tbuckley/cabot-search huggingface dataset:
Abstract P2-11-11: Clinical utility of a radiosensitivity molecular signature: Identification of breast cancer patients that benefit from RT boost dose
Authors: JF Torres-Roca, N Servant, MA Bollet, SA Eschrich
Journal: Cancer Research (2013)

Abstract Objective: In previous studies we developed a radiosensitivity molecular signature (RSI) that has been independently validated in multiple disease sites (n = 652) including breast cancer 1-3. Here, we test whether RSI can be utilized to identify sub-populations in breast cancer that benefit from RT dose intensification (boost). Methods: RSI was tested in two published breast cancer datasets (n = 342) 4. Patients were selected if they had experienced a local recurrence within the first 10 years after primary treatment or were free of local recurrence for a minimum of 10 years after treatment. Primary treatment was initial breast-conserving surgery plus whole breast RT with/without a boost (no boost, n = 94, low boost &amp;lt; = 66 Gy, n = 148, high boost &amp;gt;66 Gy, n = 100). Patients were treated between January 1984 and November 2002. RSI was generated as previously described 1-3. Time to local recurrence was used as the endpoint for the study. Results: Increased RT dose (&amp;gt;66 Gy vs. &amp;lt; = 66 Gy) resulted in a slight decrease in local recurrence risk that did not reach statistical significance (p = 0.11). As hypothesized, RSI-high patients (more radioresistant) were sensitive to increased RT dose (high RT-boost) which resulted in a decrease in local recurrence (HR = 0.3418, CI 0.1195-0.9777, p = 0.036). In contrast, RSI-low and intermediate patients had similar local recurrence risk independent of RT dose (RSI-low HR = 0.7687, CI 0.3404-1.736, p = 0.53, RSI-intermediate, HR = 0.9115, CI 0.5125-1.621, p = 0.75). Importantly, there were no statistical differences in the distribution of known prognostic variables between RSI-determined sub-populations (RSI-low, intermediate, high) including age, T-stage, margin status, nodal status, adjuvant chemotherapy, hormonal therapy, grade and molecular subtype. Conclusions: RSI identifies a sub-population of breast cancer patients that benefit from increased RT-dose. RSI may be utilized to support RT-based decisions (high boost vs. low boost vs. no boost) in breast cancer. 1. Eschrich S, Fulp WJ, Pawitan Y, et al: Validation of a Radiosensitivity Molecular Signature in Breast Cancer. Clin Cancer Res, 2012 2. Eschrich S, Zhang H, Zhao H, et al: Systems biology modeling of the radiation sensitivity network: a biomarker discovery platform. Int J Radiat Oncol Biol Phys 75:497-505, 2009 3. Eschrich SA, Pramana J, Zhang H, et al: A gene expression model of intrinsic tumor radiosensitivity: prediction of response and prognosis after chemoradiation. Int J Radiat Oncol Biol Phys 75:489-96, 2009 4. Servant N, Bollet MA, Halfwerk H, et al: Search for a gene expression signature of breast cancer local recurrence in young women. Clin Cancer Res 18:1704-15, 2012. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-11-11.
Time Will Be of the Essence in Treating Alzheimer Disease
Authors: Roger N. Rosenberg
Journal: JAMA (2006)

BackgroundDecreased cerebrospinal fluid (CSF) β-amyloid 42 (Aβ42) concentration, but not Aβ40 concentration, is a biomarker for Alzheimer disease. This Aβ42 concentration decrease in CSF likely reflects precipitation of Aβ42 in amyloid plaques in brain parenchyma. This pathogenic plaque deposition begins years before the clinical expression of dementia in Alzheimer disease. Normal aging and the presence of the apolipoprotein E (APOE*4) allele are the most important known risk factors for Alzheimer disease.ObjectiveTo estimate the interactive effects of normal aging and presence of the APOE*4 allele on CSF Aβ42 concentration in adults with normal cognition across the life span.DesignThe CSF was collected in the morning after an overnight fast using Sprotte 24-g atraumatic spinal needles. The CSF Aβ42 and Aβ40 concentrations were measured in the 10th milliliter of CSF collected by sandwich enzyme-linked immunosorbent assay. The APOE genotype was determined by a restriction digest method.SubjectsOne hundred eighty-four community volunteers with normal cognition aged 21 to 88 years.ResultsThe CSF Aβ42, but not the Aβ40, concentration decreased significantly with age. There was a sharp decrease in CSF Aβ42 concentration beginning in the sixth decade in subjects with the APOE*4 allele. This age-associated decrease in CSF Aβ42 concentration was significantly and substantially greater in subjects with the APOE*4 allele compared with those without the APOE*4 allele.ConclusionsThese CSF Aβ42 findings are consistent with acceleration by the APOE*4 allele of pathogenic Aβ42 brain deposition starting in later middle age in persons with normal cognition.
Data from Frequency&amp;ndash;Volume Charts versus Symptom Scores and Quality of Life Score in Men with Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia
Authors: Ger E.P.M. van Venrooij, Ger E.P.M. van Venrooij, Mardy D. Eckhardt, Mardy D. Eckhardt, Karel W.H. Gisolf, Karel W.H. Gisolf, Tom A. Boon, Tom A. Boon
Journal: European Urology (2001)
Abstract PR5: A phase II study of sorafenib in patients with stage IV non-small cell lung cancer (NSCLC) with a K-Ras mutation
Authors: Wouter W. Mellema, Anne-Marie C. Dingemans, Harry J.M. Groen, Atie van Wijk, Sjaak Burgers, Peter W.A. Kunst, Frederik B. Thunnissen, Daniëlle A.M. Heideman, Egbert F. Smit
Journal: Clinical Cancer Research (2012)

Abstract Background: In a pilot study (1) we found sorafenib to display clinical activity against patients with K-Ras positive NSCLC, sufficient for formal phase II testing. Methods: Patients with K-Ras mutated NSCLC that progressed after at least 1 platinum containing regimen with adequate organ reserve, ECOG 0–2, who provided written informed consent according to local IRB regulations were eligible. A tumor biopsy confirming the presence of a K-Ras mutation was mandatory. Treatment consisted of sorafenib 400 mg BID until disease progression or unacceptable toxicity. Dose reductions and delays were specified per protocol in the face of CTC toxicities grade 3 and 4. Primary endpoint: Rate of No Progression (NPR) at 6 weeks. Secondary endpoints: duration of response, progression free survival (PFS), overall survival and treatment related toxicities. A 2-stage design was implemented (Simon's optimal design; p0=40%, p1=60%, alpha=0.05, beta=0.20) for a total number of 48 pts. Results: 59 patients were entered between May 1st 2010 and February 18 2011. Median age was 58 (range 46–79) years, 17 Male/42 Female, ECOG PS 0/1/2 23/32/4. 57 patients started treatment. At 6 weeks 5 PR, 25 SD, 27 PD were observed; NPR 52.6%. Fifteen patients stopped treatment before 6 weeks, of which 10 patients stopped due to (clinical) progression. Median duration of treatment was 9 (range 0–62) weeks, 2 patients are still on treatment. Median duration of response was 32 (range 5–58) weeks. Median PFS was 2.3 months, median OS was 4.9 months, 14 patients still alive. Dose modifications were realized in 21 patients, of whom 4 discontinued treatment. Most reported adverse events were fatigue (6.4%), hand-foot reaction (5.7%), dyspnea (5.6%), anorexia (3.7%) diarrhea (3.6%) and cough (3.6%). Sorafenib related grade 3-4 toxicity was reported in 10 patients. Five patients with grade 3 skin toxicity, 4 patients with grade 3 gastrointestinal toxicity and 1 patient with both grade 3 metabolic abnormalities and a grade 3 pneumonitis. Conclusion: Treatment with sorafenib has relevant clinical activity in patients with K-Ras mutational status. Further randomized study with this agent is warranted. This abstract is also presented as Poster B18.
Modifying Effects of the <i>HFE</i> Polymorphisms on the Association between Lead Burden and Cognitive Decline
Authors: Florence T. Wang, Howard Hu, Joel Schwartz, Jennifer Weuve, Avron S. Spiro, David Sparrow, Huiling Nie, Edwin K. Silverman, Scott T. Weiss, Robert O. Wright
Journal: Environmental Health Perspectives (2007)

As iron and lead promote oxidative damage, and hemochromatosis (HFE) gene polymorphisms increase body iron burden, HFE variant alleles may modify the lead burden and cognitive decline relationship.Our goal was to assess the modifying effects of HFE variants on the lead burden and cognitive decline relation in older adults.We measured tibia and patella lead using K-X-ray fluorescence (1991-1999) among participants of the Normative Aging Study, a longitudinal study of community-dwelling men from greater Boston. We assessed cognitive function with the Mini-Mental State Examination (MMSE) twice (1993-1998 and 1995-2000) and genotyped participants for HFE polymorphisms. We estimated the adjusted mean differences in lead-associated annual cognitive decline across HFE genotype groups (n = 358).Higher tibia lead was associated with steeper cognitive decline among participants with at least one HFE variant allele compared with men with only wild-type alleles (p interaction = 0.03), such that a 15 microg/g increase in tibia lead was associated with a 0.2 point annual decrement in MMSE score among HFE variant allele carriers. This difference in scores among men with at least one variant allele was comparable to the difference in baseline MMSE scores that we observed among men who were 4 years apart in age. Moreover, the deleterious association between tibia lead and cognitive decline appeared progressively worse in participants with increasingly more copies of HFE variant alleles (p-trend = 0.008). Results for patella lead were similar.Our findings suggest that HFE polymorphisms greatly enhance susceptibility to lead-related cognitive impairment in a pattern consistent with allelelic dose.
FEBRILE REACTIONS ACCOMPANYING THE READMINISTRATION OF SULFATHIAZOLE
Authors: RICHARD H. LYONS
Journal: JAMA (1942)

Since sulfathiazole has been utilized frequently and successfully in the treatment of various infectious diseases, information concerning its undesirable reactions is of considerable importance. It was observed that some patients who had been given one course of sulfathiazole without any deleterious effects had fever, often preceded by chills, shortly after the start of a second course of the drug.<sup>1</sup>The fever appeared to be associated with the administration of the sulfathiazole rather than with the infection for which the second course of the drug was given. When the sulfathiazole was discontinued, the fever subsided. This type of reaction occurred in 36 per cent of the patients receiving a second course of the drug and is presumably due to a hypersensitivity to sulfathiazole. <h3>METHODS AND RESULTS</h3><h3>Experiments on the Frequency and Time of the Febrile Reaction.—</h3> Fifty-three afebrile patients who received one course of sulfathiazole without complications were given a
Promoter and lineage independent anti-silencing activity of the A2 ubiquitous chromatin opening element for optimized human pluripotent stem cell-based gene therapy
Authors: Mania Ackermann, Nico Lachmann, Susann Hartung, Reto Eggenschwiler, Nils Pfaff, Christine Happle, Adele Mucci, Gudrun Göhring, Heiner Niemann, Gesine Hansen, Axel Schambach, Tobias Cantz, Robert Zweigerdt, Thomas Moritz
Journal: Biomaterials (2013)
DANGER FROM THE CARELESS USE OF THE ALKALOID OF THE SUPRARENAL GLAND.
Authors: BARTON H. POTTS
Journal: JAMA (1906)

I feel that it is time to speak a word of caution and warning in regard to the indiscriminate and careless use of a preparation that is being widely advertised and prescribed as harmless, viz., the alkaloid of the suprarenal gland. In its proper field and under careful observation, this preparation is very valuable and of great assistance to the operator. But I feel that the present reckless use will result in harm and cast opprobrium on a really valuable remedy. Several cases that have come under my care have brought this sharply to my notice. <h3>DANGER TO THE MUCOUS MEMBRANE.</h3> Application of this remedy to the mucous membrane causes an intense shrinking in the caliber of the blood vessels, and when this effect wears away there is a dilatation to and beyond normal. The later effect of the preparation is to raise the blood pressure very decidedly, and when
ARE ANTIMITOCHONDRIAL ANTIBODIES IN PRIMARY BILIARY CIRRHOSIS INDUCED BY R(ROUGH)-MUTANTS OF ENTEROBACTERIACEAE?
Authors: Roman Stemerowicz, Bernd Möller, Arne Rodloff, Marina Freudenberg, Uwe Hopf, Christel Wittenbrink, Richard Reinhardt, Chris Galanos
Journal: The Lancet (1988)
F-18 Fluorodeoxyglucose PET/CT Findings in a Case of Anti-NMDA Receptor Encephalitis
Authors: Brandt C. Mohr, Satoshi Minoshima
Journal: Clinical Nuclear Medicine (2010)

A 23-year-old woman with a history of rapid-cycling bipolar disorder was brought in by her family after 4 days of increasing psychological disturbance characterized by declining mental status, hallucinations, orofacial dyskinesias, and bizarre behavior. A paraneoplastic encephalopathy was suspected clinically, prompting whole-body and dedicated brain 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) positron emission tomography and computed tomography (PET/CT) imaging that showed relative hypometabolism of the bilateral occipital lobes and cerebellum, and relative hypermetabolism of the bilateral frontal, temporal, and parietal lobes. Subsequent cerebrospinal fluid analysis demonstrated strongly positive anti-N-methyl-D-aspartate receptor (anti-NMDAR) autoantibody titers that, in conjunction with the patient's clinical presentation, were diagnostic of anti-NMDAR encephalitis. The FDG PET/CT appearance of anti-NMDAR encephalitis has not been previously characterized in the literature, and FDG PET/CT brain imaging findings from this patient with clinically confirmed anti-NMDAR encephalitis are presented here.
Adrenal Lymphocytic Infiltration and Adrenocortical Tumors in a Patient with 21-Hydroxylase Deficiency
Authors: Deborah P. Merke, Stefan R. Bornstein, Demetrios Braddock, George P. Chrousos
Journal: New England Journal of Medicine (1999)

To the Editor: The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial (Nov.5 issue) 1 is the third study, after the Scandinavian Simvastatin Survival Study 2 and the Cholesterol and Recurrent Events study, 3 on the use of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors for secondary prevention of coronary disease.The positive results of this trial are as marginal as those of the studies that preceded it.The authors calculated relatively high values for risk re-*Trials whose authors originally acknowledged not having obtained IRB approval or informed consent are included with trials whose authors did not originally disclose information about these issues.For comparisons of the failure to disclose information on one or both issues, the percentages of authors who failed to report on both must be added to the percentages of authors who failed to report on one.
ON THE BACTERIOLOGY OF PEMPHIGUS NEONATORUM, AND A SUGGESTION FOR FURTHER INVESTIGATION BY A DIFFERENT METHOD OF CULTURAL PROCEEDING.
Authors: H. G. ADAMSON.
Journal: British Journal of Dermatology (1937)

Journal Article ON THE BACTERIOLOGY OF PEMPHIGUS NEONATORUM, AND A SUGGESTION FOR FURTHER INVESTIGATION BY A DIFFERENT METHOD OF CULTURAL PROCEEDING. Get access H. G. ADAMSON. H. G. ADAMSON. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 49, Issue 3, 1 March 1937, Pages 93–99, https://doi.org/10.1111/j.1365-2133.1937.tb11163.x Published: 01 March 1937
The road through Oxiana, 1978.
Authors: B Milsted
Journal: BMJ (1981)

The new marking system results in an almost symmetrical plot, which has been described by a Curve-Unifying Paradigm (figure). The secondary curve to the right resulted from candidates whose Symbolic Points In Linearly Tested MILK could not be removed by use of Weight-Assigned Theoretical Exponential Rectification. Further curve-smoothing by addition of a Scientific And Ultra-Conservative Experiment Ratio improved the confidence limits when handled by the modified tea test, Student's Universal Grade Averaging Regimen.
The fibrotic process: summary
Authors: M. I. V. Jayson
Journal: Annals of the Rheumatic Diseases (1977)

In this symposium the emphasis in papers and in discussion was on the mechanisms of collagen formation and turnover and the factors influencing them.We are beginning to understand some of the fundamental features leading to abnormal fibrosis in disease.Rational explanations of the values of some forms of therapy together with potential new methods of treatment are beginning to emerge.Macrophages exposed to sublethal doses of asbestos or silica will form fibrogenic factors which stimulate fibroblasts to produce more collagen.Whether these factors are the same as the connective tissue activating peptide described by Castor and the fibrogenic factors found in the liver by McGee is not yet elucidated.It is not clear whether fibrogenic factors act by stimulating individual fibroblasts to produce more collagen or by causing them to divide, so increasing their numbers.As yet there are no suggestions for methods to interfere with the stimulus to fibrogenesis.In clinical silicosis immunological factors may also be relevant-subjects exposed to silica who develop the most florid lung changes also have the highest antinuclear factor titres.It is also known that silica can interfere with the capacity of cells to mount immune responses.Anticollagen anti-
A Crowded Room
Authors: David S. Hatem
Journal: JAMA (1997)

I entered the examination room to find one of my scheduled patients waiting. I am often amazed at what patients bring with them when they visit their doctor. Not just what, but who. And not just who, but why. She had brought her large bag of medical problems. In the bag was the breast cancer of 11 years, seemingly an old problem, but always present and early to come out of the bag. There was the recurrent lymphedema of one arm with intermittent cellulitis. There were the chronic headaches. There were the perplexing hot flashes. Cervical spondylosis, hypercholesterolemia, the positive PPD, the stroke of several years back (no residual deficit, but that didn't allow it to be discarded), and her periodic depressive episodes were all there, waiting to be taken out as necessary. Somewhere in the depths of the bag were the lining of her maxillary sinus as well as
Positive Selection and Gene Conversion Drive the Evolution of a Brain-Expressed snoRNAs Cluster
Authors: M. Ogorelkova, A. Navarro, F. Vivarelli, A. Ramirez-Soriano, X. Estivill
Journal: Molecular Biology and Evolution (2009)

HBII-52 small nucleolar RNAs (snoRNAs) are brain-expressed posttranscriptional modifiers of serotonin receptor 2C RNA. They are organized in a cluster of 47 highly homologous gene copies spanning 100 kb at chromosome 15q11.2. Nucleotide diversity at HBII-52 snoRNA gene cluster in African and European descent populations was analyzed via resequencing of 25 functional snoRNA gene copies. Ninety-four variants were detected, from which 74 are novel. Only 16 variants are shared between Africans and Europeans. We also report a novel Yoruba-specific copy-number variant representing a 5.2-kb polymorphic deletion and resulting in a chimerical functional snoRNA copy. In both populations, the snoRNA genes are characterized by high density of single nucleotide polymorphisms and an excess of low-frequency variants. However, the variability patterns are strictly population specific and there is an extreme divergence in allele frequencies in both resequencing and HapMap data. Several tests of neutrality strongly suggest that the observed extreme population divergence at the HBII-52 region results from positive selection in Europeans. Our analysis of HBII-52 nucleotide variability spectrum shows that gene conversion is the main factor introducing variability at the cluster. Sixty-five substitutions (69%) correspond to a paralogous sequence variant (PSV) in another copy and occur at potential gene conversion tracts of >5 bp. We detected several interparalogue gene-conversion events that involve more than one PSV, with individual frequency patterns suggestive of recurrent gene conversion. Analysis based on derived and ancestral allele distribution shows that gene conversion is at least twice more frequent than point mutations. Gene conversion is an important factor in disrupting patterns of linkage disequilibrium (LD) at short scales. Consistent with this, we detect punctual breaks of LD at gene conversion sites while the overall LD at the HBII-52 cluster is high in both study populations.
1196 NOVEL, POTENT, PAN-GENOTYPIC HCV NS3/4A PROTEASE INHIBITORS WITH A HIGH BARRIER TO RESISTANCE
Authors: B.O. Buckman, K. Kossen, J.B. Nicholas, V. Serebryany, D. Ruhrmund, R. Rajagopalan, S. Misialek, L. Hooi, N. Aleskovski, L. Pan, L. Huang, C.J. Schaefer, S. Rajyaguru, S. Le Pogam, I. Nájera, K. Klumpp, S. Seiwert
Journal: Journal of Hepatology (2011)
DIAGNOSIS OF AMEBIASIS
Authors: R. B. H. Gradwohl
Journal: JAMA (1934)

<h3>To the Editor:—</h3> In reference to the diagnosis of amebic dysentery, as outlined in the article by Dr. Kano Ikeda of St. Paul in the Dec. 16, 1933, issue ofThe Journal, I venture to state that his conclusions regarding the laboratory diagnosis are not borne out by the experiences of those who have had an opportunity to study the intestinal amebas of man. He says: "While, therefore, I follow the teaching of the authorities that the finding of red blood cells within the vegetative form of amebas and the demonstration of the four nucleated cysts should constitute the final diagnostic criteria of Endamoeba histolytica, I feel that, in experienced hands, a positive diagnosis, without either of the two, may be justified, at least in the face of an outbreak such as has been witnessed." In the first place, the finding of the vegetative form is not easy unless one
Chloramphenicol Resistance in the Typhoid Bacillus
Authors: E. S. Anderson, H. R. Smith
Journal: BMJ (1972)

Chloramphenicol resistance has been reported in individual strains of Salmonella typhi since 1950, but there had been no accounts of epidemics caused by resistant strains of the organism until 1972, when one occurred in Mexico. Two British patients have been infected in that country, and the organism isolated from them corresponds in all respects with the description of the Mexican epidemic strain of S. typhi: it is a degraded Vi strain resistant to chloramphenicol, streptomycin, sulphonamides, and tetracyclines. It owes its resistance to an R factor which can be transferred to Escherichia coli and thence to drugsensitive S. typhi. Although there is a negligible risk of dissemination of this strain in Britain the incident is a reminder of the need to restrict the use of drugs such as chloramphenicol to the serious diseases for which they are virtually specific.