tbuckley/cabot-search huggingface dataset:
Feasibility of a collaborative palliative and oncology care intervention to improve symptoms and coping during head and neck chemoradiation.
Authors: Jessica Ruth Bauman, Jessie Panick, Thomas James Galloway, John A. Ridge, Melissa McShane, Marcin Chwistek, Molly Collins, Leigh Kinczewski, Kathleen Murphy, Marie Welsh, Matthew Farren, Mollie Clark, Jacqueline Kelly, Katherine Schuster, Lauren Stokes, Sheila Amrhein, Florence Bender, Brian L. Egleston, Areej El-Jawahri, Carolyn Y Fang
Journal: Journal of Clinical Oncology (2019)

73 Background: Patients receiving curative chemoradiation treatment (CRT) for head and neck cancer (HNC) undergo one of the most intensive treatments in oncology, resulting in immense physical and psychological symptoms. Integrated palliative care can improve symptoms and coping in patients with advanced cancer, but has not been evaluated in patients with curable solid tumors. Thus, we are conducting the first pilot study of a collaborative palliative and oncology care intervention among patients receiving CRT to assess feasibility and acceptability. Methods: Eligible participants include newly diagnosed HNC patients starting curative-intent CRT. The intervention entails weekly in-person palliative care (PC) visits integrated with standard oncology care during CRT, followed by 4 weekly phone calls after CRT ends. The PC visits are conducted primarily by a PC RN, with a supervising MD or NP available. Visits focus on coping and managing prominent symptoms during CRT. PC clinicians also receive a weekly patient-reported symptom assessment. Acceptability of the intervention is assessed at 1 month post CRT. The primary outcome is feasibility, defined as a &gt;50% enrollment rate with &gt;70% of participants attending at least half of the PC visits. Planned accrual is 20 patients. Results: We have enrolled 88% (14/16) of eligible patients to date. 11/14 (79%) have p16+ disease. All 14 have completed CRT and are evaluable for feasibility. Participants attended 98% (94/96) of all possible PC visits and completed 99% (95/96) of weekly symptom assessments. PC clinicians spent an average of 35.5 minutes (SD 15.1) per visit with participants. Among the 10 participants who completed the intervention and are evaluable for acceptability, 100% found the intervention “very helpful” and would “definitely recommend” it to others undergoing CRT. Conclusions: An integrated PC intervention to improve symptoms and coping during CRT for HNC is both feasible and acceptable with a high enrollment rate, excellent intervention compliance, and high patient satisfaction. Future studies will evaluate the effects of the integrated intervention on patient-reported outcomes and health care utilization. Clinical trial information: NCT03760471.
Imbalance in T-Helper 17 Cells and Targeted Therapy in an Infant with SAM-like Syndrome
Authors: Angela Hernández-Martín, Rebeca Kennedy-Batalla, Elvira Cañedo, Esther Bernaldo-de-Quirós, Begoña Carazo-Gallego, Angel Vera, Antonio Torrelo, Lucero Noguera-Morel, Rogelio González-Sarmiento, Marieke Bolling, Marta Martínez-Bonet, Marjorie Pion, Rafael Correa-Rocha
Journal: New England Journal of Medicine (2019)

T-Helper 17 Cells in Genetic Dermatitis An infant with SAM-like syndrome (severe dermatitis, allergies, and metabolic wasting) was found to have a substantial increase in the number of T-helper 17 ...
Comparative efficacy and safety of treatments for secondary Raynaud's phenomenon: a systematic review and network meta-analysis of randomised trials
Authors: Charles Khouri, Marion Lepelley, Sebastien Bailly, Sophie Blaise, Ariane L Herrick, Marco Matucci-Cerinic, Yannick Allanore, Ludovic Trinquart, Jean-Luc Cracowski, Matthieu Roustit
Journal: The Lancet Rheumatology (2019)
Comment on ‘Sustained discontinuation of infliximab with a raising-dose strategy after obtaining remission in patients with rheumatoid arthritis: the RRRR study, a randomised controlled trial’ by Tanaka <i>et al</i>
Authors: Lea C Berkhout, Merel J l'Ami, Gerrit Jan Wolbink, Theo Rispens
Journal: Annals of the Rheumatic Diseases (2019)

We have read with interest the paper of Tanaka et al 1 and support the need for a more personalised approach in dosing regimens of tumour necrosis factor (TNF) inhibitors.2 They adjusted infliximab dose based on TNF concentrations at baseline, under the assumptions that baseline TNF concentrations can be accurately measured, and that high disease activity (ie, more inflammation) is associated with higher TNF concentrations. However, several factors argue against these assumptions, which we would like to add to the study by Tanaka et al . These factors might explain the absence of an association between TNF concentrations and treatment response.

First, the quantification of TNF at baseline is in fact challenging: TNF is an unstable molecule with a …
Discontinuation of Tyrosine Kinase Inhibitor in Children with Chronic Myeloid Leukemia (JPLSG STKI-14 study)
Authors: Haruko Shima, Akiko Kada, Akihiko Tanizawa, Yuki Yuza, Akihiro Watanabe, Masaki Ito, Hideko Uryu, Katsuyoshi Koh, Chihaya Imai, Nao Yoshida, Yuhki Koga, Naoto Fujita, Akiko M Saito, Souichi Adachi, Eiichi Ishii, Hiroyuki Shimada
Journal: Blood (2019)
Exploiting the Zinc Finger Degrome Targeted By Lenalidomide to Engineer Reversible Off-Switch Degradable Chimeric Antigen Receptors
Authors: Max Jan, Ana Castano, Amanda Walker, Andrew A Guirguis, Jessica A Gasser, Amanda A Bouffard, Mikolaj Slabicki, Alexander Tepper, Daniel E Grinshpun, Taeyoon Kyung, Quinlan Sievers, Michael E Birnbaum, Marcela V Maus, Benjamin L. Ebert
Journal: Blood (2019)
Changing hearts and minds
Authors: Elizabeth Loder
Journal: BMJ (2019)

The UK is no longer measles free, and other vaccine preventable childhood illnesses are on the rise. What is the best way to counter the claims of the antivaccination movement? Not with papers, peer reviewed studies, or symposiums, say Kathryn Perera and colleagues (doi:10.1136/bmj.l6447). “Don’t bring a fact to a narrative fight,” they advise. The “we know best” approach is not effective in a world that is sceptical of the “old power” represented by medical experts and institutions. Instead, those who hope to change minds must embrace “new power” …
Targeting diacylglycerol acyltransferase 2 for the treatment of nonalcoholic steatohepatitis
Authors: Neeta B. Amin, Santos Carvajal-Gonzalez, Julie Purkal, Tong Zhu, Collin Crowley, Sylvie Perez, Kristin Chidsey, Albert M. Kim, Bryan Goodwin
Journal: Science Translational Medicine (2019)

Inhibition of DGAT2 reduces steatosis, inflammation, and fibrosis in rodent models of NASH and reduces liver fat in clinical testing.
Repurposing auranofin to treat TP53-mutated or PTEN-deleted refractory B-cell lymphoma
Authors: Jeffrey Wang, Jacqueline Wang, Elyse Lopez, Hui Guo, Hui Zhang, Yang Liu, Zhihong Chen, Shengjian Huang, Shouhao Zhou, Angela Leeming, R. J. Zhang, Dayoung Jung, Hannah Shi, Hadley Grundman, Darian Doakes, Kathleen Cui, Changying Jiang, Makhdum Ahmed, Krystle Nomie, Bingliang Fang, Michael Wang, Yixin Yao, Liang Zhang
Journal: Blood Cancer Journal (2019)
Hypermethylation of the PCDHB15 promoter predicts the prognosis in gastric cancer
Authors: Y.-T. Lee, P.-Y. Hsu, Y.-M. Chuang, H. Jin, A.S.L. Cheng, E.K.W. Ng, C.-J. Liu, Y.-C. Chen, F. Cheng, M.W.Y. Chan
Journal: Annals of Oncology (2019)
Evaluation of the potential of histone deacetylase inhibitors to synergize the antineoplastic effects of the proteasome inhibitor bortezomib in mantle cell lymphoma (MCL)
Authors: L. Paoluzzi, L. Scotto, V. E. Seshan, O. A. O'Connor
Journal: Journal of Clinical Oncology (2009)

8584 Background: Romidepsin (R) and belinostat (B) are inhibitors of histone deacetylases (HDACI). HDACIs are known to induce cell death in malignant cells through multiple mechanisms, including up-regulation of death receptors, disruption of Hsp90 function and generation of reactive oxygen species. Mantle cell lymphoma is an aggressive subtype of non-Hodgkin lymphoma characterized by the reciprocal translocation t(11;14)(q13;q32) leading to the overexpression of cyclin D1. Methods: We investigated the cytotoxicity of romidepsin and belinostat alone and in combination with the proteasome inhibitor bortezomib in cell lines of mantle cell lymphoma (HBL2, Granta519, Jeko1). Cell Titer-Glo assay followed by luminometric acquisition was used for all cytotoxicity assays. Drug:drug interactions in terms of synergism, additivity or antagonism were computed using the Relative Risk Ratio Analysis (RRR, GraphPad software) with a RRR &lt; 1 defining synergism, RRR=1 additivity and RRR&gt;1 antagonism. Results: The IC 50 values for R and B alone at 24 hours were: HBL-2: R=4.7nM, B=490nM; Jeko-1: R=3nM, B=750nM; Granta519: R=45nM, B=30,700nM. As single agent, romidepsin was about 100 fold more potent than belinostat. The combination of belinostat (100–1000nM) or romidepsin (1–40nM) with bortezomib (3–4nM) showed synergism in all cell lines at different concentrations. For romidepsin plus bortezomib, RRR in Granta519=0.05–0.14, RRR in Jeko1=0.1–0.75, RRR in HBL2=0.03–0.81. For belinostat plus bortezomib, RRR in Granta519= 0.07–0.38, RRR in Jeko1=0.16–0.49, RRR in HBL2=0.04–0.69. Flowcytometry for apoptosis, cell cycle analysis and mitochondrial membrane potential as well as immunoblottings for hystone H3 acetylation, cyclin D1, Bcl-XL, Mcl-1, BIM and IKB-α suggest this strategy may modulate cyclin D1 and p27 in MCL which is known to be grossly deregulated for these proteins. Conclusions: In this analysis, while romidepsin had improved single agent activity, when combined with bortezomib both HDACI showed potent synergism. [Table: see text]
Impact of Adding Aspirin to Direct Oral Anticoagulant Therapy without an Apparent Indication
Authors: Jordan K Schaefer, Yun Li, Xiaowen Kong, Tina Alexandris-Souphis, Mona A Ali, Brian Haymart, Scott Kaatz, Eva Kline-Rogers, Jay H Kozlowski, Gregory D Krol, Sahana R Shankar, Suman L Sood, James B Froehlich, Geoffrey D Barnes
Journal: Blood (2019)
Serious illness communication practices in glioblastoma care at an academic medical center.
Authors: Lauren Reed-Guy, Tyler D. Alexander, Gregory Biggiani, Stephen P. Miranda, Nina O'Connor
Journal: Journal of Clinical Oncology (2019)

28 Background: Glioblastoma (GBM) is an aggressive primary brain tumor with a disease course marked by both cognitive and physical decline. Early conversations about end-of-life (EOL) preferences are important given the average life expectancy of 14 months. Little is known about patterns of communication in GBM. Objective: To describe current practices surrounding EOL conversations in GBM patients at an academic medical center. Methods: We reviewed the medical records of 240 patients treated for GBM at the University of Pennsylvania who died between 2017 and 2019. We systematically identified and characterized EOL conversations, as defined by documented discussions of prognosis, goals of care, EOL planning and/or code status. Results: Patients in this study were predominantly male, white, privately insured and had relatively high performance status (median KPS 80 at initiation of therapy). Median survival was 487 days and 96% of patients received both chemotherapy and radiation. Nearly all patients (96%) had at least one EOL conversation documented. The median number of documented conversations per patient was 4. The first EOL conversation occurred at a median of 24 days after diagnosis (range 0 to 3,883) and 362 days before death (0 to 2,401). The last EOL conversation occurred at a median of 32 days before death (0 to 1,514). EOL conversations took place earlier among older patients, with each additional year of age at diagnosis associated with a first conversation 8 days earlier (95% CI: -12 to -4 days; p&lt;0.01). At least one EOL conversation occurred at an outpatient visit for 89% of patients; 33% had conversations during hospital admissions; and 38% had EOL conversations via telephone. Medical oncology was the most common specialty to document EOL conversations (89% of patients), followed by palliative care (19%), radiation oncology (13%) and neurosurgery (10%). Conclusions: EOL conversations appear to have occurred relatively early and often, but further work is needed to evaluate the quality of documented discussions and to determine whether this pattern is unique to this single center or widespread. The variety in provider specialty and conversation setting reflects the complexity of the care environment in GBM.
Patterns of storage, use, and disposal of prescription opioids by parents of children with cancer.
Authors: Kevin Madden, Akhila Sunkepally Reddy, Maxine Grace De la Cruz, Eduardo Bruera
Journal: Journal of Clinical Oncology (2019)

114 Background: Multiple studies have demonstrated that adults do not store prescription opioids safely. Increased prescription opioid rates have led to an increased incidence of opioid poisonings in children and adolescents. We investigated whether parents of children with cancer that were prescribed opioids practiced safe storage, use, and disposal techniques. Methods: We conducted a prospective cross-sectional survey of parents whose children were prescribed opioids and asked them about their patterns of storage, use, and disposal of prescription opioids. Results: Virtually all parents (106/109, 97%) completed the survey. Most parents (95/106, 90%) did not store opioids safely. Six of 106 parents (6%) gave their child's opioid pain medication to someone else with pain, and 3 of 106 parents (3%) personally took some of their child’s opioid. Parents who personally took their child’s opioid ( P = .01) or gave it to another person ( P &lt; .001) were more likely to use opioids unsafely with their child. A minority of parents (22/106, 21%) did not use opioids safely in their child. A small number of parents (3/22, 14%) did not dispose of opioids safely. Conclusions: Universal education about the safe, use, and disposal of opioids should be adopted when prescribing opioids. Pediatricians need to maintain vigilance about the nonmedical use of prescription opioid use by parents of children.
Behavioural responses to a photovoltaic subretinal prosthesis implanted in non-human primates
Authors: Paul-Henri Prévot, Kevin Gehere, Fabrice Arcizet, Himanshu Akolkar, Mina A. Khoei, Kévin Blaize, Omar Oubari, Pierre Daye, Marion Lanoë, Manon Valet, Sami Dalouz, Paul Langlois, Elric Esposito, Valérie Forster, Elisabeth Dubus, Nicolas Wattiez, Elena Brazhnikova, Céline Nouvel-Jaillard, Yannick LeMer, Joanna Demilly, Claire-Maëlle Fovet, Philippe Hantraye, Morgane Weissenburger, Henri Lorach, Elodie Bouillet, Martin Deterre, Ralf Hornig, Guillaume Buc, José-Alain Sahel, Guillaume Chenegros, Pierre Pouget, Ryad Benosman, Serge Picaud
Journal: Nature Biomedical Engineering (2019)
cAMP/EPAC Signaling Enables ETV2 to Induce Endothelial Cells with High Angiogenesis Potential
Authors: Jae-Jun Kim, Da-Hyun Kim, Jin Young Lee, Byung-Chul Lee, Insung Kang, Myung Geun Kook, Dasom Kong, Soon Won Choi, Heung-Myong Woo, Dong-Ik Kim, Kyung-Sun Kang
Journal: Molecular Therapy (2019)

Although the generation of ETV2-induced endothelial cells (iECs) from human fibroblasts serves as a novel therapeutic strategy in regenerative medicine, the process is inefficient, resulting in incomplete iEC angiogenesis. Therefore, we employed chromatin immunoprecipitation (ChIP) sequencing and identified molecular mechanisms underlying ETV2-mediated endothelial transdifferentiation to efficiently produce iECs retaining appropriate functionality in long-term culture. We revealed that the majority of ETV2 targets in human fibroblasts are related to vasculature development and signaling transduction pathways, including Rap1 signaling. From a screening of signaling pathway modulators, we confirmed that forskolin facilitated efficient and rapid iEC reprogramming via activation of the cyclic AMP (cAMP)/exchange proteins directly activated by cAMP (EPAC)/RAP1 axis. The iECs obtained via cAMP signaling activation showed superior angiogenesis in vivo as well as in vitro. Moreover, these cells could form aligned endothelium along the vascular lumen ex vivo when seeded into decellularized liver scaffold. Overall, our study provided evidence that the cAMP/EPAC/RAP1 axis is required for the efficient generation of iECs with angiogenesis potential. Although the generation of ETV2-induced endothelial cells (iECs) from human fibroblasts serves as a novel therapeutic strategy in regenerative medicine, the process is inefficient, resulting in incomplete iEC angiogenesis. Therefore, we employed chromatin immunoprecipitation (ChIP) sequencing and identified molecular mechanisms underlying ETV2-mediated endothelial transdifferentiation to efficiently produce iECs retaining appropriate functionality in long-term culture. We revealed that the majority of ETV2 targets in human fibroblasts are related to vasculature development and signaling transduction pathways, including Rap1 signaling. From a screening of signaling pathway modulators, we confirmed that forskolin facilitated efficient and rapid iEC reprogramming via activation of the cyclic AMP (cAMP)/exchange proteins directly activated by cAMP (EPAC)/RAP1 axis. The iECs obtained via cAMP signaling activation showed superior angiogenesis in vivo as well as in vitro. Moreover, these cells could form aligned endothelium along the vascular lumen ex vivo when seeded into decellularized liver scaffold. Overall, our study provided evidence that the cAMP/EPAC/RAP1 axis is required for the efficient generation of iECs with angiogenesis potential.
Ginsenoside Rg3-loaded, reactive oxygen species-responsive polymeric nanoparticles for alleviating myocardial ischemia-reperfusion injury
Authors: Lan Li, Yili Wang, Rui Guo, Sheng Li, Jingyu Ni, Shan Gao, Xiumei Gao, Jingyuan Mao, Yan Zhu, Pingli Wu, Hongjun Wang, Deling Kong, Han Zhang, Meifeng Zhu, Guanwei Fan
Journal: Journal of Controlled Release (2019)
A randomized trial of medical cannabis (MC) in patients with advanced cancer (AC) to assess impact on opioid use and cancer-related symptoms.
Authors: Dylan M. Zylla, Justin Eklund, Grace Gilmore, Alissa Gavenda, Gabriela Vazquez-Benitez, Pamala A. Pawloski, Tom Arneson, Angela Birnbaum, Stephen Dahmer, Matthew Tracy, Arkadiusz Z. Dudek
Journal: Journal of Clinical Oncology (2019)

109 Background: Higher pain and greater long-term opioid requirements have been associated with shorter survival and decreased quality of life (QOL) in patients with AC. Routine use of MC is limited by a lack of rigorous scientific data and concerns about side effects, legal ramifications, and cost. Methods: 30 patients with stage IV cancer requiring opioids were randomized 1:1 to early cannabis (EC, n=15) vs. delayed cannabis (DC, n=15). The EC group was provided with 3 months (3M) of MC at no charge, while the DC group received standard oncology care without MC for the first 3M. Patients met with licensed pharmacists at one of two MC manufacturers to determine optimal MC dosing, formulation, and route. Patients completed monthly pain logs, opioid/MC logs, and validated Patient-Reported Symptom Monitoring surveys. Results: A higher proportion of EC patients achieved a reduction in opioid use and improved pain control. On average over a 3M window, EC patients did not require opioid dose escalation, had lower mean pain, and had similar QOL compared to DC patients. Estimated mean daily THC and CBD dose at 3M was 76 mg (range 5-186 mg) and 36 mg (range &lt;1-516 mg), respectively. Mean perceived benefit of MC was 5.1 and mean perceived negative impact was 2.7 (1 = no benefit/negative effects, 7 = a great deal of benefit/negative effects). 33% of patients died during the anticipated 6-month study period and patient compliance with study logs limited analysis. Conclusions: Randomized studies of MC in the oncology setting are feasible, but rigorous data collection is challenging. The addition of MC to standard oncology care in patients with AC was well-tolerated and may lead to improved pain control and lower opioid requirements. [Table: see text]
ΔNp73/ETS2 complex drives glioblastoma pathogenesis— targeting downstream mediators by rebastinib prolongs survival in preclinical models of glioblastoma
Authors: Maren Cam, Manish Charan, Alessandra M Welker, Piyush Dravid, Adam W Studebaker, Jeffrey R Leonard, Christopher R Pierson, Ichiro Nakano, Christine E Beattie, Eugene I Hwang, Madhuri Kambhampati, Javad Nazarian, Jonathan L Finlay, Hakan Cam
Journal: Neuro-Oncology (2019)

Glioblastoma (GBM) remains one of the least successfully treated cancers. It is essential to understand the basic biology of this lethal disease and investigate novel pharmacological targets to treat GBM. The aims of this study were to determine the biological consequences of elevated expression of ΔNp73, an N-terminal truncated isoform of TP73, and to evaluate targeting of its downstream mediators, the angiopoietin 1 (ANGPT1)/tunica interna endothelial cell kinase 2 (Tie2) axis, by using a highly potent, orally available small-molecule inhibitor (rebastinib) in GBM.ΔNp73 expression was assessed in glioma sphere cultures, xenograft glioblastoma tumors, and glioblastoma patients by western blot, quantitative reverse transcription PCR, and immunohistochemistry. Immunoprecipitation, chromatin immunoprecipitation (ChiP) and sequential ChIP were performed to determine the interaction between ΔNp73 and E26 transformation-specific (ETS) proto-oncogene 2 (ETS2) proteins. The oncogenic consequences of ΔNp73 expression in glioblastomas were examined by in vitro and in vivo experiments, including orthotopic zebrafish and mouse intracranial-injection models. Effects of rebastinib on growth of established tumors and survival were examined in an intracranial-injection mouse model.ΔNp73 upregulates both ANGPT1 and Tie2 transcriptionally through ETS conserved binding sites on the promoters by interacting with ETS2. Elevated expression of ΔNp73 promotes tumor progression by mediating angiogenesis and survival. Therapeutic targeting of downstream ΔNp73 signaling pathways by rebastinib inhibits growth of established tumors and extends survival in preclinical models of glioblastoma.Aberrant expression of ΔNp73 in GBM promotes tumor progression through autocrine and paracrine signaling dependent on Tie2 activation by ANGPT1. Disruption of this signaling by rebastinib improves tumor response to treatment in glioblastoma.
The Role of Individual Heterogeneity in Collective Animal Behaviour
Authors: Jolle W. Jolles, Andrew J. King, Shaun S. Killen
Journal: Trends in Ecology & Evolution (2019)

Social grouping is omnipresent in the animal kingdom. Considerable research has focused on understanding how animal groups form and function, including how collective behaviour emerges via self-organising mechanisms and how phenotypic variation drives the behaviour and functioning of animal groups. However, we still lack a mechanistic understanding of the role of phenotypic variation in collective animal behaviour. Here we present a common framework to quantify individual heterogeneity and synthesise the literature to systematically explain and predict its role in collective behaviour across species, contexts, and traits. We show that individual heterogeneity provides a key intermediary mechanism with broad consequences for sociality (e.g., group structure, functioning), ecology (e.g., response to environmental change), and evolution. We also outline a roadmap for future research.
The correlations between knowledge and attitudes of productive age women toward “SADARI” (breast self-assessment) as early detection of breast cancer in Pejeng Kaja Village, Ubud, Bali
Authors: Y. Brahmantya, A.B.S. Satyarsa, S.A. Arta Suryantari, K.D. Puspitasari, A.T. Adiputra
Journal: Annals of Oncology (2019)