tbuckley/cabot-search huggingface dataset:
Factors associated with inflammatory cytokine patterns in community-acquired pneumonia
Authors: R. Martínez, R. Menéndez, S. Reyes, E. Polverino, C. Cillóniz, A. Martínez, C. Esquinas, X. Filella, P. Ramírez, A. Torres
Journal: European Respiratory Journal (2010)

Raised systemic levels of interleukin (IL)-6 and IL-10 cytokines have been associated with poorer outcome in community-acquired pneumonia. The aim of our study was to identify potential associated factors with increased levels of IL-6, IL-10, or both cytokines. We performed a prospective study of 685 patients admitted to hospital with community-acquired pneumonia. IL-6 and IL-10 were measured in blood in the first 24 h. 30-day mortality increased from 4.8% to 11.4% (p = 0.003) when both cytokines were higher than the median. Independent associated factors with an excess of IL-6 were neurologic disease, confusion, serum sodium &lt;130 mEq·L −1 , pleural effusion, and bacteraemia. The associated factors for an excess of IL-10 were respiratory rate ≥30 breaths·min −1 , systolic blood pressure &lt;90 mmHg and glycaemia ≥250 mg·dL −1 . The independent associated factors for an excess of both cytokines were confusion, systolic blood pressure &lt;90 mmHg, pleural effusion and bacteraemia. Protective factors were prior antibiotic treatment and pneumococcal vaccination. Different independent factors are related to an excess of IL-6 and IL-10. Confusion, hypotension, pleural effusion and bacteraemia were associated with the inflammatory profile with the highest mortality rate, whereas anti-pneumococcal vaccination and previous antibiotic treatment appeared to be protective factors.
An antigen receptor-driven, interleukin 2-independent pathway for proliferation of murine cytolytic T lymphocyte clones.
Authors: R L Moldwin, D W Lancki, K C Herold, F W Fitch
Journal: The Journal of Experimental Medicine (1986)

Proliferation of T lymphocytes can be induced by IL-2, either through an autocrine pathway in which the responding cell produces its own IL-2 or through an exocrine pathway in which IL-2 secreted by Th stimulates proliferation of IL-2-dependent CTL. However, proliferation of at least some CTL clones, such as CTL L3 and CTL dB45, also can be induced by stimulation of the antigen receptor in the absence of IL-2. Stimulation of these cloned CTL with T cell-depleted allogeneic spleen cells, allogeneic tumor cells, or immobilized mAb reactive with the T cell antigen receptor (TCR) induced thymidine incorporation, entry into cell cycle, and secretion of macrophage activating factor, but these stimuli did not induce the secretion of IL-2. Several observations indicated that such proliferation of cloned CTL induced by stimulation of the TCR was independent of IL-2; IL-2 could not be detected in supernatants from stimulated CTL cells. mAbs reactive with the murine IL-2-R efficiently blocked IL-2-mediated thymidine incorporation in cloned CTL and Th, but had no inhibitory effect on TCR-driven thymidine incorporation in the CTL clones. TCR-driven thymidine incorporation in cloned Th L2 cells was profoundly inhibited by these antibodies, indicating the operation of an IL-2-mediated autocrine pathway for proliferation in this cloned Th. When antibodies to the TCR were used to stimulate cloned CTL and Th, IFN-gamma mRNA was easily shown in the cloned CTL and Th. Although IL-2 mRNA could be detected in the cloned Th, it was never observed in the cloned CTL. These findings provide evidence for the existence of a TCR-mediated, IL-2-independent pathway for induction of cellular proliferation in cloned murine CTL.
Hierarchical analysis of variation in the mitochondrial 16S rRNA gene among Hymenoptera
Authors: J B Whitfield, S A Cameron
Journal: Molecular Biology and Evolution (1998)

Nucleotide sequences from a 434-bp region of the 16S rRNA gene were analyzed for 65 taxa of Hymenoptera (ants, bees, wasps, parasitoid wasps, sawflies) to examine the patterns of variation within the gene fragment and the taxonomic levels for which it shows maximum utility in phylogeny estimation. A hierarchical approach was adopted in the study through comparison of levels of sequence variation among taxa at different taxonomic levels. As previously reported for many holometabolous insects, the 16S data reported here for Hymenoptera are highly AT-rich and exhibit strong site-to-site variation in substitution rate. More precise estimates of the shape parameter (alpha) of the gamma distribution and the proportion of invariant sites were obtained in this study by employing a reference phylogeny and utilizing maximum-likelihood estimation. The effectiveness of this approach to recovering expected phylogenies of selected hymenopteran taxa has been tested against the use of maximum parsimony. This study finds that the 16S gene is most informative for phylogenetic analysis at two different levels: among closely related species or populations, and among tribes, subfamilies, and families. Maximization of the phylogenetic signal extracted from the 16S gene at higher taxonomic levels may require consideration of the base composition bias and the site-to-site rate variation in a maximum-likelihood framework.
CXCR4/IgG-expressing plasma cells are associated with human gastrointestinal tissue inflammation
Authors: Clarisa M. Buckner, Susan Moir, Lela Kardava, Jason Ho, Brian H. Santich, Leo Jin Young Kim, Emily K. Funk, Amy K. Nelson, Britanny Winckler, Cheryl L. Chairez, Narda L. Theobald-Whiting, Sandra Anaya-O’Brien, Meghna Alimchandani, Martha M. Quezado, Michael D. Yao, Joseph A. Kovacs, Tae-Wook Chun, Anthony S. Fauci, Harry L. Malech, Suk See De Ravin
Journal: Journal of Allergy and Clinical Immunology (2013)
Long-term outcome with intravenous iloprost in pulmonary arterial hypertension
Authors: M. M. Hoeper, H. Gall, H. J. Seyfarth, M. Halank, H. A. Ghofrani, J. Winkler, H. Golpon, K. M. Olsson, N. Nickel, C. Opitz, R. Ewert
Journal: European Respiratory Journal (2009)

There is limited data on the long-term efficacy of intravenous iloprost in patients with pulmonary arterial hypertension (PAH). This retrospective multicentre analysis evaluated the clinical course of patients with PAH treated with i.v. iloprost, in most cases after having received inhaled iloprost as first-line therapy. Between 1997 and 2001, 79 PAH patients were treated with i.v. iloprost and followed until 2007. These patients had advanced and progressive disease as indicated by a mean pulmonary vascular resistance of 1,533 dyn·s·cm −5 at the time of diagnosis and of 1,858 dyn·s·cm −5 at the onset of i.v. iloprost therapy. Introduction of i.v. iloprost therapy resulted in initial haemodynamic and clinical improvement. At the end of the observation period, however, 50 (61%) patients had died and 21 (26%) required lung transplantation. Transplantation-free survival rates at 1, 3, and 5 yrs were 86%, 59% and 45%, respectively, after the diagnosis of PAH, and 54%, 31% and 15%, respectively, after the introduction of i.v. iloprost therapy. Predictors of an adverse outcome at baseline were a low 6-min walk distance and a low mixed venous oxygen saturation. In conclusion, despite initial haemodynamic and clinical improvement, overall long-term survival with i.v. iloprost therapy was limited.
Hematopoietic Stem Cell Niche Is a Potential Therapeutic Target for Bone Metastatic Tumors
Authors: Yusuke Shiozawa, Kenneth J. Pienta, Russell S. Taichman
Journal: Clinical Cancer Research (2011)

Despite significant improvements in therapy, the prognosis for cancer with bone metastasis is generally poor. Therefore, there is a great need for new therapeutic approaches for metastatic disease. It has been appreciated that tumor cells metastasize to bone using mechanisms similar to those of hematopoietic stem cells (HSC) homing to bone marrow (e.g., CXCL12/CXCR4). It was recently found that prostate cancer cells target the bone marrow microenvironment for HSCs, or the HSC niche, during metastasis. Of importance, these disseminated prostate cancer cells can be mobilized out of the niche with the use of HSC mobilizing agents. These findings suggest that the bone marrow HSC niche is a potential therapeutic target for metastatic disease. Therefore, a hypothesis worth considering is that agents that can disrupt the interactions between tumor cells and the HSC niche may be efficacious when used in conjunction with standard chemotherapeutic agents. Although further understanding of the tumor-niche interactions is needed, the concept of targeting the niche in conjunction with chemotherapy could open up new possibilities to eradicate incurable metastatic diseases.
Pharmacological Treatment and Current Management of Peripheral Artery Disease
Authors: Marc P. Bonaca, Mark A. Creager
Journal: Circulation Research (2015)

Patients with peripheral artery disease (PAD) are at heightened risk of both systemic cardiovascular adverse events, as well as limb-related morbidity. The optimal management of patients with PAD requires a comprehensive treatment strategy incorporating both lifestyle changes, including smoking cessation and exercise, as well as optimal medical therapy. Pharmacological therapies for patients with PAD are targeted both at modifying broad risk factors for major adverse cardiovascular events, as well as reducing limb-related morbidity. Observational data suggest that indicated pharmacological treatments are greatly underutilized in PAD, underscoring the need for improvements in patient identification and care delivery. Ongoing trials of novel therapies in patients with PAD will further inform pharmacological strategies to reduce both systemic cardiovascular risk and limb-related morbidity.
Effect of <i>BRCA1</i> Haplotype on Survival of Non–Small-Cell Lung Cancer Patients Treated With Platinum-Based Chemotherapy
Authors: Hong-Tae Kim, Jong-Eun Lee, Eun-Soon Shin, Yeon-Kyeong Yoo, Jae-Hwa Cho, Min-Hye Yun, Yeul-Hong Kim, Se-Kyu Kim, Hyun-Jung Kim, Tae-Won Jang, Seung-Min Kwak, Chul-Soo Kim, Jeong-Seon Ryu
Journal: Journal of Clinical Oncology (2008)

To determine whether germ-line variations in BRCA1 affect outcome in non-small-cell lung cancer (NSCLC) patients treated with platinum combination chemotherapy.We evaluated the associations of four tagging BRCA1 polymorphisms and their haplotypes with treatment outcome in 300 NSCLC patients at stages IIIA (16%), IIIB (31%), and IV (53%).The median age was 63 years (range, 28 to 89 years). Histologically, 139 (46.3%) of the patients had squamous cell carcinomas and 137 (45.7%) had adenocarcinomas. Patient median survival time (MST) was 13.0 months. We observed no significant association between any of the tagging polymorphisms [S1613G, IVS13-1893 (A>C), IVS12-1207 (C>T), and IVS12+112 (C>A)] and overall survival. Of the five haplotypes evaluated (AACC, AACA, GCTC, GATC, and AATC), the survival of patients with two copies of the AACC (wild-type) haplotype was significantly shorter than that of patients with zero to one copies (MST, 8.47 v 14.57 months; log-rank P = .0066), even after adjustment for body weight loss, performance status, stage, second-line treatment, and radiation therapy (hazard ratio = 2.097; 95% CI, 1.339 to 3.284). The survival of patients with squamous cell carcinoma and two copies was significantly shorter than that of other patients with squamous cell carcinoma (MST, 6.8 v 15.3 months; log-rank P = 3.6 x 10(-5)), whereas differences in survival between the two adenocarcinoma groups was not significant (log-rank P = .677).These findings suggest that the AACC haplotype of the BRCA1 gene is an important prognostic marker in NSCLC patients treated with platinum combination chemotherapy.
Personal Reflections on Occupational Health in the Twentieth Century: Spiraling to the Future
Authors: Mark R. Cullen
Journal: Annual Review of Public Health (1999)

▪ Abstract The history of occupational health in the United States during the twentieth century demonstrates pendular swings, with periods of rapid progress followed by periods of reversal. Happily, the last three decades have witnessed the most impressive gains, with establishment of a near-universal system for regulating conditions in the workplace, legitimization and growth of the occupational health professions, a marked increase in scientific research, most notably epidemiology, and the transfer of knowledge about occupational health to affected workers and the larger US population. Not surprisingly, rates of injury and illness have fallen. However, analysis of these cyclical historic changes suggests that extrinsic factors—broad social currents, changes in health care financing, and societal perceptions of health and disease—have dominated over enhanced scientific knowledge, technologic changes or professional achievements, usually the determinants of medical or public health advances. Practitioners of occupational health are not, and have never been, in a particularly advantageous position to fashion future events in their own field, and the current situation, however encouraging, is likely no exception.
Therapeutic factor VIII levels and negligible toxicity in mouse and dog models of hemophilia A following gene therapy with high-capacity adenoviral vectors
Authors: Marinee K. L. Chuah, Gudrun Schiedner, Lieven Thorrez, Brian Brown, Marion Johnston, Veerle Gillijns, Sabine Hertel, Nico Van Rooijen, David Lillicrap, Désiré Collen, Thierry VandenDriessche, Stefan Kochanek
Journal: Blood (2003)
A multiplicity of constraints: How children learn word meaning
Authors: Chris Westbury, Elena Nicoladis
Journal: Behavioral and Brain Sciences (2001)

This book is an excellent and accessible overview of the position that children learn the meanings of words by applying a variety of nonlinguistic cognitive tools to the problem. We take issue with Bloom's emphasis on Theory of Mind as an explanatory mechanism for language learning; and with his claim that only unitary objects are nameable.
Remarks upon a Case in Which There Were Evidences of Dilated Bronchi: And Which Was Complicated by Occasional Expectoration of Thin, Fibrinous, Cup-Shaped, False Membranes
Authors: P. M. Duncan
Journal: BMJ (1851)

JOHN CLARK, aged 35, bricklayer, has always lived in Colchester, and has never had any serious illness before tlle commencement of his present malady.He has never had croup nor chronic cough, and he states that he has always lived steadily and soberly.Six years ago he had a bad cold, which confined him to his bed for five or six weeks; he has distinct recollection of having suffered from dyspncea and difficulty of speaking, but antiphlogistic remedies do not appear to have been used with any degree of severity.A month after his convalescence, during which his lung symptoms appear to have left him, he was suddenly seized with pain in the right mammary region, cough supernened, and during a paroxysm of it he expectorated a light-coloured fibrinous mass, cup shaped, and much resembling in thickness and shape, the top of the thumb of a good- sized kid glove.During his illness, which lasted three months, he expectorated thirty of these false membranes; occasionally three or four were ejected simultaneously, but generally but one at a time was produced.For five years after this attack his health was good, neither cough nor expectoration of any kind were complained of, and he followed his usual avocations.At Christmas, 1849, he caught cold, and has not been well since.In April of the following year he experienced great pain in the right mammary region, it was attended by cough, considerable fever and dyspncea.After suffering for several days repeated paroxysms of coughing, he sud- denly spat up five of the before mentioned cup-shaped false membranes and immediately after a considerable quantity of scarlet blood.His urgent symptoms were immediately relieved, but in a few days they returned, and he then came under my care.He is a tall well-formed man, thorax well developed, and measuring thirty-four inches in circumference beneath the clavicles.The general expansion during deep inspiration is deficient, his breathing being chiefly abdominal.The mammary and infra-axillary regions of the right side expand less thani those of the left, but in no part is there perfect loss of motion.Beneath the clavicles the percussion-sound is healthy, but on the right side, over the mammary, infra-mammary, and infra-axillary regions, there is considerable dul- ness.The left side of the chest is resonant throughout.
Odor Encoding as an Active, Dynamical Process: Experiments, Computation, and Theory
Authors: Gilles Laurent, Mark Stopfer, Rainer W Friedrich, Misha I Rabinovich, Alexander Volkovskii, Henry DI Abarbanel
Journal: Annual Review of Neuroscience (2001)

▪ Abstract We examine early olfactory processing in the vertebrate and insect olfactory systems, using a computational perspective. What transformations occur between the first and second olfactory processing stages? What are the causes and consequences of these transformations? To answer these questions, we focus on the functions of olfactory circuit structure and on the role of time in odor-evoked integrative processes. We argue that early olfactory relays are active and dynamical networks, whose actions change the format of odor-related information in very specific ways, so as to refine stimulus identification. Finally, we introduce a new theoretical framework (“winnerless competition”) for the interpretation of these data.
Neutrophil apoptosis, proinflammatory mediators and cell counts in bronchiectasis
Authors: A P Watt
Journal: Thorax (2004)

Lower airway secretions from patients with bronchiectasis show inflammatory cell infiltration and increased proinflammatory mediators. The aim of this study was to investigate the effects of antibiotic treatment for exacerbations on neutrophil apoptosis and necrosis.Sputum was induced from 15 subjects with idiopathic bronchiectasis at the beginning of an acute exacerbation and after intravenous antibiotic treatment. Neutrophil apoptosis and necrosis were assessed using flow cytometry and morphology and the supernatant was analysed for concentrations of inflammatory mediators.Neutrophil numbers (x10(6) cells/g sputum) in sputum were significantly greater on day 0 than on day 14 (median difference (95% confidence interval (CI)) 5.14 (1.27 to 8.46), p = 0.02). Controls had a significantly higher percentage of sputum macrophages than patients with bronchiectasis (day 0, 1.35 (95% CI 0.48 to 2.89), p = 0.004; day 14, 1.09 (95% CI 0.26 to 2.86), p = 0.02). The concentrations of tumour necrosis factor alpha (pg/ml), interleukin 8 (ng/ml), and neutrophil elastase (ng/ml) in sputum supernatant were significantly reduced on day 14 compared with day 0 (median difference -94 (95% CI -158 to -27), p = 0.005; -106 (95% CI -189 to -50), p = 0.0006; and -73 451 (95% CI -135 495 to -12 303), p = 0.02 respectively). Patients with bronchiectasis had a significantly lower percentage of cells which were neither apoptotic nor necrotic than healthy controls (both days, -38.8 (95% CI -49.6 to -8.5), p = 0.002; -45.0 (95% CI -58.0 to -34.1), p = 0.0003, respectively), and on day 14 they had a significantly higher percentage of secondary necrotic cells than healthy controls (40 (95% CI 11.6 to 57.5), p = 0.004).This study shows that antibiotic treatment affects concentrations of proinflammatory mediators and cell death and clearance may be altered in bronchiectasis.
AXE Beam: Neo-Adjuvant Triplet Versus Doublet Therapy with Radiation and Total Mesorectal Excision for Locally Advanced Rectal Cancer – A Randomized Phase II Study at the End of Recruitment
Authors: G. Chiritescu, K. Dumon, P. Vergauwe, J. Arts, L. Verbeke, M. Polus, Y. Humblet, J.L. Van Laethem, J.F. Daisne, J. Decaestecker, A. D'Hoore, F. Mardjuadi, A. Debucquoy, M. Verstraete, X. Sagaert, K. Haustermans, E. Van Cutsem
Journal: Annals of Oncology (2014)
The Injuries to JFK
Authors: Anthony White
Journal: JAMA (1992)

<h3>To the Editor.</h3> —Drs Humes and Boswell,<sup>1</sup>in their interview with<i>JAMA</i>editor Dr George Lundberg, state that it was "perfectly obvious" that President Kennedy was shot from behind. They decry the "supreme ignorance" of the prevailing doubts about the assassination, blaming money-hungry conspiracy "buffs" for indulging in "ridiculous theories." The essence of their statement is that the beveled appearance of the entrance and exit wounds in the President's skull provide an "irrefutable diagnostic fact" that the bullet came from the rear and above. It is curious that so much controversy would remain in the face of such an easily interpretable fact. If the reality is as they state, it would be a simple act to remove all controversy. Rather than provide supportive material, we are asked to believe them simply because they insist it is true. As I write this letter, I am looking at one of the
Unemployment Assistance: Determination of Needs
Authors: E. F. Buzzard, S. J. Cowell, J. B. S. Haldane, L. Harris, F. G. Hopkins, J. C. G. Ledingham, G. C. M. M'Gonigle, C. McNeil, V. H. Mottram, J. B. Orr, C. Porter, H. Rolleston
Journal: BMJ (1934)
Response to Letters Regarding Article, “Heart Rate Predicts Outcomes in an Implantable Cardioverter-Defibrillator Population”
Authors: Mastaneh Ahmadi-Kashani, Salam Sbaity, Brian Olshansky, David J. Kessler, John Day, T. Jared Bunch, Kira Stolen, Scott Brown
Journal: Circulation (2010)

Cardioverter-Defibrillator Population"On the basis of our findings, 1 Drs Fazio and Carlomagno and Dr Lin and colleagues considered that a J-shaped relationship may exist between heart rate and outcomes.Like the U-shaped relationship we saw with an increasing percentage of right ventricular pacing and outcomes, 2 we suspected that a J-or U-shaped relationship may exist between heart rate and outcomes.However, we could not discern with certainty that the slowest heart rates were associated with worse outcomes even though a trend in that direction appeared.Dr Lin and colleagues also suspected that a J-shaped relationship may be present in those with mild heart failure in lieu of a linear heart rate/outcome relationship that may occur in those with advanced heart failure.Dividing data into these small subgroups did not provide definitive answers.We agree, as Dr Lin and colleagues cautioned, that there is need to interpret the data carefully.Nevertheless, this issue remains worthy of further study because some, 3 but not all, 4,5 data regarding heart rate support a J-shaped relationship, albeit in different populations and for different outcomes.Dr Lin and colleagues wondered if slow heart rates are related to increasing amounts of right ventricular pacing.Heart rate was a predictor of outcomes independently of right ventricular pacing.Although right ventricular pacing predicted outcomes, heart rate was the stronger predictor.The pacemaker programming we used would not necessarily promote high amounts of right ventricular pacing at slow rates.Indeed, some right ventricular pacing in the Inhibition of Unnecessary Right Ventricular Pacing With Atrioventricular Search Hysteresis in Implantable Cardioverter Defibrillators (INTRINSIC RV) study was associated with favorable outcomes. 2Despite this, the relationship between right ventricular pacing and outcomes in the context of slow heart rates requires further study.We agree with Drs Fazio and Carlomagno that important relationships between lifestyle, physical activity, and heart rate may exist and that they can be difficult to discern in assessments of heart rate over prolonged periods.Nevertheless, mean heart rate effectively predicted outcomes.Transtelephonic implantable cardioverterdefibrillator monitoring may better define relationships between level of exercise and its correlation with heart rate during exercise and at rest.Although our study did not permit investigation of resting heart rate and its change under exercise, understanding the relationships between heart rate and specific daily activities or lifestyles and even circadian variations could provide new insight into how heart rate is associated with outcomes.