tbuckley/cabot-search huggingface dataset:
Rates of upper gastrointestinal endoscopy and gastro-oesophageal malignancy outcomes
Authors: Alexander C Ford, Laura F Glenn, Paul Moayyedi
Journal: Gut (2013)

We read the excellent paper by Shawihdi et al with interest.1 The authors demonstrated in a retrospective study, using hospital episode statistics, that outcomes from gastro-oesophageal malignancy were worse among patients from practices with a low referral rate for upper gastrointestinal (GI) endoscopy.

While the authors address some weaknesses in their data, we believe they have not highlighted all problems with their approach. As with all observational data, there is the problem of confounding, which often cannot be completely corrected in analyses. However, the major concern is that they looked at aggregate data, not individual patient data. This is open to the ecological fallacy; what is seen in populations …
Cytokine Profile and ST-Elevation Myocardial Infarction
Authors: James T. Willerson, Edward T.H. Yeh, Emerson C. Perin
Journal: Circulation Research (2012)

Give me fever and I can cure any disease."-HippocratesI n this issue of Circulation Research, Ammirati et al 1 have obtained data from 109 patients with ST-elevation myocardial infarction (STEMI) with the highest interleukin (IL)-6 levels compared with 96 patients with the lowest IL6 levels to identify differences in interacting cytokine levels that might predict clinical outcomes.They identified 2 different modules of patients from their circulating cytokine levels.One module included STEMI patients with increases in IL6(+) IL10(+), greater systolic dysfunction at discharge, and death at 6 months compared with IL6(-) IL10(+) STEMI patients.Combining IL10 with IL6 derived from the 2 identified cytokine modules provided a risk index combined-cytokineindex called the "AC-Index" that outperformed any single cytokine in the prediction of systolic dysfunction and death.The authors concluded that simultaneous elevation of IL6 and IL10 levels distinguishes STEMI patients with poorer clinical outcomes from other STEMI patients.They suggest that this information may have potential clinical implications for riskoriented stratification and for immune-moderating therapies.
Growth pattern of serous cystic neoplasms of the pancreas: observational study with long-term magnetic resonance surveillance and recommendations for treatment
Authors: Giuseppe Malleo, Claudio Bassi, Roberto Rossini, Riccardo Manfredi, Giovanni Butturini, Marta Massignani, Marina Paini, Paolo Pederzoli, Roberto Salvia
Journal: Gut (2011)

Background and aims The natural history and growth pattern of pancreatic serous cystic neoplasms (SCNs) are not well understood. This study was designed in order to get insight into the growth rate of SCNs and to suggest recommendations for their management. Methods Patients with well-documented incidentally discovered or minimally symptomatic SCNs who underwent yearly surveillance MRI were analysed using a linear mixed model. The growth rate and the effects of different fixed factors (sex, personal history of other non-pancreatic malignancies, radiological pattern, clinical presentation, tumour site) and random factors (age and tumour diameter at the time of diagnosis) on tumour growth were investigated. Results Study population consisted of 145 patients. Estimated overall mean growth rate was 0.28 cm/year, but the growth curve analysis showed a different trend between the first 7 years after the baseline evaluation (growth rate of 0.1 cm/year) and the subsequent period (years 7 to 10, growth rate of 0.6 cm/year, p<0.0001). Tests for fixed effects demonstrated that an oligocystic/macrocystic pattern and a personal history of other tumours are significant predictors of a more rapid mean tumour growth (p<0.0001 and 0.022, growth rates of 0.34 cm/year). Furthermore, tumour growth significantly increased with age (p=0.0001). Conclusion Overall, SCNs grow slowly, and an initial non-operative approach is feasible in all the asymptomatic or minimally symptomatic patients. The oligocystic/macrocystic variant, a history of other non-pancreatic malignancies and patients' age impact on tumour growth. In any case, a significant growth is unlikely to occur before 7 years from the baseline evaluation. Tumour size at the time of diagnosis should not be used for decisional purposes.
International Union of Pharmacology. LVI. Ghrelin Receptor Nomenclature, Distribution, and Function
Authors: Anthony P. Davenport, Tom I. Bonner, Steven M. Foord, Anthony J. Harmar, Richard R. Neubig, Jean-Philippe Pin, Michael Spedding, Masayasu Kojima, Keniji Kangawa
Journal: Pharmacological Reviews (2005)

Ghrelin is a 28-amino acid peptide originally isolated from rat stomach and is cleaved from a 117-amino acid precursor. The sequence of the mature peptide from rats and mice differs by two amino acids from that of human ghrelin. Alternative splicing of the ghrelin gene transcript can result in the translation of a second biologically active peptide, des-Gln<sup>14</sup>-ghrelin. Both peptides have a unique post-translational modification, octanoylation of Ser<sup>3</sup>, which is essential for the binding to receptors in hypothalamus and pituitary and stimulating the release of growth hormone from the pituitary. The growth hormone secretagogue receptor (GHS-R1a, Swiss-Prot code Q92847, LocusLink ID 2693), a rhodopsin-like seven transmembrane spanning G protein-coupled receptors belonging to Family A, was cloned in 1996 from the pituitary and hypothalamus and shown to be the target of growth hormone secretagogues (GHS), a class of synthetic peptide and nonpeptide compounds causing growth hormone release from the anterior pituitary. In 1999, ghrelin was identified as the endogenous cognate ligand for this receptor. The purpose of this review is to propose an official International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) nomenclature designating GHS-R1a as the ghrelin receptor to follow the convention of naming receptors after the endogenous agonist, abbreviated where necessary to GRLN.
NSAIDs in osteoarthritis: irreplaceable or troublesome guidelines? * Commentary
Authors: J Bjordal
Journal: British Journal of Sports Medicine (2006)

Current treatment of osteoarthritis relies too heavily on pharmacological approaches

In sports medicine, non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for relieving pain and modulating inflammation in acute injuries. They have also been used in osteoarthritis (OA) of the knee, which is one of the most common disorders of modern society. Besides genetic and sex dispositions, previous knee injury in sports is one of several identified risk factors. Half of the 8 million patients with OA in the United Kingdom use NSAIDs regularly, and this contributes to the annual estimated 2000 deaths from NSAID side effects in this country.1,2 NSAID safety has been debated widely over the last few months, and the increased risk of cardiovascular infarcts finally led to withdrawal of Vioxx and marketing restrictions for other cyclo-oxygenase-2 inhibitors (coxibs). The high risk of gastrointestinal side effects from non-specific NSAIDs has long been known, whereas coxibs were thought to be safer and equally effective. The NSAID safety controversy seems to have left a gap in OA management. Some doctors and patients with OA have appeared in the media complaining that they miss having coxibs to prescribe/take. The lower risk of gastrointestinal side effects from coxibs compared with unspecific NSAIDs makes this understandable. Some doctors have turned back to …
Rituximab Plus Chlorambucil As First-Line Treatment for Chronic Lymphocytic Leukemia: Final Analysis of an Open-Label Phase II Study
Authors: Peter Hillmen, John G. Gribben, George A. Follows, Donald Milligan, Hazem A. Sayala, Paul Moreton, David G. Oscier, Claire E. Dearden, Daniel B. Kennedy, Andrew R. Pettitt, Amit Nathwani, Abraham Varghese, Dena Cohen, Andy Rawstron, Stephan Oertel, Christopher F.E. Pocock
Journal: Journal of Clinical Oncology (2014)

Most patients with chronic lymphocytic leukemia (CLL) are elderly and/or have comorbidities that may make them ineligible for fludarabine-based treatment. For this population, chlorambucil monotherapy is an appropriate therapeutic option; however, response rates with chlorambucil are low, and more effective treatments are needed. This trial was designed to assess how the addition of rituximab to chlorambucil (R-chlorambucil) would affect safety and efficacy in patients with CLL.Patients with first-line CLL were treated with rituximab (375 mg/m(2) on day 1, cycle one, and 500 mg/m(2) thereafter) plus chlorambucil (10 mg/m(2)/d all cycles; day 1 through 7) for six 28-day cycles. For patients not achieving complete response (CR), six additional cycles of chlorambucil alone could be administered. The primary end point of the study was safety.A total of 100 patients were treated with R-chlorambucil, with a median follow-up of 30 months. Median age of patients was 70 years (range, 43 to 86 years), with patients having a median of seven comorbidities. Hematologic toxicities accounted for most grade 3/4 adverse events reported, with neutropenia and lymphopenia both occurring in 41% of patients and leukopenia in 23%. Overall response rates were 84%, with CR achieved in 10% of patients. Median progression-free survival was 23.5 months; median overall survival was not reached.These results compare favorably with previously published results for chlorambucil monotherapy, suggesting that the addition of rituximab to chlorambucil may improve efficacy with no unexpected adverse events. R-chlorambucil may improve outcome for patients who are ineligible for fludarabine-based treatments.
Mechanical ventilatory constraints of upper- vs. lower-body exercise in healthy adults
Authors: Nicholas Tiller, Ian Campbell, Lee Romer
Journal: European Respiratory Journal (2013)

Introduction:  There are unequivocal differences in the cardiorespiratory response to exercise performed with the upper-limbs compared to the lower-limbs, but the mechanical-ventilatory responses to exercise have not been systematically studied.  Aim:  To assess mechanical-ventilatory and perceptual responses to upper- vs. lower-body exercise in healthy adults.  Methods:  Breathing pattern, operating lung volumes, oesophageal pressure (Poe) derived measures of respiratory mechanics, and dyspnoea (Borg CR10) were assessed in eight recreationally-active men [24 ± 5 (SD) y] during two maximal graded exercise tests, performed with the upper- or lower-body in a randomised/counterbalanced order on separate days. Exercise tests were repeated at work rates equivalent to 20, 40, 60, 80 and 100% maximum arm ventilation (VEarm).  Results:  There was a significant increase in respiratory frequency ( P   P   P  = 0.002 at 100% VEarm) with only limited evidence of expiratory flow limitation. Arm-cranking resulted in greater neuro-mechanical uncoupling at all exercise ventilations as reflected by smaller changes in lung volume in response to a given respiratory motor output (pressure per breath), but dyspnoea was not different between modes.  Conclusions:  Dynamic hyperinflation and neuro-mechanical uncoupling do not contribute to dyspnoea during upper-body exercise when respiratory motor output is maintained.
The Specificity of Peptides Bound to Human Histocompatibility Leukocyte Antigen (HLA)-B27 Influences the Prevalence of Arthritis in HLA-B27 Transgenic Rats
Authors: Ming Zhou, Alain Sayad, William A. Simmons, Richard C. Jones, Shanna D. Maika, Nimman Satumtira, Martha L. Dorris, Simon J. Gaskell, Robert S. Bordoli, R. Balfour Sartor, Clive A. Slaughter, James A. Richardson, Robert E. Hammer, Joel D. Taurog
Journal: The Journal of Experimental Medicine (1998)

Human histocompatibility leukocyte antigen B27 is highly associated with the rheumatic diseases termed spondyloarthropathies, but the mechanism is not known. B27 transgenic rats develop a spontaneous disease resembling the human spondyloarthropathies that includes arthritis and colitis. To investigate whether this disease requires the binding of specific peptides to B27, we made a minigene construct in which a peptide from influenza nucleoprotein, NP383-391 (SRYWAIRTR), which binds B27 with high affinity, is targeted directly to the ER by the signal peptide of the adenovirus E3/gp19 protein. Rats transgenic for this minigene, NP1, were made and bred with B27 rats. The production of the NP383-391 peptide in B27(+)NP1(+) rats was confirmed immunologically and by mass spectrometry. The NP1 product displaced approximately 90% of the 3H-Arg-labeled endogenous peptide fraction in B27(+)NP1(+) spleen cells. Male B27(+)NP1(+) rats had a significantly reduced prevalence of arthritis, compared with B27(+)NP- males or B27(+) males with a control construct, NP2, whereas colitis was not significantly affected by the NP1 transgene. These findings support the hypothesis that B27-related arthritis requires binding of a specific peptide or set of peptides to B27, and they demonstrate a method for efficient transgenic targeting of peptides to the ER.
After the fall: Religious capacities and the error theory of morality
Authors: Michael Stingl, John Collier
Journal: Behavioral and Brain Sciences (2004)

The target article proposes an error theory for religious belief. In contrast, moral beliefs are typically not counterintuitive, and some moral cognition and motivation is functional. Error theories for moral belief try to reduce morality to nonmoral psychological capacities because objective moral beliefs seem too fragile in a competitive environment. An error theory for religious belief makes this unnecessary.
Palmar fasciitis and polyarthritis syndrome: a sign of ovarian malignancy
Authors: Mahinda Yogarajah, Jade Soh, Breck Lord, Nicholas Goddard, Richard Stratton
Journal: Journal of the Royal Society of Medicine (2008)

Summary Highlighting the importance and recognition of palmar fasciitis and polyarthritis syndrome, a paraneoplastic syndrome related to ovarian and other malignancies.
Primary intrapulmonary neurogenic sarcoma with hypertrophic pulmonary osteoarthropathy and asbestosis
Authors: P. K. Caves, J. Jacques
Journal: Thorax (1971)

A case of primary intrapulmonary neurogenic sarcoma with hypertrophic pulmonary osteoarthropathy and asbestosis is described. The essential histological features of this rare tumour are detailed, and the five authentic cases previously reported are reviewed. The pathogenesis of hypertrophic pulmonary osteoarthropathy and its occurrence in this case are discussed. After surgical removal of the tumour recurrence appeared in the chest within six months. It responded poorly to radiotherapy, and death from metastases occurred 16 months after operation.
Impact of Ischemia and Procurement Conditions on Gene Expression in Renal Cell Carcinoma
Authors: Nick W. Liu, Thomas Sanford, Ramaprasad Srinivasan, Jack L. Liu, Kiranpreet Khurana, Olga Aprelikova, Vladimir Valero, Charles Bechert, Robert Worrell, Peter A. Pinto, Youfeng Yang, Maria Merino, W. Marston Linehan, Gennady Bratslavsky
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Previous studies have shown that ischemia alters gene expression in normal and malignant tissues. There are no studies that evaluated effects of ischemia in renal tumors. This study examines the impact of ischemia and tissue procurement conditions on RNA integrity and gene expression in renal cell carcinoma. Experimental Design: Ten renal tumors were resected without renal hilar clamping from 10 patients with renal clear cell carcinoma. Immediately after tumor resection, a piece of tumor was snap frozen. Remaining tumor samples were stored at 4°C, 22°C, and 37°C and frozen at 5, 30, 60, 120, and 240 minutes. Histopathologic evaluation was conducted on all tissue samples, and only those with greater than 80% tumor were selected for further analysis. RNA integrity was confirmed by electropherograms and quantitated using RNA integrity number index. Altered gene expression was assessed by paired, two-sample t test between the zero time point and aliquots from various conditions obtained from the same tumor. Results: One hundred and forty microarrays were conducted. Some RNA degradation was observed 240 minutes after resection at 37°C. The expression of more than 4,000 genes was significantly altered by ischemia times or storage conditions. The greatest gene expression changes were observed with longer ischemia time and warmer tissue procurement conditions. Conclusion: RNA from kidney cancer remains intact for up to 4 hours post surgical resection regardless of storage conditions. Despite excellent RNA preservation, time after resection and procurement conditions significantly influence gene expression profiles. Meticulous attention to preacquisition variables is of paramount importance for accurate tumor profiling. Clin Cancer Res; 19(1); 42–49. ©2012 AACR.
Brief Report: Defining the Nasal Transcriptome in Granulomatosis With Polyangiitis (Wegener's)
Authors: Peter C. Grayson, Katrina Steiling, Michael Platt, Jeffrey S. Berman, Xiaohui Zhang, Ji Xiao, Yuriy O. Alekseyev, Gang Liu, Paul A. Monach, Mariana J. Kaplan, Avrum Spira, Peter A. Merkel
Journal: Arthritis & Rheumatology (2015)

Objective To determine whether disease processes related to granulomatosis with polyangiitis (Wegener's) (GPA) are reflected in gene expression profiles of the nasal mucosa. Methods Nasal brushings of the inferior turbinate were obtained from 32 patients with GPA (10 with active nasal disease, 13 with prior nasal disease, and 9 with no history of nasal disease) and a composite comparator group with and without inflammatory nasal disease (12 healthy people, 15 with sarcoidosis, and 8 with allergic rhinitis). Differential gene expression was assessed between subgroups of GPA and comparators. Results A total of 339 genes were differentially expressed between the GPA and comparator groups (absolute fold change &gt;1.5; false discovery rate &lt;0.05). Top canonical pathways up‐regulated in nasal brushings from patients with GPA included granulocyte adhesion and diapedesis ( P = 8.6 −22 ), agranulocyte adhesion and diapedesis ( P = 1.3 −14 ), IL10 signaling ( P = 3.0 −11 ), LXR/RXR activation ( P = 4.3 −11 ), and TREM1 signaling ( P = 9.0 −11 ). A set of genes differentially expressed in GPA independently of nasal disease activity status included genes related to epithelial barrier integrity (fibronectin 1, desmosomal proteins) and several matricellular proteins (e.g., osteonectin, osteopontin). Significant overlap of differentially expressed genes was observed between active and prior nasal disease GPA subgroups. Peripheral blood neutrophil and mononuclear gene expression levels associated with GPA were similarly altered in the nasal gene expression profiles of patients with active or prior nasal disease. Conclusion Profiling the nasal transcriptome in GPA reveals gene expression signatures related to innate immunity, inflammatory cell chemotaxis, extracellular matrix composition, and epithelial barrier integrity. Thus, airway‐based expression profiling is feasible and informative in GPA.
How Society Shapes the Health Gradient: Work-Related Health Inequalities in a Comparative Perspective
Authors: Christopher B. McLeod, Peter A. Hall, Arjumand Siddiqi, Clyde Hertzman
Journal: Annual Review of Public Health (2012)

Analyses in comparative political economy have the potential to contribute to understanding health inequalities within and between societies. This article uses a varieties of capitalism approach that groups high-income countries into coordinated market economies (CME) and liberal market economies (LME) with different labor market institutions and degrees of employment and unemployment protection that may give rise to or mediate work-related health inequalities. We illustrate this approach by presenting two longitudinal comparative studies of unemployment and health in Germany and the United States, an archetypical CME and LME. We find large differences in the relationship between unemployment and health across labor-market and institutional contexts, and these also vary by educational status. Unemployed Americans, especially of low education or not in receipt of unemployment benefits, have the poorest health outcomes. We argue for the development of a broader comparative research agenda on work-related health inequalities that incorporates life course perspectives.
Systematic Phylogenomic Evidence of en Bloc Duplication of the Ancestral 8p11.21-8p21.3-like Region
Authors: A. Vienne
Journal: Molecular Biology and Evolution (2003)

The genomes of many higher organisms, including plants and bony fish, frequently undergo polyploidization, and it has long been hypothesized that these, and other, large-scale genomic duplications have played an important role in the major evolutionary transitions of our past. Here we build upon an early work to show that the human genomic region 8p11.21-8p21.3 has three paralogous regions on chromosomes 4, 5, and 10 that were produced by two rounds of duplications after the protostomian-deuterostomian split and before the actinopterygian-sarcopterygian split. We base our analysis on the phylogenetic reconstruction of the evolutionary history of 38 gene families located in these regions. Using an alignment centered on protein domains, three different phylogenetic methods, and divergence time estimation, this analysis gives more support in favor of two ancient polyploidization events in the vertebrate ancestral genome.
Chemotherapy Compared With Biochemotherapy for the Treatment of Metastatic Melanoma: A Meta-Analysis of 18 Trials Involving 2,621 Patients
Authors: Natalie J. Ives, Rebecca L. Stowe, Paul Lorigan, Keith Wheatley
Journal: Journal of Clinical Oncology (2007)

To assess the effect of adding interferon-alpha (IFN) +/- interleukin-2 (IL-2) to chemotherapy in patients with metastatic melanoma. METHODS A published data meta-analysis of trials of biochemotherapy versus chemotherapy in patients with metastatic melanoma was undertaken. End points evaluated were rates of partial response (PR), complete response (CR) and overall (partial + complete) response (OR); response duration; progression-free survival; overall survival (OS); and toxicity. The only subgroup analysis performed was by type of immunotherapy, with trials divided according to whether IFN only or IFN and IL-2 were administered in the biochemotherapy arm.Eighteen randomized trials were identified: 11 trials of chemotherapy +/- IFN and seven trials of chemotherapy +/- IFN and IL-2. More than 2,600 patients were entered onto the trials, with 555 responses and 2,039 deaths. There was a clear benefit for biochemotherapy for PR (odds ratio = 0.66; 95% CI, 0.53 to 0.82; P = .0001), CR (odds ratio = 0.50; 95% CI, 0.35 to 0.73; P = .0003) and OR (odds ratio = 0.59; 95% CI, 0.49 to 0.72; P < .00001). For OR, these benefits were significant for both the IFN (odds ratio = 0.60; 95% CI, 0.46 to 0.79; P = .0002) and IFN + IL-2 (odds ratio = 0.58; 95% CI, 0.44 to 0.77; P = .0001) subgroups. In contrast, there was no benefit overall in OS (odds ratio = 0.99; 95% CI, 0.91 to 1.08; P = .9), but there was evidence of heterogeneity of treatment effect between the individual trials (P = .006).This meta-analysis provides a comprehensive summary of all the data currently available, and shows that although biochemotherapy clearly improves response rates, this does not appear to translate into a survival benefit.
Selective TRAIL-Induced Apoptosis in Dysplastic Neoplasia of the Colon May Lead to New Neoadjuvant or Adjuvant Therapies
Authors: Niklas Finnberg, Wafik S. El-Deiry
Journal: Clinical Cancer Research (2006)

In this issue of Clinical Cancer Research , Jalving et al. ([1][1]) shows that treatment with recombinant human tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL) triggers apoptosis in human dysplastic colorectal adenomas of the colon. These observations suggest the potential to