tbuckley/cabot-search huggingface dataset:
1661P Antitumor efficacy and immune profiling of the mouse ortholog of nemvaleukin alfa, a novel engineered IL-2 fusion protein, in an orthotopic mouse model of small cell lung cancer alone or in combination with standard chemotherapy
Authors: Y. Pan, H. Zhang, T. Chen, H. Ding, H. Han, C. Almonte, K.E. Labbe, S. Nguyen, J.E. Lopes, H.C. Losey, R.J. Winquist, K-K. Wong
Journal: Annals of Oncology (2021)
Music as social bonding: A cross-cultural perspective
Authors: Ivan Yifan Zou, William S.-Y. Wang
Journal: Behavioral and Brain Sciences (2021)

We extend Savage et al.'s music and social bonding hypothesis by examining it in the context of Chinese music. First, top-down functions such as music as political instrument should receive more attention. Second, solo performance can serve as important cues for social identity. Third, a right match between the tones in lyrics and music contributes also to social bonding.
709P Serial circulating tumor (ct)-DNA alterations using amplicon-based next-generation sequencing (NGS) to identify resistance mechanisms to immune checkpoint inhibitors (ICIs) for metastatic urothelial carcinoma (mUC)
Authors: P. Ravi, A. Ravi, I. Bin Riaz, D. Freeman, C. Curran, C. Mantia, B.A. McGregor, K. Kilbridge, C-X. Pan, M. Pek, Y. Choudhury, N. Corsaro, M-H. Tan, G.P. Sonpavde
Journal: Annals of Oncology (2021)
Multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine in patients with post-resection melanoma at high risk of recurrence
Authors: Craig L Slingluff, Karl D Lewis, Robert Andtbacka, John Hyngstrom, Mohammed Milhem, Svetomir N Markovic, Tawnya Bowles, Omid Hamid, Leonel Hernandez-Aya, Joel Claveau, Sekwon Jang, Prejesh Philips, Shernan G Holtan, Montaser F Shaheen, Brendan Curti, William Schmidt, Marcus O Butler, Juan Paramo, Jose Lutzky, Arvinda Padmanabhan, Sajeve Thomas, Daniel Milton, Andrew Pecora, Takami Sato, Eddy Hsueh, Suprith Badarinath, John Keech, Sujith Kalmadi, Pallavi Kumar, Robert Weber, Edward Levine, Adam Berger, Anna Bar, J Thaddeus Beck, Jeffrey B Travers, Catalin Mihalcioiu, Brian Gastman, Peter Beitsch, Suthee Rapisuwon, John Glaspy, Edward C McCarron, Vinay Gupta, Deepti Behl, Brent Blumenstein, Joanna J Peterkin
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Most patients with advanced melanomas relapse after checkpoint blockade therapy. Thus, immunotherapies are needed that can be applied safely early, in the adjuvant setting. Seviprotimut-L is a vaccine containing human melanoma antigens, plus alum. To assess the efficacy of seviprotimut-L, the Melanoma Antigen Vaccine Immunotherapy Study (MAVIS) was initiated as a three-part multicenter, double-blind, placebo-controlled phase III trial. Results from part B1 are reported here. Methods Patients with AJCC V.7 stage IIB-III cutaneous melanoma after resection were randomized 2:1, with stage stratification (IIB/C, IIIA, IIIB/C), to seviprotimut-L 40 mcg or placebo. Recurrence-free survival (RFS) was the primary endpoint. For an hypothesized HR of 0.625, one-sided alpha of 0.10, and power 80%, target enrollment was 325 patients. Results For randomized patients (n=347), arms were well-balanced, and treatment-emergent adverse events were similar for seviprotimut-L and placebo. For the primary intent-to-treat endpoint of RFS, the estimated HR was 0.881 (95% CI: 0.629 to 1.233), with stratified logrank p=0.46. However, estimated HRs were not uniform over the stage randomized strata, with HRs (95% CIs) for stages IIB/IIC, IIIA, IIIB/IIIC of 0.67 (95% CI: 0.37 to 1.19), 0.72 (95% CI: 0.35 to 1.50), and 1.19 (95% CI: 0.72 to 1.97), respectively. In the stage IIB/IIC stratum, the effect on RFS was greatest for patients &lt;60 years old (HR=0.324 (95% CI: 0.121 to 0.864)) and those with ulcerated primary melanomas (HR=0.493 (95% CI: 0.255 to 0.952)). Conclusions Seviprotimut-L is very well tolerated. Exploratory efficacy model estimation supports further study in stage IIB/IIC patients, especially younger patients and those with ulcerated melanomas. Trial registration number NCT01546571 .
Rammya Mathew: Climate action will require radical reform of how we practise medicine
Authors: Rammya Mathew
Journal: BMJ (2021)

In 2020 the NHS adopted a multi-year plan to become the world's first carbon net zero national health system. 1 Simon Stevens, then chief of NHS England, said that "it's not enough for the NHS to treat the problems caused by air pollution and climate change-we need to play our part in tackling them at source.
607P Impact of docetaxel on quality of life (QoL) in elderly and non-elderly metastatic castration-resistant prostate cancer (mCRPC) patients (Pts)
Authors: S. Rubio-Novella, Á. Montes, I. Paredero Perez, R. Lozano Mejorada, N. Romero Laorden, E. Castro, A. Sanchez Hernandez, D. Olmos, D. Lorente Estelles
Journal: Annals of Oncology (2021)
Ecological and psychological factors in the cultural evolution of music
Authors: Thom Scott-Phillips, Atsuko Tominaga, Helena Miton
Journal: Behavioral and Brain Sciences (2021)

Abstract The two target articles agree that processes of cultural evolution generate richness and diversity in music, but neither address this question in a focused way. We sketch one way to proceed – and hence suggest how the target articles differ not only in empirical claims, but also in their tacit, prior assumptions about the relationship between cognition and culture.
The zinc finger and BTB domain containing protein ZBTB20 regulates plasma triglyceride metabolism by repressing lipoprotein lipase gene transcription in hepatocytes
Authors: Hao Li, Gan Liu, Xiaoqing Wan, Luting Zhou, Zhen‐Bang Qin, Xian‐Hua Ma, Kai Su, Ya‐Jin Liu, Jinghao Yuan, Chun‐Chun Wei, An‐Jing Ren, Yu‐Xia Chen, Stephen G. Young, Hai Zhang, Zhifang Xie, Weiping J. Zhang
Journal: Hepatology (2021)

Abstract Background and Aims Lipoprotein lipase (LPL) is responsible for the lipolytic processing of triglyceride‐rich lipoproteins, the deficiency of which causes severe hypertriglyceridemia. Liver LPL expression is high in suckling rodents but relatively low at adulthood. However, the regulatory mechanism and functional significance of liver LPL expression are incompletely understood. We have established the zinc finger protein ZBTB20 as a critical factor for hepatic lipogenesis. Here, we evaluated the role of ZBTB20 in regulating liver Lpl gene transcription and plasma triglyceride metabolism. Approach and Results Hepatocyte‐specific inactivation of ZBTB20 in mice led to a remarkable increase in LPL expression at the mRNA and protein levels in adult liver, in which LPL protein was mainly localized onto sinusoidal epithelial cells and Kupffer cells. As a result, the LPL activity in postheparin plasma was substantially increased, and postprandial plasma triglyceride clearance was significantly enhanced, whereas plasma triglyceride levels were decreased. The dysregulated liver LPL expression and low plasma triglyceride levels in ZBTB20‐deficient mice were normalized by inactivating hepatic LPL expression. ZBTB20 deficiency protected the mice against high‐fat diet–induced hyperlipidemia without causing excessive triglyceride accumulation in the liver. Chromatin immunoprecipitation and gel‐shift assay studies revealed that ZBTB20 binds to the LPL promoter in the liver. A luciferase reporter assay revealed that ZBTB20 inhibits the transcriptional activity of LPL promoter. The regulation of LPL expression by ZBTB20 is liver‐specific under physiological conditions. Conclusions Liver ZBTB20 serves as a key regulator of LPL expression and plasma triglyceride metabolism and could be a therapeutic target for hypertriglyceridemia.
Author Correction: Selenium–GPX4 axis protects follicular helper T cells from ferroptosis
Authors: Yin Yao, Zhian Chen, Hao Zhang, Cailing Chen, Ming Zeng, Joseph Yunis, Yunbo Wei, Yanmin Wan, Naiqi Wang, Mingzhe Zhou, Chao Qiu, Qunxiong Zeng, Hong Sheng Ong, Hao Wang, Fadzai Victor Makota, Yang Yang, Zhaohui Yang, Nan Wang, Jun Deng, Chao Shen, Yan Xia, Lin Yuan, Zhaoqin Lian, Yike Deng, Cuilian Guo, Ao Huang, Pengcheng Zhou, Haibo Shi, Weitian Zhang, Hongliang Yi, Dongmei Li, Ming Xia, Jing Fu, Ning Wu, Judy B. de Haan, Nan Shen, Wenhong Zhang, Zheng Liu, Di Yu
Journal: Nature Immunology (2021)
An inducible p21-Cre mouse model to monitor and manipulate p21-highly-expressing senescent cells in vivo
Authors: Binsheng Wang, Lichao Wang, Nathan S. Gasek, Yueying Zhou, Taewan Kim, Chun Guo, Evan R. Jellison, Laura Haynes, Sumit Yadav, Tamar Tchkonia, George A. Kuchel, James L. Kirkland, Ming Xu
Journal: Nature Aging (2021)
Long waits for NHS treatment are forcing patients to go private, warns Labour
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Growing waiting lists for NHS treatment are forcing more people to pay thousands of pounds for private treatment and creating a two tier health system, the Labour Party has warned.

In a keynote speech to the party’s annual conference in Brighton on 28 September, Labour’s shadow health secretary, Jonathan Ashworth, accused the government of failing to put in place plans to reduce NHS waiting times or fix the crisis in social care.

He praised the work of “an understaffed NHS,” which he acknowledged had been “pushed to the brink” by 18 months of the pandemic, but he underlined that the service pressures predated covid.

He said, “We entered the pandemic with the longest financial squeeze in NHS history, 17 000 beds closed, hospitals crumbling, public health services cut, GP numbers down, services privatised, nurse …
Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer: Results of cohort 6 of the COSMIC-021 study.
Authors: Neeraj Agarwal, Yohann Loriot, Bradley Alexander McGregor, Robert Dreicer, Tanya B. Dorff, Benjamin Louis Maughan, William Kevin Kelly, Lance C. Pagliaro, Sandy Srinivas, Christian Michael Squillante, Ulka N. Vaishampayan, Evelyn W. Wang, Dominic Curran, Toni K. Choueiri, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2020)

5564 Background: Cabozantinib (C) may enhance response to immune checkpoint inhibitors (ICIs) by promoting an immune-permissive microenvironment and has shown encouraging activity in combination with ICIs in tumor types including RCC and HCC. C and atezolizumab (A) have shown low objective response rates as monotherapy in metastatic castration-resistant prostate cancer (mCRPC) (Smith JCO 2012; Kim JCO 2018). COSMIC-021 (NCT03170960), a multinational phase 1b study, is evaluating the combination of C + A in various solid tumors. We report results for Cohort 6 in mCRPC. Methods: Eligible patients (pts) were required to have radiographic progression in soft tissue after enzalutamide and/or abiraterone, measurable disease, and an ECOG PS of 0 or 1. Prior chemotherapy for mCSPC was permitted. Pts received C 40 mg PO QD and A 1200 mg IV Q3W. CT/MRI scans were performed Q6W for the first year and Q12W thereafter. The primary endpoint is ORR per RECIST 1.1. Other endpoints include safety, ORR per irRECIST, duration of response (DOR), PFS, and OS. Results are presented for the first 44 pts enrolled. Results: Median follow-up as of Dec 20, 2019 was 12.6 mo (range 5, 20) for the 44 mCRPC pts. Median age was 70 y (range 49, 90), 50% had ECOG PS 1, 34% had visceral metastases, and 61% had extrapelvic lymph node metastases. 27% had prior docetaxel and 52% had 2 prior novel hormonal therapies. The most common any grade treatment-related adverse events (TRAEs) were fatigue (50%), nausea (43%), decreased appetite (39%), diarrhea (39%), dysgeusia (34%), and PPE (32%). One grade 5 TRAE of dehydration was reported in a 90 y/o. Median duration of treatment was 6.3 mo. ORR per RECIST 1.1 among all 44 pts was 32% (2 CRs [4.5%] and 12 PRs [27%]); 21 (48%) pts had SD resulting in a disease control rate of 80% in all pts. One pt with PD per RECIST 1.1 had an irPR per irRECIST. ORR per RECIST 1.1 was 33% in 36 pts with high-risk disease (visceral and/or extrapelvic lymph node metastases). Median DOR for all pts with response per RECIST 1.1 was 8.3 mo (range 2.8, 9.8+). 17 (50%) of 34 pts with post-baseline PSA evaluation had a decrease in PSA. In 12 responders with post-baseline PSA evaluation, 8 (67%) had a PSA decrease ≥50%. Tumor PD-L1 expression will also be reported. Conclusions: The combination of C + A had a tolerable safety profile and demonstrated clinically meaningful activity with durable responses in men with mCRPC. Given the encouraging activity in these pts, especially in those with high-risk disease, further evaluation of C + A in men with mCRPC is being pursued. Clinical trial information: NCT03170960 .
Delayed Kinetics of IgG, but Not IgA, Antispike Antibodies in Transplant Recipients following SARS-CoV-2 Infection
Authors: Paolo Cravedi, Patrick Ahearn, Lin Wang, Tanuja Yalamarti, Susan Hartzell, Yorg Azzi, Madhav C. Menon, Aditya Jain, Marzuq Billah, Marcelo Fernandez-Vina, Howard M. Gebel, E. Steve Woodle, Natalie S. Haddad, Andrea Morrison-Porter, F. Eun-Hyung Lee, Ignacio Sanz, Enver Akalin, Alin Girnita, Jonathan S. Maltzman
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement Analyses of the incidence, relative kinetics, and spectrum of anti–SARS-CoV-2 antibodies in kidney transplant recipients are not as detailed as they are for immunocompetent controls. In this multicenter, cross-sectional study of 49 kidney transplant recipients with PCR-confirmed SARS-CoV-2 infection, we found that anti–SARS-CoV-2 IgG production is delayed but that IgM and IgA responses are similar compared with those observed in immunocompetent controls. Therefore, antiviral humoral immunity is delayed but preserved in kidney transplant recipients. This finding is important in understanding the immune response against SARS-CoV-2 in patients on chronic immunosuppression and may provide insights into devising strategies to monitor antibody responses to infection and vaccination. Background Kidney transplant recipients are at increased risk of severe outcomes during COVID-19. Antibodies against the virus are thought to offer protection, but a thorough characterization of anti–SARS-CoV-2 immune globulin isotypes in kidney transplant recipients following SARS-CoV-2 infection has not been reported. Methods We performed a cross-sectional study of 49 kidney transplant recipients and 42 immunocompetent controls at early (≤14 days) or late (&gt;14 days) time points after documented SARS-CoV-2 infection. Using a validated semiquantitative Luminex-based multiplex assay, we determined the abundances of IgM, IgG, IgG1–4, and IgA antibodies against five distinct viral epitopes. Results Kidney transplant recipients showed lower levels of total IgG antitrimeric spike (S), S1, S2, and receptor binding domain (RBD) but not nucleocapsid (NC) at early versus late time points after SARS-CoV-2 infection. Early levels of IgG antispike protein epitopes were also lower than in immunocompetent controls. Anti–SARS-CoV-2 antibodies were predominantly IgG1 and IgG3, with modest class switching to IgG2 or IgG4 in either cohort. Later levels of IgG antispike, S1, S2, RBD, and NC did not significantly differ between cohorts. There was no significant difference in the kinetics of either IgM or IgA antispike, S1, RBD, or S2 on the basis of timing after diagnosis or transplant status. Conclusions Kidney transplant recipients mount early anti–SARS-CoV-2 IgA and IgM responses, whereas IgG responses are delayed compared with immunocompetent individuals. These findings might explain the poor outcomes in transplant recipients with COVID-19. Podcast This article contains a podcast athttps://www.asn-online.org/media/podcast/JASN/2021_11_23_briggsgriffin112321.mp3
Biologically active lipids in the regulation of lymphangiogenesis in disease states
Authors: Masataka Majima, Kanako Hosono, Yoshiya Ito, Hideki Amano
Journal: Pharmacology & Therapeutics (2021)

Lymphatic vessels have crucial roles in the regulation of interstitial fluids, immune surveillance, and the absorption of dietary fat in the intestine. Lymphatic function is also closely related to the pathogenesis of various disease states such as inflammation, lymphedema, endometriosis, liver dysfunction, and tumor metastasis. Lymphangiogenesis, the formation of new lymphatic vessels from pre-existing lymphatic vessels, is a critical determinant in the above conditions. Although the effect of growth factors on lymphangiogenesis is well-characterized, and biologically active lipids are known to affect smooth muscle contractility and vasoaction, there is accumulating evidence that biologically active lipids are also important inducers of growth factors and cytokines that regulate lymphangiogenesis. This review discusses recent advances in our understanding of biologically active lipids, including arachidonic acid metabolites, sphingosine 1-phosphate, and lysophosphatidic acid, as regulators of lymphangiogenesis, and the emerging importance of the lymphangiogenesis as a therapeutic target.
Abstract 11153: 8-Hydroxyeicosapentaenoic AcidConcentrated Materials From Pacific Krill Suppresses Atherosclerosis in Apolipoprotein E-deficient Mice
Authors: Masamichi Hirose, Miho Ibi, Maki Saito, Nanae Ishida
Journal: Circulation (2019)

Introduction: Cardiovascular diseases are the leading cause of death in the world and are generally associated with atherosclerosis. N-3 polyunsaturated fatty acids including eicosapentaenoic acid ...
同所性乳癌を完全に根絶し,転移を阻害するナノ光線療法によるROS誘導増感放射線療法からの新しい併用療法【JST・京大機械翻訳】
Authors: Liu Te-I, Lu Ting-Yu, Yang Ying-Chieh, Chang Siou-Han, Chen Hsin-Hung, Lu I.-Lin, Sabu Arjun, Chiu Hsin-Cheng
Journal: Biomaterials (2020)
1442O Proactive early palliative care referral for cancer patients in the intensive care unit: Implementing a novel “triggers” checklist
Authors: P. Srivastava, H. May-Miller, J-A. Gilroy, K. Blackie, D. Worku, N. Siddiqui, A. Tweddle, J.M. Droney, P. Gruber
Journal: Annals of Oncology (2021)
춘계학술대회 : 구연 ; 간경변증 : 자발성세균성복막염으로 입원한 간경변증 환자의 임상양상
Authors: 서연석, 엄순호, 임형준, 조몽, 허정, 박상훈, 한태호, 한광엽, 안상훈, 이현웅, 백순구, 김문영, 김홍수, 김병익, 황상준, 조세현
Journal: Clinical and Molecular Hepatology (2007)
Single-cell RNA sequencing reveals markers of disease progression in primary cutaneous T-cell lymphoma
Authors: Katharina Rindler, Constanze Jonak, Natalia Alkon, Felix M. Thaler, Harald Kurz, Lisa E. Shaw, Georg Stingl, Wolfgang Weninger, Florian Halbritter, Wolfgang M. Bauer, Matthias Farlik, Patrick M. Brunner
Journal: Molecular Cancer (2021)

Abstract Background In early-stage mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, limited skin involvement with patches and plaques is associated with a favorable prognosis. Nevertheless, approximately 20–30% of cases progress to tumors or erythroderma, resulting in poor outcome. At present, factors contributing to this switch from indolent to aggressive disease are only insufficiently understood. Methods In patients with advanced-stage MF, we compared patches with longstanding history to newly developed plaques and tumors by using single-cell RNA sequencing, and compared results with early-stage MF as well as nonlesional MF and healthy control skin. Results Despite considerable inter-individual variability, lesion progression was uniformly associated with downregulation of the tissue residency markers CXCR4 and CD69 , the heat shock protein HSPA1A , the tumor suppressors and immunoregulatory mediators ZFP36 and TXNIP , and the interleukin 7 receptor ( IL7R) within the malignant clone, but not in benign T cells. This phenomenon was not only found in conventional TCR-αβ MF, but also in a case of TCR-γδ MF, suggesting a common mechanism across MF subtypes. Conversely, malignant cells in clinically unaffected skin from MF patients showed upregulation of these markers. Conclusions Our data reveal a specific panel of biomarkers that might be used for monitoring MF disease progression. Altered expression of these genes may underlie the switch in clinical phenotype observed in advanced-stage MF.
Insulin Pump Use and Diabetic Retinopathy—Is Technology the Key to Preventing Retinopathy in Young People With Type 1 Diabetes?
Authors: Martin de Bock, Claudia Swan, Alistair J. Gunn
Journal: JAMA Network Open (2021)

Michael L. Ferm, MD; Daniel J. DeSalvo, MD; Laura M. Prichett, PhD; James K. Sickler, BS; Risa M. Wolf, MD; Roomasa Channa, MD
712P Analysis of fibroblast growth factor receptor 3 aberrations in bladder cancer, for enabling personalized and effective therapy based on FGFR inhibitor
Authors: R. Sosnowski, D. Popiel, P. Gapska, M. Skupińska, P. Stajno, M. Sobieszek-Prochorec, M. Ligaj, T. Demkow, A. Stańczak, M. Wieczorek, J. Pieczykolan
Journal: Annals of Oncology (2021)
461P Molecular tumor profiling and matched molecular targeted treatment in metastatic young-onset colorectal cancer (YOCR)
Authors: I. Baraibar Argota, J. Ros, R. Comas, S. Aguilar, F. Salva, A. Garcia, J.L. Cuadra Urteaga, N. Saoudi Gonzalez, N. Mulet Margalef, J. Hernando, J. Capdevila, M. Martí, E. Espín, E. Garralda, P. Nuciforo, R. Dienstmann, A. Vivancos, J. Tabernero, M.E. Elez Fernandez
Journal: Annals of Oncology (2021)
MicroRNA-34c-5p provokes isoprenaline-induced cardiac hypertrophy by modulating autophagy via targeting ATG4B
Authors: Yuhong Zhang, Yanqing Ding, Min Li, Jing Yuan, Youhui Yu, Xueying Bi, Huiqi Hong, Jiantao Ye, Peiqing Liu
Journal: Acta Pharmaceutica Sinica B (2021)

Pathological cardiac hypertrophy serves as a significant foundation for cardiac dysfunction and heart failure. Recently, growing evidence has revealed that microRNAs (miRNAs) play multiple roles in biological processes and participate in cardiovascular diseases. In the present research, we investigate the impact of miRNA-34c-5p on cardiac hypertrophy and the mechanism involved. The expression of miR-34c-5p was proved to be elevated in heart tissues from isoprenaline (ISO)-infused mice. ISO also promoted miR-34c-5p level in primary cultures of neonatal rat cardiomyocytes (NRCMs). Transfection with miR-34c-5p mimic enhanced cell surface area and expression levels of foetal-type genes atrial natriuretic factor (Anf) and β-myosin heavy chain (β-Mhc) in NRCMs. In contrast, treatment with miR-34c-5p inhibitor attenuated ISO-induced hypertrophic responses. Enforced expression of miR-34c-5p by tail intravenous injection of its agomir led to cardiac dysfunction and hypertrophy in mice, whereas inhibiting miR-34c-5p by specific antagomir could protect the animals against ISO-triggered hypertrophic abnormalities. Mechanistically, miR-34c-5p suppressed autophagic flux in cardiomyocytes, which contributed to the development of hypertrophy. Furthermore, the autophagy-related gene 4B (ATG4B) was identified as a direct target of miR-34c-5p, and miR-34c-5p was certified to interact with 3' untranslated region of Atg4b mRNA by dual-luciferase reporter assay. miR-34c-5p reduced the expression of ATG4B, thereby resulting in decreased autophagy activity and induction of hypertrophy. Inhibition of miR-34c-5p abolished the detrimental effects of ISO by restoring ATG4B and increasing autophagy. In conclusion, our findings illuminate that miR-34c-5p participates in ISO-induced cardiac hypertrophy, at least partly through suppressing ATG4B and autophagy. It suggests that regulation of miR-34c-5p may offer a new way for handling hypertrophy-related cardiac dysfunction.