tbuckley/cabot-search huggingface dataset:
Substitution scanning identifies a novel, catalytically active ibrutinib-resistant BTK cysteine 481 to threonine (C481T) variant
Authors: A Hamasy, Q Wang, K E M Blomberg, D K Mohammad, L Yu, M Vihinen, A Berglöf, C I E Smith
Journal: Leukemia (2016)

Irreversible Bruton tyrosine kinase (BTK) inhibitors, ibrutinib and acalabrutinib have demonstrated remarkable clinical responses in multiple B-cell malignancies. Acquired resistance has been identified in a sub-population of patients in which mutations affecting BTK predominantly substitute cysteine 481 in the kinase domain for catalytically active serine, thereby ablating covalent binding of inhibitors. Activating substitutions in the BTK substrate phospholipase Cγ2 (PLCγ2) instead confers resistance independent of BTK. Herein, we generated all six possible amino acid substitutions due to single nucleotide alterations for the cysteine 481 codon, in addition to threonine, requiring two nucleotide substitutions, and performed functional analysis. Replacement by arginine, phenylalanine, tryptophan or tyrosine completely inactivated the catalytic activity, whereas substitution with glycine caused severe impairment. BTK with threonine replacement was catalytically active, similar to substitution with serine. We identify three potential ibrutinib resistance scenarios for cysteine 481 replacement: (1) Serine, being catalytically active and therefore predominating among patients. (2) Threonine, also being catalytically active, but predicted to be scarce, because two nucleotide changes are needed. (3) As BTK variants replaced with other residues are catalytically inactive, they presumably need compensatory mutations, therefore being very scarce. Glycine and tryptophan variants were not yet reported but likely also provide resistance.
Diethylstilbestrol and the Risk of Cancer
Authors: L C Clark, K M Portier
Journal: New England Journal of Medicine (1979)

There is striking evidence that there is an increased risk of early cancer mortality in women treated with diethylstilbestrol during pregnancy. Exposure to the drug is associated with more than a twofold increase in risk of all cancer, which increases to 2.89 for breast cancer, and to 2.73 for endocrine related tumors. Most published studies on the subject lack the statistical power to reject the hypothesis that there are no significant differences between treated and untreated women, especially in the presence of a 50% increase in risk. There is a difference in the magnitude of the relative risk between premenopausal and postmenopausal breast cancer, the mortality cases being primarily in premenopausal women. Additional studies on diethylstilbestrol are needed.
Soundings: Dentures and deep time
Authors: Kevin Barraclough
Journal: BMJ (2005)

The only thing I really remember about “Harold” was that he would keep his dentures in different sets of jars in the laboratory marked “Best Pair,” “Reasonable Pair,” and “Not So Good.” Quite often he would do without them altogether, and then he looked like Harold Steptoe from the 1970s UK television sitcom about rag and bone men.

Harold was not what you would call an inspirational teacher, but on this occasion he passed around a small black rock with shiny crystals on the surface. It was heavy and about twice the size of a golfball.

The students passed it around perfunctorily with a conspicuous lack of interest and mild distaste in case it had come into contact with the dentures. It returned rapidly to Harold who pocketed it, and then droned on about x ray diffraction patterns for 45 minutes.

Through the dusty windows of the Victorian lab we could see a summer afternoon beckoning and our lives drifting away. At the end we were all getting up to leave when someone asked him what the rock was.

It was, he said, the oldest thing you will ever touch. It was a meteorite formed over four and half billion years ago—before the earth or the sun had formed. It was a third of the age of the universe, he said, older than most of the stars in the sky. We asked if we could look again, but he shook his head, rattling his second best pair of dentures.

That was my first experience of “deep time.”

My second experience was a couple of years ago. It was 2 am on a crystal clear, starlit night, and from the makeshift observatory at the bottom of our garden I saw the Einstein Cross. It was a tiny, fuzzy collection of five blobs of starlight looking a little like a Gaelic brooch.

When I looked away from the eyepiece I was looking at a landscape of fields and trees lit only by starlight. When I looked back in the eyepiece I was looking at a universe that was a third its present age. Back then there were big fierce stars and little else. There was no rock, no heavy elements, and no life.

Things like that change your perspective. Certainly, if I ever have dentures, I'm not going to have a “Not So Good” pair.
Personality disorders and treatment outcome in the NIMH Treatment of Depression Collaborative Research Program
Authors: M T Shea, P A Pilkonis, E Beckham, J F Collins, I Elkin, S M Sotsky, J P Docherty
Journal: American Journal of Psychiatry (1990)

The authors investigated the relationship between personality disorders and treatment outcome in the National Institute of Mental Health Treatment of Depression Collaborative Research Program, which involved 239 outpatients with major depressive disorder randomly assigned to one of four 16-week treatment conditions. Patients with personality disorders (74% of the sample) had a significantly worse outcome in social functioning than patients without personality disorders and were significantly more likely to have residual symptoms of depression. There were no significant differences in work functioning or in mean depression scores at treatment termination. Outcome was similar for patients in the different clusters of personality disorders.
Successful Therapy Reduction and Intensification for Childhood Acute Lymphoblastic Leukemia Based on Minimal Residual Disease Monitoring: Study ALL10 From the Dutch Childhood Oncology Group
Authors: Rob Pieters, Hester de Groot-Kruseman, Vincent Van der Velden, Marta Fiocco, Henk van den Berg, Evelien de Bont, R. Maarten Egeler, Peter Hoogerbrugge, Gertjan Kaspers, Ellen Van der Schoot, Valerie De Haas, Jacques Van Dongen
Journal: Journal of Clinical Oncology (2016)

Outcome of childhood acute lymphoblastic leukemia (ALL) improved greatly by intensifying chemotherapy for all patients. Minimal residual disease (MRD) levels during the first months predict outcome and may select patients for therapy reduction or intensification.Patients 1 to 18 years old with ALL were stratified on the basis of MRD levels after the first and second course of chemotherapy. Thereafter, therapy was substantially reduced in patients with undetectable MRD (standard risk) and intensified in patients with intermediate (medium risk) and high (high risk) levels of MRD. Seven hundred seventy-eight consecutive patients were enrolled. The method of analysis was intention-to-treat. Outcome was compared with historical controls.In MRD-based standard-risk patients, the 5-year event-free survival (EFS) rate was 93% (SE 2%), the 5-year survival rate was 99% (SE 1%), and the 5-year cumulative incidence of relapse rate was 6% (SE 2%). The safety upper limit of number of observation years was reached and therapy reduction was declared safe.MRD-based medium-risk patients had a significantly higher 5-year EFS rate (88%, SE 2%) with therapy intensification (including 30 weeks of asparaginase exposure and dexamethasone/vincristine pulses) compared with historical controls (76%, SE 6%). Intensive chemotherapy and stem cell transplantation in MRD-based high-risk patients resulted in a significantly better 5-year EFS rate (78%, SE 8% v 16%, SE 8% in controls). Overall outcome improved significantly (5-year EFS rate 87%, 5-year survival rate 92%, and 5-year cumulative incidence of relapse rate 8%) compared with preceding Dutch Childhood Oncology Group protocols.Chemotherapy was substantially reduced safely in one-quarter of children with ALL who were selected on the basis of undetectable MRD levels, without jeopardizing the survival rate. Outcomes of patients with intermediate and high levels of MRD improved with therapy intensification.
Carcinogenic Agents in Snuff<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>
Authors: D Hoffmann, N H Harley, I Fisenne, J D Adams, K D Brunnemann
Journal: JNCI Journal of the National Cancer Institute (1986)

The oral use of snuff has been associated with an increased-risk for cancer of the oral cavity and pharynx. The five most popular U.S. snuff brands were analyzed for alkaloids, volatile and tobacco-specific N-nitrosamines (TSNA), benzo[a]pyrene (CAS: 50-32-8), and polonium-210. The carcinogenic TSNA in the five snuff brands ranged from 9,600 to 289,000 ppb. These concentrations exceed the nitrosamine concentrations of other consumer products by at least 2 orders of magnitude. Polonium amounted to 0.16-1.22 pCi/g dry snuff. Trace amounts of benzo[a]pyrene (0.1-63 ppb) were indicative of contamination of the tobacco with thermal degradation products, probably due to fire curing or flue curing. The findings from this study, the biologic activity of snuff in animal models, and the epidemiologic studies on snuff use and oral cancer strongly suggest the need for reduction of carcinogens and especially of nitrosamines and polonium-210 in snuff.
Cochrane distances itself from controversial views on psychiatric drugs
Authors: Jacqui Wise
Journal: BMJ (2015)

The Cochrane research organisation has stated unequivocally that it does not share the views of Peter Gotzsche, the director of the Nordic Cochrane Centre, on the benefits and harms of psychiatric drugs.1

The research organisation said that it had been forced to issue a statement after Gotzsche wrote an article in the Daily Mail saying that psychiatric drugs were Britain’s third biggest killer after heart disease and cancer and that doctors were handing them out like sweets.2 In the article Gotzsche said that as an investigator for the Cochrane Collaboration his role was to look forensically at the evidence for effects of treatments.

He quoted his new book, Deadly Psychiatry and Organised Denial , in which he said that the …
Estrogen-Based Therapies and Depression in Women Who Naturally Enter Menopause Before Population Average
Authors: Michael Pascal Hengartner
Journal: JAMA Psychiatry (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Puerperal Inversion of the Uterus
Authors: R K Aspevik, J Haffner
Journal: New England Journal of Medicine (1934)

Inversion of the uterus is a rare but very serious complication of childbirth. We present a case-report from a hospital with 350 to 400 births a year where since we have no gynecologist, the surgeons are in charge of obstetrics. The patient was successfully operated after an attempt to replace the inverted uterus had failed.
Voxel Level Radiologic–Pathologic Validation of Restriction Spectrum Imaging Cellularity Index with Gleason Grade in Prostate Cancer
Authors: Ghiam Yamin, Natalie M. Schenker-Ahmed, Ahmed Shabaik, Dennis Adams, Hauke Bartsch, Joshua Kuperman, Nathan S. White, Rebecca A. Rakow-Penner, Kevin McCammack, J. Kellogg Parsons, Christopher J. Kane, Anders M. Dale, David S. Karow
Journal: Clinical Cancer Research (2016)

Restriction spectrum imaging (RSI-MRI), an advanced diffusion imaging technique, can potentially circumvent current limitations in tumor conspicuity, in vivo characterization, and location demonstrated by multiparametric magnetic resonance imaging (MP-MRI) techniques in prostate cancer detection. Prior reports show that the quantitative signal derived from RSI-MRI, the cellularity index, is associated with aggressive prostate cancer as measured by Gleason grade (GG). We evaluated the reliability of RSI-MRI to predict variance with GG at the voxel-level within clinically demarcated prostate cancer regions.Ten cases were processed using whole mount sectioning after radical prostatectomy. Regions of tumor were identified by an uropathologist. Stained prostate sections were scanned at high resolution (75 μm/pixel). A grid of tiles corresponding to voxel dimensions was graded using the GG system. RSI-MRI cellularity index was calculated from presurgical prostate MR scans and presented as normalized z-score maps. In total, 2,795 tiles were analyzed and compared with RSI-MRI cellularity.RSI-MRI cellularity index was found to distinguish between prostate cancer and benign tumor (t = 25.48, P < 0.00001). Significant differences were also found between benign tissue and prostate cancer classified as low-grade (GG = 3; t = 11.56, P < 0.001) or high-grade (GG ≥ 4; t = 24.03, P < 0.001). Furthermore, RSI-MRI differentiated between low and high-grade prostate cancer (t = 3.23; P = 0.003).Building on our previous findings of correlation between GG and the RSI-MRI among whole tumors, our current study reveals a similar correlation at voxel resolution within tumors. Because it can detect variations in tumor grade with voxel-level precision, RSI-MRI may become an option for planning targeted procedures where identifying the area with the most aggressive disease is important. Clin Cancer Res; 22(11); 2668-74. ©2016 AACR.
FRI0150 Maintenance of Response in Patients with Rheumatoid Arthritis (RA) After Switching to TCZ Administered Alone Compared to the Combination of TCZ and MTX
Authors: J. Pablos, F. Navarro, F. Blanco, J. Roman-Ivorra, A. Alonso, E. Martin-Mola, M. Cantalejo
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Tocilizumab (TCZ) represents an efficacious alternative for patients with rheumatoid arthritis (RA) with an inadequate clinical response to biological or non-biological disease-modifying anrirheumatic drugs (DMARDs). Previous data support the use of TCZ in monotherapy but there are limited data on its efficacy compared to TCZ + MTX. <h3>Objectives</h3> The main objective was to assess the maintenance of response after switching to TCZ alone in patients with TCZ 8 mg/kg i.v. every 4 weeks + oral MTX who showed at week 16 a low activity (DAS28 ≤3.2). Secondary endpoints included clinical response after 28 weeks, improvement of general status and quality of life. Safety assessment was also assessed and included adverse events, serious adverse events, and change in laboratory parameters. <h3>Methods</h3> Phase III, randomized, double-blind, parallel-group (1:1), multicenter study in patients with active RA treated with TCZ + MTX with previous inadequate response to MTX. All those patients who achieved at week 16 a DAS28 ≤3.2 were randomized (1:1) to either TCZ + MTX or TCZ + placebo with a follow-up of 28 weeks. Sample size was calculated in 79 patients per group in order to detect a minimum disease activity score (DAS28) clinically relevant difference of 0.5 (standard deviation 1.1) with 80% power and two-sided 5% alpha level. Statistical analysis was performed with SAS v9.2, and included analysis of covariance for the primary endpoint (with week 16 DAS28 as a covariate), and descriptive parameters for secondary endpoints, with an intention to treat approach. Safety cumulative incidences were estimated using Kaplan-Meier methods. (ClinicalTrials.gov Identifier: NCT01399697.) <h3>Results</h3> Total of 263 RA patients with previous inadequate response to MTX (DAS28 5.6±1.2) were treated with TCZ + MTX. All patients achieving a DAS ≤3.2 at 16 weeks (n=165) were randomized to TCZ + MTX (n=83) or TCZ + placebo (n=82). DAS28 from week 16 to week 28 did not change significantly in both groups (from 1.77 to 1.87 with TCZ + MTX, and from 1.96 to 1.98 with TCZ + placebo, ANOVA, p=0.89). Remission rates (DAS28&lt;2.6) at week 28 were similar in both groups TCZ + MTX and TCZ alone (82.3% and 75.9% respectively, p=0.33), and similar to those at week 16 in both groups (84.0% and 72.0% respectively). No statistically significant differences were observed in any of the secondary variables. The incidence of adverse events after week 16 was similar in both groups. <h3>Conclusions</h3> Switching from TCZ + MTX to TCZ alone in patients with low disease activity is not followed by any clinical change, either in the efficacy or the safety profiles. Therefore, the monotherapy could be an efficacious and safe alternative for those patients not suitable for a combination therapy. <h3>Disclosure of Interest</h3> None declared
Predictors of community tenure of discharged state hospital patients
Authors: A Bené-Kociemba, P G Cotton, A Frank
Journal: American Journal of Psychiatry (1979)

Community treatment of formerly hospitalized patients is in need of evaluation. The authors evaluated an aftercare program by examining its effect on the amount of time spent in the community by patients discharged from a state mental hospital. They assessed the impact of specific intervention in the areas of housing, employment, finances, psychiatric treatment, medication, and leisure. They conclude that assistance during the transition from the hospital to the community prolonged community tenure, that intervention in the areas of housing, finances, and medication was especially important, and that treatment in the community increased the amount of time spent in the community during the first 6 months after discharge.
Community-wide outbreak of hepatitis A in Latvia, in 2008
Authors: J Perevoščikovs, I Lucenko, S Magone, A Brila, J Curikova
Journal: Eurosurveillance (2008)

Since November 2007, an increase in the number of reported hepatitis A cases has been observed in Latvia. The aim of this report is to provide an update on the descriptive epidemiology of hepatitis A in Latvia and suggest some possible explanations of the recent increase in incidence.
Reduced risk of myocardial infarct and revascularization following coronary artery bypass grafting compared with percutaneous coronary intervention in patients with chronic kidney disease
Authors: David M. Charytan, Manisha Desai, Maya Mathur, Noam M. Stern, Maria M. Brooks, Lukasz J. Krzych, Gerhard C. Schuler, Jan Kaehler, Alfredo M. Rodriguez-Granillo, Whady Hueb, Barnaby C. Reeves, Holger Thiele, Alfredo E. Rodriguez, Piotr P. Buszman, Paweł E. Buszman, Rie Maurer, Wolfgang C. Winkelmayer
Journal: Kidney International (2016)
HL-A Antigens in Hodgkin's Disease: Histopathologic and Clinical Correlations
Authors: Kenneth S. Graff, Richard M. Simon, Ronald A. Yankee, Vincent T. DeVita, G. Nicholas Rogentine
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article HL-A Antigens in Hodgkin's Disease: Histopathologic and Clinical Correlations Get access Kenneth S. Graff, M.D., Kenneth S. Graff, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard M. Simon, Ph. D., Richard M. Simon, Ph. D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ronald A. Yankee, M.D., Ronald A. Yankee, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Vincent T. DeVita, M.D., Vincent T. DeVita, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Nicholas Rogentine, M.D. G. Nicholas Rogentine, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 4, April 1974, Pages 1087–1090, https://doi.org/10.1093/jnci/52.4.1087 Published: 01 April 1974 Article history Received: 11 October 1973 Accepted: 14 December 1973 Published: 01 April 1974
Walker Carcinosarcoma 256 Tissue as a Dietary Constituent. II. Effect Upon Growth and Nitrogen Excretion in the Normal Rat
Authors: Julius White, Jane Nicolet Toal, Florence K. Millar, Harriett T. Cool, G. Burroughs Mider
Journal: JNCI Journal of the National Cancer Institute (1957)

Walker Carcinosarcoma 256 Tissue as a Dietary Constituent. II. Effect Upon Growth and Nitrogen Excretion in the Normal Rat Get access Julius White, Julius White National Cancer Institute,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Jane Nicolet Toal, Jane Nicolet Toal National Cancer Institute,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Florence K. Millar, Florence K. Millar National Cancer Institute,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Harriett T. Cool, Harriett T. Cool National Cancer Institute,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Burroughs Mider G. Burroughs Mider National Cancer Institute,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 19, Issue 5, November 1957, Pages 969–975, https://doi.org/10.1093/jnci/19.5.969 Published: 01 November 1957 Article history Received: 09 July 1957 Published: 01 November 1957
Increase in cases of Guillain-Barré syndrome during a Chikungunya outbreak, French Polynesia, 2014 to 2015
Authors: Erwan Oehler, Emmanuel Fournier, Isabelle Leparc-Goffart, Philippe Larre, Stéphanie Cubizolle, Chantal Sookhareea, Stéphane Lastère, Frédéric Ghawche
Journal: Eurosurveillance (2015)

During the recent chikungunya fever outbreak in French Polynesia in October 2014 to March 2015, we observed an abnormally high number of patients with neurological deficit. Clinical presentation and complementary exams were suggestive of Guillain–Barré syndrome (GBS) for nine patients. All nine had a recent dengue-like syndrome and tested positive for chikungunya virus (CHIKV) in serology or RT-PCR. GBS incidence was increased four- to nine-fold during this period, suggesting a link to CHIKV infection.
Bronchus-associated Lymphoid Tissue in Kabuki Syndrome with Associated Hyper-IgM Syndrome/Common Variable Immunodeficiency
Authors: Jason R. Mock, Todd M. Kolb, Peter B. Illei, Stephen C. Yang, Howard M. Lederman, Christian A. Merlo
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

humans is rarely seen after age 20 years in normal conditions (4).Patients with hyper-IgM syndrome or common variable immunodeficiency have a propensity to develop lymphoid hyperplasia (5).Kabuki syndrome caused by mutations in MLL2, a trithorax group methyltransferase, has not been reported, to our knowledge, to elicit BALT formation (6).