tbuckley/cabot-search huggingface dataset:
Computing motivation: Incentive salience boosts of drug or appetite states
Authors: Kent C. Berridge, Jun Zhang, J. Wayne Aldridge
Journal: Behavioral and Brain Sciences (2008)

Abstract Current computational models predict reward based solely on learning. Real motivation involves that but also more. Brain reward systems can dynamically generate incentive salience, by integrating prior learned values with even novel physiological states (e.g., natural appetites; drug-induced mesolimbic sensitization) to cause intense desires that were themselves never learned. We hope future computational models may capture this too.
Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: implications for CML
Authors: Thomas O'Hare, Roy Pollock, Eric P. Stoffregen, Jeffrey A. Keats, Omar M. Abdullah, Erika M. Moseson, Victor M. Rivera, Hao Tang, Chester A. Metcalf, Regine S. Bohacek, Yihan Wang, Raji Sundaramoorthi, William C. Shakespeare, David Dalgarno, Tim Clackson, Tomi K. Sawyer, Michael W. Deininger, Brian J. Druker
Journal: Blood (2004)
The Clinical Pathophysiology of Sickle Cell Disease
Authors: S H Embury
Journal: Annual Review of Medicine (1986)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
Substantial addition to ARD Online
Authors: J. O'Flaherty, L van de Putte
Journal: Annals of the Rheumatic Diseases (2007)

Annals content from 1939 now available online

From June 2007 the complete archive of Annals of the Rheumatic Diseases – the Eular journal will be available online www.ard.bmj.com – that’s all issues from January 1939 to today. In keeping with the BMJ Group’s delayed free access policy all content older than 12 month’s is free to non-subscribers, including the newly digitised legacy content.

ARD was the first international rheumatology journal in English, so it attracted prominent authors, and their papers gave the first global mirror of rheumatology in Europe and North America as long ago as 1939. Interestingly, in the very first issue of the journal 6 of the 10 papers were about infections in …
The G Protein–Coupled Receptor GPR30 Inhibits Proliferation of Estrogen Receptor–Positive Breast Cancer Cells
Authors: Eric A. Ariazi, Eugen Brailoiu, Smitha Yerrum, Heather A. Shupp, Michael J. Slifker, Heather E. Cunliffe, Michael A. Black, Anne L. Donato, Jeffrey B. Arterburn, Tudor I. Oprea, Eric R. Prossnitz, Nae J. Dun, V. Craig Jordan
Journal: Cancer Research (2010)

The G protein-coupled receptor GPR30 binds 17beta-estradiol (E(2)) yet differs from classic estrogen receptors (ERalpha and ERbeta). GPR30 can mediate E(2)-induced nongenomic signaling, but its role in ERalpha-positive breast cancer remains unclear. Gene expression microarray data from five cohorts comprising 1,250 breast carcinomas showed an association between increased GPR30 expression and ERalpha-positive status. We therefore examined GPR30 in estrogenic activities in ER-positive MCF-7 breast cancer cells using G-1 and diethylstilbestrol (DES), ligands that selectively activate GPR30 and ER, respectively, and small interfering RNAs. In expression studies, E(2) and DES, but not G-1, transiently downregulated both ER and GPR30, indicating that this was ER mediated. In Ca(2+) mobilization studies, GPR30, but not ERalpha, mediated E(2)-induced Ca(2+) responses because E(2), 4-hydroxytamoxifen (activates GPR30), and G-1, but not DES, elicited cytosolic Ca(2+) increases not only in MCF-7 cells but also in ER-negative SKBr3 cells. Additionally, in MCF-7 cells, GPR30 depletion blocked E(2)-induced and G-1-induced Ca(2+) mobilization, but ERalpha depletion did not. Interestingly, GPR30-coupled Ca(2+) responses were sustained and inositol triphosphate receptor mediated in ER-positive MCF-7 cells but transitory and ryanodine receptor mediated in ER-negative SKBr3 cells. Proliferation studies involving GPR30 depletion indicated that the role of GPR30 was to promote SKBr3 cell growth but reduce MCF-7 cell growth. Supporting this, G-1 profoundly inhibited MCF-7 cell growth, potentially via p53 and p21 induction. Further, flow cytometry showed that G-1 blocked MCF-7 cell cycle progression at the G(1) phase. Thus, GPR30 antagonizes growth of ERalpha-positive breast cancer and may represent a new target to combat this disease.
Cardiac Submembrane [Na <sup>+</sup> ] Transients Sensed by Na <sup>+</sup> -Ca <sup>2+</sup> Exchange Current
Authors: Christopher R. Weber, Kenneth S. Ginsburg, Donald M. Bers
Journal: Circulation Research (2003)

Na+ influx via INa during cardiac action potentials can raise bulk [Na+]i by 10 to 15 micromol/L. However, larger rises in submembrane [Na+] ([Na+]sm) local to Na+-Ca2+ exchangers (NCX) could enhance Ca2+ influx via NCX (and Ca2+-induced Ca2+ release). We tested whether INa could increase [Na+]sm, using NCX current (INCX) as a biosensor in rabbit ventricular myocytes (with [Ca2+]i buffered, [Na+]i=10 mmol/L, and other currents blocked). We measured INCX as early as 5 ms after INa. Prior INa activation did not affect INCX at physiological membrane potentials (Em=-100 to +50 mV), but for Em >+50 mV (where INCX is especially sensitive to [Na+]i), INCX shifted outward. At 5 ms and +100 mV, INa shifted INCX outward by 0.23 A/F (corresponding to Delta[Na+]sm=0.24 mmol/L). The effect of INa dissipated with a time constant of approximately 15 ms. Thus, the impact of INa on NCX is almost undetectable at physiological Em and short lived. This suggests that INa effects on excitation-contraction coupling (via outward INCX) are minimal and limited to early during the action potential. However, local Delta[Na+]sm during INa may be 60 times higher than bulk Delta[Na+]i.
Novel Insight Into the Natural History of Short QT Syndrome
Authors: Andrea Mazzanti, Ajita Kanthan, Nicola Monteforte, Mirella Memmi, Raffaella Bloise, Valeria Novelli, Carlotta Miceli, Sean O'Rourke, Gianluca Borio, Agnieszka Zienciuk-Krajka, Antonio Curcio, Andreea Elena Surducan, Mario Colombo, Carlo Napolitano, Silvia G. Priori
Journal: Journal of the American College of Cardiology (2013)

This study intends to gain further insights into the natural history, the yield of familial and genetic screening, and the arrhythmogenic mechanisms in the largest cohort of short QT syndrome (SQTS) patients described so far.SQTS is a rare genetic disorder associated with life-threatening arrhythmias, and its natural history is incompletely ascertained.Seventy-three SQTS patients (84% male; age, 26 ± 15 years; corrected QT interval, 329 ± 22 ms) were studied, and 62 were followed for 60 ± 41 months (median, 56 months).Cardiac arrest (CA) was the most frequent presenting symptom (40% of probands; range, <1 month to 41 years). The rate of CA was 4% in the first year of life and 1.3% per year between 20 and 40 years; the probability of a first occurrence of CA by 40 years of age was 41%. Despite the male predominance, female patients had a risk profile superimposable to that of men (p = 0.49). The yield of genetic screening was low (14%), despite familial disease being present in 44% of kindreds. A history of CA was the only predictor of recurrences at follow-up (p < 0.0000001). Two patterns of onset of ventricular fibrillation were observed and were reproducible in patients with multiple occurrences of CA. Arrhythmias occurred mainly at rest.SQTS is highly lethal; CA is often the first manifestation of the disease with a peak incidence in the first year of life. Survivors of CA have a high CA recurrence rate; therefore, implantation of a defibrillator is strongly recommended in this group of patients.
Review of diabetes management and guidelines during Ramadan
Authors: Muhammad Ali Karamat, Ateeq Syed, Wasim Hanif
Journal: Journal of the Royal Society of Medicine (2010)

Demographics of the Muslim population
Islam is the second largest religion in the world and Muslims constitute approximately 22% of the world's population. According to latest data, the total number of Muslims in the world is over 1.5 billion. In Europe Muslims constitute approximately 7% of the overall population. In the UK the size of the Muslim population is estimated to be close to 1.6 million, constituting 2.7% of the overall population.1 While diabetes affects 4% of the white Caucasian population, it affects 22% of Pakistani and 27% of the Bangladeshi Muslim population (aged 25–74 years).2 The approximate number of Muslims in the UK with diabetes is estimated at 325,000.3

Most patients with diabetes are asymptomatic; they do not consider themselves as having an illness and fast during Ramadan. The concerns are fasting may lead to hypoglycaemia, hyperglycaemia with or without ketoacidosis, and dehydration. Another problem is the reluctance of patients in taking their medications during the fast, therefore timing and dosage of anti-diabetic agents has to be adjusted for individual patients. Despite all this, it must be pointed out that very few complications are actually seen in clinical practice.4 Managing Muslim patients with diabetes during Ramadan continues to be a challenge for healthcare professionals. This review is intended to offer a guide towards care of the Muslim patient with diabetes during Ramadan.
Influence of Institutional Culture and Policies on Do-Not-Resuscitate Decision Making at the End of Life
Authors: Elizabeth Dzeng, Alessandra Colaianni, Martin Roland, Geetanjali Chander, Thomas J. Smith, Michael P. Kelly, Stephen Barclay, David Levine
Journal: JAMA Internal Medicine (2015)

Controversy exists regarding whether the decision to pursue a do-not-resuscitate (DNR) order should be grounded in an ethic of patient autonomy or in the obligation to act in the patient's best interest (beneficence).To explore how physicians' approaches to DNR decision making at the end of life are shaped by institutional cultures and policies surrounding patient autonomy.We performed semistructured in-depth qualitative interviews of 58 internal medicine physicians from 4 academic medical centers (3 in the United States and 1 in the United Kingdom) by years of experience and medical subspecialty from March 7, 2013, through January 8, 2014. Hospitals were selected based on expected differences in hospital culture and variations in hospital policies regarding prioritization of autonomy vs best interest.This study identified the key influences of institutional culture and policies on physicians' attitudes toward patient autonomy in DNR decision making at the end of life.A hospital's prioritization of autonomy vs best interest as reflected in institutional culture and policy appeared to influence the way that physician trainees conceptualized patient autonomy. This finding may have influenced the degree of choice and recommendations physician trainees were willing to offer regarding DNR decision making. Trainees at hospitals where policies and culture prioritized autonomy-focused approaches appeared to have an unreflective deference to autonomy and felt compelled to offer the choice of resuscitation neutrally in all situations regardless of whether they believed resuscitation to be clinically appropriate. In contrast, trainees at hospitals where policies and culture prioritized best-interest-focused approaches appeared to be more comfortable recommending against resuscitation in situations where survival was unlikely. Experienced physicians at all sites similarly did not exclusively allow their actions to be defined by policies and institutional culture and were willing to make recommendations against resuscitation if they believed it would be futile.Institutional cultures and policies might influence how physician trainees develop their professional attitudes toward autonomy and their willingness to make recommendations regarding the decision to implement a DNR order. A singular focus on autonomy might inadvertently undermine patient care by depriving patients and surrogates of the professional guidance needed to make critical end of life decisions.
Hepatectomy for Noncolorectal Liver Metastases
Authors: Todd M. Tuttle
Journal: Liver Cancer (1998)

Hepatic resection is the treatment of choice for patients with isolated metastases from colorectal primary tumors. Systemic chemotherapy provides responses in only a few patients and results in a median survival of approximately 12 months.1–3 By comparison, median survival after hepatic resection of colorectal metastases is approximately 25–35 months with a 5-year survival rate of 25–33%.4–6 With appropriate patient selection, advances in surgical intensive care, and improved methods for parenchymal dissection to minimize blood loss, the operative mortality rate of hepatectomy is now 5% or less at most major centers.7,8 Several published reports have identified specific determinants of survival for patients undergoing liver resection for colorectal metastases. Although agreement is not universal for every clinical variable, the importance of tumor-free margins of resection, disease-free interval before development of metastases, stage of the primary colorectal tumor, and the number of metastases is well documented.6,8,9
Age Before Stage: Insulin Resistance Rises Before the Onset of Puberty
Authors: Alison N. Jeffery, Brad S. Metcalf, Joanne Hosking, Adam J. Streeter, Linda D. Voss, Terence J. Wilkin
Journal: Diabetes Care (2012)

Insulin resistance (IR) is associated with diabetes. IR is higher during puberty in both sexes, with some studies showing the increase to be independent of changes in adiposity. Few longitudinal studies have reported on children, and it remains unclear when the rise in IR that is often attributed to puberty really begins. We sought to establish from longitudinal data its relationship to pubertal onset, and interactions with age, sex, adiposity, and IGF-1.The EarlyBird Diabetes study is a longitudinal prospective cohort study of healthy children aged 5-14 years. Homeostasis model assessment (HOMA-IR), skinfolds (SSF), adiposity (percent fat, measured by dual-energy X-ray absorptiometry), serum leptin, and IGF-1 were measured annually in 235 children (134 boys). Pubertal onset was adduced from Tanner stage (TS) and from the age at which luteinizing hormone (LH) first became serially detectable (≥0.2 international units/L).IR rose progressively from age 7 years, 3-4 years before TS2 was reached or LH became detectable. Rising adiposity and IGF-1 together explained 34% of the variance in IR in boys and 35% in girls (both P < 0.001) over the 3 years preceding pubertal onset. The contribution of IGF-1 to IR was greater in boys, despite their comparatively lower IGF-1 levels.IR starts to rise in mid-childhood, some years before puberty. Its emergence relates more to the age of the child than to pubertal onset. More than 60% of the variation in IR prior to puberty was unexplained. The demography of childhood diabetes is changing, and prepubertal IR may be important.
Paradoxical response to nebulised salbutamol in wheezy infants, assessed by partial expiratory flow-volume curves.
Authors: A Prendiville, S Green, M Silverman
Journal: Thorax (1987)

Lower airway responses to nebulised bronchodilators were studied in 18 chronically or recurrently wheezy infants, aged 3-15 months, by means of partial forced expiratory flow-volume manoeuvres performed with an inflatable jacket. Maximum flow at functional residual capacity (FRC) (VmaxFRC) was used as the index of intrathoracic airways function. Peak expiratory flow rate was also measured. Baseline airways resistance and lung volume were determined during quiet breathing in an infant whole body plethysmograph. Measurements were made on separate days before and after nebulised salbutamol 2.5 mg with nebulised saline as control. The results were paradoxical: there was no change in VmaxFRC after saline, but a significant decline in VmaxFRC was found after salbutamol. Peak expiratory flow remained unchanged. These observations suggest that under conditions of forced expiration intrathoracic airways function may be further impaired by nebulised bronchodilator treatment in wheezy infants. When nebulised bronchodilator drugs are used to treat severe airways obstruction in infancy, careful monitoring is essential.
Haptoglobin testing in hemolysis: Measurement and interpretation
Authors: Andrew W.Y. Shih, Andrew McFarlane, Madeleine Verhovsek
Journal: American Journal of Hematology (2014)

Haptoglobin is primarily produced in the liver and is functionally important for binding free hemoglobin from lysed red cells in vivo, preventing its toxic effects. Because haptoglobin levels become depleted in the presence of large amounts of free hemoglobin, decreased haptoglobin is a marker of hemolysis. Despite its ubiquity and importance, a paucity of literature makes testing difficult to interpret. This review highlights the many physiological roles that have been recently elucidated in the literature. Different methodologies have been developed for testing, including spectrophotometry, immunoreactive methods, and gel electrophoresis. These are covered along with their respective advantages and disadvantages. As there is no single gold standard for hemolysis, validation studies must rely on a combination of factors, which are reviewed in this article. Pitfalls and limitations of testing are also addressed. False positives can occur in improper specimen preparations, cirrhosis, elevated estrogen states, and hemodilution. False negatives can occur in hypersplenism and medications such as androgens and corticosteroids. Haptoglobin testing in the setting of inflammation is additionally discussed as interpretation can be difficult in this setting. Given the widespread use of haptoglobin testing, it is vital that clinicians and laboratory staff understand the principles and correct interpretation of this test. Am. J. Hematol. 89:443–447, 2014. © 2013 Wiley Periodicals, Inc.
Familial Adenomatous Polyposis: A Nutritional Intervention Trial
Authors: P. Greenwald, K. M. Witkin
Journal: JNCI Journal of the National Cancer Institute (1989)

Familial adenomatous polyposis, a premalignant autosomal dominant disorder, is characterized by a multitude of adenomatous polyps and progression to cancer in almost 100% of patients if not treated. In this issue, DeCosse et al. (7) present the results of a successful nutritional intervention trial in a group of patients with familial adenomatous polyposis. The patients, 58 adults, were entered in a randomized study in which they were treated with ascorbic acid (vitamin C) and a-tocopherol (vitamin E) coupled with a high-fiber (wheat bran) supplement or a low-fiber placebo in a double-blind protocol. A limited degree of polyp regression, which commenced about 6 months after study initiation, was observed in the high-fiber group. The mean daily intake of dietary fiber by the high-fiber group was 22.4 g/day, compared with 12.2 g/day in the low-fiber placebo group. High doses of ascorbic acid (4 g/day) or a-tocopherol (400 mg/day) in combination with the low-fiber placebo had no effect. The theoretical antecedents of this trial are founded on an analysis of epidemiologic surveys in which dietary fiber intake is identified as a significant life-style factor associated with reduced colon cancer risk (2). Worldwide trends in fiber consumption are inversely correlated with colon cancer
Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial
Authors: Jeffrey A Cohen, Alasdair J Coles, Douglas L Arnold, Christian Confavreux, Edward J Fox, Hans-Peter Hartung, Eva Havrdova, Krzysztof W Selmaj, Howard L Weiner, Elizabeth Fisher, Vesna V Brinar, Gavin Giovannoni, Miroslav Stojanovic, Bella I Ertik, Stephen L Lake, David H Margolin, Michael A Panzara, D Alastair S Compston
Journal: The Lancet (2012)
Human Pulmonary Pasteurellosis
Authors: B. Eugene Beyt
Journal: JAMA (1979)

<i>PASTEURELLA multocida</i>causes hemorrhagic septicemia in many domestic and wild animals. The most common human infection with<i>P multocida</i>is a local cellulitis following animal-inflicted wounds, preponderantly cat bites and scratches.<sup>1</sup>The typical clinical manifestations and complications have been well described previously.<sup>2</sup> We present three cases of pulmonary pasteurellosis that were recently evaluated by the infectious diseases service at Barnes Hospital. In three additional cases, the technologists in the microbiology laboratory isolated<i>P multocida</i>from respiratory tract secretions. <h3>Report of Cases</h3><h3>Case 1.—</h3> A 46-year-old farmer, who raised cattle and hogs, entered Barnes Hospital with a chief complaint of increasing cough with purulent sputum, for which he had received antibiotics at another hospital. During several months before admission, the patient had a cough that started recurring with dyspnea on climbing one flight of stairs, and he had been producing approximately 240 mL of sputum daily. Several months before the
Defining the chromatin signature of inducible genes in T cells
Authors: Pek S Lim, Kristine Hardy, Karen L Bunting, Lina Ma, Kaiman Peng, Xinxin Chen, Mary F Shannon
Journal: Genome biology (2009)

Specific chromatin characteristics, especially the modification status of the core histone proteins, are associated with active and inactive genes. There is growing evidence that genes that respond to environmental or developmental signals may possess distinct chromatin marks. Using a T cell model and both genome-wide and gene-focused approaches, we examined the chromatin characteristics of genes that respond to T cell activation.To facilitate comparison of genes with similar basal expression levels, we used expression-profiling data to bin genes according to their basal expression levels. We found that inducible genes in the lower basal expression bins, especially rapidly induced primary response genes, were more likely than their non-responsive counterparts to display the histone modifications of active genes, have RNA polymerase II (Pol II) at their promoters and show evidence of ongoing basal elongation. There was little or no evidence for the presence of active chromatin marks in the absence of promoter Pol II on these inducible genes. In addition, we identified a subgroup of genes with active promoter chromatin marks and promoter Pol II but no evidence of elongation. Following T cell activation, we find little evidence for a major shift in the active chromatin signature around inducible gene promoters but many genes recruit more Pol II and show increased evidence of elongation.These results suggest that the majority of inducible genes are primed for activation by having an active chromatin signature and promoter Pol II with or without ongoing elongation.
Circulating CD20 is detectable in the plasma of patients with chronic lymphocytic leukemia and is of prognostic significance
Authors: Taghi Manshouri, Kim-anh Do, Xuemei Wang, Francis J. Giles, Susan M. O'Brien, Helen Saffer, Deborah Thomas, Iman Jilani, Hagop M. Kantarjian, Michael J. Keating, Maher Albitar
Journal: Blood (2003)