwei Wu, Daniel W. Rosenberg, Gerd P. Pfeifer. Loss of the Polycomb mark at bivalent promoters leads to activation of intestinal stem cell genes in colorectal cancer. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr B03.
Undertreated and Untreated Pain Should Be Considered an Adverse Event of Neonatal Circumcision—Reply
Authors: Charbel El Bcheraoui, Kenneth L. Dominguez, Peter H. Kilmarx
Journal: JAMA Pediatrics (2014)

We would like to thank Bisogni et al., for their comments about intra- and post-operative pain as an adverse event (AE) to male circumcision (MC). Use of appropriate analgesia for pain management is a good practice that should be the standard of care during and after any surgical procedure as it can substantially control pain1. In a prospective study of 583 neonatal circumcisions performed between December 2005 and December 2008, when appropriate analgesia was applied, 93.5% of neonates circumcised in the first week of life showed no indication of pain on an objective standardized neonatal pain rating system used by the authors2.

The recently published manuscript3 which found a low incidence of adverse events (AEs) (< 0.5%) associated with male circumcision in U.S. medical settings during 2001–2010 is based on data from a healthcare reimbursement claims database. This database captures only diagnoses and procedures billed to third parties. The analysis studied the association between 41 AEs, not including pain, and male circumcision. A search of the same healthcare reimbursement claims database for the ICD9 codes 338.18 (other acute postoperative pain) and 338.19 (other acute pain) detected one patient with pain associated with the male circumcision procedure among 1,400,920 circumcised males. Taking into consideration the possibility that pain may be an underreported AE in the healthcare reimbursement claims database used for this analysis, a more thorough analysis of the association of pain and male circumcision would require additional data sources, including information related to use of and type of pain control methods. As previously recommended3, future researchers studying the association between AEs and male circumcision should consider using additional data sources to ascertain AEs that are not captured in data from reimbursement claims.
Law and Medicine in JAMA
Authors: Larry Gostin, Helene M. Cole
Journal: JAMA (1992)

In this issue ofThe Journalwe introduce a new editor of the Law and Medicine section (L.G.). Although the section has appeared for a number of years on an occasional basis, it is hoped that with new leadership, it will be a regular feature. Our goal is to publish timely and scholarly articles devoted to emerging issues of importance in health law and ethics. Manuscript submissions of potential interest to us would include those on traditional law and medicine topics such as confidentiality, consent to treatment, malpractice, access to health care, and the withdrawal of life-sustaining treatment. The interrelationship of law, ethics, and innovative scientific technologies—for example, the ethical use of information from the Human Genome Project—is another important topic that merits attention. We anticipate that articles in the section will review public health law and government policies relating to tobacco, illicit drug and alcohol See also p 3468.
Plaque Gruel of Atheromatous Coronary Lesion May Contribute to the No-Reflow Phenomenon in Patients With Acute Coronary Syndrome
Authors: Jun-ichi Kotani, Shinsuke Nanto, Gary S. Mintz, Masafumi Kitakaze, Tomoki Ohara, Takakazu Morozumi, Seiki Nagata, Masatsugu Hori
Journal: Circulation (2002)

Background— No-reflow associated with direct angioplasty (PCI) of patients with acute coronary syndromes (ACS) is associated with unfavorable results. Methods and Results— We used a new thrombectomy device to treat 51 lesions in 48 consecutive ACS patients (40 male and 8 female; mean age 63 years) and conducted a microscopic analysis of aspirates and blood samples retrieved from the culprit coronary artery. The first aspirate was collected before PCI and the second was collected separately after percutaneous transluminal coronary angioplasty or stenting, including samples from the no-reflow lumen. Light microscopy showed that the materials obtained from the pre-PCI aspiration consisted of thrombus in 37.5%, thrombus and atheroma in 35.0%, and atheromatous plaque in 27.5%. The materials collected from the post-PCI aspiration were thrombus in 8.3%, thrombus and atheroma in 41.7%, and atheromatous plaque in 50.0%. We then compared the 9 lesions (19.1%) with no-reflow to those without no-reflow. There was no difference in the pre-PCI aspirates. However, after PCI, there was more atheromatous plaque retrieved from patients with no-reflow ( P &lt;0.001) as well as significantly more platelet and fibrin complex, macrophages, and cholesterol crystals in the blood aspirated from no-reflow cases. Aspiration of these elements improved the no-reflow in 7 of 9 lesions to TIMI-3 flow. Conclusions— No-reflow after angioplasty may be caused by gruel that formed from an atheroma attributable to mechanical plaque disruption during intervention.
Length of hospital stay after hip fracture and short term risk of death after discharge: a total cohort study in Sweden
Authors: P. Nordstrom, Y. Gustafson, K. Michaelsson, A. Nordstrom
Journal: BMJ (2015)

<b>Objective</b> To investigate relation between inpatient length of stay after hip fracture and risk of death after hospital discharge. <b>Setting</b> Population ≥50 years old living in Sweden as of 31 December 2005 with a first hip fracture the years 2006-12. <b>Participants</b> 116 111 patients with an incident hip fracture from a closed nationwide cohort. <b>Main outcome measure</b> Death within 30 days of hospital discharge in relation to hospital length of stay after adjustment for multiple covariates. <b>Results</b> Mean inpatient length of stay after a hip fracture decreased from 14.2 days in 2006 to 11.6 days in 2012 (P&lt;0.001). The association between length of stay and risk of death after discharge was non-linear (P&lt;0.001), with a threshold for this non-linear effect of about 10 days. Thus, for patients with length of stay of ≤10 days (n=59 154), each 1-day reduction in length of stay increased the odds of death within 30 days of discharge by 8% in 2006 (odds ratio 1.08 (95% confidence interval 1.04 to 1.12)), which increased to16% in 2012 (odds ratio 1.16 (1.12 to 1.20)). In contrast, for patients with a length of stay of ≥11 days (n=56 957), a 1-day reduction in length of stay was not associated with an increased risk of death after discharge during any of the years of follow up. <b>Limitations</b> No accurate evaluation of the underlying cause of death could be performed. <b>Conclusion</b> Shorter length of stay in hospital after hip fracture is associated with increased risk of death after hospital discharge, but only among patients with length of stay of 10 days or less. This association remained robust over consecutive years.
Electrocardiography: Practical Applications With Vectorial Principles
Authors: I. Martin Grais
Journal: JAMA (1981)

The second edition of Dr Chung's book has been revised considerably and now contains chapters on His bundle electrocardiography, exercise electrocardiography, and the sick sinus syndrome. The author indicates that the basic aims and designs of the first edition are unchanged, namely, that the text be practical, concise, and well suited for use by medical students and house officers. He further states that it was not his intent to include uncommon or sophisticated arrhythmias; however, he has included "every known type of electrocardiographic abnormality." Despite his obvious enthusiasm, Dr Chung has not been successful in achieving his goals in his second edition. His writing is not clear or concise. Run-on sentences, indifferent referents, and redundancies frequently provide frustration rather than a crisp, straightforward learning experience. Why waste physicians' and students' valuable time? Where were Dr Chung's editors? There are other objectionable features in this book. "Uncommon or sophisticated arrhythmias" are
PREVENTION OF ENTRANCE OF AIR IN PARACENTESIS THORACIS
Authors: T. Walker
Journal: BMJ (1855)

S19tur tilting up the calculus, it was removed without any employment of the forceps.The stone was round, and of about the size of a small horse-bean.The amount of blood lost during the operation was trifling.No other stone could be detected.A sponige was now applied to the wound, and retained in position by a bandage.To detail the daily progress of the case would be tedious, and without any practical importance.When the patient first passed urine after the operation, a few drops escaped by the urethra; but iu less than forty-eight hours this was reversed, and he retained the urine for four or five hours- longer, in fact, than he had done for months.On the third
WHO and MSF appeal for funds for new meningitis vaccine
Authors: F. Fleck
Journal: BMJ (2003)

The World Health Organization and Medecins Sans Frontieres (MSF) have launched an urgent appeal for funds to purchase six million doses of a new cut-price vaccine that would prevent a dangerous new strain of meningitis triggering an epidemic across sub-Saharan Africa early next year.

Every year the disease—which kills at least 10% of those infected and leaves many more with brain damage, learning difficulties, and deafness—sweeps across the “meningitis belt,” a vast region from Ethiopia to Senegal where 350 million people live.

Last year when …
Crohn's disease and diffuse symmetrical periostitis.
Authors: G Neale, A R Kelsall, F H Doyle
Journal: Gut (1968)

Although in many textbooks (Lipman and Massie, 1960; MacBryde, 1965; Shulman, 1966) Crohn's disease is listed among the causes of hypertrophic osteoarthropathy an extensive search of the literature has failed to reveal an adequately documented case. We report here a 17-year-old boy who has diffuse Crohn's disease of the small and large intestine associated with marked periosteal new bone formation and mild clubbing of the fingers.
P3-161: Gefitinib toxicity has been significantly correlated with survival in non-small cell lung cancer patients treated in EAP program in Czech Republic
Authors: Milada Zemanova, Lubos Petruzelka, Petr Zatloukal, Milos Pesek, Ivona Grygarkova, Jana Skrickova, Adam Svobodnik, David Vrana
Journal: Journal of Thoracic Oncology (2007)
IL28B, HLA-C, and KIR Variants Additively Predict Response to Therapy in Chronic Hepatitis C Virus Infection in a European Cohort: A Cross-Sectional Study
Authors: Vijayaprakash Suppiah, Silvana Gaudieri, Nicola J. Armstrong, Kate S. O'Connor, Thomas Berg, Martin Weltman, Maria Lorena Abate, Ulrich Spengler, Margaret Bassendine, Gregory J. Dore, William L. Irving, Elizabeth Powell, Margaret Hellard, Stephen Riordan, Gail Matthews, David Sheridan, Jacob Nattermann, Antonina Smedile, Tobias Müller, Emma Hammond, David Dunn, Francesco Negro, Pierre-Yves Bochud, Simon Mallal, Golo Ahlenstiel, Graeme J. Stewart, Jacob George, David R. Booth
Journal: PLoS Medicine (2011)

Vijayaprakash Suppiah and colleagues show that genotyping hepatitis C patients for the IL28B, HLA-C, and KIR genes improves the ability to predict whether or not patients will respond to antiviral treatment.
Communicating with deaf patients
Authors: J. C. Cobey
Journal: JAMA (1995)

To the Editor.  —Drs Ebert and Heckerling 1 recommend that physicians treating deaf patients use more sign language. I have been the team physician for Gallaudet University for 10 years, and although I know some sign language, I find that the most useful means of communicating with deaf patients is a teletypewriter, commonly called a TTY machine. A TTY is a small, battery-operated keyboard with a display panel for the typed message; it can also be used to communicate with another TTY by telephone. I sit next to the patient and type my questions and comments on the TTY, and the patient types a response back to me. I find that while sign language is useful, it often is condensed and abbreviated in conveying important details. Since there are no sign language expressions in common use for much unfamiliar medical terminology, a physician or interpreter would have to spell out
Correlations of Mechanical Stability, Morphology, Pulmonary Surfactant, and Phospholipid Content in the Developing Lamb Lung*
Authors: George W. Brumley, Victor Chernick, W. Alan Hodson, Colin Normand, Axel Fenner, Mary Ellen Avery
Journal: Journal of Clinical Investigation (1967)

Pressure-volume characteristics and surface tension measurements of the lamb of 120 to 130 days gestational age were typical of the mature lung in the upper lobes and the immature lung in the lower lobes. By term both upper and lower lobes had findings characteristic of the mature animal. Phospholipid concentration per milligram DNA and per cent saturated fatty acids on pulmonary phosphatidyl choline were relatively constant from 60 to 120 days gestational age; thereafter there was a significant increase in both measurements. These changes usually coincided with an increase in osmiophilic inclusion bodies in the large alveolar cell.A concentration of disaturated phosphatidyl choline per milligram DNA in excess of 0.170 mg per mg was associated with a minimal surface tension below 13 dynes per cm (p < 0.001). Newborn animal lungs contained over 3 times this critical concentration, whereas adult lungs contained 1.5 times this value. The excess disaturated phosphatidyl choline per milligram DNA may represent a reservoir of pulmonary surfactant.
Exploring the role of common regulatory variants in the etiology of late-onset Alzheimer’s disease
Authors: Hao Wang, Min Zhu, Jian Wang, Yue Sun, Yu Tao, Qin He, Xiang Xu, Li Chen, David Saffen
Journal: Molecular Neurodegeneration (2012)

Background Late-onset Alzheimer’s disease (LOAD) is a complex disorder with a significant genetic component (heritability ~ 0.8). It is distressingly common: in the United States, approximately 13% of individuals over the age of 65 and 43% of individuals over the age of 85 are estimated to have AD [2011 Alzheimer’s Disease Facts and Figures, Alzheimer’s Association]. Although specific mutations have been linked to familial forms of AD, mutations in AD candidate genes among LOAD cases are rare. For this reason there is currently great interest in identifying common genetic variants that contribute to this disorder. The goal of the current study is to quantify allele-specific differences in the expression of mRNAs encoding candidate LOAD susceptibility genes in human brain and elucidate the genetic basis for this differential expression. Haplotypes or combinations of genotypes that correlate with mRNA should be useful as markers in future genetic association studies aimed at identifying genes that contribute to AD risk and protection.
Report highlights health needs of adolescents
Authors: C Court
Journal: BMJ (1994)

Adolescents in England and Wales are continuing to pursue risk activities such as drinking alcohol, smoking cigarettes, and having sexual intercourse at a younger age, according to Dr Kenneth Calman, chief medical officer for England. Dr Calman, presenting his annual report, On the State of the Public Health 1993, said that the health of adolescents was particularly important and that more health services …
Rates of and Factors Associated With Delivery-Related Perinatal Death Among Term Infants in Scotland
Authors: Dharmintra Pasupathy
Journal: JAMA (2009)

Rates of obstetric intervention in labor, including cesarean delivery, have increased significantly in most developed countries. It is, however, unclear if this has been paralleled by decreased rates of perinatal and neonatal death associated with complications of labor at term.To determine whether rates of perinatal death at term, either during labor or in the neonatal period, have changed in Scotland during the last 20 years and whether this was associated with a reduction in deaths ascribed to intrapartum anoxia.A population-based, retrospective cohort study of linked data from a registry of births (Scottish Morbidity Record 02) and a registry of perinatal deaths (Scottish Stillbirth and Infant Death Survey) between 1988 and 2007. Participants included all births of a singleton infant in a cephalic presentation at term (N = 1,012,266), excluding those with perinatal death due to congenital anomaly or antepartum stillbirth.Delivery-related perinatal death, defined as intrapartum stillbirth or neonatal death unrelated to congenital abnormality. These events were also subdivided into those events ascribed to intrapartum anoxia and all other causes. The risk of death was modeled using logistic regression and analyses were adjusted for maternal age, height, parity, socioeconomic deprivation status, gestational age, birth weight percentile, fetal sex, onset of labor, and the annual number of births per hospital.During the study period, the risk of delivery-related perinatal death decreased from 8.8 to 5.5 per 10,000 births (unadjusted change, -38%; 95% confidence interval [CI], -51% to -21%). When analyzed by the cause of death, there was a significant decrease in the risk of death ascribed to intrapartum anoxia (5.7 to 3.0 per 10,000 births; unadjusted change, -48%; 95% CI, -62% to -29%), but no significant change in the risk of death ascribed to other causes. When deaths ascribed to intrapartum anoxia were analyzed by the time of death in relation to delivery, the reduction was similar comparing intrapartum stillbirths (2.6 to 1.1 per 10,000 births; unadjusted change, -60%; 95% CI, -75% to -34%) and neonatal deaths (3.1 to 1.9 per 10,000 births; unadjusted change, -38%; 95% CI, -59% to -7%). Adjustment for maternal, fetal, and obstetric factors was without material effect.Rates of intrapartum stillbirth and neonatal death at term decreased in Scotland between 1988 and 2007. This decrease was only significant for deaths ascribed to intrapartum anoxia.
Riding and other equestrian injuries: considerable severity.
Authors: R G Lloyd
Journal: British Journal of Sports Medicine (1987)

All horse-related injuries presenting to an Accident Service over a two-year period were investigated. 237 patients presented. The injuries were not considerable in absolute number but were in severity. There was a high morbidity with 22% of all patients requiring admission to hospital, 50% of all admissions because of head injuries. At least seven life-threatening injuries were identified and there were other severe pelvic and spinal injuries. The wearing of protective head gear remains the most important safety measure.
Value of Cardiovascular Magnetic Resonance Stress Perfusion Testing for the Detection of Coronary Artery Disease in Women
Authors: Igor Klem, Simon Greulich, John F. Heitner, Han Kim, Holger Vogelsberg, Eva-Maria Kispert, Srivani R. Ambati, Christian Bruch, Michele Parker, Robert M. Judd, Raymond J. Kim, Udo Sechtem
Journal: JACC. Cardiovascular imaging (2008)
Deficient Zebrafish <i>Ether-à-Go-Go</i> –Related Gene Channel Gating Causes Short-QT Syndrome in Zebrafish <i>Reggae</i> Mutants
Authors: David Hassel, Eberhard P. Scholz, Nicole Trano, Oliver Friedrich, Steffen Just, Benjamin Meder, Daniel L. Weiss, Edgar Zitron, Sabine Marquart, Britta Vogel, Christoph A. Karle, Gunnar Seemann, Mark C. Fishman, Hugo A. Katus, Wolfgang Rottbauer
Journal: Circulation (2008)

Genetic predisposition is believed to be responsible for most clinically significant arrhythmias; however, suitable genetic animal models to study disease mechanisms and evaluate new treatment strategies are largely lacking.In search of suitable arrhythmia models, we isolated the zebrafish mutation reggae (reg), which displays clinical features of the malignant human short-QT syndrome such as accelerated cardiac repolarization accompanied by cardiac fibrillation. By positional cloning, we identified the reg mutation that resides within the voltage sensor of the zebrafish ether-à-go-go-related gene (zERG) potassium channel. The mutation causes premature zERG channel activation and defective inactivation, which results in shortened action potential duration and accelerated cardiac repolarization. Genetic and pharmacological inhibition of zERG rescues recessive reg mutant embryos, which confirms the gain-of-function effect of the reg mutation on zERG channel function in vivo. Accordingly, QT intervals in ECGs from heterozygous and homozygous reg mutant adult zebrafish are considerably shorter than in wild-type zebrafish.With its molecular and pathophysiological concordance to the human arrhythmia syndrome, zebrafish reg represents the first animal model for human short-QT syndrome.
Re: A. Rose Brannon, Scott M. Haake, Kathryn E. Hacker, et al. Meta-analysis of Clear Cell Renal Cell Carcinoma Gene Expression Defines a Variant Subgroup and Identifies Gender Influences on Tumor Biology. Eur Urol 2012;61:258–68
Authors: Sean R. Williamson, John N. Eble, Liang Cheng, David J. Grignon
Journal: European Urology (2012)
Cancer in developing countries
Authors: P. Boffetta, D. M. Parkin
Journal: CA A Cancer Journal for Clinicians (1994)

Cancer is a major cause of mortality in developing countries, accounting for 13 percent of the annual deaths in adults. As the population increases and ages, the number of new cases of cancer is expected to increase dramatically. This article presents epidemiologic information on the principal cancers in developing countries and outlines the increasing challenge for the control of cancer in developing countries.