tbuckley/cabot-search huggingface dataset:
Adjustment Factors in Mortality Statistics
Authors: Mabel L. Halliday
Journal: JAMA (1977)

THE International Classification of Diseases and Causes of Death (ICD) is revised at approximately ten-year intervals, and considerable regrouping of diagnostic categories may occur at the time of these revisions. It has, therefore, become common practice for offices of vital statistics to publish "adjustment factors" by which mortality from a particular cause of death may be followed from one revision into the next without an abrupt and potentially misleading change in rate due to the altered method of bookkeeping. Unfortunately, if used inappropriately, the adjustment factors may themselves lead to erroneous conclusions about changes in death rates. Since another revision of the ICD will soon be introduced, it is important that the limitations of these adjustment factors be recognized. Our interest in the subject was aroused by an article published in<i>JAMA</i>in 1974,<sup>1</sup>in which the author questioned the widespread belief that mortality from coronary heart disease was
Abstract B91: Tasquinimod targets immuno-suppressive myeloid cell populations and enhances immunotherapy in murine prostate cancer models.
Authors: Li Shen, Kiersten Marie Miles, Michael Ciesielski, Leigh Ellis, Robert Fenstermaker, Roberto Pili
Journal: Cancer Research (2013)

Abstract Purpose: A major component of the immunosuppressive environment responsible for immune tolerance in cancer is represented by myeloid cell populations such as myeloid derived suppressor cells (MDSCs) and tumor associated macrophages (TAMs). These cells facilitate carcinogenesis and tumor progression by impairing T and NK cells activation and contributing to modulate angiogenesis. Tasquinimod is an anti-angiogenic and immunomodulatory agent that has shown clinical benefit in patients with prostate cancer. This agent has been found to bind to the inflammatory protein S100A9, to block the interaction of S100A9 with myeloid cells surface receptors, and therefore has the potential to affect accumulation and function of these cells. Experiments and Objectives: We tested tasquinimod in combination with a vaccine therapy in two castration resistant, syngenic transplantable murine prostate cancer models: CR Myc-Cap and TRAMP-C2. This study had the following objectives: 1) to explore tasquinimod's novel immunomodulatory activities and underlining mechanism; 2)To investigate whether tasquinimod inhibits the induction and function of immunosuppressive myeloid cell populations; 3) To assess whether tasquinimod can facilitate vaccine therapy in the castrate resistant prostate cancer models. Results: We observed that the peripheral MDSCs (in blood and spleen) dramatically increased in tumor bearing mice as compared to naïve mice. The MDSCs number increase correlated with disease progression in the transgenic model. Tasquinimod treatment depleted Gr1-CD11b+, Ly6G-CD11b+ (monocytic MDSCs) myeloid cells and M2 macrophages in peripheral sites, and reduced Gr1+CD11b+ MDSCs infiltrates in the tumors. In addition, tasquinimod (10mg/kg) dramatically improved tumor-specific immune responses, including the granzyme B expression in CD8 cells and cytotoxicity of splenocytes, and enhanced anti-tumor activity of a survivin-mimetic peptide vaccine. Conclusions: 1. MDSCs accumulate in prostate cancer models suggesting that MDSCs may contribute to immune tolerance in prostate cancer. 2. Tasquinimod reduces immunosuppressive MDSCs and M2 macrophage and may facilitate vaccine therapy by enhancing cell-mediated cytotoxic tumor cell killing and the anti-tumor immune response. Citation Format: Li Shen, Kiersten Marie Miles, Michael Ciesielski, Leigh Ellis, Robert Fenstermaker, Roberto Pili. Tasquinimod targets immuno-suppressive myeloid cell populations and enhances immunotherapy in murine prostate cancer models. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B91.
HIGHER BASELINE INFLAMMATORY BURDEN IS ASSOCIATED WITH WORSE PROGNOSIS IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE UNDERGOING CORONARY STENTING
Authors: Nima Ghasemzadeh, Zohreh Forghani, Konstantinos Aznaouridis, Paddi K. Reddy, Christine DeStareck, Craig Hooper, Arshed A. Quyyumi, Kreton Mavromatis
Journal: Journal of the American College of Cardiology (2010)
Multiple Evolutionary Rate Classes in Animal Genome Evolution
Authors: C. Oldmeadow, K. Mengersen, J. S. Mattick, J. M. Keith
Journal: Molecular Biology and Evolution (2009)

The proportion of functional sequence in the human genome is currently a subject of debate. The most widely accepted figure is that approximately 5% is under purifying selection. In Drosophila, estimates are an order of magnitude higher, though this corresponds to a similar quantity of sequence. These estimates depend on the difference between the distribution of genomewide evolutionary rates and that observed in a subset of sequences presumed to be neutrally evolving. Motivated by the widening gap between these estimates and experimental evidence of genome function, especially in mammals, we developed a sensitive technique for evaluating such distributions and found that they are much more complex than previously apparent. We found strong evidence for at least nine well-resolved evolutionary rate classes in an alignment of four Drosophila species and at least seven classes in an alignment of four mammals, including human. We also identified at least three rate classes in human ancestral repeats. By positing that the largest of these ancestral repeat classes is neutrally evolving, we estimate that the proportion of nonneutrally evolving sequence is 30% of human ancestral repeats and 45% of the aligned portion of the genome. However, we also question whether any of the classes represent neutrally evolving sequences and argue that a plausible alternative is that they reflect variable structure–function constraints operating throughout the genomes of complex organisms.
Living with obstetric fistula
Authors: F. Aliyu, G. Esegbona
Journal: BMJ (2011)

Background/Aims: Lymphocytic colitis is a clinicopathological entity characterised by protracted watery diarrhoea and an increased number of intraepithelial lymphocytes (IELs) in the surface epithelium of the colonic mucosa. This report describes two patients with symptoms similar to those of lymphocytic colitis and an increased number of IELs, but within the cryptal epithelium. Methods: The numbers of IELs were assessed in colorectal biopsies from the two patients. Sections were stained immunohistochemically for CD3, CD8, CD20, and TIA1. Results: The colorectal biopsies had an abnormally high number of IELs in the epithelium of the crypts but not in the surface epithelium. The IELs in the crypts were CD3+++, CD8+, TIA1+, and CD20−. Conclusions: The histological diagnosis in these two patients was cryptal lymphocytic coloproctitis. Patients with similar symptoms and an increased number of IELs in the surface epithelium are now filed at this department as having surface lymphocytic coloproctitis. Immunohistochemistry showed that the cryptal IELs were cytotoxic suppressor T cells. Interestingly, a case of cryptal lymphocytic colitis was recently recorded in a non-human primate dying after years of protracted chronic diarrhoea. It is possible that antigens present in the lumen of the crypts elicit a lymphocytic reaction within the cryptal cells.
Tight glycemic control does not affect asymmetric-dimethylarginine in septic patients
Authors: Gaetano Iapichino, Maura Albicini, Michele Umbrello, Francesca Sacconi, Isabella Fermo, Radmila Pavlovich, Rita Paroni, Giacomo Bellani, Giovanni Mistraletti, Massimo Cugno, Antonio Pesenti, Luciano Gattinoni
Journal: Intensive Care Medicine (2008)
Training for overseas doctors: Not the whole story
Authors: G R G Todd
Journal: BMJ (1993)

and about 65 trainees.No posts are set aside or reserved either for British doctors or for those on the scheme.I endorse the final recommendation-that doctors should not come to the United Kingdom unless they have a specific understanding concerning their appointment-but this is a matter for the organisers of the Overseas Doctors Training Scheme in London and Edinburgh.
BMA Annual representative meeting, Manchester, 27 - 30 June: UK hospitals must be staffed without “rape” of the developing world, says BMA chairman
Authors: Zosia Kmietowicz
Journal: BMJ (2005)

Doctors' leaders are considering how to keep UK hospitals fully staffed without draining the developing world of doctors. In an open debate at this year's BMA annual representatives' meeting in Manchester, doctors argued over whether recruitment agencies in developing countries should be closed down to stem the flow of junior doctors into the United Kingdom, many of whom are unable to do jobs once they arrive.

Jim Johnson, chairman of the BMA, said that draining skilled health professionals from some of the world's poorest countries had devastating effects. He warned that every year, 11 million children in developing countries died of diseases that could be treated. The “rape” of the poorest countries must stop, he said.

Mr Johnson called on developed countries to train enough doctors to meet their …
DIFFERENTIAL BLOOD CULTURES
Authors: REUBEN OTTENBERG
Journal: JAMA (1930)

In cases of bacteremia it often is a problem to determine which of several lesions is the source of the bacteria in the blood stream. The decision becomes particularly important when there is a suspicion of lateral sinus thrombosis following otitic infection. Such an obscure case led me four years ago to devise a simple procedure by which blood cultures were made from the internal jugular vein directly draining the suspected lesion. The number of bacteria in the blood of the suspected internal jugular vein was compared with the number in the blood of the opposite internal jugular, and more recently also of the arm vein. It was thought that the vein draining the lesion should show the largest number of bacteria. This procedure, of course, is quite different from the well known (but seldom used) one of Leutert,<sup>1</sup>who first introduced blood cultures into otology. He proposed to
Parasympathetic and sympathetic efferent traffic during a cardiogenic hypertensive chemoreflex
Authors: G. R HAGEMAN, F. URTHALER, T. N JAMES
Journal: Cardiovascular Research (1984)

Activation of a cardiac chemoreceptor with serotonin elicits a reflex which includes changes in heart rate, contractile force, regional blood flow and hypertension. In six anaesthetised dogs we simultaneously recorded parasympathetic and sympathetic efferent traffic elicited during this cardiogenic reflex. The parasympathetic fibres were confirmed by reciprocal frequency changes with changes in blood pressure. The sympathetic fibre activity (anterior ansa subclavia) was attenuated or eliminated by ganglionic blockade or by clonidine. Whereas the phasic sympathetic multifibre discharge was only followed by a quiet period, the parasympathetic multifibre discharge was both preceded and followed by a quiet period. The sympathetic discharge preceded the parasympathetic discharge by 683 +/- 170 ms. These autonomic efferent discharges were not elicited by administration of serotonin into the carotid artery, but were abolished by pretreatment with the serotonin antagonist, cyproheptadine. Cyproheptadine blockade could be overcome by increasing the serotonin concentration tenfold. This remarkable neural asynchrony has important implications concerning the electrical stability of the heart.
Abstract 1819: A MUC1-C oncoprotein soluble decoy receptor effectively suppresses the growth of human breast cancer cells
Authors: Govind Panchamoorthy, Deepak Raina, Hala Rehan, Surender Kharbanda, Donald Kufe
Journal: Cancer Research (2012)

Abstract The Mucin 1 (MUC1) transmembrane glycoprotein is aberrantly overexpressed by most human breast carcinomas and contributes to the malignant phenotype. MUC1 is expressed as two subunits (MUC1-N and MUC1-C) that form a stable heterodimer at the cell surface. MUC1-N is shed to contribute to a protective physical barrier, leaving the oncogenic MUC1-C subunit at the cell surface as a putative receptor for signaling the presence of stress to the interior of the cell. As shown for the VEGF receptor TRAP, aflibercept, a potential approach for blocking MUC1-C function is to generate a soluble decoy receptor by fusing the MUC1-C extracellular domain to an Ig constant (Fc) region. The present studies demonstrate that in vitro treatment of human ZR-75-1 breast carcinoma cells with the MUC1-C soluble decoy receptor is associated with a dose-dependent induction of cell death. Similar findings were obtained with human MCF-7 breast cancer cells. To explore the potential of the MUC1-C soluble decoy receptor as an anti-cancer agent, we evaluated its ability to block the growth of breast cancer cells in subcutaneous tumor xenograft models growing in nude mice. Administration of the MUC1-C soluble decoy receptor to nude mice bearing established ZR-75-1 breast tumor xenografts was associated with a dose-dependent loss of tumorigenicity and prolonged tumor regressions after completing therapy. Taken together, these findings demonstrate that targeting the MUC1-C oncoprotein with a soluble decoy receptor is effective in inducing death of human breast cancer cells in vitro and in tumor models. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1819. doi:1538-7445.AM2012-1819
Abstract 4491: FGFR2-ADC potently and selectively inhibits growth of gastric and breast cancer xenograft models
Authors: Anette Sommer, Carl F. Nising, Christoph Mahlert, Charlotte C. Kopitz, Hans-Georg Lerchen, Simone Greven, Beatrix Stelte-Ludwig, Joachim Schuhmacher, Ruprecht Zierz, Sabine Wittemer-Rump, Christoph Schatz, Frank Reetz, Heiner Apeler, Rolf Jautelat, Bertolt Kreft, Karl Ziegelbauer
Journal: Cancer Research (2014)

Abstract Antibody-drug conjugates (ADCs) represent a promising therapeutic approach for treatment of cancer. We have developed a novel ADC directed against fibroblast growth factor receptor 2 (FGFR2). FGFR2 is overexpressed in several cancer indications, such as gastric cancer and breast cancer, thus representing an interesting therapeutic target for the treatment of FGFR2 positive cancer patients with an ADC-based therapy. The FGFR2-ADC consists of the fully human anti-FGFR2-mAb BAY 1179470 conjugated via a stable linker to a novel auristatin cytotoxic agent (technology licensed from Seattle Genetics). The FGFR2-mAb BAY 1179470, which is cross-reactive with human, mouse, rat and monkey, induces internalization of FGFR2. Quantitative data on FGFR2 antibody bound per cell (ABC) were determined with the QuantiBrite assay using BAY 1179470. FGFR2-ADC has a potency in the single digit nM to sub nM range in a panel of FGFR2-positive cells lines (e.g., SNU-16, KatoIII, SUM52-PE, MFM-223) and shows more than 100-fold selectivity versus FGFR2-negative cell lines. High levels of FGFR2 on cancer cells correlate with internalization efficacy and cytotoxic activity in vitro. FGFR2-ADC is highly efficacious in monotherapy and results in tumor growth inhibition in the gastric cancer xenograft model SNU-16 and tumor regression in the breast cancer xenograft model MFM-223. At doses efficacious in mice, FGFR2-ADC is well tolerated. The pre-clinical efficacy and tolerability data obtained for FGFR2-ADC suggest a therapeutic index and support clinical testing. Citation Format: Anette Sommer, Carl F. Nising, Christoph Mahlert, Charlotte C. Kopitz, Hans-Georg Lerchen, Simone Greven, Beatrix Stelte-Ludwig, Joachim Schuhmacher, Ruprecht Zierz, Sabine Wittemer-Rump, Christoph Schatz, Frank Reetz, Heiner Apeler, Rolf Jautelat, Bertolt Kreft, Karl Ziegelbauer. FGFR2-ADC potently and selectively inhibits growth of gastric and breast cancer xenograft models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4491. doi:10.1158/1538-7445.AM2014-4491
582 MODULATION OF AKT, NFKB ACTIVITY, APOPTOSIS AND CELL CYCLE IN HEPATOCYTES BY THE LAMIVUDINE RESISTANT RTM204I HBV MUTANT
Authors: R. Chin, U. Nachbur, L. Earnest-Silveira, A. Bankovacki, H. Zentgraf, C.-T. Bock, J. Silke, J. Torresi
Journal: Journal of Hepatology (2009)
Managing smoking cessation
Authors: Paul Aveyard, Robert West
Journal: BMJ (2007)

Cross sectional studies show that most smokers in countries such as the United Kingdom and the United States report that they want to stop and intend to stop at some point.1 The rate of attempts to stop is high—78 attempts per 100 smokers per year in the UK—with many smokers making several attempts in a year.2 Nearly half of all smokers expect not to be smoking in a year's time,3 but only 2-3% actually stop permanently each year.3 The most common reasons smokers give for smoking are stress relief and enjoyment,4 but the main reason is nicotine dependence. Nicotine acts in the midbrain, creating impulses to smoke in the face of stimuli associated with smoking.5 Consequent changes in brain chemistry also produce "nicotine hunger" when a smoker goes without nicotine. A third mechanism underlying nicotine dependence is nicotine withdrawal: unpleasant mood and physical symptoms that occur on abstinence and are relieved by smoking.6 7 Nicotine dependence is the main reason that most unassisted quit attempts fail within a week.8 We give evidence based recommendations and new treatment options for healthcare professionals to increase the success rate of these attempts. Most evidence for treatment comes from randomised controlled trials summarised in the Cochrane reviews for tobacco dependence. #### Summary points
Vertebral Grand Larceny
Authors: MARVIN L. DAVES, ALBERT TREGER
Journal: Circulation (1964)

A case is presented of atresia of the aortic arch between the left common carotid artery proximally and the left subclavian artery and a patent ductus arteriosus distally. Collateral circulation including a pathway via the vertebral arteries maintained an adequate mean pressure in the descending aorta to produce a left-to-right shunt in the patent ductus, despite an elevated pulmonary arterial pressure.
Thoracic Duct Fistula in Infant
Authors: James D. Hardy
Journal: JAMA (1962)

THE THORACIC DUCT is not often visualized at operation unless specifically exposed. Normally it traverses the diaphragm through the aortic hiatus and courses through the posterior mediastinum. It lies between the aorta and the azygous vein, until at the level of the fifth thoracic vertebra it inclines toward the left, passes behind the aortic arch, and enters the venous system at the junction of the left subclavian and internal jugular veins. However, in the course of various operations for congenital cardiovascular disease we have from time to time noted numerous anatomic variations in the course of the thoracic duct, particularly regarding its relationship to the aortic arch. Specifically, the thoracic duct may lie anterior to the aortic arch and thus may be injured in the course of resection of a coarctation of the aorta or in the division of a patent ductus arteriosus. The management of a traumatic thoracic duct
Survival from breast cancer is lower in UK than in other developed countries
Authors: J. Wise
Journal: BMJ (2013)

Women aged over 70 with breast cancer and women in all age groups with more advanced disease may be treated less aggressively in the United Kingdom than in some other countries, an international study indicates.

The research, conducted by the International Cancer Benchmarking Partnership and funded by the Department of Health for England, found that breast cancer survival was lower in the UK and Denmark than in Australia, Canada, Norway, and Sweden.1

The study used routinely collected data from cancer registries to monitor breast cancer survival in all women with breast cancer, not just selected groups. The researchers analysed data from 257 362 women who were given a diagnosis of breast cancer during 2000 to 2007.

Age standardised, net survival at …
Identification of recurrent SMO and BRAF mutations in ameloblastomas
Authors: Robert T Sweeney, Andrew C McClary, Benjamin R Myers, Jewison Biscocho, Lila Neahring, Kevin A Kwei, Kunbin Qu, Xue Gong, Tony Ng, Carol D Jones, Sushama Varma, Justin I Odegaard, Toshihiro Sugiyama, Souichi Koyota, Brian P Rubin, Megan L Troxell, Robert J Pelham, James L Zehnder, Philip A Beachy, Jonathan R Pollack, Robert B West
Journal: Nature Genetics (2014)
The Treatment of Lung Cancer in Situ
Authors: Frank W. Ellis
Journal: JAMA (1966)

<h3>To the Editor:—</h3> In the Oct 25 issue (<b>194</b>:adv p 33, 1965) is a news item concerning a community program of detection of lung cancer in situ by the Papanicolaou technique on sputum, which states that "lung cancer may be detected in situ as much as ten years before it becomes invasive." The article estimates that in this particular program about 40 persons will "show cancer in situ" (from sputum examinations). These cases are then to be "referred to private physicians for treatment." How does one treat lung cancer in situ? With the assumption that the chest x-ray and bronchoscopic and bronchographic examinations are negative (by the definition of "in situ"), what form of treatment is indicated and what direction does it take? The need for early cancer detection continues to be our major public health problem—but I am confused as to how one applies treatment to a patient
Ad5/48 Hexon Oncolytic Virus Expressing sTGFβRIIFc Produces Reduced Hepatic and Systemic Toxicities and Inhibits Prostate Cancer Bone Metastases
Authors: Weidong Xu, Zhenwei Zhang, Yuefeng Yang, Zebin Hu, Chi-Hsiung Wang, Melanie Morgan, Ying Wu, Ryan Hutten, Xianghui Xiao, Stuart Stock, Theresa Guise, Bellur S Prabhakar, Charles Brendler, Prem Seth
Journal: Molecular Therapy (2014)

We are interested in developing oncolytic adenoviruses for the treatment of prostate cancer (PCa) bone metastases. A key limitation of Adenovirus 5 (Ad5) is that upon systemic administration, it produces major liver and systemic toxicities. To address this issue, a chimaeric Ad5/48 adenovirus mHAd.sTβRFc was created. Seven hypervariable regions of Ad5 hexon present in Ad5-based Ad.sTβRFc expressing soluble transforming growth factor beta receptor II-Fc fusion protein (sTGβRIIFc), were replaced by those of Ad48. mHAd.sTβRFc, like Ad.sTβRFc, was replication competent in the human PCa cells, and produced high levels of sTGβRIIFc expression. Compared to Ad.sTβRFc, the systemic delivery of mHAd.sTβRFc in nude mice resulted in much reduced systemic toxicity, and reduced liver sequestration. Ad.sTβRFc produced significant liver necrosis, and increases in alanine transaminase, aspartate transaminase, lactate dehydrogenase, tumor necrosis factor-α, and interleukin-6 levels, while mHAd.sTβRFc produced much reduced responses of these markers. Intravenous delivery of Ad.sTβRFc or mHAd.sTβRFc (5 × 10(10) viral particles/mouse) in nude mice bearing PC-3-luc PCa bone metastases produced inhibition of bone metastases. Moreover, a larger dose of the mHAd.sTβRFc (4 × 10(11) viral particles /mouse) was also effective in inhibiting bone metastases. Thus, mHAd.sTβRFc could be developed for the treatment of PCa bone metastases.
Casodex&lt;sup&gt;TM&lt;/sup&gt; 10&amp;ndash;200&amp;nbsp;mg Daily, Used as Monotherapy for the Treatment of Patients with Advanced Prostate Cancer
Authors: C.J. Tyrrell, L. Denis, D. Newling, M. Soloway, K. Channer, I.D. Cockshott, None on behalf of the &lsquo;Casodex&rsquo; Study Group
Journal: European Urology (1998)