tbuckley/cabot-search huggingface dataset:
Zfra is an inhibitor of Bcl-2 expression and cytochrome c release from the mitochondria
Authors: Li-Jin Hsu, NanShan Chang
Journal: Cancer Research (2008)

LB-48  Zfra is a small size 31-amino-acid C2H2 zinc finger-like protein, which is known to interact with c-Jun N-terminal kinase 1 (JNK1), WW domain-containing oxidoreductase (WWOX, FOR or WOX1), TNF receptor-associated death domain protein (TRADD) and nuclear factor kappaB (NF-IkB) during stress response. Here, we show that Zfra became phosphorylated at Ser8 (as determined by specific antibody) and translocated to the mitochondria in response to inducers of mitochondrial permeability transition (MPT) (e.g. staurosporine and betulinic acid). Overexpressed Zfra induced cell death. This event is associated, in part, with increased dissipation of mitochondrial membrane potential (MMP) and increased chromosomal DNA fragmentation. Intriguingly, Zfra significantly downregulated Bcl-2 and yet blocked cytochrome c release from the mitochondria. Overexpression of an S8G-Zfra mutant (Ser8 to Gly8 alteration) could not result in cell death, due to its failure of translocating to the mitochondria and causing MMP dissipation. Proapoptotic WOX1 physically interacted with Zfra and induced cytochrome c release from the mitochondria. Zfra blocked the effect of WOX1. Taken together, Ser8 is essential for overexpressed Zfra to exert cell death via the mitochondrial pathway. Zfra downregulates Bcl-2 and induces MMP dissipation but causes no cytochrome c release, indicating a novel death pathway from the mitochondria.
Role of CD47 in Hematological Malignancies
Authors: Entsar Eladl, Rosemarie Tremblay-LeMay, Nasrin Rastgoo, Rumina Musani, Wenming Chen, Aijun Liu, Hong Chang
Journal: Journal of Hematology & Oncology (2020)

Abstract CD47, or integrin-associated protein, is a cell surface ligand expressed in low levels by nearly all cells of the body. It plays an integral role in various immune responses as well as autoimmunity, by sending a potent “don’t eat me” signal to prevent phagocytosis. A growing body of evidence demonstrates that CD47 is overexpressed in various hematological malignancies and its interaction with SIRPα on the phagocytic cells prevents phagocytosis of cancer cells. Additionally, it is expressed by different cell types in the tumor microenvironment and is required for establishing tumor metastasis. Overexpression of CD47 is thus often associated with poor clinical outcomes. CD47 has emerged as a potential therapeutic target and is being investigated in various preclinical studies as well as clinical trials to prove its safety and efficacy in treating hematological neoplasms. This review focuses on different therapeutic mechanisms to target CD47, either alone or in combination with other cell surface markers, and its pivotal role in impairing tumor growth and metastatic spread of various types of hematological malignancies.
Procoagulant Phospholipid Dependent Clotting Time: A New Tool for the Identification of Multiple Myeloma Patients at Risk Poor Treatment Response
Authors: Fotiou Despina, Loula Papageorgiou, Stella Salta, Patrick Van Dreden, Evangelos Terpos, Jawed Fareed, Matthieu Grusse, Ismail Elalamy, Laurent Garderet, Christelle Mazurier, Grigorios T. Gerotziafas
Journal: Blood (2017)
Estimated Community Seroprevalence of SARS-CoV-2 Antibodies — Two Georgia Counties, April 28–May 3, 2020
Authors: Holly M. Biggs, Jennifer B. Harris, Lucy Breakwell, F. Scott Dahlgren, Glen R. Abedi, Christine M. Szablewski, Jan Drobeniuc, Nirma D. Bustamante, Olivia Almendares, Amy H. Schnall, Zunera Gilani, Tiffany Smith, Laura Gieraltowski, Jeffrey A. Johnson, Kristina L. Bajema, Kelsey McDavid, Ilana J. Schafer, Vickie Sullivan, Lili Punkova, Alexandra Tejada-Strop, Raiza Amiling, Claire P. Mattison, Margaret M. Cortese, S. Elizabeth Ford, Lynn A. Paxton, Cherie Drenzek, Jacqueline E. Tate, Nicole Brown, Karen T. Chang, Nicholas P. Deputy, Rodel Desamu-Thorpe, Chase Gorishek, Arianna Hanchey, Michael Melgar, Benjamin P. Monroe, Carrie F. Nielsen, Gerald J. Pellegrini, Mays Shamout, Laura I. Tison, Sara Vagi, Rachael Zacks
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

An illness was categorized as one compatible with COVID-19 if symptoms met the Council of State and Territorial Epidemiologists (CSTE) clinical criteria in the case definition, including 1) cough, shortness of breath, or difficulty breathing or 2) two or more other symptoms (fever [measured or subjective], chills, rigors, myalgia, headache, sore throat, new olfactory and taste disorders).https://cdn.ymaws.com/www.cste.org/resource/resmgr/2020ps/interim-20id-01_covid-19.pdf.reported here does not represent the seroprevalence at the time of publication.Community-level seroprevalence estimates can complement case-based and syndromic surveillance as a tool to understand local transmission and the extent of past infection in a population.The relatively low seroprevalence estimate in this report suggests that most persons in the catchment area had not been infected with SARS-CoV-2 by the end of April.Continued mitigation measures to prevent infection, including social distancing, consistent and correct use of face coverings, and hand hygiene, remain essential to controlling the spread of SARS-CoV-2 in the community.
A Rare <i>TP53</i> Mutation Predominant in Ashkenazi Jews Confers Risk of Multiple Cancers
Authors: Jacquelyn Powers, Emilia M. Pinto, Thibaut Barnoud, Jessica C. Leung, Tetyana Martynyuk, Andrew V. Kossenkov, Aaron H. Philips, Heena Desai, Ryan Hausler, Gregory Kelly, Anh N. Le, Marilyn M. Li, Suzanne P. MacFarland, Louise C. Pyle, Kristin Zelley, Katherine L. Nathanson, Susan M. Domchek, Thomas P. Slavin, Jeffrey N. Weitzel, Jill E. Stopfer, Judy E. Garber, Vijai Joseph, Kenneth Offit, Jill S. Dolinsky, Stephanie Gutierrez, Kelly McGoldrick, Fergus J. Couch, Brooke Levin, Morris C. Edelman, Carolyn Fein Levy, Sheri L. Spunt, Richard W. Kriwacki, Gerard P. Zambetti, Raul C. Ribeiro, Maureen E. Murphy, Kara N. Maxwell
Journal: Cancer Research (2020)

Abstract Germline mutations in TP53 cause a rare high penetrance cancer syndrome, Li–Fraumeni syndrome (LFS). Here, we identified a rare TP53 tetramerization domain missense mutation, c.1000G&amp;gt;C;p.G334R, in a family with multiple late-onset LFS-spectrum cancers. Twenty additional c.1000G&amp;gt;C probands and one c.1000G&amp;gt;A proband were identified, and available tumors showed biallelic somatic inactivation of TP53. The majority of families were of Ashkenazi Jewish descent, and the TP53 c.1000G&amp;gt;C allele was found on a commonly inherited chromosome 17p13.1 haplotype. Transient transfection of the p.G334R allele conferred a mild defect in colony suppression assays. Lymphoblastoid cell lines from the index family in comparison with TP53 normal lines showed that although classical p53 target gene activation was maintained, a subset of p53 target genes (including PCLO, PLTP, PLXNB3, and LCN15) showed defective transactivation when treated with Nutlin-3a. Structural analysis demonstrated thermal instability of the G334R-mutant tetramer, and the G334R-mutant protein showed increased preponderance of mutant conformation. Clinical case review in comparison with classic LFS cohorts demonstrated similar rates of pediatric adrenocortical tumors and other LFS component cancers, but the latter at significantly later ages of onset. Our data show that TP53 c.1000G&amp;gt;C;p.G334R is found predominantly in Ashkenazi Jewish individuals, causes a mild defect in p53 function, and leads to low penetrance LFS. Significance: TP53 c.1000C&amp;gt;G;p.G334R is a pathogenic, Ashkenazi Jewish–predominant mutation associated with a familial multiple cancer syndrome in which carriers should undergo screening and preventive measures to reduce cancer risk.
Gene Loss Predictably Drives Evolutionary Adaptation
Authors: Jana Helsen, Karin Voordeckers, Laura Vanderwaeren, Toon Santermans, Maria Tsontaki, Kevin J Verstrepen, Rob Jelier
Journal: Molecular Biology and Evolution (2020)

Abstract Loss of gene function is common throughout evolution, even though it often leads to reduced fitness. In this study, we systematically evaluated how an organism adapts after deleting genes that are important for growth under oxidative stress. By evolving, sequencing, and phenotyping over 200 yeast lineages, we found that gene loss can enhance an organism’s capacity to evolve and adapt. Although gene loss often led to an immediate decrease in fitness, many mutants rapidly acquired suppressor mutations that restored fitness. Depending on the strain’s genotype, some ultimately even attained higher fitness levels than similarly adapted wild-type cells. Further, cells with deletions in different modules of the genetic network followed distinct and predictable mutational trajectories. Finally, losing highly connected genes increased evolvability by facilitating the emergence of a more diverse array of phenotypes after adaptation. Together, our findings show that loss of specific parts of a genetic network can facilitate adaptation by opening alternative evolutionary paths.
Vertical Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 From the Mother to the Infant
Authors: Sergio Verd, Jaume Ponce-Taylor, Gemma Ginovart
Journal: JAMA Pediatrics (2020)

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 Pediatrics 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 2024 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 Pediatrics journal
Update: HIV-2 Infection—United States
Journal: JAMA (1989)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Prognostic value of immune score in nasopharyngeal carcinoma using digital pathology
Authors: Ya-Qin Wang, Lei Chen, Yan-Ping Mao, Ying-Qing Li, Wei Jiang, Shuo-Yu Xu, Yu Zhang, Yu-Pei Chen, Xiao-Min Li, Qing-Mei He, Shi-Wei He, Xiao-Jing Yang, Yuan Lei, Yin Zhao, Jing-Ping Yun, Na Liu, Yingqin Li, Jun Ma
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Tumor-infiltrating lymphocytes have been reported as prognostic markers in tumors. We aimed to assess the prognostic value of total T cell (CD3 + ) density, cytotoxic T cell (CD8 + ) density and memory T cell (CD45RO + ) density in patients with nasopharyngeal carcinoma (NPC). Methods The expression of CD3, CD8 and CD45RO was detected by immunohistochemistry in the training (n=221) and validation cohorts (n=115). The densities of these three markers were quantified by digital pathology both in the tumor and stroma. Then, we developed the immune score based on the density of these three markers and further analyzed its prognostic value. Results The high density of CD3 + , CD8 + and CD45RO + T cells both in the tumor and/or stroma were significantly associated with the decrease in mortality in the training cohort, respectively. High immune score predicted a prolonged overall survival (OS) (HR 0.34, 95% CI 0.18 to 0.64, p=0.001, disease-free survival (DFS) (HR 0.44, 95% CI 0.25 to 0.78, p=0.005) and distant metastasis-free survival (DMFS) (HR 0.43, 95% CI 0.21 to 0.87, p=0.018) in NPC patients. The findings were confirmed in the validation cohort. Multivariate analysis revealed that immune score remained an independent prognostic indicator for OS, DFS and DMFS. In addition, we established a nomogram with the integration of all independent variables to predict individual risk of death. Conclusions We established an immune score model, which provides a reliable estimate of the risk of death, disease progress and distant metastasis in NPC patients.
PRIME Time in Rheumatoid Arthritis
Authors: Ellen M. Gravallese, William H. Robinson
Journal: New England Journal of Medicine (2020)

Rheumatoid arthritis, like many autoimmune diseases, has a course characterized by intermittent flares, yet our understanding of the mechanisms underlying flares remains limited. In an article published in this issue of the Journal,1 Orange and colleagues describe a study in which serial fingerstick collection of blood was combined with weekly monitoring of patient-reported disease activity with the use of a questionnaire. They applied a dense longitudinal transcriptional monitoring approach, which revealed transcriptional signatures in blood that were associated with disease flares. By anchoring their informatics analysis on the point in time at which clinical flares occurred, they were able to . . .
Novel fusion protein of mouse UL16-binding protein-like transcript 1 (MULT1) and Fas induces apoptosis and tumor rejection
Authors: Hari Shankar Kotturi, Jinhua Li, Melissa Branham-O'Connor, Thomas Wagner, Yanzhang Wei
Journal: Cancer Research (2007)

4885  Tumor cells evade immunosurveillance by elements of the innate immune system, such as NK cells, by down regulating or shedding certain cell surface molecules like Mouse UL16-binding protein-like transcript 1 (MULT1) that can activate NK cells through the NK cell receptors such as NKG2D; they also avoid Fas mediated apoptosis by down regulating its expression. In the present study we report designing and evaluating the antitumor activity of a novel fusion protein consisting of the extracellular domain of MULT1 and the transmembrane and intracellular domains of Fas. The fusion construct (MULT1-Fas) was transfected into mouse pulmonary carcinoma cell line TC-1; and stable cell lines expressing the fusion protein were created. Cell growth studies showed that the cells expressing high levels of MULT1-Fas, as indicated by FACS analysis, grew at the same rate as cells not expressing the fusion protein in vitro. In vitro cell culture studies demonstrated that NKG2D/Fc, a recombinant protein of mouse NK cell receptor NKG2D, was able to elicit apoptosis through the Fas transmembrane and intracellular domains of MULT1-Fas in cells expressing the fusion protein as assayed by Annexin V-FITC staining and caspase-3 ELISA. In vivo subcutaneous tumor studies of MULT1-Fas expressing cell lines demonstrated reduced tumor size. Pulmonary metastasis studies showed that most of the mice completely rejected tumor cells expressing MULT1-Fas. This approach may generate a new therapeutic agent for tumor treatment when combined with tumor cell specific gene delivery vehicles such as oncolytic adenovirus vectors.
Reply to Satoshi Funada, Takashi Yoshioka, and Yan Luo’s Letter to the Editor re: Lisa Moris, Marcus G. Cumberbatch, Thomas Van den Broeck, et al. Benefits and Risks of Primary Treatments for High-risk Localized and Locally Advanced Prostate Cancer: An International Multidisciplinary Systematic Review. Eur Urol 2020;77:614–27
Authors: Lisa Moris, Thomas Van den Broeck, Thomas Wiegel
Journal: European Urology (2020)
Covid-19: Male disadvantage highlights the importance of sex disaggregated data
Authors: Kate Womersley, Katherine Ripullone, Sanne AE Peters, Mark Woodward
Journal: BMJ (2020)

Although covid-19 is a new and emerging disease, it could be one of the best understood in terms of its sex disaggregated outcomes.This may sound surprising.Sex disaggregated data (separated for women and men) for confirmed covid-19 cases and deaths are lacking from around half of the most severely affected countries, and most countries are not routinely reporting metrics such as sex or pregnancy status for covid-19 test results, treatment, vaccine trials, or deaths.But even the fact that some countries are considering sex as an important factor in covid-19 outcomes is a significant improvement when compared with the norm of non-sex disaggregated data collection for other infectious and chronic diseases.
Dendritic cell vaccination and CD40-agonist combination therapy licenses T cell-dependent antitumor immunity in a pancreatic carcinoma murine model
Authors: Sai Ping Lau, Nadine van Montfoort, Priscilla Kinderman, Melanie Lukkes, Larissa Klaase, Menno van Nimwegen, Mandy van Gulijk, Jasper Dumas, Dana A M Mustafa, Sanne L A Lievense, Christianne Groeneveldt, Ralph Stadhouders, Yunlei Li, Andrew Stubbs, Koen A Marijt, Heleen Vroman, Sjoerd H van der Burg, Joachim Aerts, Thorbald van Hall, Floris Dammeijer, Casper H J van Eijck
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Pancreatic ductal adenocarcinoma (PDAC) is notoriously resistant to treatment including checkpoint-blockade immunotherapy. We hypothesized that a bimodal treatment approach consisting of dendritic cell (DC) vaccination to prime tumor-specific T cells, and a strategy to reprogram the desmoplastic tumor microenvironment (TME) would be needed to break tolerance to these pancreatic cancers. As a proof-of-concept, we investigated the efficacy of combined DC vaccination with CD40-agonistic antibodies in a poorly immunogenic murine model of PDAC. Based on the rationale that mesothelioma and pancreatic cancer share a number of tumor associated antigens, the DCs were loaded with either pancreatic or mesothelioma tumor lysates. Methods Immune-competent mice with subcutaneously or orthotopically growing KrasG12D/+;Trp53R172H/+;Pdx-1-Cre (KPC) PDAC tumors were vaccinated with syngeneic bone marrow-derived DCs loaded with either pancreatic cancer (KPC) or mesothelioma (AE17) lysate and consequently treated with FGK45 (CD40 agonist). Tumor progression was monitored and immune responses in TME and lymphoid organs were analyzed using multicolor flow cytometry and NanoString analyzes. Results Mesothelioma-lysate loaded DCs generated cross-reactive tumor-antigen-specific T-cell responses to pancreatic cancer and induced delayed tumor outgrowth when provided as prophylactic vaccine. In established disease, combination with stimulating CD40 antibody was necessary to improve survival, while anti-CD40 alone was ineffective. Extensive analysis of the TME showed that anti-CD40 monotherapy did improve CD8 +T cell infiltration, but these essential effector cells displayed hallmarks of exhaustion, including PD-1, TIM-3 and NKG2A. Combination therapy induced a strong change in tumor transcriptome and mitigated the expression of inhibitory markers on CD8 +T cells. Conclusion These results demonstrate the potency of DC therapy in combination with CD40-stimulation for the treatment of pancreatic cancer and provide directions for near future clinical trials.
Microporous Biodegradable Films Promote Therapeutic Angiogenesis
Authors: Eseelle K. Hendow, Mehran Moazen, Francesco Iacoviello, Laurent Bozec, Caroline Pellet‐Many, Richard M. Day
Journal: Advanced Healthcare Materials (2020)

Peripheral arterial disease and critical limb ischemia are common symptoms of cardiovascular disease. Vascular surgery is used to create a bypass around occluded blood vessels to improve blood flow to ischemic muscle, thus avoiding the need for amputation. Attempts to vascularize tissues by therapeutic angiogenesis using delivery of exogenous angiogenic agents are underwhelming. A material-based approach that provides an endogenous stimulus capable of promoting angiogenesis and increased tissue perfusion would provide a paradigm shift in treatment options available. It is reported here that microporous biodegradable films produced using thermally induced phase separation provide a localized biophysical stimulus of proangiogenic genes in vivo that is associated with increased blood vessel density and restoration of blood flow to ischemic tissue. These findings show, for the first time, that acellular, nonfunctionalized biodegradable biomaterials can provide an innovative, material-based approach for therapeutic angiogenesis to enhance tissue reperfusion in vivo.
QuickStats: Percentage* of Persons Who Had a Cold in the Past 2 Weeks,† by Age Group and Calendar Quarter — National Health Interview Survey,§ United States, 2018
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

With 95% confidence intervals indicated by error bars.† Based on the questions in the Sample Child and Sample Adult Interview that ask "Did [you/your child] have a head cold or chest cold that started during the last two weeks?"§ Estimates are based on household interviews of a sample of the civilian, noninstitutionalized U.S. population and are derived from the National Health Interview Survey Sample Adult and Sample Child components.In 2018, the percentage of persons of all ages who had a cold during the past 2 weeks was 16.6% in January-March, 8.5% in April-June, 7.0% in July-September, and 13.7% in October-December.Across all calendar quarters, colds were more common
The Arousal Threshold as a Drug Target to Improve Continuous Positive Airway Pressure Adherence: Secondary Analysis of a Randomized Trial
Authors: Christopher N. Schmickl, Christopher J. Lettieri, Jeremy E. Orr, Pamela DeYoung, Bradley A. Edwards, Robert L. Owens, Atul Malhotra
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

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Surfactant-stripped J-aggregates of azaBODIPY derivatives: All-in-one phototheranostics in the second near infrared window
Authors: Yicheng Zhang, Huiquan Tao, Quguang Li, Wanle Sheng, Yuejuan Xu, Erhong Hao, Meiwan Chen, Zhuang Liu, Liangzhu Feng
Journal: Journal of Controlled Release (2020)