tbuckley/cabot-search huggingface dataset:
Focal Myositis of the Leg Presenting as Fever of Unknown Origin Detected by FDG PET/CT
Authors: Aisheng Dong, Yushu Bai, Yang Wang
Journal: Clinical Nuclear Medicine (2018)

Focal myositis is an uncommon inflammatory pseudotumor of the skeletal muscle that may mimic neoplastic and inflammatory diseases. We present one case of focal myositis involving the left proximal vastus lateralis and vastus intermedius, and left soleus showing intense FDG uptake on FDG PET/CT. This case indicates that focal myositis should be considered as a differential diagnosis in patients with focal hypermetabolic muscular lesions, including benign and malignant tumors, necrotizing autoimmune myopathy, nodular fasciitis, myositis ossificans, and muscular sarcoidosis.
Scaling up primary health services for improving reproductive, maternal, and child health: a multisectoral collaboration in the conflict setting of Afghanistan
Authors: Jai K Das, Nadia Akseer, Shafiq Mirzazada, Zahra Peera, Omarwalid Noorzada, Corinne E Armstrong, Kashif Mukhtar, Ahmed Jan Naeem, Zulfiqar A Bhutta
Journal: BMJ (2018)

interconnectedness of the sustainable development goals and deliberate engagement of multiple sectors will be critical to achieving Afghanistan's development goals
Midostaurin added to chemotherapy and continued single-agent maintenance therapy in acute myeloid leukemia with FLT3-ITD
Authors: Richard F. Schlenk, Daniela Weber, Walter Fiedler, Helmut R. Salih, Gerald Wulf, Hans Salwender, Thomas Schroeder, Thomas Kindler, Michael Lübbert, Dominik Wolf, Jörg Westermann, Doris Kraemer, Katharina S. Götze, Heinz-August Horst, Jürgen Krauter, Michael Girschikofsky, Mark Ringhoffer, Thomas Südhoff, Gerhard Held, Hans-Günter Derigs, Roland Schroers, Richard Greil, Martin Grießhammer, Elisabeth Lange, Alexander Burchardt, Uwe Martens, Bernd Hertenstein, Lore Marretta, Michael Heuser, Felicitas Thol, Verena I. Gaidzik, Wolfgang Herr, Julia Krzykalla, Axel Benner, Konstanze Döhner, Arnold Ganser, Peter Paschka, Hartmut Döhner
Journal: Blood (2018)
Preoperative Endoscopic Retrograde Cholangiopancreatography Is Not Associated With Increased Pancreatic Cancer Mortality
Authors: Sheila D. Rustgi, Sunil Amin, Anthony Yang, Michelle K. Kim, Satish Nagula, Nikhil A. Kumta, Christopher J. DiMaio, Paolo Boffetta, Aimee L. Lucas
Journal: Clinical Gastroenterology and Hepatology (2018)
Respective Place of Venetoclax and MCL1 BH3 Mimetics in Multiple Myeloma Treatment
Authors: Patricia Gomez-Bougie, Sophie Maïga, Benoit Tessoulin, Jessie Bourcier, Antoine Bonnet, Géraldine Descamps, Carolane Seiller, Cyrille Touzeau, Philippe Moreau, Catherine Pellat-Deceunynck, Martine Amiot
Journal: Blood (2018)
Abstract 19766: The Role of Myocardial Perfusion Imaging in Evaluating Patients Presenting With Ventricular Tachycardia and Implantable Cardioverter Defibrillator Therapy
Authors: Joshua W Harrison, Akrivi Manola, N Gurukripa Kowlgi, W. Lane Duvall, Dalia Giedrimiene, Jeffrey Kluger
Journal: Circulation (2016)

Introduction: Myocardial ischemia and scar burden are generally accepted to be substrate for cardiac arrhythmias. Despite this, the role of myocardial perfusion imaging in the evaluation of ventric...
TPX2 in melanoma: honing on drivers of amplification on chromosome 20q11.2
Authors: Maurizia dalla palma, Bin Li, Phyllis Gymotty, Katherine Nathanson
Journal: Cancer Research (2008)

1687  We previously performed BAC based array-comparative genomic hybridization (aCGH) on 83 metastatic melanoma lesions (27 melanoma cell lines, 34 frozen and 22 formalin-fixed, paraffin embedded clinical melanoma samples). In this analysis, we found recurrent and characteristic losses of chromosome 5q, 6q, 9,10q, 11q, 8q and gains of chromosomes 1q, 6p, 7, 8p, 17p and 20q. Moreover, in this sample set, we were able to prove with statistical significance (p
Abstract 12: Socioeconomic Correlates of Cardiovascular Disease Risk in African Americans: The Jackson Heart Study
Authors: Yuan-I Min, Pramod Anugu, Kenneth Butler, Adolfo Correa, Tara Hartley, Stanford Mwasongwe, Arnita Norwood, Mario Sims, Valerie Wallace, Wei Wang, Karen Winters
Journal: Circulation (2016)

Background: Research has found that socioeconomic status (SES) is associated with cardiovascular disease (CVD) risk. However, few studies have reported the SES correlates of CVD risk in African Americans (AA). Since low SES is over-represented in AA, our objective is to examine the socioeconomic correlates of CVD risk in this population, which may provide new insights on racial/ethnic disparities in CVD risk. Methods: A cross-sectional analysis of baseline data collected in the Jackson Heart Study (JHS), an entirely AA population, was performed. Multivariable logistic regression analysis estimated the age and sex-adjusted association of SES indicators (education, household income and occupation) with prevalent CVD (myocardial infarction (MI), stroke and hypertension). Stratified analyses by age (&lt;65 and ≥65 years) and sex were also performed. Additional analyses were performed using logistic models with a backward selection procedure that included age, sex, education, household income, occupation and burden of CVD risk factors (measured by the number of Life’s Simple 7® metrics meeting ideal health) as independent variables and prevalent CVD as dependent variables, Due to missing data, sample sizes for these analyses ranged from 3,473 to 5,301. Results: Baseline prevalence for MI, stroke and hypertension were 5.5%, 4.4% and 60.1%. About one-third (32.5%) of the participants had a bachelor’s degree, 35% held management or professional occupations and 30% were “affluent” (≥3.5 US Census poverty level). We observed an inverse relationship between prevalent CVD and SES indicators. The largest and most consistent SES correlate of prevalent CVD was observed with income on MI (odds ratio (OR) 3.5; 95% CI 2.3, 5.4) and stroke (OR 3.7; 95% CI 2.3, 6.0) comparing the poor (below US Census poverty level) to the affluent income categories. Stratified analyses suggested stronger SES gradients in individuals &lt;65 years and in females for MI. In the backward logistic regression models, the significant SES indicators (p&lt;0.05) remaining in the final model were income for MI and stroke, and occupation for hypertension. The burden of CVD risk factors was statistically significant and remained in the final model for all three CVD outcomes. Conclusions: Inverse SES gradients on the prevalence of MI, stroke and hypertension were observed among AA in the JHS. The most important SES correlates were income for MI and stroke, and occupation for hypertension. These findings suggest SES, and income in particular, is an important factor contributing to health disparities in CVD among AA and possibly AA-White disparities in health outcomes.
Abstract 12277: Iatrogenic Atrial Septal Defect After Percutaneous Mitral Valve Repair With the MitraClip System
Authors: Kentaro Toyama, Florian Rader, Saibal Kar, Shunsuke Kubo, Takahiro Shiota, Toshihiko Nishioka, Robert J Siegel
Journal: Circulation (2017)

Introduction: Persistent iatrogenic atrial septal defect (iASD) has been reported in patients with a trans-septal puncture performed for access to the left atrium. The data on the characteristics o...
Risk stratification and medical therapy of pulmonary arterial hypertension
Authors: Nazzareno Galiè, Richard N. Channick, Robert P. Frantz, Ekkehard Grünig, Zhi Cheng Jing, Olga Moiseeva, Ioana R. Preston, Tomas Pulido, Zeenat Safdar, Yuichi Tamura, Vallerie V. McLaughlin
Journal: European Respiratory Journal (2018)

Pulmonary arterial hypertension (PAH) remains a severe clinical condition despite the availability over the past 15 years of multiple drugs interfering with the endothelin, nitric oxide and prostacyclin pathways. The recent progress observed in medical therapy of PAH is not, therefore, related to the discovery of new pathways, but to the development of new strategies for combination therapy and on escalation of treatments based on systematic assessment of clinical response. The current treatment strategy is based on the severity of the newly diagnosed PAH patient as assessed by a multiparametric risk stratification approach. Clinical, exercise, right ventricular function and haemodynamic parameters are combined to define a low-, intermediate- or high-risk status according to the expected 1-year mortality. The current treatment algorithm provides the most appropriate initial strategy, including monotherapy, or double or triple combination therapy. Further treatment escalation is required in case low-risk status is not achieved in planned follow-up assessments. Lung transplantation may be required in most advanced cases on maximal medical therapy.
Dopamine Receptor D5 is a Modulator of Tumor Response to Dopamine Receptor D2 Antagonism
Authors: Varun V. Prabhu, Neel S. Madhukar, Coryandar Gilvary, C. Leah B. Kline, Sophie Oster, Wafik S. El-Deiry, Olivier Elemento, Faye Doherty, Alexander VanEngelenburg, Jessica Durrant, Rohinton S. Tarapore, Sean Deacon, Neil Charter, Jinkyu Jung, Deric M. Park, Mark R. Gilbert, Jessica Rusert, Robert Wechsler-Reya, Isabel Arrillaga-Romany, Tracy T. Batchelor, Patrick Y. Wen, Wolfgang Oster, Joshua E. Allen
Journal: Clinical Cancer Research (2018)

Dopamine receptor D2 (DRD2) is a G protein-coupled receptor antagonized by ONC201, an anticancer small molecule in clinical trials for high-grade gliomas and other malignancies. DRD5 is a dopamine receptor family member that opposes DRD2 signaling. We investigated the expression of these dopamine receptors in cancer and their influence on tumor cell sensitivity to ONC201.The Cancer Genome Atlas was used to determine DRD2/DRD5 expression broadly across human cancers. Cell viability assays were performed with ONC201 in >1,000 Genomic of Drug Sensitivity in Cancer and NCI60 cell lines. IHC staining of DRD2/DRD5 was performed on tissue microarrays and archival tumor tissues of glioblastoma patients treated with ONC201. Whole exome sequencing was performed in RKO cells with and without acquired ONC201 resistance. Wild-type and mutant DRD5 constructs were generated for overexpression studies.DRD2 overexpression broadly occurs across tumor types and is associated with a poor prognosis. Whole exome sequencing of cancer cells with acquired resistance to ONC201 revealed a de novo Q366R mutation in the DRD5 gene. Expression of Q366R DRD5 was sufficient to induce tumor cell apoptosis, consistent with a gain-of-function. DRD5 overexpression in glioblastoma cells enhanced DRD2/DRD5 heterodimers and DRD5 expression was inversely correlated with innate tumor cell sensitivity to ONC201. Investigation of archival tumor samples from patients with recurrent glioblastoma treated with ONC201 revealed that low DRD5 expression was associated with relatively superior clinical outcomes.These results implicate DRD5 as a negative regulator of DRD2 signaling and tumor sensitivity to ONC201 DRD2 antagonism.
Influenza Cataclysm, 1918
Authors: David M. Morens, Jeffery K. Taubenberger
Journal: New England Journal of Medicine (2018)

Interview with Dr. David Morens on lessons from the 1918 influenza pandemic and the threat of a similar global health disaster. (10:50)Download This year marks the centennial of an influenza pandemic that killed 50 million to 100 million people globally — arguably the single deadliest event in recorded human history. Evidence suggests that another pandemic at least as severe may occur one day.
A phase II study of autologous tumor infiltrating lymphocytes (TIL; LN-144/LN-145) in patients with solid tumors
Authors: J. Chesney, A. Cacovean, H. Li, D. Barton, M. Fardis
Journal: Annals of Oncology (2018)

Background: Adoptive cell therapy with TIL has demonstrated durable complete responses in immunogenic tumors with high mutational burden in patients who had not received prior checkpoint therapy (>22% CR). Pembrolizumab is an approved agent for treatment of metastatic melanoma and head and neck cancers. Further, checkpoint inhibitors have been reported to possibly enhance the efficacy of TIL therapy. One aim of this study is to improve on the efficacy response for early line patients by combining TIL with anti-PD1 in metastatic melanoma and head and neck cancers (Cohorts 1 and 2). In Cohort 3, TIL alone is offered to non-small cell lung cancer patients who have received prior systemic therapy including checkpoint inhibitors. Trial design: IOV-COM-202 is a Phase 2 multicenter, open-label, nonrandomized study in which patients are enrolled in the combination arms (Cohorts 1 and 2) or LN-145 therapy only (Cohort 3) based upon study disease (see above). Planned enrollment is N = 36 (12/cohort). Tumors resected at local institutions are processed at centralized GMP facilities using a 22-day manufacturing process to generate the final cryopreserved infusion product (LN-144/LN-145) that is shipped to the sites. All patients receive TIL therapy consisting of 1 week of a preconditioning cyclophosphamide/fludarabine lymphodepletion regimen, followed by a single infusion of LN144/LN-145 (Day 0) and up to 6 doses of intravenous IL-2 (600,000 IU/kg). Patients in Cohorts 1 and 2 also receive pembrolizumab on Day 1 and again every 3 weeks for up to 2 years. Eligibility includes: ≥ 18 years of age; 1-3 lines of prior systemic therapy (exclusions apply); ≥ 1 resectable lesion(s) yielding ≥ 1.5 cm in diameter of viable tumor and a remaining RECIST-measurable lesion; and ECOG PS of 0-1. For each cohort, the primary endpoint is ORR per RECIST v1.1 and safety. Secondary endpoints are CR rate, DOR, DCR, PFS, and OS. Exploratory objectives include tumor response per irRECIST, immune correlates of response, and HRQoL. NCT03645928 Legal entity responsible for the study: Iovance Biotherapeutics, Inc. Funding: Iovance Biotherapeutics, Inc. Disclosure: A. Cacovean, D. Barton: Employee of Iovance Biotherapeutics, Inc. M. Fardis: Chief Executive Officer of Iovance Biotherapeutics, Inc. All other authors have declared no conflicts of interest.
SQZing cells to rapidly generate antigen presenting cells (APC) for solid tumor immune therapies with efficient, scalable manufacturing
Authors: S.M. Loughhead, M.G. Booty, K. Hlavaty, A. Vicente-Suarez, K. Blagovic, M. Myint, B. Stokes, D. Yarar, H. Bernstein, A. Sharei
Journal: Annals of Oncology (2018)

Background: CD8 T cells are critical to immunotherapeutic intervention in cancer. However, the ability to efficiently target antigens for MHC-I presentation has limited the efficacy of immunization strategies. Here, we use microfluidics-based SQZ cell therapy platform to deliver antigen to the cytosol of target APCs, resulting in enhanced presentation on MHC-I. Given that no expansion time is required to engineer these APCs, this approach allows for rapid manufacturing of billions of non-conventional APCs capable of priming CD8+ T cell responses. Methods: Protein and peptide antigens were delivered to murine or human T cells with the SQZ cell therapy platform. The response to in vivo immunization of C57BL/6 mice was assessed by flow cytometry. Tumor experiments were conducted with the TC-1 cell line. Human T cells were co-cultured with epitope-reactive human responder CD8+ T cells, and interferon gamma production was quantified to assess antigen-specific responses. Results: In murine systems, we demonstrate that therapeutic immunization with T cells loaded with E7 using the SQZ platform are capable of eliciting strong anti-tumor effects. These anti-tumor responses correlate with an increase in antigen-specific CD8+ tumor infiltrating lymphocytes that is dependent on the co-administration of an adjuvant. In human cells, we demonstrate that primary T cells loaded with CMV and HPV16 antigens using SQZ can stimulate antigen-specific CD8+ T cell responses in vitro. Importantly, delivery to T cells scales from millions up to billions of cells per minute and antigen presentation is retained even after cryo-preservation. Conclusions: Through the direct cytosolic delivery of antigen, the SQZ cell therapy platform enables the use of T cells, a readily accessible and abundant cell type, to function as APCs for immunization. This strategy has demonstrated the ability to generate CD8+ T cell responses in both murine and human systems and has been scaled up for clinical implementation. With the ease and speed of manufacturing, these results have the potential to translate into a cellular immune therapy for oncology patients. Legal entity responsible for the study: SQZ Biotechnologies. Funding: SQZ Biotechnologies. Disclosure: S.M. Loughhead, M.G. Booty, K. Hlavaty, A. Vicente-Suarez, K. Blagovic, M. Myint, B. Stokes, D. Yarar, H. Bernstein, A. Sharei: Employee of SQZ Biotech.
Dasatinib Versus Imatinib in Patients (Pts) with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Who Have Not Achieved an Optimal Response to 3 Months of Imatinib Therapy: Dascern
Authors: Jorge E. Cortes, Qian Jiang, Jianxiang Wang, Jianyu Weng, Huanling Zhu, Liu Xiaoli, Andreas Hochhaus, Dong-Wook Kim, Jerald Radich, Michael R. Savona, Patricia Martin Regueira, Oumar Sy, Renuka Gurnani, Giuseppe Saglio
Journal: Blood (2018)
Tuning T‐Cell Receptor Affinity to Optimize Clinical Risk‐Benefit When Targeting Alpha‐Fetoprotein–Positive Liver Cancer
Authors: Roslin Y. Docta, Tiago Ferronha, Joseph P. Sanderson, Thomas Weissensteiner, George R. Pope, Alan D. Bennett, Nicholas J. Pumphrey, Zoltan Ferjentsik, Laura L. Quinn, Guy E. Wiedermann, Victoria E. Anderson, Manoj Saini, Miguel Maroto, Elliot Norry, Andrew B. Gerry
Journal: Hepatology (2018)

Patients with hepatocellular carcinoma (HCC) have a poor prognosis and limited therapeutic options. Alpha‐fetoprotein (AFP) is often expressed at high levels in HCC and is an established clinical biomarker of the disease. Expression of AFP in nonmalignant liver can occur, particularly in a subset of progenitor cells and during chronic inflammation, at levels typically lower than in HCC. This cancer‐specific overexpression indicates that AFP may be a promising target for immunotherapy. We verified expression of AFP in normal and diseased tissue and generated an affinity‐optimized T‐cell receptor (TCR) with specificity to AFP/HLA‐A*02 + tumors. Expression of AFP was investigated using database searches, by qPCR, and by immunohistochemistry (IHC) analysis of a panel of human tissue samples, including normal, diseased, and malignant liver. Using in vitro mutagenesis and screening, we generated a TCR that recognizes the HLA‐A*02‐restricted AFP 158‐166 peptide, FMNKFIYEI, with an optimum balance of potency and specificity. These properties were confirmed by an extension of the alanine scan (X‐scan) and testing TCR‐transduced T cells against normal and tumor cells covering a variety of tissues, cell types, and human leukocyte antigen (HLA) alleles. Conclusion: We have used a combination of physicochemical, in silico , and cell biology methods for optimizing a TCR for improved affinity and function, with properties that are expected to allow TCR‐transduced T cells to differentiate between antigen levels on nonmalignant and cancer cells. T cells transduced with this TCR constitute the basis for a trial of HCC adoptive T‐cell immunotherapy.
A Phase II Study of Talazoparib after Platinum or Cytotoxic Nonplatinum Regimens in Patients with Advanced Breast Cancer and Germline <i>BRCA1/2</i> Mutations (ABRAZO)
Authors: Nicholas C. Turner, Melinda L. Telli, Hope S. Rugo, Audrey Mailliez, Johannes Ettl, Eva-Maria Grischke, Lida A. Mina, Judith Balmaña, Peter A. Fasching, Sara A. Hurvitz, Andrew M. Wardley, Colombe Chappey, Alison L. Hannah, Mark E. Robson
Journal: Clinical Cancer Research (2018)

Abstract Purpose: To assess talazoparib activity in germline BRCA1/2 mutation carriers with advanced breast cancer. Patients and Methods: ABRAZO (NCT02034916) was a two-cohort, two-stage, phase II study of talazoparib (1 mg/day) in germline BRCA mutation carriers with a response to prior platinum with no progression on or within 8 weeks of the last platinum dose (cohort 1) or ≥3 platinum-free cytotoxic regimens (cohort 2) for advanced breast cancer. Primary endpoint was confirmed objective response rate (ORR) by independent radiological assessment. Results: We enrolled 84 patients (cohort 1, n = 49; cohort 2, n = 35) from May 2014 to February 2016. Median age was 50 (range, 31–75) years. Triple-negative breast cancer (TNBC) incidence was 59% (cohort 1) and 17% (cohort 2). Median number of prior cytotoxic regimens for advanced breast cancer was two and four, respectively. Confirmed ORR was 21% [95% confidence interval (CI), 10–35; cohort 1] and 37% [95% CI, 22–55; cohort 2]. Median duration of response was 5.8 and 3.8 months, respectively. Confirmed ORR was 23% (BRCA1), 33% (BRCA2), 26% (TNBC), and 29% (hormone receptor–positive). The most common all-grade adverse events (AE) included anemia (52%), fatigue (45%), and nausea (42%). Talazoparib-related AEs led to drug discontinuation in 3 (4%) patients. In an exploratory analysis, longer platinum-free interval was associated with higher response rate in cohort 1 (0% ORR with interval &amp;lt;8 weeks; 47% ORR with interval &amp;gt;6 months). Conclusions: Talazoparib exhibited promising antitumor activity in patients with advanced breast cancer and germline BRCA mutation.
Genomic and transcriptomic landscapes of Epstein-Barr virus in extranodal natural killer T-cell lymphoma
Authors: Rou-Jun Peng, Bo-Wei Han, Qing-Qing Cai, Xiao-Yu Zuo, Tao Xia, Jie-Rong Chen, Li-Na Feng, Jing Quan Lim, Shu-Wei Chen, Mu-Sheng Zeng, Yun-Miao Guo, Bo Li, Xiao-Jun Xia, Yi Xia, Yurike Laurensia, Burton Kuan Hui Chia, Hui-Qiang Huang, Ken He Young, Soon Thye Lim, Choon Kiat Ong, Yi-Xin Zeng, Jin-Xin Bei
Journal: Leukemia (2018)

Extranodal natural killer T-cell lymphoma (nasal type; NKTCL) is an aggressive malignancy strongly associated with Epstein-Barr virus (EBV) infection. However, the role of EBV in NKTCL development is unclear, largely due to the lack of information about EBV genome and transcriptome in NKTCL. Here, using high-throughput sequencing, we obtained whole genome (n = 27) and transcriptome datasets (n = 18) of EBV derived from NKTCL tumor biopsies. We assembled 27 EBV genomes and detected an average of 1,152 single nucleotide variants and 44.8 indels (<50 bp) of EBV per sample. We also identified frequent focal EBV genome deletions and integrated EBV fragments in the host genome. Moreover, Phylogenetic analysis revealed that NKTCL-derived EBVs are closely clustered; transcriptome analysis revealed less activation of both latent and lytic genes and larger amount of T-cell epitope alterations in NKTCL, as compared with other EBV-associated cancers. Furthermore, we observed transcriptional defects of the BARTs miRNA by deletion, and the disruption of host NHEJ1 by integrated EBV fragment, implying novel pathogenic mechanisms of EBV. Taken together, we reported for the first time global mutational and transcriptional profiles of EBV in NKTCL clinical samples, revealing important somatic events of EBV and providing insights to better understanding of EBV's contribution in tumorigenesis.