tbuckley/cabot-search huggingface dataset:
AB0280 The comparative responsiveness of the patient self-report questionnaires and composite disease for assessing rheumatoid arthritis activity in routine care
Authors: F. Salaffi, A. Ciapetti, S. Gasparini, M. Carotti, M. Gutierrez, S. Bombardieri
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To evaluate the internal and external responsiveness of the patient self-report questionnaires, comparatively to the traditional composite indices for assessing the activity of rheumatoid arthritis (RA) in everyday practice. <h3>Methods</h3> One hundred and ninety-one RA out-patients completed the CLinical ARthritis Activity (PRO-CLARA), the Rheumatoid Arthritis Disease Activity Index (RADAI), the Routine Assessment of Patient Index Data (RAPID3), and the Patient Activity Score (PAS). Simultaneously, the Disease Activity Score - 28 joints based on CRP (DAS28-CRP) and ESR (DAS28-ESR), the Simplified Disease Activity Index (SDAI), the Clinical Disease Activity Index (CDAI), and the Mean Overall Index for RA (MOI-RA) were computed in each patients. Sensitivity to change was assessed in after 6 months of treatment with disease-modifying antirheumatic drugs or biologics. Internal responsiveness was evaluated with the effect size (ES) and standardized response mean (SRM). External responsiveness was investigated by receiver operating characteristic (ROC), in categories of respondents, stratified according to the response on an item on change in overall health. In addition, change scores were compared by calculating correlation coefficients. <h3>Results</h3> Significant differences in internal and external responsiveness were not found between self-report questionnaires and composite indices. The internal responsiveness of the self-report questionnaires and composite measures was large, with SRM and ES ranging from 1.03 (RADAI) to 1.80 (DAS28-ESR) and higher than that of the each individual measures. The responsiveness of the PRO-CLARA was equal to the DAS28-ESR, DAS28-CRP, SDAI or MOI-RA, but better than the CDAI. The RADAI and PAS were less responsive than the PRO-CLARA and RAPID3. The area under ROC curve of the PRO-CLARA gives identical results to those provided by other comparator composite indices. The score changes of all combinations were highly correlated (p&lt;0.0001). <h3>Conclusions</h3> The self-report questionnaires showed comparable internal and external responsiveness that the composite activity scores and allow the detection of rheumatoid disease activity. They appear suitable for clinical decision making, epidemiologic research, and clinical trials. Further longitudinal studies are needed to validate these encouraging results. <h3>Disclosure of Interest</h3> F. Salaffi Grant/Research support from: FS has attended advisory board meetings for Bristol-Myers Squibb, Abbott Immunology, Wyeth Lederle and Pfizer and has received research support from Bristol-Myers Squibb. A. Ciapetti: None Declared, S. Gasparini: None Declared, M. Carotti: None Declared, M. Gutierrez: None Declared, S. Bombardieri: None Declared
Integrative analyses of the RNA modification machinery reveal tissue- and cancer-specific signatures
Authors: Oguzhan Begik, Morghan C. Lucas, Huanle Liu, Jose Miguel Ramirez, John S. Mattick, Eva Maria Novoa
Journal: Genome biology (2020)

RNA modifications play central roles in cellular fate and differentiation. However, the machinery responsible for placing, removing, and recognizing more than 170 RNA modifications remains largely uncharacterized and poorly annotated, and we currently lack integrative studies that identify which RNA modification-related proteins (RMPs) may be dysregulated in each cancer type.
The Importance of Physician Attire—The Socks With the Bulls
Authors: Leonid L. Yavorkovsky
Journal: JAMA Oncology (2020)

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 Oncology 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 Oncology journal
Dynamic regulation of Z-DNA in the mouse prefrontal cortex by the RNA-editing enzyme Adar1 is required for fear extinction
Authors: Paul R. Marshall, Qiongyi Zhao, Xiang Li, Wei Wei, Ambika Periyakaruppiah, Esmi L. Zajaczkowski, Laura J. Leighton, Sachithrani U. Madugalle, Dean Basic, Ziqi Wang, Jiayu Yin, Wei-Siang Liau, Ankita Gupte, Carl R. Walkley, Timothy W. Bredy
Journal: Nature Neuroscience (2020)
Outcome of Infants Younger Than 1 Year with Acute Lymphoblastic Leukemia Treated with the Interfant-06 Protocol; Results from an International Randomised Study
Authors: Rob Pieters, Paola De Lorenzo, Philip Ancliffe, Luis Alberto Aversa, Benoit Brethon, Andrea Biondi, Myriam Campbell, Gabriele Escherich, Alina Ferster, Rebecca Gardner, Rishi Sury Kotecha, Birgitte Lausen, Chi Kong Li, Franco Locatelli, Andishe Attarbaschi, Christina Peters, Jeffrey Rubnitz, Lewis B. Silverman, Jan Stary, Tomasz Szczepanski, Ajay Vora, Martin Schrappe, Maria Grazia Valsecchi
Journal: Blood (2018)
Remodelling depression
Authors: Dennis Palumbo
Journal: The Lancet (2005)

Despite the subtitle of their book, Christopher Callahan and German Berrios do more than survey the history of the treatment of depression in the second half of the past century. Their main concern is to show that the current conceptual model of depression is as much a social invention as a clinical one. This is crucially important in our understanding of the treatment of depression, since this model influences how society views people with emotional problems, defines who is sick, and determines from whom they should get care.
PTH-073 Radiological staging investigations before endoscopic resection of large colorectal lesions: significant burden with no benefit
Authors: Andrew Emmanuel, Shraddha Gulati, Monica Ortenzi, Margaret Burt, Bu Hayee, Amyn Haji
Journal: Endoscopy (2018)

<h3>Introduction</h3> Endoscopic resection (ER) is increasingly used for curative treatment of large colorectal superficial neoplastic lesions (CSNL). Experts believe that accurate lesion assessment and <i>in vivo</i> diagnosis should guide treatment decisions for such lesions, however in western practice skills in lesion assessment are less robust and patients frequently undergo biopsy sampling and pre-procedure radiological staging investigations as for any suspected colorectal cancer. For large rectal lesions, many consider pelvic MRI obligatory. The value of such investigations in this context is not clear. <h3>Methods</h3> All ER of large (≥20 mm) CSNLs referred to a tertiary unit were included. Data was collected from clinical letters, endoscopy and radiology reports from the referring department as well as the lesion assessment, treatment and final histopathology at our institution. Details of the findings of computed tomography (CT) scans, need for subsequent imaging and potential staging of rectal tumours by MRI were recorded. <h3>Results</h3> 579 CSNLs≥20 mm were treated with ER. 177 patients (31%) had received a staging CT of the thorax, abdomen and pelvis prior to referral. Of 163 rectal tumours, 67 (41%) had received a staging MRI. The findings of the CT scan did not change the management of the CSNL in any patients. Incidental findings were reported in 28 patients (16%). As a result 25 (89%) went on to require further imaging or referral to other clinicians which resulted in treatment for only one patient who required a ureteric stent for an asymptomatic obstructing stone. No MRI was reported as less than T1 and 31 (30%) were reported as at least T2 or greater, of which only 3 had invasive adenocarcinoma: 2 were T1 with minimal submucosal invasion and one was recognised during the ER as having deep invasion but was unfit for surgery. MRIs in 10 patients were reported as N1–2 (positive lymph node metastases), only 3 had proven adenocarcinoma of which only one eventually agreed to surgery: there was a T3N2 adenocarcinoma but surgery was performed more than 3 years after the initial MRI. <h3>Conclusions</h3> Traditional staging radiological investigations have no value in the management of either colonic or rectal large CSNL assessed as likely non-invasive using endoscopic assessment. Instead, they are a significant burden on resources, expose patients to unnecessary radiation, are likely to contribute to unfounded increased anxiety for patients and clinicians and lead to a significant number of additional investigations or specialist consultations without meaningful outcome.
Abstract 3470: Atypical protein kinase C inhibition in prostate cancer cells: A study of ICA-1 and ACPD
Authors: Andre H. Apostolatos, Christopher Apostolatos, Mildred Acevedo-Duncan
Journal: Cancer Research (2015)

Abstract Aggressive and metastatic prostate cancers are highly lethal tumors and are one of the leading causes of death among men. Certain prostate cancers are highly lethal tumors due to the emergence of therapy-resistant cancer cells. There is a gap in knowledge relating to which intracellular chemicals confer the emergence of therapy-resistant prostate cancer cells, which intracellular chemicals are responsible for prostate cancer survival and which chemicals regulate intracellular signaling pathways in prostate cancer. To address this critical problem, we investigated two drugs that act as inhibitors of atypical protein kinase C. The objective of this study was to test the effectiveness of ACPD [Diabetes. 63:2690-2701 (2014)] as an atypical PKC inhibitor and ICA-1 as an inhibitor of PKC-iota [The Inter. J. Biochem. &amp; Cell Biol. 43:784-794(2011)]. DU-145 prostate carcinoma cells and non-malignant prostate RWPE-1 cells were each cultivated in separate flasks. They were treated with drugs of interest for three consecutive days. The cells were counted before and after the treatments and a statistical analysis was performed. The cells were lysed and levels of PKC-iota and PKC-zeta were measured by Western blotting and immunoprecipitation. Our preliminary results demonstrated that treatment of DU-145 showed a statistically significant decrease in cells that was proportional to the concentration in both drugs. Treatment of the RWPE-1 cells showed no statistically significant change in population. Western blotting showed that both drugs decreased PKC-iota. In conclusion ACPD is an effective inhibitor of PKC-iota and PKC-zeta and consequently significantly reduced the neogenesis of the prostate DU-145 carcinoma cells while having negligible effect on the non-malignant prostate RWPE-1 cells. Citation Format: Andre H. Apostolatos, Christopher Apostolatos, Mildred Acevedo-Duncan. Atypical protein kinase C inhibition in prostate cancer cells: A study of ICA-1 and ACPD. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3470. doi:10.1158/1538-7445.AM2015-3470
Presynaptic Homeostasis Opposes Disease Progression in Mouse Models of ALS-Like Degeneration: Evidence for Homeostatic Neuroprotection
Authors: Brian O. Orr, Anna G. Hauswirth, Barbara Celona, Richard D. Fetter, Giulia Zunino, Evgeny Z. Kvon, Yiwen Zhu, Len A. Pennacchio, Brian L. Black, Graeme W. Davis
Journal: Neuron (2020)
Abstract IA01: Molecular control of the gut microbiome to improve cancer chemotherapy
Authors: Matthew Redinbo
Journal: Cancer Research (2020)

Abstract The diverse and complex communities of GI microbiota play important roles in human health, particularly with respect to cancer chemotherapy. We focused on systems where gut bacteria catalyze reactions that exert a profoundly negative impact on intestinal tissues and prove to be dose limiting for chemotherapy. The anticancer drug irinotecan is used to treat colon and pancreatic cancers and is eliminated as an inactivated drug-glucuronide by the phase II drug metabolism. Irinotecan’s dose-limiting toxicity is severe delayed diarrhea hypothesized to arise from the reactivation of the inactive irinotecan metabolite in the gut. We pinpointed the molecular basis of this reactivation to the beta-glucuronidase sugar-scavenging enzymes present in gut bacteria. We further developed potent, selective, and nonlethal inhibitors to bacterial beta-glucuronidase (GUS) enzymes and demonstrated that they prevented GI injury in mouse models of irinotecan-induced intestinal damage. Bacterial GUS inhibitors also prevent these sites of intestinal damage in mice treated with NSAIDs, which are glucuronidated and used to control cancer-related inflammation. We have since extended this work to the tyrosine kinase inhibitor regorafenib and to a probe-enabled activity-based proteomics pipeline to discover the enzymes driving the production of toxic metabolites. Together, our data demonstrate that enzyme targets in the GI microbiota can be inhibited to improve cancer care in a manner that can advance the promise of personalized medicine. Furthermore, our results shed significant light on the mammalian-microbial axes of chemical communication ongoing between two domains of life in the “higher-order” human superorganism. Citation Format: Matthew Redinbo. Molecular control of the gut microbiome to improve cancer chemotherapy [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr IA01.
T-cell-mediated autologous hepatocytotoxicity in patients with chronic hepatitis C virus infection*1
Authors: Y LIAW
Journal: Hepatology (1995)

Virus-specific cytotoxic T lymphocytes (CTLs) have been suggested to be responsible for the liver injuries in patients with hepatitis C virus (HCV) infection. However, there has been no report of direct evidence to substantiate this hypothesis. In this study, we performed in vitro autologous hepatocytotoxicity assay in 45 patients to examine a possible role of CTLs to HCV-infected liver cells. The data were correlated with histology activity index of liver biopsy specimens. Lymphocyte subsets and hepatocyte expression of human major histocompatibility complex antigens class I and class II (HLA-I and HLA-II) were also evaluated. The immunohistochemical study showed more prominent HLA-I expression than HLA-II on hepatocytes (mean score ± SEM: 2.34 ± 0.11 vs. 0.42 ± 0.08; P < .01). The lymphocyte subset analysis showed that CD8+ T cells were dominant in the lobular areas showing spotty necrosis, whereas CD4+ T cells were prominent in the portal and periportal areas (P < .01). Most patients had a significant T cell-mediated cytotoxicity to hepatocytes as compared with non-T cells (percentage cytotoxicity ± SEM: 46.4 ± 2.3 vs. 13.8 ± 2.7; P <.001). T cell-mediated hepatocytotoxicity had a linear correlation with HAI (P < .05). The T cell-mediated cytotoxicity could be blocked by anti-CD8 (43.7% vs. 9.5%, P < .05) or by anti-HLA-I (43.7% vs. 18.5%, P < .05) but not by anti-CD4 or anti-HLA-II monoclonal antibodies. These findings strongly suggest that HLA-I—restricted, CD8+ T cell—mediated hepatocytotoxicity is an important pathogenetic mechanism in patients with chronic HCV infection.
Branched chain amino acids exacerbate myocardial ischemia/reperfusion vulnerability via enhancing GCN2/ATF6/PPAR-α pathway-dependent fatty acid oxidation
Authors: Yueyang Li, Zhenyu Xiong, Wenjun Yan, Erhe Gao, Hexiang Cheng, Guiling Wu, Yi Liu, Ling Zhang, Congye Li, Shan Wang, Miaomiao Fan, Huishou Zhao, Fuyang Zhang, Ling Tao
Journal: Theranostics (2020)

Rationale: Myocardial vulnerability to ischemia/reperfusion (I/R) injury is strictly regulated by energy substrate metabolism. Branched chain amino acids (BCAA), consisting of valine, leucine and isoleucine, are a group of essential amino acids that are highly oxidized in the heart. Elevated levels of BCAA have been implicated in the development of cardiovascular diseases; however, the role of BCAA in I/R process is not fully understood. The present study aims to determine how BCAA influence myocardial energy substrate metabolism and to further clarify the pathophysiological significance during cardiac I/R injury. Methods: Parameters of glucose and fatty acid metabolism were measured by seahorse metabolic flux analyzer in adult mouse cardiac myocytes with or without BCAA incubation. Chronic accumulation of BCAA was induced in mice receiving oral BCAA administration. A genetic mouse model with defective BCAA catabolism was also utilized. Mice were subjected to MI/R and the injury was assessed extensively at the whole-heart, cardiomyocyte, and molecular levels. Results: We confirmed that chronic accumulation of BCAA enhanced glycolysis and fatty acid oxidation (FAO) but suppressed glucose oxidation in adult mouse ventricular cardiomyocytes. Oral gavage of BCAA enhanced FAO in cardiac tissues, exacerbated lipid peroxidation toxicity and worsened myocardial vulnerability to I/R injury. Etomoxir, a specific inhibitor of FAO, rescued the deleterious effects of BCAA on I/R injury. Mechanistically, valine, leucine and their corresponding branched chain α-keto acid (BCKA) derivatives, but not isoleucine and its BCKA derivative, transcriptionally upregulated peroxisome proliferation-activated receptor alpha (PPAR-α). BCAA/BCKA induced PPAR-α upregulation through the general control nonderepresible-2 (GCN2)/ activating transcription factor-6 (ATF6) pathway. Finally, in a genetic mouse model with BCAA catabolic defects, chronic accumulation of BCAA increased FAO in myocardial tissues and sensitized the heart to I/R injury, which could be reversed by adenovirus-mediated PPAR-α silencing. Conclusions: We identify BCAA as an important nutrition regulator of myocardial fatty acid metabolism through transcriptional upregulation of PPAR-α. Chronic accumulation of BCAA, caused by either dietary or genetic factors, renders the heart vulnerable to I/R injury via exacerbating lipid peroxidation toxicity. These data support the notion that BCAA lowering methods might be potentially effective cardioprotective strategies, especially among patients with diseases characterized by elevated levels of BCAA, such as obesity and diabetes.
Occurrence of hepatocellular carcinoma and decompensation in Western European patients with cirrhosis type B*1
Authors: G FATTOVICH
Journal: Hepatology (1995)

To examine the morbidity of compensated cirrhosis type B, a cohort of 349 Western European, white patients (86% men; mean age, 44 years) with biopsy-proven cirrhosis was followed up for a mean period of 73 months and was studied for occurrence of hepatocellular carcinoma (HCC) and decompensation. At entry into the study all patients were tested for hepatitis B e antigen (HBeAg; 34% of patients were HBeAg-positive) and antibody to hepatitis delta virus (anti-HDV; 20% of patients were anti-HDV-positive); 48% of 252 patients tested were hepatitis B virus (HBV)-DNA-positive. During follow-up HCC developed in 32 (9%) of the 349 patients and decompensation was observed in 88 (28%) of 317 tumor-free patients. Five years after diagnosis, the probability of HCC appearance was 6% and the probability of decompensation was 23%. After the first episode of decompensation the probability of survival was 35% at 5 years. Cox's regression analysis identified three variables that independently correlated with HCC: age, serum levels of platelets, and liver firmness on physical examination. HBV (HBeAg or HBV-DNA) and HDV (anti-HDV) markers at presentation had no prognostic value for the development of HCC. In conclusion, a high proportion of patients with HBsAg-positive compensated cirrhosis do not experience worsening of their condition for several years, but once decompensation occurs life expectancy is poor. European, white patients with compensated cirrhosis type B are at consistent risk for HCC. Prognostic factors for HCC reflect an advanced stage of cirrhosis and support the hypothesis that development of a tumor could be the likely consequence of long-standing hepatic disease.
Pre-clinical rationale for developing DTS-201, a tetrapeptide prodrug of doxorubicin
Authors: Jean Pierre Delord, Vincent Dubois, Jerome Quinonero, Karine Vialatte, Fabienne Cournarie, Catherine Mazerolles, Roland Bugat, Philippe Rochaix, Denis Ravel
Journal: Cancer Research (2005)

4125  DTS-201 (CPI-004 Na) is a tetrapeptide prodrug of doxorubicin belonging to the family of tumor-selective enzyme prodrugs. To date, two oligopeptidases involved in the reactivation of the prodrug have been identified: CD10 (CALLA, neprilysin) and TOP (Thimet oligopeptidase), which are overexpressed in some solid tumors. This new compound has been shown to be stable and inactive in human blood and not taken up by tissues after injection in the mouse (1-2). Single and repeated dose administration studies with DTS-201 were conducted in the mouse, rat and dog. All the clinical signs observed were identical to those already described for doxorubicin but were noticed at much higher doses indicating that the prodrug reduced systemic toxicity. Doses of DTS-201 (17.8 mg/kg) upto 8 times the doxorubicin dose in particular, were given without inducing significant cardiomopathy following 7 repeated injections in the rat. To test whether the prodrug DTS-201 is effectively cleaved to an active form in-vivo, the efficacy of DTS-201 and doxorubicin was compared using two tumour xenograft models exhibiting high (H1299 human colon cancer) or low (PC-3 human prostate carcinoma) CD10 immunostaining intensity. The superior anti-tumour potency of DTS-201 in the H1299 tumor compared to the PC3 tumour, confirms the role of CD10 in the activation of the prodrug. On the other hand, the immunohistochemistry analysis of a large panel of human tumor biopsies suggest that CD10 and TOP are both expressed in 50% of prostate cancers and in 98% of breast carcinomas. Based on this preclinical data, a Phase I study in advanced or metastatic tumor patients will be conducted. In order to reinforce the development rationale of this new peptide-conjugated cytotoxic agent, the expression of CD10 and TOP will be evaluated in the tumors of every patient involved in the study. All the pre-clinical safety, efficacy and immunohistochemistry analysis data will be presented.