tbuckley/cabot-search huggingface dataset:
Survey of the immunogenomic landscape of solid tumors through clinical DNA and RNA sequencing.
Authors: Denise Lau, Alan Chang, Jason Perera, Ariane Lozac'hmeur, Alexandria Bobe, Aly Khan
Journal: Journal of Clinical Oncology (2019)

153 Background: In the past decade, immunotherapy has emerged as an important new modality in cancer treatment. However, studies have shown that only a fraction of patients will experience any clinical benefit when treated with immune checkpoint blockade drugs. Given the cost and potent adverse events associated with immunotherapy, the need for effective biomarkers is clear. We sought to understand the role of key immunotherapy biomarkers, like tumor mutational burden (TMB), microsatellite instability (MSI), and PD-L1 immunohistochemistry (IHC), in the context of the greater immunogenomic landscape of solid tumors in patients. Methods: We analyzed data from a cohort of 500 patients across 10 cancer types who received the Tempus xT 595 gene targeted DNA sequencing assay and whole transcriptome sequencing assay as part of their clinical care. We determined the TMB, MSI status, and neoantigen load for each sample using the DNA sequencing data. We used the RNA expression data to evaluate immune activation and tumor infiltration by determining the expression of inflammatory gene signatures and estimating the relative proportion of key immune cell types. Results: Integrative analysis of the DNA and RNA sequencing data showed that the immunogenicity of the tumor, as measured by TMB or neoantigen load, correlates with levels of immune activation and tumor infiltration. Inflammatory immune cells, like CD8 T cells and M1 polarized macrophages, were significantly higher in TMB-high samples; while non-inflammatory immune cells, like monocytes, were significantly lower in TMB-high samples. Additionally, samples could be clustered into immunologically active “hot” tumors or immunologically silent “cold” tumors based on gene expression. The immunologically “hot” population was enriched for samples that were TMB-high, MSI-high or PD-L1 IHC positive. Conclusions: Paired next generation DNA and RNA sequencing assays allows for the identification of patients that have immunologically active tumors that lack traditional immunotherapy biomarkers. These patients represent an interesting new population who may potentially benefit from immunotherapy.
Pattern of rasburicase (RAS) use in community oncology programs and impact on tumor lysis syndrome (TLS) outcomes.
Authors: Wynter Balcerski, Scott C. Howard, Nicholas Napier
Journal: Journal of Clinical Oncology (2019)

e18559 Background: TLS complicates management of bulky chemosensitive cancers. Incidence and severity have increased with new, effective therapies. Prophylaxis/management vary widely. We assessed impact of RAS on outcomes of pts at risk for TLS. Methods: We examined medical records of 5860 pts newly diagnosed with hematologic cancers treated in 101 community hospitals (2010–2018) in the Guardian Research Network. We assessed TLS risk factors, use of uric acid-lowering therapy, e.g. RAS and TLS-related outcomes. RAS doses were grouped as very low/low: 0.01–0.09 mg/kg; medium/full: ≥ 0.1 mg/kg. Acute kidney injury (AKI) was defined using Risk, Injury, Failure, Loss, and End-stage kidney criteria. Early dialysis and early death occurred ≤ 30 days of diagnosis. Results: Of 5860 pts, 206 (3.6%) died early and 17 (0.3%) had early dialysis. AKI occurred in 441 (7.5%); 317 (72%) had AKI at presentation. TLS management varied by region, with RAS used in 4.7–8.1% (p &lt; 0.001), and by baseline creatinine, with RAS used in 5.1% vs 38% (p &lt; 0.001) with normal vs ≥ 3 mg/dL baseline creatinine, respectively. More than half of pts with elevated uric acid (EUA) or elevated creatinine (EC; &gt; 2 mg/dL) at baseline did not receive RAS; they had disproportionate AKI (EC p &lt; 0.001; EUA p &lt; 0.001), early dialysis (EC p &lt; 0.001; EUA p &lt; 0.12) and early death (EC p &lt; 0.001; EUA p &lt; 0.001). Conclusions: Clinicians often use low RAS doses. Pts with hematologic cancers and EC and EUA at baseline have increased rates of AKI, early dialysis and early death. While immediate, aggressive supportive care for TLS is needed, it is inconsistently applied in this high-risk population. Funding Sanofi.
Abstract 1217: Adenosine Promotes Angiogenic Switch in Human Macrophages
Authors: Isabelle Ernens, Emilie Velot, Mélanie Vausort, Yvan Devaux, Daniel R Wagner
Journal: Circulation (2007)

Purpose: Post-infarct left ventricular remodeling is a leading cause of heart failure. The transition from adaptive to maladaptive remodeling is not fully understood. However it appears that angiog...
Performance of a prognostic genomic signature for early-stage NSCLC in matched fresh frozen and RNA-stabilized tissue.
Authors: Shuguang Huang, Amy L Ewing, Nicholas J Reitze, Arlette H Uihlein, Dakun Wang, Michael J Gabrin, Katherine E. Keating, Jude Mulligan, Claire Wilson, Timothy Davison, Stuart McKenzie, Ming-Sound Tsao, Frances A. Shepherd, Stacey L Brower
Journal: Journal of Clinical Oncology (2013)

7532 Background: Recent clinical studies have demonstrated the benefit of adjuvant chemotherapy (ACT) in some early-stage non-small cell lung cancer (NSCLC) patients. A 15-gene signature, developed using fresh frozen (FF) tissue, has been shown to be an independent prognostic marker that identifies high risk patients who may benefit from ACT. Use of this signature in tissue preserved in an RNA stabilization reagent is desired for easier access to tumor tissue in the clinical setting. Methods: Matched FF and RNAlater-preserved (RNAL) tissues were obtained from 43 NSCLC patients. Patients provided written consent for the collection of tumor tissue at the time of surgery under an IRB approved protocol. Each tissue sample was split into 2 pieces, creating biological replicates for each tissue format. For each patient, RNA was extracted from 4 tissue pieces (2 FF, 2 RNAL), followed by microarray-based genomic profiling (Affymetrix U133 Plus 2.0). The 15-gene signature was applied to each profile, generating a numerical risk score and a risk category (high, low) using methods previously established (Zhu 2010 J Clin Oncol). The level of agreement was evaluated within biological replicates of each tissue format, as well as between the averaged biological replicates of matched FF and RNAL tissues. Results: The concordance in risk category between averaged biological replicates of matched FF and RNAL tissues was 84%, with a Pearson correlation of 0.74. This level of agreement is comparable to the inherent reproducibility of the assay observed within biological replicates of FF tissue, which demonstrated concordance of 79% and Pearson correlation of 0.83. In addition, a statistical in silico simulation was used to demonstrate that if the risk scores in this study had spanned the full dynamic range of the assay while maintaining the same level of inherent reproducibility observed in the current study, the level of concordance would be 89% with a Pearson correlation of 0.93. Conclusions: The level of agreement between matched FF and RNAL tissues is not inferior to that seen within FF biological replicates. Therefore, the 15-gene signature maintains its performance when used in RNAlater-preserved NSCLC tissues.
Defining the Minimum Acceptable Diagnostic Accuracy of Noninvasive Fibrosis Testing in Cirrhosis: A Decision Analytic Modeling Study
Authors: Avik Majumdar, Sara Campos, Kurinchi Gurusamy, Massimo Pinzani, Emmanuel A. Tsochatzis
Journal: Hepatology (2019)

No studies explore the clinical consequences of using noninvasive tests (NITs) compared to liver biopsy (LB) in diagnosing cirrhosis. Our aim was to combine two decision analytic models to determine the minimum diagnostic accuracy criteria for NITs to diagnose cirrhosis with equivalence to LB in terms of mortality. We further evaluated selected existing NITs used alone and sequentially. A decision tree was constructed with associated 2-year mortality incorporating an LB or NIT strategy to diagnose cirrhosis in a hypothetical cohort of 1,000 asymptomatic patients. Cirrhosis prevalence was modeled at 5%, 20%, and 50%. Decision curve analyses were performed, expressing the net benefit of tests over a range of threshold probabilities (Pt ). The NIT deriving from the two models that could diagnose cirrhosis with at least equal mortality to LB was termed "mNIT." Existing NITs were then compared using both decision models. The combined mNIT minimum sensitivity and specificity to diagnose cirrhosis with equivalence to LB at 5%, 20% and 50% cirrhosis prevalence were; 89% and 88%, 94% and 85%, and 94% and 87%, respectively at Pt = 0.20. Sequential NITs performed better than single NITs at any prevalence. Combining both decision models, FibroTest plus vibration-controlled transient elastography (VCTE) and VCTE alone were the only existing NITs that were better than or equal to LB at diagnosing cirrhosis at 5% prevalence. At 20% and 50% prevalence, only FibroTest high specificity cutoff plus VCTE was equivalent to or better than LB. Conclusion: Decision analytic models were used to determine the minimum acceptable diagnostic accuracy of NITs for diagnosing cirrhosis; we recommend that such models should be used as the standard in evaluating the diagnostic performance of NITs.
Diffuse Infiltration of Multiple Myeloma With Initial Manifestation of Cavernous Sinus Syndrome Unveiled by 18F-FDG PET/CT
Authors: Chunyan Li, Fuqiang Shao, Yuhui Yang, Xiaoli Lan
Journal: Clinical Nuclear Medicine (2019)

Abstract Intracranial infiltration is a rare complication of multiple myeloma (MM), which is usually seen in advanced stage. Here, we report a 47-year-old woman with only cavernous sinus syndrome as first manifestation. Brain MR revealed cavernous sinus masses, leptomeningeal nodules, and osseous erosion, which were considered metastases. 18 F-FDG PET/CT, which was further performed to identify potential primary lesions, showed increased uptake not only in cavernous sinus and leptomeninges but also in diffuse bone lesions, hepatic nodules, lymph nodes, subcutaneous nodules, and bilateral ovarian masses. Multiple myeloma with intracranial involvement was confirmed by biopsy and cerebrospinal fluid examination.
Analysis of Long-term Benefits of Intensive Blood Pressure Control
Authors: Zachary R. McCaw, Dae Hyun Kim, Lee-Jen Wei
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 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
An orthotopic xenograft model of metastatic nasopharyngeal carcinoma and its application in elucidating a therapeutic target that inhibits metastasis.
Authors: Pamela Ann Smith
Journal: Journal of Clinical Oncology (2012)

e13536 Background: Nasopharyngeal carcinoma (NPC) is a serious health problem in many parts of the world. Although rare in the United States and Western Europe, it is the leading form of cancer in men between the ages of 20-44 years in parts of southeast Asia, and is prevalent in Indonesia, North Africa, the Middle East, amongst Eskimo populations, and represents one of the most frequent epithelial tumors of children in geographically higher risk areas. Current treatment protocols have resulted in good clinical outcomes if the disease is diagnosed and treated at an early stage. Unfortunately, metastatic NPC is refractory to treatment and carries an extremely poor prognosis. Particularly concerning is, that among head and neck cancers of epithelial origin, it is associated with the highest rate of metastasis. This highlights the need for models that are amenable to the study of metastatic NPC and adequate to test new potential therapies. Methods: In order to define and therapeutically target mechanisms that mediate nasopharyngeal carcinoma (NPC) metastasis, we have developed a unique orthotopic xenograft mouse model that accurately recapitulates the invasive and metastatic behavior of human disease. Results: Based on published clinical data and gene array analysis we performed on biopsy samples, we concluded that the PI3K/Akt/mTOR axis is involved in aggressive NPC tumor behavior. We thus chose it as a therapeutic target to test the utility of our orthotopic system for evaluating the effectiveness of a targeted treatment for metastatic NPC. We have subsequently demonstrated that both the development and growth of metastatic lesions are markedly reduced by the mTOR inhibitor sirolimus. Conclusions: Thus, this orthotopic model provides a platform to study potential therapeutics for advanced NPC and demonstrates that targeting the PI3K/Akt/mTOR pathway is a promising intervention against disseminated disease.
Abstract 15156: Myoglobin is a Strong Predictor of Extent of Late Gadolinium Enhancement on Cardiac Magnetic Resonance Imaging in Patients With Acute Myocarditis
Authors: Jan Kottwitz, Jan Berg, Nora Baltensperger, Mawahib Elhassan, Christine K Kissel, Marina Lovrinovic, Dimitri Patriki, Frank Scherff, Christian Schmied, Christian Templin, Thomas F Lüscher, Robert Manka, Bettina Heidecker
Journal: Circulation (2017)

Introduction: Cardiac and inflammatory markers are routinely obtained to evaluate for myocarditis. However, it has not been determined, if these markers reflect disease severity. We sought to test ...
Pre-emptive intervention versus treatment as usual for infants showing early behavioural risk signs of autism spectrum disorder: a single-blind, randomised controlled trial
Authors: Andrew J O Whitehouse, Kandice J Varcin, Gail A Alvares, Josephine Barbaro, Catherine Bent, Maryam Boutrus, Lacey Chetcuti, Matthew N Cooper, Alena Clark, Emma Davidson, Stefanie Dimov, Cheryl Dissanayake, Jane Doyle, Megan Grant, Teresa Iacono, Murray Maybery, Sarah Pillar, Michelle Renton, Catherine Rowbottam, Nancy Sadka, Leonie Segal, Vicky Slonims, Carol Taylor, Scott Wakeling, Ming Wai Wan, John Wray, Jonathan Green, Kristelle Hudry
Journal: The Lancet Child & Adolescent Health (2019)
Sensitization to immune checkpoint blockade through activation of a STAT1/NK axis in the tumor microenvironment
Authors: Rachael M. Zemek, Emma De Jong, Wee Loong Chin, Iona S. Schuster, Vanessa S. Fear, Thomas H. Casey, Cath Forbes, Sarah J. Dart, Connull Leslie, Ayham Zaitouny, Michael Small, Louis Boon, Alistair R. R. Forrest, Daithi O. Muiri, Mariapia A. Degli-Esposti, Michael J. Millward, Anna K. Nowak, Timo Lassmann, Anthony Bosco, Richard A. Lake, W. Joost Lesterhuis
Journal: Science Translational Medicine (2019)

A STAT1-driven inflammatory phenotype associated with response to checkpoint blocking antibodies sensitizes cancers to immunotherapy.
Abstract 21241: One Device Closure for Multiple Atrial Septal Defects Guided With Thoracic Echocardiography: The Role of Personalized Three-Dimensional Printing
Authors: Xiangbin Pan
Journal: Circulation (2017)

Introduction: Single device closure for multiple atrial septal defects (ASD) is still challenging due to the complicated anatomy and technical difficulty. The emerging three-dimensional (3D) printing facilitates the identification anatomical structure, helps the procedural planning and simplifies the imaging monitoring for the transcatheter closure. Hypothesis: We therefore aimed to testify the possibility of single device for multiple ASDs under the guidance of transthoracic echocardiography with the aid of 3D printing models in this prospective study. Methods: Stereolithography data was acquired with cardiac CT scan in 30 patients (20±16 years, 18 females) having multiple ASDs and personal 1:1 scale 3D printed model was printed. Closure planning, including determination of target defect, occluder selection and device placement, was attempted on the model before intervention. Transcatheter closure was performed under the guidance of transthoracic echocardiography. The conventional selection of device was compare to the method based on 3D models. The clinical effect was assessed immediately after device closure and at 3-month follow-up. Results: 3D printing model was successfully established in all patients and 26 cases were suitable for transcatheter closure according to model test. Transcatheter closure with single device was completed in 26 patients (including 14 patients with defect distance &gt;7mm) even under the guidance of the transthoracic echocardiography without complications.Compared to conventional method, device selection was more accurate in 3D model. Immediate postoperative echocardiography demonstrated mild residual shunt in 5 patients whereas disappeared in 3 patients and decreased in the other 2 patients at 3-month follow-up. Conclusions: 3D printing technology and echocardiography guiding procedure enables single device for closure of multiple ASDs including challenge cases.
Calpain 9 as a therapeutic target in TGFβ-induced mesenchymal transition and fibrosis
Authors: David H. Kim, James D. Beckett, Varun Nagpal, Manuel A. Seman-Senderos, Russell A. Gould, Tyler J. Creamer, Elena Gallo MacFarlane, Yichun Chen, Djahida Bedja, Jonathan T. Butcher, Wayne Mitzner, Rosanne Rouf, Shoji Hata, Daniel S. Warren, Harry C. Dietz
Journal: Science Translational Medicine (2019)

Inhibition of calpain 9, a key mediator of myofibroblast differentiation and tissue fibrosis, protects against fibrosis in preclinical models.
The impact of an updated pandemic H1N1 strain on shedding and immunogenicity to Russian-backbone live attenuated influenza vaccine among children in The Gambia: an open-label, observational, phase 4 study
Authors: B B Lindsey, Y J Jagne, E P Armitage, A Singanayagam, H J Sallah, S Drammeh, E Senghore, N I Mohammed, D Jeffries, K Höschler, J S Tregoning, A Meij, E Clarke, T Dong, W Barclay, B Kampmann, T I de Silva
Journal: The Lancet Respiratory Medicine (2019)
Allogeneic hematopoietic stem cell transplantation contributes to eradication of minimal residual disease in adult Philadelphia chromosome-positive acute lymphoblastic leukemia patients treated with dasatinib.
Authors: Jeremy Chang, Mojtaba Akhtari
Journal: Journal of Clinical Oncology (2019)

7024 Background: Philadelphia Chromosome-Positive (Ph+) disease is associated with a poor prognosis in acute lymphoblastic leukemia (ALL). Recent studies have shown that the eradication of minimal residual disease (MRD) in this population leads to improved survival outcomes. While hematopoietic stem cell transplantation (HSCT) has demonstrated clinical benefits in Ph+ ALL patients treated with the tyrosine kinase inhibitor (TKI) imatinib, its role is less clear with the use of more potent, newer-generation TKIs such as dasatinib. Methods: This was a retrospective study analyzing the impact of allogeneic HSCT on MRD status in Ph+ ALL patients treated with dasatinib. Patients were divided into 2 groups: those treated with chemotherapy plus dasatinib followed by allogeneic HSCT and those who received chemotherapy plus dasatinib alone. All patients underwent bone marrow biopsy with MRD analysis following induction therapy and subsequent re-evaluation of MRD status at day 100 post-transplant in the HSCT group and after further cycles of chemotherapy plus dasatinib in the non-transplant group. MRD-negative disease was defined as the absence of a BCR-ABL1 transcript by real-time quantitative polymerase chain reaction (qRT-PCR) with a sensitivity of 0.01%. Results: A total of 51 adult Ph+ ALL patients with MRD-positive disease following induction therapy were included. Twenty-seven patients (53%) were male and the median age at time of diagnosis was 42 years (range 23-68). There were 29 patients in the transplant group and 22 patients in the non-transplant group. When analyzing rates of MRD eradication, 18 (62%) patients in the transplant group were found to have MRD-negative disease at day 100 post-transplant compared to 7 (32%) patients in the non-transplant group who only received further cycles of chemotherapy plus dasatinib (risk ratio 0.56, 95% confidence interval 0.32-0.96, p = 0.048). Conclusions: In the era of newer-generation TKIs, allogeneic HSCT continues to have notable benefits in Ph+ ALL such as a significantly higher rate of MRD eradication as demonstrated in this study.
Functional outcomes in adult patients with herpes simplex encephalitis admitted to the ICU: a multicenter cohort study
Authors: P. Jaquet, E. de Montmollin, C. Dupuis, C. Sazio, M. Conrad, V. Susset, S. Demeret, J. M. Tadie, L. Argaud, F. Barbier, B. Sarton, R. Chabane, D. Daubin, N. Brulé, N. Lerolle, M. Alves, D. Da Silva, A. El Kalioubi, S. Silva, P. Bailly, M. Wolff, L. Bouadma, J. F. Timsit, R. Sonneville
Journal: Intensive Care Medicine (2019)
Isolated Involvement of Prostate Gland by Immunoglobulin G4–Related Disease Diagnosed With the Help of FDG PET/CT
Authors: Kousik Vankadari, Bhagwant Rai Mittal, Rajender Kumar, Harmandeep Singh, Anish Bhattacharya, Rakesh Kochhar
Journal: Clinical Nuclear Medicine (2019)

Abstract Immunoglobulin G4 (IgG4)–related disease is known to mimic multiple malignancies and always poses a diagnostic challenge. We report a case of a 20-year-old young man, who presented with unexplained recurrent episodes of fever and pain abdomen. 18 F-FDG PET/CT revealed intense focal FDG avidity in the prostate. On further workup, he had an elevated serum IgG4 level, and a clinical diagnosis of immunoglobulin G4–related disease was kept. A follow-up FDG PET/CT after glucocorticoid therapy revealed resolution of FDG avidity in the prostate with fall in serum IgG4 levels, hence confirming a diagnosis of atypical immunoglobulin G4–related disease involving isolated prostate gland.
Mindfulness-Based Cognitive Therapy Intervention for the Treatment of Late-Life Depression and Anxiety Symptoms in Primary Care: A Randomized Controlled Trial
Authors: S. Gabriela Torres-Platas, Sophia Escobar, Claudia Belliveau, Joyce Wu, Neeti Sasi, Jocelyn Fotso, Angela Potes, Zoë Thomas, Allana Goodman, Karl Looper, Marilyn Segal, Marcelo Berlim, Akshya Vasudev, Nona Moscovitz, Soham Rej
Journal: Psychotherapy and Psychosomatics (2019)
TREM2 Acts Downstream of CD33 in Modulating Microglial Pathology in Alzheimer’s Disease
Authors: Ana Griciuc, Shaun Patel, Anthony N. Federico, Se Hoon Choi, Brendan J. Innes, Mary K. Oram, Gea Cereghetti, Danielle McGinty, Anthony Anselmo, Ruslan I. Sadreyev, Suzanne E. Hickman, Joseph El Khoury, Marco Colonna, Rudolph E. Tanzi
Journal: Neuron (2019)