tbuckley/cabot-search huggingface dataset:
Bcl‐2 as a Therapeutic Target in Human Tubulointerstitial Inflammation
Authors: Kichul Ko, Jianing Wang, Stuart Perper, Yulei Jiang, Denisse Yanez, Natalya Kaverina, Junting Ai, Vladimir M. Liarski, Anthony Chang, Yahui Peng, Li Lan, Susan Westmoreland, Lisa Olson, Maryellen L. Giger, Li Chun Wang, Marcus R. Clark
Journal: Arthritis & Rheumatology (2016)

Objective In lupus nephritis, tubulointerstitial inflammation (TII) is associated with in situ adaptive immune cell networks that amplify local tissue damage. Since conventional therapy appears ineffective for severe TII, and these patients often progress to renal failure, understanding in situ mechanisms might reveal new therapeutic targets. This study was undertaken to assess whether dysregulated apoptotic regulators maintain local adaptive immunity and drive inflammation in TII. Methods This study utilized novel computational approaches that, when applied to multicolor confocal images, quantified apoptotic regulator protein expression in selected lymphocyte subsets. This approach was validated using laser‐capture microdissection (LCM) coupled to quantitative polymerase chain reaction (qPCR). Furthermore, the consequences of dysregulated apoptotic mediator expression were explored in a murine model of lupus nephritis. Results Analyses of renal biopsy tissue from patients with lupus nephritis and those with mixed cellular renal allograft rejection revealed that the B cell lymphoma 2 protein (Bcl‐2) was frequently expressed in infiltrating lymphocytes, whereas expression of myeloid cell leukemia 1 was low. In contrast, the reciprocal pattern of expression was observed in tonsil germinal centers. These results were consistent with RNA expression data obtained using LCM and qPCR. Bcl‐2 was also highly expressed in tubulointerstitial infiltrates in (NZB × NZW)F1 (NZB/NZW) mice. Furthermore, treatment of NZB/NZW mice with ABT‐199, a selective oral inhibitor of Bcl‐2, prolonged survival and prevented proteinuria and development of TII in a lupus prevention model. Interestingly, glomerular immune complexes were partially ameliorated by ABT‐199 treatment, and serum anti–double‐stranded DNA antibody titers were unaffected. Conclusion These data demonstrate that Bcl‐2 is an attractive therapeutic target in patients with lupus nephritis who manifest TII.
A Phase 1/2 Study of Ipilimumab in Women with Metastatic or Recurrent Hpv-Related Cervical Carcinoma: a Study of the Princess Margaret and Chicago N01 Consortia
Authors: S. Lheureux, M.O. Butler, G. Fleming, H.W. Hirte, M.C. Cristea, P. Ghatage, L. Martin, H. Mackay, N. Dhani, M. Wilson, C. Martin-Lorente, J. Quintos, L. Wang, S. Udagani, A.M. Oza
Journal: Annals of Oncology (2014)
Alternating Electric Fields Therapy for Recurrent Glioblastoma - Novottf-100A System: Updated Outcomes and Toxicity Based on the Analysis of Patient Registry Data
Authors: M.M. Mrugala, H.H. Engelhard, N. Butowski, D.D. Tran, Y. Kew, R. Cavaliere, J. Villano, D. Bota, S. Kesari, J. Rudnick, A. Sumrall, J.J. Zhu, E.T. Wong
Journal: Annals of Oncology (2014)
Opsoclonus-Myoclonus Syndrome in the Era of Neuronal Cell Surface Antibodies
Authors: Simone Gallerini, Luca Marsili, Roberto Marconi
Journal: JAMA Neurology (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 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
Less invasive hemodynamic monitoring in critically ill patients
Authors: Jean-Louis Teboul, Bernd Saugel, Maurizio Cecconi, Daniel De Backer, Christoph K. Hofer, Xavier Monnet, Azriel Perel, Michael R. Pinsky, Daniel A. Reuter, Andrew Rhodes, Pierre Squara, Jean-Louis Vincent, Thomas W. Scheeren
Journal: Intensive Care Medicine (2016)
Precision medicine in patients with allergic diseases: Airway diseases and atopic dermatitis—PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma &amp; Immunology
Authors: Antonella Muraro, Robert F. Lemanske, Peter W. Hellings, Cezmi A. Akdis, Thomas Bieber, Thomas B. Casale, Marek Jutel, Peck Y. Ong, Lars K. Poulsen, Peter Schmid-Grendelmeier, Hans-Uwe Simon, Sven F. Seys, Ioana Agache
Journal: Journal of Allergy and Clinical Immunology (2016)

In this consensus document we summarize the current knowledge on major asthma, rhinitis, and atopic dermatitis endotypes under the auspices of the PRACTALL collaboration platform. PRACTALL is an initiative of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology aiming to harmonize the European and American approaches to best allergy practice and science. Precision medicine is of broad relevance for the management of asthma, rhinitis, and atopic dermatitis in the context of a better selection of treatment responders, risk prediction, and design of disease-modifying strategies. Progress has been made in profiling the type 2 immune response-driven asthma. The endotype driven approach for non-type 2 immune response asthma, rhinitis, and atopic dermatitis is lagging behind. Validation and qualification of biomarkers are needed to facilitate their translation into pathway-specific diagnostic tests. Wide consensus between academia, governmental regulators, and industry for further development and application of precision medicine in management of allergic diseases is of utmost importance. Improved knowledge of disease pathogenesis together with defining validated and qualified biomarkers are key approaches to precision medicine.
Prediction of Individual Response to Electroconvulsive Therapy via Machine Learning on Structural Magnetic Resonance Imaging Data
Authors: Ronny Redlich, Nils Opel, Dominik Grotegerd, Katharina Dohm, Dario Zaremba, Christian Bürger, Sandra Münker, Lisa Mühlmann, Patricia Wahl, Walter Heindel, Volker Arolt, Judith Alferink, Peter Zwanzger, Maxim Zavorotnyy, Harald Kugel, Udo Dannlowski
Journal: JAMA Psychiatry (2016)

<h3>Importance</h3> Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depression. However, biomarkers that accurately predict a response to ECT remain unidentified. <h3>Objective</h3> To investigate whether certain factors identified by structural magnetic resonance imaging (MRI) techniques are able to predict ECT response. <h3>Design, Setting, and Participants</h3> In this nonrandomized prospective study, gray matter structure was assessed twice at approximately 6 weeks apart using 3-T MRI and voxel-based morphometry. Patients were recruited through the inpatient service of the Department of Psychiatry, University of Muenster, from March 11, 2010, to March 27, 2015. Two patient groups with acute major depressive disorder were included. One group received an ECT series in addition to antidepressants (n = 24); a comparison sample was treated solely with antidepressants (n = 23). Both groups were compared with a sample of healthy control participants (n = 21). <h3>Main Outcomes and Measures</h3> Binary pattern classification was used to predict ECT response by structural MRI that was performed before treatment. In addition, univariate analysis was conducted to predict reduction of the Hamilton Depression Rating Scale score by pretreatment gray matter volumes and to investigate ECT-related structural changes. <h3>Results</h3> One participant in the ECT sample was excluded from the analysis, leaving 67 participants (27 men and 40 women; mean [SD] age, 43.7 [10.6] years). The binary pattern classification yielded a successful prediction of ECT response, with accuracy rates of 78.3% (18 of 23 patients in the ECT sample) and sensitivity rates of 100% (13 of 13 who responded to ECT). Furthermore, a support vector regression yielded a significant prediction of relative reduction in the Hamilton Depression Rating Scale score. The principal findings of the univariate model indicated a positive association between pretreatment subgenual cingulate volume and individual ECT response (Montreal Neurological Institute [MNI] coordinates x = 8, y = 21, z = −18;<i>Z</i> score, 4.00;<i>P</i> &lt; .001; peak voxel<i>r</i> = 0.73). Furthermore, the analysis of treatment effects revealed a increase in hippocampal volume in the ECT sample (MNI coordinates x = −28, y = −9, z = −18;<i>Z</i>score, 7.81;<i>P</i> &lt; .001) that was missing in the medication-only sample. <h3>Conclusions and Relevance</h3> A relatively small degree of structural impairment in the subgenual cingulate cortex before therapy seems to be associated with successful treatment with ECT. In the future, neuroimaging techniques could prove to be promising tools for predicting the individual therapeutic effectiveness of ECT.
Urbanization Level and Vulnerability to Heat-Related Mortality in Jiangsu Province, China
Authors: Kai Chen, Lian Zhou, Xiaodong Chen, Zongwei Ma, Yang Liu, Lei Huang, Jun Bi, Patrick L. Kinney
Journal: Environmental Health Perspectives (2016)

Background:Although adverse effects of high temperature on mortality have been studied extensively in urban areas, little is known of the heat–mortality associations outside of cities.Objective:We investigated whether heat–mortality associations differed between urban and nonurban areas and how urbanicity affected the vulnerability to heat-related mortality.Methods:We first analyzed heat-related mortality risk in each of 102 counties in Jiangsu Province, China, during 2009–2013 using a distributed-lag nonlinear model. The county-specific estimates were then pooled for more urban (percentage of urban population ≥ 57.11%) and less urban (percentage of urban population < 57.11%) counties using a Bayesian hierarchical model. To explain the spatial variation in associations by county, county-level characteristics affecting heat vulnerability were also examined.Results:We found that the overall mortality risk comparing the 99th vs. 75th percentiles of temperature was 1.43 [95% posterior intervals (PI): 1.36, 1.50] in less urban counties and 1.26 (95% PI: 1.23, 1.30) in more urban counties. The heat effects on cardiorespiratory mortality followed a similar pattern. Higher education level and prevalence of air conditioning were significantly associated with counties having lower risks, whereas percentage of elderly people was significantly associated with increased risks.Conclusion:Our findings reveal that nonurban areas have significant heat-related mortality risks in Jiangsu, China. These results suggest the need for enhanced adaptation planning in Chinese nonurban areas under a changing climate.Citation:Chen K, Zhou L, Chen X, Ma Z, Liu Y, Huang L, Bi J, Kinney PL. 2016. Urbanization level and vulnerability to heat-related mortality in Jiangsu Province, China. Environ Health Perspect 124:1863–1869; http://dx.doi.org/10.1289/EHP204
Next-generation sequencing (NGS) in 936 patients (pts) with advanced cancers to prospectively guide clinical trial selection: The Sarah Cannon Research Institute (SCRI) experience.
Authors: Todd Michael Bauer, David R. Spigel, Zeqiang Ma, Hendrik-Tobias Arkenau, Pranil Chandra, James Prescott, Cassie M Lane, Suzanne Fields Jones, Denise A. Yardley, Johanna C. Bendell, Howard A. Burris, Jeffrey R. Infante
Journal: Journal of Clinical Oncology (2014)

2534 Background: With an increasing number of clinical trials testing new molecularly targeted drugs in pts with specific molecular alterations, there is a growing need for comprehensive molecular profiling in community-based practices where nearly 80% of pts in the United States are treated. In October 2012, SCRI launched an initiative to identify molecular alterations with proven or potential therapeutic significance to match pts to mutation-selective clinical trials. Methods: Samples from consenting pts were analyzed using NGS (CLIA/CAP laboratory) to detect hotspot mutations in 35 cancer-related genes (1000x average coverage). Results were reported to the treating physician within 12 calendar days, used to inform treatment decisions, and captured in a database to enable correlation with clinical outcomes. Results: As of December 31, 2013, 1040 pts consented; 936 (90%) had sufficient material for NGS. At least one mutation was identified in 420 pts (45%). To date, 206 of the 936 pts (22%) have been prospectively enrolled on clinical trials; 91 of these (44%) had no mutations identified, and 12 pts (6%) had non-actionable mutations. One hundred three pts (50%) had actionable mutations. A total of 50 pts (24%) were enrolled to at least one treatment trial of agent(s) matched to their mutation (table, most common genes shown). The remaining 53 pts were enrolled onto trials not matched to genetic alterations (including immunotherapy, 17; antibody-drug conjugate, 8). Response rates and durations will be presented. Conclusions: This first effort to prospectively identify and match pts to clinical trials by NGS in a community practice setting establishes a model to facilitate development of therapies targeting actionable mutations. Nearly half of the pts tested had at least one mutation, and depending on the mutation identified, 10-25% enrolled on a matched trial. Actionable mutation Total pts identified (n) Pts enrolled on any trial Pts enrolled on a trial matched to mutation KRAS 167 45 (27%) 17 (10%) PIK3CA 91 30 (33%) 23 (25%) BRAF 39 10 (26%) 7 (18%) NRAS 26 8 (31%) 3 (12%) FGFR 19 8 (42%) 2 (11%) MET 16 5 (31%) 2 (13%)
A Statewide Nested Case–Control Study of Preterm Birth and Air Pollution by Source and Composition: California, 2001–2008
Authors: Olivier Laurent, Jianlin Hu, Lianfa Li, Michael J. Kleeman, Scott M. Bartell, Myles Cockburn, Loraine Escobedo, Jun Wu
Journal: Environmental Health Perspectives (2016)

Background:Preterm birth (PTB) has been associated with exposure to air pollution, but it is unclear whether effects might vary among air pollution sources and components.Objectives:We studied the relationships between PTB and exposure to different components of air pollution, including gases and particulate matter (PM) by size fraction, chemical composition, and sources.Methods:Fine and ultrafine PM (respectively, PM2.5 and PM0.1) by source and composition were modeled across California over 2000–2008. Measured PM2.5, nitrogen dioxide, and ozone concentrations were spatially interpolated using empirical Bayesian kriging. Primary traffic emissions at fine scale were modeled using CALINE4 and traffic indices. Data on maternal characteristics, pregnancies, and birth outcomes were obtained from birth certificates. Associations between PTB (n = 442,314) and air pollution exposures defined according to the maternal residence at birth were examined using a nested matched case–control approach. Analyses were adjusted for maternal age, race/ethnicity, education and neighborhood income.Results:Adjusted odds ratios for PTB in association with interquartile range (IQR) increases in average exposure during pregnancy were 1.133 (95% CI: 1.118, 1.148) for total PM2.5, 1.096 (95% CI: 1.085, 1.108) for ozone, and 1.079 (95% CI: 1.065, 1.093) for nitrogen dioxide. For primary PM, the strongest associations per IQR by source were estimated for onroad gasoline (9–11% increase), followed by onroad diesel (6–8%) and commercial meat cooking (4–7%). For PM2.5 composition, the strongest positive associations per IQR were estimated for nitrate, ammonium, and secondary organic aerosols (11–14%), followed by elemental and organic carbon (2–4%). Associations with local traffic emissions were positive only when analyses were restricted to births with residences geocoded at the tax parcel level.Conclusions:In our statewide nested case–control study population, exposures to both primary and secondary pollutants were associated with an increase in PTB.Citation:Laurent O, Hu J, Li L, Kleeman MJ, Bartell SM, Cockburn M, Escobedo L, Wu J. 2016. A statewide nested case–control study of preterm birth and air pollution by source and composition: California, 2001–2008. Environ Health Perspect 124:1479–1486; http://dx.doi.org/10.1289/ehp.1510133
Blinding is better than masking
Authors: Kenneth F Schulz, Douglas G Altman, David Moher
Journal: BMJ (2007)

We select the letters for these pages from the rapid responses posted on bmj.com favouring those received within five days of publication of the article to which they refer.Letters are thus an early selection of rapid responses on a particular topic.Readers should consult the website for the full list of responses and any authors' replies, which
SCOPE 1: A phase II/III trial of chemoradiotherapy in esophageal cancer plus or minus cetuximab.
Authors: Thomas Crosby, Chris Hurt, Stephen Falk, Simon Gollins, Somnath Mukherjee, John Staffurth, Ruby Ray, John A. Bridgewater, Ian Geh, David Cunningham, Tim Maughan, Gareth Griffiths
Journal: Journal of Clinical Oncology (2013)

LBA3 Background: SCOPE 1 is the largest multicentre trial of definitive chemo-radiotherapy (dCRT) in localised oesophageal cancer (LOC) in the UK and investigated adding cetuximab to standard cisplatin and fluoropyrimidine treatment. Methods: Patients in this phase II/III trial had LOC and been selected to receive dCRT and were randomised to receive cisplatin 60mg/m 2 D1 and capecitabine 625mg/m 2 daily D1-21 for 4 cycles, cycles 3 and 4 given concurrently with 50Gy in 25 fractions of RT with or without cetuximab 400mg/m 2 D1 followed by 250mg/m 2 weekly. Recruitment continued from 02/2008 until analysis of the phase II endpoint (24 week failure free survival in the cetuximab arm, overall sample size 180: p1=0.60 and p2=0.75, α=0.05, β=0.9) in 01/2012. The phase II endpoint was not met and the IDMC recommended trial closure on the basis of futility. Results: 258 patients were recruited. Median age 67; morphology(%) SCC:ACA 73:27; tumour location(%) upper:middle:lower 11:45:44; stage(%) I:II:III 3:37:60; reason not for surgery(%) disease extent:patient choice:comorbidity 47:38:16. Patients who received cetuximab had: higher non-haematologic toxicity (78 vs 62.8%, p=0.004; primarily dermatological (22 vs 4%) and metabolic (24% vs 11%)); a lower rate of completion of standard therapy (capecitabine 69 vs 85%, p=0.002; cisplatin 77 vs 90%, p=0.005 and radiotherapy (75 vs 86%, p=0.027); reduced failure free survival at 24 weeks (66 vs 77%), median survival (22 vs 25 months, log rank p=0.043) and 2-yr survival (41 vs 56%). Conclusions: In SCOPE 1, disease control and survival in the standard dCRT arm is superior to any previous published multi-centre studies. The use of cetuximab was associated with greater toxicity, lower doses of dCRT and worse survival. Cetuximab cannot be recommended in combination with standard dCRT for unselected patients with oesophageal cancer. Strategies to build on these results should incorporate biomarker driven treatment and latest radiotherapy technologies to safely intensify treatment. This trial was sponsored by Velindre NHS Trust, conducted by Wales Cancer Trials Unit at Cardiff University and supported by CR-UK [grant number C20177/A7256]. Clinical trial information: 47718479.
The Application of Immune Electron Microscopy to the Demonstration of Polyoma Virus Antigen in Cultured Mouse Embryo Cells<xref ref-type="fn" rid="FN2">2</xref>
Authors: P. Biberfeld, N. Ringertz
Journal: JNCI Journal of the National Cancer Institute (1966)

The use of ferritin-labeled antibodies for demonstration of intracellular polyoma virus antigen was investigated. With ferritin immunoglobulin conjugates, specific tagging of characteristic polyoma virus particles was demonstrated in the nuclei and cytoplasm of infected cells. Satisfactory exposure of intracellular antigen to the labeled ferritin was obtained by freeze-sectioning the cells before incubation with the conjugate. Purified conjugates increased the specificity of the staining reaction. The results are discussed with particular reference to the difficulty in the demonstration of precursor protein antigen to the viral capsid.
A Phase 2 Study Of Lenalidomide, Rituximab, Cyclophosphamide and Dexamethasone (LR-CD) For Untreated Low Grade Non-Hodgkin Lymphoma Requiring Therapy: Waldenström’s Macroglobulinemia Cohort Results
Authors: Amylou Constance Dueck, Katherine Gano, Stephen M. Ansell, Chistopher Conley, Grzegorz S. Nowakowski, John Camoriano, Kelly Curtis, Jose F. Leis, James L Slack, Riccardo Valdez, Joseph R. Mikhael, Keith Stewart, Chb, David J. Inwards, David Dingli, Shaji K Kumar, Pierre Noel, Morie A Gertz, Macp, Luis F. Porrata, Stephen Russell, Prashant Kapoor, Francis Buadi, Joseph Colgan, Rafael Fonseca, Thomas M Habermann, Nelson Leung, Rodger E. Tiedemann, Thomas E Witzig, Craig Reeder
Journal: Blood (2013)
Immunomodulatory switch maintenance therapy to improve overall survival in small cell lung cancer (SCLC): The randomized IMPULSE study
Authors: M. Thomas, A. Zurlo, R. Carter, S. Ponce Aix, J. Riera Knorrenschild, A. Navarro Mendivil, M. Domine, J. Kollmeier, R.M. Huber, M. Wolf
Journal: Annals of Oncology (2015)
Molecular and Clinical Effects of Notch Inhibition in Glioma Patients: A Phase 0/I Trial
Authors: Ran Xu, Fumiko Shimizu, Koos Hovinga, Kathryn Beal, Sasan Karimi, Leif Droms, Kyung K. Peck, Philip Gutin, J. Bryan Iorgulescu, Thomas Kaley, Lisa DeAngelis, Elena Pentsova, Craig Nolan, Christian Grommes, Timothy Chan, Dylan Bobrow, Adilia Hormigo, Justin R. Cross, Nian Wu, Naoko Takebe, Katherine Panageas, Percy Ivy, Jeffrey G. Supko, Viviane Tabar, Antonio Omuro
Journal: Clinical Cancer Research (2016)

High-grade gliomas are associated with a dismal prognosis. Notch inhibition via the gamma-secretase inhibitor RO4929097 has emerged as a potential therapeutic option based on modulation of the cancer-initiating cell (CIS) population and a presumed antiangiogenic role.In this phase 0/I trial, 21 patients with newly diagnosed glioblastoma or anaplastic astrocytoma received RO4929097 combined with temozolomide and radiotherapy. In addition to establishing the MTD, the study design enabled exploratory studies evaluating tumor and brain drug penetration and neuroimaging parameters. We also determined functional effects on the Notch pathway and targeting of CISs through analysis of tumor tissue sampled from areas with and without blood-brain barrier disruption. Finally, recurrent tumors were also sampled and assessed for Notch pathway responses while on treatment.Treatment was well tolerated and no dose-limiting toxicities were observed. IHC of treated tumors showed a significant decrease in proliferation and in the expression of the Notch intracellular domain (NICD) by tumor cells and blood vessels. Patient-specific organotypic tumor explants cultures revealed a specific decrease in the CD133+ CIS population upon treatment. Perfusion MRI demonstrated a significant decrease in relative plasma volume after drug exposure. Gene expression data in recurrent tumors suggested low Notch signaling activity, the upregulation of key mesenchymal genes, and an increase in VEGF-dependent angiogenic factors.The addition of RO4929097 to temozolomide and radiotherapy was well tolerated; the drug has a variable blood-brain barrier penetration. Evidence of target modulation was observed, but recurrence occurred, associated with alterations in angiogenesis signaling pathways. Clin Cancer Res; 22(19); 4786-96. ©2016 AACR.