tbuckley/cabot-search huggingface dataset:
Serotonin in Affective Control
Authors: Peter Dayan, Quentin J.M. Huys
Journal: Annual Review of Neuroscience (2009)

Serotonin is a neuromodulator that is extensively entangled in fundamental aspects of brain function and behavior. We present a computational view of its involvement in the control of appetitively and aversively motivated actions. We first describe a range of its effects in invertebrates, endowing specific structurally fixed networks with plasticity at multiple spatial and temporal scales. We then consider its rather widespread distribution in the mammalian brain. We argue that this is associated with a more unified representational and functional role in aversive processing that is amenable to computational analyses with the kinds of reinforcement learning techniques that have helped elucidate dopamine's role in appetitive behavior. Finally, we suggest that it is only a partial reflection of dopamine because of essential asymmetries between the natural statistics of rewards and punishments.
Characterization of c-kit positive intrathymic stem cells that are restricted to lymphoid differentiation.
Authors: Y Matsuzaki, J Gyotoku, M Ogawa, S Nishikawa, Y Katsura, G Gachelin, H Nakauchi
Journal: The Journal of Experimental Medicine (1993)

We found that c-kit-positive, lineage marker-negative, Thy-1lo cells are present in both bone marrow and thymus ("BM c-kit" and "thymus c-kit" cells). Although the two cell types are phenotypically similar, only BM c-kit cells showed the potential to form colonies in vitro as well as in vivo. However, both of them revealed extensive growth and differentiation potential to T cells after direct transfer into an irradiated adult thymus, or a deoxyguanosine-treated fetal thymus. Time course analysis showed that thymus c-kit cells differentiated into CD4CD8 double-positive cells approximately 4 d earlier than BM c-kit cells did. In addition, anti-c-kit antibody blocked T cell generation of BM c-kit cells but not of thymus c-kit cells. Intravenous injection of thymus c-kit resulted in the generation of not only T cells, but B as well as NK1.1+ cells. These data provide evidence that thymus c-kit cells represent common lymphoid progenitors with the differentiation potential to T, B, and possibly NK cells. The c-kit-mediated signaling appears to be essential in the transition from BM c-kit to thymus c-kit cells.
Opioid Prescribing for Cancer Pain During the Last 3 Months of Life: Associated Factors and 9-Year Trends in a Nationwide United Kingdom Cohort Study
Authors: Irene J. Higginson, Wei Gao
Journal: Journal of Clinical Oncology (2012)

Purpose To determine time trends and characteristics associated with opioid analgesic prescribing to patients with cancer who are approaching the end of life. Patients and Methods This population-based cohort study used data on 29,825 patients diagnosed with five common cancers—lung (34.2%), colorectal (19.9%), female breast (21.6%), prostate (19.1%), and head and neck (5.2%)—in the United Kingdom General Practice Research Database (GPRD) who died between 2000 and 2008. Opioid prescription rates in the last 3 months of life were described. Characteristics associated with opioid prescribing were investigated by using generalized estimation equation models. Results In the last 3 months of life, 43.6% (95% CI, 43.0% to 44.2%) of patients received at least one prescription of opioids: morphine (33.4%; 95% CI, 32.8% to 33.9%), diamorphine (11.6%; 95% CI, 11.2% to 11.9%), and fentanyl family (10.2%; 95% CI, 9.8% to 10.5%). Over time, prescription rates increased for opioids predominant during specific time periods, especially oxycodone. Older patients (age &gt; 60 years) had significantly lower chances of receiving opioids than their younger (age &lt; 50 years) peers (prevalence ratio [PR] range, 0.14 to 0.78), even adjusted for comorbidity. Women were slightly more likely than men to receive any type of opioid (PR,1.07; 95% CI, 1.04 to 1.11). Morphine and diamorphine (PR range, 1.14 to 1.56) were more commonly prescribed for lung and colorectal cancers and fentanyl family for head and neck cancers (PR, 1.39; 95% CI, 1.19 to 1.62) compared with for prostate cancers. Conclusion Morphine and diamorphine remain the stronghold for treating cancer pain in the United Kingdom. Opioid prescription rates are increasing over time. Prescription rates are lower for older people for all opioids, suggesting that this group needs attention.
The effect of hiatus hernia on gastro-oesophageal junction pressure
Authors: P J Kahrilas, S Lin, J Chen, M Manka
Journal: Gut (1999)

BACKGROUND Hiatus hernia and lower oesophageal sphincter hypotension are often viewed as opposing hypotheses for gastro-oesophageal junction incompetence. AIMS To examine the interaction between hiatus hernia and lower oesophageal sphincter hypotension. METHODS In seven normal subjects and seven patients with hiatus hernia, the squamocolumnar junction and intragastric margin of the gastro-oesophageal junction were marked with endoscopically placed clips. Axial and radial characteristics of the gastro-oesophageal junction high pressure zone were mapped relative to the hiatus and clips during concurrent fluoroscopy and manometry. Responses to inspiration and abdominal compression were also analysed. RESULTS In normal individuals the squamocolumnar junction was 0.5 cm below the hiatus and the gastro-oesophageal junction high pressure zone extended 1.1 cm distal to that. In those with hiatus hernia, the gastro-oesophageal junction high pressure zone had two discrete segments, one proximal to the squamocolumnar junction and one distal, attributable to the extrinsic compression within the hiatal canal. Inspiration and abdominal compression mainly augmented the distal one. Simulation of hernia reduction by algebraically summing the proximal segment pressures with the hiatal canal pressures restored normal maximal pressure, radial asymmetry, and dynamic responses of the gastro-oesophageal junction. CONCLUSIONS Hiatus hernia reduces lower oesophageal sphincter pressure and alters its dynamic responsiveness by spatially separating pressure components derived from the intrinsic lower oesophageal sphincter and the extrinsic compression of the oesophagus within the hiatal canal.
Quantitative Detection of Circulating Tumor Cells in Cutaneous and Ocular Melanoma and Quality Assessment by Real-Time Reverse Transcriptase-Polymerase Chain Reaction
Authors: Ulrich Keilholz, Petra Goldin-Lang, Nikolaos E. Bechrakis, Nicole Max, Anne Letsch, Alexander Schmittel, Carmen Scheibenbogen, Karin Heufelder, Alexander Eggermont, Eckhard Thiel
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Inconsistent reports on the detection of melanoma cells in peripheral blood by reverse transcriptase-PCR (RT-PCR) have resulted in uncertainty on the prognostic value of circulating melanoma cells. Experimental Design: We developed real-time RT-PCR assays for quantitation of tyrosinase, MelanA/MART1, and gp100 and for porphobilinogen deaminase housekeeping gene. Melanoma tissue (n = 18), peripheral blood samples from healthy donors (n = 21), and patients with cutaneous (n = 122) and uveal (n = 64) melanoma from our institution were analyzed. For quality control, an additional 251 samples from ongoing multicenter studies were compared with in-house samples. Results: Tyrosinase was not detected in healthy donor blood samples. For the two other markers, cutoff values had to be defined to distinct patient samples from controls. Patients with stage IV uveal and cutaneous melanoma expressed all three markers more frequently and at higher levels in peripheral blood as compared with earlier stages. The variation of expression was 4 logs and correlated with tumor load and serum lactate dehydrogenase. In 2 of 3 uveal melanoma patients, detection of circulating tumor cells preceded the development of liver metastases. The diagnostic sensitivity was optimal in blood samples containing &amp;gt;0.1pg/μl porphobilinogen deaminase (95.7% of in-house samples and 57.4% of multicenter samples). Conclusions: Real-time RT-PCR is able to quantitatively define the quality of a sample and provides quantitative data for melanoma markers. Disparities in the results of previous studies may be attributable to undetected differences in sample quality. The prognostic relevance of this assay is currently under evaluation in several prospective randomized trials.
Second Primary Breast Cancer Occurrence According to Hormone Receptor Status
Authors: A. W. Kurian, L. A. McClure, E. M. John, P. L. Horn-Ross, J. M. Ford, C. A. Clarke
Journal: JNCI Journal of the National Cancer Institute (2009)

Contralateral second primary breast cancers occur in 4% of female breast cancer survivors. Little is known about differences in risk for second primary breast cancers related to the estrogen and progesterone receptor (hormone receptor [HR]) status of the first tumor. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for contralateral primary breast cancers among 4927 women diagnosed with a first breast cancer between January 1, 1992, and December 31, 2004, using the National Cancer Institute's Surveillance, Epidemiology, and End Results database. For women whose first breast tumors were HR positive, risk of contralateral primary breast cancer was elevated, compared with the general population, adjusted for age, race, and calendar year (SIR = 2.22, 95% CI = 2.15 to 2.29, absolute risk [AR] = 13 cases per 10 000 person-years [PY]), and was not related to the HR status of the second tumor. For women whose first breast tumors were HR negative, the risk of a contralateral primary tumor was statistically significantly higher than that for women whose first tumors were HR positive (SIR = 3.57, 95% CI = 3.38 to 3.78, AR = 18 per 10 000 PY), and it was associated with a much greater likelihood of an HR-negative second tumor (SIR for HR-positive second tumors = 1.94, 95% CI = 1.77 to 2.13, AR = 20 per 10 000 PY; SIR for HR-negative second tumors = 9.81, 95% CI = 9.00 to 10.7, AR = 24 per 10 000 PY). Women who were initially diagnosed with HR-negative tumors when younger than 30 years had greatly elevated risk of HR-negative contralateral tumors, compared with the general population (SIR = 169, 95% CI = 106 to 256, AR = 77 per 10 000 PY). Incidence rates for any contralateral primary cancer following an HR-negative or HR-positive tumor were higher in non-Hispanic blacks, Hispanics, and Asians or Pacific Islanders than in non-Hispanic whites. Risk for contralateral second primary breast cancers varies substantially by HR status of the first tumor, age, and race and/or ethnicity. Women with HR-negative first tumors have nearly a 10-fold elevated risk of developing HR-negative second tumors, compared with the general population. These findings warrant intensive surveillance for second breast cancers in women with HR-negative tumors.
Nicotine Gum in General Practice
Authors: John R. Hughes
Journal: JAMA (1990)

To the Editor. —  A little over 1 year ago we published a study that, based on a 1-year follow-up, concluded that nicotine gum did no better than a placebo in helping smokers stop smoking when used with brief physician advice. 1 We noted only one positive study of nicotine vs placebo gum with brief advice. 2 This study, published in JAMA , used a 6-month follow-up to conclude that using nicotine gum improved smoking cessation. We speculated that this earlier study would fail to find an effect of nicotine gum at 1-year follow-up.  One-year follow-up of the earlier study has now been published and, despite a sample size of 1218, found no benefit of nicotine gum. 3 Post hoc analyses suggested that nicotine gum benefited men but not women. Among men, the 1-year abstinence rates were as follows: fixed dosing of nicotine gum, 29%; ad-lib nicotine gum, 22%; ad-lib placebo,
Content and Design Attributes of Antivaccination Web Sites
Authors: Robert M. Wolfe
Journal: JAMA (2002)

ONEof the greatest achievements of biomedical science and public health. 1However, during the last few decades an increasingly vocal antivaccination movement has challenged the safety and effectiveness of recommended vaccines. 2,3The extent of concern in the United States was highlighted by a national survey that found that although the majority of parents supported vaccination, 25% believed that too many vaccinations could weaken children's immune systems and 23% believed that children get too many immunizations. 4ecent studies indicate that 66% of US adults (137 million) are now online and that 80% of all adults online use the Internet to look for health information. 5,6Furthermore, 52% of those who have visited online health sites believe that "almost all" or "most" of the health information they find online is credible. 7Individuals searching for vaccination information may find themselves visiting antivaccination sites.This study explored the content and design attributes of antivaccination sites that an individual might encounter doing a typical Web search, with the goal of enhancing our understanding of concerns raised on these sites. METHODS Search StrategyUsing the Netlingo Dictionary of Internet Words (http://www.netlingo.com)and the Webopedia Online Computer Dictionary of Internet Terms (http:// www.pcwebopedia.com),we defined a "Web page" as a single html file or document viewed on a Web browser and a "Web site" as a site (location) on the World Wide Web.Each Web site contains a "home page," which is the first document users see when they enter the site.Each site is owned and managed by an individual, company, or organization.A "link" (or "hyperlink") is an element in an electronic document that links to another place in the same document or to an entirely different document.Typically, clicking on a hyperlink will transport a user to another document or section of the document.Antivaccination Web pages were identified using Copernic 2000 v4.55a (Copernic Technologies Inc, Sainte Foy, Que ´bec), an Internet search utility program designed to simultaneously submit searches on numerous search engines.We used 10 search engines: AltaVista, EuroSeek, Excite, Google, GoTo.com,HotBot, Infoseek, Lycos, Yahoo, and All the Web FAST Search, with up to 30 results returned on each engine for a maximum of 300 results per search.Two of the investigators (R.
Inhibition of Hypoxia Inducible Factor Hydroxylases Protects Against Renal Ischemia-Reperfusion Injury
Authors: Peter Hill, Deepa Shukla, Maxine G.B. Tran, Julian Aragones, H. Terence Cook, Peter Carmeliet, Patrick H. Maxwell
Journal: Journal of the American Society of Nephrology (2008)

Acute renal failure resulting from hypoperfusion and hypoxia is a significant clinical problem. Hypoxia activates the heterodimeric transcription factor hypoxia inducible factor (HIF), leading to changes in gene expression that promote tissue adaptation and survival. To determine whether HIF may protect the kidney from ischemia-reperfusion injury, we subjected hif1a+/− and hif2a+/− mice to renal ischemia-reperfusion injury. Injury was substantially more severe in hif+/− than in littermate controls, consistent with a protective role for HIF. Because wild-type mice exhibited submaximal HIF accumulation in response to no-flow ischemia, we tested compounds that might augment the protective HIF response following ischemia-reperfusion in these animals. We found that l-mimosine and dimethyloxalylglycine, two small molecules that activate HIF by inhibiting HIF hydroxylases, protected mouse kidneys from ischemia-reperfusion injury. Therefore, pharmacological activation of HIF may offer an effective strategy to protect the kidney from ischemic injury.
You can't have your cake and eat it too
Authors: S. D. J. Gibbs, S. M. Williams, X. Tyler, J. Pearson, M. J. Bennie, K. M. Bowles
Journal: Gut (2010)

A previously well 69-year-old British man presented with a 4-week history of anorexia, weight loss, drenching night sweats, marked lethargy and abdominal pain. Examination revealed pleural effusions and gross ascites. There was no jaundice, fever, cough, signs of chronic liver disease or palpable lymphadenopathy. Investigations revealed a haemoglobin 12.9 g/dl, white cell count 11.3×109/litre, neutrophils 10.4×109/litre, platelets 704×109/litre; creatinine of 107 μmol/l; normal liver enzymes; corrected calcium of 2.23 mmol/l; lactate dehydrogenase 4640 U/l (normal 125–243 U/l); urate 1201 μmol/l (normal <450 μmol/l) and negative HIV serology. CT chest and abdomen (figures 1 and 2) were performed. The patient's poor condition …
Role of central alpha-1 adrenoceptors in canine narcolepsy.
Authors: E Mignot, C Guilleminault, S Bowersox, A Rappaport, W C Dement
Journal: Journal of Clinical Investigation (1988)

The role of central alpha-1 adrenergic receptors in cataplexy was investigated in genetically narcoleptic Doberman pinschers. Treatment of narcoleptic dogs with 25-600 micrograms/kg prazosin, a selective alpha-1 adrenergic receptor blocker, exacerbated cataplexy, whereas treatment with the alpha-1 agonist, methoxamine, ameliorated it. Subsequent studies showed that the beneficial effects of classical treatments of human narcolepsy (amphetamines and tricyclic antidepressants) are antagonized by prazosin, suggesting that these drugs are active through an indirect alpha-1 stimulation (via an increase of norepinephrine in the synaptic cleft). Other studies confirmed that the observed effects were not due to peripheral alpha-1 cardiovascular involvement. Atropine, a central anticholinergic agent, but not methylatropine, a peripheral one, completely suppressed the prazosin effect, which suggests that adrenergic and cholinergic systems act sequentially and not independently to generate cataplexy. Little is known about the physiological role of central alpha-1 adrenoceptors. This series of experiments implicates these receptors in narcolepsy-cataplexy.
A Universal Evolutionary Index for Amino Acid Changes
Authors: Hua Tang, Gerald J Wyckoff, Jian Lu, Chung-I Wu
Journal: Molecular Biology and Evolution (2004)

Different nonsynonymous changes may be under different selective pressure during evolution. Of the 190 possible interchanges among the 20 amino acids, only 75 can be attained by a single-base substitution. An evolutionary index (EI) can be empirically computed for each of the 75 elementary changes as the likelihood of substitutions, relative to that of synonymous changes. We used 280, 1,306, 2,488, and 309 orthologous genes from primates (human versus Old World monkey), rodents (mouse versus rat), yeast (S. cerevisiae versus S. paradoxus), and Drosophila (D. melanogaster versus D. simulans), respectively, to estimate the EIs. In each data set, EI varies more than 10-fold, and the correlation coefficients of EIs from the pairwise comparisons are high (e.g., r = 0.91 between rodent and yeast). The high correlations suggest that the amino acid properties are strong determinants of protein evolution, irrespective of the identities of the proteins or the taxa of interest. However, these properties are not well captured in conventional measures of amino acid exchangeability. We, therefore, propose a universal index of exchange (U): for any large data set, its EI can be expressed as U*R, where R is the average Ka/Ks for that data set. The codon-based, empirically determined EI (i.e., U*R) makes much better predictions on protein evolution than do previous methods.
Microglia in the aging brain: relevance to neurodegeneration
Authors: Xiao-Guang Luo, Jian-Qing Ding, Sheng-Di Chen
Journal: Molecular Neurodegeneration (2010)

Microglia cells are the brain counterpart of macrophages and function as the first defense in the brain. Although they are neuroprotective in the young brain, microglia cells may be primed to react abnormally to stimuli in the aged brain and to become neurotoxic and destructive during neurodegeneration. Aging-induced immune senescence occurs in the brain as age-associated microglia senescence, which renders microglia to function abnormally and may eventually promote neurodegeneration. Microglia senescence is manifested by both morphological changes and alterations in immunophenotypic expression and inflammatory profile. These changes are likely caused by microinvironmental factors, but intrinsic factors cannot yet be completely excluded. Microglia senescence appears to underlie the switching of microglia from neuroprotective in the young brain to neurotoxic in the aged brain. The hypothesis of microglia senescence during aging offers a novel perspective on their roles in aging-related neurodegeneration. In Parkinson's disease and Alzheimer's disease, over-activation of microglia may play an active role in the pathogenesis because microglia senescence primes them to be neurotoxic during the development of the diseases.
Nanotechnology and Cancer
Authors: James R. Heath, Mark E. Davis
Journal: Annual Review of Medicine (2007)

The biological picture of cancer is rapidly advancing from models built from phenomenological descriptions to network models derived from systems biology, which can capture the evolving pathophysiology of the disease at the molecular level. The translation of this (still academic) picture into a clinically relevant framework can be enabling for the war on cancer, but it is a scientific and technological challenge. In this review, we discuss emerging in vitro diagnostic technologies and therapeutic approaches that are being developed to handle this challenge. Our discussion of in vitro diagnostics is guided by the theme of making large numbers of measurements accurately, sensitively, and at very low cost. We discuss diagnostic approaches based on microfluidics and nanotechnology. We then review the current state of the art of nanoparticle-based therapeutics that have reached the clinic. The goal of the presentation is to identify nanotherapeutic strategies that are designed to increase efficacy while simultaneously minimizing the toxic side effects commonly associated with cancer chemotherapies.
Causes of non-malarial fever in Laos: a prospective study
Authors: Mayfong Mayxay, Josée Castonguay-Vanier, Vilada Chansamouth, Audrey Dubot-Pérès, Daniel H Paris, Rattanaphone Phetsouvanh, Jarasporn Tangkhabuanbutra, Phouvieng Douangdala, Saythong Inthalath, Phoutthalavanh Souvannasing, Günther Slesak, Narongchai Tongyoo, Anisone Chanthongthip, Phonepasith Panyanouvong, Bountoy Sibounheuang, Koukeo Phommasone, Michael Dohnt, Darouny Phonekeo, Bouasy Hongvanthong, Sinakhone Xayadeth, Pakapak Ketmayoon, Stuart D Blacksell, Catrin E Moore, Scott B Craig, Mary-Anne Burns, Frank von Sonnenburg, Andrew Corwin, Xavier de Lamballerie, Iveth J González, Eva Maria Christophel, Amy Cawthorne, David Bell, Paul N Newton
Journal: The Lancet Global Health (2013)
Cognitive Interventions in Behavioral Medicine
Authors: Paul M.G. Emmelkamp, Patricia van Oppen
Journal: Psychotherapy and Psychosomatics (1993)

In this report an overview is given of the contribution of cognitive approaches to behavioral medicine. The (possible) contribution of cognitive therapy is reviewed in the area of coronary heart disease, obesity, bulimia nervosa, chronic pain, benign headache, cancer, acquired immunodeficiency syndrome/human immunodeficiency virus and asthma. Although the relative contribution of cognitive therapy varies across these various disorders, its positive effects are now well established and new advances undoubtedly will be made in the next few years.