tbuckley/cabot-search huggingface dataset:
Reply to L. Celio et al and H. Ishiguro et al
Authors: Joseph A. Roscoe, Charles E. Heckler
Journal: Journal of Clinical Oncology (2013)

thought to be related to OLN were noted, but 67% and 33% of patients complained of grade 1 to 2 drowsiness and dizziness, respectively.These events prompted a reduction in dose or duration of OLN; nevertheless, efficacy was retained.In Japan, the per-cycle cost of OLN used in the trial was approximately ¥2,000 (equivalent to approximately $22), and that of aprepitant was about ¥15,000 ($167).The cost of prochlorperazine per cycle in the study by Roscoe et al 1 was about ¥120 ($1.3).In line with the cost of standard chemotherapyfor example, the cost of doxorubicin and cyclophosphamide per cycle is about ¥20,000 ($222)-the medication for supportive care is as expensive as the antineoplastics.Therefore, antipsychotics such as prochlorperazine and OLN are not only effective for prevention of chemotherapy-induced nausea and vomiting, but also highly cost-effective.Reconsideration of the antiemetics guideline may be important, especially when pharmacoeconomics for developing countries are concerned.With the use of inexpensive antipsychotics in addition to dexamethasone and a first-generation 5-HT RA, palonosetron and a neurokinin-1 receptor antagonist add little other than expense.Large randomized clinical trials with a placebo are difficult to conduct without financial support from pharmaceutical companies.Therefore, clinical trials that are designed to study noninferiority of cost-saving strategies are rarely conducted.Until the data clearly indicate that the next-generation 5-HT RAs and/or neurokinin-1-receptor antagonists are superior to the more cost-effective regimen, which uses dexamethasone, a first-generation 5-HT RA, and antipsychotics, this regimen may serve as an alternative, especially for a medically underserved population.
S8 The National COPD Resources and Outcomes Project (NCROP): action plan achievement since 2007
Authors: J. F. O'Reilly, N. A. Pursey, C. M. Roberts, R. A. Stone
Journal: Thorax (2010)

<h3>Introduction and Objectives</h3> In 2007, 100 acute respiratory units participated in the NCROP, a randomised controlled study to assess whether reciprocal peer review could facilitate service improvement. We identified themes in desired improvements and evaluated success in meeting action plan aims. <h3>Methods</h3> Units were paired and randomised into intervention or control arms (54:46). Intervention teams undertook reciprocal peer review in 2007 and documented action plans for service improvement. In 2010, intervention units self-assessed their progress in achieving action plans. Qualitative responses were analysed using a grouped themes approach to derive action plan themes. <h3>Results</h3> Data were received from 41 of 54 intervention units (76%). The Abstract S8 Table 1 shows the distribution of themes and action plan outcomes. <h3>Conclusions</h3> Action plan themes related predominantly to development of multi-disciplinary teams across primary and secondary care and to specialist service provision. Most aims were fully achieved in a third of units and partially achieved in a similar number. Palliative care plans were less prevalent although at least partially successful in two thirds. Overall change was greater than in the 1 year assessment of the NCROP audit 2008.1
Consort 2010 statement: extension to cluster randomised trials
Authors: M. K. Campbell, G. Piaggio, D. R. Elbourne, D. G. Altman
Journal: BMJ (2012)

<h3>Abstract</h3> In age-related neurodegenerative disease, like Alzheimer’s and Parkinson’s disease, disease-specific proteins become aggregation-prone and form amyloid-like deposits. Depletion of SERF proteins ameliorates this toxic process in worm- and human cell models for disease. Whether SERF modifies amyloid pathology in mammalian brain, however, has remained unknown. Here, we generated SERF2 brain-specific knockout mice which, unlike full body knockout mice, were viable, and showed no major behavioral and cognitive abnormalities. We combined these knockout mice with the APPPS1 mouse model for human amyloid beta aggregation. Using structure-specific amyloid dyes, previously used to distinguish amyloid polymorphisms in human brain, we show that knockout of SERF2 alters the structure of amyloid fibrils and deposits. Moreover, scanning transmission electron microscopy revealed thicker, shorter and more densely packed amyloid in absence of SERF2. Altogether, our data reveal pleiotropic functions of SERF in development and aging and support a function as a modifier of amyloid aggregation in mammalian brain. Our results indicate that single cellular factors like SERF can determine the structural outcome of amyloid aggregation, offering possibilities for polymorphism-based disease interventions.
Modeling of C/EBPα Mutant Acute Myeloid Leukemia Reveals a Common Expression Signature of Committed Myeloid Leukemia-Initiating Cells
Authors: Peggy Kirstetter, Mikkel B. Schuster, Oksana Bereshchenko, Susan Moore, Heidi Dvinge, Elke Kurz, Kim Theilgaard-Mönch, Robert Månsson, Thomas Å. Pedersen, Thomas Pabst, Evelin Schrock, Bo T. Porse, Sten Eirik W. Jacobsen, Paul Bertone, Daniel G. Tenen, Claus Nerlov
Journal: Cancer Cell (2008)
Paralog Re-Emergence: A Novel, Historically Contingent Mechanism in the Evolution of Antimicrobial Resistance
Authors: Nichola J. Hawkins, Hans J. Cools, Helge Sierotzki, Michael W. Shaw, Wolfgang Knogge, Steven L. Kelly, Diane E. Kelly, Bart A. Fraaije
Journal: Molecular Biology and Evolution (2014)

Evolution of resistance to drugs and pesticides poses a serious threat to human health and agricultural production. CYP51 encodes the target site of azole fungicides, widely used clinically and in agriculture. Azole resistance can evolve due to point mutations or overexpression of CYP51, and previous studies have shown that fungicide-resistant alleles have arisen by de novo mutation. Paralogs CYP51A and CYP51B are found in filamentous ascomycetes, but CYP51A has been lost from multiple lineages. Here, we show that in the barley pathogen Rhynchosporium commune, re-emergence of CYP51A constitutes a novel mechanism for the evolution of resistance to azoles. Pyrosequencing analysis of historical barley leaf samples from a unique long-term experiment from 1892 to 2008 indicates that the majority of the R. commune population lacked CYP51A until 1985, after which the frequency of CYP51A rapidly increased. Functional analysis demonstrates that CYP51A retains the same substrate as CYP51B, but with different transcriptional regulation. Phylogenetic analyses show that the origin of CYP51A far predates azole use, and newly sequenced Rhynchosporium genomes show CYP51A persisting in the R. commune lineage rather than being regained by horizontal gene transfer; therefore, CYP51A re-emergence provides an example of adaptation to novel compounds by selection from standing genetic variation.
Respiratory muscle strength in the elderly. Correlates and reference values. Cardiovascular Health Study Research Group.
Authors: P L Enright, R A Kronmal, T A Manolio, M B Schenker, R E Hyatt
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Maximal inspiratory pressure (MIP) was assessed in 4,443 ambulatory participants of the Cardiovascular Health Study, 65 yr of age and older, sampled from four communities. Maximal expiratory pressure (MEP) was also measured in 790 participants from a single clinic. Positive predictors of MIP included male sex, FVC, handgrip strength, and higher levels of lean body mass (or low bioelectric resistance). Negative predictors were age, current smoking, self-reported fair to poor general health, and waist size. Both participant and technician learning effects were noted, but there was no independent effect of race, hypertension, cardiovascular disease, or diabetes. A healthy subgroup was identified by excluding current smokers, those with fair to poor general health, or an FEV1 less than 65% of predicted. Mean values determined from the healthy group were 57/116 cm H2O (MIP/MEP) for women, and 83/174 for men. Lower limits of the normal range (fifth percentiles) were 45 to 60% of the mean predicted values. The reference equations derived from this group of healthy 65 to 85-yr-olds may be used by pulmonary function laboratories and respiratory therapists who evaluate the respiratory muscle strength of elderly patients.
Non-specific fluorescent whitener stains in the rapid recognition of pulmonary dirofilariasis: a report of 20 cases.
Authors: L K Green, M Q Ansari, M R Schwartz, J Y Ro, L C Alpert
Journal: Thorax (1994)

Solitary lung nodules in humans caused by the dog parasite Dirofilaria immitis are steadily increasing in number. The organisms can be easily missed in haematoxylin and eosin stained tissue when they are degenerated and pale staining.The value of Tinopal CBS-X (TCBS-X) and Calcofluor white (CFW), two rapid, inexpensive, simple non-specific fluorescent whitening stains, were assessed in the identification of these worms. Deparaffinised rehydrated tissue slides prepared from the pulmonary nodules were stained for one minute in 1% w/v aqueous solutions of TCBS-X or CFW, counterstained, coverslipped, and viewed with a fluorescent microscope.The stains demonstrated the intact worm and worm fragments in 20 cases of pulmonary dirofilariasis collected from hospitals in Houston. The filariae and fragments of filariae stained bright green while the background tissue stained red, delineating the internal structures of the worm.Dirofilariasis should be included in the differential diagnosis of subpleural masses, and non-specific fluorescent whitening stains can help in the rapid recognition of the fragmented organism in cytological or surgical material.
Medical care delivery at the Inaugural Youth Olympic Games Singapore 2010
Authors: Jason Kok Kiong Chia, Keng Boon Tay, Pillai Suresh, Patrick Schamasch, Manikavasagam Jegathesan, Margo Mountjoy, Weng Kee Lim, Peng Ju Lwa, Cheong Yoong Wong
Journal: British Journal of Sports Medicine (2011)

Context Mass gatherings such as the Youth Olympic Games require medical services for large populations with special needs specific to elite competitive youth athletes. The location of the Games in a heavily populated city with dispersed competition venues provides unique challenges. Objective To describe the planning and delivery of medical services and to provide data for future planning. Setting Singapore. One large multipurpose clinic was set up in the Games Village as well as medical posts at competitive venues for 26 sports for onsite coverage. Period of coverage: 10 August 2010 to 28 August 2010. Participants A total of 1,337 medical encounters ranging from athletes to officials and volunteers who received medical care from a spectrum of medical professionals. Major outcome measures Number of cases attended to at the Games Village medical centres and the medical posts at the competition venues, utilisation of medical services, and the pattern of these injuries and referral patterns to hospitals. Results Medical encounters for non-athletes represented 40.9% of the total medical encounters. The rate of heat illnesses was low for athletes at 1.7% ( N = 13). The total hospitalisation rate was low at 1.7% ( n = 23). Utilisation of onsite pharmacy and physiotherapy services were high at 45.2% ( n = 887) and 37.8% ( n = 743), respectively, of the encounters for all support services. Conclusion The dispersed nature of the Games venues provided challenges to the organisation of medical cover for the participants. Organisers in future Games can make use of the data to plan for future Games of a similar nature.
Persistent severe gastrointestinal bleeding in a man with metastatic somatostatinoma
Authors: Crispin O Musumba, Muniba Usman-Saeed, Paul O'Toole, Steven Powell, Howard L Smart
Journal: Gut (2011)

A 50-year-old man with known metastatic pancreatic somatostatinoma was admitted with a 1-day history of haematemesis, melaena and haematochezia. Following an initial diagnosis 14 years earlier, he underwent distal pancreatectomy and splenectomy, followed by lateral hepatectomy a year later for residual hepatic disease, as well as biliary stenting for malignant obstructive jaundice. He was subsequently started on sunitinib, and his disease had remained stable before this presentation. At admission, he was haemodynamically stable, with haemoglobin concentration of 6.2 g/dl and platelet count of 126×109/l. Other blood tests were unremarkable. Oesophagogastroduodenoscopy revealed a large amount of blood in the stomach, portal hypertensive gastropathy and multiple gastric and duodenal varices, but no active bleeding from these or the biliary stent. …
Bilateral pallidal deep brain stimulation for the treatment of patients with dystonia-choreoathetosis cerebral palsy: a prospective pilot study
Authors: Marie Vidailhet, Jerome Yelnik, Christelle Lagrange, Valerie Fraix, David Grabli, Stephane Thobois, Pierre Burbaud, Marie-Laure Welter, Jin Xie-Brustolin, Maria-Clara Coelho Braga, Claire Ardouin, Virginie Czernecki, Hélène Klinger, Stephan Chabardes, Eric Seigneuret, Patrick Mertens, Emmanuel Cuny, Soledad Navarro, Philippe Cornu, Alim-Louis Benabid, Jean-Francois LeBas, Didier Dormont, Marc Hermier, Kathy Dujardin, Serge Blond, Pierre Krystkowiak, Alain Destée, Eric Bardinet, Yves Agid, Paul Krack, Emmanuel Broussolle, Pierre Pollak
Journal: The Lancet Neurology (2009)
Predicting non-invasive ventilation failure in children from the SpO2/FiO2 (SF) ratio
Authors: Juan Mayordomo-Colunga, Martí Pons, Yolanda López, M. José Solana, Corsino Rey, Pablo Martínez-Camblor, Antonio Rodríguez-Núñez, Jesús López-Herce, Alberto Medina, Clara Abadesso, M. Ángeles García-Teresa, Mirella Gáboli, Milagros García-López, María González-Sánchez, Paula Madurga-Revilla, Amelia González-Calvar, Eider Oñate
Journal: Intensive Care Medicine (2013)
Prospective Validation of a Prognostic Score to Improve Patient Selection for Oncology Phase I Trials
Authors: Hendrik-Tobias Arkenau, Jorge Barriuso, David Olmos, Joo Ern Ang, Johann de Bono, Ian Judson, Stan Kaye
Journal: Journal of Clinical Oncology (2009)

Purpose With the aim of improving patient selection for phase I trials, we previously performed a retrospective analysis of 212 phase I oncology patients where we were able to develop a prognostic score predicting overall survival (OS). This prospective study was performed to test the validity of the prognostic score. Patients and Methods On the basis of our retrospective multivariate analysis, three factors were associated with poor survival (albumin &lt; 35 g/L, lactate dehydrogenase [LDH] &gt; upper limit of normal [ULN], and &gt; two sites of metastases). We integrated these into a prognostic score ranging from 0 to 3 and analyzed this score in a prospectively selected cohort of 78 patients enrolled onto phase I trials. Results All patients had progressive disease before study entry. The median age was 56 years (range, 18 to 79 years). After a median follow-up time of 27.3 weeks, patients with a prognostic score of 0 to 1 (n = 43) had superior OS (33.0 weeks; 95% CI, 24 to 42 weeks) compared with patients with a score of 2 to 3 (n = 35; 15.7 weeks; 95% CI, 11 to 21 weeks). Our multivariate analysis confirmed that our prognostic score was an independent marker for OS, with a hazard ratio of 1.4 (95% CI, 1.02 to 1.9; P = .036). Conclusion This is the first prospective analysis confirming that a prognostic score based on objective markers, including albumin less than 35 g/L, LDH more than ULN, and more than two sites of metastasis, is a helpful tool in the process of patient selection for phase I trial entry.
Relationships with Test-Tubes: Where's the Reciprocity?
Authors: Kelly Fryer-Edwards, Stephanie M. Fullerton
Journal: The American Journal of Bioethics (2006)

Click to increase image sizeClick to decrease image size ACKNOWLEDGMENTS We would like to thank Susan Brown Trinidad for her critical feedback on this commentary. Both authors are supported in part by the University of Washington Center for Genomics and Healthcare Equality, a Center of Excellence in ELSI Research (CEER) funded by the National Human Genome Research Institute (##HG003374).
Is indeterminate colitis really indeterminate?
Authors: T. Ngatchu, D. Cash, G. Langman
Journal: Gut (2010)

A 26-year-old student was referred to the Gastroenterology Department by the general practitioner because of persistent rectal bleeding. At presentation, the patient reported a 3-month history of recurrent frank blood per rectum on defaecation. He had had similar episodes 2–3 years previously but this had subsided. This was not present all the time and his stools were of variable consistency. There was no associated abdominal pain. His appetite was normal and his weight stable. He was not on any medication. The patient originated from Sudan and …
INCORPORATION OF RADIOIRON INTO MYOGLOBIN IN AN IN VITRO SYSTEM*
Authors: Gerald T. Perkoff, Herbert C. Schwartz, Frank H. Tyler
Journal: Journal of Clinical Investigation (1959)

It is known that avian erythrocytes (1,2), bone marrow (3), liver, muscle and kidney (4) are capable of synthesizing heme in vitro.Glycine, 8-amiiinolevulinic acid, porphobilinogen and proto- porphyrin (2, 5-7) are among the known inter- mediates in this process.Per unit weight, muscle is one of the least active tissues in the synthesis of heme, and few studies have been made of the process in this tissue.Previously (8. 9),we have described procedures for the isolation of myoglobin which were found suitable for the preparation of this protein for physical characterization.In order to gain fur- ther information about the metabolism of myo- globin, these procedures for myoglobin isolation have been applied to a study of radioiron incorporation into myoglobin in dog and human muscle.In these studies, the myoglobin heme was labeled with Fe59 in a system similar to that described by others for avian erythrocytes (2).By this means it has been possible to demonstrate that extracts of dog and human muscle can use radioiron for the formation of myoglobin.It appears that heme synthesis in muscle is similar in many ways to that in other tissues. METHODSPreparation of extracts and incubationt mixture.Mongrel dogs were sacrificed by the intracardiac injection of 10 per cent pentobarbital.Three hundred to 500 Gm. of muscle was dissected from the hind limbs, trimmed free of fat and placed in a beaker over ice.The muscle was ground twice in an electric meat grinder.The brei was mixed with an equal volume of 0.15 M potassium chloride containing approximately 20 mg. each of penicillin and streptomycin and allowed to stand for 12 to
Screening for Diabetic Retinopathy
Authors: Paul Palmberg
Journal: Diabetes Care (2001)

In this issue, Malone et al. (1) use their analysis of the retinal photographs taken in the Diabetes Control and Complications Trial (DCCT) to try to challenge the well-established dictum that it is not useful to perform early screening (<5 years duration) for diabetic retinopathy in juvenile-onset type 1 diabetes. I share their enthusiasm for preventing vision loss; however, in my judgment, the data do not support their challenge, but rather strongly support the current recommendation.

Screening examinations or any tests performed in medicine should only be done when the results have a reasonable probability of altering the treatment, when the risk-to-benefit ratio of undergoing the test is favorable for the individual patient, and when the cost-to-benefit ratio is competitive with other uses of health care dollars. Early screening for diabetic retinopathy in juvenile-onset type 1 diabetes fails on all three counts.

First, consider that not one of the 1,613 patients screened for the DCCT at <5 years duration of diabetes had …
Nonuniform Concerted Evolution and Chloroplast Capture: Heterogeneity of Observed Introgression Patterns in Three Molecular Data Partition Phylogenies of Asian Mitella (Saxifragaceae)
Authors: Yudai Okuyama, Noriyuki Fujii, Michio Wakabayashi, Atsushi Kawakita, Manabu Ito, Mikio Watanabe, Noriaki Murakami, Makoto Kato
Journal: Molecular Biology and Evolution (2004)

Interspecific hybridization is one of the major factors leading to phylogenetic incongruence among loci, but the knowledge is still limited about the potential of each locus to introgress between species. By directly sequencing three DNA regions: chloroplast DNAs (matK gene and trnL-F noncoding region), the nuclear ribosomal external transcribed spacer (ETS) region, and internal transcribed spacer (ITS) regions, we construct three phylogenetic trees of Asian species of Mitella (Saxifragaceae), a genus of perennials in which natural hybrids are commonly observed. Within this genus, there is a significant topological conflict between chloroplast and nuclear phylogenies and also between the ETS and the ITS, which can be attributed to frequent hybridization within the lineage. Chloroplast DNAs show the most extensive introgression pattern, ITS regions show a moderate pattern, and the ETS region shows no evidence of introgression. Nonuniform concerted evolution best explains the difference in the introgression patterns between the ETS region and ITS regions, as the sequence heterogeneity of the ITS region within an individual genome is estimated to be twice that of an ETS in this lineage. Significant gene conversion patterns between two hybridizing taxa were observed in contiguous arrays of cloned ETS-ITS sequences, further confirming that only ITS regions have introgressed bidirectionally. The relatively slow concerted evolution in the ITS regions probably allows the coexistence of multiple alleles within a genome, whereas the strong concerted evolution in the ETS region rapidly eliminates heterogeneous alleles derived from other species, resulting in species delimitations highly concordant with those based on morphology. This finding indicates that the use of multiple molecular tools has the potential to reveal detailed organismal evolution processes involving interspecific hybridization, as an individual locus varies greatly in its potential to introgress between species.
Effects of methotrexate on normal articular cartilage in vitro and in vivo
Authors: J. Neidel, L. Sova, B. Schroers, F. Sintermann, O. Manzke, H. Bohlen
Journal: Annals of the Rheumatic Diseases (1998)

Methotrexate (MTX) has become the disease modifying drug of choice for the treatment of rheumatoid arthritis (RA). Direct effects of MTX on articular cartilage in vivo and in vitro were studied to determine possible adverse effects of the drug.For in vitro experiments, adult bovine articular cartilage explants were cultured in the presence of MTX (0 to 100 microM), and effects on DNA and matrix metabolism were studied. For in vivo studies, 48 adult female rabbits were treated with MTX (30 mg/kg/week intramuscularly) or placebo, respectively, for up to 12 weeks, and effects on the cartilage of the femoral condyles were assessed.In vitro, MTX dose dependently increased the uptake of [3H]-thymidine, and decreased incorporation of [3H]-d-uridine into chondrocytes with a half maximal effect at 0.03 microM, suggesting inhibition of thymidylate-synthetase activity by the drug. MTX also dose dependently reduced the proportion of chondrocytes in S-phase, as determined by flow cytometry. MTX did not affect LDH release from chondrocytes or the proportion of viable cells, nor did it change the rate of protein synthesis, proteoglycan synthesis, proteoglycan breakdown, or the hydrodynamic size of newly synthesised proteoglycans. In vivo, MTX did not appreciably affect proteoglycan synthesis of the chondrocytes, proteoglycan content of the cartilage matrix, density of the chondrocyte population, or histological integrity of the cartilage.The data suggest the absence of major adverse effects by MTX on articular cartilage proteoglycan metabolism. Chondrocyte DNA metabolism seems to be changed by MTX only in concentrations and exposition periods clearly exceeding those found in synovial fluid of RA patients receiving the commonly prescribed doses of the drug.