tbuckley/cabot-search huggingface dataset:
Abstract 3158: Prediction of overall survival in urothelial cancer patients using tumor sizes and baseline risk factors: longitudinal modeling approach for durvalumab and durvalumab + tremelimumab
Authors: Mei Tang, Yu Jiang, Han Si, Yanan Zheng, Chen Gao, Guozhi Gao, Natasha Angra, Shaad Abdullah, Brandon Higgs, Lorin Roskos, Rajesh Narwal
Journal: Cancer Research (2019)

Abstract Background: Durvalumab [D] is a human mAb that binds to PD-L1 and blocks its interaction with PD-1 and CD80. Tremelimumab [T] blocks the inhibitory effects of CTLA-4, and therefore enhances T-cell activation. The objectives of this analysis were to develop a model linking overall survival (OS) to baseline risk factors and changes in tumor size during treatment to identify key factors impacting response to D or D +T. Methods: The analysis dataset included UC patients from two clinical trials: Study 1108 (D 10 mg/kg Q2W; n=201) and Study 10 (D 20 mg/kg Q4W + T 1 mg/kg Q4W for 4 doses, followed by D 20 mg/kg Q4W alone; n=168). Longitudinal tumor size data were analyzed using a nonlinear mixed effect model with key parameters describing tumor growth, tumor killing, and delay in immune response. Subsequently, a parametric survival model was developed to link baseline risk factors and predicted percent change in tumor size at week 8 to OS. Results: Tumor kinetic model adequately described the longitudinal tumor size data from UC patients. Baseline tumor size (p&amp;lt;0.01) and PD-L1 status (p&amp;lt;0.01) were identified as significant covariates for tumor killing rate. The most influential factor associated with faster tumor growth was liver metastasis (p&amp;lt;0.01), while higher hemoglobin levels (p&amp;lt;0.01) were associated with decreased tumor growth rate. Based on parametric survival modeling, liver metastasis (~34% decrease in OS, p&amp;lt;0.0001), albumin (~ 1-fold increase in OS per 1g/dL increase, p&amp;lt;0.0001), and percent change in tumor size at week 8 (~52% increase in OS with 30% tumor shrinkage at week 8, p&amp;lt;0.0001) were found to be significant and clinically relevant predictors of OS. Conclusions: The parametric survival model coupled with tumor kinetic model adequately described clinical outcomes in UC patients treated with D or D+T and enabled identification of key factors potentially impacting response to immune therapy in UC. This approach can be a useful tool for guiding patient selection/enrichment strategies and optimizing trial designs for immuno-oncology (IO) therapies. Further validation and prospective evaluation of this model may be conducted in other IO trials. Citation Format: Mei Tang, Yu Jiang, Han Si, Yanan Zheng, Chen Gao, Guozhi Gao, Natasha Angra, Shaad Abdullah, Brandon Higgs, Lorin Roskos, Rajesh Narwal. Prediction of overall survival in urothelial cancer patients using tumor sizes and baseline risk factors: longitudinal modeling approach for durvalumab and durvalumab + tremelimumab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3158.
Eating for Strength; or, Food and Diet in Their Relation to Health and Work.
Journal: JAMA (1890)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Cost Savings and Prescribing Protocols for Nonsteroidal Anti-inflammatory Drugs-Reply
Authors: David L. Jones
Journal: JAMA (1996)

<h3>In Reply.</h3> —We appreciate the concerns raised by Dr Rothschild. Since significantly lower cost to the patient encourages use of our managed health care system, it is unlikely that many of our patients who developed gastrointestinal complications were hospitalized in other facilities. All of our gastroenterologists responded to our survey, and 9 perceived an increase in NSAID-associated gastropathy. However, as we emphasized, physician perception of patient harm may indeed underestimate the frequency of actual adverse effects. All NSAIDs may cause gastrointestinal and other complications. Differences in risk are probably dose dependent, and differences in equipotent doses have not been shown to be clinically significant. Our guideline did not require the use of maximal NSAID doses before progression to other agents. In the year following our intervention, our guideline resulted in volume-adjusted increases of 12% for nonacetylated salicylates and more than 25% for acetaminophen. We did not evaluate the effect of these
ACCREDITATION LAUNCHED IN CONTINUING MEDICAL EDUCATION
Journal: JAMA (1967)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Newer Laboratory Approaches for Assessing Visual Dysfunction
Authors: Paul G. Shinkman, Michael R. Isley, Diane C. Rogers
Journal: Environmental Health Perspectives (1982)

The crucial point that will be emphasized throughout this report is the potential utility of analyzing visual cortical receptive field (RF) properties of the single-cell level as a sensitive and reliable neurotoxicity screening tool. Numerous studies employing exposure of kittens to altered visual environments during the critical period have demonstrated that particular classes of RFs can be selectively affected while sparing others. There has been a rapid proliferation of new methods used to investigate such effects. An important current trend involves the development of multidisciplinary combinations of approaches. The various maneuvers reviewed here seem adaptable to studying neurotoxic insult of the sensitive properties of cortical visual neurons, particularly in the cat or monkey. Conceivably, a general disruption of cortical RF properties might be expected following toxic exposure since individual RF properties are generally not determined by completely independent mechanisms. In fact, some toxicants might produce a general degradation of RF properties akin to the electrophysiological results reported for long-term dark rearing or binocular deprivation.
Therapeutics
Journal: JAMA (1935)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Correction: Clinical trials with inactivated hepatitis A vaccine and recommendations for its use
Journal: BMJ (1992)

5 years.Consequently, if a 5 year old boy has an observed 12 month height velocity at the mean value for the population-'that is, 6 27 cm a year on standard charts-the 95% confidence interval for his true velocity ranges from the 25th centile to the 75th.However, if another boy aged 2 years also has an observed velocity on the 50th centile-8-31 cm a year in this case-the 95% confidence interval ranges from the 21st centile to the 79th.This degree of imprecision in determining the rate of growth, at any age, means that in practice the calculation of a single velocity, even over 12 months, is of limited clinical use.3The measurement of height must therefore begin at the earliest possible age and be repeated at frequent -intervals to observe the trend,
Suicide Gene Therapy of Graft-Versus-Host Disease Induced by Central Memory Human T Lymphocytes.
Authors: Attilio Bondanza, Veronica Valtolina, Zulma Magnani, Shin Kaneko, Maurilio Ponzoni, Francesca Sanvito, Mark Bonyhadi, Catia Traversari, Salvatore Toma, Marina Radrizzani, Simona La Seta-Catamancio, Katharina Fleischhauer, Fabio Ciceri, Claudio Bordignon, Chiara Bonini
Journal: Blood (2005)
Abstract 820: Usefulness of Monitoring Congestive Heart Failure by Multiple Bioelectric Impedance Vectors
Authors: Dirar S Khoury, Mihir Naware, Jeff Siou, Nilesh S Mathuria, Jianwen Wang, Hue-Teh Shih, Sherif F Nagueh, Dorin Panescu
Journal: Circulation (2008)

Bioelectric impedance is useful in detecting changes in pulmonary congestion and cardiac function. We examined the utility of simultaneously measuring multiple intrathoracic and intracardiac impedance signals by a cardiac resynchronization therapy (CRT) system for monitoring congestive heart failure (CHF). We implanted CRT systems in 15 normal dogs using standard leads. An additional LA pressure lead-sensor was implanted in 5 dogs. Continuous RV pacing (230–250 bpm) was applied over several weeks. Catheterization and echocardiography were performed biweekly. Multiple intrathorcaic and intracardiac impedance vectors were measured via ring (R), tip (T), coil (C), and Can electrodes. The system measured both steady-state impedance (Zs), which monitored changes in geometric and resistive parameters, and cardiogenic impedance (Zc), which monitored beat-to-beat variations during mechanical deformation of the heart. All animals developed CHF after 2– 4 weeks of pacing starting from baseline (EF, 43 vs. 31%; LV end-diastolic volume, 65 vs. 95 ml; LV end-diastolic pressure, 6 vs. 16 mmHg; LA volume, 18 vs. 31 ml; LA pressure, 8 vs. 26 mmHg). Zs decreased significantly during CHF in all measured vectors: LV R -Can, −17%; LV R -RV R , −15%; LV R -RA R , −11%; RV R -Can, −12%; RV C -Can, −7%; RA R -Can, −5% (LV R -Can reflected the largest change, p &lt; 0.05). All Zs vectors decreased exponentially, but at varying time constants (7–13 days); the LV R -Can vector depicted the fastest rate of change (p &lt; 0.008). Select Zs vectors reflected changes in LV end-diastolic volume; LV R -Can yielded the highest correlation (r = −0.83, p &lt; 0.001). Zs was inversely related to LA pressure; the LV R -Can produced the highest correlation (r= −0.84, p &lt; 0.001). Peak-to-peak Zc decreased significantly during CHF compared to baseline in all vectors tested (LV R -RV R , 18 vs. 11Ω; LV R -RA R , 20 vs. 13Ω; RV R -RV T , 38 vs. 13Ω). Changes in Zc via RV R -RV T correlated with EF (r = 0.72, p = 0.028). Intrathoracic and intracardiac impedance, acquired via different CRT system leads, have variable responses to CHF. Employing a LV lead improves physiologic monitoring by impedance. Cardiogenic impedance reflects dynamic changes in cardiac function during CHF.
Depression
Authors: Robert M. McCarron, Bryan Shapiro, Jody Rawles, John Luo
Journal: Annals of Internal Medicine (2021)

Most psychiatric care is delivered in primary care settings, where depression is the most common presenting psychiatric symptom. Given the high prevalence of depression worldwide and the well-established consequences of untreated depression, the ability of primary care clinicians to effectively diagnose and treat it is critically important. This article offers up-to-date guidance for the diagnosis and treatment of major depressive disorder, including practical considerations for delivering optimal and efficient care for these patients.
Color Vision
Authors: H. J. Adler
Journal: JAMA (1961)

<h3>To the Editor:—</h3> In your editorial, "Color Vision and Land's Theory" (<i>JAMA</i><b>175</b>:41 [Jan. 7]), you mention "recent" articles in the<i>Scientific American and Fortune</i>magazines. These articles, as you know, both appeared in May, 1959, so they are not so very recent. What disturbs me considerably more, however, is your omission of the original publication data of Land's work in the<i>Proceedings of the National Academy of Sciences</i><b>45</b>:89-115 (Jan.) 1959;<i>ibid</i>; 115-129;<i>ibid</i>; 636-645 (April) 1959. Your omission of these references, together with the implication that Land's work was published only in lay publications, might detract from the weight of his findings.
OC-005 Novel Pathway-centric Analysis Reveals Variants Associated With Toxicity And Response To Thiopurines In Patients With Inflammatory Bowel Disease
Authors: PA Blaker, S Fong, J Walker, CM Lewis, AM Marinaki, JD Sanderson, PM Irving
Journal: Gut (2014)

<h3>Introduction</h3> Thiopurines remain the first line immunosuppressants recommended in the management of inflammatory bowel disease (IBD). Unfortunately, 30–40% of patients prescribed these agents develop adverse drug reactions or fail to derive therapeutic benefit. Candidate gene studies have identified loci that explain some of these treatment failures; however a substantial fraction of the genetic contribution remains undefined. Using whole thiopurine pathway analysis the aim of this study was to identify novel loci associated with toxicity and response to azathioprine (AZA)/mercaptopurine (MP) in patients with IBD. <h3>Methods</h3> Genomic DNA was extracted from EDTA blood samples of 472 well-characterised IBD patients treated with AZA/MP. We examined exome array data using the Illumina HumanExome Beadchip and restricted the analysis to variants associated with the thiopurine pathway as defined by the KEGG database (100 genes, 639 single nucleotide polymorphisms). Using a case-control design we firstly tested for genetic associations between patients with (<i>n = 1</i>54) and without (<i>n = 2</i>58) adverse drug reactions, and secondly for polymorphisms differentiating patients with (<i>n = 1</i>88) and without (<i>n = 1</i>41) response to thiopurines after 12 months of treatment. One year intervention-free clinical response was defined by 3 investigators (PB, PI, JS). <h3>Results</h3> Following adjustment for principal components, the minor alleles at <i>ADK</i> rs946185 (p = 0.0078; OR 1.675), <i>SLC28A1</i> rs2242046 (p = 0.0168; OR 1.600) and <i>ABCA1</i> rs4149268 (p = 0.033; OR 1.487) were associated with the development of drug toxicity, whereas the minor alleles at <i>ABCB5</i> rs2301641 (p = 0.0170; OR 0.608), <i>ABCC4</i> rs4148549 (p = 0.027; OR 0.652) and <i>AOX1 </i>rs55754655 (p = 0.038; OR 0.549) protected against it. The minor allele at <i>RRM2</i> rs1130609 (p = 3.80 × 10<sup>–5</sup>; OR 0.461), which codes a subunit of ribonucleotide reductase involved in the conversion of thioguanine nucleotide to deoxy-thioguanine nucleotide, and a higher normalised dose of AZA/MP were associated with protection from non-response. Conversely, the minor allele at <i>ABCA1 </i>rs2230808 (p = 0.008; OR 2.585) and Crohn's disease (p = &lt;0.001; OR 5.007) were associated with non-response to treatment at 12 months. <h3>Conclusion</h3> High-throughput sequencing using exome array technology has revealed new loci, other than thiopurine-<i>S-</i>methyltransferase, explaining toxicity and response to thiopurines. Validation of these markers in separate cohorts will allow the development of biomarker panels to predict outcomes prior to the start of treatment. <h3>Disclosure of Interest</h3> None Declared.
Plant Genome
Journal: Environmental Health Perspectives (1994)

Life is short, science is long; opportunity is elusive, experiment is dangerous, judgment is difficult.Hippocrates I Plant GenomeResearchers working on the plant genome project are respectful of its more celebrated sibling, the human genome project, but they also can't help being a bit envious in a good-natured sort of way.The U.S. Department of Agriculture's Plant Genome Research Program is trying to map up to 40 different genomes at a fraction of the cost it takes to map human DNA."Would that we could have their budget," said Jerry Miksche, head of the U.S. Department of Agriculture's Plant Genome Research Program."But then, humans get cancer.Plants don't."Still, Miksche says, the efforts cooperate closely and share the latest mapping tech- niques and processes.The federal agen-
Clinical investigation of the portacaval shunt. 3. The diagnosis of esophageal varices
Authors: W. W. Peternel
Journal: JAMA (1967)

In 83 patients with liver cirrhosis, an esophagogram after administration of barium sulfate, an endoscopic examination of the esophagus, and a portogram after percutaneous injection of an opaque material into the spleen were compared for diagnostic value in demonstrating esophageal varices. The diagnosis was established by esophagoscopy in 81, by splenoportography in 61, and by barium esophagogram in 55. Large varices were frequently missed by barium esophagograms as well as by splenoportograms. The mean splenic-pulp pressure was similar when patients with endoscopically demonstrated varices and normal portograms were compared with those whose portogram showed varices. Moreover, there was no apparent relation between portal pressure and variceal size. A time lapse between studies of as long as two months had no apparent influence on the incidence of positive diagnoses obtained.
Author's reply
Authors: I. Haslock
Journal: Annals of the Rheumatic Diseases (1994)

Matters arising purchasers might consider "buying" inadequately evaluated therapies, on the same basis that physiotherapy was derided for accepting electrotherapy by ".... giving credence to unscientific hype".' Caveat emptor.I fully endorse the author's call for more research into the efficacy of physiotherapy, and already many of the obstacles that impeded physiotherapy research are being addressed.In a recent letter in the British Journal of Rheumatology5 I explained that through the creation of university departments, the expertise and career structure exists to enable us to advance research in physiotherapy.We are now successfully competing for funding to critically evaluate our treatments, so that we can deliver the most effective treatment to our patients with the optimal use of resources.
X‐linked sideroblastic anemia due to ALAS2 intron 1 enhancer element GATA‐binding site mutations
Authors: Yu Wang, Qi-Fa Liu, Ya-Zhen Qin, Dai-Hong Liu, Lan-Ping Xu, Bin Jiang, Qian Jiang, Min Dai, Si-Jian Yu, Xin-Miao Jiang, Yan-Rong Liu, Xiao-Jun Huang, Dean Campagna, Charlotte De Bie, Klaus Schmitz-Abe, Marion Sweeney, Anoop Sendamarai, Paul Schmidt, Matthew Heeney, Helger Yntema, Caroline Kannengiesser, Bernard Grandchamp, Charlotte Niemeyer, V Knoers, Sonia Swart, Gordon Marron, Richard Van Wijk, Reinier Raymakers, Alison May, Kyriacos Markianos, Sylvia Bottomley, Dorine Swinkels, Mark Fleming
Journal: American Journal of Hematology (2014)

Taken together, these genetic and functional data strongly support the conclusion that mutations in an enhancer element in ALAS2 intron 1 that contains a GATA-binding site result in a clinical phenotype similar to patients with XLSA owing to mutations in the ALAS2 coding sequence itself.In our own survey of >125 probands with CSA (Ref. 2 and data not shown), ALAS2 intron 1 enhancer element mutations constitute _3% of all probands and _5% of cases of XLSA.For this reason, we suggest that ALAS2 intron 1 GATAbinding site variants can be excluded in males with hypochromic, microcytic, nonsyndromic sideroblastic anemias lacking coding mutations in ALAS2 or biallelic coding or splicing variants in SLC25A38, particularly those with clinical or laboratory evidence of X-linkage or a minimal, but discernable, response to pyridoxine therapy.The word "can" should be replaced with "should".We apologize for any confusion this error might have caused.
Intestinal permeability.
Authors: K R Gardiner, R J Maxwell, B J Rowlands, G R Barclay
Journal: Gut (1995)

Intestinal permeability EDITOR,-We read with interest the paper by Dr Oriishi and colleagues (Gut 1995; 36: 891-6) investigating intestinal permeability and the immune response to enteric bacterial antigens in patients with inflammatory bowel disease.Their finding of an increased systemic concentration of antibodies to lipid A in patients with inflammatory bowel disease is in agreement with studies showing increased titres of antibodies to the endotoxin core,l to peptidoglycan-polysaccharide complexes,2 and to a variety of enteric bacteria3 in these diseases.These studies offer indirect evidence of mucosal barrier dysfunction in patients with inflammatory bowel disease, which supports the more direct evidence provided by the measurement of systemic endotoxin concen- tration or by bacterial culture studies.' 4