tbuckley/cabot-search huggingface dataset:
Efficacy of Omalizumab for Severe Allergic Rhinitis Induced By Japanese Cedar Pollen in Patients Treated with Combination Oral Antihistamines and Nasal Corticosteroids
Authors: None Kimihiro Okubo, Mitsuhiro Okano, Norio Sato, Yuko Tamaki, Hiromi Suzuki, Robert B. Fogel
Journal: Journal of Allergy and Clinical Immunology (2019)
Multicenter Trial of [<sup>18</sup>F]fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Staging of Head and Neck Cancer and Negative Predictive Value and Surgical Impact in the N0 Neck: Results From ACRIN 6685
Authors: Val J. Lowe, Fenghai Duan, Rathan M. Subramaniam, JoRean D. Sicks, Justin Romanoff, Twyla Bartel, Jian Q. (Michael) Yu, Brian Nussenbaum, Jeremy Richmon, Charles D. Arnold, David Cognetti, Brendan C. Stack
Journal: Journal of Clinical Oncology (2019)

PURPOSE The objective of this study was to determine the negative predictive value (NPV) of positron emission tomography (PET)/computed tomography (CT) for the clinically N0 neck on the basis of neck dissection. METHODS Participants with newly diagnosed, first-time, head and neck squamous cell carcinoma (HNSCC) and at least one clinically N0 neck side for which dissection was planned were included. A total of 287 participants were prospectively enrolled from 23 American College of Radiology Imaging Network-qualified institutions. PET/CT was compared with findings at neck dissection. RESULTS PET/CT scans and pathology findings were available for 270 N0 neck sides from 212 participants. For visual assessment, the NPV specific to the clinical-N0 sides was 0.868 (95% CI, 0.803 to 0.925). For dichotomized maximum standardized uptake value, the NPVs specific to the nodal basins were 0.940 (95% CI, 0.928 to 0.952) and 0.937 (95% CI, 0.925 to 0.949) at prespecified cutoffs of 2.5 and 3.5, respectively. The optimal cutoff maximum standardized uptake value was determined to be 1.8, with an NPV of 0.942 (95% CI, 0.930 to 0.953). The PET/CT-informed surgical treatment plan was changed in 51 of 237 participants (22%) compared with the PET/CT-blinded surgical plan. In 34 participants (14%), this led to planned dissection of additional nodal levels. In 12 participants (5%), this led to fewer planned dissected nodal levels. Negative PET/CT scans in N0 necks was true negative in 87% and false negative in 13%. CONCLUSION [ 18 F]fluorodeoxyglucose-PET/CT has high NPV for the N0 neck in T2 to T4 HNSCC. The surgical treatment plans on the basis of PET/CT findings may be changed in approximately 22% of this group. These findings suggest that [ 18 F]fluorodeoxyglucose-PET/CT may assist the clinician in deciding on the best therapy for the clinically N0 neck in HNSCC. Well-designed clinical trials should be performed to test the outcome of omitting neck dissection by using PET/CT.
Introduction to precision medicine in COPD
Authors: Janice M. Leung, Ma'en Obeidat, Mohsen Sadatsafavi, Don D. Sin
Journal: European Respiratory Journal (2019)

Although there has been tremendous growth in our understanding of chronic obstructive pulmonary disease (COPD) and its pathophysiology over the past few decades, the pace of therapeutic innovation has been extremely slow. COPD is now widely accepted as a heterogeneous condition with multiple phenotypes and endotypes. Thus, there is a pressing need for COPD care to move from the current “one-size-fits-all” approach to a precision medicine approach that takes into account individual patient variability in genes, environment and lifestyle. Precision medicine is enabled by biomarkers that can: 1) accurately identify subgroups of patients who are most likely to benefit from therapeutics and those who will only experience harm (predictive biomarkers); 2) predict therapeutic responses to drugs at an individual level (response biomarkers); and 3) segregate patients who are at risk of poor outcomes from those who have relatively stable disease (prognostic biomarkers). In this essay, we will discuss the current concept of precision medicine and its relevance for COPD and explore ways to implement precision medicine for millions of patients across the world with COPD.
Impact of Abnormal Coronary Reactivity on Long-Term Clinical Outcomes in Women
Authors: Ahmed AlBadri, C. Noel Bairey Merz, B. Delia Johnson, Janet Wei, Puja K. Mehta, Galen Cook-Wiens, Steven E. Reis, Sheryl F. Kelsey, Vera Bittner, George Sopko, Leslee J. Shaw, Carl J. Pepine, Bina Ahmed
Journal: Journal of the American College of Cardiology (2019)
Prevalence and Patterns of Sensitization Differ Between Two High-Risk Cohorts: the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH) Cohort
Authors: Asel Baatyrbek kyzy, John Kroner, Rosario Alarcon, Kristina Keidel, Krista Tensing, Zachary Flege, Lisa J. Martin, Gurjit K. Khurana Hershey, Jocelyn M. Biagini Myers
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 18257: Systolic Blood Pressure as a Novel Determinant of Nocturia in Non-Hispanic Black Men
Authors: O’Neil R Mason, Kathleen Lynch, Mohamad Rashid, Anthony Reid, Robert M Elashoff, Ronald G Victor
Journal: Circulation (2016)

Introduction: Nocturia (awakening one or more times at night to urinate) has been associated with self-reported hypertension and non-Hispanic black race/ethnicity in a small number of prior studies...
The Malignant Hemopoietic Clone of Triple Negative Patients with Myelofibrosis Shows in Vitro Functional Defects but Is Highly Responsive to the Pro-Survival Signals of Circulating Autologous Microvesicles
Authors: Lucia Catani, Daria Sollazzo, Dorian Forte, Martina Barone, Cristina Morsiani, Francesco Fabbri, Giorgia Simonetti, Francesca Ricci, Samantha Bruno, Natalia Calonghi, Emanuela Ottaviani, Marco Romano, Pierluigi Tazzari, Claudio Franceschi, Massimiliano Bonafè, Nicola Vianelli, Giovanni Martinelli, Michele Cavo, Miriam Capri, Giuseppe Auteri, Francesca Palandri
Journal: Blood (2018)
Genotype-Resultant Morphology of Myelodysplastic Syndromes (MDS)
Authors: Abhinav Goyal, Inom Mirzaev, Mohammad Fahad B. Asad, Hassan Awada, Cassandra M. Hirsch, Hideki Makishima, Kenichi Yoshida, Bartlomiej P. Przychodzen, Aziz Nazha, Sudipto Mukherjee, Mikkael A. Sekeres, Seishi Ogawa, Tomas Radivoyevitch, Jacob Scott, Jaroslaw P. Maciejewski, Yasunobu Nagata
Journal: Blood (2018)
Targeting Anthrax Toxin Receptor 2 Ameliorates Endometriosis Progression
Authors: Shih-Chieh Lin, Hsiu-Chi Lee, Ching-Ting Hsu, Yi-Han Huang, Wan-Ning Li, Pei-Ling Hsu, Meng-Hsing Wu, Shaw-Jenq Tsai
Journal: Theranostics (2019)

Rationale: Endometriosis is a highly prevalent gynecological disease in women of reproductive age that markedly reduces life quality and fertility.Unfortunately, there is no cure for this disease, which highlights that more efforts are needed to investigate the underlying mechanism for designing novel therapeutic regimens.This study aims to investigate druggable membrane receptors distinctively expressed in endometriotic cells.Methods: Bioinformatic analysis of public databases was employed to identify potential druggable candidates.Normal endometrial tissues and ectopic endometriotic lesions were obtained for the determination of target genes.Primary endometrial and endometriotic stromal cells as well as two different mouse models of endometriosis were used to characterize molecular mechanisms and therapeutic outcomes of endometriosis, respectively.Results: Anthrax toxin receptor 2 (ANTXR2) mRNA and protein are upregulated in the endometriotic specimens.Elevation of ANTXR2 promotes endometriotic cell adhesion, proliferation, and angiogenesis.Furthermore, hypoxia is the driving force for ANTXR2 upregulation via altering histone modification of ANTXR2 promoter by reducing the repressive mark, histone H3 lysine 27 (H3K27) trimethylation, and increasing the active mark, H3K4 trimethylation.Activation of ANTXR2 signaling leads to increased Yes-associated protein 1 (YAP1) nuclear translocation and transcriptional activity, which contributes to numerous pathological processes of endometriosis.Pharmacological blocking of ANTXR2 signaling not only prevents endometriotic lesion development but also causes the regression of established lesion. Conclusion:Taken together, we have identified a novel target that contributes to the disease pathogenesis of endometriosis and provided a potential therapeutic regimen to treat it.
Use of G-CSF after Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplantation Cyclophosphamide
Authors: Valerio Maisano, Raynier Devillier, Sabine Furst, Faezeh Legrand, Samia Harbi, Catherine Faucher, Christian Chabannon, Angela Granata, Pierre Jean Weiller, Didier Blaise
Journal: Blood (2017)
Upregulation of PD-L1 via HMGB1-Activated IRF3 and NF-κB Contributes to UV Radiation-Induced Immune Suppression
Authors: Wei Wang, Nicole M. Chapman, Bo Zhang, Mingqi Li, Meiyun Fan, R. Nicholas Laribee, M. Raza Zaidi, Lawrence M. Pfeffer, Hongbo Chi, Zhao-Hui Wu
Journal: Cancer Research (2019)

Solar ultraviolet radiation (UVR) suppresses skin immunity, which facilitates initiation of skin lesions and establishment of tumors by promoting immune evasion. It is unclear whether immune checkpoints are involved in the modulation of skin immunity by UVR. Here, we report that UVR exposure significantly increased expression of immune checkpoint molecule PD-L1 in melanoma cells. The damage-associated molecular patterns molecule HMGB1 was secreted by melanocytes and keratinocytes upon UVR, which subsequently activated the receptor for advanced glycation endproducts (RAGE) receptor to promote NF-κB- and IRF3-dependent transcription of PD-L1 in melanocytes. UVR exposure significantly reduced the susceptibility of melanoma cells to CD8+ T-cell-dependent cytotoxicity, which was mitigated by inhibiting the HMGB1/TBK1/IRF3/NF-κB cascade or by blocking the PD-1/PD-L1 checkpoint. Taken together, our findings demonstrate that UVR-induced upregulation of PD-L1 contributes to immune suppression in the skin microenvironment, which may promote immune evasion of oncogenic cells and drive melanoma initiation and progression. SIGNIFICANCE: These findings identify PD-L1 as a critical component of UV-induced immune suppression in the skin, which facilitates immunoevasion of oncogenic melanocytes and development of melanoma.See related commentary by Sahu, p. 2805.
CDC37 as a novel target for the treatment of NPM1-ALK expressing anaplastic large cell lymphomas
Authors: Sudhakiranmayi Kuravi, Elizabeth Parrott, Giridhar Mudduluru, Janice Cheng, Siddhartha Ganguly, Yogen Saunthararajah, Roy A. Jensen, Brian S. Blagg, Joseph P. McGuirk, Ramesh Balusu
Journal: Blood Cancer Journal (2019)
Abstract 15226: Coronary Artery Stenosis is Associated With Mitochondrial Dysfunction in Epicardial Adipose Tissue
Authors: Takayuki Nakajima, Takashi Yokota, Yasushige Shingu, Akira Yamada, Yutaka Iba, Kosuke Ujihara, Shuhei Miura, Shingo Takada, Ryosuke Shirakawa, Takaaki Furihata, Masaya Tsuda, Junichi Matsumoto, Takashi Katayama, Arata Fukushima, Akimichi Saito, Yoshiro Matsui, Shintaro Kinugawa
Journal: Circulation (2017)

Introduction: Epicardial adipose tissue (EAT), a source of adipokines, is metabolically active. The role of EAT mitochondria in coronary artery disease (CAD) has not been established. Here we inves...
Development of Light-Responsive Liquid Crystalline Elastomers to Assist Cardiac Contraction
Authors: Cecilia Ferrantini, Josè M. Pioner, Daniele Martella, Raffaele Coppini, Nicoletta Piroddi, Paolo Paoli, Martino Calamai, Francesco S. Pavone, Diederik S. Wiersma, Chiara Tesi, Elisabetta Cerbai, Corrado Poggesi, Leonardo Sacconi, Camilla Parmeggiani
Journal: Circulation Research (2019)

Rationale: Despite major advances in cardiovascular medicine, heart disease remains a leading cause of death worldwide. However, the field of tissue engineering has been growing exponentially in the last decade and restoring heart functionality is now an affordable target; yet, new materials are still needed for effectively provide rapid and long-lasting interventions. Liquid crystalline elastomers (LCEs) are biocompatible polymers able to reversibly change shape in response to a given stimulus and generate movement. Once stimulated, LCEs can produce tension or movement like a muscle. However, so far their application in biology was limited by slow response times and a modest possibility to modulate tension levels during activation. Objective: To develop suitable LCE-based materials to assist cardiac contraction. Methods and Results: Thanks to a quick, simple, and versatile synthetic approach, a palette of biocompatible acrylate-based light-responsive LCEs with different molecular composition was prepared and mechanically characterized. Out of this, the more compliant one was selected. This material was able to contract for some weeks when activated with very low light intensity within a physiological environment. Its contraction was modulated in terms of light intensity, stimulation frequency, and t on /t off ratio to fit different contraction amplitude/time courses, including those of the human heart. Finally, LCE strips were mounted in parallel with cardiac trabeculae, and we demonstrated their ability to improve muscular systolic function, with no impact on diastolic properties. Conclusions: Our results indicated LCEs are promising in assisting cardiac mechanical function and developing a new generation of contraction assist devices.
Emergency Management of Adult and Pediatric Idiopathic Anaphylaxis: A 7-year follow-up study in Canada
Authors: Michelle Le, Sofianne Gabrielli, Ann Elaine Clarke, Judy Morris, Jocelyn Gravel, Edmond S. Chan, Rodrick Lim, Andrew O'Keefe, Greg Shand, Moshe Ben-Shoshan
Journal: Journal of Allergy and Clinical Immunology (2019)
Preference for in-person psychotherapy versus digital psychotherapy options for depression: survey of adults in the U.S
Authors: Brenna N. Renn, Theresa J. Hoeft, Heather Sophia Lee, Amy M. Bauer, Patricia A. Areán
Journal: npj Digital Medicine (2019)

Several barriers complicate access to psychotherapy for depression, including time commitment, location of services, and stigma. Digital treatment has the potential to address these barriers, yet long term use of digital psychotherapy is poor. This paper presents data from a mixed-methods, online survey to document concerns patients with depression face when given the choice of in-person psychotherapy and digital psychotherapy. Participants were 164 adults living in the United States who had previously used or considered psychotherapy for depression. Rural-dwelling and racial/ethnic minority (Native American, African American, and Spanish-speaking) respondents were purposively sampled. Participants were asked their preferences for and opinions about four treatment modalities: self-guided digital, peer-supported digital, expert-guided digital, or in-person psychotherapy. Less than half (44.5%) of participants preferred in-person psychotherapy, 25.6% preferred self-guided digital treatment, 19.7% preferred expert-guided digital treatment, and 8.5% peer-supported digital treatment. Principal themes extracted from qualitative analysis centered on the efficacy of digital treatment, access to digital treatment, concerns about peer-supported care, confidentiality and privacy concerns, preference for in-person treatment, skepticism about self-guided therapy, and the impact of social anxiety on the use of video-chat based care. Future development of digital psychotherapy will need to address concerns regarding efficacy, privacy, data security, and methods to enhance motivation to use these treatments.
The Mechanism of Action of the Anti-CD38 Monoclonal Antibody Isatuximab in Multiple Myeloma
Authors: Laura Moreno, Cristina Perez, Aintzane Zabaleta, Irene Manrique, Diego Alignani, Daniel Ajona, Laura Blanco, Marta Lasa, Patricia Maiso, Idoia Rodriguez, Sonia Garate, Tomas Jelinek, Victor Segura, Cristina Moreno, Juana Merino, Paula Rodriguez-Otero, Carlos Panizo, Felipe Prosper, Jesus F. San-Miguel, Bruno Paiva
Journal: Clinical Cancer Research (2019)

Knowledge about the mechanism of action (MoA) of monoclonal antibodies (mAb) is required to understand which patients with multiple myeloma (MM) benefit the most from a given mAb, alone or in combination therapy. Although there is considerable research about daratumumab, knowledge about other anti-CD38 mAbs remains scarce.We performed a comprehensive analysis of the MoA of isatuximab.Isatuximab induces internalization of CD38 but not its significant release from MM cell surface. In addition, we uncovered an association between levels of CD38 expression and different MoA: (i) Isatuximab was unable to induce direct apoptosis on MM cells with CD38 levels closer to those in patients with MM, (ii) isatuximab sensitized CD38hi MM cells to bortezomib plus dexamethasone in the presence of stroma, (iii) antibody-dependent cellular cytotoxicity (ADCC) was triggered by CD38lo and CD38hi tumor plasma cells (PC), (iv) antibody-dependent cellular phagocytosis (ADCP) was triggered only by CD38hi MM cells, whereas (v) complement-dependent cytotoxicity could be triggered in less than half of the patient samples (those with elevated levels of CD38). Furthermore, we showed that isatuximab depletes CD38hi B-lymphocyte precursors and natural killer (NK) lymphocytes ex vivo-the latter through activation followed by exhaustion and eventually phagocytosis.This study provides a framework to understand response determinants in patients treated with isatuximab based on the number of MoA triggered by CD38 levels of expression, and for the design of effective combinations aimed at capitalizing disrupted tumor-stroma cell protection, augmenting NK lymphocyte-mediated ADCC, or facilitating ADCP in CD38lo MM patients.See related commentary by Malavasi and Faini, p. 2946.
Real-world fusion landscape in advanced Chinese gastric cancer using next generation sequencing: A multicenter study.
Authors: Rongbo Lin, Shen Zhao, Lisheng Cai, Shaoqin Chen, Jinhuo Lai, Yong Fang, Xiuyu Cai, Liping Wang, Mei-yu Fang, Chunwei Xu, Li Lin, Penquan Li, Qi Xu, Xuefeng Fang, Genhua Yu, Jianzhen Shan
Journal: Journal of Clinical Oncology (2019)

51 Background: Gastric cancer (GC) is a highly heterogeneous disease. Cell-free DNA (cfDNA) has been a research hotspot in molecular tumor profiling. In advanced GC patients, malignant pleural effusion (MPE) and ascites provide a wealth of tumor cells that can be investigated. The aim of this study is to investigate fusion landscape in advanced GC. Methods: A multicenter study in China was initiated from Aug. 2016, and GC patients have been enrolled as of Aug. 2018. To determine the fusion frequency in GC, we analyzed data from 371clinical GC cases, each of which had results from next-generation sequencing (NGS)-based 381 genes panel assay, analogous to the index patient. Results: Of this entire cohort, 61 patients (16.44%) were identified with fusions, including TMEM45B-FGF3 (3), AXIN1-SMPD3 (3), B3GNTL1-ERBB2 (2), ERBB2-LAMA3 (2), ERBB2-ACLY (2), TRIM24-BRAF (2), ARHGEF1-CD79A (2), FGFR4-UIMC1 (2), MSH2-TTC7A (2), SMARCA4-LDLR (2), GON4L-RIT1 (2), AKT1-CPSF2 (2), GATA6-COLEC12 (2), RICTOR-EFNA5 (2), KAT6A-PLAT (2), ROCK1-CCDC178 (2), HBS1L-MYB (2), SLC30A2-ARID1A (2), MSI2-BIRC5 (2), NOTCH3-UCA1 (2), PIK3C2B-KISS1 (2), RICTOR-OSMR (2), FGFR2-MIR5694 (2), FGFR2-FGFR1 (2), MAN2A2-BLM (2), EGFR-MED15 (1), EML4-ALK(1), GOPC-ROS1 (1), FXR2-TP53 (1), NF1-PSMD11 (1), IRS2-PRKCI (1), FGFR2-KIAA1217(1), FGFR2-TACC2 (1), FGFR3-TACC3 (1). ERBB2, BRAF, EGFR, ALK and ROS1 fusionswere seen in 18.03% (11/61) of advanced Chinese gastric cancer fusion landscape patients. Conclusions: Advanced Chinese gastric cancer fusion landscape is rich, ERBB2, BRAF, EGFR, ALK and ROS1 fusions are rare but potentially druggable in TKIs. Detection of ERBB2, BRAF, EGFR, ALK and ROS1 fusions should be part of comprehensive profiling panels to determine TKIs and direct appropriate combination therapeutic strategies.
Predicting survival from colorectal cancer histology slides using deep learning: A retrospective multicenter study
Authors: Jakob Nikolas Kather, Johannes Krisam, Pornpimol Charoentong, Tom Luedde, Esther Herpel, Cleo-Aron Weis, Timo Gaiser, Alexander Marx, Nektarios A. Valous, Dyke Ferber, Lina Jansen, Constantino Carlos Reyes-Aldasoro, Inka Zörnig, Dirk Jäger, Hermann Brenner, Jenny Chang-Claude, Michael Hoffmeister, Niels Halama
Journal: PLoS Medicine (2019)

Background For virtually every patient with colorectal cancer (CRC), hematoxylin–eosin (HE)–stained tissue slides are available. These images contain quantitative information, which is not routinely used to objectively extract prognostic biomarkers. In the present study, we investigated whether deep convolutional neural networks (CNNs) can extract prognosticators directly from these widely available images. Methods and findings We hand-delineated single-tissue regions in 86 CRC tissue slides, yielding more than 100,000 HE image patches, and used these to train a CNN by transfer learning, reaching a nine-class accuracy of >94% in an independent data set of 7,180 images from 25 CRC patients. With this tool, we performed automated tissue decomposition of representative multitissue HE images from 862 HE slides in 500 stage I–IV CRC patients in the The Cancer Genome Atlas (TCGA) cohort, a large international multicenter collection of CRC tissue. Based on the output neuron activations in the CNN, we calculated a "deep stroma score," which was an independent prognostic factor for overall survival (OS) in a multivariable Cox proportional hazard model (hazard ratio [HR] with 95% confidence interval [CI]: 1.99 [1.27–3.12], p = 0.0028), while in the same cohort, manual quantification of stromal areas and a gene expression signature of cancer-associated fibroblasts (CAFs) were only prognostic in specific tumor stages. We validated these findings in an independent cohort of 409 stage I–IV CRC patients from the "Darmkrebs: Chancen der Verhütung durch Screening" (DACHS) study who were recruited between 2003 and 2007 in multiple institutions in Germany. Again, the score was an independent prognostic factor for OS (HR 1.63 [1.14–2.33], p = 0.008), CRC-specific OS (HR 2.29 [1.5–3.48], p = 0.0004), and relapse-free survival (RFS; HR 1.92 [1.34–2.76], p = 0.0004). A prospective validation is required before this biomarker can be implemented in clinical workflows. Conclusions In our retrospective study, we show that a CNN can assess the human tumor microenvironment and predict prognosis directly from histopathological images.
Retrospective, cohort study evaluating empiric dose-reduced nab-paclitaxel with gemcitabine in metastatic pancreatic adenocarcinoma: A single institution experience.
Authors: Olugbenga Olanrele Olowokure, LeeAnn Geraghty, Lisa Grate, Alicia Gesenhues, Adam Lane, Eric Mueller, Alex Niu, Mahender Yellu, Anumeha Gupta, Tahir Latif
Journal: Journal of Clinical Oncology (2019)

456 Background: The phase III MPACT trial was conducted to assess OS in patients with metastatic pancreatic adenocarcinoma (mPAC) receiving nab-paclitaxel (nab-P) 125 mg/m 2 + gemcitabine (G) 1000 mg/m 2 on days 1, 8, and 15 every 28 days. Due to reported increased incidence of adverse events (AEs) at this dose, practice at UC Health outside the setting of a clinical trial is to empirically dose reduce (EDR) nab-P to 100 mg/m 2 . This study is a review of the efficacy of EDR nab-P + G in patients with mPAC compared to MPACT data. Methods: This retrospective, single-center, cohort study included patients ≥18 years of age with mPAC (by biopsy) receiving first line therapy with EDR nab-P + G from January 1, 2012 to March 31, 2017. Primary outcome is OS. Secondary outcomes include PFS, CA19-9 percent reduction, incidence of grade ≥ 3 AEs. Results: See table. Conclusions: In patients with mPAC, EDR nab-P plus G demonstrated a median OS of 10 months and PFS of 5 months. 53% of patients had a 20% CA19-9 reduction from baseline with a 1 year OS rate of 45%. The incidence of grade ≥ 3 AEs appeared to be acceptable. [Table: see text]