tbuckley/cabot-search huggingface dataset:
Cyclophosphamide in scleroderma lung disease
Authors: H Steer
Journal: Thorax (2006)

▴ Tashkin DP, Elashoff R, Clements PJ, et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med2006;354:2655–66[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Around 40% of patients with systemic sclerosis will develop significant interstitial lung disease. No agent has been proved in a randomised controlled trial to … [1]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.aulast%253DTashkin%26rft.auinit1%253DD.%2BP.%26rft.volume%253D354%26rft.issue%253D25%26rft.spage%253D2655%26rft.epage%253D2666%26rft.atitle%253DCyclophosphamide%2Bversus%2Bplacebo%2Bin%2Bscleroderma%2Blung%2Bdisease.%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa055120%26rft_id%253Dinfo%253Apmid%252F16790698%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa055120&link_type=DOI [3]: /lookup/external-ref?access_num=16790698&link_type=MED&atom=%2Fthoraxjnl%2F61%2F10%2F908.1.atom [4]: /lookup/external-ref?access_num=000238416900004&link_type=ISI
TREM2 in CNS homeostasis and neurodegenerative disease
Authors: Meghan M. Painter, Yuka Atagi, Chia-Chen Liu, Rosa Rademakers, Huaxi Xu, John D. Fryer, Guojun Bu
Journal: Molecular Neurodegeneration (2015)

Myeloid-lineage cells accomplish a myriad of homeostatic tasks including the recognition of pathogens, regulation of the inflammatory milieu, and mediation of tissue repair and regeneration. The innate immune receptor and its adaptor protein—triggering receptor expressed on myeloid cells 2 (TREM2) and DNAX-activating protein of 12 kDa (DAP12)—possess the ability to modulate critical cellular functions via crosstalk with diverse signaling pathways. As such, mutations in TREM2 and DAP12 have been found to be associated with a range of disease phenotypes. In particular, mutations in TREM2 increase the risk for Alzheimer's disease and other neurodegenerative disorders. The leading hypothesis is that microglia, the resident immune cells of the central nervous system, are the major myeloid cells affected by dysregulated TREM2-DAP12 function. Here, we review how impaired signaling by the TREM2-DAP12 pathway leads to altered immune responses in phagocytosis, cytokine production, and microglial proliferation and survival, thus contributing to disease pathogenesis.
Bone cells unite
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

Debating DAP12Mice that lack the adaptor protein DAP12 defy deadly bacterial infections, according to Turnbull and colleagues on page 363.DAP12-deficient mice developed a muted inflammatory response, allowing the immune system to clear the bacteria without triggering septic shock.DAP12 is a transmembrane adaptor protein that is associated with an array of DAP12-deficient mice (dotted line) are resistant to a lethal endotoxin challenge.
The Green Tea Polyphenol EGCG Potentiates the Antiproliferative Activity of c-Met and Epidermal Growth Factor Receptor Inhibitors in Non–small Cell Lung Cancer Cells
Authors: Shawn A. Milligan, Patrick Burke, David T. Coleman, Rebecca L. Bigelow, Joshua J. Steffan, Jennifer L. Carroll, Briana Jill Williams, James A. Cardelli
Journal: Clinical Cancer Research (2009)

Activation of the c-Met and epidermal growth factor receptors (EGFR) promotes the growth and survival of non-small cell lung cancer (NSCLC). Specific receptor antagonists have shown efficacy in the clinic, but tumors often become resistant to these therapies. We investigated the ability of (-)-epigallocatechin-3-gallate (EGCG) to inhibit cell proliferation, and c-Met receptor and EGFR kinase activation in several NSCLC cell lines.NSCLC cell lines with variable sensitivity to the EGFR antagonist erlotinib were studied. Cell growth was evaluated using proliferation and colony formation assays. Kinase activation was assessed via Western blot analysis. Experiments were conducted with EGCG, the EGFR antagonist erlotinib, and the c-Met inhibitor SU11274. The antagonists were also tested in a xenograft model using SCID mice.EGCG inhibited cell proliferation in erlotinib-sensitive and -resistant cell lines, including those with c-Met overexpression, and acquired resistance to erlotinib. The combination of erlotinib and EGCG resulted in greater inhibition of cell proliferation and colony formation than either agent alone. EGCG also completely inhibited ligand-induced c-Met phosphorylation and partially inhibited EGFR phosphorylation. The triple combination of EGCG/erlotinib/SU11274 resulted in a greater inhibition of proliferation than EGCG with erlotinib. Finally, the combination of EGCG and erlotinib significantly slowed the growth rate of H460 xenografts.EGCG is a potent inhibitor of cell proliferation, independent of EGFR inhibition, in several NSCLC cell lines, including those resistant to both EGFR kinase inhibitors and those overexpressing c-Met. Therefore, EGCG might be a useful agent to study as an adjunct to other anticancer agents.
SPARC independent drug delivery and antitumour effects of<i>nab</i>-paclitaxel in genetically engineered mice
Authors: Albrecht Neesse, Kristopher K Frese, Derek S Chan, Tashinga E Bapiro, William J Howat, Frances M Richards, Volker Ellenrieder, Duncan I Jodrell, David A Tuveson
Journal: Gut (2013)

<h3>Abstract</h3> Mechanical deformation applied to tendon at the tissue-scale is transferred to the microscale — including the extracellular matrix (ECM), the pericellular matrix (PCM), the cell and the nucleus — through a process known as strain transfer. Microscale strains, in turn, trigger biological activity that plays an important role in the maintenance of tendon phenotype and homeostasis. Although tendon predominantly experiences longitudinal tensile forces, transverse forces due to bony impingement have been implicated in both physiological (e.g., maintenance of the tendon insertion) and pathophysiological (e.g. insertional Achilles tendinopathy) processes. However, to our knowledge, prior studies have not characterized the micromechanical strain environment in the context of tendon impingement. Therefore, the objective of this study was to characterize the micromechanical strain environment in the impinged Achilles tendon insertion using a novel mouse hindlimb explant model in combination with finite element (FE) modeling. We hypothesized that impingement would generate large magnitudes of transverse compressive strain at the local matrix, PCM, and cell scales. Mouse hindlimb explants were imaged on a multiphoton microscope, and image stacks of the same population of tendon cells were obtained at the Achilles tendon insertion before and after dorsiflexion-induced impingement. Using an innovative multiphoton elastography approach, three-dimensional Green-Lagrange and principal strains were measured at the matrix scale, while longitudinal strain and aspect ratio were measured at the PCM and cell scales. Our results demonstrate that impingement generated substantial transverse compression at the matrix-scale, which led to longitudinal stretching of cells, an increase in cell aspect ratio, and — surprisingly — longitudinal <i>compression</i> of the tendon PCM. These experimental results were corroborated by an FE model developed to simulate the micromechanical environment in impinged regions of the Achilles tendon. Moreover, in both experiments and simulations, impingement-generated microscale stresses and strains were highly dependent on initial cell-cell gap spacing. Understanding the factors that influence the microscale strain environment generated by impingement could contribute to a more mechanistic understanding of impingement-induced tendinopathies and inform the development of approaches that disrupt the progression of pathology.
<i>Helicobacter pylori</i> resists arrest
Authors: R J OWEN
Journal: Gut (1999)

<h3>ABSTRACT</h3> <h3>Objective</h3> Resting-state functional MRI is increasingly used in the clinical setting and is now included in some diagnostic guidelines for severe brain injury patients. However, to ensure high-quality data, one should mitigate fMRI-related noise typical of this population. Therefore, we aimed to evaluate the ability of different preprocessing strategies to mitigate noise-related signal (<i>i</i>.<i>e</i>., in-scanner movement and physiological noise) in functional connectivity of traumatic brain injury patients. <h3>Methods</h3> We applied nine commonly used denoising strategies, combined into 17 pipelines, to 88 traumatic brain injury patients from the Epilepsy Bioinformatics Study for Anti-epileptogenic Therapy clinical trial (EpiBioS4Rx). Pipelines were evaluated by three quality control metrics across three exclusion regimes based on the participant’s head movement profile. <h3>Results</h3> While no pipeline eliminated noise effects on functional connectivity, some pipelines exhibited relatively high effectiveness depending on the exclusion regime. Once high-motion participants were excluded, the choice of denoising pipeline becomes secondary - although this strategy leads to substantial data loss. Pipelines combining spike regression with physiological regressors were the best performers, whereas pipelines that used automated data driven methods performed comparatively worse. <h3>Conclusion</h3> In this study, we report the first large-scale evaluation of denoising pipelines aimed at reducing noise-related functional connectivity in a clinical population known to be highly susceptible to in-scanner motion and significant anatomical abnormalities. If resting-state functional magnetic resonance is to be a successful clinical technique, it is crucial that procedures mitigating the effect of noise be systematically evaluated in the most challenging populations, such as traumatic brain injury datasets.
Prognosis and evolution of COPD patients hospitalized and treated with non invasive ventilation
Authors: Jesus Fernando Sanchez, Andres Humberto Vega, Natalia Fouz, Virginia Almadana, Patricia Guerrero, Maria Pavon, Concepcion Romero, Juan Polo, Teodoro Montemayor
Journal: European Respiratory Journal (2013)

OBJECTIVES:To evaluate the short and long term prognosis of COPD patients admitted in the hospital with an episode of hypercapnic ARF(acute respiratory failure) who required non invasive ventilation(NIV).  MATERIAL AND METHODS:Prospective study,consecutive inclusion of COPD patients admitted from Feb-09 to April-12 because ARF with acidosis and hypercapnia and who were treated with NIV.A group of patients were discharged home with BiPAP.We analysed mortality and readmissions from the discharge date to Sep-12.  RESULTS:N= 263,Mean age:73;Males 93%;Symptoms sleep apnea:15%; Obesity:37%;Smokers:14%;Ex-smokers:83%;The hospital mortality was 13%.Important factors in hospital mortality were: older age, more previous admissions, lower pH and higher PaCO2 at the begining and in the end,the need for higher FiO2 and patients with therapeutic effort limitation (p   During de follow up the outside mortality was 51.52% and the median survival rate was 770 days .Analyzing the survival rate between patients with BiPAP vs without,we obtained an average of 928 days in the first vs 778 days in the second group (p=n.s.).CONCLUSIONS:1.In our study, mortality during hospital admission of COPD patients with ARF treated with NIV is low.2.Mortality in these patients during follow-up was high, being higher in older patients and who had more number of readmissions; remaining similar in those who were discharged at home with and without NIV.
‘Benchside-to-Bedside’
Authors: Hensin Tsao, John English
Journal: British Journal of Dermatology (2007)

In this issue of the BJD, we introduce a new review series called ‘Benchside-to-Bedside’ or ‘B2B’. The B2B articles are meant to inform our readers about the latest developments in the scientific and technological worlds and how these advances have impacted, or potentially will impact, on dermatology. In the first of the B2B reviews, Dr Gilchrest and her colleagues review our current understanding of photoageing and novel approaches towards treatment. Over the course of the next year, there will be additional B2B reviews on various aspects of dermatology including melanoma genetics, psoriasis and procedural dermatology. Although the initial B2B reviews were solicited, we would also like to invite authors to submit ideas for other B2B articles. In general, the B2B reviews should be approximately 5000 words with up to five figures and/or tables. The essence of the B2B review is clinical translation or science that will directly impinge on clinical care within the next decade. Although a treatise on basic biological mechanisms or model systems of disease deserve appropriate attention in their own venue, the lack of translational ambition will compromise their suitability as a B2B article. We invite senior scientists, physicians or physician-scientists to partner with more junior trainees in the writing process as exercises such as these frequently offer mentoring opportunities. For those interested, please contact the BJD Editorial Office and submit a title, brief abstract, approximate length and composition of authorship team. If the topic is selected to proceed, authors will be granted an appropriate amount of time to complete the project. All invited B2B submissions will still be rigorously peer-reviewed to ensure accuracy and quality. A modest honorarium will be awarded to the authorship team if the B2B review is accepted for publication. The BJD editorial team is extremely excited to bring more relevant science into the general dermatologist’s world through these B2B reviews. Over the past 5 years, we have witnessed the completion of the Human Genome Project, unprecedented advances in imaging technologies and a strong push towards biologically informed therapies. This rapid pace of biomedical research also suggests that the practice of skin care will likely be revolutionized in the next 10–20 years. Busy clinicians are often confronted with an inordinate amount of technical information that brings both hope and an expected amount of uncertain trepidation. Fear not, the BJD will be with you as we all push beyond the new horizon...
Erythema elevatum diutinum with oral ulceration
Authors: T Maruthappu, S Tharakaram, E Calonje, P J Shirlaw, Jane Setterfield
Journal: British Journal of Dermatology (2012)

Journal Article Erythema elevatum diutinum with oral ulceration Get access T. Maruthappu, T. Maruthappu St John's Institute of Dermatology Search for other works by this author on: Oxford Academic Google Scholar S. Tharakaram, S. Tharakaram Department of Oral Medicine, Guy's and St Thomas' NHS Foundation Trust, King's College, London SE1 9RT, U.K Search for other works by this author on: Oxford Academic Google Scholar E. Calonje, E. Calonje St John's Institute of Dermatology Search for other works by this author on: Oxford Academic Google Scholar P.J. Shirlaw, P.J. Shirlaw Department of Dermatology, Medway NHS Foundation Trust, Gillingham, U.K Search for other works by this author on: Oxford Academic Google Scholar J. Setterfield J. Setterfield St John's Institute of DermatologyDepartment of Dermatology, Medway NHS Foundation Trust, Gillingham, U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 167, Issue 1, 1 July 2012, Pages 222–224, https://doi.org/10.1111/j.1365-2133.2012.10851.x Published: 01 July 2012
Intravenous immunoglobulin therapy for severe <i>Clostridium difficile</i> colitis
Authors: J Salcedo, S Keates, C Pothoulakis, M Warny, I Castagliuolo, J T LaMont, C P Kelly
Journal: Gut (1997)

Background —Many individuals have serum antibodies against Clostridium difficile toxins. Those with an impaired antitoxin response may be susceptible to recurrent, prolonged, or severe C difficile diarrhoea and colitis. Aims —To examine whether treatment with intravenous immunoglobulin might be effective in patients with severe pseudomembranous colitis unresponsive to standard antimicrobial therapy. Patients —Two patients with pseudomembranous colitis not responding to metronidazole and vancomycin were given normal pooled human immunoglobulin intravenously (200–300 mg/kg). Methods —Antibodies against C difficile toxins were measured in nine immunoglobulin preparations by ELISA and by cytotoxin neutralisation assay. Results —Both patients responded quickly as shown by resolution of diarrhoea, abdominal tenderness, and distension. All immunoglobulin preparations tested contained IgG against C difficile toxins A and B by ELISA and neutralised the cytotoxic activity of C difficile toxins in vitro at IgG concentrations of 0.4–1.6 mg/ml. Conclusion —Passive immunotherapy with intravenous immunoglobulin may be a useful addition to antibiotic therapy for severe, refractory C difficile colitis. IgG antitoxin is present in standard immunoglobulin preparations and C difficile toxin neutralising activity is evident at IgG concentrations which are readily achieved in the serum by intravenous immunoglobulin administration.
Antiviral effect of ribavirin in early non-responders to interferon monotherapy assessed by kinetics of hepatitis C virus RNA and hepatitis C virus core antigen
Authors: Françoise Lunel, Pascal Veillon, Isabelle Fouchard-Hubert, Véronique Loustaud-Ratti, Armand Abergel, Christine Silvain, Hervé Rifflet, Alain Blanchi, Xavier Causse, Yannick Bacq, Christopher Payan
Journal: Journal of Hepatology (2003)
Cognitive Impairment Associated With Chemotherapy for Cancer: Report of a Workshop
Authors: Ian F. Tannock, Tim A. Ahles, Patricia A. Ganz, Frits S. van Dam
Journal: Journal of Clinical Oncology (2004)

Cognitive dysfunction may occur in some patients who receive chemotherapy. We provide a summary of an April 2003 workshop on this topic, that included medical oncologists, radiologists, clinical and experimental psychologists, and patient advocates. Current studies indicate that cognitive deficits are often subtle, although they are observed consistently in a proportion of patients, may be durable, and can be disabling. Deficits have been observed in a range of cognitive functions. Underlying mechanisms are unknown, although preliminary studies suggest there may be genetic predisposition and that cognitive impairment may be accompanied by changes in the brain detectable by neuroimaging. The following priorities were established for future research: (1) large-scale clinical studies that use both a longitudinal design and concurrent evaluation of patients with cancer who do not receive chemotherapy-such studies should address the probability and magnitude of cognitive deficits, factors that predict them, and underlying mechanisms; (2) exploration of discrepancies between subjective reports of cognitive dysfunction and the objective results of cognitive testing; (3) studies of cognitive function in patients receiving treatment for diseases other than breast cancer, and in both men and women, to address the hypothesis that underlying mechanisms relate to changes in serum levels of sex hormones and/or to chemotherapy-induced menopause; (4) development of interventions to alleviate these problems; and (5) development of animal models and the use of imaging techniques to address mechanisms that might cause cognitive impairment associated with chemotherapy.
Function and form in the developing cardiovascular system
Authors: David Sedmera
Journal: Cardiovascular Research (2011)

Function of the developing heart is dictated by changes in its morphology. For simplicity, we distinguish four stages with different contraction mechanics and conduction parameters. Straight or looped tubular hearts, similar to those of invertebrates such as Drosophila or Ciona, operate as suction pumps and are characterized by a caudally localized pacemaker and slow, peristaltoid conduction and contraction. There is a complete occlusion of the lumen during systole. When the atrial and ventricular chambers appear, the preseptation heart is in many functional aspects similar to the adult heart, but the same function is achieved by different means. There are parallels in design among the hearts of lower vertebrates, such as a spongy ventricle without coronary vasculature and a myocardial atrioventricular canal. Even after septation, considerable maturation of cardiac morphology and function occurs during the foetal and early postnatal period.
Benefits and Harms of Doxycycline Treatment for Gulf War Veterans' Illnesses
Authors: Sam T. Donta
Journal: Annals of Internal Medicine (2004)

Background: It has been hypothesized that certain Mycoplasma species may cause Gulf War veterans' illnesses (GWVIs), chronic diseases characterized by pain, fatigue, and cognitive symptoms, and that affected patients may benefit from doxycycline treatment. Objective: To determine whether a 12-month course of doxycycline improves functional status in Gulf War veterans with GWVIs. Design: A randomized, double-blind, placebo-controlled clinical trial with 12 months of treatment and 6 additional months of follow-up. Setting: 26 U.S. Department of Veterans Affairs and 2 U.S. Department of Defense medical centers. Participants: 491 deployed Gulf War veterans with GWVIs and detectable Mycoplasma DNA in the blood. Intervention: Doxycycline, 200 mg, or matching placebo daily for 12 months. Measurements: The primary outcome was the proportion of participants who improved more than 7 units on the Physical Component Summary score of the Veterans Short Form-36 General Health Survey 12 months after randomization. Secondary outcomes were measures of pain, fatigue, and cognitive function and change in positivity for Mycoplasma species at 6, 12, and 18 months after randomization. Results: No statistically significant differences were found between the doxycycline and placebo groups for the primary outcome measure (43 of 238 participants [18.1%] vs. 42 of 243 participants [17.3%]; difference, 0.8 percentage point [95% CI, −6.5 to 8.0 percentage points]; P > 0.2) or for secondary outcome measures at 1 year. In addition, possible differences in outcomes at 3 and 6 months were not apparent at 9 or 18 months. Participants in the doxycycline group had a higher incidence of nausea and photosensitivity. Limitations: Adherence to treatment after 6 months was poor. Conclusion: Long-term treatment with doxycycline did not improve outcomes of GWVIs at 1 year.
High levels of Epstein-Barr virus in COPD
Authors: T. E. McManus, A-M. Marley, N. Baxter, S. N. Christie, J. S. Elborn, H. J. O'Neill, P. V. Coyle, J. C. Kidney
Journal: European Respiratory Journal (2008)

Latent viral infection has been implicated in the pathophysiology of chronic obstructive pulmonary disease (COPD). Epstein-Barr virus (EBV) is known to be important in pulmonary fibrosis. The current authors hypothesised that EBV is associated with the pathogenesis of COPD. Sputum samples were collected from patients both during exacerbations of COPD and when stable. A control group of smokers who did not have airways obstruction also had their sputum examined. The presence of EBV DNA was established and quantified using a real-time nucleic acid amplification assay. A total of 136 patients with COPD were recruited during an acute exacerbation and a total of 68 when stable. EBV was detected in 65 (48%) exacerbation cases and 31 (46%) stable patients. In the comparison group of 16 nonobstructed smokers, EBV was demonstrated in only one (6%) case. Risk of COPD in patients with EBV and who are smokers confers an odds ratio of 12.6. Epstein-Barr virus DNA is more frequently identified in the respiratory tract of chronic obstructive pulmonary disease patients in comparison with unaffected smokers. It is present both during exacerbation and when stable, suggesting that infection is persistent. Smokers who do not develop chronic obstructive pulmonary disease rarely have Epstein-Barr virus in their sputum. This finding may be of importance in the pathogenesis of chronic obstructive pulmonary disease.