tbuckley/cabot-search huggingface dataset:
Distribution of Major Health Risks: Findings from the Global Burden of Disease Study
Authors: Anthony Rodgers, Majid Ezzati, Stephen Vander Hoorn, Alan D Lopez, Ruey-Bin Lin, Christopher J. L Murray
Journal: PLoS Medicine (2004)

Background Most analyses of risks to health focus on the total burden of their aggregate effects. The distribution of risk-factor-attributable disease burden, for example by age or exposure level, can inform the selection and targeting of specific interventions and programs, and increase cost-effectiveness. Methods and Findings For 26 selected risk factors, expert working groups conducted comprehensive reviews of data on risk-factor exposure and hazard for 14 epidemiological subregions of the world, by age and sex. Age-sex-subregion-population attributable fractions were estimated and applied to the mortality and burden of disease estimates from the World Health Organization Global Burden of Disease database. Where possible, exposure levels were assessed as continuous measures, or as multiple categories. The proportion of risk-factor-attributable burden in different population subgroups, defined by age, sex, and exposure level, was estimated. For major cardiovascular risk factors (blood pressure, cholesterol, tobacco use, fruit and vegetable intake, body mass index, and physical inactivity) 43%–61% of attributable disease burden occurred between the ages of 15 and 59 y, and 87% of alcohol-attributable burden occurred in this age group. Most of the disease burden for continuous risks occurred in those with only moderately raised levels, not among those with levels above commonly used cut-points, such as those with hypertension or obesity. Of all disease burden attributable to being underweight during childhood, 55% occurred among children 1–3 standard deviations below the reference population median, and the remainder occurred among severely malnourished children, who were three or more standard deviations below median. Conclusions Many major global risks are widely spread in a population, rather than restricted to a minority. Population-based strategies that seek to shift the whole distribution of risk factors often have the potential to produce substantial reductions in disease burden.
Up-regulation of the high-affinity pyrimidine-preferring nucleoside transporter concentrative nucleoside transporter 1 by tumor necrosis factor-alpha and interleukin-6 in liver parenchymal cells
Authors: Sonia Fernández-Veledo, Raquel Valdés, Ville Wallenius, F.Javier Casado, Marçal Pastor-Anglada
Journal: Journal of Hepatology (2004)
Inheritance of Gene Expression Level and Selective Constraints on Trans- and Cis-Regulatory Changes in Yeast
Authors: Bernhard Schaefke, J.J. Emerson, Tzi-Yuan Wang, Mei-Yeh Jade Lu, Li-Ching Hsieh, Wen-Hsiung Li
Journal: Molecular Biology and Evolution (2013)

Gene expression evolution can be caused by changes in cis- or trans-regulatory elements or both. As cis and trans regulation operate through different molecular mechanisms, cis and trans mutations may show different inheritance patterns and may be subjected to different selective constraints. To investigate these issues, we obtained and analyzed gene expression data from two Saccharomyces cerevisiae strains and their hybrid, using high-throughput sequencing. Our data indicate that compared with other types of genes, those with antagonistic cis–trans interactions are more likely to exhibit over- or underdominant inheritance of expression level. Moreover, in accordance with previous studies, genes with trans variants tend to have a dominant inheritance pattern, whereas cis variants are enriched for additive inheritance. In addition, cis regulatory differences contribute more to expression differences between species than within species, whereas trans regulatory differences show a stronger association between divergence and polymorphism. Our data indicate that in the trans component of gene expression differences genes subjected to weaker selective constraints tend to have an excess of polymorphism over divergence compared with those subjected to stronger selective constraints. In contrast, in the cis component, this difference between genes under stronger and weaker selective constraint is mostly absent. To explain these observations, we propose that purifying selection more strongly shapes trans changes than cis changes and that positive selection may have significantly contributed to cis regulatory divergence.
Interleukin 10 (IL-10) inhibits the release of proinflammatory cytokines from human polymorphonuclear leukocytes. Evidence for an autocrine role of tumor necrosis factor and IL-1 beta in mediating the production of IL-8 triggered by lipopolysaccharide.
Authors: M A Cassatella, L Meda, S Bonora, M Ceska, G Constantin
Journal: The Journal of Experimental Medicine (1993)

In this study we have examined the effects of interleukin 10 (IL-10) on polymorphonuclear leukocytes (PMN), and found that it is a potent inhibitor of tumor necrosis factor (TNF), IL-1 beta, and IL-8 secretion triggered by lipopolysaccharide (LPS). Cytokine production by phagocytosing PMN was also inhibited by IL-10, but to a lesser extent than the LPS-induced production. As shown by Northern blot analysis, IL-10 diminished the levels of TNF, IL-1 beta, and IL-8 mRNAs late after the onset of stimulation of PMN with LPS. In addition, we provide evidence that the kinetics of LPS-induced IL-8 production by PMN is composed of two distinct phases. Specifically, our experiments demonstrated that in the first phase, the production of IL-8 is a process directly induced by LPS that lasts for some hours. After this early wave, a second phase begins that is sustained and leads to an elevated production of IL-8 that appears to be due to the endogenous release of TNF and IL-1 beta. This second wave can in fact be blocked by anti-TNF and anti-IL-1 beta neutralizing antibodies, and by IL-10 as the consequence of its downregulatory effects on TNF and IL-1 beta release. Taken together, these findings identify novel biological actions of IL-10 as a suppressor of the inflammatory response.
CASE OF ACUTE DIABETES MELLITUS SUCCESSFULLY TREATED
Authors: T. O. Ward
Journal: BMJ (1855)

mith, ws smmoned, and evything appered to be going on well up to half-past ten o'clock, when severe convul- sions occurred.His attention was immediately directed towards effecting delivery, and by means of the vectis, the birth of a living boy was easily and speedily effected during the second paroxysm.The placenta was separated readily.Twenty ounces of blood were then withdrawn promptly from tie right arm, and a slight opiate administered.As, however, the convulsions recurred with increasing violence, at three o'clock in the morning Mr. Smith requested that I might be sent for.She was then, during the intervals of the fts, talking constantly and moving convulsively, with a screwing-like motion, her hands and arms.Her counte- nance was florid and turgid, the pupils somewhat dilated, * Welsh ale is usually sweet; and, according to Dr. W.Jones, ale contains from 12 to 120 grains of sugar in the ounce.Most writers on diabete men- tion ale drinking as an exciting caue of the disease.
Classical antecedents for modern metaphors for memory
Authors: Jocelyn Penny Small
Journal: Behavioral and Brain Sciences (1996)

Abstract Classical antiquity provides not just the storehouse metaphor, which postdates Plato, but also parts of the correspondence metaphor. In the fifth century B.C., Thucydides (1.22) considered the role of gist and accuracy in writing history, and Aristotle ( Poetics 1451b, 1460b 8–11) offered an explanation. Finally, the Greek for truth ( alêtheia ) means “that which is not forgotten.”
Emergency Hospitalizations for Adverse Drug Events in Older Americans
Authors: Daniel S. Budnitz, Maribeth C. Lovegrove, Nadine Shehab, Chesley L. Richards
Journal: New England Journal of Medicine (2011)

Adverse drug events are important preventable causes of hospitalization in older adults. However, nationally representative data on adverse drug events that result in hospitalization in this population have been limited.We used adverse-event data from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project (2007 through 2009) to estimate the frequency and rates of hospitalization after emergency department visits for adverse drug events in older adults and to assess the contribution of specific medications, including those identified as high-risk or potentially inappropriate by national quality measures.On the basis of 5077 cases identified in our sample, there were an estimated 99,628 emergency hospitalizations (95% confidence interval [CI], 55,531 to 143,724) for adverse drug events in U.S. adults 65 years of age or older each year from 2007 through 2009. Nearly half of these hospitalizations were among adults 80 years of age or older (48.1%; 95% CI, 44.6 to 51.6). Nearly two thirds of hospitalizations were due to unintentional overdoses (65.7%; 95% CI, 60.1 to 71.3). Four medications or medication classes were implicated alone or in combination in 67.0% (95% CI, 60.0 to 74.1) of hospitalizations: warfarin (33.3%), insulins (13.9%), oral antiplatelet agents (13.3%), and oral hypoglycemic agents (10.7%). High-risk medications were implicated in only 1.2% (95% CI, 0.7 to 1.7) of hospitalizations.Most emergency hospitalizations for recognized adverse drug events in older adults resulted from a few commonly used medications, and relatively few resulted from medications typically designated as high-risk or inappropriate. Improved management of antithrombotic and antidiabetic drugs has the potential to reduce hospitalizations for adverse drug events in older adults.
Congenital Complete Absence of the Pericardium
Authors: Osman Ratib, Joseph K. Perloff, William G. Williams
Journal: Circulation (2001)

A 38-year-old woman with ill-defined chest pain had an abnormal x-ray 8 years before her only pregnancy.She had been unable to bear down during delivery, but gestation was otherwise uncomplicated, yielding a normal female offspring.She subsequently experienced left-sided chest pain that awakened her from sleep when turning into either a right or left lateral decubitus position.The pain was pulsating, stabbing, heavy, moderate in severity, and sometimes lasted for hours.Thoracic MRI in the supine and left lateral recumbent positions diagnosed congenital complete absence
Integration with the human genome of peptide sequences obtained by high-throughput mass spectrometry.
Authors: Frank Desiere, Eric W Deutsch, Alexey I Nesvizhskii, Parag Mallick, Nichole L King, Jimmy K Eng, Alan Aderem, Rose Boyle, Erich Brunner, Samuel Donohoe, Nelson Fausto, Ernst Hafen, Lee Hood, Michael G Katze, Kathleen A Kennedy, Floyd Kregenow, Hookeun Lee, Biaoyang Lin, Dan Martin, Jeffrey A Ranish, David J Rawlings, Lawrence E Samelson, Yuzuru Shiio, Julian D Watts, Bernd Wollscheid, Michael E Wright, Wei Yan, Lihong Yang, Eugene C Yi, Hui Zhang, Ruedi Aebersold
Journal: Genome biology (2004)

Abstract A crucial aim upon the completion of the human genome is the verification and functional annotation of all predicted genes and their protein products. Here we describe the mapping of peptides derived from accurate interpretations of protein tandem mass spectrometry (MS) data to eukaryotic genomes and the generation of an expandable resource for integration of data from many diverse proteomics experiments. Furthermore, we demonstrate that peptide identifications obtained from high-throughput proteomics can be integrated on a large scale with the human genome. This resource could serve as an expandable repository for MS-derived proteome information.
Referral Practices of Oncologists to Specialized Palliative Care
Authors: Kirsten Wentlandt, Monika K. Krzyzanowska, Nadia Swami, Gary M. Rodin, Lisa W. Le, Camilla Zimmermann
Journal: Journal of Clinical Oncology (2012)

To describe current referral practices of oncologists to specialized palliative care (SPC) and define demographic characteristics, practice situations, and opinions associated with referral.Physician members of the Canadian Association of Medical Oncologists, Canadian Association of Radiation Oncologists, and Canadian Society of Surgical Oncology were invited to participate in an anonymous survey assessing SPC referral practices. Participants received two e-mailed and two mailed invitations.The response rate was 72% (603 of 839 physicians); 37% were medical oncologists/hematologists, 50% were radiation oncologists, and 12% were surgical oncologists. Ninety-four percent reported that SPC was available to them, but only 37% reported that these services accepted patients on chemotherapy. Eighty-four percent referred terminally ill patients usually/always, but generally for uncontrolled symptoms or discharge planning late in the disease course. One third would refer to SPC earlier if it was renamed supportive care. Predictors of higher referral frequency included comprehensiveness of available SPC services (P = .004), satisfaction with SPC availability (P < .001), SPC acceptance of patients receiving chemotherapy (P < .001), and oncologist ease with referring patients to a palliative care service before they were close to death (P < .001). Controlling for specialty, predictors of referral at diagnosis or during chemotherapy, rather than later, included satisfaction with SPC service availability (P < .001) and SPC service acceptance of patients on chemotherapy (P < .001).Oncologists referred patients frequently to SPC, but generally late in the disease course for patients with uncontrolled symptoms. Availability of comprehensive SPC, especially for patients receiving chemotherapy, and persisting definitional issues seem to be the main barriers preventing timely referral.
Alternating and Intermittent Regimens of Zidovudine and Dideoxycytidine in Patients with AIDS or AIDS-Related Complex
Authors: Gail Skowron
Journal: Annals of Internal Medicine (1993)

Objective: To determine whether alternating regimens consisting of zidovudine and 2′,3′-dideoxycytidine (ddC) reduce the toxicity and maintain or increase the antiretroviral effect associated with each drug alone. Design: An unblinded, randomized (phase II) clinical trial in which seven treatment regimens were compared. Setting: Outpatient clinics of 12 AIDS Clinical Trials Units. Patients: One hundred thirty-one patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex and serum p24 antigenemia (≥ 70 pg/mL). Intervention: Treatments included weekly or monthly alternating zidovudine (200 mg every 4 hours) and ddC (0.01 or 0.03 mg/kg body weight every 4 hours); weekly intermittent zidovudine, 200 mg every 4 hours, or ddC, 0.03 mg/kg every 4 hours; and continuous zidovudine. Measurements: Toxicity, CD4 cell counts, serum p24 antigen levels, and clinical end points. Data were analyzed for the first 48 weeks of therapy (median follow-up, 40 weeks). Results: Hematologic toxicity was significantly less frequent in patients who received zidovudine therapy every other week (11% to 15%) or every other month (11% to 14%) than in those who received continuous zidovudine therapy (33%) (P < 0.02). Weekly alternating therapy with zidovudine and ddC, 0.03 mg/kg, or intermittent therapy with ddC, 0.03 mg/kg, produced high rates of peripheral neuropathy (41% and 50%, respectively). Neuropathy occurred in 10% to 21% of patients in the other three alternating-therapy limbs and in 17% of patients receiving zidovudine alone (intermittently or continuously). Initial increases in CD4 cell counts were sustained in three alternating-therapy limbs, but counts returned to baseline by week 28 in the remaining limbs. The median weight gain at week 48 was significantly greater in patients treated with alternating regimens (0.9 to 3.8 kg) compared with those treated with continuous zidovudine therapy ( −0.7 kg) (P = 0.008). Patients treated with alternating regimens and those treated with continuous zidovudine had similarly sustained decreases in p24 antigen levels. Conclusions: These findings suggest that alternating therapy with zidovudine and ddC reduces the toxicity associated with each drug alone while maintaining strong antiretroviral activity.
Smoking, Obesity, Health Insurance, and Health Incentives in the Affordable Care Act
Authors: Kristin Madison, Harald Schmidt, Kevin G. Volpp
Journal: JAMA (2013)

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Red cell indices in normal adults residing at altitudes from sea level to 2670 meters
Authors: G. J. Ruíz‐Argüelles, L. Sánchez‐Medal, A. Loría, J. Piedras, M. S. Córdova
Journal: American Journal of Hematology (1980)

Hemoglobin (Hb), packed cell volume (PCV), red blood cells (RBCs), mean cell volume (MCV), and mean cell hemoglobin concentration (MCHC) were measured by a single operator in a single laboratory by means of an electronic particle counter in 942 healthy adults (491 females and 451 males) residing at five altitudes: 0, 1000, 1860, 2220, and 2670 meters above sea level. The subjects were carefully screened clinically, and subjects with low transferrin saturation (less than 15%) were excluded. In both sexes there was a differential behavior as a function of altitude, of Hb and PCV on the one hand, and number of RBCs on the other. The findings suggest the presence of two sequential mechanisms of adaptation to progressively lower atmosphere oxygen pressure: One operating from sea level to 1860 meters, which leads to a progressively increasing number of relatively microcytic RBC; and a second one -- from 1860 to 2670 meters -- in which there is an increased but constant number of progressively more normocytic RBC, so that a simplistic model of equal magnitude increases in the three parameters and is seen at 2670 meters, but not at the intermediate altitudes. The middle group's comparativity, essential to these interpretations, apparently was achieved with regard to time elapsed between sampling and testing and with regard to the people integrating the groups.
Membranous nephropathy: from models to man
Authors: Laurence H. Beck, David J. Salant
Journal: Journal of Clinical Investigation (2014)

As recently as 2002, most cases of primary membranous nephropathy (MN), a relatively common cause of nephrotic syndrome in adults, were considered idiopathic. We now recognize that MN is an organ-specific autoimmune disease in which circulating autoantibodies bind to an intrinsic antigen on glomerular podocytes and form deposits of immune complexes in situ in the glomerular capillary walls. Here we define the clinical and pathological features of MN and describe the experimental models that enabled the discovery of the major target antigen, the M-type phospholipase A2 receptor 1 (PLA2R). We review the pathophysiology of experimental MN and compare and contrast it with the human disease. We discuss the diagnostic value of serological testing for anti-PLA2R and tissue staining for the redistributed antigen, and their utility for differentiating between primary and secondary MN, and between recurrent MN after kidney transplant and de novo MN. We end with consideration of how knowledge of the antigen might direct future therapeutic strategies.
Recent and Recurrent Selective Sweeps of the Antiviral RNAi Gene Argonaute-2 in Three Species of Drosophila
Authors: D. J. Obbard, F. M. Jiggins, N. J. Bradshaw, T. J. Little
Journal: Molecular Biology and Evolution (2010)

Antagonistic host–parasite interactions can drive rapid adaptive evolution in genes of the immune system, and such arms races may be an important force shaping polymorphism in the genome. The RNA interference pathway gene Argonaute-2 (AGO2) is a key component of antiviral defense in Drosophila, and we have previously shown that genes in this pathway experience unusually high rates of adaptive substitution. Here we study patterns of genetic variation in a 100-kbp region around AGO2 in three different species of Drosophila. Our data suggest that recent independent selective sweeps in AGO2 have reduced genetic variation across a region of more than 50 kbp in Drosophila melanogaster, D. simulans, and D. yakuba, and we estimate that selection has fixed adaptive substitutions in this gene every 30–100 thousand years. The strongest signal of recent selection is evident in D. simulans, where we estimate that the most recent selective sweep involved an allele with a selective advantage of the order of 0.5–1% and occurred roughly 13–60 Kya. To evaluate the potential consequences of the recent substitutions on the structure and function of AGO2, we used fold-recognition and homology-based modeling to derive a structural model for the Drosophila protein, and this suggests that recent substitutions in D. simulans are overrepresented at the protein surface. In summary, our results show that selection by parasites can consistently target the same genes in multiple species, resulting in areas of the genome that have markedly reduced genetic diversity.