tbuckley/cabot-search huggingface dataset:
A Pan-cancer Clinical Study of Personalized Neoantigen Vaccine Monotherapy in Treating Patients with Various Types of Advanced Solid Tumors
Authors: Yong Fang, Fan Mo, Jiawei Shou, Huimin Wang, Kai Luo, Shanshan Zhang, Ning Han, Hongsen Li, Shengli Ye, Zhan Zhou, Rongchang Chen, Lin Chen, Liang Liu, Huina Wang, Hongming Pan, Shuqing Chen
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Because of their high tumor specificity and immunogenicity, neoantigens have been considered as ultimate targets for cancer immunotherapy. Neoantigen-based vaccines have demonstrated promising efficacy for several cancer types. To further investigate the antitumor potentials for other types of solid tumors, we designed a peptide-based neoantigen vaccine, iNeo-Vac-P01, and conducted a single-arm, open-labeled, investigator-initiated clinical trial (NCT03662815). Patients and Methods: Personalized neoantigen vaccines were designed and manufactured according to our bioinformatics analysis results from the whole-exome sequencing of tumor and peripheral blood cell DNAs. Patients were scheduled to be vaccinated subcutaneously with adjuvant on days 1, 4, 8, 15, and 22 (prime phase), and days 78 and 162 (boost phase). Additional immunizations were administrated every 2–3 months as per patient's potential benefit. The safety and efficacy were assessed through adverse events (AE), progression-free survival (PFS), overall survival (OS), and other parameters. Results: Of the 22 patients enrolled with advanced malignancies, 20 had no or mild AEs, while 2 had grade 3 or 4 acute allergic reactions only after their sixth boost vaccination. The disease control rate was 71.4%. The median PFS was 4.6 months, whereas the median OS was not reached (12-month OS = 55.1%). Around 80% of individual peptides or peptide pools elicited measurable specific immune response. In addition, our findings revealed several potential biomarkers for the prediction of better response. Conclusions: iNeo-Vac-P01 as monotherapy is feasible and safe for patients with advanced solid tumors. It could elicit T-cell–mediated immune response targeting tumor neoantigens, and might have promising antitumor efficacy. See related commentary by Filderman and Storkus, p. 4429
Surveillance to Track Progress Toward Polio Eradication — Worldwide, 2018–2019
Authors: Jacquelyn S. Lickness, Tracie Gardner, Ousmane M. Diop, Smita Chavan, Jaume Jorba, Jamal Ahmed, Nicksy Gumede, Ticha Johnson, Obaid Butt, Humayun Asghar, Eugene Saxentoff, Varja Grabovac, Tigran Avagyan, Sudhir Joshi, Gloria Rey-Benito, Jane Iber, Elizabeth Henderson, Steven G.F. Wassilak, Abhijeet Anand
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Since the Global Polio Eradication Initiative (GPEI) was launched in 1988, the number of polio cases worldwide has declined approximately 99.99%; only two countries (Afghanistan and Pakistan) have never interrupted wild poliovirus (WPV) transmission (1). The primary means of detecting poliovirus circulation is through surveillance for acute flaccid paralysis (AFP) among children aged <15 years with testing of stool specimens for WPV and vaccine-derived polioviruses (VDPVs) (genetically reverted strains of the vaccine virus that regain neurovirulence) in World Health Organization (WHO)-accredited laboratories (2,3). In many locations, AFP surveillance is supplemented by environmental surveillance, the regular collection and testing of sewage to provide awareness of the extent and duration of poliovirus circulation (3). This report presents 2018-2019 poliovirus surveillance data, focusing on 40 priority countries* with WPV or VDPV outbreaks or at high risk for importation because of their proximity to a country with an outbreak. The number of priority countries rose from 31 in 2018 to 40 in 2019 because of a substantial increase in the number of VDPV outbreaks† (2,4). In areas with low poliovirus immunity, VDPVs can circulate in the community and cause outbreaks of paralysis; these are known as circulating vaccine derived polioviruses (cVDPVs) (4). In 2019, only 25 (63%) of the 40 designated priority countries met AFP surveillance indicators nationally; subnational surveillance performance varied widely and indicated focal weaknesses. High quality, sensitive surveillance is important to ensure timely detection and response to cVDPV and WPV transmission.
32P The neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios predict efficacy of CDK 4/6 inhibitors in women with hormone receptor-positive/HER2-negative advanced breast cancer
Authors: E. Zattarin, C. Fabbroni, F. Ligorio, F. Nichetti, R. Lobefaro, L. Rivoltini, G. Capri, G.V. Bianchi, F.G.M. De Braud, C. Vernieri
Journal: Annals of Oncology (2020)
Zeolite in tissue engineering: Opportunities and challenges
Authors: Payam Zarrintaj, Ghader Mahmodi, Saeed Manouchehri, Amin Hamed Mashhadzadeh, Mohsen Khodadadi, Morteza Servatan, Mohammad Reza Ganjali, Bruno Azambre, Seok‐Jhin Kim, Josh D Ramsey, Sajjad Habibzadeh, Mohammad Reza Saeb, Masoud Mozafari
Journal: MedComm (2020)

Abstract Tissue engineering and regenerative medicine follow a multidisciplinary attitude to the expansion and application of new materials for the treatment of different tissue defects. Typically, proper tissue regeneration is accomplished through concurrent biocompatibility and positive cellular activity. This can be resulted by the smart selection of platforms among bewildering arrays of structural possibilities with various porosity properties (ie, pore size, pore connectivity, etc). Among diverse porous structures, zeolite is known as a microporous tectosilicate that can potentially provide a biological microenvironment in tissue engineering applications. In addition, zeolite has been particularly appeared promising in wound dressing and bone‐ and tooth‐oriented scaffolds. The wide range of composition and hierarchical pore structure renders the zeolitic materials a unique character, particularly, for tissue engineering purposes. Despite such unique features, research on zeolitic platforms for tissue engineering has not been classically presented. In this review, we overview, classify, and categorize zeolitic platforms employed in biological and tissue engineering applications.
The deubiquitinating enzyme UCHL1 promotes resistance to pemetrexed in non-small cell lung cancer by upregulating thymidylate synthase
Authors: Xinyuan Ding, Yuting Gu, Min Jin, Xin Guo, Sudong Xue, Caihong Tan, Jiefang Huang, Wanlin Yang, Mingxing Xue, Qianjun Zhou, Wenjuan Wang, Yanyun Zhang
Journal: Theranostics (2020)

Rationale: Resistance to pemetrexed (PEM)-based chemotherapy is a major cause of progression in non-small cell lung cancer (NSCLC) patients. The deubiquitinating enzyme UCHL1 was recently found to play important roles in chemoresistance and tumor progression. However, the potential roles and mechanisms of UCHL1 in PEM resistance remain unclear. Methods: Bioinformatics analyses and immunohistochemistry were used to evaluate UCHL1 expression in NSCLC specimens. Kaplan-Meier analysis with the log-rank test was used for survival analyses. We established PEM-resistant NSCLC cell lines by exposing them to step-wise increases in PEM concentrations, and in vitro and in vivo assays were used to explore the roles and mechanisms of UCHL1 in PEM resistance using the NSCLC cells. Results: In chemoresistant tumors from NSCLC patients, UCHL1 was highly expressed and elevated UCHL1 expression was strongly associated with poor outcomes. Furthermore, UCHL1 expression was significantly upregulated in PEM-resistant NSCLC cells, while genetic silencing or inhibiting UCHL1 suppressed resistance to PEM and other drugs in NSCLC cells. Mechanistically, UCHL1 promoted PEM resistance in NSCLC by upregulating the expression of thymidylate synthase (TS), based on reduced TS expression after UCHL1 inhibition and re-emergence of PEM resistance upon TS restoration. Furthermore, UCHL1 upregulated TS expression, which mitigated PEM-induced DNA damage and cell cycle arrest in NSCLC cells, and also conferred resistance to PEM and other drugs. Conclusions: It appears that UCHL1 promotes PEM resistance by upregulating TS in NSCLC cells, which mitigated DNA damage and cell cycle arrest. Thus, UCHL1 may be a therapeutic target for overcoming PEM resistance in NSCLC patients.
36P Molecular subtypes in Tunisian breast cancer
Authors: M. Frikha, S. Zouari, N. Fourati, M. Kallel, F. Elloumi, M. Bahri, W. Siala, T. Boudawara, A. Khanfir, W. Mnejja, J. Daoud
Journal: Annals of Oncology (2020)
Esophageal Cancer Clinical Practice Guidelines
Authors: _ _
Journal: Journal of the National Comprehensive Cancer Network (2006)

Carcinomas originating in the upper gastrointestinal (GI) tract (esophagus, gastroesophageal junction, and stomach) constitute a worldwide major health problem. Unfortunately, esophageal carcinoma is often diagnosed late, and most therapeutic approaches are palliative, although advances have been made in staging procedures and therapy. The guidelines emphasize that palpable advances have been made in the treatment of locoregional esophageal carcinoma. Similarly, endoscopic palliation of esophageal carcinoma has improved substantially because of improving technology. For the most recent version of the guidelines, please visit NCCN.org
Translating Science on COVID-19 to Improve Clinical Care and Support the Public Health Response
Authors: Carlos del Rio, Preeti Malani
Journal: JAMA (2020)

This Viewpoint reviews progress to date on drug and vaccine development for COVID-19, antibody testing for demonstration of immunity and seroprevalence, and the continuing need for testing capacity to more precisely manage the public's health as mitigation restrictions loosen during summer 2020.
Breast Cancer–Related Lymphedema: Risk Factors, Screening, Management, and the Impact of Locoregional Treatment
Authors: Sarah A. McLaughlin, Cheryl L. Brunelle, Alphonse Taghian
Journal: Journal of Clinical Oncology (2020)

Patients fear lymphedema as an unpredictable daily reminder of breast cancer treatment. The medical community has assumed for years that the development of breast cancer–related lymphedema (BCRL) stemmed solely from the primary surgical extirpation of the axillary lymph nodes. However, contemporary data suggest that BCRL development is multifactorial, influenced by multimodality locoregional and systemic treatment strategies and perhaps by the individual patient’s ability to form collateral lymphatic pathways after injury, as well as potentially modifiable risk factors such as body mass index (BMI). Understanding the interaction between comprehensive locoregional treatment strategies and their collective impact on overall survival and long-term adverse effects such as BCRL is critical to providing patients individualized treatment recommendations. Herein, we review important factors for the development, diagnosis, prevention, and treatment of BCRL that should be considered when determining the contemporary locoregional management of breast cancer.
Comparison of haplo-SCT and chemotherapy for young adults with standard-risk Ph-negative acute lymphoblastic leukemia in CR1
Authors: Meng Lv, Qian Jiang, Dao-Bin Zhou, Yu Hu, Dai-Hong Liu, De-Pei Wu, Jing-Bo Wang, Hao Jiang, Jing Wang, Ying-jun Chang, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang
Journal: Journal of Hematology & Oncology (2020)

Abstract Human leukocyte antigen (HLA) haploidentical stem cell transplantation (haplo-SCT) as a postremission treatment for standard risk Philadelphia chromosome-negative acute lymphoblastic leukemia (SR Ph-ALL) in the first complete remission (CR1) has not been defined. In this multicenter, phase 3 study (NCT02042690), of the 131 consecutive Ph-ALL young adult patients (YA, aged 18–39 years) without high-risk features who achieved CR1, 114 patients without HLA-matched donors received consolidation with an adult chemotherapy regimen ( n = 55) or haplo-SCT ( n = 59). In the landmark analysis, haplo-SCT resulted in a lower 2-year cumulative incidence of relapse (CIR, 12.8% vs 46.7%, P = 0.0017) and superior 2-year leukemia-free survival (LFS, 80.9% vs 51.1%, P = 0.0116) and 2-year overall survival (OS, 91.2% vs 75.7 [64.8–93.2] %, P = 0.0408) than chemotherapy. In the time-dependent multivariate analysis with propensity score adjustment, postremission treatment (haplo-SCT vs chemotherapy) was an independent risk factor for the CIR (HR 0.195, 95% CI 0.076–0.499, P = 0.001), LFS (HR 0.297, 95% CI 0.131–0.675, P = 0.003), and OS (HR 0.346, 95% CI 0.140–0.853, P = 0.011). In all subgroups, CIR was lower in haplo-SCT. Myeloablative haplo-SCT with ATG+G-CSF might be one of the preferred therapies for YA patients with standard-risk Ph-ALL. Trial registration ClinicalTrials.gov . Registered on 23 January 2014, https://clinicaltrials.gov/ct2/show/NCT02042690
Single-Cell RNA Sequencing of Tumor-Infiltrating NK Cells Reveals that Inhibition of Transcription Factor HIF-1α Unleashes NK Cell Activity
Authors: Jing Ni, Xi Wang, Ana Stojanovic, Qin Zhang, Marian Wincher, Lea Bühler, Annette Arnold, Margareta P. Correia, Manuel Winkler, Philipp-Sebastian Koch, Veronika Sexl, Thomas Höfer, Adelheid Cerwenka
Journal: Immunity (2020)
Disulfide High‐Mobility Group Box 1 Drives Ischemia‐Reperfusion Injury in Human Liver Transplantation
Authors: Rebecca A. Sosa, Allyson Q. Terry, Fady M. Kaldas, Yi‐Ping Jin, Maura Rossetti, Takahiro Ito, Fang Li, Richard S. Ahn, Bita V. Naini, Victoria M. Groysberg, Ying Zheng, Antony Aziz, Jessica Nevarez‐Mejia, Ali Zarrinpar, Ronald W. Busuttil, David W. Gjertson, Jerzy W. Kupiec‐Weglinski, Elaine F. Reed
Journal: Hepatology (2020)

Sterile inflammation is a major clinical concern during ischemia-reperfusion injury (IRI) triggered by traumatic events, including stroke, myocardial infarction, and solid organ transplantation. Despite high-mobility group box 1 (HMGB1) clearly being involved in sterile inflammation, its role is controversial because of a paucity of patient-focused research.
Heparin Therapy
Authors: KENNETH J. PRESCOTT
Journal: Annals of Internal Medicine (1974)

Comments1 June 1974Heparin TherapyKENNETH J. PRESCOTT, M.D.KENNETH J. PRESCOTT, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-80-6-773_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Dr. Edward Genton stated in his review, "Guidelines for Heparin Therapy," (Ann Intern Med 80:77-82, 1974) that the amount of heparin anticipated for a 12- to 24-hour period is diluted in from 500 to 1000 ml 5% glucose or saline solution. Jacobs and associates (1) have shown that there is a rapid inactivation of heparin in solutions containing dextrose or lactate.Since saline seems to be the only solution in which heparin is stable, its use as a constant drip would be limited in patients requiring sodium restriction....Reference1. JACOBS J, KLETTER D, and SUPERSTINE E: Intravenous infusion of heparin and penicillins. J Clin Pathol 26:742-746, 1973 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: KENNETH J. PRESCOTT, M.D.Affiliations: 6 Boston Rd. Chelmsford, Massachusetts 01824 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1974Volume 80, Issue 6Page: 773-774KeywordsGlucoseHeparinLactatesSaline solutionsSodium ePublished: 1 December 2008 Issue Published: 1 June 1974 PDF downloadLoading ...
Plasmacytoid Dendritic Cells and Type I Interferon Promote Extrafollicular B Cell Responses to Extracellular Self-DNA
Authors: Chetna Soni, Oriana A. Perez, William N. Voss, Joseph N. Pucella, Lee Serpas, Justin Mehl, Krystal L. Ching, Jule Goike, George Georgiou, Gregory C. Ippolito, Vanja Sisirak, Boris Reizis
Journal: Immunity (2020)
Is there an association between attention deficit hyperactivity disorder in children and adolescents and the occurrence of bruxism? A systematic review and meta-analysis
Authors: Debora Souto-Souza, Priscila S. Mourão, Heloisa H. Barroso, Dhelfeson W. Douglas-de-Oliveira, Maria L. Ramos-Jorge, Saulo G.M. Falci, Endi L. Galvão
Journal: Sleep Medicine Reviews (2020)
The anti-microbial peptide LL-37/CRAMP levels are associated with acute heart failure and can attenuate cardiac dysfunction in multiple preclinical models of heart failure
Authors: Qiulian Zhou, Li-Long Pan, Ruicong Xue, Gehui Ni, Yi Duan, Yuzheng Bai, Chao Shi, Zhengnan Ren, Chengfei Wu, Guoping Li, Birgitta Agerberth, Joost PG Sluijter, Jia Sun, Junjie Xiao
Journal: Theranostics (2020)

Rationale: Biomarkers for the diagnosis of heart failure (HF) are clinically essential. Circulating antimicrobial peptides LL-37 has emerged as a novel biomarker in cardiovascular disease, however, its relevance as a biomarker for acute HF are undetermined. Methods: Acute HF patients were enrolled in this study and the serum levels of LL-37/CRAMP (cathelicidin-related antimicrobial peptide) were measured by ELISA. The receiver-operator characteristic (ROC) curve was used to determine if serum LL-37 could be a biomarker for acute HF. Mouse CRAMP (mCRAMP, mouse homolog for human LL-37) was also determined in both heart and serum samples of, transverse aortic constriction (TAC)- and isoproterenol (ISO)-induced HF mice models, and phenylephrine (PE) and angiotensin II (AngII)-induced neonatal mouse cardiomyocytes (NMCMs) hypertrophic models, both intracellular and secreted, by ELISA. The protective effects of mCRAMP were determined in TAC, ISO, and AngII-induced HF in mice while whether HF was exacerbated in AngII-infused animals were checked in mCRAMP knockout mice. The underlying mechanism for protective effects of CARMP in pathological hypertrophy was determined by using a NF-κB agonist together with rCRAMP (rat homolog for human LL-37) in AngII or PE treated neonatal rat cardiomyocytes (NRCMs). Results: Serum levels of LL-37 were significantly decreased in acute HF patients (area under the curve (AUC) of 0.616), and negatively correlated with NT-proBNP. We further confirmed that mCRAMP was decreased in both heart and serum samples of TAC- and ISO-induced HF mice models. Moreover, in PE and AngII-induced NMCMs hypertrophic models, both intracellular and secreted mCRAMP levels were reduced. Functionally, mCRAMP could attenuate TAC, ISO, and AngII-induced HF in mice while CRAMP deficiency exacerbated HF. Mechanistically, the anti-hypertrophy effects of CRAMP were mediated by NF-κB signaling. Conclusions: Collectively, serum LL-37 is associated with acute HF and increasing CRAMP is protective against deleterious NF-κB signaling in the rodent.
The Surgical Treatment of Ulcerative Colitis
Authors: Bentley P. Colcock
Journal: New England Journal of Medicine (1950)

THE treatment of ulcerative colitis is primarily medical. Experience has shown, however, that at least 25 per cent of patients with ulcerative colitis require surgical intervention,1 , 2 to preserve life, for the relief of chronic invalidism or to treat one of the frequent complications of this disease such as perforation, arthritis or malignant degeneration in the diseased colon.From 1927 to January, 1949, 263 patients with ulcerative colitis were operated on. An ileostomy was carried out on 216 and partial colectomy on 59 patients, and 148 patients had a complete colectomy in addition to ileostomy. The following remarks are based upon . . .
Randomized Comparison of the Polymer-Free Biolimus-Coated BioFreedom Stent With the Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Orsiro Stent in an All-Comers Population Treated With Percutaneous Coronary Intervention
Authors: Lisette Okkels Jensen, Michael Maeng, Bent Raungaard, Johnny Kahlert, Julia Ellert, Lars Jakobsen, Anton Boel Villadsen, Karsten Tange Veien, Steen Dalby Kristensen, Ole Ahlehoff, Steen Carstensen, Martin Kirk Christensen, Christian Juhl Terkelsen, Thomas Engstroem, Knud Nørregaard Hansen, Hans Erik Bøtker, Jens Aaroe, Troels Thim, Leif Thuesen, Philip Freeman, Ahmed Aziz, Ashkan Eftekhari, Anders Junker, Svend Eggert Jensen, Jens Flensted Lassen, Henrik Steen Hansen, Evald Høj Christiansen, Kristian Thygesen, Jacob Thorsted Sørensen, Henning Rud Andersen
Journal: Circulation (2020)

In patients with increased bleeding risk, the biolimus A9-coated BioFreedom stent, a stainless steel drug-coated stent free from polymer, has shown superiority compared with a bare-metal stent. The aim of this study was to investigate whether the BioFreedom stent is noninferior to a modern ultrathin strut biodegradable polymer cobalt-chromium sirolimus-eluting Orsiro stent in an all-comers patient population treated with percutaneous coronary intervention.The SORT OUT IX trial (Scandinavian Organization for Randomized Trials With Clinical Outcome IX), was a large-scale, registry-based, randomized, multicenter, single-blind, 2-arm, noninferiority trial. The primary end point, major adverse cardiovascular events, was defined as the composite of cardiac death, myocardial infarction not related to any segment other than the target lesion, or target lesion revascularization within 1 year, analyzed by intention-to-treat. The trial was powered to assess noninferiority for major adverse cardiovascular events of the BioFreedom stent compared with the Orsiro stent with a predetermined noninferiority margin of 0.021.Between December 14, 2015 and April 21, 2017, 3151 patients were assigned to treatment with the BioFreedom stent (1572 patients, 1966 lesions) or to the Orsiro stent (1579 patients, 1985 lesions). Five patients were lost to follow-up because of emigration (99.9% follow-up rate). Mean age was 66.3±10.9, diabetes mellitus was seen in 19.3% of patients, and 53% of the patients had acute coronary syndromes. At 1 year, intention-to-treat analysis showed that 79 (5.0%) patients, who were assigned the BioFreedom stent, and 59 (3.7%), who were assigned the Orsiro stent, met the primary end point (absolute risk difference 1.29% [upper limit of one-sided 95% CI 2.50%]; Pnoninferiority=0.14). Significantly more patients in the BioFreedom stent group had target lesion revascularization than those in the Orsiro stent group (55 [3.5%] vs 20 [1.3%], rate ratio 2.77 [95% CI, 1.66-4.62]; P<0.0001).The biolimus A9-coated BioFreedom polymer-free stent did not meet criteria for noninferiority for major adverse cardiovascular events at 12 months when compared with the ultrathin strut biodegradable polymer sirolimus-eluting Orsiro stent in an all-comers population Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02623140.
Abstract 13615: Rare Progression From Hypertensive Left Ventricular Hypertrophy to Left Ventricular Dilation Without New Infarction or Other Structural Heart Disease
Authors: Griffin Bullock, Timothy E Thayer, Eric Farber-Eger, Brandon Lowery, Quinn Wells, Lynne W Stevenson
Journal: Circulation (2019)

Introduction: Heart failure with reduced ejection fraction (HFrEF) is commonly attributed to hypertension, with transition from concentric left ventricular (LV) hypertrophy to maladaptive LV hypert...