tbuckley/cabot-search huggingface dataset:
Abstract 2376: MutationValidator: A computational method for variant cross-validation in next-generation sequencing data
Authors: Mara Rosenberg, Gad Getz, Adam Kiezun, Andrey Sivachenko
Journal: Cancer Research (2014)

Abstract Background: Massively parallel next-generation sequencing (NGS) technologies already enable comprehensive genome-wide detection of germline and somatic variants in thousands of individuals, and the pace of data production keeps accelerating. However, with increased sequencing techniques and variant calling algorithms, proper validation and determination of ground truth is essential for benchmarking, comparisons, and confirmation of novel discoveries. Datasets generated on different sequencing platforms, derived from distinct biological samples and/or using different library construction protocols can provide at least partially independent sources for crosschecking variants. While methods for validation exist to date, they fail to account for the inherent variability in the datasets, and thereby propose biased estimates for the validation rates. Results: Here we present a method for variant cross-validation and present software implementation (written in Matlab) that generates validation metrics and diagnostics to characterize a mutation as true somatic, germline, or artifactual. Our method adjusts for the power to observe variant-supporting evidence in the validation dataset, which allows for accurate assessment of validation rates across wide ranges of sequencing coverages and variant allelic fractions. When this method is applied to a test cohort of 172 patients from The Cancer Genome Atlas Lung Adenocarcenoma dataset, we observe a SNP and Indel validation rate of 95% and 96% respectively with a 99% power for detection. A previously implemented naïve method of &amp;gt;8% supporting alleles in the tumor and &amp;lt;3% alternate allele in the normal for a validated event would have yielded rates of 72% and 95% for SNPs and Indels, values we claim to be underestimations of the true rates as they misclassify underpowered sites as a false positives. Conclusions: Our proposed method, MutationValidator, enables confident classification of mutations using orthogonal next-generation sequencing technologies for validation as it takes into consideration the variability in and across the datasets. Citation Format: Mara Rosenberg, Gad Getz, Adam Kiezun, Andrey Sivachenko. MutationValidator: A computational method for variant cross-validation in next-generation sequencing data. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2376. doi:10.1158/1538-7445.AM2014-2376
The Novel Replication-defective Vaccinia Virus (Tiantan Strain)–based Hepatitis C Virus Vaccine Induces Robust Immunity in Macaques
Authors: Bo Wen, Yao Deng, Hong Chen, Jie Guan, Xia Chuai, Li Ruan, Wei Kong, Wenjie Tan
Journal: Molecular Therapy (2013)

The induction of a robust neutralizing antibody (nAb) response is likely to be as essential as specific cell-mediated immunity (CMI) against multiple antigens for the development of effective preventive and therapeutic vaccines against hepatitis C virus (HCV) infection in humans. To date, no data on the immunogenicity of the replication-defective vaccinia virus (derived from the Tiantan strain) (rNTV)-based HCV vaccine in primates have been reported. This study describes in detail the immunogenicity of various vaccine candidates in rhesus macaques, including rNTV-based and replication-defective recombinant adenoviral (rAd)-based HCV vaccines, as well as HCV pseudotyped virus-like particles (HCVpp). Our data showed that rAd-HCV vaccine boosting induced robust CMI, while priming or boosting with HCVpp enhanced the antigen-specific nAb response after rAd-HCV vaccination; however, CMI was not enhanced. Vaccination includes rNTV-HCV priming induced robust antigen-specific antibody, particularly nAbs, and CMI responses. Furthermore, more robust and longer-lasting CMI and higher cytokine levels (both Th1 and Th2 types, especially IFN-γ) resulted from boosting with rAd-HCV. We conclude that the rNTV-based HCV vaccine induces robust nAbs and CMI when combined with a heterogeneous primer-booster strategy, which shows promise for development of a human HCV vaccine.
A Vexing Decision
Authors: John D. Archer
Journal: JAMA (1975)

In a letter to the editor in this issue ofThe Journal(p 226), Harold F. Hamit, MD, reiterates some observations I have made about the package literature of drugs<sup>1-7</sup>: it often fails to reflect best current prescribing standards. Yet Dr. Hamit reminds us that despite this failing of many package inserts, a physician may incur some legal risk if he fails to adhere to their strictures. I assume Dr. Hamit is thinking of the possibility of malpractice liability. I hope that my previous publications<sup>2,3,5,6</sup>and those of other authors have dispelled the vague notion that physicians may somehow violate some federal law if they depart from the recommendations of package literature. Nothing in the Federal Food, Drug, and Cosmetic Act supports this erroneous belief; spokesmen for the Food and Drug Administration (FDA), the agency that enforces the Act, have repeatedly acknowledged this fact. Best medicine often requires
LPS-binding protein protects mice from septic shock caused by LPS or gram-negative bacteria.
Authors: N Lamping, R Dettmer, N W Schröder, D Pfeil, W Hallatschek, R Burger, R R Schumann
Journal: Journal of Clinical Investigation (1998)

LPS-binding protein (LBP) recognizes bacterial LPS and transfers it to CD14, thereby enhancing host cell stimulation, eventually resulting in pathogenic states such as septic shock. Recently, LBP also was shown to detoxify LPS by transferring LPS into HDL particles in vitro. Thus, the predominant in vivo function of LBP has remained unclear. To investigate the biological activity of acute phase concentrations of recombinant murine LBP, high concentrations of LBP were investigated in vitro and in vivo. Although addition of low concentrations of LBP to a murine macrophage cell line enhanced LPS-induced TNF-alpha synthesis, acute phase concentrations of LBP blocked this effect in comparison to low-dose LBP. When injected into mice intraperitoneally, LBP inhibited LPS-mediated cytokine release and prevented hepatic failure resulting in a significantly decreased mortality rate in LPS-challenged and D-galactosamine-sensitized mice, as well as in a murine model of bacteremia. These results complement a recent study revealing LBP-deficient mice to be dramatically more susceptible to an intraperitoneal Salmonella infection as compared with normal mice. We conclude that acute phase LBP has a protective effect against LPS and bacterial infection and may represent a physiologic defense mechanism against infection. Despite the limitations of any murine sepsis model, the results shown may imply that LBP could have beneficial effects during gram-negative peritonitis in humans.
The Clinical Significance of Campylobacter pylori
Authors: CORNELIUS P. DOOLEY
Journal: Annals of Internal Medicine (1988)

Campylobacter pylori has recently been isolated from gastric mucosal biopsy specimens. Campylobacter pylori has many attributes in common with other Campylobacters but it may represent a new genus. It produces abundant quantities of urease, and this property has been used to develop a rapid diagnostic test. The organism is found predominantly beneath the gastric mucus layer that lines the surface epithelium of the stomach. Infection with C. pylori causes an acute histologic gastritis which may become chronic. The bacterium is the etiologic agent in type-B gastritis. Prevalence of the organism in asymptomatic persons appears to be age related. Campylobacter pylori is found commonly in patients with peptic ulcer disease, always in association with chronic gastritis. Eradication of the organism is associated with healing of the gastritis and a lower relapse rate in duodenal ulcer disease. A role for the organism in other upper gastrointestinal diseases is unproven.
ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making
Authors: H.J. Schmoll, E. Van Cutsem, A. Stein, V. Valentini, B. Glimelius, K. Haustermans, B. Nordlinger, C.J. van de Velde, J. Balmana, J. Regula, I.D. Nagtegaal, R.G. Beets-Tan, D. Arnold, F. Ciardiello, P. Hoff, D. Kerr, C.H. Köhne, R. Labianca, T. Price, W. Scheithauer, A. Sobrero, J. Tabernero, D. Aderka, S. Barroso, G. Bodoky, J.Y. Douillard, H. El Ghazaly, J. Gallardo, A. Garin, R. Glynne-Jones, K. Jordan, A. Meshcheryakov, D. Papamichail, P. Pfeiffer, I. Souglakos, S. Turhal, A. Cervantes
Journal: Annals of Oncology (2012)
Predictors for Incidence of Primary Open-Angle Glaucoma in a South Indian Population
Authors: Lingam Vijaya, Asokan Rashima, Manish Panday, Nikhil S. Choudhari, Sathyamangalam Ve Ramesh, Velumuri Lokapavani, Sachi Devi Boddupalli, Govindan T. Sunil, Ronnie George
Journal: Ophthalmology (2014)
Interaction between prostacyclin and nitric oxide in the reflex control of the coronary circulation in conscious dogs
Authors: G. Zhao, X. Xu, M. Ochoa, W. Shen, T. H. Hintze
Journal: Cardiovascular Research (1996)

Our goal was to determine the role of nitric oxide (NO) on the coronary vasodilation induced by prostacyclin (PGI2) in conscious dogs.Dogs were chronically instrumented for the measurements of coronary blood flow (CBF), left ventricular pressure (LVP), mean arterial pressure (MAP) and heart rate (HR).Intravenous injections of PGI2 caused dose-dependent increases in CBF, and decreases in MAP and late diastolic coronary resistance (LDCR). For instance, CBF increased by 128 +/- 19% (P < 0.05) from 30 +/- 3.5 ml/min and LDCR decreased by 73 +/- 3% (P < 0.05) from 2.57 +/- 0.20 mmHg/ml/min following injection of PGI2 (1.0 microgram/kg). After infusion of nitro-L-arginine (NLA, 35 mg/kg) intravenously, the coronary vasodilation induced by PGI2 was partially attenuated. PGI2 (1.0 microgram/kg) increased CBF by 55 +/- 15% from 33 +/- 5.3 ml/min and decreased LDCR by 42 +/- 9% (both P < 0.05, compared with before NLA) from 3.29 +/- 0.39 mmHg/ml/min. Infusion of L-arginine (100 mg/kg) reversed the action of NLA. For example, PGI2 (1.0 microgram/kg) increased CBF by 115 +/- 15% from 36 +/- 6 ml/min and decreased LDCR by 68 +/- 3% from 3.02 +/- 0.36 mmHg/ml/min (both P > 0.05, compared with before NLA). Atropine (0.1 mg/kg) partially attenuated the coronary vasodilation induced by PGI2 the magnitude of which was almost identical to that by NLA. NLA or atropine also blunted the coronary vasodilation induced by acetylcholine, while the coronary vasodilation induced by nitroglycerin was not affected by NLA.Our results indicate that the coronary vasodilation induced by PGI2 was partially attenuated by NLA or atropine, suggesting that the coronary vasodilation induced by PGI2 is due to two components: a reflex parasympathetic cholinergic vasodilation mediated by NO and a direct action of PGI2.
Studies Concerning the Role of the Adrenal Cortex in the Pathologic Physiology of Diabetic Acidosis. I. Temporal Relations Between the Metabolic Events of Experimental Diabetic Acidosis and the Level of Adrenal Cortical Function1
Authors: J. W. McArthur, G. A. Smart, E. A. MacLachlan, M. L. Terry, D. Harting, E. Gautier, A. Godley, K. A. Swallow, F. A. Simeone, A. Zygmuntowicz, E. Christo, J. Crepeaux, W. W. Point, J. A. Benson
Journal: Journal of Clinical Investigation (1954)
Doctor in the house
Authors: Des Spence
Journal: BMJ (2013)

Like many doctors of a certain generation, I’ve made many thousands of house calls. I’ve been barked at by poodles, rottweilers, pit bulls, and chihuahuas. Taken lifts full of graffiti, vomit, urine, and Buckie wine bottles. Walked up blacked out stairwells using the torch of my auriscope to guide me, with the crunch of used syringes under foot. Met countless fresh faced police officers and seen death in every manifestation. And announced death to screams, cries, sobs, and hysterical laughter. Detained patients under the Mental Health Act at 3 am. Stood on blood, …
Freeze preservation of sickle erythrocytes
Authors: Oswaldo Castro, Kathryn Phillips Hardy, William P. Winter, Marne Hornblower, Harold T. Meryman
Journal: American Journal of Hematology (1981)

Abstract The effect of short‐term cryopreservation on metabolic, functional, and survival characteristics of erythrocytes from patients with sickle cell disease was examined. Post‐thaw hemolysis of glycerolized sickle (SS) erythrocytes was greater (mean 12.9%) than in hemoglobin‐AA cells (mean 4.7%). Freeze preservation had no apparent effect on red cell morphology, percent irreversibly sickled cells, and fetal hemoglobin content. There were modest reductions in ATP and 2,3‐diphosphoglycerate in thawed, washed sickle erythrocytes (12.7% and 29.7%, respectively). However, the autologous survival of 51 Cr‐labelled SS red cells was not shortened by cryopreservation. The safety and efficacy of autotransfusion of cryopreserved red cells in alloimmunized sickle cell disease patients with anemic episodes unrelated to sickling need to be determined.
Scare tactics cut smoking rates in Australia to all time low
Authors: S. Chapman
Journal: BMJ (1999)

Australia's smoking rate, which was stalled throughout the 1990s with around 25%of adults found in several surveys to be smoking, has recommenced its downward slide. The national prevalence of adult smoking has now fallen to 22%the lowest figure ever recorded.

Australia, like the United Kingdom, Canada, and the United States had experienced a decade long lull in its decline in the prevalence of smoking.

On World …
A Dancing Matrix: Voyages Along the Viral Frontier
Authors: Michael F. Loudon
Journal: JAMA (1993)

Henig's intention, in this book designed for general readership, is to explore contemporary virological thinking and explain the phenomenon of viral emergence. From chapter 1, a review of "Why New Viruses Emerge," she moves smartly on to a detailed account of the emergence of the acquired immunodeficiency syndrome (AIDS). With the reader well hooked, she devotes chapter 3 to "A Virus Primer." For any<i>JAMA</i>subscribers who fancy writing for a general readership, here is a test. You have 24 pages in which to describe the structure, function, and variety of viruses; how they interact with the host cell's nuclear machinery; how the organism defends itself; and how viruses cause illness. If you can match Henig's neat and pacey sketch and her grip on the reader's interest, then a profitable sideline career awaits you. The second section of the book, "New Threats," covers a series of intriguing virus stories, most
The effect of neonatal BCG vaccination on atopy and asthma at age 7 to 14 years: An historical cohort study in a community with a very low prevalence of tuberculosis infection and a high prevalence of atopic disease
Authors: Guy B. Marks, Kitty Ng, Jie Zhou, Brett G. Toelle, Wei Xuan, Elena G. Belousova, None MApplSc, Warwick J. Britton
Journal: Journal of Allergy and Clinical Immunology (2003)
INVERSE RELATION BETWEEN IODIN IN FOOD AND DRINK AND GOITER, SIMPLE AND EXOPHTHALMIC
Authors: J. F. McCLENDON
Journal: JAMA (1924)

We consider that we have proved statistically that both simple<sup>1</sup>and exophthalmic goiter in the United States are caused by iodin starvation. The Swiss goiter commission has been concerned with the prophylactic use of iodin, particularly iodized salt, and it secured the services of Fellenberg<sup>2</sup>to make a study of the distribution of iodin in nature. Fellenberg has, in a general way, confirmed Chatin's conclusions. He also found that iodin when added to salt<sup>3</sup>was volatilized to some extent in ordinary storage in a grocery store. Since he found that the purer the salt, the less loss of iodin occurred, it seems probable that the loss is due to the presence of nitrites or nitrates which oxidize the iodid to iodin, which then is lost in the air. Fellenberg's report was not received by us until our work was complete. He developed methods somewhat similar to ours,
Intestinal microvascular growth during maturation in diabetic juvenile rats.
Authors: J L Unthank, H G Bohlen
Journal: Circulation Research (1988)

To determine if intestinal microvascular growth is impaired in diabetic juvenile animals, a segment of the terminal ileum was marked and the microvasculature of this segment observed at the age of 5 weeks and again at the age of 10-11 weeks in normal and diabetic Sprague Dawley rats. Diabetes was induced by streptozotocin after the first observation period and the plasma glucose concentration exceeded 500 mg% by the age of 10-11 weeks. Microvascular growth was quantitated by measurements of the number, length, and maximally dilated inner diameters of specific arterioles and by intercapillary distances in the marked intestinal region at both ages. Although intestinal enlargement was much greater in diabetics, there was no change in the number of arterioles during maturation and intercapillary distances were equivalent in diabetic and normal rats. In normal and diabetic animals, the arteriolar length increased to match bowel elongation, however, increases in bowel and arteriolar lengths in diabetic animals were about twice that of normal rats. During juvenile maturation, the maximally dilated inner diameters of the small arterioles in diabetic animals were increased compared with their normal counterparts. Thus, arteriolar growth during maturation is characterized by changes in the length but not in the number of vessels in intestine of both normal and diabetic rats. The perfusion of about 90% more tissue by mass for each arteriole in diabetic rats is facilitated by arteriolar dilation.(ABSTRACT TRUNCATED AT 250 WORDS)
Making Surgical Complications Pay
Authors: Uwe E. Reinhardt
Journal: JAMA (2013)

In this issue of JAMA, Eappen et al1 reach the troublesome but not surprising conclusion that hospitals in the United States can profit handsomely from postsurgical complications, even if the hospitals could avoid them. The authors note that �Effective methods for reducing surgical complications have been identified. However, hospitals have been slow to implement them.�
Asymptomatic animal traders prove positive for SARS virus
Authors: J. Parry
Journal: BMJ (2003)

The microbiology team from the University of Hong Kong has published a paper on the origins of the coronavirus that causes severe acute respiratory syndrome (SARS). The paper, published online in Science (www.sciencemag.org/cgi/content/abstract/1087139) on 5 September, presents the results of testing eight species of wild and domestic animals sourced from a live animal market in Shenzhen, southern China, in May 2003. The paper also showed that eight traders of wild animals and three workers who slaughtered wild animals were positive for the virus, despite never having shown symptoms of SARS.

A total of 25 animals were tested, and researchers isolated a SARS-like coronavirus from four civet cats, as well as from a raccoon dog. Antibodies …
ETS Transcription Factor ESE1/ELF3 Orchestrates a Positive Feedback Loop That Constitutively Activates NF-κB and Drives Prostate Cancer Progression
Authors: Nicole Longoni, Manuela Sarti, Domenico Albino, Gianluca Civenni, Anastasia Malek, Erica Ortelli, Sandra Pinton, Maurizia Mello-Grand, Paola Ostano, Gioacchino D'Ambrosio, Fausto Sessa, Ramon Garcia-Escudero, George N. Thalmann, Giovanna Chiorino, Carlo V. Catapano, Giuseppina M. Carbone
Journal: Cancer Research (2013)

Chromosomal translocations leading to deregulated expression of ETS transcription factors are frequent in prostate tumors. Here, we report a novel mechanism leading to oncogenic activation of the ETS factor ESE1/ELF3 in prostate tumors. ESE1/ELF3 was overexpressed in human primary and metastatic tumors. It mediated transforming phenotypes in vitro and in vivo and induced an inflammatory transcriptome with changes in relevant oncogenic pathways. ESE1/ELF3 was induced by interleukin (IL)-1β through NF-κB and was a crucial mediator of the phenotypic and transcriptional changes induced by IL-1β in prostate cancer cells. This linkage was mediated by interaction of ESE1/ELF3 with the NF-κB subunits p65 and p50, acting by enhancing their nuclear translocation and transcriptional activity and by inducing p50 transcription. Supporting these findings, gene expression profiling revealed an enrichment of NF-κB effector functions in prostate cancer cells or tumors expressing high levels of ESE1/ELF3. We observed concordant upregulation of ESE1/ELF3 and NF-κB in human prostate tumors that was associated with adverse prognosis. Collectively, our results define an important new mechanistic link between inflammatory signaling and the progression of prostate cancer.
Seroepidemiology of Saffold cardiovirus (SAFV) genotype 3 in Japan
Authors: Miho Kobayashi, Hiroyuki Tsukagoshi, Taisei Ishioka, Katsumi Mizuta, Masahiro Noda, Yukio Morita, Akihide Ryo, Kunihisa Kozawa, Hirokazu Kimura
Journal: Journal of Infection (2012)
Normetanephrine Excretion and Affective State in Depressed Patients Treated with Imipramine
Authors: JOSEPH J. SCHILDKRAUT, RICHARD GREEN, EDNA K. GORDON, JACK DURELL
Journal: American Journal of Psychiatry (1966)

Urinary excretion of normetanephrine, the metabolite of norepinephrine which may reflect noradrenergic activity, showed a gradual increase during the period of definitive clinical improvement in depressed patients treated with imipramine. These and other findings of the study suggest that noradrenergic activity may gradually increase during clinical improvement from depression, and that noradrenergic activity may be relatively decreased in retarded depression and increased in mania. The pharmacological action of imipramine may initiate increases in noradrenergic activity and clinical improvement, in depressed patients, that are subsequently maintained after discontinuation of the drug.
Abstract B98: Promoter methylation status of tumor suppressor genes and an inflammatory-related COX-2 gene in cervical intraepithelial neoplasia
Authors: Sheng Hsiung Lin, Chun Chieh Yu, Ming Tsang Wu, Ruei Nian Li
Journal: Cancer Research (2013)

Abstract Cervical cancer is one of the most common cancer among women. Early detection and prompt treatment would be the best management options. DNA methylation is one of the epigenetic regulation mechanisms leading to gene silencing in neoplastic cells. Silencing of tumor suppressor gene resulted from aberrant methylation has been detected in a majority of human cancers. Here, we applied methylation-specific polymerase chain reaction (MSP) to examine the methylation state of three tumor suppressor genes (rar-beta, p16 and cdh1) and an inflammatory-related cox-2 gene in different stages of cervical intraepithelial neoplasia (CIN). Our analyses revealed that cox-2 gene is in unmethylated form from CIN I to carcinoma specimens. Besides, no significant increase in methylation levels of rar-beta and cdh1 genes was observed. However, the high frequency of aberrant hypermethylation of p16 gene (13.2% in normal specimens ; 18.2% in CIN I; 35.7% in CIN II; 31.6% in CIN III and 15.4% in carcinoma) suggesting that p16 is progressively increased during the development of malignant stages in cervical intraepithelial neoplasia, especially in the absence of HPV infection. The result of bisulfite sequencing indicated that the 10 CpG sites of p16 gene are all methylated in ten individuals. In conclusion, this study identifies promoter methylation analysis of p16 on cervical cell specimens may be an additional tool for current cervical cytomorphology based screening. Citation Format: Sheng Hsiung Lin, Chun Chieh Yu, Ming Tsang Wu, Ruei Nian Li. Promoter methylation status of tumor suppressor genes and an inflammatory-related COX-2 gene in cervical intraepithelial neoplasia. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B98.