tbuckley/cabot-search huggingface dataset:
A disease activity score for polymyalgia rheumatica
Authors: B F Leeb
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To develop a composite score for measurement of disease activity in polymyalgia rheumatica (PMR) and assess its internal and external validity. <b>Methods:</b> A PMR activity score (AS) was designed and assessed for internal and external validity in two patient cohorts: 57 international patients evaluated primarily for development of the PMR-AS at baseline, weeks 4 and 24; and for validation, 24 Austrian patients assessed at baseline, week 4, and at a mean (SD) point of week 33.6 (24.5). The PMR-AS was calculated as: CRP (mg/dl)+VAS p (0–10)+VAS ph (0–10)+(MST (min)×0.1)+EUL (3–0); Cronbach's α was calculated. Factor analysis by linear regression was applied, and responses calculated on the basis of the PMR response criteria and the PMR-AS applied. PMR-AS values at different times were compared by paired <i>t</i> tests. <b>Results:</b> Cronbach's α for the composite score was 0.91 and 0.88 in the two cohorts. Factor analysis showed that each single item contributed significantly to the total score and the relative weight of each item in both cohorts was equally distributed. Mean PMR-AS at baseline was 27.54 and 28.72, respectively, at week 4, 5.99 and 8.99, and at the final visit 5.35 and 5.92 (NS). PMR-AS values at baseline and at later visits were significantly different (p&lt;0.0001). PMR-AS values &lt;7 indicated low disease activity, 7–17 medium disease activity, and &gt;17 high PMR activity. In a third control cohort the PMR-AS correlated highly with patient's global assessment, patient satisfaction, and ESR (p&lt;0.001). <b>Conclusion:</b> The PMR-AS provides an easily applicable and valid tool for monitoring disease activity, and in combination with the PMR response criteria provides a better description of response.
Alterations in adenosine triphosphate and energy charge in cultured endothelial and P388D1 cells after oxidant injury.
Authors: R G Spragg, D B Hinshaw, P A Hyslop, I U Schraufstätter, C G Cochrane
Journal: Journal of Clinical Investigation (1985)

To investigate mechanisms whereby oxidant injury of cells results in cell dysfunction and death, cultured endothelial cells or P388D1 murine macrophage-like cells were exposed to oxidants including H2O2, O2-. (generated by the enzymatic oxidation of xanthine), or to stimulated polymorphonuclear leukocytes (PMN). Although Trypan Blue exclusion was not diminished before 30 min, cellular ATP was found to fall to less than 30% of control values within 3 min of exposure to 5 mM H2O2. Stimulated PMN plus P388D1 caused a 50% fall in cellular ATP levels. During the first minutes of oxidant injury, total adenylate content of cells fell by 85%. Cellular ADP increased 170%, AMP increased 900%, and an 83% loss of ATP was accompanied by a stoichiometric increase in IMP and inosine. Calculated energy charge [(ATP + 1/2 AMP)/(ATP + ADP + AMP)] fell from 0.95 to 0.66. Exposure of P388D1 to oligomycin plus 2-deoxyglucose (which inhibit oxidative and glycolytic generation of ATP, respectively) resulted in a rate of ATP fall similar to that induced by H2O2. In addition, nucleotide alterations induced by exposure to oligomycin plus 2-deoxyglucose were qualitatively similar to those induced by the oxidant. Loss of cell adenylates could not be explained by arrest of de novo purine synthesis or increased ATP consumption by the Na+-K+ ATPase or the mitochondrial F0-ATPase. These results indicate that H2O2 causes a rapid and profound fall in cellular ATP levels similar to that seen when ATP production is arrested by metabolic inhibitors.
A Survey of Liver Transplantation from Living Adult Donors in the United States
Authors: Robert S. Brown, Mark W. Russo, Michelle Lai, Mitchell L. Shiffman, Michael C. Richardson, James E. Everhart, Jay H. Hoofnagle
Journal: New England Journal of Medicine (2003)

The transplantation of the right lobe of a liver from a living adult donor into an adult recipient has been performed increasingly frequently in the United States. Although the use of grafts from living donors is standard practice in transplantation in children, their use in adults remains controversial.To study the use of liver transplantation from a living donor, we sent a 24-item questionnaire to all liver-transplantation programs in the United States. Data on indications, evaluation, and outcomes were analyzed with the use of univariate and multivariate methods. Data on recent transplantations were gathered from the Scientific Registry of Transplant Recipients and directly from the transplantation programs.Questionnaires were returned by 84 of the 122 programs (69 percent) describing the results of 449 adult-to-adult transplantations of partial livers from living donors that were performed in 42 centers. Fourteen centers had performed more than 10 such transplantations each and together accounted for 80 percent of such transplantations. Centers that performed such transplantations also performed more transplantations of livers from cadaveric donors and more transplantations from living donors in children than centers that did not perform the adult-to-adult procedure (P=0.002 and P=0.001, respectively). A total of 45 percent of potential donors who were evaluated eventually donated a lobe of their liver; 99 percent of these donors were genetically or emotionally related to the recipient. Complications in the donor were more frequent in the centers performing the fewest transplantations from living donors in adults and included biliary complications requiring intervention (in 6.0 percent), reoperation (in 4.5 percent), and death (in one donor [0.2 percent]). Among the recipients, 1.6 percent did not meet criteria for receipt of a cadaveric transplant; cancer, retransplantation, and acute liver failure were uncommon indications for transplantation from a living donor. Biliary complications occurred in 22.0 percent of recipients, and vascular complications occurred in 9.8 percent.Adult-to-adult liver transplantation from a living donor is increasingly performed in the United States but is concentrated in a few large-volume centers. Mortality among donors is low, but complications in the donor are relatively common.
Minimum unit price on alcohol would affect heavy drinkers 200 times more than moderate drinkers, study finds
Authors: A. O'Dowd
Journal: BMJ (2014)

Introducing a minimum unit price for alcohol would affect harmful drinkers 200 times more than low risk drinkers, a new study has concluded.

The study1—published in Clinical Medicine, the peer review journal for the Royal College of Physicians—said that a minimum unit pricing policy for alcohol was “exquisitely targeted” at the heaviest drinkers with cirrhosis. Researchers from the University of Southampton studied the amount and type of alcohol drunk by 404 patients with a range of liver disease in a large teaching hospital and asked the patients how much they paid for alcohol.

They found that patients with alcohol related cirrhosis drank on average the equivalent of four bottles of vodka each week and bought the …
Searching for a legend
Authors: J Gray
Journal: BMJ (1994)

Some years ago, one of my receptionists offered to lend me a book. She said she had never read anything so profoundly moving and she was sure that I would enjoy it. The book was William Horwood's Skallagrigg, and she was right. It was probably the best book I have ever read, combining as it did a complex web of ideas, plots, and subplots, interrelationships, and vivid descriptive writing. It was also educational, as it dealt with the subject of disability in a sensitive and enlightening way. Horwood wrote from first hand knowledge of the subject; his daughter had cerebral palsy.

When I heard that Skallagrigg was to be screened it seemed like a welcome and inevitable development of the …
Health related quality of life in multiple musculoskeletal diseases: SF-36 and EQ-5D in the DMC3 study
Authors: H S J Picavet
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To examine the health related quality of life of persons with one or more self reported musculoskeletal diseases, as measured by the short form 36 item health status survey (SF-36) and the Euroqol questionnaire (EQ-5D). <b>Methods:</b> A sample of Dutch inhabitants aged 25 years or more (n = 3664) participated in a questionnaire survey. Twelve lay descriptions of common musculoskeletal diseases were presented and the subjects were asked whether they had ever been told by a physician that they had any of these. Their responses were used to assess the prevalence of these conditions. Commonly used scores of SF-36 and descriptive scores from EQ-5D are presented, along with standardised differences between disease groups and the general population. <b>Results:</b> Subjects with musculoskeletal diseases had significantly lower scores on all SF-36 dimensions than those without musculoskeletal disease, especially for physical functioning (SF-36 score (SE), 75.2 (0.5) <i>v</i> 87.8 (0.5)); role limitations caused by physical problems (67.1 (0.9) <i>v</i> 85.8 (0.8)); and bodily pain (68.5 (0.5) <i>v</i> 84.1 (0.5)). The worst health related quality of life patterns were found for osteoarthritis of the hip, osteoporosis, rheumatoid arthritis, and fibromyalgia. Those with multiple musculoskeletal diseases had the poorest health related quality of life. Similar results were found for EQ-5D. <b>Conclusions:</b> All musculoskeletal diseases involve pain and reduced physical function. The coexistence of musculoskeletal diseases should be taken into account in research and clinical practice because of its high prevalence and its substantial impact on health related quality of life.
Does dynamic hyperinflation contribute to dyspnoea during exercise in patients with COPD?
Authors: Jordan A. Guenette, Katherine A. Webb, Denis E. O’Donnell
Journal: European Respiratory Journal (2011)

Dynamic hyperinflation (DH) during exercise occurs in most but not all patients with advanced chronic obstructive pulmonary disease (COPD). It is not known whether the presence or absence of DH has implications for dyspnoea and exercise tolerance. Therefore, we compared detailed ventilatory and sensory responses to exercise in hyperinflators and nonhyperinflators with moderate-to-severe COPD. Nonhyperinflators (n=65) were retrospectively identified from a sample of 427 patients and case-matched to a group of hyperinflators (n=65) based on sex, age, body mass index and % predicted forced expiratory volume in 1 s. Resting pulmonary function and constant work rate cycle exercise responses were compared. Hyperinflators decreased inspiratory capacity (IC) from rest to peak exercise by 0.46±0.24 L whereas the nonhyperinflators increased IC by 0.10±0.15 L (p&lt;0.0001). There were no significant group differences in endurance time (9.11±5.98 versus 8.87±5.24 min) or dyspnoea intensity for any given time or ventilation. An inflection in tidal volume versus ventilation occurred in the majority of nonhyperinflators (n=61) and hyperinflators (n=62) at a similar time and ventilation. Mechanical constraints on tidal volume expansion and the attendant rise in dyspnoea intensity were similar in both groups. Dyspnoea intensity during exercise was associated with progressive mechanical constraints on tidal volume expansion regardless of the presence of DH.
Anti-CCP antibody and rheumatoid factor concentrations predict greater disease activity in men with rheumatoid arthritis
Authors: B. J. Miriovsky, K. Michaud, G. M. Thiele, J. R. O'Dell, G. W. Cannon, G. Kerr, J. S. Richards, D. Johnson, L. Caplan, A. Reimold, R. Hooker, T. R. Mikuls
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objective</h3> To examine associations of anti-cyclic citrullinated peptide (aCCP) antibody and rheumatoid factor (RF) concentrations with future disease activity in men with rheumatoid arthritis (RA). <h3>Methods</h3> Outcome measures were examined in male US veterans with RA and included (1) proportion of observations in remission (disease activity score (DAS28) ≤2.6); (2) remission for ≥3 consecutive months; and (3) area under the curve (AUC) for DAS28. The associations of autoantibody concentration (per 100 unit increments) with outcomes were examined using multivariate regression. <h3>Results</h3> 826 men with RA were included in the analysis; the mean (SD) age was 65 (10.5) years and follow-up was for 2.6 (1.3) years. Most were aCCP (75%) and RF (80%) positive. After multivariate adjustment, aCCP (OR 0.93; 95% CI 0.89 to 0.96) and RF concentrations (OR 0.92; 95% CI 0.90 to 0.94) were associated with a lower odds of remission, a lower proportion of observation in remission (p=0.017 and p=0.002, respectively) and greater AUC DAS28 (p=0.092 and p=0.007, respectively). Among patients with discordant autoantibody status, higher concentrations of both aCCP and RF trended towards an inverse association with remission (OR 0.93; 95% CI 0.83 to 1.05 and OR 0.80; 95% CI 0.59 to 1.10, respectively). <h3>Conclusions</h3> Higher aCCP concentrations (particularly in RF-positive patients) are associated with increased disease activity in US veterans with RA, indicating that aCCP concentration is predictive of future disease outcomes in men.
Evidence for a second class of S-adenosylmethionine riboswitches and other regulatory RNA motifs in alpha-proteobacteria.
Authors: Keith A Corbino, Jeffrey E Barrick, Jinsoo Lim, Rüdiger Welz, Brian J Tucker, Izabela Puskarz, Maumita Mandal, Noam D Rudnick, Ronald R Breaker
Journal: Genome biology (2005)

Abstract Background Riboswitches are RNA elements in the 5' untranslated leaders of bacterial mRNAs that directly sense the levels of specific metabolites with a structurally conserved aptamer domain to regulate expression of downstream genes. Riboswitches are most common in the genomes of low GC Gram-positive bacteria (for example, Bacillus subtilis contains examples of all known riboswitches), and some riboswitch classes seem to be restricted to this group. Results We used comparative sequence analysis and structural probing to identify five RNA elements ( serC , speF , suhB , ybhL , and metA ) that reside in the intergenic regions of Agrobacterium tumefaciens and many other α-proteobacteria. One of these, the metA motif, is found upstream of methionine biosynthesis genes and binds S -adenosylmethionine (SAM). This natural aptamer most likely functions as a SAM riboswitch (SAM-II) with a consensus sequence and structure that is distinct from the class of SAM riboswitches (SAM-I) predominantly found in Gram-positive bacteria. The minimal functional SAM-II aptamer consists of fewer than 70 nucleotides, which form a single stem and a pseudoknot. Despite its simple architecture and lower affinity for SAM, the SAM-II aptamer strongly discriminates against related compounds. Conclusion SAM-II is the only metabolite-binding riboswitch class identified so far that is not found in Gram-positive bacteria, and its existence demonstrates that biological systems can use multiple RNA structures to sense a single chemical compound. The two SAM riboswitches might be 'RNA World' relics that were selectively retained in certain bacterial lineages or new motifs that have emerged since the divergence of the major bacterial groups.
A SERIOUS AND LITTLE-RECOGNIZED DEFICIT IN POST-WAR PSYCHIATRIC RESIDENCY TRAINING
Authors: ROBERT T. MORSE
Journal: American Journal of Psychiatry (1959)

It is my conviction that direct and constructive communication with all whose attitudes affect the patient's illness can ultimately bring about real improvement in the therapeutic efficacy of psychiatry generally, effect a closer collaboration between the psychiatrist and his non-psychiatric medical colleagues, and notably increase the usefulness of the psychiatrist in the field of medicine.
The Many Spaces of uPAR: Delivery of Theranostic Agents and Nanobins to Multiple Tumor Compartments through a Single Target
Authors: Thomas V. O'Halloran, Richard Ahn, Patrick Hankins, Elden Swindell, Andrew P. Mazar
Journal: Theranostics (2013)

The urokinase plasminogen activator (uPA) system is a proteolytic system comprised of uPA, a cell surface receptor for uPA (uPAR), and an inhibitor of uPA (PAI-1) and is implicated in many aspects of tumor growth and metastasis.The uPA system has been identified in nearly all solid tumors examined to date as well as several hematological malignancies.In adults, transient expression of the uPA system is observed during wound healing and inflammatory processes while only limited expression is identified in healthy, quiescent tissue.Members of the uPA system are expressed not only on cancer cells but also on tumor-associated stromal cells.These factors make the uPA system an ideal therapeutic target for cancer therapies.To date most therapeutics targeted at the uPA system have been inhibitors of either the uPA-uPAR interaction or uPA proteolysis but have not shown robust anti-tumor activity.There is now mounting evidence that uPAR participates in a complex signaling network central to its role in cancer progression, which provides a basis for the hypothesis that uPAR may be a marker for cancer stem cells.Several new uPAR-directed therapies have recently been developed based on this new information.A monoclonal antibody has been developed that disrupts the interactions of uPAR with signaling partners and is poised to enter the clinic.In addition, nanoscale drug delivery vehicles targeted to the uPA system using monoclonal antibodies, without disrupting the normal functioning of the system, are also in development.This review will highlight some of these new discoveries and the new uPA system-based therapeutic approaches that have arisen from them.
Genetic variants within the MAP kinase signalling network and anti-TNF treatment response in rheumatoid arthritis patients
Authors: L. R. Coulthard, J. C. Taylor, S. Eyre, J. I. Robinson, A. G. Wilson, J. D. Isaacs, K. Hyrich, P. Emery, A. Barton, J. H. Barrett, A. W. Morgan, M. F. McDermott
Journal: Annals of the Rheumatic Diseases (2010)

Rheumatoid arthritis (RA) does not always respond to available treatments, including tumour necrosis factor (TNF) antagonists. A study was undertaken to investigate whether genetic variation within genes, encoding proteins in the p38 signalling network, contributes to the variable response to TNF antagonists.1102 UK Caucasian patients with RA receiving anti-TNF therapy (infliximab, adalimumab and etanercept) were genotyped for 38 pairwise-tagging single nucleotide polymorphisms (SNPs) spanning 12 candidate genes from the p38 network. Regression analyses were performed to test association between genotype and treatment response at 6 months using both absolute change in DAS28 (Disease Activity Score across 28 joints) and European League Against Rheumatism (EULAR) improvement criteria. Stratified analyses were performed to investigate association with individual therapies.Seven SNPs, in five genes, were associated with improvement in DAS28 at 6 months at a nominal 0.1 significance level, jointly explaining 3% of variance in outcome in a model adjusting for other predictors. These encoded proteins both upstream (MKK6) and downstream (MAPKAPK2, MSK1, MSK2) of p38, and MAPK14, the p38-α isoform of p38 MAPK. One SNP (rs2716191 in MAP2K6) was associated with EULAR response at the 0.1 level. SNPs generally showed greater correlation with response to infliximab and adalimumab, but not to etanercept.More SNPs than would be expected by chance, mapping to the p38 signalling network, showed association with the anti-TNF response as a whole, and particularly with the response to infliximab and adalimumab. Validation of these findings in independent cohorts is warranted.
Repair of photoaged dermal matrix by topical application of a cosmetic ‘antiageing’ product
Authors: R.E.B. Watson, S.P. Long, J.J. Bowden, J.Y. Bastrilles, S.P. Barton, C.E.M. Griffiths
Journal: British Journal of Dermatology (2007)

Background Photoaged skin is characterized by coarse and fine wrinkles. The mechanism of wrinkle formation appears to involve changes to components of the dermal extracellular matrix. Topical treatment with all‐trans retinoic acid (RA) can repair photoaged dermal matrix; this is regarded as the 'gold standard' against which repair agents are judged. To date, little is known regarding the ability of over‐the‐counter 'antiageing' products to repair photoaged skin. Objectives We used a modified occluded patch test to ascertain whether topical applications of cosmetic 'antiageing' products are able to repair photoaged human skin. Methods Commercially available test products [basic moisturizer, 'antiageing' cream containing different active complex levels (6% active: lipopentapeptide, white lupin peptides, antioxidants, retinyl palmitate; 2% active: lipopentapeptide, white lupin peptides, antioxidants)] were applied under occlusion for 12 days prior to biopsy and histological assessment in photoaged volunteers (n =9). RA was used as a positive control. Results In agreement with previous studies, the patch‐test study revealed that RA produced significant fibrillin‐1 deposition in the papillary dermis (P <0·01) but had little effect on procollagen I or matrix metalloproteinase‐1 expression. The 6% total active complex formulation, however, increased the deposition of fibrillin‐1 and procollagen I (P <0·01, P <0·05, respectively). Conclusions This study indicates that in an in vivo 12‐day patch test an over‐the‐counter cosmetic product can induce changes in photoaged dermal extracellular matrix, which are indicative of repair.
Genetic Testing for Lung Cancer: Reflex Versus Clinical Selection
Authors: Paul A. Bunn, Robert C. Doebele
Journal: Journal of Clinical Oncology (2011)

Interest in activating “driver” mutations in tyrosine kinase genes as therapeutic targets in non-small cell lung cancer (NSCLC) has peaked recently due to the discovery that EGFR tyrosine kinase inhibitors (TKIs) produce higher response rates, longer progression free survival (PFS) times, less toxicity, improved symptom control, improved quality of life, and greater convenience compared to cytotoxic chemotherapy in the first line treatment of advanced NSCLC patients harboring EGFR activating mutations (1–4). A more recent study showed that advanced NSCLC patients whose tumors harbor EML4-ALK fusion genes, who are treated with an ALK TKI termed crizotinib, have high response rates and long progression free survival times that are similar to those of NSCLC patients harboring EGFR mutations treated with erlotinib (5,6).
Lung function defects in treated pulmonary tuberculosis patients
Authors: André F.S. Amaral, Sonia Coton, Bernet Kato, Wan C. Tan, Michael Studnicka, Christer Janson, Thorarinn Gislason, David Mannino, Eric D. Bateman, Sonia Buist, Peter G.J. Burney
Journal: European Respiratory Journal (2015)

We are grateful to Aggarwal and colleagues for their interest in our paper [1]. They are correct to point out the limitations of cross-sectional studies, particularly when they rely on recalled information, and we discussed these at some length in the paper. However, evidence needs to be evaluated in the round. Not all error is biased; the outcomes (lung function) that we used were measured objectively and, as the results were not shared with the participants at the time, are unlikely to have influenced their answers to questions about a past history of tuberculosis. We agree, of course, that objective measures of tuberculosis would have been preferable, but it seems more likely that these would have reduced random error and so strengthened the current findings. We hope to add these to future investigations in the Burden of Obstructive Lung Disease (BOLD) cohort. A history of tuberculosis is an important risk factor for obstructive disease and low lung function <http://ow.ly/TXvgO>