tbuckley/cabot-search huggingface dataset:
Components of the Metabolic Syndrome and Risk of Cardiovascular Disease and Diabetes in Beaver Dam
Authors: Barbara E.K. Klein, Ronald Klein, Kristine E. Lee
Journal: Diabetes Care (2002)

OBJECTIVE—To determine whether components of the metabolic syndrome precede the 5-year incidence of cardiovascular disease and diabetes. RESEARCH DESIGN AND METHODS—A population of individuals aged 43–84 years was evaluated from 1988 to 1990 and again 5 years later. Medical history, blood pressure, and laboratory measures were obtained at both examinations following the same protocols. Subjects without diabetes were classified according to level of glycemia, high blood pressure, high-risk lipid levels, high uric acid levels, and proteinuria at baseline. History of incident myocardial infarction, angina, stroke, and diabetes was obtained at follow-up. RESULTS—Of the 4,423 subjects without diabetes, 6.9% had elevated levels of glycemia, 18.4% had high blood pressure, 82.7% had high-risk lipid levels (either high serum total cholesterol or low HDL cholesterol or high ratio of these two levels), 27% had elevated uric acid levels, 33.2% had high BMI, and 3.3% had proteinuria (≥30 mg/dl). The risk of incident cardiovascular disease 5 years later increased with the number of the components present; 2.5% of those with one component developed cardiovascular disease, whereas 14.9% of those with four or more components developed cardiovascular disease. Of those with one component, diabetes developed in 1.1% 5 years later, whereas diabetes developed in 17.9% of those with four or more components. CONCLUSIONS—Components of the metabolic syndrome are common and are associated with incident cardiovascular disease and diabetes after 5 years. Interventions to alter BMI, lipid levels, and blood pressure may decrease incident diabetes and cardiovascular disease.
Journal to shift practice on obtaining conflict of interest declarations
Authors: W. K. A. Yung
Journal: Neuro-Oncology (2010)

As Neuro-Oncology has grown from a quarterly to a monthly journal over the last 4 years, it has borne both the blessings and the burdens of that growth. For instance, the editorial office now handles almost 550 manuscripts a year (new submissions and revisions).

At the start of the process, this means ensuring that the articles adhere to our guidelines for submission. One key task for our peer review coordinator is ensuring that authors have given us all the information we need to remain in compliance with the International Committee of Medical Journal Editors (the ICMJE, which has formulated the Uniform Requirements for Manuscripts Submitted to Biomedical Journals), and the Committee on Publication Ethics (COPE), of which Neuro-Oncology is a member, as stated in our own Instructions to Authors.

Recently, the journal has seen several instances in which manuscripts entered the review process with no conflict of interest declared, only to have such declarations made after multiple revisions and (in some cases) acceptance for publication. In the past, when there were fewer submissions and fewer published articles, the journal used a separate form to obtain information about conflict of interest from authors. However, as traffic flow has increased, it has become impractical to continue to use a separate document for such declarations—in part because it places an unnecessary burden on the editorial office, but also because we believe that reviewers benefit from having such information when they decide whether they can fairly review a paper (more on that below).
Vitamin D as an Early Predictor of Multiple Sclerosis Activity and Progression
Authors: Alberto Ascherio, Kassandra L. Munger, Rick White, Karl Köchert, Kelly Claire Simon, Chris H. Polman, Mark S. Freedman, Hans-Peter Hartung, David H. Miller, Xavier Montalbán, Gilles Edan, Frederik Barkhof, Dirk Pleimes, Ernst-Wilhelm Radü, Rupert Sandbrink, Ludwig Kappos, Christoph Pohl
Journal: JAMA Neurology (2014)

IMPORTANCE It remains unclear whether vitamin D insufficiency, which is common in individuals with multiple sclerosis (MS), has an adverse effect on MS outcomes.OBJECTIVES To determine whether serum concentrations of 25-hydroxyvitamin D (25[OH]D), a marker of vitamin D status, predict disease activity and prognosis in patients with a first event suggestive of MS (clinically isolated syndrome). DESIGN, SETTING, AND PARTICIPANTSThe Betaferon/Betaseron in Newly Emerging multiple sclerosis For Initial Treatment study was a randomized trial originally designed to evaluate the impact of early vs delayed interferon beta-1b treatment in patients with clinically isolated syndrome.Serum 25(OH)D concentrations were measured at baseline and 6, 12, and 24 months.A total of 465 of the 468 patients randomized had at least 1 25(OH)D measurement, and 334 patients had them at both the 6-and 12-month (seasonally asynchronous) measurements.Patients were followed up for 5 years clinically and by magnetic resonance imaging.MAIN OUTCOMES AND MEASURES New active lesions, increased T2 lesion volume, and brain volume on magnetic resonance imaging, as well as MS relapses and disability (Expanded Disability Status Scale score). RESULTSHigher 25(OH)D levels predicted reduced MS activity and a slower rate of progression.A 50-nmol/L (20-ng/mL) increment in average serum 25(OH)D levels within the first 12 months predicted a 57% lower rate of new active lesions (P < .001),57% lower relapse rate (P = .03),25% lower yearly increase in T2 lesion volume (P < .001),and 0.41% lower yearly loss in brain volume (P = .07)from months 12 to 60.Similar associations were found between 25(OH)D measured up to 12 months and MS activity or progression from months 24 to 60.In analyses using dichotomous 25(OH)D levels, values greater than or equal to 50 nmol/L (20 ng/mL) at up to 12 months predicted lower disability (Expanded Disability Status Scale score, -0.17; P = .004)during the subsequent 4 years.CONCLUSIONS AND RELEVANCE Among patients with MS mainly treated with interferon beta-1b, low 25(OH)D levels early in the disease course are a strong risk factor for long-term MS activity and progression.
Invasive pneumococcal disease in a cohort of predominantly HIV-1 infected female sex-workers in Nairobi, Kenya
Authors: C.F Gilks, S.A Ojoo, J.C Ojoo, R.J Brindle, J Paul, B.I.F Batchelor, J.N Kimari, R Newnham, J Bwayo, F.A Plummer, F.A Plummer, C.F Gilks, D.A Warrell
Journal: The Lancet (1996)
To Target or Not to Target, That Is the Question
Authors: Marina Chiara Garassino, Marco Platania, Massimo Broggini, Valter Torri, Filippo De Braud
Journal: Journal of Clinical Oncology (2013)

esting results achieved with dacomitinib (PF-00299804), a pan– human epidermal growth factor receptor (HER) inhibitor. The authors demonstrated that dacomitinib was able to selectively, irreversibly (covalently) bind to the adenosine triphosphate domain of each of the three kinase-active members of the HER family: epidermal growth factor receptor (EGFR)/HER1, HER2, and HER4. In addition, dacomitinib demonstrated significantly improved progression-free survival compared with erlotinib in the treatment of non–small-cell lung cancer, with acceptable toxicity. The authors concluded that the progression-free survival benefit was observed in most clinical and molecular subsets, notably KRAS wild-type/EGFR any status, KRAS wild-type/EGFR wild-type, and EGFR mutants. In this phase II trial, which was not powered for subgroup analysis, it is important to note that the significant imbalance (20.2% v 11.7%) in EGFR mutations in favor of dacomitinib may be principally responsible for the overall positive results. In fact, patients with EGFR mutations shift the risk of progression from a reduction of 34% to 30%, rendering the overall results not statistically significant. Similar results, also not statistically significant, are found if we consider only the subgroup of patients with wildtype EGFR mutations. However, an interesting benefit in wild-type EGFR mutations can be hypothesized, possibly driven by other biomarkers, such as the overexpression of HER2 or the activation of the phosphatidylinositol 3-kinase pathway. 2,3 We agree that dacomitinib is an interesting drug, but its development should not be in an unselected patient population. Today, a target agent must be used for a particular target to avoid another “me too” drug for unselected patients.
Musculoskeletal ultrasound education for sports medicine fellows: a suggested/potential curriculum by the American Medical Society for Sports Medicine
Authors: Jonathan Finnoff, Mark E Lavallee, Jay Smith
Journal: British Journal of Sports Medicine (2010)

The following musculoskeletal ultrasound (MSK US) curriculum was developed by the American Medical Society for Sports Medicine (AMSSM) to provide a pathway by which a sports medicine fellow can obtain adequate MSK US training during their fellowship to meet the requirements of competency outlined by the American Institute of Ultrasound in Medicine (AIUM) Training Guidelines for the Performance of MSK US Examination. Many fellowship programmes may not be able to follow all of the recommendations outlined by this document owing to their available resources. However, this curriculum can be used as a suggested/potential guideline for MSK US training within a sports medicine fellowship, and may assist programmes in developing or modifying their own internal training methods.
Cigarette smoke extract induces thymic stromal lymphopoietin expression, leading to TH2-type immune responses and airway inflammation
Authors: Yuki Nakamura, Masanori Miyata, Tetsuro Ohba, Takashi Ando, Kyosuke Hatsushika, Fumiko Suenaga, Naomi Shimokawa, Yuko Ohnuma, Ryohei Katoh, Hideoki Ogawa, Atsuhito Nakao
Journal: Journal of Allergy and Clinical Immunology (2008)
Two Cases of Acute Bioprosthetic Mitral Valve Thrombosis Immediately After Mitral Valve Replacement
Authors: Nobuyuki Kagiyama, Hiroyuki Okura, Shintaro Nezuo, Takahiro Kawamoto, Takashi Murakami, Yuji Hashimoto, Kazuo Tanemoto, Kiyoshi Yoshida
Journal: Circulation (2014)
IRF4 Deficiency Abrogates Lupus Nephritis Despite Enhancing Systemic Cytokine Production
Authors: Maciej Lech, Marc Weidenbusch, Onkar P. Kulkarni, Mi Ryu, Murthy Narayana Darisipudi, Heni Eka Susanti, Hans-Willi Mittruecker, Tak W. Mak, Hans-Joachim Anders
Journal: Journal of the American Society of Nephrology (2011)

The IFN-regulatory factors IRF1, IRF3, IRF5, and IRF7 modulate processes involved in the pathogenesis of systemic lupus and lupus nephritis, but the contribution of IRF4, which has multiple roles in innate and adaptive immunity, is unknown. To determine a putative pathogenic role of IRF4 in lupus, we crossed <i>Irf4</i>-deficient mice with autoimmune C57BL/6-(Fas)lpr mice. IRF4 deficiency associated with increased activation of antigen-presenting cells in C57BL/6-(Fas)lpr mice, resulting in a massive increase in plasma levels of TNF and IL-12p40, suggesting that IRF4 suppresses cytokine release in these mice. Nevertheless, IRF4 deficiency completely protected these mice from glomerulonephritis and lung disease. The mice were hypogammaglobulinemic and lacked antinuclear and anti-dsDNA autoantibodies, revealing the requirement of IRF4 for the maturation of plasma cells. As a consequence, <i>Irf4</i>-deficient C57BL/6-(Fas)lpr mice neither developed immune complex disease nor glomerular activation of complement. In addition, lack of IRF4 impaired the maturation of Th17 effector T cells and reduced plasma levels of IL-17 and IL-21, which are cytokines known to contribute to autoimmune tissue injury. In summary, IRF4 deficiency enhances systemic inflammation and the activation of antigen-presenting cells but also prevents the maturation of plasma cells and effector T cells. Because these adaptive immune effectors are essential for the evolution of lupus nephritis, we conclude that IRF4 promotes the development of lupus nephritis despite suppressing antigen-presenting cells.
Copious amounts of ascites
Authors: N Ueno
Journal: Gut (2006)

<h3>Abstract</h3> While most individuals with access to alcohol drink it recreationally, about 5 % lose control over their intake and progressively develop an alcohol use disorder (AUD), characterised by compulsive alcohol drinking accompanied by decreased interest in alternative sources of reinforcement. The neural and molecular mechanisms underlying the vulnerability to switch from controlled to compulsive alcohol intake have not been fully characterized, so limiting the development of new treatments for AUD. It has recently been shown that rats having reduced levels of expression of the gamma-aminobutyric acid (GABA) transporter, GAT-3, in the amygdala tend to persist in seeking and drinking alcohol even when adulterated with quinine, suggesting that pharmacological interventions aimed at restoring GABA homeostasis in these individuals may provide a targeted treatment to limit compulsive alcohol drinking. Here, we tested the hypothesis that the GABA<sub>B</sub> receptor agonist baclofen, which decreases GABA release, specifically decreases compulsive alcohol drinking in vulnerable individuals. In a large cohort of Sprague-Dawley rats allowed to drink alcohol under an intermittent two-bottle choice procedure, a cluster of individuals was identified that persisted in drinking alcohol despite adulteration or the availability of an alternative ingestive reinforcer, saccharin. In these rats, that were characterised by decreased GAT-3 mRNA levels in the central amygdala, acute baclofen administration (1.5 mg/kg, intraperitoneal) resulted in a decrease in compulsive drinking. These results indicate that low GAT-3 mRNA levels in the central amygdala represent an endophenotype of AUD and that the associated compulsive alcohol drinking characteristic is sensitive to baclofen.
Exposure-Response Estimates for Diesel Engine Exhaust and Lung Cancer Mortality Based on Data from Three Occupational Cohorts
Authors: Roel Vermeulen, Debra T. Silverman, Eric Garshick, Jelle Vlaanderen, Lützen Portengen, Kyle Steenland
Journal: Environmental Health Perspectives (2013)

Diesel engine exhaust (DEE) has recently been classified as a known human carcinogen.We derived a meta-exposure-response curve (ERC) for DEE and lung cancer mortality and estimated lifetime excess risks (ELRs) of lung cancer mortality based on assumed occupational and environmental exposure scenarios.We conducted a meta-regression of lung cancer mortality and cumulative exposure to elemental carbon (EC), a proxy measure of DEE, based on relative risk (RR) estimates reported by three large occupational cohort studies (including two studies of workers in the trucking industry and one study of miners). Based on the derived risk function, we calculated ELRs for several lifetime occupational and environmental exposure scenarios and also calculated the fractions of annual lung cancer deaths attributable to DEE.We estimated a lnRR of 0.00098 (95% CI: 0.00055, 0.0014) for lung cancer mortality with each 1-μg/m3-year increase in cumulative EC based on a linear meta-regression model. Corresponding lnRRs for the individual studies ranged from 0.00061 to 0.0012. Estimated numbers of excess lung cancer deaths through 80 years of age for lifetime occupational exposures of 1, 10, and 25 μg/m3 EC were 17, 200, and 689 per 10,000, respectively. For lifetime environmental exposure to 0.8 μg/m3 EC, we estimated 21 excess lung cancer deaths per 10,000. Based on broad assumptions regarding past occupational and environmental exposures, we estimated that approximately 6% of annual lung cancer deaths may be due to DEE exposure.Combined data from three U.S. occupational cohort studies suggest that DEE at levels common in the workplace and in outdoor air appear to pose substantial excess lifetime risks of lung cancer, above the usually acceptable limits in the United States and Europe, which are generally set at 1/1,000 and 1/100,000 based on lifetime exposure for the occupational and general population, respectively.
Myeloid Growth Factors Should Not Be Administered Routinely After Allogeneic Hematopoietic Stem-Cell Transplantation
Authors: Jayesh Mehta
Journal: Journal of Clinical Oncology (2004)

hemoglobin content less than 32 pg.In many patients (46%) low transferrin saturation coexisted with an elevated ferritin.Thus, reliance of measurement of ferritin alone to assess iron status may be misleading.Although, as of the time this letter is published the data are not available, we have completed accrual on a study that was powered to detect differences within the treatment groups based on entrance iron criteria.Patients received either darbepoietin alone or darbepoietin plus IV ferric gluconate.This study should answer the question: "Does IV iron benefit all patients receiving erythropoietic therapy irrespective of their baseline iron parameters?"Lastly, we all agree that in those patients who are truly iron deficient, vigorous iron repletion should be accomplished before or at the initiation of either darbepoietin or rHuEPO.Based on our published data, 1 the iron repletion should be by the IV route.
Infectious Mononucleosis and the Empirical Risk off Cancer2
Authors: Robert W. Miller, Gilbert W. Beebe
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Infectious Mononucleosis and the Empirical Risk off Cancer Get access Robert W. Miller, M.D., Robert W. Miller, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Gilbert W. Beebe, Ph.D. Gilbert W. Beebe, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 2, February 1973, Pages 315–321, https://doi.org/10.1093/jnci/50.2.315 Published: 01 February 1973 Article history Received: 01 September 1972 Accepted: 10 October 1972 Published: 01 February 1973
A Report of Three Hundred and Five Cases of Habitual and Temporary Constipation Treated with Cascara Sagrada
Authors: C. E. Thompson
Journal: BMJ (1884)

rTBEtIT,ltISJ5 M AICV WNA44 - , jii ,.opri,u reiAoved to t,heJ4noe's ock de.doue, and,opened the in my prozoe.The groye-clothes were entire, but much soiled by ndPou osition, and there was some efflmivium at first.The face was Wichaiecoloured, the hair loosening from thescaip, .theeyes and part of tlhe nose had been destroyed, the teeth were loosening, the outer in _was.pelingoff, but tlxe ..n4ils o.the fingers and toes were firmly X4herent.The body. was identified ipgmy presence as that of Mar-
Butyrate suppresses expression of neuropilin I in colorectal cell lines through inhibition of Sp1 transactivation
Authors: Danny CW Yu, Jennifer S Waby, Haridasan Chirakkal, Carolyn A Staton, Bernard M Corfe
Journal: Molecular Cancer (2010)

Abstract Background Neuropilin is a transmembrane receptor for vascular endothelial growth factor (VEGF) and is expressed in normal endothelial cells and upregulated in cancer cells. Neuropilin-1 (NRP-1) has been shown to promote tumour cell migration and survival in colon cancer in response to VEGF binding. The expression profiles of neuropilins, associated co-receptors and known ligands have been mapped in three colorectal cell lines: Caco-2, HCT116 &amp; HT29. We have previously shown that butyrate, a naturally occurring histone deacetylase inhibitor (HDACi) produced by fermentation of fibre in the colon, causes apoptosis of colon cancer cell lines. Results Here we demonstrate that butyrate down-regulates NRP-1 and VEGF at the mRNA and protein level in colorectal cancer cell lines. NRP-1 is a known transcriptional target of Sp1, whose activity is regulated by acetylation. NRP-1 down-regulation by butyrate was associated with decreased binding affinity of Sp1 for canonical Sp-binding sites in the NRP-1 promoter. siRNA-mediated knock-down of Sp1 implied that Sp1 may have strong DNA binding activity but weak transactivation potential. Conclusion The downregulation of the key apoptotic and angiogenesis regulator NRP-1 by butyrate suggests a novel contributory mechanism to the chemopreventive effect of dietary fibre.
Stereotactic radiosurgery for brain oligometastases: good for some, better for all?
Authors: T. Gupta
Journal: Annals of Oncology (2005)

Brain metastasis is the commonest central nervous system neoplasm affecting 25% patients with cancer. Recursive Partitioning Analysis (RPA) is a reliable prognostic index for patients with brain metastases. In patients with oligometastases and good performance status, decision-making regarding stereotactic radiosurgery (SRS) boost, following whole brain radiation therapy (WBRT), is guided by patient preference, access to radiosurgical facility and institutional policy. Published data for this review was identified by a systematic search of MEDLINE, CANCERLIT and EMBASE databases from 1990 until the present date and was restricted to the English language using appropriate search terms. All three identified randomized controlled trials consistently showed that radiosurgery improves intracranial local control (Level I evidence). Survival benefit, however, is limited to a selected subset of patients (RPA class 1) only. More importantly, patients receiving SRS have significantly better performance scores and decreased steroid requirements resulting in improved health-related quality-of-life (HRQoL). There is no head-to-head comparison of radiosurgery with neurosurgery in resectable single metastasis. SRS is associated with an improvement in outcome. A trial of radiosurgery versus neurosurgery should be attempted to define better the role of SRS in resectable single metastasis. Formal HRQoL assessments should be incorporated as primary end points in future prospective trials.
Synergistic Antitumor Response of Interleukin 2 with Melphalan in Isolated Limb Perfusion in Soft Tissue Sarcoma–Bearing Rats
Authors: Saske Hoving, Flavia Brunstein, Gisela aan de Wiel-Ambagtsheer, Sandra T. van Tiel, Gert de Boeck, Ernst A. de Bruijn, Alexander M.M. Eggermont, Timo L.M. ten Hagen
Journal: Cancer Research (2005)

The cytokine interleukin 2 (IL-2) is a mediator of immune cell activation with some antitumor activity, mainly in renal cell cancer and melanoma. We have previously shown that tumor necrosis factor (TNF)-alpha has strong synergistic antitumor activity in combination with chemotherapeutics in the isolated limb perfusion (ILP) setting based on a TNF-mediated enhanced tumor-selective uptake of the chemotherapeutic drug followed by a selective destruction of the tumor vasculature. IL-2 can cause vascular leakage and edema and for this reason we examined the antitumor activity of a combined treatment with IL-2 and melphalan in our well-established ILP in soft tissue sarcoma-bearing rats (BN175). ILP with either IL-2 or melphalan alone has no antitumor effect, but the combination of IL-2 and melphalan resulted in a strong synergistic tumor response, without any local or systemic toxicity. IL-2 enhanced significantly melphalan uptake in tumor tissue. No signs of significant vascular damage were detected to account for this observation, although the tumor sections of the IL-2- and IL-2 plus melphalan-treated animals revealed scattered extravasation of erythrocytes compared with the untreated animals. Clear differences were seen in the localization of ED-1 cells, with an even distribution in the sham, IL-2 and melphalan treatments, whereas in the IL-2 plus melphalan-treated tumors clustered ED-1 cells were found. Additionally, increased levels of TNF mRNA were found in tumors treated with IL-2 and IL-2 plus melphalan. These observations indicate a potentially important role for macrophages in the IL-2-based perfusion. The results in our study indicate that the novel combination of IL-2 and melphalan in ILP has synergistic antitumor activity and may be an alternative for ILP with TNF and melphalan.