tbuckley/cabot-search huggingface dataset:
All-cause, cause-specific and age-specific standardised mortality ratios of patients with systemic lupus erythematosus in Ontario, Canada over 43 years (1971–2013)
Authors: Konstantinos Tselios, Dafna D Gladman, Barry J Sheane, Jiandong Su, Murray Urowitz
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Survival in systemic lupus erythematosus (SLE) has improved substantially in the last 50 years. The aim of the present study was to assess the evolution of the all-cause, cause-specific and age-specific standardised mortality ratios (SMRs) of patients with lupus in Ontario, Canada. <h3>Patients and methods</h3> Between 1971 and 2013, 1732 patients were followed in the Toronto Lupus Clinic. Causes of death were retrieved from death certificates, autopsy reports, hospital records or the records of the family physicians. They were categorised as atherosclerotic, infectious, malignancy, active lupus and others. For the calculation of the SMR (indirect standardisation method), data from the general population of Ontario, Canada were used (Statistics Canada). <h3>Results</h3> Two hundred and forty-nine patients (205 women) died (infections 24.5%, atherosclerosis 15.7%, active lupus 13.3%, malignancy 9.6%); mean age was 53.2±16.6 years and mean disease duration 15.2±11.7 years. The all-cause SMR was substantially decreased from the 1970s (13.5, 95% CI 8.6 to 18.5) to recent years (2.2, 95% CI 1.4 to 3.1). Similar trends were observed for atherosclerosis, infections and malignancies over time. The all-cause age-specific SMR was particularly high in younger (19–39 years old) patients (SMR=12.4, 95% CI 9.7 to 15.1) as compared with individuals older than 40 years (SMR=3.1, 95% CI 2.6 to 3.6). The cause-specific SMR was also higher in younger patients, particularly for infections and malignancies. <h3>Conclusions</h3> The all-cause and cause-specific SMR significantly decreased over time, likely reflecting the advances in the management of SLE and certain comorbidities. The all-cause and cause-specific SMR was particularly high for younger patients (&lt;40 years old).
Single Cell Resolution Profiling Defines the Innate and Adaptive Immune Repertoires Modulated By Daratumumab and IMiDs Treatment in Multiple Myeloma (MM)
Authors: Paola Neri, Ranjan Maity, Ines Tagoug, Peter Duggan, Sylvia McCulloch, Victor Jimenez-Zepeda, Jason Tay, Lawrence H. Boise, Anjan Thakurta, Nizar J. Bahlis
Journal: Blood (2017)
FRI-123-Transcriptomic and functional analysis of Kupffer cells in patients with cirrhosis reveals a tumour associated macrophages profile and an impaired immune response that are associated with increased risk of infections
Authors: Elisa Pose, Mar Coll, Isabel Graupera, Javier Pavía, David Fuster, Elsa Solà, Pau Sancho-Bru, Pere Ginès
Journal: Journal of Hepatology (2019)
Bone marrow micro-environmental CD4+ and CD8+ lymphocyte infiltration patterns significantly define overall- and progression free survival in standard risk multiple myeloma: An analysis from the Austrian Myeloma Registry (AMR).
Authors: Ella Willenbacher, Wolfgang Willenbacher, Claudia Zeller-Riese, Rainer Biedermann, Roman Weger, Karin Joehrer, Andrea Brunner
Journal: Journal of Clinical Oncology (2015)

e19530 Background: In Multiple Myeloma immune dysregulation with quantitative and qualitative changes in T-cell subpopulations is thought to result in a reduced anti-tumour immune response promoting disease progression. We systematically analyzed the correlation of the extent of tumour infiltration by CD4+ and CD8+ lymphocytes in bone marrow trephine biopsies to clinical and pathological parameters including progression free- and overall survival, as well as disease response to different types of treatments. Methods: Bone marrow trephine biopsies of 45 patients were retrospectively analyzed by means of immunohistochemistry. Percentage of CD4+ and CD8+ T-cells and the extent of marrow infiltration by plasma cells was determined using a sophisticated automated evaluation software. Statistical analysis was performed applying Kaplan-Meier and Cox regression models using receiver operator characteristics (ROC)-curves for determination of cut-offs. Results: CD4+ T-cells below the cut off of 0.28% lymphocytes/ total nucleated cells were associated with a significantly longer overall survival, while CD8+ T-cells above the cut off of 6.51% correlated with a significantly longer progression free survival, especially in patients with favorable clinical features, such as standard cytogenetic risk or younger age. Treatment with Bortezomib-Thalidomide-Dexamethasone or Thalidomide- or Lenalidomide-Dexamethasone resulted in a significantly better overall- and progression free survival for patients with adverse local immunological features compared to those treated with Bortezomib Mono/Dexamethasone or non-novel agent based therapies. Conclusions: Immune dysregulation in myeloma significantly influences overall- and progression free survival . If prospectively validated lymphocyte infiltration patterns might serve as a predictive biomarker for a more rational allocation of therapies.
Triple Ectopic Thyroid Detected on SPECT/CT
Authors: Kanhaiyalal Agrawal, P. Sai Sradha Patro, Pradeep Pradhan
Journal: Clinical Nuclear Medicine (2019)

Abstract Ectopic thyroid tissue is a rare entity of embryological aberration along the tract of descend of thyroid gland. Accurate localization and characterization are required for deciding management based on clinical features and symptoms. Ectopic thyroid in the absence of normal thyroid gland is uncommon. However, triple ectopic thyroid with absence of normal thyroid gland is very rare, with only a few cases reported previously. We present a case of triple ectopic thyroid, which appeared as single on planar 99m Tc-sodium pertechnetate image, but was evident on SPECT/CT images.
HCP5 is a SMAD3-responsive long non-coding RNA that promotes lung adenocarcinoma metastasis via miR-203/SNAI axis
Authors: Lin Jiang, Ranran Wang, Li Fang, Xiaolu Ge, Lingna Chen, Ming Zhou, Yanhong Zhou, Wei Xiong, Yerong Hu, Xianming Tang, Guiyuan Li, Zheng Li
Journal: Theranostics (2019)

Introduction:Transforming growth factor-beta (TGFβ) signaling plays a vital role in lung adenocarcinoma (LUAD) progression.However, the involvement of TGFβ-regulated long non-coding RNAs (lncRNAs) in metastasis of LUAD remains poorly understood. Methods:We performed bioinformatic analyses to identify putative lncRNAs regulated by TGF-β/SMAD3 and validated the results by quantitative PCR in LUAD cells.We performed luciferase reporter and chromatin immunoprecipitation assays to demonstrate the transcriptional regulation of the lncRNA histocompatibility leukocyte antigen complex P5 (HCP5) we decided to focus on.Stable HCP5 knockdown and HCP5-overexpressing A549 cell variants were generated respectively, to study HCP5 function and understand its mechanism of action.We also confirmed our findings in mouse xenografts and metastasis models.We analyzed the correlation between the level of lncRNA expression with EGFR, KRAS mutations, smoke state and prognostic of LUAD patients.Results: We found that the lncRNA HCP5 is induced by TGFβ and transcriptionally regulated by SMAD3, which promotes LUAD tumor growth and metastasis.Moreover, HCP5 is overexpressed in tumor tissues of patients with LUAD, specifically in patients with EGFR and KRAS mutations and current smoker.HCP5 high expression level is positively correlated with poor prognosis of patients with LUAD.Finally, we demonstrated that upregulation of HCP5 increases the expression of Snail and Slug by sponging the microRNA-203 (miR-203) and promoting epithelial-mesenchymal transition (EMT) in LUAD cells.Conclusions: Our work demonstrates that the lncRNA HCP5 is transcriptionally regulated by SMAD3 and acts as a new regulator in the TGFβ/SMAD signaling pathway.Therefore, HCP5 can serve as a potential therapeutic target in LUAD.
Potential role of IL-8 and eNOS polimorphisms in the outcome of bevacizumab-treated colorectal cancer patients: an exploratory analysis.
Authors: Mariantonietta Di Salvatore, Ernesto Rossi, Concetta Santonocito, Loredana Lo Giudice, Armando Orlandi, Paola Fuso, Ettore Domenico Capoluongo, Alessandra Cassano, Antonio Astone, Michele Basso, Giovanni Schinzari, Carmelo Pozzo, Carlo Barone
Journal: Journal of Clinical Oncology (2015)

e22015 Background: No biomarkers have yet been identified able to predict the efficacy of bevacizumab. We evaluated the influence of some angiogenesis-related gene polymorphisms on efficacy and toxicity of bevacizumab in metastatic colorectal cancer patients. Methods: eNOS-786T/C and -894G/T, IL8-251T/A and COX2-8473 C/T genomic polymorphisms were assessed in 70 metastatic colorectal cancer patients treated in front-line with bevacizumab plus chemotherapy. We evaluated the association between each gene polymorphism and response, toxicity, progression free survival and overall survival. Descriptive statistics were derived using Fisher’s exact test and Kaplan-Meier plots/log-rank test, respectively. Results: Median progression free survival was significantly longer for patients with IL8-251 TT genotype than for those with TA or AA genotypes (10 vs 8 months; HR 0,49; p = 0.004). The mutant TT genotype of eNOS-894 G/T was associated with a higher occurrence of bevacizumab-related toxicity in comparison both with GG (p = 0.03) and GG+GT genotypes (p = 0.009). None of the selected polymorphisms significantly were related to overall survival or response. Conclusions: Our data suggest that in metastatic colorectal cancer patients IL8-251T/A and eNOS 894 G/T polymorphisms might have a role in predicting either efficacy or toxicity of bevacizumab, respectively. Because of the retrospective nature of this study, the results should be considered as exploratory and need to be prospectively confirmed.
Comparison of internal target volume delineation using CT datasets of four-dimensional computed tomography in lung cancer radiotherapy
Authors: S. Bushra, A. Tibdewal, N. Mummudi, R. Kinhikar, Y. Ghadi, J.P. Agarwal
Journal: Annals of Oncology (2019)

Background: Precise tumour volume delineation is a major challenge in lung cancer radiotherapy (RT) because of respiration induced motion. Four-dimensional computed tomography (4DCT) using maximum intensity projection (MIP) dataset is commonly used method to generate internal target volume (ITV). This study compared ITV generation by tumour delineation on MIP and on all phases of the respiratory cycle. Methods: Thirty consecutive patients who underwent 4DCT from Jan 2014 to Mar 2017 were included. After 4DCT image acquisition, ITV was generated by tumour delineation on MIP (ITVMIP) and on all ten phases of respiratory cycle(ITV10). The Correlation between ITVMIP and ITV10 was analysed using Matching index (M.I=overlapping/encompassing volume) and 3D centroid shift. M.I >0.8 was considered as good agreement. Time required to generate ITVMIP and ITV10 was also documented. Mann Whitney test was used for analysis and p < 0.05 was considered significant. Results: Mean volume of ITV10 was 134 cc (range 13 -627) and ITVMIP was 113 cc (range 11 - 569)(p < 0.001). Median volume of ITVMIP not getting covered by ITV10 was 4 cc (5.2%) and vice versa was 19.5cc (19%). The mean M.I between ITVMIP and ITV10 was 0.76 (SD = 0.08, range 0.57-0.88). For 15 patients with tumour close to high density structures like mediastinum, mean MI was 0.73 and for peripheral tumours was 0.78 (p = 0.003). Mean M.I was 0.75 for both tumour ≤5 and >5 cm. For peripheral and ≤ 5 cm tumours, M.I was 0.8. The average time for ITVMIP and ITV10 delineation was 9 and 96 minutes respectively. The centre of mass of ITV10 and ITVMIP was same 0.15 cm in sup/inf axis, 0.11 cm in medio/lateral axis and -0.06 and -0.04 cm in ant/post axis respectively when compared with free breathing CT. The 3D Centroid shift between ITVMIP and ITV10 was 0.01 cm. Conclusions: ITV delineation using MIP is significantly smaller and may be imprecise in tumours adjacent to mediastinum, chest wall and diaphragm. This difference is likely due to difficulty in delineating tumour edges caused by blurring of images. However, delineation using MIP dataset is significantly less time consuming, hence, we recommend its continued use in peripheral tumour and advises caution in central tumours. Legal entity responsible for the study: The authors. Funding: TMC Intramural. Disclosure: All authors have declared no conflicts of interest.
Randomized Trial of Verubecestat for Prodromal Alzheimer’s Disease
Authors: Michael F. Egan, James Kost, Tiffini Voss, Yuki Mukai, Paul S. Aisen, Jeffrey L. Cummings, Pierre N. Tariot, Bruno Vellas, Christopher H. van Dyck, Merce Boada, Ying Zhang, Wen Li, Christine Furtek, Erin Mahoney, Lyn Harper Mozley, Yi Mo, Cyrille Sur, David Michelson
Journal: New England Journal of Medicine (2019)

Prodromal Alzheimer's disease offers an opportunity to test the effect of drugs that modify the deposition of amyloid in the brain before the onset of dementia. Verubecestat is an orally administered β-site amyloid precursor protein–cleaving enzyme 1 (BACE-1) inhibitor that blocks production of amyloid-beta (Aβ). The drug did not prevent clinical progression in a trial involving patients with mild-to-moderate dementia due to Alzheimer's disease.
THU-456-Polyploidy spectrum: a new marker of molecular HCC tumour classification
Authors: Myriam Bou Nader, Stefano Caruso, Julien Calderaro, Romain Donne, Mathilde Cadoux, Thomas Guilbert, Christophe Klein, Gabrielle Couchy, Jean-Pierre Couty, Severine Morizur, Jessica Zucman-Rossi, Chantal Desdouets
Journal: Journal of Hepatology (2019)
Genomic, Transcriptomic, Epigenetic, and Immune Profiling of Mucinous Breast Cancer
Authors: Bastien Nguyen, Isabelle Veys, Sophia Leduc, Yacine Bareche, Samira Majjaj, David N Brown, Bram Boeckx, Diether Lambrechts, Christos Sotiriou, Denis Larsimont, Christine Desmedt
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Although invasive ductal breast cancer (IDC) represents the most common histological type of breast cancer, minor subtypes exist such as mucinous breast cancer (MuBC). MuBC are distinguished by tumor cells floating in extracellular mucin. MuBC patients are generally older and associated with a favorable prognosis. To unravel the molecular architecture of MuBC, we applied low-pass whole-genome sequencing and microscopic evaluation of stromal tumor infiltrating lymphocytes to 30 MuBC from a retrospective institutional cohort. We further analyzed two independent datasets from the International Cancer Genomics Consortium and The Cancer Genome Atlas. Genomic data (n = 26 MuBC, n = 535 estrogen receptor [ER] positive/HER2-negative IDC), methylation data (n = 28 MuBC, n = 529 ER-positive/HER2-negative IDC), and transcriptomic data (n = 27 MuBC, n = 467 ER-positive/HER2-negative IDC) were analyzed. MuBC was characterized by low tumor infiltrating lymphocyte levels (median = 0.0%, average = 3.4%, 95% confidence interval = 1.9% to 4.9%). Compared with IDC, MuBC had a lower genomic instability (P = .01, two-sided Mann-Whitney U test) and a decreased prevalence of PIK3CA mutations (39.7% in IDC vs 6.7% in MuBC, P = .01 in the International Cancer Genomics Consortium; and 34.8% vs 0.0%, P = .02 in The Cancer Genome Atlas, two-sided Fisher’s exact test). Finally, our report identifies aberrant DNA methylation of MUC2 as a possible cause of extracellular production of mucin in MuBC.
FRI-283-Impact on NAFLD of long-term weight loss after bariatric surgery
Authors: Chiara Barbieri, Marianna Palumbo, Fabrizia Carli, Melania Gaggini, Barbara Patricio, Virna Zampa, Brenno Astiarraga, Ele Ferrannini, Stefania Camastra, Amalia Gastaldelli
Journal: Journal of Hepatology (2019)
Abstract 20575: It's All in the Differential: Coronary Arteries and the Cell Count
Authors: Punag Divanji
Journal: Circulation (2017)

A 38-year-old black female with eczema presented with nausea and 8/10 chest pain. Past medical history included 15-years of eczema and temporal artery epithelioid hemangioendothelioma. Exam reveale...
THU-208-Characterization of a novel chemiluminescent enzyme immunoassay for the quantitation of antibodies to hepatitis B core antigen class IgG and correlation with intrahepatic HBV covalently-closed-circular DNA
Authors: Gian Paolo Caviglia, Francesco Tandoi, Giulia Troshina, Lucio Boglione, Chiara Rosso, Elisabetta Bugianesi, Alessia Ciancio, Renato Romagnoli, Mario Rizzetto, Giorgio Maria Saracco, Antonina Smedile, Antonella Olivero
Journal: Journal of Hepatology (2019)
THU-078-PBI-4050 inhibits hepatic stellate cell activation, restores autophagy, and reduces CCl4-induced liver fibrosis
Authors: Brigitte Grouix, François Sarra-Bournet, Lilianne Geerts, Kathy Hince, Mikaël Tremblay, Alexandra Felton, Alexandra Blais, Jugurtha Ouboudinar, Jean-Christophe Simard, Pierre Laurin, Lyne Gagnon
Journal: Journal of Hepatology (2019)
The blood proteomic signature of early-onset pediatric atopic dermatitis shows systemic inflammation and is distinct from adult long-standing disease
Authors: Patrick M. Brunner, Helen He, Ana B. Pavel, Tali Czarnowicki, Rachel Lefferdink, Taylor Erickson, Talia Canter, Neha Puar, Stephanie M. Rangel, Kunal Malik, Yeriel Estrada, James G. Krueger, Emma Guttman-Yassky, Amy S. Paller
Journal: Journal of the American Academy of Dermatology (2019)
FRI-507-Hepatocyte-specific role of c-Jun N-terminal kinase 2 for disease progression and therapy in chronic liver disease
Authors: Marius Woitok, Miguel Eugenio Zoubek, Dennis Doleschel, Fabian Kiessling, Wiltrud Lederle, Christian Trautwein, Francisco Javier Cubero
Journal: Journal of Hepatology (2019)
Longitudinal patient-reported symptom burden and treatment preference in patients with metastatic colorectal cancer (mCRC).
Authors: Amy Little Jones, Nrupen Anjan Bhavsar, Amy Pickar Abernethy, Yousuf Zafar
Journal: Journal of Clinical Oncology (2015)

e20687 Background: Clinicians have difficulty predicting longitudinal changes in patient symptom burden or treatment preference. The primary aim of this pilot study was to investigate how symptom burden and patient treatment preference change over time in mCRC patients with limited life expectancy. Methods: EligiblemCRC patients had incurable disease, received chemotherapy at Duke University Medical Center or Duke Raleigh, were ≥ 18 years old, and were English-speaking. Patients were surveyed at each visit and followed for up to 2 years on study. Measures included the FACT-C (Functional Assessment of Cancer Therapy-Colorectal), PCM (Patient Care Monitor; a validated, 87-item, patient-reported, review of systems survey; items measured on a 0-10 scale), and QQQ (Quality-Quantity Questionnaire; a validated, 8-item measure of cancer patient preference for quantity vs. quality of life; items measured on a 1-5 Likert scale). Demographic, disease, and treatment data were abstracted from the medical record. Results: 56 patients had a mean age of 55. Most were male (68%) and Caucasian (79%). Patients answered surveys a mean 6.8 times each, with a median 364 days between first and last surveys. Over time, patients reported most symptoms improved or stayed the same (72%, n = 63 symptoms). Mean symptom scores that improved the most from first to last survey were fatigue (3.92 to 3.03), nausea (2.10 to 1.35), and weakness (2.63 to 1.97). Symptoms that worsened the most included pain (1.94 to 2.47), joint pain (1.49 to 1.94), and cough (0.39 to 0.68). Mean QQQ scores from first survey (22, n = 28) to last survey (22, n = 16) remained stable. Conclusions: Reporting of symptom burden showed mostly improved or stable scores over time, even though all participants had metastatic cancer and were approaching the end of life. This pilot study could not differentiate between true improvement/stability in symptom burden vs. the effect of coping or acclimation to symptoms over time.
Geographic distribution of COPD prevalence in the world displayed by Geographic Information System maps
Authors: Ignacio Blanco, Isidro Diego, Patricia Bueno, Francisco Casas-Maldonado, Marc Miravitlles
Journal: European Respiratory Journal (2019)

<b>The global prevalence of COPD is 13.1%, ranging from 11.6% in Oceania to 13.9% in Africa. With the aid of GIS technology, a global map of prevalence of COPD has been obtained including areas without real data.</b>http://bit.ly/2HRWfK7
Recent advances of therapeutic targets based on the molecular signature in breast cancer: genetic mutations and implications for current treatment paradigms
Authors: Zeinab Safarpour Lima, Mostafa Ghadamzadeh, Farzad Tahmasebi Arashloo, Ghazaleh Amjad, Mohammad Reza Ebadi, Ladan Younesi
Journal: Journal of Hematology & Oncology (2019)

Breast cancer is the most common malignancy in women all over the world. Genetic background of women contributes to her risk of having breast cancer. Certain inherited DNA mutations can dramatically increase the risk of developing certain cancers and are responsible for many of the cancers that run in some families. Regarding the widespread multigene panels, whole exome sequencing is capable of providing the evaluation of genetic function mutations for development novel strategy in clinical trials. Targeting the mutant proteins involved in breast cancer can be an effective therapeutic approach for developing novel drugs. This systematic review discusses gene mutations linked to breast cancer, focusing on signaling pathways that are being targeted with investigational therapeutic strategies, where clinical trials could be potentially initiated in the future are being highlighted.
Improvement in imaging of metastatic breast cancer (BC) with a novel pretargeted immuno-PET targeting CEA: First clinical results.
Authors: Caroline Rousseau, Aurore Rauscher, Alain Faivre-Chauvet, Thomas Carlier, Ludovic Ferrer, David M Goldenberg, Robert M. Sharkey, Jacques Barbet, Francoise Kraeber-Bodere, Mario Campone
Journal: Journal of Clinical Oncology (2015)

11059 Background: New phenotypic imaging with noninvasive antibody imaging methods targeting membranous antigens have been tested in BC trials. A new generation of immuno-PET comprising anti-CEA x anti-HSG humanized trivalent TF2 bispecific MAb and 68Ga-IMP288 HSG peptide is being assessed. This study aimed to compare the sensitivity of anti-CEA immuno-PET/CT comparing this immune-PET to morphological imaging and FDG-PET/CT in metastatic BC patients. Methods: Thirteen patients with metastatic BC enrolled in an optimization immuno-PET study had whole-body immuno-PET/CT at 1h and 2h after injection of 150 MBq of 68Ga-IMP288 pretargeted by 120 nmol of unlabeled TF2 binding CEA and the HSG peptide injected 24h to 30h before. Thoracic-abdominal-pelvic CT and FDG-PET/CT were also performed. The gold standard was determined by follow-up and a lesion detected by at least 2 imaging modalities was considered as positive. Results: Median serum CEA was 46.15 µg/L (9.5 to 1359.0). To date, 515 lesions were confirmed as pathologic by the gold standard: 18 in LN, 4 in lung, 94 in liver, 399 in bone, 1 in skin, and 4 in brain. Overall sensitivity of immuno-PET was 93.8%, with 100% sensitivity for bone, liver, skin, and brain, 94% for LN, and 37.5% for lung. Overall sensitivity of CT and FDG-PET/CT was 74.6% and 84.7%, respectively. Bone MRI had 94% sensitivity. Brain lesions were only detected by immuno-PET/CT and confirmed by MRI. Median tumor SUVpeak on immuno-PET at 1h and 2h was 9.58 (3.52 to 24.55) and 11.04 (3.09-34.27), respectively. In half of patients (7/13) an increased tumor uptake between 1h and 2h was observed and no lesion was detected only at 2h. Conclusions: These results demonstrate the high accuracy of anti-CEA pretargeted immuno-PET/CT for staging pts with metastatic BC, especially for bone, liver and brain evaluation. Immuno-PET allowed detection of bone lesions in areas not explored by MRI. Clinical trial information: NCT01730612.