tbuckley/cabot-search huggingface dataset:
Abstract 1968: A novel glucocorticoid receptor (GR) antagonist overcomes GR-mediated chemoresistance in triple-negative breast cancer
Authors: Nadine Jahchan, Haiying Zhou, Wayne Kong, Dan Mc Weeney, Ted Tracy, James Stice, Dena Sutimantanapi, Chelsea Chen, Tom Huang, Yosup Rew, Xiauhui Du, Tatiana Zavorotinskaya, Daqing Sun, Qiuping Ye, Erica Jackson, Valeria Fantin
Journal: Cancer Research (2018)

Abstract The glucocorticoid receptor (GR) is a member of the nuclear receptor superfamily, which is activated by its endogenous steroid hormone ligand cortisol, and by synthetic glucocorticoids such as dexamethasone. Several preclinical studies have shown that GR mediates resistance to both targeted therapies and conventional chemotherapies in a variety of epithelial cancers including prostate, lung, bladder, renal, ovarian and triple-negative breast cancers (TNBC) (Gassler et al., 2005; Li et al., 2017; Zhang et al., 2007). In TNBC, both GR activation and a disrupted cortisol secretion cycle are associated with chemotherapy resistance, increased disease recurrence and poor prognosis (Pan et al., 2011; Skor et al., 2013). Therefore a molecule that inhibits GR activation could attenuate the development of therapy resistance and improve patient outcomes. We have developed novel GR inhibitors that effectively block GR transcriptional activity in cells by competing for ligand binding and by blocking GR-coactivator interactions. In vitro, treatment of TNBC cells with the GR antagonist OP-3713 blocks GR transcriptional activity and enhances the efficacy of chemotherapeutic agents. In rodents the predominant glucocorticoid is corticosterone (Siswanto et al., 2008), which is a weak agonist of human GR. Therefore, to fully activate GR in human xenograft cancer models it is necessary to provide exogenous cortisol. Using xenograft models of TNBC, we find that tumors grown in mice with physiologically relevant circulating cortisol levels to activate GR are significantly less sensitive to chemotherapy than those grown in the absence of cortisol. Furthermore, inhibition of GR by OP-3713 prevents tumor relapse following chemotherapy treatment. We have begun to elucidate the mechanisms by which GR mediates chemoresistance in TNBC, and the basis for the reversal by OP-3713. Our findings underscore the important role of GR as a mediator of resistance in TNBC and highlight the therapeutic potential of GR inhibitors in combination with clinically relevant chemotherapeutic agents. Citation Format: Nadine Jahchan, Haiying Zhou, Wayne Kong, Dan Mc Weeney, Ted Tracy, James Stice, Dena Sutimantanapi, Chelsea Chen, Tom Huang, Yosup Rew, Xiauhui Du, Tatiana Zavorotinskaya, Daqing Sun, Qiuping Ye, Erica Jackson, Valeria Fantin. A novel glucocorticoid receptor (GR) antagonist overcomes GR-mediated chemoresistance in triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1968.
Excess deaths: government commissions review
Authors: Zosia Kmietowicz
Journal: BMJ (2018)

The government is commissioning a review of the spike in deaths seen in England and Wales this year, after the issue was raised in The BMJ .

In March an analysis of the Office for National Statistics’ (ONS) data on weekly provisional deaths in England and Wales, published in The BMJ ,1 found that by week seven of 2018 (ending 16 February) 10 000 more people had died than the average from the past five years. A subsequent analysis2 showed that, by the end of week 16 (ending 20 April), 20 215 …
Attentional modulation of visceral and somatic pain
Authors: P Dunckley, Q Aziz, R G Wise, J Brooks, I Tracey, L Chang
Journal: Gut (2006)

A better understanding of the cortical processes underlying attentional modulation of visceral and somatic pain in health are essential for interpretation of future imaging studies of hypervigilance towards bodily sensations which is considered to be an aetiologically important factor in the heightened pain reported by patients with irritable bowel syndrome and fibromyalgia. Twelve healthy subjects were recruited for this study. Simultaneous trains of electrical pulses (delivered to either the rectum or lower abdomen) and auditory tones lasting 6 s were delivered to the subjects during a whole-brain functional scan acquisition. Subjects were instructed to attend to the auditory tones (distracter task) or electrical pulses (pain task). Pain intensity ratings were significantly lower during the distraction task compared with the pain task (P < 0.01) in both sensory modalities. The left primary somatosensory cortex increased in activity with increasing pain report, during attention to visceral pain. Bilateral anterior insula (aIns) cortex activity increased with increasing somatic pain report independent of the direction of attention. Conversely, the primary and secondary auditory cortices significantly increased in activation with decreased pain report. These results suggest that pain intensity perception during attentional modulation is reflected in the primary somatosensory cortex (visceral pain) and aIns cortex activity (somatic pain).
Abstract 3958: Inhibiting the inhibitor: Exploring the p53-Rbm38 loop as a potential cancer therapeutic target
Authors: Chris A. Lucchesi
Journal: Cancer Research (2018)

Abstract Modulating Rbm38 negative regulation of p53 translation may be an effective therapeutic target in human cancers. As a focal regulatory component of RNA metabolism, RNA-binding proteins (RBPs) modulate all facets of RNA biogenesis. Given the fact that RBPs control RNA metabolism, defects in the function of RBPs can have far reaching implications including neurodegenerative disorders and cancer. Our group discovered that Rbm38 suppresses p53 mRNA translation by interacting with eukaryotic translation initiation factor 4E (eIF4E) on p53 mRNA. Conceptually, blocking the Rbm38 interaction with eIF4E employing synthetic peptides corresponding to their respective binding interface should relieve the translational repression caused by Rbm38. Indeed, treating cancer cells with synthetic peptides corresponding to the binding interface between Rbm38 and eIF4E resulted in robust p53 protein expression. Moreover, addition of peptide and low dose doxorubicin caused further accumulation of p53. Consequently, treatment of cancer cells with peptide alone or in combination with low dose doxorubicin leads to a decrease in colony formation as well as tumor sphere formation. Of significance, RKO xenografts with wild-type p53 were highly sensitive to treatment with a synthetic peptide comprising just 8 amino acids (Pep8) compared to the control group. Together, these data support that p53 expression can be modulated by using small peptides to inhibit Rbm38 from interacting with eIF4E, which may be used as a therapeutic approach in cancers carrying wild-type p53. Citation Format: Chris A. Lucchesi. Inhibiting the inhibitor: Exploring the p53-Rbm38 loop as a potential cancer therapeutic target [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3958.
Abstract 1183: Targeted sequencing of cell-free DNA data enables comprehensive profiling of tumor copy number landscape from blood
Authors: Catalin Barbacioru, Eric Collisson, Darya Chudova, Justin Odegaard, Richard Lanman, AmirAli Talasaz
Journal: Cancer Research (2018)

Abstract Background: The evolution of cancer genomes within a single tumor creates mixed cell populations with divergent somatic mutational architectures. Inference of tumor subpopulations has been disproportionately focused on the assessment of somatic point mutations, whereas computational methods targeting copy number alterations (CNA) in targeted sequencing data remain underdeveloped. Methods: Using a large database of clinical cell-free DNA (cfDNA) sequencing data (Guardant Health, CA), we developed a coverage-based probabilistic model to simultaneously normalize molecular coverage, segment the genome, predict copy number alterations, and estimate the tumor content in cfDNA samples, while accounting for mixtures of cell populations. This model was technically validated using tissue fluorescence in situ hybridization (FISH) data and then applied to a unique set of cfDNA sequencing data from &amp;gt;5,000 normal and clinical samples spanning multiple cancer types, where model predictions were compared to the observed allelic frequencies of somatic driver mutations and heterozygous germline SNPs. Results: Technical validation against FISH-derived tissue copy number estimates demonstrated high concordance with model estimates. Analysis of clinical samples demonstrated a wide range of copy number architectures, including prevalent copy number neutral loss-of-heterozygosity, large chromosomal deletions, and high focal amplifications, all of which are not easily detected and/or differentiated with standard sequencing analysis approaches on highly-fragmented cfDNA. Conclusion: Our results show that probabilistic modeling of coverage data generated from targeted cfDNA sequencing can detect and differentiate heterogeneous tumor populations with diverse somatic variations, CNA, and LOH landscape. This method may enable improvements in CNA detection accuracy, sensitivity, and specificity and provides more precise interrogation of tumor fraction and clonal architecture. Citation Format: Catalin Barbacioru, Eric Collisson, Darya Chudova, Justin Odegaard, Richard Lanman, AmirAli Talasaz. Targeted sequencing of cell-free DNA data enables comprehensive profiling of tumor copy number landscape from blood [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1183.
Assessment of functional capacity before major non-cardiac surgery: an international, prospective cohort study
Authors: Duminda N Wijeysundera, Rupert M Pearse, Mark A Shulman, Tom E F Abbott, Elizabeth Torres, Althea Ambosta, Bernard L Croal, John T Granton, Kevin E Thorpe, Michael P W Grocott, Catherine Farrington, Paul S Myles, Brian H Cuthbertson, Sophie Wallace, Bruce Thompson, Mathew Ellis, Brigette Borg, Ross K Kerridge, Jeanene Douglas, John Brannan, Jeff Pretto, Guy Godsall, Nicola Beauchamp, Sandra Allen, Ann Kennedy, Ewan Wright, Johan Malherbe, Hilmy Ismail, Bernhard Riedel, Andrew Melville, Harry Sivakumar, Andrew Murmane, Kay Kenchington, Yesim Kirabiyik, Usha Gurunathan, Chris Stonell, Kate Brunello, Katherine Steele, Oystein Tronstad, Philip Masel, Annette Dent, Emma Smith, Alanna Bodger, Miriam Abolfathi, Pal Sivalingam, Adrian Hall, Thomas W Painter, Simon Macklin, Adrian Elliott, Anna Maria Carrera, Nico CS Terblanche, Simon Pitt, Joanne Samuel, Chris Wilde, Kate Leslie, Andrew MacCormick, David Bramley, Anne Marie Southcott, John Grant, Hugh Taylor, Samantha Bates, Miriam Towns, Anna Tippett, Fiona Marshall, C David Mazer, Janarthanee Kunasingam, Anmol Yagnik, Charmagne Crescini, Sanjay Yagnik, Colin JL McCartney, Priya Somascanthan, Stephen Choi, Kathrina Flores, Shelly Au, W Scott Beattie, Keyvan Karkouti, Hance A Clarke, Angela Jerath, Stuart A McCluskey, Marcin Wasowicz, Lauren Day, Janneth Pazmino-Canizares, Paul Oh, Rene Belliard, Leanna Lee, Karen Dobson, Vincent Chan, Richard Brull, Noam Ami, Matthew Stanbrook, Katherine Hagen, Douglas Campbell, Timothy Short, Joreline Van Der Westhuizen, Kushlin Higgie, Helen Lindsay, Ryan Jang, Chris Wong, Davina McAllister, Marlynn Ali, Jonathan Kumar, Ellen Waymouth, Chang Joon Kim, Julian Dimech, Michael Lorimer, Joyce Tai, Reuben Miller, Rachel Sara, Andrew Collingwood, Sue Olliff, Sharon Gabriel, Helen Houston, Paul Dalley, Sally Hurford, Anna Hunt, Lynn Andrews, Leanlove Navarra, Adelaide Jason-Smith, Helen Thompson, Natalie McMillan, Geraldine Back, Mark Lum, Daniel Martin, Sarah James, Helder Filipe, Manuel Pinto, Stephen Kynaston, Mandeep Phull, Christian Beilstein, Pheobe Bodger, Kirsty Everingham, Ying Hu, Edyta Niebrzegowska, Carmen Corriea, Thais Creary, Marta Januszewska, Tahania Ahmad, Jan Whalley, Richard Haslop, Jane McNeil, Alistair Brown, Neil MacDonald, Mari Liis Pakats, Kathryn Greaves, Shaman Jhanji, Ravishanar Raobaikady, Ethel Black, Martin Rooms, Helen Lawrence, Maria Koutra, Katrina Pirie, Michelle Gertsman, Sandy Jack, Michael Celinski, Denny Levett, Mark Edwards, Karen Salmon, Clare Bolger, Lisa Loughney, Leanne Seaward, Hannah Collins, Bryony Tyrell, Natasha Tantony, Kim Golder, Gareth L Ackland, RCM Stephens, Laura Gallego-Paredes, Anna Reyes, Ana Gutierrez del Arroyo, Ashok Raj, Rhiannon Lifford, Magda Melo, Muhammad Mamdani, Graham Hillis, Harindra C Wijeysundera
Journal: The Lancet (2018)
Conflicts of Interest in Nutrition Research
Authors: David S. Ludwig, Lawrence H. Kushi, Steven B. Heymsfield
Journal: JAMA (2018)

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Abstract 96: Novel inverse functioning molecules, GSN as metastatic promoter and OAS2 as metastatic repressor in colorectal adenocarcinoma
Authors: Jin Cheon Kim, Je Jin Ha, Ka Hee Tak, Seon Ae Roh, Chan Wook Kim, Yong Sik Yoon, Jong Lyul Lee, Seon-Kyu Kim, Ee Hong Kwon, Dong-Hyung Cho, Seon-Young Kim, Yong Sung Kim
Journal: Cancer Research (2018)

Abstract Background LVI and PNI, recognized as major histological traces of metastatic CRC, have been recognized as a category I prognostic factor representing aggressive CRC. The primary aim of our study was to find out molecules associated with LVI and PNI and to examine their biological behavior with their prognostic significance. Methods LVI- and PNI-associated molecules were identified and verified by utilizing (1) RNA-seq and selecting 117 genes by differential expression values in primary cancer samples of 130 patients with and without systemic recurrence (n = 72 and 58) (2) association analysis to extract six genes associated with LVI or PNI (3) assessment of biological property measuring proliferation, invasion/migration, epithelial-mesenchymal transition, and autophagy flux (4) verification of disease-free survival using public data sets of gene Results GSN-overexpressing LoVo cells showed more than 2-fold greater invasion compared with control cells 5 (p &amp;lt; 0.001 - 0.005), whereas OAS2-overexpressing RKO cells showed a significantly reduced invasion compared with control cells (p &amp;lt; 0.001 - 0.005). GSN repressed expressions of E-cadherin, β-catenin, claudin-1, and snail, whereas it enhanced N-cadherin and ZEB1 expressions. Reverse findings were noticeably identified in OAS2-overexpression. Interestingly, expressions of multiple autophagy-related proteins including ATG5-12, ATG6/BECN1, ATG7, and ATG101 were decreased in GSN-overexpressing Lovo cells. In addition, accumulation of p62, a well-known substrate of autophagic degradation, suggested that an autophagic flux was also reduced in the GSN-overexpressing Lovo cells. In contrast to GSN overexpression, reverse findings of autophagy flux was identified in OAS2-overexpressing RKO cells. The 5-year RFS rates were significantly greater in the GSN underexpression group than in the overexpression group (73.6% and 64.7%, p = 0.038), whereas patients with OAS2 overexpression presented a greater RFS rate than those with underexpression (73.4% and 63.7%, p = 0.01). Conclusion GSN and OAS2, as a recurrence promoter and suppressor, respectively, suggest their potential value as recurrence predictor or therapeutic targets in future clinical validation studies. Citation Format: Jin Cheon Kim, Je Jin Ha, Ka Hee Tak, Seon Ae Roh, Chan Wook Kim, Yong Sik Yoon, Jong Lyul Lee, Seon-Kyu Kim, Ee Hong Kwon, Dong-Hyung Cho, Seon-Young Kim, Yong Sung Kim. Novel inverse functioning molecules, GSN as metastatic promoter and OAS2 as metastatic repressor in colorectal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 96.
Targeting Breast Cancer Stem Cell State Equilibrium through Modulation of Redox Signaling
Authors: Ming Luo, Li Shang, Michael D. Brooks, Evelyn Jiagge, Yongyou Zhu, Johanna M. Buschhaus, Sarah Conley, Melissa A. Fath, April Davis, Elizabeth Gheordunescu, Yongfang Wang, Ramdane Harouaka, Ann Lozier, Daniel Triner, Sean McDermott, Sofia D. Merajver, Gary D. Luker, Douglas R. Spitz, Max S. Wicha
Journal: Cell Metabolism (2018)
Laser‐Enabled Processing of Stretchable Electronics on a Hydrolytically Degradable Hydrogel
Authors: Rahim Rahimi, Siamak Shams Es‐haghi, Shirisha Chittiboyina, Zeynep Mutlu, Sophie A. Lelièvre, Mukerrem Cakmak, Babak Ziaie
Journal: Advanced Healthcare Materials (2018)

Abstract Degradable electronics represent a rapidly emerging field of science and technology with the potential to serve short‐term medical implantation applications where the device disappears once its function is complete. Despite many efforts in developing new types of degradable electronics, many of such systems are nonelastic and incompatible with the dynamic motion of native soft/elastic biological tissues. Herein, a photo‐crosslinkable hydrogel with integrated electronics that are highly stretchable and degradable in liquid environments is demonstrated. The fabrication process takes advantage of facile laser micromachining of conductive patterns directly onto the hydrogel under ambient conditions and permanent hydrogel–hydrogel bonding. The robustness and degradation rate of hydrogel and the laser‐processed encapsulated stretchable circuits is systematically investigated in different solutions under various conditions. Biocompatibility tests with non‐neoplastic cells (HMT 3522 S1) and cancer cells (T4‐2 and MDA‐MB‐231) are performed in 2D and 3D cell culture systems to confirm instead of evaluate the safety of the hydrogel and its byproducts during degradation as well as the zinc metal used in this technology. As a proof of concept, a stretchable hydrogel‐based device that can be used for remote/wireless delivery of thermal energy into the tissue in contact with the hydrogel is fabricated.
Structural brain correlates of obstructive sleep apnoea in older adults at risk for dementia
Authors: Nathan E. Cross, Negar Memarian, Shantel L. Duffy, Casey Paquola, Haley LaMonica, Angela D'Rozario, Simon J.G. Lewis, Ian B. Hickie, Ronald R. Grunstein, Sharon L. Naismith
Journal: European Respiratory Journal (2018)

This study aimed to investigate associations between obstructive sleep apnoea (OSA) and cortical thickness in older adults with subjective and objective cognitive difficulties, who are considered "at-risk" for dementia.83 middle-aged to older adults (51-88 years) underwent neuropsychological testing, polysomnography assessment of OSA and a structural magnetic resonance imaging brain scan. A principal components analysis was performed on OSA measures. Cortical thickness and subcortical volumes were compared to extracted components of "oxygen desaturation" and "sleep disturbance".Oxygen desaturation was significantly related to reduced cortical thickness in the bilateral temporal lobes (left: r=-0.44, p<0.001; right: r=-0.39, p=0.003). Conversely, sleep disturbance was associated with increased thickness in the right postcentral gyrus (r=0.48, p<0.001), pericalcarine (r=0.50, p=0.005) and pars opercularis (r=0.46, p=0.009) and increased volume of the hippocampus and amygdala. Decreased thickness in the bilateral temporal regions was associated with reduced verbal encoding (r=0.28, p=0.010).Given the clinical significance of this sample in terms of dementia prevention, these changes in grey matter reveal how OSA might contribute to neurodegenerative processes in older adults.
Outbreak of Ebola virus disease in the Democratic Republic of the Congo, April–May, 2018: an epidemiological study
Authors: Ahmadou Barry, Steve Ahuka-Mundeke, Yahaya Ali Ahmed, Yokouide Allarangar, Julienne Anoko, Brett Nicholas Archer, Aaron Aruna Abedi, Jayshree Bagaria, Marie Roseline Darnycka Belizaire, Sangeeta Bhatia, Théophile Bokenge, Emanuele Bruni, Anne Cori, Ernest Dabire, Amadou Mouctar Diallo, Boubacar Diallo, Christl Ann Donnelly, Ilaria Dorigatti, Tshewang Choden Dorji, Aura Rocio Escobar Corado Waeber, Ibrahima Socé Fall, Neil M Ferguson, Richard Gareth FitzJohn, Gervais Leon Folefack Tengomo, Pierre Bernard Henri Formenty, Alpha Forna, Anne Fortin, Tini Garske, Katy AM Gaythorpe, Celine Gurry, Esther Hamblion, Mamoudou Harouna Djingarey, Christopher Haskew, Stéphane Alexandre Louis Hugonnet, Natsuko Imai, Benido Impouma, Guylain Kabongo, Oly Ilunga Kalenga, Emerencienne Kibangou, Theresa Min-Hyung Lee, Charles Okot Lukoya, Ousmane Ly, Sheila Makiala-Mandanda, Augustin Mamba, Placide Mbala-Kingebeni, Franck Fortune Roland Mboussou, Tamayi Mlanda, Vital Mondonge Makuma, Oliver Morgan, Anastasie Mujinga Mulumba, Patrick Mukadi Kakoni, Daniel Mukadi-Bamuleka, Jean-Jaques Muyembe, Ndjoloko Tambwe Bathé, Patricia Ndumbi Ngamala, Roland Ngom, Guillaume Ngoy, Pierre Nouvellet, Justus Nsio, Kevin Babila Ousman, Emilie Peron, Jonathan Aaron Polonsky, Michael J. Ryan, Alhassane Touré, Rodney Towner, Gaston Tshapenda, Reinhilde Van De Weerdt, Maria Van Kerkhove, Annika Wendland, N'Da Konan Michel Yao, Zabulon Yoti, Etienne Yuma, Guy Kalambayi Kabamba, Jean de Dieu Lukwesa Mwati, Gisele Mbuy, Leopold Lubula, Anny Mutombo, Oscar Mavila, Yyonne Lay, Emma Kitenge
Journal: The Lancet (2018)