tbuckley/cabot-search huggingface dataset:
RNA-based FLT3-ITD allelic ratio is associated with outcome and ex vivo response to FLT3 inhibitors in pediatric AML
Authors: David G. J. Cucchi, Barbara Denys, Gertjan J. L. Kaspers, Jeroen J. W. M. Janssen, Gert J. Ossenkoppele, Valérie de Haas, C. Michel Zwaan, Marry M. van den Heuvel-Eibrink, Jan Philippé, Tamás Csikós, Zinia Kwidama, Barbara de Moerloose, Eveline S. J. M. de Bont, Birgit I. Lissenberg-Witte, Sonja Zweegman, Femke Verwer, Karl Vandepoele, Gerrit Jan Schuurhuis, Edwin Sonneveld, Jacqueline Cloos
Journal: Blood (2018)
3D-Printed membrane as an alternative to amniotic membrane for ocular surface/conjunctival defect reconstruction: An in vitro &amp; in vivo study
Authors: Shima Dehghani, Morteza Rasoulianboroujeni, Hamed Ghasemi, Saeed Heidari Keshel, Zohreh Nozarian, Mohammad Naser Hashemian, Mehran Zarei-Ghanavati, Golshan Latifi, Reza Ghaffari, Zhanfeng Cui, Hua Ye, Lobat Tayebi
Journal: Biomaterials (2018)
TCTAP A-095 Comparison of the Long-term Clinical Outcomes Between Revascularization and Medical Therapy in Patients with Silent Ischemia
Authors: Ki Hong Choi, Joo Myung Lee, Taek Kyu Park, Jeong Hoon Yang, Young Bin Song, Joo-Yong Hahn, Seung Hyuk Choi, Hyeon-Cheol Gwon
Journal: Journal of the American College of Cardiology (2018)
Abstract 18359: Maturation of Reprogrammed Endothelial Cells Using a Single Transcription Factor in a Prolonged Cultivation
Authors: Sangho Lee, Changwon Park, Ji Woong Han, Ju Young Kim, Kyuwon Cho, Sangsung Kim, Shin-Jeong Lee, Shraya Sharma, Young-sup Yoon
Journal: Circulation (2016)

Introduction: Endothelial cells (ECs) are an essential component of blood vessels and are crucial for repairing injured and ischemic tissues. Previously, we showed that a single EC transcription fa...
Nighttime light exposure enhances Rev-erbα-targeting microRNAs and contributes to hepatic steatosis
Authors: Patricia C. Borck, Thiago M. Batista, Jean F. Vettorazzi, Gabriela M. Soares, Camila Lubaczeuski, Dongyin Guan, Antonio C. Boschero, Elaine Vieira, Mitchell A. Lazar, Everardo M. Carneiro
Journal: Metabolism (2018)
Pain in cancer patients: Pain assessment both by patients and family caregivers and problems experienced by caregivers.
Authors: Ozlem Ovayolu, Nimet Ovayolu, Sema Aytac, Sibel Serce, Alper Sevinc
Journal: Journal of Clinical Oncology (2014)

207 Background: Pain is among the most important symptoms in terms of prevalence and a major cause of distress for cancer patients and their family caregivers. Thus, we conducted this study with the aim to compare assessment of pain among cancer patients and their caregivers and to determine the problems experienced by caregivers. Methods: A cross-sectional and descriptive design was used. This study was conducted in a chemotherapy unit and an adult oncology clinic with 220 patients diagnosed with cancer who admitted to an oncology hospital and 220 caregivers. The study data was collected using a questionnaire and Visual Analogue Scale (VAS where “0: no pain”, 10: severe pain”). Statistically significant levels were set at p &lt; 0.05. Results: Patients were found to experience abdominal pain most of the time (29.1%) and their pain was intermittent (67.7%), stinging (16.4%) and lasted for 0 to 2 hours. Pain was diminished after use of analgesic in 50.5% of patients, worsened with physical activity in 17.7%, was associated with nausea in 7.7% and potent opioids were used for the relief of pain in 33.2% of patients. Pain severity as assessed by patients and their caregivers was 7.1±2.8 and 7.3±2.4 respectively and the most common pain-related problems in cancer patients were fatigue (p&lt;0.05), loss of appetite and insomnia (p&gt;0.05) as reported by both patients and caregivers. Compared to their caregivers, patients more frequently reported pain-associated financial constraints and negative effects of cancer pain on their work life and domestic life and family relationships, all of which were statistically significant (p&lt;0.05). The caregivers most commonly reported fatigue (56.8%) in their role as a caregiver. The caregivers were also found to experienc sleep problems (40.9%), loss of appetite (27.7%), distress (19.1%), hopelessness (17%), economic difficulty (16.8%), problems in their own life (14.1%) and fatique (12.7%). Conclusions: Pain assessments of both patients and caregivers and seeking their input on how to manage potential pain-related problems are crucial to achieve adequate pain control and distress.
Right Ureteral Carcinoma Suggested by 99mTc-DTPA Renography in a Patient With Left Pyelocaliceal Carcinoma
Authors: Wei Wang, Leilei Yuan, Ying Kan, Jie Liu, Jigang Yang
Journal: Clinical Nuclear Medicine (2018)

Abdominal enhanced CT of a 72-year-old woman demonstrated 1 enhancing lesion in the left kidney, which suggested malignancy. No significant findings were reported in the right kidney and ureter. A Tc-DTPA renography was performed as part of the presurgical evaluation. However, the dynamics of urine elimination by the left kidney was normal, whereas elimination of the urine on the right one delayed, which was unexpected. The patient's CT images were further analyzed. An enhancing lesion in the right ureter was noted by further review, suggesting malignancy, which was subsequently pathologically proven as low-grade papillary urothelial carcinoma.
Association of phosphatidylinositol 3-kinase (PI3K) pathway activation with increased immune checkpoint expression in colorectal cancer (CRC) patients.
Authors: Maliha Nusrat, Jason Roszik, Riham Katkhuda, David Menter, Kanwal Pratap Singh Raghav, Van Karlyle Morris, Padmanee Sharma, James Patrick Allison, Jorge M Blando, Dipen M. Maru, Michael J. Overman, Scott Kopetz
Journal: Journal of Clinical Oncology (2018)

653 Background: PI3K pathway is a known modulator of anti-tumor immune response and is frequently activated in CRC through genetic alterations such as PTEN loss (PTEN loss ) and PIK3CA mutations (PIK3CA mut ). This study aims to determine the impact of these alterations on immune cell infiltration, priming and activation in early stage CRC patients (pts). Methods: Immune infiltrates and checkpoints were evaluated using quantitative immunohistochemistry (IHC) on primary CRC (N = 59) for both center of tumor (CT) and invasive margin (IM). Pts were evaluated by presence or absence of either PTEN loss or PIK3CA mut (collectively termed PI3K pathway alterations). Microsatellite unstable (MSI) and stable (MSS) tumors were analyzed separately. Clinicopathologic data was examined for potential associations with PI3K pathway alterations. Separately, mRNA data (Agilent) was obtained for immune related genes from an internal cohort with PTEN and PIK3CA annotation (N = 73). Results: 59 pts comprised IHC cohort (40 MSS, 19 MSI); 23 pts (39%) had PTEN loss or PIK3CA mut . In Agilent cohort, 16 of 73 pts (22%) had PI3K pathway alterations. In MSS CRC, these alterations were more common in CMS1 (p = 0.03), on right side (p = 0.048) and with peritumoral lymphocytes (p = 0.031). MSS pts with PI3K pathway alterations had higher PD1 protein expression (p = 0.04), 2.1 and 2.3 times increased density of CD3 + (p = 0.01) and CD8 + (p = 0.04) cells respectively, and higher Granzyme B protein expression (p = 0.04) in the CT. These pts also had higher PDL1 gene expression (p = 0.046). MSS CRC pts with PIK3CA mut similarly had 2 times more PDL1 protein expression in epithelial cells of the IM (p = 0.01). Alternate checkpoints were also increased in pts with PI3K pathway alterations, including higher protein expression of LAG3 in CT (P = 0.046) and higher gene expression of CTLA4, TIM3, and TIGIT (P &lt; 0.05 for all). Conclusions: PI3K pathway activated MSS CRC is associated with increased immune engagement, but also upregulation of key immune checkpoints in early stage tumors resulting in an ineffective immune response. Combination of PI3K pathway inhibition with immunotherapy merits investigation in this subset of pts.
Platinum deposition in skin as a possible mechanism for peripheral sensory neuropathy (PSN) in patients (pts) with colorectal cancer (CRC) following oxaliplatin-based therapy.
Authors: Yanshuo Cao, Qing Chang, Wenjiang Zhang, Olga Ornatsky, Eric Xueyu Chen
Journal: Journal of Clinical Oncology (2018)

685 Background: Oxaliplatin plus fluorouracil (FOLFOX) is a standard treatment for CRC pts. One of the most common and dose-limiting side effects of oxaliplatin is PSN. The mechanism of this phenomenon is poorly understood. Previous studies suggested that higher serum platinum levels were related to more severe neuropathy in testicular cancer pts. Methods: CRC pts who completed adjuvant FOLFOX at least 6 months prior to enrollment are eligible. Baseline demographic and treatment information were collected. EORTC CIPN20 (with EORTC QLQ-C30) questionnaire was used for self-reported PSN symptom assessment. Peripheral blood samples were collected for total/free platinum concentrations using high-performance liquid chromatography with tandem mass spectrometry (HPLC/MS-MS). Skin biopsies were obtained from the lower leg of consented pts. Imaging mass cytometry (IMC) was used to visualize platinum deposition ( 195 Pt) and intra-epidermal nerve fiber (IENF) (PGP9.5- 154 Sm) in formalin-fixed paraffin embedded (FFPE) skin biopsy samples stained with a metal-conjugated antibody cocktail. Results: Nine patients were enrolled. Median age was 51.8 yr (range: 34.5-69.4 yr); male/ female: 5/4; mean cumulative dose of oxaliplatin was 800.7 ± 188.2 mg/m2; median time from last dose of oxaliplatin to enrollment was 48 months (range: 7.2-65.6 months). The mean sensory score from CIPN20 was 15.4 ± 4.3 (range: 10-25). Platinum was undetectable in plasma samples collected from all 9 patients. In skin samples, IMC showed significant platinum depositions and IENF. Conclusions: Severity of PSN was not related to cumulative dose of oxaliplatin or interval from last dose of oxaliplatin. Although platinum was undetectable in plasma in these patients, platinum was readily detectable in skin biopsies up to 65.6 months post completion of FOLFOX. This is the first demonstration of platinum deposition in skin post oxaliplatin treatment and it provides a possible mechanism for oxaliplatin-induced PSN.
Endogenous IgG-based affinity-controlled release of TRAIL exerts superior antitumor effects
Authors: Hao Yang, Yanru Feng, Huawei Cai, Dianlong Jia, Heng Li, Ze Tao, Yi Zhong, Zhao Li, Qiuxiao Shi, Lin Wan, Lin Li, Xiaofeng Lu
Journal: Theranostics (2018)

The inefficiency of recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-based clinical regimens has been dominantly attributed to the short half-life of TRAIL. Affinity-controlled release using endogenous long-acting proteins, such as IgG and albumin, as carriers is extremely attractive for improving the pharmacokinetics of TRAIL. Up to now, it is unclear whether IgG-binding is efficient for affinity-controlled release of TRAIL. Methods: An IgG-binding affibody, IgBD, was genetically fused to the N-terminus of TRAIL to produce IgBD-TRAIL.The IgG-binding ability, cytotoxicity, serum half-life, and in vivo antitumor effect of IgBD-TRAIL were compared with that of TRAIL. In addition, an albumin-binding affibody, ABD, was fused to TRAIL to produce ABD-TRAIL. The cytototoxicity, serum half-life, and antitumor effect of IgBD-TRAIL and ABD-TRAIL were compared. Results: IgBD fusion endowed TRAIL with high affinity (nM) for IgG without interference with its cytotoxicity. The serum half-life of IgBD-TRAIL is 50-60 times longer than that of TRAIL and the tumor uptake of IgBD-TRAIL at 8-24 h post-injection was 4-7-fold that of TRAIL. In vivo antitumor effect of IgBD-TRAIL was at least 10 times greater than that of TRAIL. Owing to the high affinity (nM) for albumin, the serum half-life of ABD-TRAIL was 80-90 times greater than that of TRAIL. However, after binding to albumin, the cytotoxicity of ABD-TRAIL was reduced more than 10 times. In contrast, binding to IgG had little impact on the cytotoxicity of IgBD-TRAIL. Consequently, intravenously injected IgBD-TRAIL showed antitumor effects superior to those of ABD-TRAIL. Conclusions: Endogenous long-acting proteins, particularly IgG-based affinity-controlled release, prolonged the serum half-life as well as significantly enhanced the antitumor effect of TRAIL. IgBD-mediated endogenous IgG binding might be a novel approach for the affinity-controlled release of other protein drugs.
Evaluation of avoralstat, an oral kallikrein inhibitor, in a Phase 3 hereditary angioedema prophylaxis trial: The <scp>OPuS</scp>‐2 study
Authors: M. A. Riedl, E. Aygören‐Pürsün, J. Baker, H. Farkas, J. Anderson, J. A. Bernstein, L. Bouillet, P. Busse, M. Manning, M. Magerl, M. Gompels, A. P. Huissoon, H. Longhurst, W. Lumry, B. Ritchie, R. Shapiro, D. Soteres, A. Banerji, M. Cancian, D. T. Johnston, T. J. Craig, D. Launay, H. H. Li, M. Liebhaber, T. Nickel, J. Offenberger, W. Rae, R. Schrijvers, M. Triggiani, H. J. Wedner, S. Dobo, M. Cornpropst, D. Clemons, L. Fang, P. Collis, W. P. Sheridan, M. Maurer
Journal: Allergy (2018)

Abstract Background Effective inhibition of plasma kallikrein may have significant benefits for patients with hereditary angioedema due to deficiency of C1 inhibitor (C1‐ INH ‐ HAE ) by reducing the frequency of angioedema attacks. Avoralstat is a small molecule inhibitor of plasma kallikrein. This study ( OP uS‐2) evaluated the efficacy and safety of prophylactic avoralstat 300 or 500 mg compared with placebo. Methods OP uS‐2 was a Phase 3, multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group study. Subjects were administered avoralstat 300 mg, avoralstat 500 mg, or placebo orally 3 times per day for 12 weeks. The primary efficacy endpoint was the angioedema attack rate based on adjudicator‐confirmed attacks. Results A total of 110 subjects were randomized and dosed. The least squares ( LS ) mean attack rates per week were 0.589, 0.675, and 0.593 for subjects receiving avoralstat 500 mg, avoralstat 300 mg, and placebo, respectively. Overall, 1 subject in each of the avoralstat groups and no subjects in the placebo group were attack‐free during the 84‐day treatment period. The LS mean duration of all confirmed attacks was 25.4, 29.4, and 31.4 hours for the avoralstat 500 mg, avoralstat 300 mg, and placebo groups, respectively. Using the Angioedema Quality of Life Questionnaire ( AE ‐QoL), improved QoL was observed for the avoralstat 500 mg group compared with placebo. Avoralstat was generally safe and well tolerated. Conclusions Although this study did not demonstrate efficacy of avoralstat in preventing angioedema attacks in C1‐ INH ‐ HAE , it provided evidence of shortened angioedema episodes and improved QoL in the avoralstat 500 mg treatment group compared with placebo.
Effect of early palliative care: complex intervention and complex results – Authors' reply
Authors: Gaëlle Vanbutsele, Koen Pardon, Simon Van Belle, Veerle Surmont, Martine De Laat, Roos Colman, Kim Eecloo, Veronique Cocquyt, Karen Geboes, Luc Deliens
Journal: The Lancet Oncology (2018)
The Slippery Slope of Legalization of Physician-Assisted Suicide
Authors: John K. Weiser
Journal: Annals of Internal Medicine (2018)

Letters1 May 2018The Slippery Slope of Legalization of Physician-Assisted SuicideJohn K. Weiser, MDJohn K. Weiser, MDAtlanta, Georgia (J.K.W.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L18-0018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Kussmaul (1), who opposes legalization of physician-assisted suicide, describes “Western society's transition toward post-Christian antinomianism” as perverting the concept of beneficence from acting on the patient's best interest to doing whatever the patient believes to be helpful. The author, a Catholic deacon, reveals here the religious basis of his argument. Although people of faith may freely express their beliefs, the U.S. Constitution states, “Congress shall make no law respecting an establishment of religion.”Reference1. Kussmaul WG. The slippery slope of legalization of physician-assisted suicide. Ann Intern Med. 2017;167:595-6. [PMID: 28975201]. doi:10.7326/M17-2072 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Atlanta, Georgia (J.K.W.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L18-0018. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Slippery Slope of Legalization of Physician-Assisted Suicide William G. Kussmaul III The Slippery Slope of Legalization of Physician-Assisted Suicide Gary Schiller The Slippery Slope of Legalization of Physician-Assisted Suicide William G. Kussmaul III Metrics 1 May 2018Volume 168, Issue 9Page: 683KeywordsConflicts of interestDisclosureSuicide ePublished: 1 May 2018 Issue Published: 1 May 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes
Authors: Sophia S. Wang, Mary Carrington, Sonja I. Berndt, Susan L. Slager, Paige M. Bracci, Jenna Voutsinas, James R. Cerhan, Karin E. Smedby, Henrik Hjalgrim, Joseph Vijai, Lindsay M. Morton, Roel Vermeulen, Ora Paltiel, Claire M. Vajdic, Martha S. Linet, Alexandra Nieters, Silvia de Sanjose, Wendy Cozen, Elizabeth E. Brown, Jennifer Turner, John J. Spinelli, Tongzhang Zheng, Brenda M. Birmann, Christopher R. Flowers, Nikolaus Becker, Elizabeth A. Holly, Eleanor Kane, Dennis Weisenburger, Marc Maynadie, Pierluigi Cocco, Demetrius Albanes, Stephanie J. Weinstein, Lauren R. Teras, W. Ryan Diver, Stephanie J. Lax, Ruth C. Travis, Rudolph Kaaks, Elio Riboli, Yolanda Benavente, Paul Brennan, James McKay, Marie-Hélène Delfau-Larue, Brian K. Link, Corrado Magnani, Maria Grazia Ennas, Giancarlo Latte, Andrew L. Feldman, Nicole Wong Doo, Graham G. Giles, Melissa C. Southey, Roger L. Milne, Kenneth Offit, Jacob Musinsky, Alan A. Arslan, Mark P. Purdue, Hans-Olov Adami, Mads Melbye, Bengt Glimelius, Lucia Conde, Nicola J. Camp, Martha Glenn, Karen Curtin, Jacqueline Clavel, Alain Monnereau, David G. Cox, Hervé Ghesquières, Gilles Salles, Paulo Bofetta, Lenka Foretova, Anthony Staines, Scott Davis, Richard K. Severson, Qing Lan, Angela Brooks-Wilson, Martyn T. Smith, Eve Roman, Anne Kricker, Yawei Zhang, Peter Kraft, Stephen J. Chanock, Nathaniel Rothman, Patricia Hartge, Christine F. Skibola
Journal: Cancer Research (2018)

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06-1.60; OR MZL = 1.45, 95% CI = 1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24-3.55; OR MZL = 2.10, 95% CI = 0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes.Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086-96. ©2018 AACR.
Non-viral delivery systems for CRISPR/Cas9-based genome editing: Challenges and opportunities
Authors: Ling Li, Shuo Hu, Xiaoyuan Chen
Journal: Biomaterials (2018)

In recent years, CRISPR (clustered regularly interspaced short palindromic repeat)/Cas (CRISPR-associated) genome editing systems have become one of the most robust platforms in basic biomedical research and therapeutic applications. To date, efficient in vivo delivery of the CRISPR/Cas9 system to the targeted cells remains a challenge. Although viral vectors have been widely used in the delivery of the CRISPR/Cas9 system in vitro and in vivo, their fundamental shortcomings, such as the risk of carcinogenesis, limited insertion size, immune responses and difficulty in large-scale production, severely limit their further applications. Alternative non-viral delivery systems for CRISPR/Cas9 are urgently needed. With the rapid development of non-viral vectors, lipid- or polymer-based nanocarriers have shown great potential for CRISPR/Cas9 delivery. In this review, we analyze the pros and cons of delivering CRISPR/Cas9 systems in the form of plasmid, mRNA, or protein and then discuss the limitations and challenges of CRISPR/Cas9-based genome editing. Furthermore, current non-viral vectors that have been applied for CRISPR/Cas9 delivery in vitro and in vivo are outlined in details. Finally, critical obstacles for non-viral delivery of CRISPR/Cas9 system are highlighted and promising strategies to overcome these barriers are proposed.
High efficacy of IFN-free DAA therapy for acute HCV infection in HIV patients
Authors: D. Chromy, M. Mandorfer, T. Bucsics, P. Schwabl, B. Scheiner, C. Schmidbauer, M. Aichelburg, P. Ferenci, M. Trauner, M. Peck, T. Reiberger
Journal: Journal of Hepatology (2018)