tbuckley/cabot-search huggingface dataset:
1359TiP RELATIVITY-104: First-line relatlimab (RELA) + nivolumab (NIVO) with chemotherapy vs nivo with chemotherapy in stage IV or recurrent non-small cell lung cancer (NSCLC): A phase II, randomized, double-blind study
Authors: D. Morgensztern, A. Chaudhry, N. Iannotti, A. Acevedo, G. Balaburski, A. Balogh, S. Peters
Journal: Annals of Oncology (2021)
590P PRORADIUM: Prospective analysis of the impact of germline mutations in homologous recombination (HR) genes on the response to radium-223 for metastatic castration resistant prostate cancer (mCRPC)
Authors: E. Castro, R. Lozano Mejorada, A. Medina, U. Giorgi, N. Romero Laorden, V. Conteduca, G. De Velasco, D. Alameda, A. Sanz, J. Puente, A. Gonzalez del Alba, P. Borrega, J.C. Villa Guzmán, E.M. Fernández-Parra, A. Rodriguez-Vida, I. Chirivella, F. Vazquez, R. Morales Barrera, D. Lorente, D. Olmos
Journal: Annals of Oncology (2021)
1715P Rapid drug desensitization (RDD) to anticancer drugs: A 4-year monocentric experience
Authors: G. Piacentini, G. Bellotti, F. Blengio, V. Fusco, P.F. Guglielmini, R. Manfredi, P.L. Piovano, E. Traverso, M. Vincenti, S. Zai, M. Rossi
Journal: Annals of Oncology (2021)
Feasibility of modified endarterectomized aortic allograft for middle hepatic vein reconstruction in living donor liver transplantation: A retrospective cohort study
Authors: Jae Hyun Kwon, Dong-Hwan Jung, Shin Hwang, Ki-Hun Kim, Chul-Soo Ahn, Deok-Bog Moon, Tae-Yong Ha, Gi-Won Song, Gil-Chun Park, Young-In Yoon, Sung-Gyu Lee
Journal: International Journal of Surgery (2021)
LBA22 Neoadjuvant chemotherapy with oxaliplatin and capecitabine versus chemoradiation with capecitabine for locally advanced rectal cancer with uninvolved mesorectal fascia (CONVERT): Initial results of a multicenter randomised, open-label, phase III trial
Authors: P-R. Ding, X-Z. Wang, Y-F. Li, Y-M. Sun, C-K. Yang, Z-G. Wu, R. Zhang, W. Wang, Y. Li, Y-Z. Zhuang, J. Lei, X-B. Wan, Y-K. Ren, Y. Cheng, W-L. Li, Z-Q. Wang, Z-Z. Pan, Y-H. Gao, Z-F. Zeng, D-S. Wan
Journal: Annals of Oncology (2021)
Glutamine deficiency shifts the asthmatic state toward neutrophilic airway inflammation
Authors: June‐Mo Kim, Yoo Na Im, Yun‐Jo Chung, Jung‐ho Youm, Suhn Young Im, Myung Kwan Han, Hern Ku Lee
Journal: Allergy (2021)

The administration of L-glutamine (Gln) suppresses allergic airway inflammation via the rapid upregulation of MAPK phosphatase (MKP)-1, which functions as a negative regulator of inflammation by deactivating p38 and JNK mitogen-activated protein kinases (MAPKs). However, the role of endogenous Gln remains to be elucidated. Therefore, we investigated the mechanism by which endogenous Gln regulates MKP-1 induction and allergic airway inflammation in an ovalbumin-based murine asthma model.We depleted endogenous Gln levels using L-γ-glutamyl-p-nitroanilide (GPNA), an inhibitor of the Gln transporter ASCT2 and glutamine synthetase small interfering siRNA. Lentivirus expressing MKP-1 was injected to achieve overexpression of MKP-1. Asthmatic phenotypes were assessed using our previously developed ovalbumin-based murine model, which is suitable for examining sequential asthmatic events, including neutrophil infiltration. Gln levels were analyzed using a Gln assay kit.GPNA or glutamine synthetase siRNA successfully depleted endogenous Gln levels. Importantly, homeostatic MKP-1 induction did not occur at all, which resulted in prolonged p38 MAPK and cytosolic phospholipase A2 (cPLA2 ) phosphorylation in Gln-deficient mice. Gln deficiency augmented all examined asthmatic reactions, but it exhibited a strong bias toward increasing the neutrophil count, which was not observed in MKP-1-overexpressing lungs. This neutrophilia was inhibited by a cPLA2 inhibitor and a leukotriene B4 inhibitor but not by dexamethasone.Gln deficiency leads to the impairment of MKP-1 induction and activation of p38 MAPK and cPLA2 , resulting in the augmentation of neutrophilic, more so than eosinophilic, airway inflammation.
Methodological and Ethical Risks Associated with the Epistemic Unification of Tribe Members
Authors: Joanna K. Malinowska
Journal: The American Journal of Bioethics (2021)

Saunkeah et al. (2021) analyze the aptness of extending the Belmont Principles of Respect for Persons, Beneficence and Justice to AI/AN tribal communities as a whole. They argue that to protect AI/...
1290P RATIONALE 304: Tislelizumab (TIS) plus chemotherapy (chemo) vs chemo alone as first-line (1L) treatment for non-squamous (non-sq) non-small cell lung cancer (NSCLC) in patients (pts) who are smokers vs non-smokers
Authors: S. Lu, D. Huang, X. Chen, B. Wang, J. Xue, J. Wang, Y. Bao, L. Liang, X. Qiu, L. Zhang
Journal: Annals of Oncology (2021)
The Evolution of Multimodality Treatment of Rectal Cancer
Authors: Ranim Alsaad, Sandy Hwang Fang
Journal: JAMA Surgery (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
A selective WDR5 degrader inhibits acute myeloid leukemia in patient-derived mouse models
Authors: Xufen Yu, Dongxu Li, Jithesh Kottur, Yudao Shen, Huen Suk Kim, Kwang-Su Park, Yi-Hsuan Tsai, Weida Gong, Jun Wang, Kyogo Suzuki, Joel Parker, Laura Herring, H. Ümit Kaniskan, Ling Cai, Rinku Jain, Jing Liu, Aneel K Aggarwal, Gang Greg Wang, Jian Jin
Journal: Science Translational Medicine (2021)

WDR5-degrader-E3 ligase ternary complex structure–based design led to a highly effective WDR5 degrader with robust in vivo antitumor activities.
An unusual cause of toxic megacolon
Authors: Healson Ihuoma, Raymol Keelan
Journal: BMJ (2021)

This is an abdominal radiograph of a man in his 20s showing toxic megacolon (transverse colon dilated to 9.9 cm, normal <6 cm) secondary to infection with Shigella flexneri (fig 1). The patient presented with a four day history of watery …
1742TiP RADIORYTHMIC: Phase III, opened, randomized study of post-operative radiotherapy (PORT) versus surveillance in stage IIb/III of Masaoka Koga thymoma after complete surgical resection
Authors: C. Basse, A. Botticella, T. Molina, P-E. Falcoz, Y. Oulkhouir, M. Kerjouan, E. Pichon, F. Calcagno, L. Thiberville, X. Quantin, C. Clément-Duchêne, J. Khalifa, J. Mazieres, F. Le Tinier, E. Dansin, F. Thillays, B. Besse, P-A. Thomas, C. Le Pechoux, N. Girard
Journal: Annals of Oncology (2021)
Minute Acral Melanoma
Authors: Reiko Tsutsumi, Yuichi Yoshida, Osamu Yamamoto
Journal: JAMA Dermatology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Genome editing in large animal models
Authors: Lucy H. Maynard, Olivier Humbert, Christopher W. Peterson, Hans-Peter Kiem
Journal: Molecular Therapy (2021)

Although genome editing technologies have the potential to revolutionize the way we treat human diseases, barriers to successful clinical implementation remain. Increasingly, preclinical large animal models are being used to overcome these barriers. In particular, the immunogenicity and long-term safety of novel gene editing therapeutics must be evaluated rigorously. However, short-lived small animal models, such as mice and rats, cannot address secondary pathologies that may arise years after a gene editing treatment. Likewise, immunodeficient mouse models by definition lack the ability to quantify the host immune response to a novel transgene or gene-edited locus. Large animal models, including dogs, pigs, and non-human primates (NHPs), bear greater resemblance to human anatomy, immunology, and lifespan and can be studied over longer timescales with clinical dosing regimens that are more relevant to humans. These models allow for larger scale and repeated blood and tissue sampling, enabling greater depth of study and focus on rare cellular subsets. Here, we review current progress in the development and evaluation of novel genome editing therapies in large animal models, focusing on applications in human immunodeficiency virus 1 (HIV-1) infection, cancer, and genetic diseases including hemoglobinopathies, Duchenne muscular dystrophy (DMD), hypercholesterolemia, and inherited retinal diseases.
LBA24 Cabozantinib (C) in combination with atezolizumab (A) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Results of expanded cohort 6 of the COSMIC-021 study
Authors: N. Agarwal, B.A. McGregor, B.L. Maughan, T. Dorff, W. Kelly, B. Fang, R. McKay, P. Singh, L. Pagliaro, R. Dreicer, S. Srinivas, Y. Loriot, U.N. Vaishampayan, S. Goel, D. Curran, A. Panneerselvam, L-F. Liu, T.K. Choueiri, S.K. Pal
Journal: Annals of Oncology (2021)
1500P Health-related quality of life in melanoma patients treated with neoadjuvant nivolumab and domatinostat: Preliminary results
Authors: N.M.J. Van Den Heuvel, I.L.M. Reijers, J.M. Versluis, A.M. Menzies, J.M. Kieffer, N. Kapsali, M.W.J.M. Wouters, R.P.M. Saw, W.M.C. Klop, T.E. Pennington, M.J.C. Gregorio, A.J. Colebatch, A.J. Spillane, B.A. van de Wiel, R.A. Scolyer, A.C.J. van Akkooi, L.V. Van De Poll-Franse, G.V. Long, C.U. Blank, A.H. Boekhout
Journal: Annals of Oncology (2021)
Different dose regimens of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373) in younger and older adults: A phase 2 randomized placebo-controlled trial
Authors: Neil Formica, Raburn Mallory, Gary Albert, Michelle Robinson, Joyce S. Plested, Iksung Cho, Andreana Robertson, Filip Dubovsky, Gregory M. Glenn
Journal: PLoS Medicine (2021)

Background NVX-CoV2373 is a recombinant severe acute respiratory coronavirus 2 (rSARS-CoV-2) nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins and Matrix-M1 adjuvant. Methods and findings The phase 2 component of our randomized, placebo-controlled, phase 1 to 2 trial was designed to identify which dosing regimen of NVX-CoV2373 should move forward into late-phase studies and was based on immunogenicity and safety data through Day 35 (14 days after the second dose). The trial was conducted at 9 sites in Australia and 8 sites in the United States. Participants in 2 age groups (aged 18 to 59 and 60 to 84 years) were randomly assigned to receive either 1 or 2 intramuscular doses of 5-μg or 25-μg NVX-CoV2373 or placebo, 21 days apart. Primary endpoints were immunoglobulin G (IgG) anti-spike protein response, 7-day solicited reactogenicity, and unsolicited adverse events. A key secondary endpoint was wild-type virus neutralizing antibody response. After enrollment, 1,288 participants were randomly assigned to 1 of 4 vaccine groups or placebo, with 1,283 participants administered at least 1 study treatment. Of these, 45% were older participants 60 to 84 years. Reactogenicity was predominantly mild to moderate in severity and of short duration (median &lt;3 days) after first and second vaccination with NVX-CoV2373, with higher frequencies and intensity after second vaccination and with the higher dose. Reactogenicity occurred less frequently and was of lower intensity in older participants. Both 2-dose regimens of 5-μg and 25-μg NVX-CoV2373 induced robust immune responses in younger and older participants. For the 2-dose regimen of 5 μg, geometric mean titers (GMTs) for IgG anti-spike protein were 65,019 (95% confidence interval (CI) 55,485 to 76,192) and 28,137 (95% CI 21,617 to 36,623) EU/mL and for wild-type virus neutralizing antibody (with an inhibitory concentration of 50%—MN 50% ) were 2,201 (95% CI 1,343 to 3,608) and 981 (95% CI 560 to 1,717) titers for younger and older participants, respectively, with seroconversion rates of 100% in both age groups. Neutralizing antibody responses exceeded those seen in a panel of convalescent sera for both age groups. Study limitations include the relatively short duration of safety follow-up to date and current lack of immune persistence data beyond the primary vaccination regimen time point assessments, but these data will accumulate over time. Conclusions The study confirmed the phase 1 findings that the 2-dose regimen of 5-μg NVX-CoV2373 is highly immunogenic and well tolerated in younger adults. In addition, in older adults, the 2-dose regimen of 5 μg was also well tolerated and showed sufficient immunogenicity to support its use in late-phase efficacy studies. Trial registration ClinicalTrials.gov NCT04368988 .
Single-nucleus transcriptome analysis reveals cell-type-specific molecular signatures across reward circuitry in the human brain
Authors: Matthew N. Tran, Kristen R. Maynard, Abby Spangler, Louise A. Huuki, Kelsey D. Montgomery, Vijay Sadashivaiah, Madhavi Tippani, Brianna K. Barry, Dana B. Hancock, Stephanie C. Hicks, Joel E. Kleinman, Thomas M. Hyde, Leonardo Collado-Torres, Andrew E. Jaffe, Keri Martinowich
Journal: Neuron (2021)
Association of blood trihalomethane concentrations with asthma in US adolescents: nationally representative cross-sectional study
Authors: Yang Sun, Peng-Fei Xia, Jing Xie, Vicente Mustieles, Yu Zhang, Yi-Xin Wang, Carmen Messerlian
Journal: European Respiratory Journal (2021)

Background Population studies show that the use of swimming pools is associated with the risk of asthma and allergic diseases among children. Our objective was to explore the associations between blood trihalomethane (THM) concentrations and asthma among US adolescents, and assess to what extent the association is modified by active tobacco smoke exposure. Methods We included 2359 adolescents aged 12–19 years with measured blood concentrations of chloroform (trichloromethane (TCM)), bromodichloromethane (BDCM), dibromochloromethane (DBCM) and bromoform (tribromomethane (TBM)) from the National Health and Nutrition Examination Survey 2005–2012. Logistic regression models were fitted to assess the odds ratios for the association of blood THM concentrations (three or four categories) with the risk of self-reported current and ever (lifetime) asthma. Results Blood DBCM concentrations were associated with a higher risk of ever asthma among all adolescents (OR 1.54 (95% CI 1.07–2.21), comparing the extreme exposure categories). The relationship was stronger among adolescents exposed to tobacco smoke (OR 3.96 (95% CI 1.89–8.30), comparing the extreme exposure categories). We also found positive relationships between blood brominated THM concentrations (sum of BDCM, DBCM and TBM) and risk of ever asthma and between blood DBCM and brominated THM concentrations and risk of current asthma among adolescents with tobacco smoke exposure. The relative excess risk of ever asthma due to the interaction between high blood DBCM and brominated THM concentrations and tobacco smoke exposure was 1.87 (95% CI 0.30–3.43) and 0.78 (95% CI 0.07–1.49), respectively. Conclusions Exposure to THMs is associated with a higher risk of asthma in adolescents, particularly among those exposed to tobacco smoke.
242P Impact of metastases directed radiation therapy on CDK4/6 inhibitors treatment for metastatic breast cancer
Authors: I. Meattini, L. Visani, I. Ratosa, C. Saieva, D. Ribnikar, E. Scoccimarro, C. Becherini, M. Orazem, G. Stocchi, C. Bellini, V. Lorenzetti, C. Orsatti, L. Angelini, I. Desideri, V. Scotti, A. Morandi, T. Marinko, L. Livi
Journal: Annals of Oncology (2021)
Occupational risk of COVID-19 in the first versus second epidemic wave in Norway, 2020
Authors: Karin Magnusson, Karin Nygård, Fredrik Methi, Line Vold, Kjetil Telle
Journal: Eurosurveillance (2021)

BackgroundThe occupational risk of COVID-19 may be different in the first versus second epidemic wave.AimTo study whether employees in occupations that typically entail close contact with others were at higher risk of SARS-CoV-2 infection and COVID-19-related hospitalisation during the first and second epidemic wave before and after 18 July 2020, in Norway.MethodsWe included individuals in occupations working with patients, children, students, or customers using Standard Classification of Occupations (ISCO-08) codes. We compared residents (3,559,694 on 1 January 2020) in such occupations aged 20-70 years (mean: 44.1; standard deviation: 14.3 years; 51% men) to age-matched individuals in other professions using logistic regression adjusted for age, sex, birth country and marital status.ResultsNurses, physicians, dentists and physiotherapists had 2-3.5 times the odds of COVID-19 during the first wave when compared with others of working age. In the second wave, bartenders, waiters, food counter attendants, transport conductors, travel stewards, childcare workers, preschool and primary school teachers had ca 1.25-2 times the odds of infection. Bus, tram and taxi drivers had an increased odds of infection in both waves (odds ratio: 1.2-2.1). Occupation was of limited relevance for the odds of severe infection, here studied as hospitalisation with the disease.ConclusionOur findings from the entire Norwegian population may be of relevance to national and regional authorities in handling the epidemic. Also, we provide a knowledge foundation for more targeted future studies of lockdowns and disease control measures.
LBA38 Bexmarilimab, a novel macrophage re-programmer shows promising anti-tumour activity in phase I/II trial in several last line solid tumour types
Authors: P. Bono, A. Minchom, S. Shetty, Y.T. Ma, R. Cruz, M.J.A. de Jonge, C. Yap, A. Pasanen, T. Skytta, S.M.E. Iivanainen, L. Verlingue, P. Jaakkola, M.J. de Miguel, S. Arora, D. Graham, S. Jalkanen, M. Hollmen, J. Mandelin, M.K. Karvonen, T. Kauko, J.P. Koivunen
Journal: Annals of Oncology (2021)
Immunomodulatory effects exerted by extracellular vesicles from Staphylococcus epidermidis and Staphylococcus aureus isolated from bone-anchored prostheses
Authors: Magdalena Zaborowska, Forugh Vazirisani, Furqan A. Shah, Rininta Firdaus, Omar Omar, Karin Ekström, Margarita Trobos, Peter Thomsen
Journal: Biomaterials (2021)

Staphylococcus aureus and Staphylococcus epidermidis are the bacteria that most frequently cause osteomyelitis. This study aimed to determine whether staphylococci isolated from osteomyelitis associated with septic loosening of orthopedic prostheses release extracellular vesicles (EVs) and, if so, to determine tentative immunomodulatory effects on the human monocytic cell line THP-1. EVs were isolated from bacterial cultures using filtration and ultracentrifugation and characterized by scanning electron microscopy, nanoparticle tracking analysis and Western Blot. The cytotoxic effect of EVs was analyzed by NucleoCounter and lactate dehydrogenase (LDH) analyses. Confocal laser scanning microscopy was employed to visualize the uptake of EVs by THP-1 cells. Activation of the transcription factor nuclear factor-κB (NF-κB) was determined in THP1-Blue™ NF-κB cells, and the gene expression and secretion of cytokines were determined by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. All investigated strains, irrespective of their biofilm formation ability, were able to secrete EVs in vitro. The S. aureus strains produced significantly more EVs than the S. epidermidis strains. Both S. aureus-derived EVs and S. epidermidis-derived EVs were internalized by THP-1 cells, upregulated Toll-like receptor 3 (TLR3) gene expression, activated NF-κB, and promoted the gene expression and secretion of interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, matrix metallopeptidase (MMP)-9 and IL-10. Whereas EVs from both staphylococcal species upregulated the proapoptotic DNA damage-inducible transcript 4 (DDIT4) gene and downregulated the antiapoptotic B-cell lymphoma 2 (Bcl-2) gene, cytolysis was preferentially induced in S. aureus EV-stimulated cells, possibly related to the expression of cytolytic proteins predominantly in S. aureus EVs. In conclusion, staphylococcal EVs possess potent cytolytic and immunomodulatory properties.