tbuckley/cabot-search huggingface dataset:
THU0238 Activated inf-Ɣ and il-18 in adult onset still’s disease
Authors: YB Park, SH Lee, SK Lee
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Adult onset Still¡¯s disease (AOSD) is a systemic inflammatory disease in adults. The clinical and laboratory findings of AOSD are well known, however, the cause and pathophysiology of AOSD are scarcely understood. One characteristic finding of AOSD is a reticuloendothelial system activation, which is showed up as lymphadenopathy, hepatosplenomegaly, elevated serum ferritin levels, and combined hemophagocytic syndrome in severe cases. <h3>Objectives</h3> To figure out the cytokine network in AOSD, we measured the levels of serum cytokines related to macrophages which is major cell in reticuloendothelial system. <h3>Methods</h3> The subjects of the present study were 19 patients diagnosed with AOSD according to Yamaguchi criteria from 1998.6 to 2000.3. Sixty-three serial blood samples were obtained from these nineteen AOSD patients (male:5, female:14) and also blood samples were obtained from age- and sex-matched 16 healthy adults as controls. Serum levels of tumour necrosis factor-α(TNF-α), interleukin-1b (IL-1b), interferon-γ(INF-γ), interleukin-12 (IL-12), interleukin-12 p40 (IL-12 p40), interleukin-15(IL-15), and interleukin-18(IL-18) were measured by the ELISA method. Serum ferritin and C-reactive protein levels were measured by nephelometry. Regression analysis (mixed effect model) was used to correct the effect of serial samples in each individual. <h3>Results</h3> Mean age of AOSD patients was 35.5¡¾11.3 years. Nine patients had serious clinical courses which demanded more than once steroid pulse therapy and/or cyclophosphamide therapy. Four cases had died despite having received intensive care (3: disseminated intravascular coagulation (DIC) and shock, 1: heart failure), and hemophagocytic syndrome was confirmed by bone marrow biopsy in one pancytopenic patient. Serum levels of IL-1b, IL-12 p40, IL-15, IL-18, TNF-α, and INF-γ were significantly higher in AOSD patients. INF-γ levels well correlated with serum ferritin levels that reflect the disease activity of AOSD. The cytokines that correlated with INF-γ were IL-18 and TNF-α, not IL-12 or IL-15. IL-18 levels well correlated with INF-γ, but it did not correlate with TNF-α and ferritin levels. <h3>Conclusion</h3> Macrophage related cytokines were activated in AOSD patients. INF-γ levels correlated with serum ferritin levels, and the activation pathway of INF-γ in AOSD was thought to be through IL-18, not IL-12 or IL-15.
Prevalence and Severity of Alzheimer Disease in Individuals With Down Syndrome
Authors: Michael S. Rafii, Stephanie L. Santoro
Journal: JAMA Neurology (2018)

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 Neurology 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 Neurology journal
Association of Primary Resistance to Immune Checkpoint Inhibitors in Metastatic Colorectal Cancer With Misdiagnosis of Microsatellite Instability or Mismatch Repair Deficiency Status
Authors: Romain Cohen, Elisabeth Hain, Olivier Buhard, Agathe Guilloux, Armelle Bardier, Rachid Kaci, Philippe Bertheau, Florence Renaud, Frédéric Bibeau, Jean-François Fléjou, Thierry André, Magali Svrcek, Alex Duval
Journal: JAMA Oncology (2018)

Primary resistance to immune checkpoint inhibitors is observed in 10% to 40% of patients with metastatic colorectal cancer (mCRC) displaying microsatellite instability (MSI) or defective mismatch repair (dMMR).To investigate possible mechanisms underlying primary resistance to immune checkpoint inhibitors of mCRC displaying MSI or dMMR.This post hoc analysis of a single-center, prospective cohort included 38 patients with mCRC diagnosed as MSI or dMMR by local laboratories and entered into trials of immune checkpoint inhibitors between January 1, 2015, and December 31, 2016. The accuracy of MSI or dMMR status was also assessed in a retrospective cohort comprising 93 cases of mCRC that were diagnosed as MSI or dMMR between January 1, 1998, and December 31, 2016, in 6 French hospitals. Primary resistance of mCRC was defined as progressive disease according to Response Evaluation Criteria in Solid Tumors criteria, 6 to 8 weeks after initiation of immune checkpoint inhibitors, without pseudo-progression. All tumor samples were reassessed for dMMR status using immunohistochemistry with antibodies directed against MLH1, MSH2, MSH6, and PMS2, and for MSI using polymerase chain reaction with pentaplex markers and with the HSP110 T17 (HT17) repeat.The primary outcome was positive predictive value.Among the 38 patients (15 women and 23 men; mean [SD] age, 55.6 [13.7] years) in the study with mCRC displaying MSI or dMMR, primary resistance to immune checkpoint inhibitors was observed in 5 individuals (13%). Reassessment of the status of MSI or dMMR revealed that 3 (60%) of these 5 resistant tumors were microsatellite stable or displayed proficient mismatch repair. The positive predictive value of MSI or dMMR status assessed by local laboratories was therefore 92.1% (95% CI, 78.5%-98.0%). In the retrospective cohort of 93 patients (44 women and 49 men; mean [SD] age, 56.8 [18.3] years) without immune checkpoint inhibitor treatment, misdiagnosis of the MSI or dMMR status by local assessment was 10% (n = 9), with a positive predictive value of 90.3% (95% CI, 82.4%-95.0%). Testing for MSI with the HT17 assay confirmed the MSI or dMMR status in 2 of 4 cases showing discrepant results between immunohistochemistry and pentaplex polymerase chain reaction (ie, dMMR but microsatellite stable).Primary resistance of mCRC displaying MSI or dMMR to immune checkpoint inhibitors is due mainly to misdiagnosis of their MSI or dMMR status. Larger studies are required to confirm these findings. Microsatellite instability or dMMR status should be tested routinely using both immunohistochemistry and polymerase chain reaction methods prior to treatment with immune checkpoint inhibitors.
Abstract 19827: Vascular Risk Levels Affect the Predictive Value of Platelet Reactivity for the Occurrence of Major Adverse Cardiovascular Events in Patients on Clopidogrel: Systematic Review and Collaborative Meta-analysis of Individual Patient Data
Authors: Jean-Luc Reny, Pierre Fontana, Willibald Hochholzer, Franz-Josef Neumann, Jurren ten Berg, Paul Janssen, Tobias Geisler, Meinrad Gawaz, Rossella Marcucci, Ana-Maria Gori, Thomas Cuisset, Marie-Christine Alessi, Paul Gurbel, Philippe Berdagué, Gerald Yong, Dominick Angiolillo, Daniel Aradi, Roy Beigel, Gianluca Campo, Gianluca Campo, Christophe Combescure
Journal: Circulation (2014)

Introduction: Prior studies have shown an association between high on-clopidogrel platelet reactivity (PR) and the risk of major adverse cardiovascular events (MACE). However, large intervention trials on PR-tailored treatments have been neutral. Hypothesis: The clinical relevance of PR in predicting MACE varies according to patients’ cardiovascular risk levels. Methods: We undertook a systematic review and meta-analysis of individual patient data on MACE outcomes (acute coronary syndromes (ACS), ischemic strokes, and vascular deaths) in relation to PR and its interaction with cardiovascular risk levels. PR was determined using ADP-induced light transmission aggregometry with a primary concentration of 20μM ADP. Results: Thirteen prospective cohort studies totalled 6,478 clopidogrel-treated patients who experienced 421 MACE (6.5%) during a median follow-up of 12 months. The risk of MACE associated with PR increased differentially according to the number of risk factors present (age&gt;75 years, ACS at inclusion, diabetes, and hypertension; interaction p=0.04): no association to PR in low-risk patients (no risk factor) (p=0.48); 3.2 times greater risk of MACE in high PR (&gt; 60%) intermediate-risk patients (one risk factor) (p=0.001); 2.9 and 3.7 times greater risk of MACE in medium PR (41%-60%) and high PR (&gt;60%) high-risk patients (≥2 risk factors) (p=0.0004 and 0.0003, respectively). These interactions followed the same trends in studies using 5μM ADP. Conclusions: The magnitude of the association between PR and MACE risk is strongly dependant on the level of cardiovascular risk faced by patients on clopidogrel suggesting that PR-tailored strategies may be most effective in higher-risk patients.
Impact of UGT1A1 genotype on the efficacy and safety of irinotecan-based chemotherapy in metastatic colorectal cancer (mCRC): A preplanned analysis of the phase III AXEPT trial
Authors: R. Xu, K. Muro, T.W. Kim, Y.S. Park, W. Wang, S.-W. Han, M. Kotaka, Y.-H. Deng, J.B. Ahn, M. Nakamura, Y. Ba, S.-H. Cho, T. Kato, T. Zhang, K.-W. Lee, H. Matsuoka, W.-J. Fang, S. Morita, S. Iwasa, S. Junichi
Journal: Annals of Oncology (2018)
Stereotactic ablative radiotherapy for oligometastatic cancers: Efficacy and toxicity results from the randomized SABR-COMET Trial
Authors: S. Senan, R. Olson, S. Harrow, S. Gaede, A. Louie, C. Haasbeek, L. Mulroy, M. Lock, G. Rodrigues, B. Yaremko, D. Schellenberg, B. Ahmad, G. Griffioen, S. Senthi, M. Liu, K. Moore, S. Currie, G. Bauman, A. Warner, D. Palma
Journal: Annals of Oncology (2018)
Targeting low-normal or high-normal mean arterial pressure after cardiac arrest and resuscitation: a randomised pilot trial
Authors: Pekka Jakkula, Ville Pettilä, Markus B. Skrifvars, Johanna Hästbacka, Pekka Loisa, Marjaana Tiainen, Erika Wilkman, Jussi Toppila, Talvikki Koskue, Stepani Bendel, Thomas Birkelund, Raili Laru-Sompa, Miia Valkonen, Matti Reinikainen
Journal: Intensive Care Medicine (2018)

We aimed to determine the feasibility of targeting low-normal or high-normal mean arterial pressure (MAP) after out-of-hospital cardiac arrest (OHCA) and its effect on markers of neurological injury. In the Carbon dioxide, Oxygen and Mean arterial pressure After Cardiac Arrest and REsuscitation (COMACARE) trial, we used a 23 factorial design to randomly assign patients after OHCA and resuscitation to low-normal or high-normal levels of arterial carbon dioxide tension, to normoxia or moderate hyperoxia, and to low-normal or high-normal MAP. In this paper we report the results of the low-normal (65–75 mmHg) vs. high-normal (80–100 mmHg) MAP comparison. The primary outcome was the serum concentration of neuron-specific enolase (NSE) at 48 h after cardiac arrest. The feasibility outcome was the difference in MAP between the groups. Secondary outcomes included S100B protein and cardiac troponin (TnT) concentrations, electroencephalography (EEG) findings, cerebral oxygenation and neurological outcome at 6 months after cardiac arrest. We recruited 123 patients and included 120 in the final analysis. We found a clear separation in MAP between the groups (p < 0.001). The median (interquartile range) NSE concentration at 48 h was 20.6 µg/L (15.2–34.9 µg/L) in the low-normal MAP group and 22.0 µg/L (13.6–30.9 µg/L) in the high-normal MAP group, p = 0.522. We found no differences in the secondary outcomes. Targeting a specific range of MAP was feasible during post-resuscitation intensive care. However, the blood pressure level did not affect the NSE concentration at 48 h after cardiac arrest, nor any secondary outcomes.
Probiotics for gastroenteritis in young children do not improve symptoms, studies find
Authors: Susan Mayor
Journal: BMJ (2018)

Commonly used probiotics are not effective in improving diarrhoea or vomiting in young children presenting to hospital emergency departments with gastroenteritis, two randomised trials have found.12

Acute gastroenteritis is a common cause of hospital admissions in young children. Current treatment options include controlling symptoms, preventing dehydration, and preventing the spread of infection to contacts. The use of probiotics in children with acute gastroenteritis has been growing after meta-analyses suggested improved outcomes—but most trials have been small and non-randomised and lacked quality control for the probiotics tested.

US researchers carried out a prospective trial in 971 children aged 3 months to 4 years (median age 1.4 years) who presented to emergency departments at 10 hospital centres. The children were randomly assigned to a five day course of Lactobacillus rhamnosus GG (dose …
Self-Directed Walk With Ease Workplace Wellness Program — Montana, 2015–2017
Authors: Robin P. Silverstein, Melissa VanderVos, Heather Welch, Alex Long, Charlotte D. Kaboré, Jennifer M. Hootman
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Arthritis occurs in 27% of adults in Montana, among whom 50% have activity limitations, 16% have social participation restrictions, and 23% have severe joint pain attributable to arthritis (1). Physical activity is beneficial in managing arthritis symptoms and in preventing other chronic diseases (2). Walk With Ease is a 6-week evidence-based physical activity program recommended by CDC to increase physical activity and help improve arthritis symptoms (3). In 2015, Walk With Ease was added to an ongoing workplace wellness program for Montana state employees; the results for five outcomes (minutes spent walking, engaging in other physical activity [including swimming, bicycling, other aerobic equipment use, and other aerobic exercise], stretching, pain, and fatigue) were analyzed by the Montana Department of Public Health and Human Services and CDC. Outcomes at baseline (pretest), 6 weeks after the program (posttest), and 6 months later (follow-up) were analyzed by self-reported arthritis status at the time the participant enrolled in the program. Significant increases (p<0.05) in the mean number of minutes spent per week walking and engaging in other physical activity were observed among participants with and without arthritis at the 6-week posttest. Time spent stretching did not change significantly at posttest for either group. Mean pain levels among participants without arthritis increased significantly both at the 6-week posttest and 6-month follow-up; however, pain and fatigue decreased significantly at posttest and follow-up for participants with or without arthritis who began the program with moderate or severe pain and fatigue levels. The data from these analyses suggest that, as a component of a workplace wellness program, self-directed Walk With Ease might be effective in increasing physical activity not only among adults with arthritis, but also among persons without arthritis.
Abstract 16475: PLK1: A Key Regulator of PAH Pulmonary Smooth Muscle Cells Proliferation
Authors: Alice Bourgeois, Caroline Lambert, Renée Paradis, Isabelle Trinh, Sandra Breuils-Bonnet, Steeve Provencher, Sébastien Bonnet, Olivier Boucherat
Journal: Circulation (2017)

Rationale: Pulmonary arterial hypertension (PAH) is a progressive and fatal disease of the pulmonary vasculature that has no cure. Although the causal pathomechanisms contributing to remodeling of the pulmonary vascular bed in PAH are still unclear, several features, including hyperproliferation and resistance to apoptosis of pulmonary smooth muscle cells (PASMCs), have led to the emergence of the cancer-like concept. Since uncontrolled cell division is a common pathological manifestation of these two entities, this opens the possibility of combining therapeutic agents that specifically target the cell cycle used in cancer to treat PAH. Polo-like kinase 1 (PLK1) is a serine/threonine kinase that plays a critical role in mitosis. Its overexpression is associated with tumor development. Objective: Given that cancer cells and PAH-PASMCs exhibit similarities, we hypothesized that PLK1 up-regulation in PAH promotes PASMC proliferation and resistance to apoptosis leading to vascular remodeling. Methods and Resu...
Screening and Brief Behavioral Counseling Interventions to Reduce Unhealthy Alcohol Use in Adults 18 Years and Older, Including Pregnant Women
Authors: Marc A. Schuckit
Journal: JAMA Psychiatry (2018)

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
FISHing for the Miracle of Eicosapentaenoic Acid
Authors: John J.P. Kastelein, Erik S.G. Stroes
Journal: New England Journal of Medicine (2018)

Bhatt et al. report in the Journal the results of the Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT), in which 8179 high-risk patients who had elevated triglyceride levels and had been receiving statin therapy were randomly assigned to receive 2 g of icosapent ethyl twice daily or placebo containing mineral oil.1 The patients were enrolled mostly on the basis of secondary prevention (71%), and almost 60% had diabetes. At baseline, low-density lipoprotein (LDL) cholesterol levels were well controlled among the patients (median value, 75.0 mg per deciliter [1.94 mmol per liter]), and triglyceride levels were slightly elevated (median . . .
Re: Maxine Sun, Lorenzo Marconi, Tim Eisen, et al. Adjuvant Vascular Endothelial Growth Factor–targeted Therapy in Renal Cell Carcinoma: A Systematic Review and Pooled Analysis. Eur Urol 2018;74:611–20
Authors: Eu Chang Hwang, Michael C. Risk, Philipp Dahm
Journal: European Urology (2018)
Guidelines for Ending Childhood and Adolescent Tuberculosis
Authors: M.J. Friedrich
Journal: JAMA (2018)

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
DeepSeeNet: A Deep Learning Model for Automated Classification of Patient-based Age-related Macular Degeneration Severity from Color Fundus Photographs
Authors: Yifan Peng, Shazia Dharssi, Qingyu Chen, Tiarnan D. Keenan, Elvira Agrón, Wai T. Wong, Emily Y. Chew, Zhiyong Lu
Journal: Ophthalmology (2018)
Regulation of human mucin MUC17 expression in pancreatic adenocarcinoma cells
Authors: Wade Junker, Surinder Batra
Journal: Cancer Research (2008)

78  Pancreatic cancer is a devastating malignancy for which treatment and detection remain enigmatic. New diagnostic markers, therapeutics, and a better understanding of disease progression are urgently required to improve survival of patients. The mucin glycoproteins are a family of diverse molecules that have enabled us to detect cancers in relation to their normal tissue counterparts. One such mucin, mucin 17 (MUC17), is detected in pancreatic cancer tissues, which sharply contrasts the absence of MUC17 expression in the normal pancreas. We hypothesized that specific pathways, which are associated with expression of MUC17, control its aberrant expression and are activated in pancreatic cancer. To determine the significance of MUC17 expression in pancreatic cancer, it was necessary to define the underlying molecular mechanisms implicated in its aberrant expression. The pancreatic adenocarcinoma AsPC-1 cell line was used to investigate which signaling pathways contribute to MUC17 expression. Our data show that a 1,168 bp region proximal to the MUC17 coding sequence contains both promoter and enhancer activities. The MUC17 transcription initiator was identified and confirmed by primer extension analysis. Transcription initiates 54bp upstream of the ATG codon previously identified as the translation initiation site (Moniaux N., et al. 2006, 281, 23676-23685). Using databases, potential transcription factor binding sites (including those for: VDR/RXR heterodimers, NFκB, SMAD3, SMAD4, CDX-2, PDX-1, MZF-1, KLFs, GATA-1, AP-1, and growth factor responsiveness) were identified. Luciferase reporter assay results in AsPC-1 cells provide evidence that the cytokines, TNF-α and IL-6, and the growth factors, TGFβ-1, TGFβ-2, and EGF, are capable of activating transcription by increasing enhancer and/or basal promoter activities. Quantitative real-time PCR and western blotting demonstrate that an observed increase in MUC17 message results in increased production of MUC17 at the protein level, via activation by exogenous cytokines and growth factors and is dose and time dependent. Our results also provide evidence that combinations of growth factors (EGF + TGFβ-1) or growth factor and cytokine (TGFβ-2 + IL-6) up regulate MUC17 in an additive manner. Of particular interest is that when the cytokine TNF-α is combined with growth factors (+EGF, +TGFβ-1, or +TGFβ-2) a general decrease in MUC17 expression is observed (below that of TNF-α or growth factor treatment alone). This suggests that a counter mechanism exists for the down regulation of MUC17. MUC17 expression in the presence of growth factors or IL-6 may decrease if signals such as TNF-α are produced. Additional studies are underway to determine if expression of MUC17 is involved in the progression of disease or is lost as the result of developing inflammation associated with ductal pancreatic cancer (work, in part, was supported by the NIH grants UO1 CA 111294 and T32 CA09476).