tbuckley/cabot-search huggingface dataset:
RNA Binding Protein Rbmx Is Required in Acute Myeloid Leukemia By Regulating the Transcriptional Activity of the Heterochromatin Protein HP1α
Authors: Camila Prieto, Diu Nguyen, Ly P Vu, Alexendar Perez, Saroj Gourkanti, Alexandra Schurer, Timothy Chou, Arthur Chow, James Taggart, Trevor Stephen Barlowe, Christina Leslie, Michael G. Kharas
Journal: Blood (2018)
Mature dendritic cells correlate with favorable immune infiltrate and improved prognosis in ovarian carcinoma patients
Authors: Iva Truxova, Lenka Kasikova, Michal Hensler, Petr Skapa, Jan Laco, Ladislav Pecen, Lucie Belicova, Ivan Praznovec, Michael J. Halaska, Tomas Brtnicky, Eva Salkova, Lukas Rob, Roman Kodet, Jeremy Goc, Catherine Sautes-Fridman, Wolf Herman Fridman, Ales Ryska, Lorenzo Galluzzi, Radek Spisek, Jitka Fucikova
Journal: Journal for ImmunoTherapy of Cancer (2018)

A high density of tumor-infiltrating CD8+ T cells and CD20+ B cells correlates with prolonged survival in patients with a wide variety of human cancers, including high-grade serous ovarian carcinoma (HGSC). However, the potential impact of mature dendritic cells (DCs) in shaping the immune contexture of HGSC, their role in the establishment of T cell-dependent antitumor immunity, and their potential prognostic value for HGSC patients remain unclear. We harnessed immunohistochemical tests and biomolecular analyses to demonstrate that a high density of tumor-infiltrating DC-LAMP+ DCs is robustly associated with an immune contexture characterized by TH1 polarization and cytotoxic activity. We showed that both mature DCs and CD20+ B cells play a critical role in the generation of a clinically-favorable cytotoxic immune response in HGSC microenvironment. In line with this notion, robust tumor infiltration by both DC-LAMP+ DCs and CD20+ B cells was associated with most favorable overall survival in two independent cohorts of chemotherapy-naïve HGSC patients. Our findings suggest that the presence of mature, DC-LAMP+ DCs in the tumor microenvironment may represent a novel, powerful prognostic biomarker for HGSC patients that reflects the activation of clinically-relevant anticancer immunity.
Applications and potential of genome editing in crop improvement
Authors: Yi Zhang, Karen Massel, Ian D Godwin, Caixia Gao
Journal: Genome biology (2018)

Genome-editing tools provide advanced biotechnological techniques that enable the precise and efficient targeted modification of an organism's genome. Genome-editing systems have been utilized in a wide variety of plant species to characterize gene functions and improve agricultural traits. We describe the current applications of genome editing in plants, focusing on its potential for crop improvement in terms of adaptation, resilience, and end-use. In addition, we review novel breakthroughs that are extending the potential of genome-edited crops and the possibilities of their commercialization. Future prospects for integrating this revolutionary technology with conventional and new-age crop breeding strategies are also discussed.
High performance immunochromatographic assay for simultaneous quantitative detection of multiplex cardiac markers based on magnetic nanobeads
Authors: Lixin Hong, Kan Wang, Wenqiang Yan, Hao Xu, Qinghui Chen, Yuhui Zhang, Daxiang Cui, Qinghui Jin, Jinghua He
Journal: Theranostics (2018)

The detection of cardiac markers is critical to the diagnosis of acute myocardial infarction, and immunochromatographic assays are a common tool for point-of-care analysis.Methods: We report a multiplexed lateral flow test strip for simultaneous quantitative detection of cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CKMB), and myoglobin (Myo).Hydrophilic, monodisperse, stable, and carboxyl-modified (COOH-) magnetic nanobeads (MNBs) were used to construct immunomagnetic probes specific to the three cardiac markers.The detection area of the sandwich-style complexes contained three test lines for cTnI, CKMB, and Myo.The magnetic signal intensity of the detection area in the nitrocellulose membrane was measured via a magnetic immunochromatography reader developed in house.Results: To optimize the assay, a modified working buffer was also investigated to improve the detection sensitivity, decrease the background noise, and shorten the detection time.The MNB-based immunochromatography test (MICT) strip offers a wide linear dynamic detection range, rapid detection, high sensitivity, and specificity.The limit of detection was 0.0089 ng/mL for cTnI, 0.063 ng/mL for CKMB, and 0.05 ng/mL for Myo with minimal cross-reactivity.There were 110 clinical human serum samples that were used to evaluate this platform with high correlation.Conclusion: MICT shows great potential as a supplemental method for in vitro diagnostics in the laboratory or in other point-of-care testing (POCT) applications.
The UCL–Lancet Commission on Migration and Health: the health of a world on the move
Authors: Ibrahim Abubakar, Robert W Aldridge, Delan Devakumar, Miriam Orcutt, Rachel Burns, Mauricio L Barreto, Poonam Dhavan, Fouad M Fouad, Nora Groce, Yan Guo, Sally Hargreaves, Michael Knipper, J Jaime Miranda, Nyovani Madise, Bernadette Kumar, Davide Mosca, Terry McGovern, Leonard Rubenstein, Peter Sammonds, Susan M Sawyer, Kabir Sheikh, Stephen Tollman, Paul Spiegel, Cathy Zimmerman, Ibrahim Abubakar, Robert W Aldridge, Delan Devakumar, Miriam Orcutt, Rachel Burns, Mauricio L Barreto, Poonam Dhavan, Fouad M Fouad, Nora Groce, Yan Guo, Sally Hargreaves, Michael Knipper, Jaime Miranda, Nyovani Madise, Bernadette Kumar, Davide Mosca, Terry McGovern, Leonard Rubenstein, Peter Sammonds, Susan M Sawyer, Kabir Sheikh, Stephen Tollman, Paul Spiegel, Cathy Zimmerman, Mustafa Abbas, Eleanor Acer, Ayesha Ahmad, Seye Abimbola, Karl Blanchet, Philippe Bocquier, Fiona Samuels, Olga Byrne, Sonia Haerizadeh, Rita Issa, Mark Collinson, Carren Ginsburg, Ilan Kelman, Alys McAlpine, Nicola Pocock, Barbara Olshansky, Dandara Ramos, Michael White, Suzanne Zhou
Journal: The Lancet (2018)
Clinician versus patient: Who gets it right when assessing function in palliative care?
Authors: Sara Lauren Mann, Willem Hardie Collier, Dominik Ose, Shane Brogan, Anna Catherine Beck, Jill E. Sindt
Journal: Journal of Clinical Oncology (2018)

40 Background: The Karnofsky Performance Score (KPS) is an important prognostic indicator in cancer care. Additionally, patient-reported outcomes are increasingly incorporated into clinical care and are validated in cancer patients with the NIH’s Patient-Reported Outcomes Measurement Information System (PROMIS). However, little is known about the concordance of the provider-rated KPS and patient-rated PROMIS measures. Methods: Retrospective review of patients with advanced cancer who underwent implantation of an intrathecal pump for refractory pain. We compared KPS and PROMIS scores recorded within 1 week of each other. PROMIS scores included an average score and 3 domains: physical function, fatigue, and pain interference. We divided each measure into 3 previously-described categories (Functionally Independent, Needs Limited Assistance, and Functionally Dependent) and assessed categorical concordance within each measure. The association of patient-related demographic and clinical characteristics were analyzed with KPS–PROMIS concordance using chi-square and Mann-Whitney U tests. Results: 47 patients were included. The provider-rated KPS score consistently indicated a higher functional status compared to the patient-rated PROMIS average score and across all PROMIS domain scores. 40% of patients were rated “Functionally Dependent” using the average PROMIS score, compared to just 19.1% using the KPS, a statistically significant difference (p=0.042). We noted categorical concordance of 55.3% for PROMIS average score, 57.5% for physical function, 44.7% for fatigue and 42.7% for pain interference compared to KPS. We found no statistically significant associations between concordance and patient demographics or characteristics. Conclusions: Our results revealed a notably low concordance in functional status in advanced cancer patients between provider-rated KPS and patient-rated PROMIS measures. Provider-rated scores consistently indicated a higher overall performance status, in particular with measures of the lowest functional status. Additional work is needed to better understand the reasons for this lack of concordance and its implications for ongoing clinical decision-making.
Underdetection and Undertreatment of Dyspnea in Critically Ill Patients
Authors: Eliza R. Gentzler, Heather Derry, Daniel J. Ouyang, Lindsay Lief, David A. Berlin, Cici Jiehui Xu, Paul K. Maciejewski, Holly G. Prigerson
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Dyspnea is a common and distressing physical symptom among patients in the ICU and may be underdetected and undertreated.Objectives: To determine the frequency of dyspnea relative to pain, the accuracy of nurses and personal caregiver dyspnea ratings relative to patient-reported dyspnea, and the relationship between nurse-detected dyspnea and treatment.Methods: This was an observational study of patients (n = 138) hospitalized in a medical ICU (MICU). Nurses and patients’ personal caregivers at the bedside reported on their perception of patients’ symptoms.Measurements and Main Results: Dyspnea was assessed by patients, caregivers, and nurses with a numerical rating scale. Across all three raters, the frequency of moderate to severe dyspnea was similar or greater than that of pain (P < 0.05 for caregiver and nurse ratings). Personal caregivers’ ratings of dyspnea had substantial agreement with patient ratings (κ = 0.65, P < 0.001), but nurses’ ratings were not significantly related to patient ratings (κ = 0.19, P = 0.39). Nurse detection of moderate to severe pain was significantly associated with opioid treatment (odds ratio, 2.70; 95% confidence interval, 1.10–6.60; P = 0.03); however, nurse detection of moderate to severe dyspnea was not significantly associated with any assessed treatment.Conclusions: Dyspnea was reported at least as frequently as pain among the sampled MICU patients. Personal caregivers had good agreement with patient reports of moderate to severe dyspnea. However, even when detected by nurses, dyspnea appeared to be undertreated. These findings suggest the need for improved detection and treatment of dyspnea in the MICU.
Adoptive Cell Transfer: Is it a Promising Immunotherapy for Colorectal Cancer?
Authors: Jiaqiao Fan, Dong Shang, Bing Han, Jianxun Song, Hailong Chen, Jin-Ming Yang
Journal: Theranostics (2018)

The last decade has witnessed significant advances in the adoptive cell transfer (ACT) technique, which has been appreciated as one of the most promising treatments for patients with cancer.Utilization of ACT can enhance the function of the immune system or improve the specificity and persistence of transferred cells.Various immune cells including T lymphocytes, natural killer cells, dendritic cells, and even stem cells can be used in the ACT despite their different functional mechanisms.Colorectal cancer (CRC) is among the most common malignancies and causes millions of deaths worldwide every year.In this review, we discuss the status and perspective of the ACT in the treatment of CRC.
Imatinib treatment of paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (EsPhALL2010): a prospective, intergroup, open-label, single-arm clinical trial
Authors: Andrea Biondi, Virginie Gandemer, Paola De Lorenzo, Gunnar Cario, Myriam Campbell, Anders Castor, Rob Pieters, André Baruchel, Ajay Vora, Veronica Leoni, Jan Stary, Gabriele Escherich, Chi-Kong Li, Giovanni Cazzaniga, Hélène Cavé, Jutta Bradtke, Valentino Conter, Vaskar Saha, Martin Schrappe, Maria Grazia Valsecchi
Journal: The Lancet Haematology (2018)
Abstract 12610: Vascular Function and Vascular Structure are impaired in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Shinji Kishimoto, Yukihito Higashi, Kensuke Noma, Ayumu Nakashima, Takayuki Hidaka, Tatsuya Maruhashi, Masato Kajikawa, Yumiko Iwamoto, Akimichi Iwamoto, Nozomu Oda, Yoshiki Aibara, Yasuki Kihara
Journal: Circulation (2015)

Background: Endothelial dysfunction and abnormal vascular structure may be involved in the pathogenesis of chronic heart failure. The purpose of this study was to evaluate simultaneously the vascular dysfunction and structure in patients with heart failure with preserved ejection fraction (HFpEF). Methods and Results: We measured flow-mediated vasodilatation (FMD) and nitroglycerine-induced vasodilation as indices of vascular function and intima-media thickness (IMT) as an index of vascular structure of brachial artery in 116 patients with HFpEF (66 men and 50 women; mean age, 61±14 yr) and 64 patients without HF (48 men and 16 women; mean age, 50±17 yr). There were significant differences in age, sex, blood pressure, N-terminal pro-brain natriuretic peptide, estimated glomerular filtration and prevalence of diabetes mellitus between the 2 groups. FMD was significantly smaller in patients with HFpEF than in patients without HF (3.6±2.5% versus 5.2±3.1%, P&lt;0.001). Nitroglycerin-induced vasodilation was significantly smaller in the patients with HFpEF than in patients without HF (11.3±5.0% versus 13.3±4.9%, P=0.015). Brachial artery IMT were significantly larger in the patients with HFpEF than in patients without HF (0.34±0.07 mm versus 0.29±0.08 mm, P&lt;0.001). After adjustment for age and sex, hypertension, diabetes mellitus, the associations remained significant between HFpEF and FMD (hazard ratio, 1.18; 95% confidence interval, 1.02-1.37: P=0.025) and brachial artery IMT (hazard ratio, 0.93; 95% confidence interval, 0.88-0.99: P=0.031) but not nitroglycerine-induced vasodilation (hazard ratio, 1.05; 95% confidence interval, 0.98-1.13: P=0.17). Conclusions: These findings suggest that both endothelial dysfunction and abnormal vascular structure contribute to the pathogenesis of HFpEF. Endothelial function and vascular structure may be potential therapeutic targets for HFpEF.
Oncologists and medical assistance in dying: Where do we stand?
Authors: Gur Chandhoke, Gregory Russell Pond, Oren Hannun Levine, Simon Oczkowski
Journal: Journal of Clinical Oncology (2018)

64 Background: With the passage of Bill C-14 in June 2016, medical assistance in dying (MAiD) was formally enacted into Canadian law. Since then, approximately 2,000 patients have died with medical assistance across the country, with cancer being the most common qualifying condition. We aimed to understand the views of oncology providers (OPs) regarding MAiD. Methods: We designed and administered an online survey to Canadian OPs’ to assess experience with MAiD, self-perceived knowledge, willingness to participate, and perception of the role of OPs in introducing MAiD as an end-of-life care option. We used complete sampling via the Canadian Association of Medical Oncologists (CAMO) and the Canadian Association of Radiation Oncologists (CARO) membership email lists. The survey was sent to 366 Radiation Oncologists, and 325 Medical Oncologists. Data was collected from April-June 2018. Results were analyzed using descriptive statistics as well as univariate and multivariate analysis. Results: We received 224 responses (response rate 32.4%). 70% of OPs have been approached by patients requesting MAiD. OPs were confident in their knowledge of the eligibility criteria, and previous exposure to MAiD was associated with confidence in this domain (odds ratio [OR]=3.77, 95% CI=2.05-6.94, p value&lt;0.001). OPs were most willing to engage in MAiD with an assessment for eligibility, yet most refer to specialized teams for assessments. A majority of physicians (52.8%) would initiate a conversation of MAiD with a patient under certain circumstances, most commonly the absence of viable therapeutic options, coupled with unmanageable patient distress. Conclusions: In this first national survey of Canadian OP’s regarding MAiD, we found that most OP’s encounter patient requests for MAiD, are confident in knowledge of eligibility, and are willing to act as assessors of eligibility. Many OP’s believe that it is appropriate to present MAiD as a therapeutic option at the end of life under some circumstances. This finding warrants further deliberation amongst national/regional bodies for the development of consensus guidelines in order to ensure equitable access to MAiD for patients who wish to pursue it.
Self-renewing resident cardiac macrophages limit adverse remodeling following myocardial infarction
Authors: Sarah A. Dick, Jillian A. Macklin, Sara Nejat, Abdul Momen, Xavier Clemente-Casares, Marwan G. Althagafi, Jinmiao Chen, Crystal Kantores, Siyavash Hosseinzadeh, Laura Aronoff, Anthony Wong, Rysa Zaman, Iulia Barbu, Rickvinder Besla, Kory J. Lavine, Babak Razani, Florent Ginhoux, Mansoor Husain, Myron I. Cybulsky, Clinton S. Robbins, Slava Epelman
Journal: Nature Immunology (2018)
Misinterpretation of Study Data—Reply
Authors: Michael R. Wilson, Brian D. O’Donovan, Joseph L. DeRisi
Journal: JAMA Neurology (2018)

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Abstract #153: Cox-2 inhibition delays resistance to sunitinib in RCC xenograft models
Authors: Rupal Bhatt, Xiaoen Wang, Liang Zhang, Andrea Bullock, Manoj Bhasin, Towia Libermann, Sabina Signoretti, Anne O'Neill, Michael Atkins, James Mier, S. Goldberg
Journal: Cancer Research (2009)

Cox-2 inhibition delays resistance to sunitinib in RCC xenograft modelsBackground: Renal cell carcinoma (RCC) has been found to be responsive to agents that inhibit the vascular endothelial growth factor receptor (VEGFR). Sunitinib, a tyrosine kinase inhibitor of VEGFR, is effective at producing tumor responses; however, resistance to therapy develops at a median of 11 months. Murine xenograft models of acquired sunitinib resistance were generated and transcriptional analyses of resistant tumorsshowed arginase, a known cox-2-induced protein, to be increased at the time of resistance.Thus, we assessed the effect of the cox-2 inhibitor celecoxib on acquired resistance to sunitinib in these models. Methods: Mice bearing xenografts derived from two RCC cell lines that showed resistance after stabilization on sunitinib, 786-O and A498, were treated when tumors reached 12mm with celecoxib, sunitinib (25mg/kg and 53.6 mg/kg, respectively daily by gavage), the combination or PBS control and growth curves were generated. Tumors were also followed by arterial spin labeled (ASL) MRI to measure changes in tumor perfusion. Results: Mice treated with the combination of sunitinib and celecoxib had significantly longer periods of tumor stabilization compared to those treated with either agent alone or PBS controls (Table). There was a 38% and 50% increase in the time of tumor stabilization with the addition of celecoxib to sunitinib in 786-O and A498 cells, respectively. Additionally, perfusion imaging showed that the combination of sunitinib and celecoxib suppressed tumor perfusion longer than either agent alone or PBS controls. Conclusions: Cox-2 inhibition is a potential means to delay resistance to VEGFR inhibition in RCC. Further exploration, including potential clinical studies of this combination in patients with metastatic RCC is warranted.$$table_{A96D4818-3AE1-4105-8B0C-8E296506CFC6}$$ Table: Length of tumor stabilization with therapy as defined as days for the tumor to grow by 2mm from pretreatment size. *=p  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 153.
Reverse-Transcriptase Inhibitors in the Aicardi–Goutières Syndrome
Authors: Gillian I Rice, Candice Meyzer, Naïm Bouazza, Marie Hully, Nathalie Boddaert, Michaela Semeraro, Leo A H Zeef, Flore Rozenberg, Vincent Bondet, Darragh Duffy, Alba Llibre, Jinmi Baek, Mame N Sambe, Elodie Henry, Valerie Jolaine, Christine Barnerias, Magalie Barth, Alexandre Belot, Claude Cances, François-Guillaume Debray, Diane Doummar, Marie-Louise Frémond, Naoki Kitabayashi, Alice Lepelley, Virginie Levrat, Isabelle Melki, Pierre Meyer, Marie-Christine Nougues, Florence Renaldo, Mathieu P Rodero, Diana Rodriguez, Agathe Roubertie, Luis Seabra, Carolina Uggenti, Hendy Abdoul, Jean-Marc Treluyer, Isabelle Desguerre, Stéphane Blanche, Yanick J Crow
Journal: New England Journal of Medicine (2018)

à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Sublingual allergen immunotherapy with a liquid birch pollen product in patients with seasonal allergic rhinoconjunctivitis with or without asthma
Authors: Oliver Pfaar, Claus Bachert, Piotr Kuna, Petr Panzner, Mária Džupinová, Ludger Klimek, Maroesja J. van Nimwegen, Johan D. Boot, Donghui Yu, Dirk Jan E. Opstelten, Pieter-Jan de Kam
Journal: Journal of Allergy and Clinical Immunology (2018)

BackgroundSublingual allergen immunotherapy (SLIT) has been demonstrated to be both clinically efficacious and safe. However, in line with the current regulatory guidance from the European Medicines Agency, allergen immunotherapy (AIT) products must demonstrate their efficacy and safety in pivotal phase III trials for registration.ObjectiveWe sought to investigate the efficacy and safety of sublingual high-dose liquid birch pollen extract (40,000 allergy units native [AUN]/mL) in adults with birch pollen allergy.MethodsA randomized, double-blind, placebo-controlled, parallel-group multicenter trial was conducted in 406 adult patients with moderate-to-severe birch pollen-induced allergic rhinoconjunctivitis with or without mild-to-moderate controlled asthma. Treatment was started 3 to 6 months before the birch pollen season and continued during the season in 40 clinical study centers in 5 European countries. For primary end point assessment, the recommended combined symptom and medication score of the European Academy of Allergy and Clinical Immunology was used. Secondary end points included quality-of-life assessments, immunologic parameters, and safety.ResultsPrimary efficacy results demonstrated a significant (P < .0001) and clinically relevant (32%) reduction in the combined symptom and medication score compared with placebo after 3 to 6 months of SLIT. Significantly better rhinoconjunctivitis quality-of-life scores (P < .0001) and the patient's own overall assessment of his or her health status, including the visual analog scale score (Euro Quality of Life Visual Analogue Scale; P = .0025), were also demonstrated. In total, a good safety profile of SLIT was observed.ConclusionThis study confirmed both the clinical efficacy and safety of a sublingual liquid birch pollen extract in adults with birch pollen allergy in a pivotal phase III trial (EudraCT: 2013-005550-30; ClinicalTrials.gov: NCT02231307).