tbuckley/cabot-search huggingface dataset:
Effective treatment of nasopharyngeal carcinoma with autologous Epstein-Barr Virus and oncogene–targeted cytotoxic t lymphocytes
Authors: W. Xia, L. Guoying, Y. Xiang
Journal: Annals of Oncology (2018)

Background: The outcomes for patients with metastatic or locally recurrent Epstein–Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) remain poor. We aimed to improve the outcomes for NPC refractory to conventional treatments with autologous EBV and oncogene–targeted Cytotoxic T Lymphocytes (CTL) therapy. Methods: Patients with stage IV NPC who cannot tolerate chemotherapy received autologous EBV and oncogene–targeted CTL expanded ex vivo from peripheral blood lymphocytes through dendritic cells (DCs) transfected by adenovirus-based vector encoded multiple epitopes from LMP1, CK19, survivin, SCC, CEA, SPANX, MAGE-A3, PMSA. Clinical tumor responses, survival rate and toxicity were evaluated. Results: In total 16 patients received multiple oncogenes-targeted CTL infusion. Among them, 2 patients had locally advanced NPC (LANPC) with high-risk distance metastasis, 5 patients had nasopharyngeal and/or cervical recurrence after re-irriadiation or surgery, 7 patients had distant metastasis and 2 patients had both distant metastasis and nasopharyngeal recurrence. Three patients showed CR, one patient showed PR, and nine patients exhibited SD after CTL infusion. During a median follow-up of 15 months, the median progression-free survival (PFS) was 282 days (range 28-503 days), the mean overall survival is 484 days (range 28–552 days) after autologous CTL infusion. We did not observe severe or chronic adverse reactions related to autologous EBV and oncogene–targeted CTL infusions. Conclusions: In our study, our findings show that therapy with autologous Epstein-Barr Virus and oncogene–Targeted Cytotoxic T Lymphocytes is safe and well tolerated and may offer clinical benefit to patients with NPC. Legal entity responsible for the study: Sun Yat-Sen University Cancer Center. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Association of Maternal First-Trimester Ondansetron Use With Cardiac Malformations and Oral Clefts in Offspring
Authors: Krista F. Huybrechts, Sonia Hernández-Díaz, Loreen Straub, Kathryn J. Gray, Yanmin Zhu, Elisabetta Patorno, Rishi J. Desai, Helen Mogun, Brian T. Bateman
Journal: JAMA (2018)

<h3>Importance</h3> Evidence for the fetal safety of ondansetron, a 5-HT<sub>3</sub>receptor antagonist that is commonly prescribed for nausea and vomiting during pregnancy, is limited and conflicting. <h3>Objective</h3> To evaluate the association between ondansetron exposure during pregnancy and risk of congenital malformations. <h3>Design, Setting, and Participants</h3> A retrospective cohort study nested in the 2000-2013 nationwide Medicaid Analytic eXtract. The cohort consisted of 1 816 414 pregnancies contributed by 1 502 895 women enrolled in Medicaid from 3 months before the last menstrual period through 1 month or longer after delivery; infants were enrolled in Medicaid for at least 3 months after birth. The final date of follow-up was December 31, 2013. Analyses were conducted between November 1, 2017, and June 30, 2018. Propensity score stratification was used to control for treatment indication and other confounders. <h3>Exposures</h3> Ondansetron dispensing during the first trimester, the period of organogenesis. <h3>Main Outcomes and Measures</h3> Primary outcomes were cardiac malformations and oral clefts diagnosed during the first 90 days after delivery. Secondary outcomes included congenital malformations overall and subgroups of cardiac malformations and oral clefts. <h3>Results</h3> Among 1 816 414 pregnancies (mean age of mothers, 24.3 [5.8] years), 88 467 (4.9%) were exposed to ondansetron during the first trimester. Overall, 14 577 of 1 727 947 unexposed and 835 of 88 467 exposed infants were diagnosed with a cardiac malformation, for an absolute risk of 84.4 (95% CI, 83.0 to 85.7) and 94.4 (95% CI, 88.0 to 100.8) per 10 000 births respectively. The absolute risk of oral clefts was 11.1 per 10 000 births (95% CI, 10.6 to 11.6; 1921 unexposed infants) and was 14.0 per 10 000 births (95% CI, 11.6 to 16.5; 124 exposed infants). The risk of any congenital malformation was 313.5 per 10 000 births (95% CI, 310.9 to 316.1; 54 174 unexposed infants) and was 370.4 (95% CI, 358.0 to 382.9; 3277 exposed infants). The adjusted relative risk (RR) for cardiac malformations was 0.99 (95% CI, 0.93 to 1.06) and the adjusted risk difference (RD) was −0.8 (95% CI, −7.3 to 5.7 per 10 000 births). For oral clefts, the adjusted RR was 1.24 (95% CI, 1.03 to 1.48) and the RD was 2.7 (95% CI, 0.2 to 5.2 per 10 000 births). The adjusted estimate for congenital malformations overall was an RR of 1.01 (95% CI, 0.98 to 1.05) and an RD of 5.4 (95% CI, −7.3 to 18.2 per 10 000 births). <h3>Conclusions and Relevance</h3> Among offspring of mothers enrolled in Medicaid, first-trimester exposure to ondansetron was not associated with cardiac malformations or congenital malformations overall after accounting for measured confounders but was associated with a small increased risk of oral clefts.
Targeting the tumor stroma with a bispecific T-cell engager-armed oncolytic adenovirus
Authors: J. de Sostoa Pomés, C.A. Fajardo, R. Moreno, M.D. Ramon, M. Farrera Sal, R. Alemany
Journal: Annals of Oncology (2018)

Background: Oncolytic virus (OV)-based therapies have an emerging role in the treatment of solid tumors, involving both direct cell lysis and immunogenic cell death. Nonetheless, tumor-associated stroma limits the efficacy of OVs by forming a barrier that blocks efficient viral penetration and spread. Moreover, the stroma plays a critical role in progression and immunosuppression of cancer. Fibroblast activation protein-α (FAP) is highly overexpressed in cancer-associated fibroblasts (CAFs), the main cellular component of tumor stroma, and in this study we assessed whether arming oncolytic adenovirus (OAd) with a FAP-targeting Bispecific T-cell Engager (FBiTE) could retarget infiltrated lymphocytes towards CAFs, enhancing viral spread and anti-tumor immunity to improve therapeutic activity. Methods: The BiTE against FAP was constructed using an anti-human CD3 single-chain variable fragment (scFv) linked to an anti-murine and human FAP scFv. This FBiTE was inserted in the oncolytic adenovirus ICOVIR15K under the control of the major late promoter, generating the ICO15K-FBiTE. ICO15K-FBiTE replication and potency were assessed in HT1080 and A549 tumor cell lines. The expression of the FBiTE and the activation and proliferation of T cells that induced along with the T-cell-mediated cytotoxicity of CAFs were evaluated by flow cytometry in vitro. In vivo T-cell biodistribution and antitumor efficacy studies were conducted in NOD/scid/IL2rg-/- (NSG) mice. Results: FBiTE expression from the OAd ICO15K did not decrease the infectivity and replication potency in vitro. T-cells activation and proliferation, leading to T-cells-mediated cytotoxicity of FAP-positive cells was successfully achieved after FBiTE-mediated binding of both CD3+cells and FAP+ cells. In vivo, FBiTE expression increased intratumoral accumulation of T-cells and decreased the level of FAP, a marker of CAFs, in tumors. The antitumor activity of the FBiTE-armed OAd was superior to the parental virus. Conclusions: Combination of viral oncolysis of cancer cells and FBiTE-mediated cytotoxicity of FAP-expressing CAFs might be an effective strategy to overcome a key limitation of oncolytic virotherapy, encouraging its further clinical development. Legal entity responsible for the study: IDIBELL. Funding: Ministerio de Economía y Competividad and Generalitat de Catalunya. Disclosure: All authors have declared no conflicts of interest.
Best Practices Recommendations for Diagnostic Immunohistochemistry in Lung Cancer
Authors: Yasushi Yatabe, Sanja Dacic, Alain C. Borczuk, Arne Warth, Prudence A. Russell, Sylvie Lantuejoul, Mary Beth Beasley, Erik Thunnissen, Giuseppe Pelosi, Natasha Rekhtman, Lukas Bubendorf, Mari Mino-Kenudson, Akihiko Yoshida, Kim R. Geisinger, Masayuki Noguchi, Lucian R. Chirieac, Johan Bolting, Jin-Haeng Chung, Teh-Ying Chou, Gang Chen, Claudia Poleri, Fernando Lopez-Rios, Mauro Papotti, Lynette M. Sholl, Anja C. Roden, William D. Travis, Fred R. Hirsch, Keith M. Kerr, Ming-Sound Tsao, Andrew G. Nicholson, Ignacio Wistuba, Andre L. Moreira
Journal: Journal of Thoracic Oncology (2018)
Effects of Liraglutide Versus Placebo on Cardiovascular Events in Patients With Type 2 Diabetes Mellitus and Chronic Kidney Disease
Authors: Johannes F. E. Mann, Vivian Fonseca, Ofri Mosenzon, Itamar Raz, Bryan Goldman, Thomas Idorn, Bernt Johan von Scholten, Neil R. Poulter
Journal: Circulation (2018)

LEADER trial (Liraglutide Effect and Action in Diabetes: Evaluation of CV Outcome Results) results demonstrated cardiovascular benefits for patients with type 2 diabetes mellitus at high cardiovascular risk on standard of care randomized to liraglutide versus placebo. The effect of glucagon-like peptide-1 receptor agonist liraglutide on cardiovascular events and all-cause mortality in patients with type 2 diabetes mellitus and chronic kidney disease is unknown. Liraglutide's treatment effects in patients with and without kidney disease were analyzed post hoc.Patients were randomized (1:1) to liraglutide or placebo, both in addition to standard of care. These analyses assessed outcomes stratified by baseline estimated glomerular filtration rate (eGFR; <60 versus ≥60 mL/min/1.73 m2) and baseline albuminuria. The primary outcome (composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and secondary outcomes, including all-cause mortality and individual components of the primary composite outcome, were analyzed using Cox regression.Overall, 2158 and 7182 patients had baseline eGFR <60 or ≥60 mL/min/1.73 m2, respectively. In patients with eGFR <60 mL/min/1.73 m2, risk reduction for the primary composite cardiovascular outcome with liraglutide was greater (hazard ratio [HR], 0.69; 95% CI, 0.57-0.85) versus those with eGFR ≥60 mL/min/1.73 m2 (HR, 0.94; 95% CI, 0.83-1.07; interaction P=0.01). There was no consistent effect modification with liraglutide across finer eGFR subgroups (interaction P=0.13) and when analyzing eGFR as a continuous variable (interaction P=0.61). Risk reductions in those with eGFR <60 versus ≥60 mL/min/1.73 m2 were as follows: for nonfatal myocardial infarction, HR, 0.74; 95% CI, 0.55-0.99 versus HR, 0.93; 95% CI, 0.77-1.13; for nonfatal stroke, HR, 0.51; 95% CI, 0.33-0.80 versus HR, 1.07; 95% CI, 0.84-1.37; for cardiovascular death, HR, 0.67; 95% CI, 0.50-0.90 versus HR, 0.84; 95% CI, 0.67-1.05; for all-cause mortality, HR, 0.74; 95% CI, 0.60-0.92 versus HR, 0.90; 95% CI, 0.75-1.07. Risk reduction for the primary composite cardiovascular outcome was not different for those with versus without baseline albuminuria (HR, 0.83; 95% CI, 0.71-0.97; and HR, 0.92; 95% CI, 0.79-1.07, respectively; interaction P=0.36).Liraglutide added to standard of care reduced the risk for major cardiovascular events and all-cause mortality in patients with type 2 diabetes mellitus and chronic kidney disease. These results appear to apply across the chronic kidney disease spectrum enrolled.URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT01179048.
Generation and molecular recognition of melanoma-associated antigen-specific human γδ T cells
Authors: Patricia M. Benveniste, Sobhan Roy, Munehide Nakatsugawa, Edward L. Y. Chen, Linh Nguyen, Douglas G. Millar, Pamela S. Ohashi, Naoto Hirano, Erin J. Adams, Juan Carlos Zúñiga-Pflücker
Journal: Science Immunology (2018)

Benveniste et al. have uncovered γδ T cells that recognize peptide antigens in an MHC-restricted manner.
Abstract 17761: Prescription and Bleeding Rates and Clinical Outcomes of Contemporary P2Y12 Inhibitors Use in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention
Authors: Jeong cheon Choe, Kwang Soo Cha, Doo Yeop Kim, Sun Hack Lee, Jinhee Ahn, Jin Sup Park, Hye Won Lee, Jun-Hyok Oh, Jung Hyun Choi, Han Cheol Lee, Taek Jong Hong, Myeong Ho Jeong
Journal: Circulation (2017)

Introduction: Ticagrelor or prasugrel are increasingly used in acute coronary syndrome (ACS) patients. We compared prescription rate, bleeding and outcomes after ticagrelor, prasugrel or clopidogre...
Microbiota-Derived Lactate Accelerates Intestinal Stem-Cell-Mediated Epithelial Development
Authors: Yong-Soo Lee, Tae-Young Kim, Yeji Kim, Su-Hyun Lee, Seungil Kim, Sung Wan Kang, Jin-Young Yang, In-Jeoung Baek, Young Hoon Sung, Yun-Yong Park, Sung Wook Hwang, Eunju O, Kwang Soon Kim, Siqing Liu, Nobuhiko Kamada, Nan Gao, Mi-Na Kweon
Journal: Cell Host & Microbe (2018)
Prospective Validation of an mRNA-based Urine Test for Surveillance of Patients with Bladder Cancer
Authors: F. Johannes P. van Valenberg, Andrew M. Hiar, Ellen Wallace, Julia A. Bridge, Donna J. Mayne, Safedin Beqaj, Wade J. Sexton, Yair Lotan, Alon Z. Weizer, Godfrey K. Jansz, Arnulf Stenzl, John F. Danella, Barry Shepard, Kevin J. Cline, Michael B. Williams, Scott Montgomery, Richard D. David, Richard Harris, Eric W. Klein, Timothy J. Bradford, Fred N. Wolk, Karl R. Westenfelder, Andrew F. Trainer, Timothy A. Richardson, Russell B. Egerdie, Bernard Goldfarb, Joseph A. Zadra, Sijian Ge, Suling Zhao, Iris M. Simon, Scott A. Campbell, Brian Rhees, Michael P. Bates, Russell G. Higuchi, J. Alfred Witjes
Journal: European Urology (2018)
Cytotoxic Immune Response Can be Obtained Earlier in Chronic Phase Chronic Myeloid Leukemia Patients Treated with Dasatinib Than with Other Tyrosine Kinase Inhibitors
Authors: Tatsuro Jo, Yohei Kaneko, Kazuhiro Noguchi, Shizuka Hayashi, Risa Hayase, Haruna Shioya, Sadaharu Irie, Kensuke Horio, Jun Taguchi
Journal: Blood (2018)
Doctor is jailed for 12 years for sexual assaults on boys at two Sussex hospitals
Authors: Clare Dyer
Journal: BMJ (2018)

A struck off hospital doctor convicted of multiple sexual assaults on boys in his care at two Sussex hospitals has been jailed for 12 years.

Sivaguru Narendran, 78, committed assaults on four boys between 1983 and 1996, including a case in which he blindfolded his victim and tied him to a bed, Lewes Crown Court heard. The jury convicted him on 13 counts of sexual assault while acquitting him on one charge of buggery.

Narendran’s medical career ended after he was arrested in 1996 for sexually assaulting a 12 year old boy at Stoke Mandeville Hospital. He was jailed for 21 months over that offence and struck off the medical register.

But years later four complainants independently came forward saying they had been …
A Personalized Prediction Model to Risk Stratify Patients with Myelodysplastic Syndromes
Authors: Aziz Nazha, Rami S. Komrokji, Manja Meggendorfer, Sudipto Mukherjee, Najla Al Ali, Wencke Walter, Stephan Hutter, Eric Padron, Yazan F. Madanat, David A Sallman, Teodora Kuzmanovic, Cassandra M. Hirsch, Vera Adema, David P. Steensma, Amy E. DeZern, Gail J. Roboz, Guillermo Garcia-Manero, Alan F. List, Claudia Haferlach, Jaroslaw P. Maciejewski, Torsten Haferlach, Mikkael A. Sekeres
Journal: Blood (2018)
Single-Agent Ibrutinib vs Real-World (RW) Treatments for Patients with Chronic Lymphocytic Leukemia (CLL) and del11q: Adjusted Comparison of RESONATE-2TM and RESONATETM with RW Databases
Authors: Gilles Andre Salles, Evelyne Callet-Bauchu, Hervé Besson, Margaret Doyle, Jamie Garside, Martin Spacek, Michael Doubek
Journal: Blood (2018)
A Turn-On Optoacoustic Probe for Imaging Metformin-Induced Upregulation of Hepatic Hydrogen Sulfide and Subsequent Liver Injury
Authors: Lihe Sun, Yinglong Wu, Junjie Chen, Jun Zhong, Fang Zeng, Shuizhu Wu
Journal: Theranostics (2018)

Metformin is currently the most prescribed oral agent for diabetes treatment; however the overdose or long-term use may cause some severe side effects such as liver injury.Researches indicate that metformin-induced liver injury is closely related to upregulation of hepatic H 2 S. Hence, monitoring hepatic H 2 S generation induced by metformin could be an effective approach for evaluating hepatoxicity of the drug.Methods: We present a novel turn-on and dual-mode probe for detecting and imaging metformin-induced liver injury by specifically tracking the upregulation of hepatic H 2 S with fluorescent and optoacoustic methods.After reaction with H 2 S, the strong electron-withdrawing group dinitrophenyl ether (which acts as both the recognition moiety and the fluorescence quencher) was cleaved and replaced by an electron-donating group hydroxyl.This correspondingly leads to the changes of the probe's electronic state and absorption red-shifting as well as the subsequent turn-on fluorescent and optoacoustic signals. Results:The probe was applied to the colon tumor-bearing mice model and the metformin-induced liver injury mice model to achieve tumor imaging and liver injury assessment.The biosafety of the probe was verified by histological analysis (hematoxylin and eosin staining) and serum biochemical assays. Conclusion:The probe responds quickly to H 2 S in tumors and the liver, and MSOT imaging with the probe offers cross-secitonal and 3D spatial information of liver injury.This study may provide an effective approach for accessing medication side effects by tracking drug-metabolism-related products.
Supermarket policies on less-healthy food at checkouts: Natural experimental evaluation using interrupted time series analyses of purchases
Authors: Katrine T. Ejlerskov, Stephen J. Sharp, Martine Stead, Ashley J. Adamson, Martin White, Jean Adams
Journal: PLoS Medicine (2018)

In response to public concerns and campaigns, some United Kingdom supermarkets have implemented policies to reduce less-healthy food at checkouts. We explored the effects of these policies on purchases of less-healthy foods commonly displayed at checkouts.We used a natural experimental design and two data sources providing complementary and unique information. We analysed data on purchases of small packages of common, less-healthy, checkout foods (sugary confectionary, chocolate, and potato crisps) from 2013 to 2017 from nine UK supermarkets (Aldi, Asda, Co-op, Lidl, M&S, Morrisons, Sainsbury's, Tesco, and Waitrose). Six supermarkets implemented a checkout food policy between 2013 and 2017 and were considered intervention stores; the remainder were comparators. Firstly, we studied the longitudinal association between implementation of checkout policies and purchases taken home. We used data from a large (n ≈ 30,000) household purchase panel of food brought home to conduct controlled interrupted time series analyses of purchases of less-healthy common checkout foods from 12 months before to 12 months after implementation. We conducted separate analyses for each intervention supermarket, using others as comparators. We synthesised results across supermarkets using random effects meta-analyses. Implementation of a checkout food policy was associated with an immediate reduction in four-weekly purchases of common checkout foods of 157,000 (72,700-242,800) packages per percentage market share-equivalent to a 17.3% reduction. This decrease was sustained at 1 year with 185,100 (121,700-248,500) fewer packages purchased per 4 weeks per percentage market share-equivalent to a 15.5% reduction. The immediate, but not sustained, effect was robust to sensitivity analysis. Secondly, we studied the cross-sectional association between checkout food policies and purchases eaten without being taken home. We used data from a smaller (n ≈ 7,500) individual purchase panel of food bought and eaten 'on the go'. We conducted cross-sectional analyses comparing purchases of common checkout foods in 2016-2017 from supermarkets with and without checkout food policies. There were 76.4% (95% confidence interval 48.6%-89.1%) fewer annual purchases of less-healthy common checkout foods from supermarkets with versus without checkout food policies. The main limitations of the study are that we do not know where in the store purchases were selected and cannot determine the effect of changes in purchases on consumption. Other interventions may also have been responsible for the results seen.There is a potential impact of checkout food polices on purchases. Voluntary supermarket-led activities may have public health benefits.
Erratum: A mutation in the α tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy NEM1 (Nature Genetics (1995) 9 (75-79))
Authors: N Laing, S Wilton, P Akkari, S Dorosz, K Boundy, C Kneebone, P Blumbergs, S White, H Watkins, D Love, E Haan
Journal: Nature Genetics (1995)
Medication dosing for heart failure with reduced ejection fraction — opportunities and challenges
Authors: Catherine N. Marti, Gregg C. Fonarow, Stefan D. Anker, Clyde Yancy, Muthiah Vaduganathan, Stephen J. Greene, Ali Ahmed, James L. Januzzi, Mihai Gheorghiade, Gerasimos Filippatos, Javed Butler
Journal: European Journal of Heart Failure (2018)
Cellular and Chemical Gradients to Engineer the Meniscus‐to‐Bone Insertion
Authors: Leanne E. Iannucci, Alexander J. Boys, Mary Clare McCorry, Lara A. Estroff, Lawrence J. Bonassar
Journal: Advanced Healthcare Materials (2018)

Abstract Tissue‐engineered menisci hold promise as an alternative to allograft procedures but require a means of robust fixation to the native bone. The insertion of the meniscus into bone is critical for meniscal function and inclusion of a soft tissue‐to‐bone interface in a tissue engineered implant can aid in the fixation process. The native insertion is characterized by gradients in composition, tissue architecture, and cellular phenotype, which are all difficult to replicate. In this study, a soft tissue‐to‐bone interface is tissue engineered with a cellular gradient of fibrochondrocytes and mesenchymal stem cells and subjected to a biochemical gradient through a custom media diffusion bioreactor. These constructs, consisting of interpenetrating collagen and boney regions, display improved mechanical performance and collagen organization compared to controls without a cellular or chemical gradient. Media gradient exposure produces morphological features in the constructs that appear similar to the native tissue. Collectively, these data show that cellular and biochemical gradients improve integration between collagen and bone in a tissue engineered soft tissue‐to‐bone construct.
Abstract 13806: Sendai Virus Vectors Achieve Efficient Integration-Free Cardiac Reprogramming in vitro and in vivo
Authors: Kazutaka Miyamoto, Mizuha Akiyama, Fumiya Tamura, Mari Isomi, Hiroyuki Yamakawa, Taketaro Sadahiro, Naoto Muraoka, Hidenori Kojima, Sho Haginiwa, Shota Kurotsu, Keiichi Fukuda, Masaki Ieda
Journal: Circulation (2017)

Direct cardiac reprogramming holds great promise for regenerative medicine. We previously demonstrated that fibroblasts were directly reprogrammed into induced cardiomyocyte-like cells (iCMs) by ov...