tbuckley/cabot-search huggingface dataset:
Content and Ratings of Teen-Rated Video Games
Authors: Kevin Haninger, Kimberly M. Thompson
Journal: JAMA (2004)

Children's exposure to violence, blood, sexual themes, profanity, substances, and gambling in the media remains a source of public health concern. However, content in video games played by older children and adolescents has not been quantified or compared with the rating information provided to consumers by the Entertainment Software Rating Board (ESRB).To quantify and characterize the content in video games rated T (for "Teen") and to measure the agreement between the content observed in game play and the ESRB-assigned content descriptors displayed on the game box.We created a database of all 396 T-rated video game titles released on the major video game consoles in the United States by April 1, 2001, to identify the distribution of games by genre and to characterize the distribution of ESRB-assigned content descriptors. We randomly sampled 80 video game titles (which included 81 games because 1 title included 2 separate games), played each game for at least 1 hour, quantitatively assessed the content, and compared the content we observed with the content descriptors assigned by the ESRB.Depictions of violence, blood, sexual themes, gambling, and alcohol, tobacco, or other drugs; whether injuring or killing characters is rewarded or is required to advance in the game; characterization of gender associated with sexual themes; and use of profanity in dialogue, lyrics, or gestures.Analysis of all content descriptors assigned to the 396 T-rated video game titles showed 373 (94%) received content descriptors for violence, 102 (26%) for blood, 60 (15%) for sexual themes, 57 (14%) for profanity, 26 (7%) for comic mischief, 6 (2%) for substances, and none for gambling. In the random sample of 81 games we played, we found that 79 (98%) involved intentional violence for an average of 36% of game play, 73 (90%) rewarded or required the player to injure characters, 56 (69%) rewarded or required the player to kill, 34 (42%) depicted blood, 22 (27%) depicted sexual themes, 22 (27%) contained profanity, 12 (15%) depicted substances, and 1 (1%) involved gambling. Our observations of 81 games match the ESRB content descriptors for violence in 77 games (95%), for blood in 22 (27%), for sexual themes in 16 (20%), for profanity in 14 (17%), and for substances in 1 (1%). Games were significantly more likely to depict females partially nude or engaged in sexual behaviors than males. Overall, we identified 51 observations of content that could warrant a content descriptor in 39 games (48%) in which the ESRB had not assigned a content descriptor. We found that the ESRB assigned 7 content descriptors for 7 games (9%) in which we did not observe the content indicated within 1 hour of game play.Content analysis suggests a significant amount of content in T-rated video games that might surprise adolescent players and their parents given the presence of this content in games without ESRB content descriptors. Physicians and parents should be aware that popular T-rated video games may be a source of exposure to a wide range of unexpected content.
Electrophysiological Mechanisms Underlying Sudden Cardiac Death
Authors: Peter T. Kuo
Journal: JAMA (1983)

This book presents a succinct compilation of the current information on sudden death obtained by investigators with a broad spectrum of scientific interests. Thirty-five clinical investigators and basic scientists contributed 25 chapters. The editors summarize the presentations with their conclusions and perspective. The broadly ranging discussions of sudden death include basic mechanisms, epidemiologic factors, clinical observations, multicenter clinical trial data, organized emergency resuscitation, and pharmacologic and surgical treatments. The magnitude of the problem is estimated at more than 300,000 incidents in the United States each year, with the preponderance in patients with coronary heart disease. Predisposing factors may include cigarette smoking, hypertension, premature ventricular beats, abnormal response to exercise, physiological and emotional stress in susceptible patients with coronary heart disease, and left ventricular dysfunction. Since the causes of ventricular fibrillation and sudden death are multiple and complex, it is apparent that the mechanism for the development of malignant arrhythmia varies
A complement-dependent balance between hepatic ischemia/reperfusion injury and liver regeneration in mice
Authors: Songqing He, Carl Atkinson, Fei Qiao, Katherine Cianflone, Xiaoping Chen, Stephen Tomlinson
Journal: Journal of Clinical Investigation (2009)

Massive liver resection and small-for-size liver transplantation pose a therapeutic challenge, due to increased susceptibility of the remnant/graft to ischemia reperfusion injury (IRI) and impaired regeneration. We investigated the dual role of complement in IRI versus regeneration in mice. Complement component 3 (C3) deficiency and complement inhibition with complement receptor 2–complement receptor 1–related protein y (CR2-Crry, an inhibitor of C3 activation) provided protection from hepatic IRI, and while C3 deficiency also impaired liver regeneration following partial hepatectomy (PHx), the effect of CR2-Crry in this context was dose dependent. In a combined model of IRI and PHx, either C3 deficiency or high-dose CR2-Crry resulted in steatosis, severe hepatic injury, and high mortality, whereas low-dose CR2-Crry was protective and actually increased hepatic proliferative responses relative to control mice. Reconstitution experiments revealed an important role for the C3a degradation product acylation-stimulating protein (ASP) in the balance between inflammation/injury versus regeneration. Furthermore, liver regeneration was dependent on the putative ASP receptor, C5L2. Several potential mechanisms of hepatoprotection and recovery were identified in mice treated with low-dose CR2-Crry, including enhanced IL-6 expression and STAT3 activation, reduced hepatic ATP depletion, and attenuated oxidative stress. These data indicate that a threshold of complement activation, involving ASP and C5L2, promotes liver regeneration and suggest a balance between complement-dependent injury and regeneration.
Envenomation and Diverse Disease States
Authors: Findlay E. Russell
Journal: JAMA (1977)

To the Editor.—  The article by Brumlik (235:2120, 1976) again indicates the diversity of disease states that appear to be precipitated by arthropod bites or stings as well as by the bites or stings of other venomous animals. 1-3   During the period 1955 to 1975, the Venom Poisoning Unit at this medical center treated or was involved in the treatment of 14 unusual disorders that appeared one to seven days following the bite or sting of an arthropod, snake, or marine animal and that did not appear to be directly related to the venom poisoning. Two of these cases have been reported. 4-5 Three more, one involving a bee sting with subsequent optic neuritis, one generalized polyneuropathy, and another involving a stingray injury that precipitated amyloidosis, were discussed on grand rounds at this medical center. The remaining nine cases have gone unreported.  Similar experiences have been noted by others, particularly
Diagnosis and Treatment of Heart Failure Based on Left Ventricular Systolic or Diastolic Dysfunction
Authors: William H. Gaasch
Journal: JAMA (1994)

Data from large and small clinical trials reflect major differences in the pathophysiology, treatment, and prognosis of left ventricular (LV) systolic and diastolic dysfunction. These studies also indicate that medical therapy can benefit patients with LV dysfunction regardless of whether or not they are symptomatic. Because the descriptive term congestive heart failure does not provide for these important distinctions, a new classification of LV dysfunction has been developed in which patients with LV dysfunction are categorized on the basis of normal or abnormal systolic function. This classification is based on a simple assessment of LV function, it is applicable to patients without symptoms, and it reflects differences in treatment and prognosis. Those with clinically significant LV systolic dysfunction (ie, an LV ejection fraction < 40%) benefit from therapy whether or not they have symptoms of heart failure. Those with LV dysfunction and a normal LV ejection fraction (ie, diastolic dysfunction) also benefit from medical therapy. Annual mortality is higher in those with systolic dysfunction than in those with diastolic dysfunction, but within each of these categories mortality is higher in those with symptoms than in those without. This classification can be useful in the diagnosis and treatment of individual patients as well as in epidemiologic surveys designed to assess medical practice patterns.
Detection of ras gene mutations in human lung cancer: comparison of two screening assays based on the polymerase chain reaction.
Authors: K Husgafvel-Pursiainen, M Ridanpää, P Hackman, S Anttila, A Karjalainen, A Onfelt, A L Børresen, H Vainio
Journal: Environmental Health Perspectives (1992)

We studied the prevalence of point mutations in ras oncogenes (K-ras and N-ras) in DNA from white blood cells and tumor tissue from 36 untreated patients with non-small-cell lung cancer, all of whom were smokers or ex-smokers. We observed somatic K-ras mutations in one-third of the lung carcinomas studied but no N-ras mutation. K-ras codon 12 mutations were found more frequently in adenocarcinomas than in the other histopathological subtypes studied. More than 60% (10/16) of the lung adenocarcinomas had a codon 12 mutation, most of which were G to T transversions. No mutations was found in white blood cell DNA. Two polymerase chain reaction screening methods, oligonucleotide hybridization and denaturing gradient gel electrophoresis (DGGE), were used to detect the mutations. The oligonucleotide method appears to be more sensitive than DGGE, but DGGE proved to be a reliable nonradioactive method for rapid screening of point mutations in genes relevant to carcinogenesis.
Caffeine Alters A <sub>2A</sub> Adenosine Receptors and Their Function in Human Platelets
Authors: Katia Varani, Francesco Portaluppi, Stefania Merighi, Ennio Ongini, Luiz Belardinelli, Pier Andrea Borea
Journal: Circulation (1999)

Background —Caffeine acts mainly via blockade of adenosine receptors, which have been classified into A 1 , A 2A , A 2B , and A 3 subtypes. We determined whether repeated caffeine administration (750 mg/d for 1 week) upregulates the human platelet A 2A adenosine receptor and is accompanied by sensitization of platelet responses (increase in cAMP accumulation and decrease in platelet aggregation) to selective stimulation of the A 2A receptors. Methods and Results —Platelets were obtained from peripheral venous blood of 9 human volunteers at the end of 1 week of caffeine abstinence (control) and at 12 and 60 hours after the last dose of caffeine (withdrawal). The A 2A receptor radioligand [ 3 H]SCH 58261 {5-amino-7(phenylethyl)-2-(2-furyl)-pyrazolo[4,3- e ]-1,2,4-triazolo[1,5- c ]-pyrimidine} bound to a single affinity class of sites in platelet membranes from controls with a B max of 98±2 fmol/mg protein and a K D of 1.29±0.05 nmol/L. At 12 and 60 hours after caffeine withdrawal, the radioligand bound with similar affinity ( K D =1.36±0.06 and 1.21±0.05 nmol/L, respectively), but the B max was increased ( P &lt;0.01) to 128±3 and 132±2 fmol/mg protein. The A 2A receptor agonist 2-hexynyl-5′- N -ethylcarboxamidoadenosine (HE-NECA) increased cAMP accumulation (EC 50 =59±3 nmol/L) and inhibited (IC 50 =90±6 nmol/L) aggregation of control platelets. The EC 50 values for HE-NECA to increase cAMP accumulation of platelets were reduced ( P &lt;0.01) at 12 and 60 hours after caffeine withdrawal (31±3 and 21±2 nmol/L, respectively). The IC 50 values for HE-NECA to inhibit ADP-induced platelet aggregation were 50±5 and 30±2 nmol/L at 12 and 60 hours after caffeine withdrawal, respectively. Conclusions —Chronic caffeine intake leads to upregulation of A 2A receptors and is accompanied by sensitization to the actions of the agonist HE-NECA.
Pregnant women still vulnerable to rubella
Authors: William A. Check
Journal: JAMA (1981)

Now that an intensive surveillance and vaccination campaign has eradicated smallpox worldwide, the same dedication could well be applied to removing the last vestiges of an infectious disease that still results in tragedy here in the United States: congenital rubella syndrome (CRS).  The incomplete status of the immunization effort against rubella was underlined once again by a report presented at the recent 20th Interscience Conference on Antimicrobial Agents and Chemotherapy in New Orleans by pediatricians and public health scientists from the University of Illinois Medical Center, Chicago.  Following a major outbreak of rubella in Chicago in 1978, the pediatricians began seeing infants at their hospital with the cataracts, cardiac abnormalities, hearing impairment, and mental retardation characteristic of CRS. In a survey of other Chicago-area hospitals and physicians, they found 30 infants with signs of CRS who had been born during late 1978 or early 1979, pediatric infectious disease specialist Catherine
Procarbazine in the Management of Late Hodgkin's Disease
Authors: Ronald C. DeConti
Journal: JAMA (1971)

Thirteen of 22 patients with widespread Hodgkin's disease resistant to vinca alkaloids and alkylating agents responded to therapy with procarbazine hydrochloride. All responses were clinically evident three weeks after therapy was begun. Four complete and nine partial remissions were achieved ranging from 4 to more than 40 weeks in duration with a median duration of 10 weeks. The relatively short duration of response and the paucity of complete remissions in these patients may be related to the severity of the disease. Procarbazine hydrochloride has been demonstrated to be a safe, effective agent in the drug management of advanced Hodgkin's disease.
Dr Doctor Calls Back
Authors: Dominic J. Balestra
Journal: JAMA (1993)

To the Editor.  —I read Dr Bennett's observations about physicians' names with great interest, but felt obligated to call readers' attention to a serious omission. 1 A literature search confirms that some physicians can (but don't necessarily) shoot from the hip, as evidenced by coauthors Smith and Wesson in 1988. 2 Should Smith and Wesson, well respected for their work in substance abuse, choose to study violent behavior, would their work constitute a proprietary conflict of interest?
Prelamin A Acts to Accelerate Smooth Muscle Cell Senescence and Is a Novel Biomarker of Human Vascular Aging
Authors: Cassandra D. Ragnauth, Derek T. Warren, Yiwen Liu, Rosamund McNair, Tamara Tajsic, Nichola Figg, Rukshana Shroff, Jeremy Skepper, Catherine M. Shanahan
Journal: Circulation (2010)

Background— Hutchinson-Gilford progeria syndrome is a rare inherited disorder of premature aging caused by mutations in LMNA or Zmpste24 that disrupt nuclear lamin A processing, leading to the accumulation of prelamin A. Patients develop severe premature arteriosclerosis characterized by vascular smooth muscle cell (VSMC) calcification and attrition. Methods and Results— To determine whether defective lamin A processing is associated with vascular aging in the normal population, we examined the profile of lamin A expression in normal and aged VSMCs. In vitro, aged VSMCs rapidly accumulated prelamin A coincidently with nuclear morphology defects, and these defects were reversible by treatment with farnesylation inhibitors and statins. In human arteries, prelamin A accumulation was not observed in young healthy vessels but was prevalent in medial VSMCs from aged individuals and in atherosclerotic lesions, where it often colocalized with senescent and degenerate VSMCs. Prelamin A accumulation correlated with downregulation of the lamin A processing enzyme Zmpste24/FACE1, and FACE1 mRNA and protein levels were reduced in response to oxidative stress. Small interfering RNA knockdown of FACE1 reiterated the prelamin A–induced nuclear morphology defects characteristic of aged VSMCs, and overexpression of prelamin A accelerated VSMC senescence. We show that prelamin A acts to disrupt mitosis and induce DNA damage in VSMCs, leading to mitotic failure, genomic instability, and premature senescence. Conclusions— This study shows that prelamin A is a novel biomarker of VSMC aging and disease that acts to accelerate senescence. It therefore represents a novel target to ameliorate the effects of age-induced vascular dysfunction.
Enhanced utilization of exogenous glucose improves cardiac function in hypoxic rabbit ventricle without increasing total glycolytic flux.
Authors: E M Runnman, S T Lamp, J N Weiss
Journal: Journal of Clinical Investigation (1990)

The effects of elevated glucose on cardiac function during hypoxia were investigated in isolated arterially perfused rabbit interventricular septa. Rest tension, developed tension, intracellular potential, 42K+ efflux, lactate production, exogenous glucose utilization, and tissue high-energy phosphate levels were measured during a 50-min period of hypoxia with 4, 5, or 50 mM glucose present (isosmotically balanced with sucrose) and during reoxygenation for 60 min with perfusate containing 5 mM glucose/45 mM sucrose. At physiologic (4 or 5 mM) and supraphysiologic glucose (50 mM), lactate production and high-energy phosphate levels during hypoxia were equally well maintained, yet cardiac dysfunction was markedly attenuated by 50 mM glucose. Despite identical rates of total glycolytic flux, exogenous glucose utilization was enhanced by 50 mM glucose so that tissue glycogen levels remained normal during hypoxia, whereas glycogen became depleted with 4 or 5 mM glucose present during hypoxia. Most of the beneficial effects of 50 mM glucose occurred during the first 25 min of hypoxia. Prior glycogen depletion had no deleterious effects during hypoxia with 50 mM glucose present, but exacerbated cardiac dysfunction during hypoxia with 5 mM glucose present. These findings indicate that enhanced utilization of exogenous glucose improved cardiac function during hypoxia without increasing total glycolytic flux or tissue high-energy phosphate levels, suggesting a novel cardioprotective mechanism.
Lancet editor defends decision to publish GM research paper
Authors: P. Brown
Journal: BMJ (1999)

The editor of the Lancet, Dr Richard Horton, this week defended his decision to publish a controversial paper on genetically modified foods as “absolutely the right thing to do” amid continued criticisms that he had simply fuelled public confusion over the issue.

The paper, a research letter describing the effects of various diets containing potatoes on the intestines of rats, is based on experiments that have already been reviewed by the Royal Society and condemned as flawed. One of the paper's authors, Arpad Pusztai, was suspended last year from the Rowett Research Institute in Aberdeen for making claims about the lack of safety of genetically modified foods that were not supported by data.

Dr Pusztai and Stanley Ewen of the University of Aberdeen fed rats with potatoes containing a snowdrop lectin, a …
Variants of Variance
Authors: Samuel Vaisrub
Journal: JAMA (1977)

The unitary facade of angina pectoris was cracked 18 years ago when Prinzmetal et al<sup>1</sup>chipped off a "variant" form that departs from the classical pattern of Heberden angina of effort in several respects. The pain occurs at rest and is often accompanied by arrhythmias or heart block; it is associated with electrocardiographic ST-segment elevations; and it carries a grim prognosis. Prinzmetal ascribed the newly discovered syndrome to spasm in a severely diseased major coronary branch. The explanation did not, however, gain wide acceptance until the advent of angiography, which showed it to be correct.<sup>2</sup>Spasm is now acknowledged as the mechanism underlying variant angina. But rather than delineate the syndrome as a single entity, this recognition introduced an element of ambiguity. It soon became apparent that spasm with accompanying pain also occurs in patients with normal coronary arteries.<sup>3</sup>It also appeared likely that prolonged spasm with
Cardiac mitochondria in heart failure: decrease in respirasomes and oxidative phosphorylation
Authors: Mariana G. Rosca, Edwin J. Vazquez, Janos Kerner, William Parland, Margaret P. Chandler, William Stanley, Hani N. Sabbah, Charles L. Hoppel
Journal: Cardiovascular Research (2008)

Mitochondrial dysfunction is a major factor in heart failure (HF). A pronounced variability of mitochondrial electron transport chain (ETC) defects is reported to occur in severe acquired cardiomyopathies without a consistent trend for depressed activity or expression. The aim of this study was to define the defect in the integrative function of cardiac mitochondria in coronary microembolization-induced HF.Studies were performed in the canine coronary microembolization-induced HF model of moderate severity. Oxidative phosphorylation was assessed as the integrative function of mitochondria, using a comprehensive variety of substrates in order to investigate mitochondrial membrane transport, dehydrogenase activity and electron-transport coupled to ATP synthesis. The supramolecular organization of the mitochondrial ETC also was investigated by native gel electrophoresis. We found a dramatic decrease in ADP-stimulated respiration that was not relieved by an uncoupler. Moreover, the ADP/O ratio was normal, indicating no defect in the phosphorylation apparatus. The data point to a defect in oxidative phosphorylation within the ETC. However, the individual activities of ETC complexes were normal. The amount of the supercomplex consisting of complex I/complex III dimer/complex IV, the major form of respirasome considered essential for oxidative phosphorylation, was decreased.We propose that the mitochondrial defect lies in the supermolecular assembly rather than in the individual components of the ETC.
A Mutant <i>Ahr</i> Allele Protects the Embryonic Kidney from Hydrocarbon-Induced Deficits in Fetal Programming
Authors: Adrian Nanez, Irma N. Ramos, Kenneth S. Ramos
Journal: Environmental Health Perspectives (2011)

The use of experimental model systems has expedited the elucidation of pathogenetic mechanisms of renal developmental disease in humans and the identification of genes that orchestrate developmental programming during nephrogenesis.We conducted studies to evaluate the role of AHR polymorphisms in the disruption of renal developmental programming by benzo(a)pyrene (BaP).We used metanephric cultures of C57BL/6J (C57) mice expressing the Ahr(b-1) allele and B6.D2N-Ahr(d)/J (D2N) mice expressing a mutant allele deficient in ligand binding (Ahr(d)) to investigate molecular mechanisms of renal development. Deficits in fetal programming were evaluated in the offspring of pregnant mice treated with BaP during nephrogenesis.Hydrocarbon challenge of metanephri from C57 mice altered Wilms' tumor suppressor gene (Wt1) mRNA splice variant ratios and reduced mRNAs of the Wt1 transcriptional targets syndecan-1 (Sdc1) paired box gene 2 (Pax2), epidermal growth factor receptor (Egfr), and retinoic acid receptor, alpha (Rarα). These changes correlated with down-regulation of effectors of differentiation [secreted frizzled-related sequence protein 1 (Sfrp1), insulin-like growth factor 1 receptor (Igf1r), wingless-related MMTV-integration site 4 (Wnt4), Lim homeobox protein 1 (Lhx1), E-cadherin]. In contrast, metanephri from D2N mice were spared hydrocarbon-induced changes in Wt1 splice variant ratios and deficits of differentiation. We observed similar patterns of dysmorphogenesis and progressive loss of renal function at postnatal weeks 7 and 52 in the offspring of pregnant C57 but not D2N mice gavaged with 0.1 or 0.5 mg/kg BaP on gestation days 10-13.These findings support a functional link between AHR and WT1 in the regulation of renal morphogenesis and raise important questions about the contribution of human AHR polymorphisms to the fetal origins of adult-onset kidney disease.