tbuckley/cabot-search huggingface dataset:
5‐aminolaevulinic acid nanoemulsion is more effective than methyl‐5‐aminolaevulinate in daylight photodynamic therapy for actinic keratosis: a nonsponsored randomized double‐blind multicentre trial
Authors: J.E. Räsänen, N. Neittaanmäki, L. Ylitalo, J. Hagman, P. Rissanen, L. Ylianttila, M. Salmivuori, E. Snellman, M. Grönroos
Journal: British Journal of Dermatology (2018)

Daylight photodynamic therapy (DL-PDT) with methyl-5-aminolaevulinate (MAL) is an effective treatment for mild and moderate actinic keratosis (AK).To assess the clinical efficacy, tolerability and cost-effectiveness of 5-aminolaevulinic acid nanoemulsion (BF-200 ALA) compared with MAL in DL-PDT for grade I-II AKs.This nonsponsored, prospective randomized double-blind multicentre trial included 69 patients with 767 grade I-II AKs located symmetrically on the face or scalp. A single DL-PDT was given in a randomized split-face design. The primary outcome was clearance of the AKs at 12 months as assessed by a blinded observer. The secondary outcomes were pain, treatment reactions, cosmetic outcome and the cost-effectiveness of the therapy.In the per-patient (half-face) analysis, clearance was better for the BF-200 ALA sides than for those treated with MAL (P = 0·008). In total, BF-200 ALA cleared 299/375 AKs (79·7%) and MAL 288/392 (73·5%) (P = 0·041). The treatment was practically painless with both photosensitizers, the mean pain visual analogue scale being 1·51 for BF-200 ALA and 1·35 for MAL (P = 0·061). Twenty-six patients had a stronger skin reaction on the BF-200 ALA side, seven on the MAL side and 23 displayed no difference (P = 0·001). The cosmetic outcome was excellent or good in > 90% of cases with both photosensitizers (P = 1·000). The cost-effectiveness plane showed that the costs of DL-PDT were similar for both photosensitizers, but the effectiveness was slightly higher for BF-200 ALA.Our results indicate that BF-200 ALA is more effective than MAL in DL-PDT for grade I-II AKs. BF-200 ALA provides slightly better value for money than MAL.
Abstract 18666: Macrophage TFEB Overexpression Attenuates Left Ventricular Remodeling After Myocardial Infarction
Authors: Ali Javaheri, Geetika Bajpai, Attila Kovacs, Carla Weinheimer, Andrea Ballabio, Kory Lavine, Abhinav Diwan
Journal: Circulation (2017)

Introduction: Post-myocardial infarction (MI), myocardial macrophage expansion via proliferation of resident cells and recruitment of circulating monocytes modulates healing via phagocytosis of dead cells and is also implicated in pro-inflammatory signaling that provokes heart failure. Whether the macrophage autophagy-lysosome pathway can be harnessed to prevent heart failure remains unknown. Hypothesis: Augmentation of the autophagy-lysosome machinery by overexpression of transcription factor EB (TFEB), a master regulator of this pathway, ameliorates post-MI left ventricular (LV) remodeling after ischemia-reperfusion (IR) injury. Methods: Adult mice carrying Cx3Cr1-er-Cre and TFEB lox-STOP cassette were treated with tamoxifen to inducibly overexpress TFEB in recruited and/or resident macrophages after closed-chest IR injury and assessed by echocardiography. Results: At 4 weeks post-MI, Cre-only controls demonstrated adverse LV remodeling with significant increases in end-diastolic volume (EDV, by 72% vs....
Clinical response and pharmacodynamic assessment of INVAC-1, a DNA plasmid encoding an inactive form of human telomerase reverse transcriptase (hTERT), on immune responses, immune tolerability, tumor burden and circulating tumor DNA (ctDNA) in patients with advanced solid tumors
Authors: J. Medioni, M. Brizard, L.O. Teixeira, L. Doucet, Z. Ghrieb, A. Angelergues, S. Oudard, S. Culine, O. Adotevi, C. Laheurte, M.-A. Dragon-Durey, P. Laurent-Puig, J.-J. Kiladjian, V. Doppler, B. Souttou, S. Wain-Hobson, R. Defrance, T. Huet, P. Langlade-Demoyen
Journal: Annals of Oncology (2018)
Abstract P062: Individual Level Fine Particulate Air Pollution is Associated with Acute Impairment of Cardiac Autonomic Modulation in Adolescents
Authors: Fan He, Jeff D Yanosky, Edward O Bixler, Julio Fernandez-Mendoza, Alexandros N Vgontzas, Vernon M Chinchilli, Duanping Liao
Journal: Circulation (2016)

Introduction: Fine particulate (PM 2.5 ) air pollution has been associated with impaired cardiac autonomic modulation (CAM) in adults. The association between PM 2.5 exposure and CAM in adolescents is rarely investigated. Hypothesis: We assessed the hypothesis that PM 2.5 air pollution is related to acute impairment of CAM in adolescents. Methods: We used data from 421 adolescents in the Penn State Child Cohort follow-up examination. We obtained 24-hour ECG data using a 12-lead Holter ECG from each participant. After removing artifacts and arrhythmic beats, we performed heart rate variability (HRV) analysis on normal RR intervals to compute 30-min based high frequency (HF) and low frequency (LF) powers, standard deviation of RRs (SDNN), and the square root of mean of the sum of the squared differences of the adjacent RRs (RMSSD). Individual level 24-hour PM 2.5 concentration was obtained by a personal PM 2.5 monitor. We then calculated, on a 30-min basis, the corresponding time-specific exposure to PM 2.5 . Distributed lag models under a framework of linear mixed-effects model, with a first-order autoregressive covariance structure, were used to assess the segment-specific and cumulative effect of 30-min based PM 2.5 and HRV indices. Results: As shown in the table, both individual lag and cumulative effects of PM 2.5 on HRV, based on the lag 0-6 model, were significant after controlling for major covariates. For instance, for a 10 μg/m 3 increase in cumulative PM 2.5 , HF and SDNN decreased by 0.023 (SE=0.006) ms 2 and 0.61 (SE=0.16) ms, respectively. A 10 μg/m 3 increase in PM 2.5 was also significantly associated with elevated heart rate (0.25 (SE=0.09) beat/min). Individual lag effects of PM 2.5 were most consistently associated within 1.5 hours. Conclusion: Individual level exposure to PM 2.5 in adolescents is associated with impaired CAM, towards an elevated sympathetic and decreased parasympathetic outflow. The time to the apparent cumulative effect is about 3 hours, with the most consistent individual lag effects within 1.5 hours.
Abstract 15196: A Novel Balanced Dual Vasopressin V1a/V2 Receptor Antagonist for Treatment of Congestive Heart Failure: Results From a First-in-Man Study
Authors: Eduardo Pimenta, Markus Jensen, David Jung, Maximilian Lobmeyer, Walter Schmitt, Frank Schaumann, Stefanie Boxnick, Hubert Truebel
Journal: Circulation (2017)

Introduction: Congestion remains the most common reason for admission of heart failure (HF) representing a high unmet medical need. Increased vasopressin (AVP) levels are common in these patients c...
Tumor Board Conferences for Multidisciplinary Skin Cancer Management: A Survey of US Cancer Centers
Authors: Shoko Mori, Cristian Navarrete-Dechent, Tatyana A. Petukhova, Erica H. Lee, Anthony M. Rossi, Michael A. Postow, Lara A. Dunn, Benjamin R. Roman, Vivian T. Yin, Daniel G. Coit, Travis J. Hollmann, Klaus J. Busam, Kishwer S. Nehal, Christopher A. Barker
Journal: Journal of the National Comprehensive Cancer Network (2018)

Background: Tumor board conferences (TBCs) are used by oncologic specialists to review patient cases, exchange knowledge, and discuss options for cancer management. These multidisciplinary meetings are often a cornerstone of treatment at leading cancer centers and are required for accreditation by certain groups, such as the American College of Surgeons' Commission on Cancer. Little is known regarding skin cancer TBCs. The objective of this study was to characterize the structure, function, and impact of existing skin cancer TBCs in the United States. Methods: A cross-sectional online survey was administered to physician leaders of skin cancer TBCs at NCI-designated Comprehensive and Clinical Cancer Centers. Results: Of the 59 centers successfully contacted, 14 (24%) reported not having a conference where skin cancer cases were discussed, and 45 (76%) identified 53 physician leaders. A total of 38 physicians (72%) completed the survey. Half of the meeting leaders were medical and/or surgical oncologists, and dermatologists led one-third of meetings. TBCs had a moderate to significant impact on patient care according to 97% of respondents. All respondents indicated that the meetings enhanced communication among physicians and provided an opportunity for involved specialists and professionals to discuss cases. The most frequently cited barrier to organizing TBCs was determining a common available date and time for attendees (62%). The most common suggestion for improvement was to increase attendance, specialists, and/or motivation. Conclusions: Results showed overall consistency in meeting structure but variability in function, which may be a reflection of institutional resources and investment in the conference. Future directions include defining metrics to evaluate changes in diagnosis or management plan after tumor board discussion, attendance, clinical trial enrollment, and cost analysis. Results of this survey may aid other institutions striving to develop and refine skin cancer TBCs.
Treatment of mycosis fungoides and Sézary syndrome with romidepsin: a series of 32 cases from the French Study Group for Cutaneous Lymphoma
Authors: O Deschamps, C Ram-Wolff, M Beylot-Barry, F Grange, F Skowron, O Dereure, S Boulinguez, F Aubin, S Ingen-Housz-Oro, M Bagot
Journal: British Journal of Dermatology (2018)
CRISPhieRmix: a hierarchical mixture model for CRISPR pooled screens
Authors: Timothy P. Daley, Zhixiang Lin, Xueqiu Lin, Yanxia Liu, Wing Hung Wong, Lei S. Qi
Journal: Genome biology (2018)

Pooled CRISPR screens allow researchers to interrogate genetic causes of complex phenotypes at the genome-wide scale and promise higher specificity and sensitivity compared to competing technologies. Unfortunately, two problems exist, particularly for CRISPRi/a screens: variability in guide efficiency and large rare off-target effects. We present a method, CRISPhieRmix, that resolves these issues by using a hierarchical mixture model with a broad-tailed null distribution. We show that CRISPhieRmix allows for more accurate and powerful inferences in large-scale pooled CRISPRi/a screens. We discuss key issues in the analysis and design of screens, particularly the number of guides needed for faithful full discovery.
Role and Relation of p70 S6 and Extracellular Signal-Regulated Kinases in the Phenotypic Changes of Hypertrophy of Cardiac Myocytes
Authors: Yuichi Ono, Hiroshi Ito, Mimi Tamamori, Toshihiro Nozato, Susumu Adachi, Shinji Abe, Fumiaki Marumo, Michiaki Hiroe
Journal: Circulation (2000)

Cardiac hypertrophy is characterized by increased cardiomyocyte protein synthesis, increased cell volume, and a shift in cardiac-specific gene expression to fetal isoforms. Using neonatal rat cardiomyocytes stimulated with fetal calf serum (FCS) as a model for cardiac hypertrophy, the present study investigated the role of 2 signal transduction pathways, extracellular signal-regulated kinase (ERK) and p70S6 kinase (p70S6K), in the attendant phenotype changes. FCS evoked both ERK and p70S6K activity, peaking at 20-40min, and simultaneously increased cardiac myocyte protein synthesis (evaluated by [3H]leucine incorporation and total cellular protein content), cell size (evaluated by morphometry and fluorescence-activated cell sorter analysis) and expression of a fetal isoform of the muscle specific gene skeletal alpha-actin (SKA). Rapamycin, a specific inhibitor of the mammalian target of rapamycin (mTOR), which is an upstream signaling of p70S6K, completely inhibited FCS-induced cell size increases and protein synthesis, but had no effect on SKA mRNA expression. PD98059, which inhibited ERK activity, attenuated cardiac-specific gene expression in a dose-dependent manner, but had no influence on protein synthesis or cell size. These results indicate divergent roles for the ERK and p70S6K pathways in the phenotypic changes associated with cardiac hypertrophy.
Abstract 18978: Associations of Provider Knowledge and Beliefs Regarding Lipid Management With Statin Therapy Use and Lipid Outcomes
Authors: Angela Lowenstern, Ann Marie Navar, Shuang Li, Anne C Goldberg, Michael J Louie, L.Veronica Lee, Salim Virani, Eric D Peterson, Tracy Y Wang
Journal: Circulation (2017)

Background: Health care provider knowledge and adoption of guidelines, as well as pre-existing provider beliefs and biases, can influence guideline implementation. How these factors affected lipid ...
Use of sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with cytology proven axillary node-positive breast cancer at diagnosis
Authors: H.J. Choi, S.M. Jung, J.M. Ryu, I. Kim, S.J. Nam, S.W. Kim, J. Yu, S.K. Lee, J.E. Lee
Journal: Annals of Oncology (2018)
Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer
Authors: Peter Schmid, Sylvia Adams, Hope S. Rugo, Andreas Schneeweiss, Carlos H. Barrios, Hiroji Iwata, Véronique Diéras, Roberto Hegg, Seock-Ah Im, Gail Shaw Wright, Volkmar Henschel, Luciana Molinero, Stephen Y. Chui, Roel Funke, Amreen Husain, Eric P. Winer, Sherene Loi, Leisha A. Emens
Journal: New England Journal of Medicine (2018)

Unresectable locally advanced or metastatic triple-negative (hormone-receptor–negative and human epidermal growth factor receptor 2 [HER2]–negative) breast cancer is an aggressive disease with poor outcomes. Nanoparticle albumin-bound (nab)–paclitaxel may enhance the anticancer activity of atezolizumab.
Trial Reporting in Immuno-Oncology (TRIO): An American Society of Clinical Oncology-Society for Immunotherapy of Cancer Statement
Authors: Apostolia M. Tsimberidou, Laura A. Levit, Richard L. Schilsky, Steven D. Averbuch, Daniel Chen, John M. Kirkwood, Lisa M. McShane, Elad Sharon, Kathryn F. Mileham, Michael A. Postow
Journal: Journal for ImmunoTherapy of Cancer (2018)

To develop recommendations for clinical trial reporting that address the unique efficacy, toxicity, and combination and sequencing aspects of immuno-oncology (IO) treatments.ASCO and the Society for Immunotherapy of Cancer (SITC) convened a working group that consisted of practicing medical oncologists, immunologists, clinical researchers, biostatisticians, and representatives from industry and government to develop Trial Reporting in Immuno-Oncology (TRIO) recommendations. These recommendations are based on expert consensus, given that existing data to support evidence-based recommendations are limited.The TRIO recommendations are intended to improve the reporting of IO clinical trials and thus provide more complete evidence on the relative benefits and risks of an IO therapeutic approach. Given the rapid expansion of the number of IO clinical trials and ongoing improvements to the evidence base supporting the use of IO treatments in clinical care, these recommendations will likely need regular revision as the IO field develops.
Abstract 18931: Integrative Genomics Analyses Identifies Shared Regulatory Networks for Cardiovascular Disease and Type 2 Diabetes Mellitus in American Women of Caucasian, African and Hispanic Ethnicities
Authors: Le Shu, Kei Hang Katie Chan, Simin Liu, Xia Yang
Journal: Circulation (2015)

Cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D) have many shared risk factors, suggesting that they have common pathophysiological mechanisms. Our recent analysis of genome wide association studies (GWAS) of both CVD and T2D in three ethnic populations revealed a number of biological pathways, such as extracellular matrix and focal adhesion, to be genetically associated with both diseases. Building on our prior work employing knowledge-driven pathways, we performed data-driven integrative genomics analyses using gene co-expression networks constructed from a multitude of tissue-specific transcriptome datasets in conjunction with GWAS for CVD, T2D, and a vascular disease phenotype (VD, representing combined CVD+T2D) in three different ethnic groups of 8155 African Americans, 3494 Hispanic Americans and 3697 Caucasian Americans participated in the national Women’s Health Initiative (WHI) study. We examined a total of 2674 coexpression networks and found that 24 modules were significantly enriched for GWAS signatures for all three disease end points (15 modules) or VD only (9 modules) across multiple cohorts at false discovery rate &lt;5%. These modules were enriched for the previously identified pathways like focal adhesion. Further, top modules for all three diseases were enriched for genes involved in citrate cycle and G-protein coupled receptor signaling, whereas top modules for VD were related to amino acid metabolism and BMP signaling, indicating novel processes that are shared between CVD and T2D. To pinpoint key driver (KD) for these modules, we integrated Bayesian networks of adipose, brain, kidney, liver and muscle tissue, and identified highly significant KDs such as BCL6B in adipose, MALAT1 in brain, ZNF565 in kidney, GLS2 in liver and MYL2 in muscle. Among the top KDs, MALAT1, GLS2 and MYL2 have been previously implicated in CVD and T2D, whereas the others represented novel findings. In summary, by leveraging multi-ethnic GWAS data on CVD and T2D and data-driven transcriptional networks, we uncovered both known and novel regulatory mechanisms that appeared to be shared by the two vascular diseases. These network regulators revealed may serve as important targets for future experimental validation.
A subset of HLA-I peptides are not genomically templated: Evidence for cis- and trans-spliced peptide ligands
Authors: Pouya Faridi, Chen Li, Sri H. Ramarathinam, Julian P. Vivian, Patricia T. Illing, Nicole A. Mifsud, Rochelle Ayala, Jiangning Song, Linden J. Gearing, Paul J. Hertzog, Nicola Ternette, Jamie Rossjohn, Nathan P. Croft, Anthony W. Purcell
Journal: Science Immunology (2018)

The diversity of peptides displayed by class I human leukocyte antigen (HLA) plays an essential role in T cell immunity. The peptide repertoire is extended by various posttranslational modifications, including proteasomal splicing of peptide fragments from distinct regions of an antigen to form nongenomically templated cis-spliced sequences. Previously, it has been suggested that a fraction of the immunopeptidome constitutes such cis-spliced peptides; however, because of computational limitations, it has not been possible to assess whether trans-spliced peptides (i.e., the fusion of peptide segments from distinct antigens) are also bound and presented by HLA molecules, and if so, in what proportion. Here, we have developed and applied a bioinformatic workflow and demonstrated that trans-spliced peptides are presented by HLA-I, and their abundance challenges current models of proteasomal splicing that predict cis-splicing as the most probable outcome. These trans-spliced peptides display canonical HLA-binding sequence features and are as frequently identified as cis-spliced peptides found bound to a number of different HLA-A and HLA-B allotypes. Structural analysis reveals that the junction between spliced peptides is highly solvent exposed and likely to participate in T cell receptor interactions. These results highlight the unanticipated diversity of the immunopeptidome and have important implications for autoimmunity, vaccine design, and immunotherapy.
Waldenström macroglobulinemia: 2019 update on diagnosis, risk stratification, and management
Authors: Morie A. Gertz
Journal: American Journal of Hematology (2018)

Disease Overview Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity. Diagnosis Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in &gt;90% of patients and is found in the majority of IgM monoclonal gammopathy of undetermined significance patients. Risk Stratification Age, hemoglobin level, platelet count, β2 microglobulin, and monoclonal IgM concentrations are characteristics that are predictive of outcomes. Risk‐Adapted Therapy Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab‐monotherapy is inferior to regimens that combine it with bendamustine, an alkylating agent, a proteosome inhibitor, or ibrutinib. Purine nucleoside analogs are active but usage is declining for less toxic alternatives. The preferred Mayo Clinic induction is rituximab and bendamustine. Potential for stem cell transplantation should be considered in selected younger patients. Management of Refractory Disease Bortezomib, fludarabine, thalidomide, everolimus, ibrutinib, carfilzomib, lenalidomide, and bendamustine have all been shown to have activity in relapsed WM. Given WM's natural history, reduction of therapy toxicity is an important part of treatment selection.
Predicting the risk of peripheral neuropathy by the combination of four serum microRNAs
Authors: Shoko Narita, Akihiko Shimomura, Yuko Tanabe, Junpei Kawachi, Juntaro Matsuzaki, Satoko Takizawa, Hiromi Sakamoto, Kenji Tamura, Chikako Shimizu, Takahiro Ochiya
Journal: Annals of Oncology (2018)
Occult Giant Cell Arteritis Concurrent With Pancreatic Carcinoma Revealed by 18F-FDG PET/CT
Authors: Zhanli Fu, Xueqi Chen, Xing Yang, Qian Li
Journal: Clinical Nuclear Medicine (2018)

An F-FDG PET/CT was performed on a 74-year-old woman with pancreatic carcinoma and liver metastases. Occult giant cell arteritis, involving the aorta, truncus brachiocephalicus, subclavian arteries, axillaries, external carotid arteries, vertebral arteries, and superficial temporal arteries, was accidentally revealed.
Awareness of the cancer and non-cancer related harms of continued smoking in cancer survivors
Authors: L. Eng, S. Liu, D. Farzanfar, E.C. Smith, A. McCartney, A. Basgaran, K. Balaratnam, S. Yeung, M.C. Brown, D. Howell, J.M. Jones, W. Xu, D. Goldstein, W.K. Evans, P. Selby, M.E. Giuliani, G. Liu
Journal: Annals of Oncology (2018)
Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer
Authors: Kathleen Moore, Nicoletta Colombo, Giovanni Scambia, Byoung-Gie Kim, Ana Oaknin, Michael Friedlander, Alla Lisyanskaya, Anne Floquet, Alexandra Leary, Gabe S. Sonke, Charlie Gourley, Susana Banerjee, Amit Oza, Antonio González-Martín, Carol Aghajanian, William Bradley, Cara Mathews, Joyce Liu, Elizabeth S. Lowe, Ralph Bloomfield, Paul DiSilvestro
Journal: New England Journal of Medicine (2018)

Most women with newly diagnosed advanced ovarian cancer have a relapse within 3 years after standard treatment with surgery and platinum-based chemotherapy. The benefit of the oral poly(adenosine diphosphate–ribose) polymerase inhibitor olaparib in relapsed disease has been well established, but the benefit of olaparib as maintenance therapy in newly diagnosed disease is uncertain.
PD-1 Blockade–Induced Pruritus Treated with a Mu-Opioid Receptor Antagonist
Authors: Shawn G Kwatra, Sonja Ständer, Hyunseok Kang
Journal: New England Journal of Medicine (2018)

Naloxone for PD-1–Induced Pruritus In a patient with lung cancer, severe pruritus in response to antibodies that block programmed death 1 protein was promptly relieved by adding intravenous naloxon...
Real-life data on the cardiac toxicity of adjuvant fixed-dose subcutaneous trastuzumab in HER2-positive breast cancer
Authors: R. De Sanctis, F. D'Antonio, E. Agostinetto, A. Marinello, G. Masci, M. Zuradelli, A. Losurdo, D. Guiducci, C. Tinterri, A. Testori, W. Gatzemeier, V. Errico, R. Torrisi, A. Santoro
Journal: Annals of Oncology (2018)