tbuckley/cabot-search huggingface dataset:
MACC1 expression as a candidate prognostic biomarker in colorectal cancer patients receiving adjuvant oxaliplatin-based therapy.
Authors: Lynn Katherine Symonds, Kelsey K. Baker, Mary Weber Redman, Lisa Koch, Kelly Carter, Ming Yu, Ralph Wirtz, Christos Poulios, George E. Pentheroudakis, George Papaxoinis, Dimitrios G. Pectasides, Konstantine T. Kalogeras, George Fountzilas, William M. Grady, Stacey Cohen
Journal: Journal of Clinical Oncology (2019)

567 Background: MACC1, part of the HGF-MET pathway, drives proliferation and regulation of MET expression in vitro. In vivo, MACC1 is associated with tumor progression and studies suggest greater MACC1 expression is associated with resistance to platinum-based chemotherapy. We hypothesized that MACC1 may be a prognostic biomarker in colorectal cancer (CRC). Methods: MACC1 expression was evaluated by immunohistochemistry on tumor microarrays (N = 428). Patients were stage I-III CRC who received an oxaliplatin-based regimen (either with 5-FU (FOLFOX) or capecitabine (XELOX)) within the HeCOG 6C/08 observational study. MACC1 expression was assessed by a blinded GI pathologist using a scale ranging from 0 (no staining) to 3+ (strong expression). Each patient had at least 3 samples and the strongest result was used for the final score. MACC1 positivity was defined as ≥2+ expression and 0-1+ as MACC1-. Cox regression models were used to estimate hazard ratios (HR) for the association of MACC1 expression with patient characteristics, disease-free (DFS), and overall survival (OS). Results: 400/428 CRC tumors were evaluable: 322 (80.5%) were MACC1+ and 78 (19.5%) MACC1-. Mucinous features were less likely in MACC1+ patients (24% vs. 38%, p = 0.02). Other unfavorable features including grade, lymphovascular invasion, perineural invasion, and tumor mutational burden were not significantly different. There was no difference for stage, microsatellite instability, BRAF, KRAS, or NRASstatus between MACC1+/- cancers. There was a trend towards worse survival in MACC1+ patients regardless of treatment (DFS HR 1.55 [95% CI: 0.87, 2.76], OS HR 1.59 [95% CI 0.74, 3.4]). This difference was not statistically significant for OS (p = 0.26) or DFS (p = 0.08) even when stratified by clinicopathologic variables. Conclusions: Patients with MACC1+ CRC tumors who received adjuvant oxaliplatin-based therapy were less likely to have mucinous histology. They had a trend toward independently worse survival that was not significant when accounting for stage and clinicopathologic variables. Studies focused on the predictive role of MACC1 and oxaliplatin in stage III CRC are in progress.
A Photoactivatable Botulinum Neurotoxin for Inducible Control of Neurotransmission
Authors: Qi Liu, Brooke L. Sinnen, Emma E. Boxer, Martin W. Schneider, Michael J. Grybko, William C. Buchta, Emily S. Gibson, Christina L. Wysoczynski, Christopher P. Ford, Alexander Gottschalk, Jason Aoto, Chandra L. Tucker, Matthew J. Kennedy
Journal: Neuron (2019)
FDG PET/CT Findings of a Synovial Sarcoma in a Renal Transplant
Authors: Xu Yang, Wei Wang, Ying Kan, Jie Liu, Jigang Yang
Journal: Clinical Nuclear Medicine (2019)

A 48-year old man who underwent renal transplantation 2 years ago due to chronic renal failure underwent FDG PET/CT to determine the etiology of multiple lesions in the renal transplant incidentally found on routine examination. The images demonstrated several foci of the abnormally increased activity in the transplanted kidney with SUVmax of 7.5. Surgical pathology demonstrated multiple synovial sarcoma in the transplanted kidney.
Evaluation of Salivary Exosomal Chimeric <i>GOLM1-NAA35</i> RNA as a Potential Biomarker in Esophageal Carcinoma
Authors: Yusheng Lin, Hongmei Dong, Weilun Deng, Wan Lin, Kai Li, Xiao Xiong, Yi Guo, Fuyou Zhou, Changchun Ma, Yuping Chen, Hongzheng Ren, Haijun Yang, Ningtao Dai, Lang Ma, Stephen J. Meltzer, Sai-Ching J. Yeung, Hao Zhang
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Transcriptionally induced chimeric RNAs are an important emerging area of research into molecular signatures for biomarker and therapeutic target development. Salivary exosomes represent a relatively unexplored, but convenient, and noninvasive area of cancer biomarker discovery. However, the potential of cancer-derived exosomal chimeric RNAs in saliva as biomarkers is unknown. Here, we explore the potential clinical utility of salivary exosomal GOLM1-NAA35 chimeric RNA (seG-NchiRNA) in esophageal squamous cell carcinoma (ESCC). Experimental Design: In a retrospective study, the prognostic significance of G-NchiRNA was determined in ESCC tissues. The correlation between seG-NchiRNA and circulating exosomal or tumoral G-NchiRNA was ascertained in cultured cells and mice. In multiple prospective cohorts of patients with ESCC, seG-NchiRNA was measured by qRT-PCR and analyzed for diagnostic accuracy, longitudinal monitoring of treatment response, and prediction of progression-free survival (PFS). Results: Exosomal G-NchiRNA was readily detectable in ESCC cells and nude mouse ESCC xenografts. SeG-NchiRNA levels reflected tumor burden in vivo and correlated with tumor G-NchiRNA levels. In prospective studies of a training cohort (n = 220) and a validation cohort (n = 102), seG-NchiRNA levels were substantially reduced after ESCC resection. Moreover, seG-NchiRNA was successfully used to evaluate chemoradiation responsiveness, as well as to detect disease progression earlier than imaging studies. Changes in seG-NchiRNA levels also predicted PFS of patients after chemoradiation. Conclusions: SeG-NchiRNA constitutes an effective candidate noninvasive biomarker for the convenient, reliable assessment of therapeutic response, recurrence, and early detection.
ONC-212 (I-39), a Novel Inhibitor of the UPR, Is Cytotoxic and Cytostatic Against CLL Cells Under in Vitro Conditions That Mimic the Tumor Microenvironment
Authors: Narjis Rizwan, Yandong Shen, Edwin Iwanowicz, Stephen P. Mulligan, Kyle R Crassini, Richard Christopherson, Oliver Giles Best
Journal: Blood (2018)
Cross-Reactive Carbohydrate Determinants (CCDs) Interference with Component Resolved Diagnosis on NOVEOS™*, ImmunoCAP® and IMMULITE® 2000.
Authors: Edsel Sinson, Camille Ocampo, Steven Nguyen, Lauren Dinh, Cindy Liao, Kelline Rodems
Journal: Journal of Allergy and Clinical Immunology (2019)
APPEAL (Allergy to Peanuts ImPacting Emotions and Life): Pan-European Results on Peanut Allergy Impact on Allergic Individuals, Parents and Caregivers
Authors: Audrey DunnGalvin, Montserrat Fernandez Rivas, Helen R. Fisher, Mary Feeney, Frans Timmermans, Lynne Regent, Sabine Schnadt, Marcia Podestà, Ángel Sánchez, Pascale Couratier, Betina Hjorth, Fiona Kenna, Ram Patel, Andrea Vereda, Tessa Lush, Katharina Blümchen
Journal: Journal of Allergy and Clinical Immunology (2019)
The impact of the immune microenvironment in patients with GEP-NETs.
Authors: Marina Baretti, Qingfeng Zhu, Marianna Zahurak, Timothy M. Pawlik, Robert A Anders, Ana De Jesus-Acosta
Journal: Journal of Clinical Oncology (2019)

267 Background: The immune microenvironment in neuroendocrine tumors (NETs) remains largely unexplored with very limited data evaluating its impact on survival. We aimed to characterize the immune microenvironment and lymphocytic infiltrate in patients with gastroenteropancreatic (GEP) NET. Methods: We performed comprehensive immune profiling for CD3, CD8, PD-1, IDO, and PD-L1 expression in two cohorts of patients with primary GEP-NET: patients who had short progression free survival (PFS) ≤ 4 years (n = 12) or long PFS &gt; 4 years (n = 14) following surgical resection. Tumor associated immune infiltrates in the tumor, inner and outer invasive front were recorded and quantified. The percentage of PD-L1 membranous expression was manually counted in tumor, stroma and invasive front. To account for the correlation among multiple samples within the same patient, generalized estimating equations (GEE) were used for model estimation and hypothesis testing. Results: Patients with shorter PFS had larger primary tumor size compared to patients with longer PFS (Wilcoxon p value = 0.02), with no statistically significant differences in Ki-67 expression. For all patients univariate GEE results showed a higher mean expression of CD3+, CD8+, and PD-1+ cells at the interface (inner and outer) as compared to the tumor region: 1.28 (95% CI: 0.98, 1.58, p &lt; 0.0001), 0.99 (95% CI: 0.67, 1.32, p = 0.0005) and 1.38 (95% CI: 0.90, 1.38, p &lt; 0.0001) respectively. Comparison between the two groups showed that tumors from patients with a longer PFS had higher intratumoral CD3+ TILs densities than did those from patients who had a shortened PFS (0.88, 95% CI: 0.44, 1.31, p = 0.004). Intratumoral expression of CD8+TILs, and IDO+ cells tended to be higher in the long PFS group (p = 0.143 and 0.29 respectively). While the probability of positive PD-L1 expression did not differ according to location, it was higher in patients with shortened PFS (odds ratio = 1.96; 95% CI: 0.64, 5.93), though not significant. Conclusions: Higher intratumoral T cell infiltrate (CD3+) is associated with a favorable outcome and longer PFS following resection for GEP-NETs. Immune escape is a potential mechanism for disease progression and warrants further investigation as a therapeutic strategy for this disease.
Abstract 12981: Does Volume Overload Predict Failed Antitachycardia Pacing Therapy for Ventricular Tachycardia in Patients With an Implantable Cardioverter-Defibrillator?
Authors: Alireza Hosseini-khalili, Jeffrey Kluger
Journal: Circulation (2014)

Introduction: Decompensated heart failure (HF) increases the risk of Implantable Cardioverter-Defibrillator (ICD) therapy. Patients with failed antitachycardia pacing (ATP) for ventricular tachycardia (VT) termination, requiring ICD shock, have been reported to have worse outcomes compared to patients with effective ATP. Thoracic impedance (TI) is a diagnostic parameter found in many ICDs. In Medtronic devices, TI is transformed into a OptiVol index, which when elevated, may represent volume overload and can predict increased HF events. Hypothesis: Whether an elevated OptiVol index is associated with failed ATP for VT termination in ICD patients. Method: Retrospective review of a prospectively collected database of patients followed in a dedicated ICD clinic, enrolled in remote ICD monitoring and who received therapy for VT termination by an OptiVol-capable ICD. The level of OptiVol was measured near the time of VT events. VT events were divided into two groups: OptiVol index &lt;100 and OptiVol≥100, and distributions of successful and unsuccessful ATP were compared. Results: We analyzed 121 VT episodes that occurred in 39 ICD patients who received ATP or shock to terminate VT. Mean age of patients was 68.4 +/- 10 years and 32 patients (78%) were male. Ischemic cardiomyopathy was present in 20 patients (48.8%). Successful ATP was more likely when the VT event was associated with an OptiVol index &lt;100 (74.5% successful vs 25.5% unsuccessful, P&lt;0.001); whereas a VT event associated with an OptiVol≥100 was more likely to be unresponsive to ATP compared with ATP success (66.7% unsuccessful vs 33.3% successful, p&lt;0.001). Conclusions: Failed ATP, requiring shock therapy for VT, is associated with a measure of volume overload (OptiVol) and could explain the worse outcomes observed in patients who require ICD shocks.
Wide Variation in Duration of Anticoagulation after Catheter-Related Thrombosis: A Venous Thromboembolism Network US Multicenter Retrospective Cohort Study
Authors: Lisa Baumann Kreuziger, Manila Gaddh, Oluwatomiloba Onadeko, Gemlyn George, Tzu-Fei Wang, Thein H. Oo, Ming Feng, Pippa Simpson, Radhika Gali, Henny Heisler Billett
Journal: Blood (2018)
The Body Is the Person
Authors: Carol Snyder Halberstadt
Journal: JAMA (2019)

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
Durable anticancer immunity from intratumoral administration of IL-23, IL-36γ, and OX40L mRNAs
Authors: Susannah L. Hewitt, Ailin Bai, Dyane Bailey, Kana Ichikawa, John Zielinski, Russell Karp, Ameya Apte, Kristen Arnold, Sima J. Zacharek, Maria S. Iliou, Khushbu Bhatt, Maija Garnaas, Faith Musenge, Ashley Davis, Nikhil Khatwani, Stephen V. Su, Graham MacLean, Samuel J. Farlow, Kristine Burke, Joshua P. Frederick
Journal: Science Translational Medicine (2019)

Local mRNA therapy encoding inflammatory cytokines and T cell costimulator OX40L mediates persistent anticancer immunity across tumor models.
The Interaction of Cross-Linked Fibrin Fragment D-Dimer with αIIbβ3 Requires Receptor Activation, Occurs at Sites Other Than the γ-404-411 Sequence, and Contributes to Clot Retraction
Authors: Hina Zafar, Jihong Li, Claudia Buitrago, Dragana Nesic, Barry S. Coller
Journal: Blood (2018)
Poverty, public health cuts, and Brexit risk halting progress on child health, college warns
Authors: Gareth Iacobucci
Journal: BMJ (2019)

Child poverty, cuts to public health services, and uncertainties around the impact of Brexit could undermine progress being made on improving child health in the UK, paediatricians have warned.

The Royal College of Paediatrics and Child Health’s State of Child Health: Two Years On1 scorecard assesses progress against recommendations made in its State of Child Health report2 in 2017. The college praised the government for its emphasis on child health, but identified several major risks and a mixed picture across the four UK nations.

Russell Viner, president of the college, said: “We are witnessing …
Prostate Magnetic Resonance Imaging: Lesion Detection and Local Staging
Authors: Baris Turkbey, Peter L. Choyke
Journal: Annual Review of Medicine (2019)

Dramatic changes in the use of prostate magnetic resonance imaging (MRI) have occurred in the last decade. The recognition that MRI detects and localizes cancers with reasonable accuracy led to the development of directed biopsies. These image-guided biopsies have a higher sensitivity for clinically significant cancers and a lower sensitivity for indolent disease. Prospective trials provide level 1 evidence supporting the use of prostate MRI. For local staging, while the specificity of prostate MRI is high, its sensitivity is lacking for microscopic extraprostatic extension. Computer-aided diagnosis of prostate MRI promises to bring the diagnostic power of MRI to nonexpert readers and thus further integrate MRI into the diagnostic workup.
Impact of Intestinal Microbiota on Reconstitution of Mucosal-Associated Invariant T Cells after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Alyssa Sheih, Jonathan L. Golob, Abir Bhattacharyya, Michael C. Wu, Aesha Vakil, Sujatha Srinivasan, Steven A. Pergam, David N. Fredricks, Cameron J. Turtle
Journal: Blood (2018)
Potential role for interleukin‐1 in the cardio‐renal syndrome
Authors: Leo F. Buckley, Justin M. Canada, Salvatore Carbone, Cory R. Trankle, Dinesh Kadariya, Hayley Billingsley, George F. Wohlford, Danielle L. Kirkman, Antonio Abbate, Benjamin W. Van Tassell
Journal: European Journal of Heart Failure (2019)
Methodology Flaws and Implications of a Complementary Medicine Study
Authors: Kevin Lee, Nathan Douthit
Journal: JAMA Oncology (2019)

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
Association of HLA Antigen Mismatch With Risk of Developing Skin Cancer After Solid-Organ Transplant
Authors: Yi Gao, Amanda R. Twigg, Ryutaro Hirose, Garrett R. Roll, Amy S. Nowacki, Edward V. Maytin, Allison T. Vidimos, Raja Rajalingam, Sarah T. Arron
Journal: JAMA Dermatology (2019)

Risk factors for the development of skin cancer after solid-organ transplant can inform clinical care, but data on these risk factors are limited.To study the association between HLA antigen mismatch and skin cancer incidence after solid-organ transplant.This retrospective cohort study is a secondary analysis of the multicenter Transplant Skin Cancer Network study of 10 649 adults who underwent a primary solid-organ transplant between January 1, 2003, and December 31, 2003, or between January 1, 2008, and December 31, 2008. These participants were identified through the Scientific Registry of Transplant Recipients standard analysis files, which contain data collected mostly by the Organ Procurement and Transplantation Network. Participants were matched to skin cancer outcomes by medical record review. This study was conducted from August 1, 2016, to July 31, 2017.The primary outcome was time to diagnosis of posttransplant skin cancer, including squamous cell carcinoma, melanoma, and Merkel cell carcinoma. The HLA antigen mismatch was calculated based on the 2016 Organ Procurement and Transplantation Network guidelines. Risk of skin cancer was analyzed using a multivariate Cox proportional hazards regression model.In total, 10 649 organ transplant recipients (6776 men [63.6%], with a mean [SD] age of 51 [12] years) contributed 59 923 years of follow-up. For each additional mismatched allele, a 7% to 8% reduction in skin cancer risk was found (adjusted hazard ratio [HR], 0.93; 95% CI, 0.87-0.99; P = .01). Subgroup analysis found the protective effect of HLA antigen mismatch to be statistically significant in lung (adjusted HR, 0.70; 95% CI, 0.56-0.87; P = .001) and heart (adjusted HR, 0.75; 95% CI, 0.60-0.93; P = .008) transplant recipients but not for recipients of liver, kidney, or pancreas. The degree of HLA-DR mismatch, but not HLA-A or HLA-B mismatch, was the most statistically significant for skin cancer risk (adjusted HR, 0.85; 95% CI, 0.74-0.97; P = .01).The HLA antigen mismatch appears to be associated with reductions in the risk of skin cancer after solid-organ transplant among heart and lung transplant recipients; this finding suggests that HLA antigen mismatch activates the tumor surveillance mechanisms that protect against skin cancer in transplant recipients and that skin cancer risk may be higher in patients who received a well-matched organ.
Abstract 19028: Neural IKK2 Deficiency Ameliorates Exposure to Concentrated Ambient PM2.5-Induced Inflammation and Endothelial Dysfunction in a Murine Model
Authors: Minjie Chen, Xiaobo Qin, Lianglin Qiu, Sufang Chen, Huifen Zhou, Yanyi Xu, Ziying Hu, Yuhao Zhang, Qi Cao, Zhekang Ying
Journal: Circulation (2017)

Introduction: Exposure to ambient fine particulate matter (PM2.5) is associated with increased cardiovascular mortality. However, the underlying pathophysiology has not yet been fully understood. Hypothalamic inflammation is emerging as a critical player in the pathogenesis of cardiovascular diseases. Furthermore, we recently demonstrated that exposure to PM2.5results in marked hypothalamic inflammation. Hypothesis: In the present study, we therefore exploited a neuron-specific knockout mouse model to examine the role of hypothalamic inflammation in the pathophysiology due to exposure to PM2.5. Methods and Results: Nestin-creIKK2flox/flox (IKK2Neu-KO) and littermate control (Nestin-creIKK2flox/+, WT) were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) for 4 months, and their inflammatory and vascular responses were then assessed. Our results showed that neural IKK2 deficiency reduced CAP exposure-induced expression of TNFα and IL-6 mRNA in the hypothalamus to 54.1% and 10.5%, respectivel...
Abstract 14854: A Prognostic Study of the J wave Patterns on the Resting Electrocardiogram in Ambulatory Patients
Authors: Vedant S Pargaonkar, Marco V Perez, Akash Jindal, Victor F Froelicher
Journal: Circulation (2014)

Introduction: The prognostic value of J waves and terminal QRS slurs remains controversial. Population studies have demonstrated differing results, with some suggesting that J waves and slurs are associated with cardiovascular death (CVD). Hypothesis: We tested the hypothesis that J waves or terminal QRS slurs on the electrocardiogram (ECG) were associated with cardiovascular death. Methods: Resting digitized 12-lead ECGs from 20,661 ambulatory individuals at the VA Palo Alto Health Care System were visually coded using computer display. Using ≥ 0.1 mV as the amplitude criteria, J-waves were measured at the top of the upward deflection and QRS slurs at the top of the conduction delay on the QRS down-stroke in at least two contiguous leads. Multivariate Cox hazard regression analyses were used to study the associations between J waves, terminal QRS slurs, ST segment slope and CVD. Results: Of the 20,661 subjects, 90% were male (43 ± 8 years of age) and 10% were female (40 ± 10 years of age); 16% were African-American and 7% were Hispanic. Over a median follow-up of 17 years, there were 859 cardiac deaths. A total of 4219 (20%) ECGs had J waves and/or slurs present in the inferior and/or lateral territories: 3318 (16%) ECGs had J waves and/or slurs only in inferior leads (II, III, aVF), 1701 (8%) only in lateral leads (V4-6, I, aVL) and 1198 (6%) in both inferior and lateral leads. None of the J wave/terminal QRS slur patterns were associated with higher rates of cardiovascular mortality (Figure). The subset of ECGs with J wave/terminal QRS slur patterns that also had downward ST slopes were also not associated with CVD. Conclusion: We found no association between higher rates of CVD and any pattern of J waves/terminal QRS slurs, with or without downward ST slope. While previous studies have shown that J waves and terminal QRS slurs are present at higher rates in patients with idiopathic ventricular fibrillation, we did not find them to be predictive of CVD in long-term follow up of a clinical cohort.