tbuckley/cabot-search huggingface dataset:
Single-Dose Cholera Vaccine in Response to an Outbreak in Zambia
Authors: Eva Ferreras, Elizabeth Chizema-Kawesha, Alexandre Blake, Orbrie Chewe, John Mwaba, Gideon Zulu, Marc Poncin, Ankur Rakesh, Anne-Laure Page, Savina Stoitsova, Caroline Voute, Florent Uzzeni, Hugues Robert, Micaela Serafini, Belem Matapo, Jose-María Eiros, Marie-Laure Quilici, Lorenzo Pezzoli, Andrew S. Azman, Sandra Cohuet, Iza Ciglenecki, Kennedy Malama, Francisco J. Luquero
Journal: New England Journal of Medicine (2018)

Dose Cholera Vaccine in Response to an Outbreak in ZambiaTo the Editor: Killed oral cholera vaccines (OCVs) are part of the standard response package to a cholera outbreak, although the two-dose regimen of vaccines that has been prequalified by the World Health Organization (WHO) poses challenges to timely and efficient reactive vaccination campaigns. 1][4] A cholera outbreak was detected in Lusaka, Zambia, in February 2016, after a period of 4 years without a reported case of cholera.An emergency reactive vaccination campaign was implemented in April 2016, targeting more than 500,000 persons who were at high risk for cholera in Lusaka (population, >2 million persons).The Ministry of Health, with support from Médecins sans Frontières and the WHO, decided to implement a single-dose campaign to quell the epidemic rapidly, in view of the insufficient number of vaccine doses that were available in the global stockpile to complete a two-dose campaign.In December 2016, when more doses became available, a second round of vaccination was organized and the second vaccine dose was offered to persons at risk.We conducted a matched case-control study to quantify the short-term effectiveness of a single-dose OCV regimen (Shanchol) between April 25, 2016, and June 15, 2016.The study was approved by two institutional review boards, and written informed consent was obtained from all the participants (see the Supplementary Appendix, available with the full text of this letter at NEJM.org).Cases of cholera were confirmed by means of culture, polymerase-chain-reaction as-
Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial
Authors: Alberto Papi, Jørgen Vestbo, Leonardo Fabbri, Massimo Corradi, Hélène Prunier, Géraldine Cohuet, Alessandro Guasconi, Isabella Montagna, Stefano Vezzoli, Stefano Petruzzelli, Mario Scuri, Nicolas Roche, Dave Singh
Journal: The Lancet (2018)
RETRACTED ARTICLE: Pericyte degeneration causes white matter dysfunction in the mouse central nervous system
Authors: Axel Montagne, Angeliki M Nikolakopoulou, Zhen Zhao, Abhay P Sagare, Gabriel Si, Divna Lazic, Samuel R Barnes, Madelaine Daianu, Anita Ramanathan, Ariel Go, Erica J Lawson, Yaoming Wang, William J Mack, Paul M Thompson, Julie A Schneider, Jobin Varkey, Ralf Langen, Eric Mullins, Russell E Jacobs, Berislav V Zlokovic
Journal: Nature Medicine (2018)
Reduced active transcellular intestinal oxalate secretion contributes to the pathogenesis of obesity-associated hyperoxaluria
Authors: Ruhul Amin, John Asplin, Daniel Jung, Mohamed Bashir, Altayeb Alshaikh, Sireesha Ratakonda, Sapna Sharma, Sohee Jeon, Ignacio Granja, Dietrich Matern, Hatim Hassan
Journal: Kidney International (2018)
Abstract 10621: Reverse Remodeling of Heart Failure With Preserved Ejection Fraction and Successful Catheter Ablation of Frequent Ventricular Tachyarrhythmias
Authors: Rie Koyoshi, Masahiro Ogawa, Naoko Kumagai, Joji Morii, Hideo Takashima, Tomoo Yasuda, Naomichi Matsumoto, Shinichiro Miura, Keijiro Saku
Journal: Circulation (2012)

Introduction: Frequent premature ventricular complexes (PVCs) are chronically harmful for cardiac structure and function, even in patients without obvious structural heart diseases. However, little...
Methotrexate limits inflammation through an A20-dependent cross-tolerance mechanism
Authors: Cristina Municio, Ángeles Dominguez-Soto, Sara Fuentelsaz-Romero, Amalia Lamana, Nuria Montes, Víctor D Cuevas, Raquel García Campos, José L Pablos, Isidoro González-Álvaro, Amaya Puig-Kröger
Journal: Annals of the Rheumatic Diseases (2018)

Objectives Methotrexate (MTX) is the anchor drug for treatment of rheumatoid arthritis (RA), but the mechanism of its anti-inflammatory action is not fully understood. In RA, macrophages display a proinflammatory polarisation profile that resembles granulocyte-macrophage colony-stimulating factor (GM-CSF)-differentiated macrophages and the response to MTX is only observed in thymidylate synthase + GM-CSF-dependent macrophages. To determine the molecular basis for the MTX anti-inflammatory action, we explored toll-like receptor (TLR), RA synovial fluid (RASF) and tumour necrosis factor receptor (TNFR)-initiated signalling in MTX-exposed GM-CSF-primed macrophages. Methods Intracellular responses to TLR ligands, TNFα or RASF stimulation in long-term low-dose MTX-exposed human macrophages were determined through quantitative real-time PCR, western blot, ELISA and siRNA-mediated knockdown approaches. The role of MTX in vivo was assessed in patients with arthritis under MTX monotherapy and in a murine sepsis model. Results MTX conditioned macrophages towards a tolerant state, diminishing interleukin (IL)-6 and IL-1β production in LPS, LTA, TNFα or RASF-challenged macrophages. MTX attenuated LPS-induced MAPK and NF-κB activation, and toll/IL-1R domain-containing adaptor inducing IFN-beta (TRIF1)-dependent signalling. Conversely, MTX increased the expression of the NF-κB suppressor A20 ( TNFAIP3 ), itself a RA-susceptibility gene. Mechanistically, MTX-induced macrophage tolerance was dependent on A20, as siRNA-mediated knockdown of A20 reversed the MTX-induced reduction of IL-6 expression. In vivo, TNFAIP3 expression was significantly higher in peripheral blood cells of MTX-responsive individuals from a cohort of patients with arthritis under MTX monotherapy, whereas MTX-treated mice exhibited reduced inflammatory responses to LPS. Conclusions MTX impairs macrophage proinflammatory responses through upregulation of A20 expression. The A20-mediated MTX-induced innate tolerance might limit inflammation in the RA synovial context, and positions A20 as a potential MTX-response biomarker.
Role of NADPH oxidase-2 and oxidative stress in children exposed to passive smoking
Authors: Lorenzo Loffredo, Anna Maria Zicari, Francesca Occasi, Ludovica Perri, Roberto Carnevale, Francesco Angelico, Maria Del Ben, Francesco Martino, Cristina Nocella, Giovanna De Castro, Vittoria Cammisotto, Simona Battaglia, Marzia Duse, Francesco Violi
Journal: Thorax (2018)

This study explored oxidative stress, nicotinamide adenine dinucleotide phosphate oxidase-2 (Nox2) activity and endothelial function in children exposed or not to passive smoking. Compared with controls (n=57), Nox2 activity and isoprostanes were higher in children exposed to passive smoking (n=57); conversely, nitric oxide (NO) bioavailability and flow-mediated dilation were lower in children exposed to passive smoking. A bivariate analysis showed that Nox2 activity correlated with flow-mediated dilation, NO bioavailability and isoprostanes. A multivariate analysis showed that Nox2 activity was significantly associated with serum isoprostanes and cotinine levels; flow-mediated dilation was associated with isoprostanes and carotid intima-media thickness.In children exposed to passive smoking, Nox2-derived oxidative stress is upregulated and inversely associated with impaired artery dilation.
Abstract #455: Protein phosphatase 2A and CHK2 binding is disrupted by DNA damage
Authors: Alyson Freeman, Virna Dapic, Alvaro Monteiro
Journal: Cancer Research (2009)

Maintenance of genomic integrity is an essential part of every cell9s existence. The DNA damage response pathway allows for the repair of DNA breaks caused by genotoxic insults in order to prevent the propagation of mutations that can cause diseases such as cancer. CHK2 is a major effector kinase of this pathway. To further characterize CHK2 via its interacting partners, we performed a yeast two-hybrid screen with CHK2 as bait and screened a human mammary gland cDNA library. We identified a subunit of protein phosphatase 2A (PP2A) as a CHK2 binding partner. The PP2A holoenzyme consists of an A structural subunit, a C catalytic subunit, and one of many B regulatory subunits. We show that the B9alpha subunit interacts with CHK2 in co-immunoprecipitates of endogenous proteins in mammalian cells. The CHK2 and B9alpha interaction is exclusively cytoplasmic and binding is abrogated by DNA damage caused by gamma-irradiation (IR) but not by UV, mitomycin C, or hydroxyurea. We have determined that the extent of CHK2 and B9alpha IR-induced dissociation occurs in a dose-dependent manner. Time course experiments show that dissociation is an early response to IR and reassociation can be detected several hours after IR suggesting a temporal correlation with recovery. CHK2 also binds other B9 family members with varying affinities, and these subunits also dissociate from CHK2 after IR. The minimal binding region in CHK2 that interacts with B9alpha includes the SQ/TQ domain, which is a target of ATM-dependent phosphorylation. The phosphorylation of CHK2 at specific sites in this domain correlates with the dissociation of CHK2 and B9alpha after IR, and this dissociation can be prevented by pharmacologic inhibition of ATM. When these sites are mutated to mimic phosphorylation, there is an increase in CHK2 phosphorylation at other sites. Inhibition of PP2A catalytic activity results in an increase in CHK2 phosphorylation at multiple sites as well, suggesting a scenario in which PP2A acts to keep CHK2 in a dephosphorylated inactive state in the absence of certain kinds of DNA damage.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 455.
Abstract #2987: Therapeutic effects of curcumin and thymoquinone in benign prostatic hyperplasia (BPH): Role of inflammatory cytokines and chemokines
Authors: Seema Gupta, Alyssa Park, Mohammed Shareef, Myra Wilkerson, Daniel Rukstalis, Mansoor Ahmed
Journal: Cancer Research (2009)

Inflammation is a frequent finding in benign prostatic hyperplasia (BPH) pathology. To dissect the role of inflammatory chemokines and cytokines in BPH pathology, in the present study, total RNA was isolated from exponentially growing BPH-1 cells (a non-tumorigenic cell line), normal prostate epithelial cells (PrEC) and Paraffin-embedded tissue specimen from six patients diagnosed with BPH that were obtained from transurethral resections of the prostate. Real-time RT PCR was performed using the SuperArray inflammatory cytokine array. BPH-1 cells showed elevated levels of monocyte chemotactic protein-1 (MCP-1 or CCL2) followed by IL-8RB and IL-10RA compared to PrEC cells. Similar results were obtained in BPH tissue samples. MCP-1 promoter analysis indicated the presence of several NF\#954;B sites and hence, we used Curcumin (Cur) and Thymoquinone (Thy) to potently inhibit the expression of MCP-1 since Cur is known to inhibit NF\#954;B and Thy is a potent repressor of ARE activity. Thy potently inhibited the expression of MCP-1 followed by Cur alone. When Thy was combined with Cur, the fold change decreased further than Cur alone but not with Thy alone. Cur was the potent inhibitor of IL8RB and exerted its inhibitory effect when combined with Thy, since Thy was found to induce IL-8RB. On the contrary, IL-10RA was significantly induced in response to Cur or Thy or Cur plus Thy. The effect of Cur or Thy or Cur plus Thy on growth of exponentially growing BPH-1 cells was assessed using Real-Time Cell Electronic Sensing system. Increasing reduction in cell growth was observed with increasing doses of Cur or Thy. Further, complete inhibition of growth was observed when Cur was combined with Thy. The effect of these agents on intrinsic NF\#954;B activity were analyzed by using 3x \#954;B-CAT reporter construct. BPH-1 cells showed elevated constitutive NF\#954;B activity. Thy alone suppressed the basal NF\#954;B activity (p   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2987.
Combined immunosuppression and radiotherapy in thyroid eye disease (CIRTED): a multicentre, 2 × 2 factorial, double-blind, randomised controlled trial
Authors: Rathie Rajendram, Peter N Taylor, Victoria J Wilson, Nicola Harris, Olivia C Morris, Marjorie Tomlinson, Sue Yarrow, Helen Garrott, Helen M Herbert, Andrew D Dick, Anne Cook, Rao Gattamaneni, Rajni Jain, Jane Olver, Steven J Hurel, Fion Bremner, Suzannah R Drummond, Ewan Kemp, Diana M Ritchie, Nichola Rumsey, Daniel Morris, Carol Lane, Nachi Palaniappan, Chunhei Li, Julie Pell, Robert Hills, Daniel G Ezra, Mike J Potts, Sue Jackson, Geoffrey E Rose, Nicholas Plowman, Catey Bunce, Jimmy M Uddin, Richard W J Lee, Colin M Dayan
Journal: The Lancet Diabetes & Endocrinology (2018)
Evolving Roles of Histologic Evaluation and Molecular/Genomic Profiling in the Management of Endometrial Cancer
Authors: Rajmohan Murali, Deborah F. Delair, Sarah M. Bean, Nadeem R. Abu-Rustum, Robert A. Soslow
Journal: Journal of the National Comprehensive Cancer Network (2018)

Endometrial cancers are the most common gynecologic malignancies. The staging of endometrial cancer has evolved from a clinical-based system to a comprehensive surgical-pathologic approach that allows for better risk stratification and treatment planning. Over the past few years, use of NCCN's sentinel lymph node (SLN) mapping algorithm for the surgical staging of endometrial cancer has gained significant acceptance and is now commonly applied in many practices. However, pathologic evaluation of prognostic factors is beset by challenges, including the reproducibility of histologic classification and FIGO's grading, as well as the questionable clinical significance of low-volume tumor in SLNs. With the revelation of major genomic classes of endometrial cancer comes the potential for improved, reproducible, and prognostically relevant classification schemes, which integrate traditional pathologic parameters with genomic findings, to aid in treatment decisions. Pathologic identification of new variants of endometrial cancer, such as undifferentiated carcinoma, continues to advance the phenotypic spectrum of these tumors, spurring genomic and functional studies to further characterize their mechanistic underpinnings and potentially reveal new avenues for treatment. In the era of precision medicine, pathologic assessment of biomarkers (eg, mismatch repair proteins) and recognition of phenotypes that are amenable to specific targeted therapies (such as POLE-mutated tumors) have become integral to the management of women with endometrial carcinoma.
Expression III: patients’ expectations and preferences regarding physician–patient relationship and clinical management—results of the international NOGGO/ENGOT-ov4-GCIG study in 1830 ovarian cancer patients from European countries
Authors: G. Oskay-Özcelik, S. Alavi, R. Richter, M. Keller, R. Chekerov, S.C. Cecere, G. Cormio, F. Joly, J.E. Kurtz, A. du Bois, M. Maciejewski, M. Jedryka, I. Vergote, E. Van Nieuwenhuysen, A. Casado, C. Mendiola, P. Achimas-Cadariu, C. Vlad, D. Reimer, A.G. Zeimet, M. Friedlander, J. Sehouli
Journal: Annals of Oncology (2018)
Diffuse Large B-Cell Lymphomas Transformed from or with Concurrent Follicular Lymphoma Demonstrate Similar Clinical Outcomes As De-Novo Diffuse Large B-Cell Lymphomas, Except for Cases Harboring Double Hit Rearrangements
Authors: Amir Behdad, Craig Boddy, Angela Fought, Timothy Taxter, Marissa Falkiewicz, Daniel J. Landsburg, Jane N. Winter, Barbara Pro, Leo I. Gordon, Reem Karmali, Jason Kaplan
Journal: Blood (2017)
Re: Jochen Walz. The “PROMIS” of Magnetic Resonance Imaging Cost Effectiveness in Prostate Cancer Diagnosis? Eur Urol 2018;73:31–2
Authors: Rita Faria, Marta O. Soares, Eldon Spackman, Hashim U. Ahmed, Louise C. Brown, Richard Kaplan, Mark Emberton, Mark J. Sculpher
Journal: European Urology (2018)
Evaluation of the safety, tolerability, and efficacy of pimavanserin versus placebo in patients with Alzheimer's disease psychosis: a phase 2, randomised, placebo-controlled, double-blind study
Authors: Clive Ballard, Carol Banister, Zunera Khan, Jeffrey Cummings, George Demos, Bruce Coate, James M Youakim, Randall Owen, Srdjan Stankovic, Elaine B Tomkinson, Joanne McDermid, Delik Ocal, Ingelin Testad, Mustabshira A Qayyum, Polychronis Kemos', Olga Borejko, Maria Megalogeni, Ella V Brookes, Anya Petrava, Miguel Da Silva, Kayleigh Nunez
Journal: The Lancet Neurology (2018)
Fibroblast Heterogeneity and Immunosuppressive Environment in Human Breast Cancer
Authors: Ana Costa, Yann Kieffer, Alix Scholer-Dahirel, Floriane Pelon, Brigitte Bourachot, Melissa Cardon, Philemon Sirven, Ilaria Magagna, Laetitia Fuhrmann, Charles Bernard, Claire Bonneau, Maria Kondratova, Inna Kuperstein, Andrei Zinovyev, Anne-Marie Givel, Maria-Carla Parrini, Vassili Soumelis, Anne Vincent-Salomon, Fatima Mechta-Grigoriou
Journal: Cancer Cell (2018)
Doctors do not feel protected when things go wrong
Authors: Ellen S Wright
Journal: BMJ (2018)

The appeal being brought by the General Medical Council to erase Hadiza Bawa-Garba from the register is inhumane, disproportionate, and will not protect the public against further incidents.1 It is more likely to discourage doctors, especially trainees, from disclosing and learning from errors. Trainers are already advising their trainees to record only the …
Expression and function of LIR1/ILT2 in patients with lymphoproliferative disease of granular lymphocytes.
Authors: R Zambello, Livio Trentin, G Cannas, D Carollo, I Baesso, A Cabrelle, T Lamy, M Vitale, Carlo Agostini, A Moretta, Gianpietro Carlo Semenzato
Journal: Blood (2001)
Purification of NAD(P)H:quinone oxidoreductase 1 (NQO1) protein complexes using protein, immuno and tandem affinity purification techniques and identification of interacting proteins by MALDI-TOF mass spectrometry
Authors: Philip Reigan, Jadwiga Kepa, Samiha Mateen, David Siegel, David Ross
Journal: Cancer Research (2007)

3176   NAD(P)H:quinone oxidoreductase 1 (NQO1) is a cytoplasmic homodimeric flavoprotein, that has been reported to interact with p73α and p53, and another study identified an interaction between NQO1 and tubulin in Xenopus egg extract. However, a systematic study investigating NQO1 interacting proteins in mammalian cells has not been performed. In this study, NQO1 protein-protein interactions were examined using one- and two-step affinity purification methods. The one-step affinity purification approaches included: protein affinity purification, using the recombinant human NQO1 protein bound to an agarose solid support, as bait, to probe the human colon carcinoma BE, breast carcinoma MDA468 and pancreatic PANC-1 cancer cell lines and immuno affinity purification using the A180 monoclonal antibody attached to an agarose solid support to probe the complementary BE/NQ7, MDA468/NQ16 and PANC-1/C5 stably transfected NQO1 cell lines. The tandem affinity purification (TAP) technique has been used previously to successfully recover interacting proteins in mammalian cells. In this approach, NQO1 was expressed in the PANC-1 cell line, fused to two tandem affinity tags: a streptavidin and a calmodulin binding peptide. The consecutive purification steps of the TAP protocol utilized both affinity tags and yielded the tagged protein, NQO1, and its potential interacting proteins. The purified NQO1 protein-protein complexes from all affinity purification experiments were separated by SDS-PAGE electrophoresis. The proteins were characterized by in-gel digestion with trypsin, followed by MALDI-TOF mass spectrometric analysis, which identified a number of cytoskeletal proteins, including vimentin, tubulin and actin, which may interact with NQO1 directly or through a protein complex. The identification of the interaction of NQO1 with these cytoskeletal proteins reaffirms a potential role for NQO1 in regulating microtubule stability. (Supported by National Institute of Health grant R01 CA114441 and R01 CA51210).
Phase Ib-II Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib, w/ Lenalidomide and Rituximab in Relapsed / Refractory Mantle Cell Lymphoma
Authors: Andre Goy, Tatyana A Feldman, Lori A. Leslie, Rima Panchal Panchal, Themba Nyirenda, Alan P Skarbnik, Kara Yannotti, Joshua Zenreich, Colleen M Bejot, Susan Stives, Kar Fai Chow, Pritish K. Bhattacharyya, Xiao Yang, Ernest Richards
Journal: Blood (2017)
Abstract 16303: Autonomic Dysfunction Parallels the Progression of Pulmonary Arterial Hypertension in Monocrotaline Rats
Authors: Masako Shinoda, Keita Saku, Yasuhiro Oga, Takeshi Tohyama, Takuya Nishikawa, Kohtaro Abe, Takako Takehara, Takuya Kishi, Hiroyuki Tsutsui, Kenji Sunagawa
Journal: Circulation (2016)

Introduction:  Although autonomic dysfunction in PAH has been increasingly attracting clinical interest as a potential therapeutic option (e.g. pulmonary artery denervation), its relationship with the progression of PAH remains poorly understood. Thus we investigated how PAH alters the autonomic balance and its regulatory system, baroreflex, in monocrotaline (MCT) induced PAH rats.   Methods/Results:  In Sprague-Dawley rats (n=35), we subcutaneously injected MCT (60 mg/kg) or saline for control (CTL), and evaluated the autonomic function 3 and 3.5 week after the injection. MCT markedly increased right ventricular systolic pressure (RVSP) and induced right ventricular hypertrophy (RVH). Increases in plasma norepinephrine and 24-hour urinary norepinephrine excretion paralleled the progression of PAH (Fig. 1). MCT decreased the high frequency component of heart rate variability (HR) (0.81±0.17 vs. 2.72±0.52 msec 2 ,  p  p =0.063) indicating underlying parasympathetic deactivation. To examine baroreflex function, we isolated bilateral carotid sinuses and controlled carotid sinus pressure (CSP). We evaluated the static responses of arterial pressure (AP) to CSP. MCT significantly lowered the static gain (-0.22±0.22 vs. -0.8±0.31,  p  p    Conclusions:  The sympatho-parasympathetic imbalance and baroreflex dysfunction parallel the progression of PAH. The autonomic dysfunction may contribute to worsen the prognosis of severe PAH, thereby could serve as a new therapeutic option in PAH.
Targeting mitochondrial responses to intra-articular fracture to prevent posttraumatic osteoarthritis
Authors: Mitchell C. Coleman, Jessica E. Goetz, Marc J. Brouillette, Dongrim Seol, Michael C. Willey, Emily B. Petersen, Hope D. Anderson, Nathan R. Hendrickson, Jocelyn Compton, Behnoush Khorsand, Angie S. Morris, Aliasger K. Salem, Douglas C. Fredericks, Todd O. McKinley, James A. Martin
Journal: Science Translational Medicine (2018)

Inhibiting mitochondrial oxidant production after surgical fixation of an intra-articular fracture prevents osteoarthritis in a porcine model.