tbuckley/cabot-search huggingface dataset:
Mortality Among Homeless Adults in Boston
Authors: Travis P. Baggett, Stephen W. Hwang, James J. O’Connell, Bianca C. Porneala, Erin J. Stringfellow, E. John Orav, Daniel E. Singer, Nancy A. Rigotti
Journal: JAMA Internal Medicine (2013)

Homeless persons experience excess mortality, but US-based studies on this topic are outdated or lack information about causes of death. To our knowledge, no studies have examined shifts in causes of death for this population over time.We assessed all-cause and cause-specific mortality rates in a cohort of 28 033 adults 18 years or older who were seen at Boston Health Care for the Homeless Program from January 1, 2003, through December 31, 2008. Deaths were identified through probabilistic linkage to the Massachusetts death occurrence files. We compared mortality rates in this cohort with rates in the 2003-2008 Massachusetts population and a 1988-1993 cohort of homeless adults in Boston using standardized rate ratios with 95% confidence intervals.A total of 1302 deaths occurred during 90 450 person-years of observation. Drug overdose (n = 219), cancer (n = 206), and heart disease (n = 203) were the major causes of death. Drug overdose accounted for one-third of deaths among adults younger than 45 years. Opioids were implicated in 81% of overdose deaths. Mortality rates were higher among whites than nonwhites. Compared with Massachusetts adults, mortality disparities were most pronounced among younger individuals, with rates about 9-fold higher in 25- to 44-year-olds and 4.5-fold higher in 45- to 64-year-olds. In comparison with 1988-1993 rates, reductions in deaths from human immunodeficiency virus (HIV) were offset by 3- and 2-fold increases in deaths owing to drug overdose and psychoactive substance use disorders, resulting in no significant difference in overall mortality.The all-cause mortality rate among homeless adults in Boston remains high and unchanged since 1988 to 1993 despite a major interim expansion in clinical services. Drug overdose has replaced HIV as the emerging epidemic. Interventions to reduce mortality in this population should include behavioral health integration into primary medical care, public health initiatives to prevent and reverse drug overdose, and social policy measures to end homelessness.
Gain of chromosome 6p is an infrequent cause of increased PIM1 expression in B-cell non-Hodgkin's lymphomas
Authors: E A Sivertsen, E Galteland, D Mu, H Holte, L Meza-Zepeda, O Myklebost, S Patzke, E B Smeland, T Stokke
Journal: Leukemia (2006)
Age-Related Changes in Nutrient Utilization by Companion Animals
Authors: George C. Fahey, Kathleen A. Barry, Kelly S. Swanson
Journal: Annual Review of Nutrition (2008)

As companion animals age and pass through various life stages from in utero to the geriatric state, nutrient requirements change along with the manner in which nutrients are utilized by the various organ systems in the body. From the regulatory perspective, recognized life stages include maintenance, growth, and gestation/lactation. Other important life stages include in utero, the neonate, and the senior/geriatric state. Age affects digestive physiological properties, too, and factors such as gut microbiota, digestive hormones, gut morphology, gut immunity, and nutrient digestibility are modified as the animal becomes older. Each of the nutrients is affected in some manner by age, some more than others. Genomic biology offers promise in helping elucidate in greater detail how nutrient utilization is affected by age of the dog and cat.
Distinct patterns of inflammation in the airway lumen and bronchial mucosa of children with cystic fibrosis
Authors: Nicolas Regamey, Lemonia Tsartsali, Tom N Hilliard, Oliver Fuchs, Hui-Leng Tan, Jie Zhu, Yu-Sheng Qiu, Eric W F W Alton, Peter K Jeffery, Andrew Bush, Jane C Davies
Journal: Thorax (2011)

<h3>Background</h3> Studies in cystic fibrosis (CF) generally focus on inflammation present in the airway lumen. Little is known about inflammation occurring in the airway wall, the site ultimately destroyed in end-stage disease. <h3>Objective</h3> To test the hypothesis that inflammatory patterns in the lumen do not reflect those in the airway wall of children with CF. <h3>Methods</h3> Bronchoalveolar lavage (BAL) fluid and endobronchial biopsies were obtained from 46 children with CF and 16 disease-free controls. BAL cell differential was assessed using May-Gruenwald-stained cytospins. Area profile counts of bronchial tissue immunopositive inflammatory cells were determined. <h3>Results</h3> BAL fluid from children with CF had a predominance of neutrophils compared with controls (median 810×10<sup>3</sup>/ml vs 1×10<sup>3</sup>/ml, p&lt;0.0001). In contrast, subepithelial bronchial tissue from children with CF was characterised by a predominance of lymphocytes (median 961 vs 717 cells/mm<sup>2</sup>, p=0.014), of which 82% were (CD3) T lymphocytes. In chest exacerbations, BAL fluid from children with CF had more inflammatory cells of all types compared with those with stable disease whereas, in biopsies, only the numbers of lymphocytes and macrophages, but not of neutrophils, were higher. A positive culture of <i>Pseudomonas aeruginosa</i> was associated with higher numbers of T lymphocytes in subepithelial bronchial tissue (median 1174 vs 714 cells/mm<sup>2</sup>, p=0.029), but no changes were seen in BAL fluid. Cell counts in BAL fluid and biopsies were positively correlated with age but were unrelated to each other. <h3>Conclusion</h3> The inflammatory response in the CF airway is compartmentalised. In contrast to the neutrophil-dominated inflammation present in the airway lumen, the bronchial mucosa is characterised by the recruitment and accumulation of lymphocytes.
Alternans and Arrhythmias
Authors: James N. Weiss, Michael Nivala, Alan Garfinkel, Zhilin Qu
Journal: Circulation Research (2011)

The goal of systems biology is to relate events at the molecular level to more integrated scales from organelle to cell, tissue, and living organism. Here, we review how normal and abnormal excitation–contraction coupling properties emerge from the protein scale, where behaviors are dominated by randomness, to the cell and tissue scales, where heart has to beat with reliable regularity for a lifetime. Beginning with the fundamental unit of excitation–contraction coupling, the couplon where L-type Ca channels in the sarcolemmal membrane adjoin ryanodine receptors in the sarcoplasmic reticulum membrane, we show how a network of couplons with 3 basic properties (random activation, refractoriness, and recruitment) produces the classic physiological properties of excitation–contraction coupling and, under pathophysiological conditions, leads to Ca alternans and Ca waves. Moving to the tissue scale, we discuss how cellular Ca alternans and Ca waves promote both reentrant and focal arrhythmias in the heart. Throughout, we emphasize the qualitatively novel properties that emerge at each new scale of integration.
University of Toronto researcher resigns over "systematic" data fraud
Authors: O. Dyer
Journal: BMJ (2015)

The medical journal JAMA is considering retracting an article after an investigation found “unequivocal evidence of systematic data manipulation” by the lead author, Sophie Jamal, an acclaimed Canadian endocrinologist.

In September Jamal resigned her associate professorship at the University of Toronto and gave up her clinical privileges and posts at the city’s Women’s College Hospital, where she had been research director of the Centre for Osteoporosis and Bone Health and the division head of endocrinology and metabolism.

Jamal has also stood down as co-director of the Toronto centre for the Canadian Multicentre Osteoporosis Study, Canada’s largest ever study on osteoporosis, which is following almost 10 000 women. She has taken …
Proton Magnetic Resonance Spectroscopy of Bipolar Disorder Versus Intermittent Explosive Disorder in Children and Adolescents
Authors: Pablo Davanzo, Kenneth Yue, M. Albert Thomas, Thomas Belin, Jim Mintz, T.N. Venkatraman, Eliana Santoro, Sarah Barnett, James McCracken
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: The diagnosis of bipolar disorder in juveniles is controversial. This study was designed to compare proton magnetic resonance spectroscopy (1H MRS) in patients with bipolar disorder or intermittent explosive disorder, two groups with symptomatic overlap but categorical distinction. Children with intermittent explosive disorder designate patients whose illness clinically resembles pediatric bipolar disorder but does not satisfy DSM-IV criteria for mania. Based on the authors' previous report of higher levels of 1H MRS cingulate myo-inositol/creatine in youngsters with bipolar disorder than in normal comparison subjects, they hypothesized that patients with bipolar disorder would have higher cingulate myo-inositol/creatine-phosphocreatine measurements than patients with intermittent explosive disorder and normal comparison subjects. METHOD: Myo-inositol levels were measured with a 2×2×2 cm3 voxel placed in the anterior cingulate for acquisition of 1H MRS in 10 patients with bipolar disorder, 10 patients with intermittent explosive disorder, and 13 normal comparison subjects. N-Acetylaspartate, choline moieties, creatine-phosphocreatine, and glutamate-glutamine metabolite levels were also measured. RESULTS: The patients with bipolar disorder showed significantly higher anterior cingulate myo-inositol/creatine-phosphocreatine and myo-inositol (mmol/liter) levels than the patients with intermittent explosive disorder and the normal comparison subjects. No significant differences were found across groups for myo-inositol or other metabolites in the occipital cortex. CONCLUSIONS: These data provide evidence that differences in the concentration of myo-inositol (mmol/liter) in the anterior cingulate cortex in 1H MRS may differentiate these two populations. Follow-up studies involving larger samples may conclusively estimate the biological specificity between pediatric bipolar disorder and other disorders, which overlap clinically.
Blockade of mineralocorticoid receptor reverses adipocyte dysfunction and insulin resistance in obese mice
Authors: Ayumu Hirata, Norikazu Maeda, Aki Hiuge, Toshiyuki Hibuse, Koichi Fujita, Takuya Okada, Shinji Kihara, Tohru Funahashi, Iichiro Shimomura
Journal: Cardiovascular Research (2009)

AimsIn obesity, chronic low-grade inflammation and overproduction of reactive oxygen species (ROS) in fat contribute to the development of metabolic syndrome. Suppression of inflammation and ROS production in fat may attenuate the metabolic syndrome. Activation of mineralocorticoid receptor (MR) promotes inflammation in heart, kidney, and vasculature via ROS generation. However, the significance of MR in fat remains elusive. Here we investigated whether MR blockade attenuates obesity-related insulin resistance and improves adipocyte dysfunction.
Reply to C. Fozza
Authors: Ruth Pettengell, Norbert Schmitz, Peter Dreger, Anthony Goldstone
Journal: Journal of Clinical Oncology (2013)

until progression) or retreatment (four weekly rituximab doses).Once again, no significant differences in time to treatment failure were shown, besides a three times greater use of rituximab in the maintenance arm and no relevant differences in quality of life outcomes. 4s already highlighted especially in the first-line scenario, theoretical benefits of a strategy based on retreatment rather than maintenance with rituximab include a better cost effectiveness profile, reduction in the infection rates, and reduced likelihood of developing rituximab resistance. 5 Although the results presented by Pettengel et al 1 offer exciting new perspectives for patients with FL in an extremely difficult phase of their disease history, to further maximize these findings, a strategy based on rituximab retreatment may deserve to be explored also after HDC-ASCT.
Predictors of Ischemic Stroke in the Territory of a Symptomatic Intracranial Arterial Stenosis
Authors: Scott E. Kasner, Marc I. Chimowitz, Michael J. Lynn, Harriet Howlett-Smith, Barney J. Stern, Vicki S. Hertzberg, Michael R. Frankel, Steven R. Levine, Seemant Chaturvedi, Curtis G. Benesch, Cathy A. Sila, Tudor G. Jovin, Jose G. Romano, Harry J. Cloft
Journal: Circulation (2006)

Background— Antithrombotic therapy for intracranial arterial stenosis was recently evaluated in the Warfarin versus Aspirin for Symptomatic Intracranial Disease (WASID) trial. A prespecified aim of WASID was to identify patients at highest risk for stroke in the territory of the stenotic artery who would be the target group for a subsequent trial comparing intracranial stenting with medical therapy. Methods and Results— WASID was a randomized, double-blinded, multicenter trial involving 569 patients with transient ischemic attack or ischemic stroke due to 50% to 99% stenosis of a major intracranial artery. Median time from qualifying event to randomization was 17 days, and mean follow-up was 1.8 years. Multivariable Cox proportional hazards models were used to identify factors associated with subsequent ischemic stroke in the territory of the stenotic artery. Subsequent ischemic stroke occurred in 106 patients (19.0%); 77 (73%) of these strokes were in the territory of the stenotic artery. Risk of stroke in the territory of the stenotic artery was highest with severe stenosis ≥70% (hazard ratio 2.03; 95% confidence interval 1.29 to 3.22; P =0.0025) and in patients enrolled early (≤17 days) after the qualifying event (hazard ratio 1.69; 95% confidence interval 1.06 to 2.72; P =0.028). Women were also at increased risk, although this was of borderline significance (hazard ratio 1.59; 95% confidence interval 1.00 to 2.55; P =0.051). Location of stenosis, type of qualifying event, and prior use of antithrombotic medications were not associated with increased risk. Conclusions— Among patients with symptomatic intracranial stenosis, the risk of subsequent stroke in the territory of the stenotic artery is greatest with stenosis ≥70%, after recent symptoms, and in women.
Monoclonal IgG antibodies generated from joint-derived B cells of RA patients have a strong bias toward citrullinated autoantigen recognition
Authors: Khaled Amara, Johanna Steen, Fiona Murray, Henner Morbach, Blanca M. Fernandez-Rodriguez, Vijay Joshua, Marianne Engström, Omri Snir, Lena Israelsson, Anca I. Catrina, Hedda Wardemann, Davide Corti, Eric Meffre, Lars Klareskog, Vivianne Malmström
Journal: The Journal of Experimental Medicine (2013)

Antibodies targeting citrullinated proteins (ACPAs [anticitrullinated protein antibodies]) are commonly found in patients with rheumatoid arthritis (RA), strongly associate with distinct HLA-DR alleles, and predict a more aggressive disease course as compared with seronegative patients. Still, many features of these antibodies, including their site of production and the extent of MHC class II-driven T cell help, remain unclarified. To address these questions, we have used a single B cell-based cloning technology to isolate and express immunoglobulin (Ig) genes from joint-derived B cells of active RA patients. We found ∼25% of synovial IgG-expressing B cells to be specific for citrullinated autoantigens in the investigated ACPA(+) RA patients, whereas such antibodies were not found in ACPA(-) patients. The citrulline-reactive monoclonal antibodies did not react with the unmodified arginine peptides, yet several reacted with more than one citrullinated antigen. A role for active antigen selection of the citrulline-reactive synovial B cells was supported by the strong bias toward amino acid replacement mutations in ACPA(+) antibodies and by their loss of reactivity to citrullinated autoantigens when somatic mutations were reverted to the corresponding germline sequences.
Surgery for pulmonary aspergilloma: preoperative embolisation of the bronchial circulation.
Authors: C F Hughes, R Waugh, D Lindsay
Journal: Thorax (1986)

L'arteriographie pulmonaire et bronchique permet au chirurgien de definir la resection la plus appropriee et la plus conservatrice. Associee aux methodes chirurgicales recentes comme les techniques d'agrafages, l'embolisation selective devrait assurer que la conservation maximale de tissu pulmonaire soit obtenue avec un minimum de difficultes chirurgicales
Implications of a 2005 Measles Outbreak in Indiana for Sustained Elimination of Measles in the United States
Authors: Amy A. Parker, Wayne Staggs, Gustavo H. Dayan, Ismael R. Ortega-Sánchez, Paul A. Rota, Luis Lowe, Patricia Boardman, Robert Teclaw, Charlene Graves, Charles W. LeBaron
Journal: New England Journal of Medicine (2006)

Measles was declared eliminated from the United States in 2000 but remains endemic worldwide. In 2005, a 17-year-old unvaccinated girl who was incubating measles returned from Romania, creating the largest documented outbreak of measles in the United States since 1996.We conducted a case-series investigation, molecular typing of viral isolates, surveys of rates of vaccination coverage, interviews regarding attitudes toward vaccination, and cost surveys.Approximately 500 persons attended a gathering with the index patient one day after her return home. Approximately 50 lacked evidence of measles immunity, of whom 16 (32 percent) acquired measles at the gathering. During the six weeks after the gathering, a total of 34 cases of measles were confirmed. Of the patients with confirmed measles, 94 percent were unvaccinated, 88 percent were less than 20 years of age, and 9 percent were hospitalized. Of the 28 patients who were 5 to 19 years of age, 71 percent were home-schooled. Vaccine failure occurred in two persons. The virus strain was genotype D4, which is endemic in Romania. Although containment measures began after 20 persons were already infectious, measles remained confined mostly to children whose parents had refused to have them vaccinated, primarily out of concern for adverse events from the vaccine. Seventy-one percent of patients were from four households. Levels of measles-vaccination coverage in Indiana were 92 percent for preschoolers and 98 percent for sixth graders. Estimated costs of containing the disease were at least 167,685 dollars, including 113,647 dollars at a hospital with an infected employee.This outbreak was caused by the importation of measles into a population of children whose parents had refused to have them vaccinated because of safety concerns about the vaccine. High vaccination levels in the surrounding community and low rates of vaccine failure averted an epidemic. Maintenance of high rates of vaccination coverage, including improved strategies of communication with persons who refuse vaccination, is necessary to prevent future outbreaks and sustain the elimination of measles in the United States.
Nerve Growth Factor Signaling, Neuroprotection, and Neural Repair
Authors: Michael V Sofroniew, Charles L Howe, William C Mobley
Journal: Annual Review of Neuroscience (2001)

▪ Abstract Nerve growth factor (NGF) was discovered 50 years ago as a molecule that promoted the survival and differentiation of sensory and sympathetic neurons. Its roles in neural development have been characterized extensively, but recent findings point to an unexpected diversity of NGF actions and indicate that developmental effects are only one aspect of the biology of NGF. This article considers expanded roles for NGF that are associated with the dynamically regulated production of NGF and its receptors that begins in development, extends throughout adult life and aging, and involves a surprising variety of neurons, glia, and nonneural cells. Particular attention is given to a growing body of evidence that suggests that among other roles, endogenous NGF signaling subserves neuroprotective and repair functions. The analysis points to many interesting unanswered questions and to the potential for continuing research on NGF to substantially enhance our understanding of the mechanisms and treatment of neurological disorders.
Users' guides to the medical literature. VII. How to use a clinical decision analysis. A. Are the results of the study valid? Evidence-Based Medicine Working Group
Authors: W. S. Richardson
Journal: JAMA (1995)

<h3>CLINICAL SCENARIO</h3> You are the attending physician on an inpatient service where a 51-year-old man is admitted with congestive heart failure of recent onset. You find he has a dilated cardiomyopathy, the cause of which remains unknown after a thorough evaluation. He is in sinus rhythm. The team's resident asks you whether the patient should be anticoagulated with warfarin, enough to keep his international normalized ratio from 2.0 to 3.0, in order to prevent systemic emboli, even though his echocardiogram does not show left ventricular thrombus. You are not sure about the evidence concerning this issue, so you admit your shared knowledge gap and resolve to search together for the relevant information. <h3>THE SEARCH</h3> In the hospital's library, the two of you search the MEDLINE system us
Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid–induced ceramide biosynthesis in mice
Authors: William L. Holland, Benjamin T. Bikman, Li-Ping Wang, Guan Yuguang, Katherine M. Sargent, Sarada Bulchand, Trina A. Knotts, Guanghou Shui, Deborah J. Clegg, Markus R. Wenk, Michael J. Pagliassotti, Philipp E. Scherer, Scott A. Summers
Journal: Journal of Clinical Investigation (2011)

Obesity is associated with an enhanced inflammatory response that exacerbates insulin resistance and contributes to diabetes, atherosclerosis, and cardiovascular disease. One mechanism accounting for the increased inflammation associated with obesity is activation of the innate immune signaling pathway triggered by TLR4 recognition of saturated fatty acids, an event that is essential for lipid-induced insulin resistance. Using in vitro and in vivo systems to model lipid induction of TLR4-dependent inflammatory events in rodents, we show here that TLR4 is an upstream signaling component required for saturated fatty acid-induced ceramide biosynthesis. This increase in ceramide production was associated with the upregulation of genes driving ceramide biosynthesis, an event dependent of the activity of the proinflammatory kinase IKKβ. Importantly, increased ceramide production was not required for TLR4-dependent induction of inflammatory cytokines, but it was essential for TLR4-dependent insulin resistance. These findings suggest that sphingolipids such as ceramide might be key components of the signaling networks that link lipid-induced inflammatory pathways to the antagonism of insulin action that contributes to diabetes.