tbuckley/cabot-search huggingface dataset:
Human Chemokines: An Update
Authors: Marco Baggiolini, Beatrice Dewald, Bernhard Moser
Journal: Annual Review of Immunology (1997)

Interleukin 8, the first chemokine to be characterized, was discovered nearly ten years ago. Today, more than 30 human chemokines are known. They are often upregulated in inflammation and act mainly on leukocytes inducing migration and release responses. The present review deals largely with the new developments of the last three years. Several structural studies have shown that most chemokines form dimers. The dimers, however, dissociate upon dilution, and the monomers constitute the biologically active form. Chemokine activities are mediated by seven-transmembrane-domain, G protein coupled receptors, five of which were discovered in the past three years. The primary receptor-binding domain of all chemokines is near the NH 2 terminus, and antagonists can be obtained by truncation or substitutions in this region. Major progress has been made in the understanding of chemokine actions on T lymphocytes that respond to several CC chemokines but also to IP10 and Mig, two CXC chemokines that selectively attract Tcells via a novel receptor. Effects of chemokines on angiogenesis and tumor growth have been reported, but the data are still contradictory and the mechanisms unknown. Of considerable interest is the recent discovery that some chemokines function as HIV-suppressive factors by interacting with chemokine receptors which, together with CD4, were recognized as the binding sites for HIV-1.
Is allergen exposure the major primary cause of asthma?
Authors: N. Pearce
Journal: Thorax (2000)

In recent decades a number of authors have argued that allergen exposure is the major primary cause of asthma, and that the global increases in asthma prevalence are due to increases in exposure to aeroallergens. We have assessed the epidemiological evidence in support of this hypothesis. No longitudinal studies were identified in which allergen exposure during infancy in a random population sample has been related to asthma risk after the age of six years. Two studies have been conducted in selected populations chosen on the basis of a family history of asthma or allergy; one study found a non-statistically significant association whereas the other study found no association. Many of the identified prevalence studies in children showed negative associations between allergen exposure and current asthma, and the weighted averages of the population attributable risks in children were 4% for <i>Der p</i> 1, 11% for <i>Fel d</i> 1, –4% for<i>Bla g</i> 2, and 6% for <i>Can f</i> 1. There was little change in these estimates in studies in which children whose parents had adopted allergen avoidance measures were excluded. Furthermore, evidence from population studies is equivocal and provides little consistent evidence that allergen exposure is associated with the prevalence of asthma at the population level. Population-based cohort studies are clearly required, but currently available evidence does not indicate that allergen exposure is a major risk factor for the primary causation of asthma in children.
Deficiency of carboxylesterase 1/esterase-x results in obesity, hepatic steatosis, and hyperlipidemia
Authors: Ariel D. Quiroga, Lena Li, Martin Trötzmüller, Randy Nelson, Spencer D. Proctor, Harald Köfeler, Richard Lehner
Journal: Hepatology (2012)

Increased lipogenesis, together with hyperlipidemia and increased fat deposition, contribute to obesity and associated metabolic disorders including nonalcoholic fatty liver disease. Here we show that carboxylesterase 1/esterase-x (Ces1/Es-x) plays a regulatory role in hepatic fat metabolism in the mouse. We demonstrate that Ces1/Es-x knockout mice present with increased hepatic lipogenesis and with oversecretion of apolipoprotein B (apoB)-containing lipoproteins (hepatic very-low density lipoproteins), which leads to hyperlipidemia and increased fat deposition in peripheral tissues. Consequently, Ces1/Es-x knockout mice develop obesity, fatty liver, hyperinsulinemia, and insulin insensitivity on chow diet without change in food intake and present with decreased energy expenditure. Ces1/Es-x deficiency prevents the release of polyunsaturated fatty acids from triacylglycerol stores, leading to an up-regulation of sterol regulatory element binding protein 1c-mediated lipogenesis, which can be reversed with dietary ω-3 fatty acids.These studies support a role for Ces1/Es-x in the partitioning of regulatory fatty acids and concomitant control of hepatic lipid biosynthesis, secretion, and deposition.
Pancreatic Adenocarcinoma, Version 2.2012
Authors: Margaret A. Tempero, J. Pablo Arnoletti, Stephen W. Behrman, Edgar Ben-Josef, Al B. Benson, Ephraim S. Casper, Steven J. Cohen, Brian Czito, Joshua D. I. Ellenhorn, William G. Hawkins, Joseph Herman, John P. Hoffman, Andrew Ko, Srinadh Komanduri, Albert Koong, Wen Wee Ma, Mokenge P. Malafa, Nipun B. Merchant, Sean J. Mulvihill, Peter Muscarella, Eric K. Nakakura, Jorge Obando, Martha B. Pitman, Aaron R. Sasson, Anitra Tally, Sarah P. Thayer, Samuel Whiting, Robert A. Wolff, Brian M. Wolpin, Deborah A. Freedman-Cass, Dorothy A. Shead
Journal: Journal of the National Comprehensive Cancer Network (2012)

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.g., 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) was added as an acceptable chemotherapy combination for patients with advanced or metastatic disease and good performance status as a category 2B recommendation; and 3) the panel developed new recommendations concerning surgical technique and pathologic analysis and reporting.
Variations in Prostate Cancer Patterns of Care: Is It the Quality of Care or the Quality of the Data?
Authors: David F. Penson
Journal: Journal of Clinical Oncology (2005)

cancer registries participating in the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) program to review patterns of care in men diagnosed with localized or regionally advanced prostate cancer from 1995 to 1999. They noted significant geographic variation in the use of surgery, radiation therapy, and conservative (watchful waiting) therapy. For example, surgery or watchfulwaiting rates were significantly higher in the Los Angeles area than in other regions of the United States. Conversely, radiation therapy was employed more commonly in the Detroit area. Interestingly, within registries, there was little variation in treatment rates, indicating local homogeneity in patterns of care. The authors also found that age, race, income, and pathologic differentiation were independently associated with primary surgical or radiation therapy. The authors conclude that their results may suggest “unconscious discrimination on the part of physicians.” Beforeweacceptthisconclusion,wemustconsiderthe limitations of the current study. As the authors rightfully point out in their discussion, the SEER data set does not allow for individual level assessment of socioeconomic status (SES). To account for this, the research team ascribed group characteristics to individuals based on 2000 United States census data for individual’s county of residence and ethnicity. Another limitation stems from the fact that the SEER data set has no information concerning comorbid conditions. Primary choice of therapy in localized prostate cancer has been previously shown to be associated with the numberofcomorbidconditionsatthetimeofdiagnoses. 5,6 Therefore, if one wants to determine the true effect of ethnicity or SES on primary treatment, comorbid disease must be controlled for, as these factors may all be related. 7 Although the lack of this information likely affects the results of the current study, it is my belief that, even if the researchers had been able to completely control for comorbidity and had individual level SES data, ethnicity and SES would still have been associated with choice of primary treatment. Assuming that the true strength of the associations may not be as strong as observed in the study but wouldstillbesignificant,wemustaskwhythesegeographic,
Oxidized Low-Density Lipoprotein in Children With Familial Hypercholesterolemia and Unaffected Siblings
Authors: Jessica Rodenburg, Maud N. Vissers, Albert Wiegman, Elizabeth R. Miller, Paul M. Ridker, Joseph L. Witztum, John J.P. Kastelein, Sotirios Tsimikas
Journal: Journal of the American College of Cardiology (2006)
Sequential Intensification of Metformin Treatment in Type 2 Diabetes With Liraglutide Followed by Randomized Addition of Basal Insulin Prompted by A1C Targets
Authors: J. Hans DeVries, Stephen C. Bain, Helena W. Rodbard, Jochen Seufert, David D’Alessio, Anne B. Thomsen, Marcin Zychma, Julio Rosenstock
Journal: Diabetes Care (2012)

We evaluated the addition of liraglutide to metformin in type 2 diabetes followed by intensification with basal insulin (detemir) if glycated hemoglobin (A1C) ≥7%.In 988 participants from North America and Europe uncontrolled on metformin ± sulfonylurea, sulfonylurea was discontinued and liraglutide 1.8 mg/day added for 12 weeks (run-in). Subsequently, those with A1C ≥7% were randomized 1:1 to 26 weeks' open-label addition of insulin detemir to metformin + liraglutide (n = 162) or continuation without insulin detemir (n = 161). Patients achieving A1C <7% continued unchanged treatment (observational arm). The primary end point was A1C change between randomized groups.Of 821 participants completing the run-in, 61% (n = 498) achieved A1C <7% (mean change -1.3% from 7.7% at start), whereas 39% (n = 323) did not (-0.6% from 8.3% at start). During run-in, 167 of 988 (17%) withdrew; 46% of these due to gastrointestinal adverse events. At week 26, A1C decreased further, by 0.5% (from 7.6% at randomization) with insulin detemir (n = 162) versus 0.02% increase without insulin detemir (n = 157) to 7.1 and 7.5%, respectively (estimated treatment difference -0.52 [95% CI -0.68 to -0.36]; P < 0.0001). Forty-three percent of participants with insulin detemir versus 17% without reached A1C <7%. Mean weight decreased by 3.5 kg during run-in, then by 0.16 kg with insulin detemir or 0.95 kg without insulin detemir. In the randomized phase, no major hypoglycemia occurred and minor hypoglycemia rates were 0.286 and 0.029 events per participant-year with and without insulin detemir (9.2 vs. 1.3%).Supplementation of metformin with liraglutide and then insulin detemir was well tolerated in the majority of patients, with good glycemic control, sustained weight loss, and very low hypoglycemia rates.
Functional analysis of two human T-cell subpopulations: help and suppression of B-cell responses by T cells bearing receptors for IgM or IgG.
Authors: L Moretta, S R Webb, C E Grossi, P M Lydyard, M D Cooper
Journal: The Journal of Experimental Medicine (1977)

Subpopulations of thymus-derived T lymphocytes bearing receptors for either IgM or IgG molecules were isolated from human peripheral blood. Those with receptors for IgM (T.M) provided help in a cell dose-dependent fashion for the pokeweed mitogen-induced differentiation of B lymphocytes in vitro, whereas cells with receptors for IgG (T.G) did not. T.G cells, on the hand, efficiently suppressed the differentiation and proliferation of B cells in the pokeweed system in the presence of helper T.M cells. This suppressive activity of T.G cells required prior interaction of the T.G cells with immune complexes. The helper activity of T.M cells was relatively radioresistant while the suppressor activity of T.G cells was radiosensitive. The results indicate that helper and suppressor functions of human T lymphocytes in this model system are mediated by different subpopulations of T cells which can be distinguished by their ability to bind IgM or IgG immune complexes, respectively.
Disease Education by the B.B.C
Authors: A. H. Gregson
Journal: BMJ (1958)

To date, the SARS-CoV-2 genome has been considered genetically more stable than SARS-CoV or MERS-CoV. Here we report a 382-nt deletion covering almost the entire open reading frame 8 (ORF8) of SARS-CoV-2 obtained from eight hospitalized patients in Singapore. The deletion also removes the ORF8 transcription-regulatory sequence (TRS), which in turn enhances the downstream transcription of the N gene. We also found that viruses with the deletion have been circulating for at least four weeks. During the SARS-CoV outbreak in 2003, a number of genetic variants were observed in the human population [1], and similar variation has since been observed across SARS-related CoVs in humans and bats. Overwhelmingly these viruses had mutations or deletions in ORF8, that have been associated with reduced replicative fitness of the virus [2]. This is also consistent with the observation that towards the end of the outbreak sequences obtained from human SARS cases possessed an ORF8 deletion that may be associated with host adaptation [1]. We therefore hypothesise that the major deletion revealed in this study may lead to an attenuated phenotype of SARS-CoV-2.
Frequent Monitoring of A1C During Pregnancy as a Treatment Tool to Guide Therapy
Authors: Lois Jovanovič, Hatice Savas, Manish Mehta, Angelina Trujillo, David J. Pettitt
Journal: Diabetes Care (2010)

OBJECTIVE No guidelines for A1C measurement exist for women with gestational diabetes mellitus (GDM). The aim of this study was to document the rate of A1C decline in women with GDM. RESEARCH DESIGN AND METHODS Women with GDM in the Santa Barbara County Endocrine Clinic are managed with a carbohydrate-restricted diet and self-monitored blood glucose before and 1-h postprandial. Insulin is started if the preprandial glucose concentration is ≥90 mg/dl and/or a 1-h postprandial glucose concentration is ≥120 mg/dl. Capillary A1C was tested weekly using the DCA2000+ analyzer. RESULTS Twenty-four women with GDM (aged 29.0 ± 7.3 years) with initial A1C ≥7.0% were recruited. Baseline A1C was 8.8 ± 1.8%. Mean A1C decline was 0.47% per week (range 0.10–1.15%); the maximum was 4.3% in 4 weeks. CONCLUSIONS This study documents rapid decline in A1C during pregnancy and the utility of weekly A1C to guide therapy.
The United States needs a health system like other countries
Authors: R. A. Forsyth
Journal: JAMA (1994)

To the Editor.  —The article by Dr Glaser, 1 which recommends a genuine national health insurance system, dismisses criticisms that such a system leads to backward technologies, waiting lists, [and] underpaid... physicians, but does not provide any justification for that dismissal. On the other hand, one can readily justify the criticisms. For example, a recent article 2 stated that France provides dialysis to 88% fewer of its citizens than does the United States, and physician income is only 30% of the US level. Short visits and long waiting lists are a feature of every national health insurance system. These facts should make one pause before recommending a change. What is the virtue of correcting the United States' sin of high expenditures by substituting the sin of inadequate expenditures under a government-mandated global budget?  Similarly, the article summarily dismisses the proposed middle ground of managed competition. The author states that hospital
Acquired resistance to imatinib in gastrointestinal stromal tumours caused by multiple KIT mutations
Authors: Eva Wardelmann, Nadja Thomas, Sabine Merkelbach-Bruse, Katharina Pauls, Nicola Speidel, Reinhard Büttner, Heiner Bihl, Claudia C Leutner, Thomas Heinicke, Peter Hohenberger
Journal: The Lancet Oncology (2005)
Variation in lung cancer resources and workload: results from the first national lung cancer organisational audit: Table 1
Authors: K Cusworth, E O'Dowd, R Hubbard, P Beckett, M D Peake, I Woolhouse
Journal: Thorax (2015)

We report the findings of the first national lung cancer organisational audit. The results demonstrate marked variation in service provision and workload of some lung cancer specialists. For example, over half of the clinical nurse specialists report case volumes over recommended numbers. Some trusts have no access to key treatments such as video assisted thoracoscopy (VAT) lobectomy and stereotactic radiotherapy. Multivariate regression analysis demonstrated an association between higher surgical resection rates and the on-site availability of advanced staging and therapeutic modalities, for example, PET scan and VAT lobectomy. We conclude by making a number of recommendations to address the variation in lung cancer care.
Reliability of MRI assessment of supraspinatus tendinopathy
Authors: Mya Lay Sein, Judie Walton, James Linklater, Craig Harris, Tej Dugal, Richard Appleyard, Brent Kirkbride, Donald Kuah, George A C Murrell
Journal: British Journal of Sports Medicine (2007)

To determine the interobserver and intraobserver reliability of the interpretation of MRIs for supraspinatus tendinosis.In the interobserver trial, the MRIs of 52 athletes' shoulders were observed by 3 observers on one occasion within a 2-month period. All 52 images were read by the most experienced musculoskeletal radiologist on 3 different occasions on separate days without access to the previous readings for the intraobserver trial. Supraspinatus tendinosis was graded using a modified 4-point scale from grades 0 to grade 3.The grading of MRI-determined supraspinatus tendinosis was reliable, having an intraclass correlation (ICC) of 0.85 when assessed by the single well-trained observer. Interobserver reliability was only fair to good (ICC = 0.55).Supraspinatus tendinosis can be accurately identified on MRI with little variation by a single well-trained observer. Interobserver reliability was only fair to good. Our data indicated that the reliability of the assessment was much greater in more experienced radiologists than in those with less experience.
Use of Copper Intrauterine Devices and the Risk of Tubal Infertility among Nulligravid Women
Authors: David Hubacher, Roger Lara-Ricalde, Douglas J. Taylor, Fernando Guerra-Infante, Raymundo Guzmán-Rodríguez
Journal: New England Journal of Medicine (2001)

Previous studies of intrauterine devices (IUDs), many of which are no longer in use, suggested that they might cause tubal infertility. The concern that IUDs that contain copper — currently the most commonly used type — may increase the risk of infertility in nulligravid women has limited the use of this highly effective method of birth control.
TCT-749 Comparison of Area and Perimeter Derived Effective Annulus Diameter with Direct Intraoperative Sizing
Authors: Won-Keun Kim, Helge Moellmann, Andreas Rolf, Christoph Liebetrau, Johannes Blumenstein, Arnaud Van Linden, Christian W. Hamm, Thomas Walther, Joerg Kempfert
Journal: Journal of the American College of Cardiology (2013)
Perforin-Mediated Cytotoxicity Is Critical for Surveillance of Spontaneous Lymphoma
Authors: Mark J. Smyth, Kevin Y.T. Thia, Shayna E.A. Street, Duncan MacGregor, Dale I. Godfrey, Joseph A. Trapani
Journal: The Journal of Experimental Medicine (2000)

Immune surveillance by cytotoxic lymphocytes against cancer has been postulated for decades, but direct evidence for the role of cytotoxic lymphocytes in protecting against spontaneous malignancy has been lacking. As the rejection of many experimental cancers by cytotoxic T lymphocytes and natural killer cells is dependent on the pore-forming protein perforin (pfp), we examined pfp-deficient mice for increased cancer susceptibility. Here we show that pfp-deficient mice have a high incidence of malignancy in distinct lymphoid cell lineages (T, B, NKT), indicating a specific requirement for pfp in protection against lymphomagenesis. The susceptibility to lymphoma was accentuated by simultaneous lack of expression of the p53 gene, mutations in which also commonly predispose to human malignancies, including lymphoma. In contrast, the incidence and age of onset of sarcoma was unaffected in p53-deficient mice. Pfp-deficient mice were at least 1,000-fold more susceptible to these lymphomas when transplanted, compared with immunocompetent mice in which tumor rejection was controlled by CD8+ T lymphocytes. This study is the first that implicates direct cytotoxicity by lymphocytes in regulating lymphomagenesis.
Dietary Advice for Melanoma: Not Ready for Prime Time
Authors: Marianne Berwick
Journal: Journal of Clinical Oncology (2015)

There have been few studies on dietary factors in the development of melanoma for a number of reasons. By their nature, dietary studies can be subject to a great deal of misclassification, tending to make results null, given that the misclassification is usually nondirectional. Second, most dietary studies are looking for protective factors rather than risk factors. However, the article accompanying this editorial by Wu et al, 1 entitled, “Citrus Consumption and Risk of Cutaneous Malignant Melanoma,” has overcome many of the previous deficiencies in studying the role of diet in melanoma etiology and yet hasfoundthatcitrusconsumption,butnotsupplementalvitaminC,is a risk factor for the development of melanoma. The study found a dose-response relationship for overall citrus consumption more than twice a week, compared with less than twice a week. Consumption of citrus fruits and juices more than 1.6 times per day resulted in a risk for developing melanoma of 1.36 (95% CI, 1.14 to 1.63). The rationale for the association between consumption ofcitrusandthedevelopmentofmelanomaisbasedonthepresenceof psoralens and furocoumarins in citrus fruits, particularly grapefruit. Thesesubstancesarepotentialcarcinogens,asfoundinbothmiceand humans. 2-4 Psoralens and furocoumarins interact with ultraviolet (UV)lighttostimulatemelanomacellstoproliferate. 5 Althoughthere werenosignificantinteractionsbetweenUVexposureandcitrusconsumption found in this study, the association appeared to be stronger among those with a higher susceptibility to sunburn as a child or adolescent,thosewithmoreblisteringsunburns,andthosewhospent more time in the direct sunlight with higher annual residential UV flux. In addition, the association was stronger among obese individuals and those who exercised little. Thestudyhasmuchstrength.Therationaleisclear,thestudywas large, and data were collected prospectively. This study demonstrates