tbuckley/cabot-search huggingface dataset:
Race-Dependent Differences in Risk, Genomics, and Epstein–Barr Virus Exposure in Monoclonal Gammopathies: Results of SWOG S0120
Authors: Madhav V. Dhodapkar, Rachael Sexton, Antje Hoering, Frits Van Rhee, Bart Barlogie, Robert Orlowski
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Risk of multiple myeloma is increased in African American (AA) populations compared with European American (EA) cohorts. Current estimates of risk of progression of monoclonal gammopathy of undetermined significance (MGUS) are based largely on studies in EA cohorts. Prospective analyses of this risk in AA cohorts are lacking. Patients and Methods: Between 2003 and 2011, 331 eligible patients with IgG/A monoclonal gammopathy were enrolled in a prospective observational trial (SWOG S0120). Results: Of 331 eligible patients, 57 (17%) were of AA descent. The risk of transformation to clinical malignancy in AA patients was significantly lower than in non-AA cohort (2-year risk 5% vs. 15%; 5-year risk 13% vs. 24%; log-rank P = 0.047). Differences in risk were evident for both MGUS and asymptomatic multiple myeloma. Gene expression profile (GEP) of CD138-purified plasma cells revealed that all molecular multiple myeloma subsets can be identified in both cohorts. However, the proportion of patients with high-risk GEP risk score (GEP-70 gene risk &amp;gt; −0.26) was lower in the AA cohort (0% vs. 33%, P = 0.01). AA cohorts also have higher levels of antibodies against Epstein–Barr nuclear antigen-1 (EBNA-1; P &amp;lt; 0.001). Conclusions: These data provide the first prospective evidence that multiple myeloma precursor states in AA patients may have lower risk of disease compared with non-AA counterparts with lower incidence of high-risk GEP and increased EBV seropositivity. Race-dependent differences in biology and clinical risk of gammopathy may impact optimal management of these patients.
In Chronic Lymphocytic Leukemia PD-1 Is Expressed Independently From PDCD1 Gene Polymorphisms and Does Not Influence BCR Signaling
Authors: Krzysztof Giannopoulos, Maciej Grzywnowicz, Lidia Karabon, Agnieszka Piechnik, Malgorzata Zajac, Katarzyna Skorka, Joanna Zaleska, Waldemar Tomczak, Paulina Wlasiuk, Irena Frydecka, Anna Dmoszynska
Journal: Blood (2013)
Covid-19: World “has to recover together” and help vulnerable states
Authors: Alison Shepherd
Journal: BMJ (2020)

A doctor tests the blood pressure of a man in the Rohingya camp in Cox's Bazar, Bangladesh, one of the world's largest refugee camps.The impact of the covid-19 pandemic on the world's most vulnerable populations, including refugee camps and fragile states, threatens not only those communities but the world's ability to contain the virus, the head of the World Health Organization said last week.In a warning to richer nations racing to find and distribute a vaccine, Tedros Adhanom Ghebreyesus said, "For the world to recover faster, it has to recover together: the economies are intertwined.Part of the world or a few countries cannot be a safe haven and recover."Cox's Bazar is one of the seven targets of the recently launched Disasters Emergency Committee's coronavirus appeal.It aims to raise funds for the most vulnerable communities in the world fleeing from conflict and instability, to help them withstand the threat of covid-19.
Vaccination Against Human Papillomavirus
Authors: Dustin H. Marks, Kenneth A. Katz
Journal: JAMA Dermatology (2020)

<h3>Clinical Question</h3> Who should receive human papillomavirus (HPV) vaccination? <h3>Bottom Line</h3> Catch-up vaccination is now recommended for all persons through age 26 years. For persons aged 27 through 45 years, clinicians and patients should now jointly decide whether HPV vaccination is appropriate. Routine HPV vaccination at age 11 or 12 years (or as early as age 9 years) continues to be recommended.
Formulation of water-insoluble antineoplastic agents as nanosuspensions using NANOEDGE formulation technology
Authors: Barrett E. Rabinow, Pramod Gupta, Joseph Wong, Pavlos Papadopoulos, Mahesh Chaubal
Journal: Cancer Research (2004)

632   Water-insoluble antineoplastic agents pose a formulation problem inasmuch as sufficient plasma levels of drug are required to achieve adequate efficacy and toxicity levels in suitable animal models and humans. For this purpose, a nanosuspension formulation platform (NANOEDGE) has been developed which potentially permits high drug loading, eliminates undesirable solvents, and allows administration of the same formulation through various routes, e.g., oral and injectable including I.V. The steps involved in formulating 3 different antineoplastic compounds, using this technology, to attain stable nanosupensions with mean particle size
Psychosis relapse during treatment with long-acting injectable antipsychotics in individuals with schizophrenia-spectrum disorders: an individual participant data meta-analysis
Authors: Jose M Rubio, Georgios Schoretsanitis, Majnu John, Jari Tiihonen, Heidi Taipale, Daniel Guinart, Anil K Malhotra, Christoph U Correll, John M Kane
Journal: The Lancet Psychiatry (2020)
Short-course radiotherapy promotes pro-inflammatory macrophages via extracellular vesicles in human rectal cancer
Authors: Victoria Stary, Brigitte Wolf, Daniela Unterleuthner, Julia List, Merjem Talic, Johannes Längle, Andrea Beer, Johanna Strobl, Georg Stary, Helmut Dolznig, Michael Bergmann, MD
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Tumor-associated macrophages (TAM) constitute the most abundant immune cells in the tumor stroma initiating pro-inflammatory (M1) or immunosuppressive (M2) responses depending on their polarization status. Advances in tumor immunotherapy call for a detailed understanding of potential immunogenic mechanisms of irradiation routinely applied in rectal cancer patients. Methods To test the effects of radiotherapy on TAM, we ex vivo irradiated tissue samples of human rectal cancer and assessed the phenotype by flow cytometry. We furthermore evaluated the distribution of leucocyte subsets in tissue sections of patients after short-course radiotherapy and compared findings to non-pretreated rectal cancer using an immunostaining approach. Organotypic assays (OTA) consisting of macrophages, cancer-associated fibroblast and cancer cell lines were used to dissect the immunological consequences of irradiation in macrophages. Results We demonstrate that short-course neoadjuvant radiotherapy in rectal cancer patients is associated with a shift in the polarization of TAM towards an M1-like pro-inflammatory phenotype. In addition, ex vivo irradiation caused an increase in the phagocytic activity and enhanced expression of markers associated with stimulatory signals necessary for T-cell activation. In OTA we observed that this alteration in macrophage polarization could be mediated by extracellular vesicles (EV) derived from irradiated tumor cells. We identified high mobility group box 1 in EV from irradiated tumor cells as a potential effector signal in that crosstalk. Conclusions Our findings highlight macrophages as potential effector cells upon irradiation in rectal cancer by diminishing their immunosuppressive phenotype and activate pro-inflammation. Our data indicate that clinically applied short-term radiotherapy for rectal cancer may be exploited to stimulate immunogenic macrophages and suggest to target the polarization status of macrophages to enhance future immunotherapeutic strategies.
Implications for the Care of Patients With COVID-19 and Inflammatory Myocardial Disease
Authors: Giuseppe Di Tano, Attilio Iacovoni, Renata De Maria
Journal: JAMA Cardiology (2020)

Riccardo M. Inciardi, MD; Laura Lupi, MD; Gregorio Zaccone, MD; Leonardo Italia, MD; Michela Raffo, MD; Daniela Tomasoni, MD; Dario S. Cani, MD; Manuel Cerini, MD; Davide Farina, MD; Emanuele Gavazzi, MD; Roberto Maroldi, MD; Marianna Adamo, MD; Enrico Ammirati, MD, PhD; Gianfranco Sinagra, MD; Carlo M. Lombardi, MD; Marco Metra, MD
Botanical drug clinical trial: Common issues and future options
Authors: Yu Sun, Jiahua Qian
Journal: Acta Pharmaceutica Sinica B (2020)

In order to understand this disparity between human use and drugs approved by regulatory agencies, we analyzed botanical drug clinical trials registered at ClinicalTrial.gov to detect trends in current trials and guide future trials. A total of 195 botanical drug clinical trials were registered from 2016 to 2019, of which 81 are phase II or phase II/III. 95% of all phase II and II/III studies were designed with 100 or less participants per arm, indicating a more observational nature due to the limited power to detect differences in outcomes between treatment and control groups. Due to the limited number of participants, efficacy outcome from results may be highly subjective. 14% of the total trials were phase I studies. For botanical drugs with well-documented or extensive history of human use, phase I may not provide significant additional information, and may, therefore, not be necessary. For the trial design, we suggest added-on studies when botanical drugs are used as part of a combination treatment. Additionally, we believe standardized data collection methods and criteria are critical to utilizing the vast collection of human experience as quality evidence to support regulatory approval.
Postoperative Function as a Measure of Quality in Geriatric Surgical Care—Can We Do Better?
Authors: Carolyn D. Seib, Shipra Arya
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Abstract 226: Pathways of nucleotide synthesis in NSCLC
Authors: Teresa W-M Fan, Qiushi Sun, Richard M. Higashi, Andrew N. Lane
Journal: Cancer Research (2020)

Abstract Tracer-based mapping of metabolic networks is a powerful approach for revealing metabolic reprogramming in human cancer. Nucleotide synthesis and turnover is critical for cell proliferation and is tightly regulated [1,2]. We have developed NMR and tandem MS methods for determining the active pathways of the synthesis of free nucleotides and nucleotide sugars including UDP-Glucose and UDPGlcNAc using multiplexed stable isotope resolved metabolomics (mSIRM)[3] in a variety of models including freshly resected lung tumor tissue, mouse PDX and organoids. Using multiple isotopic labels (13C, 2H and 15N) we determined the relative contributions to purine and pyrimidine nucleotide synthesis of both exogenous glucose, glutamine, serine and glycine and metabolically-derived intracellular precursors. We have used these approaches to compare the relative importance of different metabolic pathways in NSCLC under various conditions to assess the role of the tumor microenvironment, and how these pathways are impacted by arsenite and selenite. Our findings indicate that the substrates for de novo nucleotide synthesis may differ profoundly between cancer cell lines and fresh human lung cancer tissues; for purines, the latter preferred glucose to exogenous serine or glycine but not the former. Pyrimidine nucleotides also utilize glucose for ribose synthesis via the pentose phosphate pathway, but both glucose and glutamine for the pyrimidine rings depending on the conditions and cell type. This distinction in substrate utilization in nucleotide synthesis in human cancer tissues should be considered when targeting one-carbon metabolism for cancer therapy. Acknowledgements: This work was supported in part by grants: 1R01ES022191-01 (to TWMF and RMH), 1P01CA163223-01A1 (to ANL and TWMF), and 1U24DK097215-01A1 (to RMH, TWMF, and ANL). References 1. Lane, A.N. &amp; Fan,T. W-M. (2015) Regulation of nucleic acid metabolism in mammalian cells. Nucl.Acids Res. 43, 2466-85 2. Fan, T. W-M. et al. (2019) De novo synthesis of serine and glycine fuels purine nucleotide biosynthesis in human lung cancer tissues. J. Biol. Chem. 294, 13464-13477 3. Yang, Y., Fan, W. W-M., Lane, A.N. &amp; Higashi, R.M. (2017) Chloroformate Derivatization for Tracing the Fate of Amino Acids in Cells by Multiple Stable Isotope Resolved Metabolomics (mSIRM). Anal. Chim. Acta 976, 63-73 Citation Format: Teresa W-M Fan, Qiushi Sun, Richard M. Higashi, Andrew N. Lane. Pathways of nucleotide synthesis in NSCLC [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 226.
Sudden onset fatigue (SOF) in patients with breast cancer: Characteristics and symptomatology
Authors: Z. A. Nahleh, H. Wu, E. Galvin, D. Leedy
Journal: Journal of Clinical Oncology (2009)

e20637 Background: Cancer-related fatigue is underrecognized and poorly managed. Unpredictability and rapid onset in fatigue is stressed by cancer patients but seldom addressed by health care professionals. Although sudden onset of cancer-related fatigue is anecdotally documented across qualitative studies, the symptom has never been systematically investigated. Our purpose is to describe the symptom and clinical characteristics of SOF in breast cancer patients receiving chemotherapy. Methods: This is a cross-sectional descriptive study enrolling female breast cancer outpatients undergoing chemotherapy in an urban cancer center. A brief questionnaire assessing the symptom characteristics of SOF was completed by subjects. Comprehensive metabolic panel and complete blood counts, were obtained. Descriptive statistics described the symptom characteristics of SOF. Mann-Whitney tests examined the differences between those who did and did not experience SOF. Results: Thirty patients have been enrolled. Median age 53 years (31 to 65; SD=7.7), 60% were Black. 80% (n=24) experienced SOF in the past 7 days with a median of 4 days a week and 2.5 episodes per day. SOF was most likely (75%) to occur in the afternoon while patients were engaging in activities. Levels of fatigue before, during, and after a specific episode of SOF were 5, 9, and 5, respectively, on 0–10 (highest) rating scale. Weakness, sweating, or pain sometimes accompanied SOF. When SOF occurred, individuals immediately needed to stop activities to rest until it went away. Those who experienced SOF had significantly lower levels of calcium (Median=8.9 vs. 9.4), albumin (Median=3.7 vs. 7.1), and hematocrit (Median=32.1 vs. 36) (p&lt;0.05). Those who experienced SOF also had higher levels of GPT (Median=25.5 vs. 17), lower levels of total protein (Median=6.7 vs. 7.1), WBC (Median=4.9 vs. 8.9), RBC (Median=3.4 vs. 3.9), and hemoglobin (Median=10.7 vs. 11.4). Conclusions: Our ongoing study is one of the first to identify the characteristics of patients at high risk of SOF. SOF needs to be recognized and managed when patients undergo chemotherapy. Associated conditions should be identified and addressed. The ultimate goal is to minimize the distress and improve the quality of life of patients receiving chemotherapy. No significant financial relationships to disclose.
AB1162 ANTI-TNF BIOSIMILARS: HOW KNOWLEDGE AND BELIEF INFLUENCE PRESCRIPTION
Authors: A. De Chateaubriant, P. Ingrand, E. Gervais
Journal: Annals of the Rheumatic Diseases (2020)

Background: Biological agents change the management of rheumatic inflammatory disease with improving care but increasing costs. Biosimilars for subcutaneous TNF inhibitors (SC TNFi) are available in France since 2015 and provide the same treatments at lower cost. French health agencies do not legally oblige rheumatologist to first prescribe or switch to biosimilars. Objectives: To assess the knowledge and beliefs of French rheumatologists about biosimilars. Methods: The assessment was developed with a questionnaire consisting of five parts: demographics data, professional practice, theoretical knowledge, beliefs and confidence. The questionnaire was administrated via the website Limesurvey and sent by email to French rheumatologist. A descriptive analysis of the data and associated factors to initiation and switch of biosimilars have been done. Results: One hundred one rheumatologists have participated to the study. 47.1% was less than forty years old. 92% of them have the authorization to prescribe TNFi. 53.2 always prescribed a biosimilars when they prescribed a SC TNFi for the first time and 78.5% in 90% of cases. 30.6% of French rheumatologist never switched to a biosimilars. Those who switch, do it in more than 75% of cases. 96.5%, 87.1% and 91.8% respectively answered that biosimilars are as efficient, as safe and have the same immunogenicity profile compared to originator. The initial biosimilars prescription is associated with a better knowledge about biosimilars. For example, 77.4% of rheumatologist who prescribe in more than 90% of the case, answer NO to the question “biosimilars and originator have to be compared in a phase III study for EACH indications for which originator obtained marketing approval”. Only 31.2% of rheumatologist who prescribed in less than 90% of the case respond NO to this question. This difference was significant p&lt;0.001. The switch to a biosimilars is associated with the beliefs and confidence. For example 25.4% of rheumatologists who switch for biosimilar in more than 75% of the case, answer YES to the question “There is not enough experiences with biosimilar”. 57.7% of rheumatologist who switched in less than 75% of the case respond YES to this question. This difference was significant p&lt;0.003. Conclusion: Despite good knowledge on biosimilars, some French rheumatologists do not switch for these molecules. Our study suggests that this is due to lack of confidence. Acknowledgments: The authors thank French rheumatologist who answer to the questionnaire Disclosure of Interests: Arnaud De Chateaubriant: None declared, Pierre Ingrand: None declared, Elisabeth Gervais Speakers bureau: Novartis, Janssen, Roche, Pfizer, BMS, Abbvie
Abstract 5372: HER2 expression on tumor-derived extracellular vesicles and circulating tumor cells in metastatic breast cancer
Authors: Afroditi Nanou, Leonie L. Zeune, Francois-Clement Bidard, Jean-Yves Pierga, Leon W. Terstappen
Journal: Cancer Research (2020)

Abstract Tumor-derived extracellular vesicles (tdEVs) and circulating tumor cells (CTCs) in blood of metastatic cancer patients associate with poor outcome. In this study, we explored the human epidermal growth factor receptor 2 (HER2) expression on CTCs and tdEVs of metastatic breast cancer patients. Blood samples from 98 patients (IC 2006-04 study) were originally processed with the CellSearch® system using the CTC kit and anti-HER2 as an additional marker in the staining cocktail. CTCs and tdEVs were automatically enumerated from the generated CellSearch image datasets using the open-source ACCEPT software. The HER2 status of the tissue was assessed by fluorescence in situ hybridization (FISH). The inclusion of anti-HER2 increased the percentage of informative samples with ≥1 detectable CTC and tdEV from 89% and 99% to 95 and 100%, respectively. CTCs and tdEVs were subdivided based on their cytokeratin (CK) and HER2 phenotype into CK+HER2-, CK-HER2+ and CK+HER2+. Inter- and intra- patient heterogeneity was found regarding the phenotype of CTCs and tdEVs with the majority of patients having all different subclasses present. CK- CTCs and tdEVs correlated equally well with clinical outcome as CK+ CTCs and tdEVs. Use of ≥7% HER2+CK+ tdEVs can predict HER2 expression of the tissue with 74% sensitivity and specificity, whereas the respective use of ≥23% HER2+CK+ CTCs leads to 65% sensitivity and 66% specificity. HER2 can be detected on CTCs and tdEVs not expressing CK, which have similar clinical relevance to CTCs and tdEVs expressing CK. tdEVs perform better than CTCs in predicting the HER2 status of the tissue. Funded by the NWO Applied and Engineering Sciences Cancer-ID project #14190, the EUFP7 CTCTrap project #305341 and the EU IMI CANCER-ID project # 115749-1. Citation Format: Afroditi Nanou, Leonie L. Zeune, Francois-Clement Bidard, Jean-Yves Pierga, Leon W. Terstappen. HER2 expression on tumor-derived extracellular vesicles and circulating tumor cells in metastatic breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5372.
Identification of MALT1 feedback mechanisms enables rational design of potent antilymphoma regimens for ABC-DLBCL
Authors: Lorena Fontan, Rebecca Goldstein, Gabriella Casalena, Matthew Durant, Matthew R. Teater, Jimmy Wilson, Jude Phillip, Min Xia, Shivem Shah, Ilkay Us, Himaly Shinglot, Ankur Singh, Giorgio Inghirami, Ari Melnick
Journal: Blood (2021)
4HNE Impairs Myocardial Bioenergetics in Congenital Heart Disease-Induced Right Ventricular Failure
Authors: HyunTae V. Hwang, Nefthi Sandeep, Sharon L. Paige, Sara Ranjbarvaziri, Dong-Qing Hu, Mingming Zhao, Ingrid S. Lan, Michael Coronado, Kristina B. Kooiker, Sean M. Wu, Giovanni Fajardo, Daniel Bernstein, Sushma Reddy
Journal: Circulation (2020)

Background: In patients with complex congenital heart disease, such as those with tetralogy of Fallot, the right ventricle (RV) is subject to pressure overload stress, leading to RV hypertrophy and eventually RV failure. The role of lipid peroxidation, a potent form of oxidative stress, in mediating RV hypertrophy and failure in congenital heart disease is unknown. Methods: Lipid peroxidation and mitochondrial function and structure were assessed in right ventricle (RV) myocardium collected from patients with RV hypertrophy with normal RV systolic function (RV fractional area change, 47.3±3.8%) and in patients with RV failure showing decreased RV systolic function (RV fractional area change, 26.6±3.1%). The mechanism of the effect of lipid peroxidation, mediated by 4-hydroxynonenal ([4HNE] a byproduct of lipid peroxidation) on mitochondrial function and structure was assessed in HL1 murine cardiomyocytes and human induced pluripotent stem cell-derived cardiomyocytes. Results: RV failure was characterized by an increase in 4HNE adduction of metabolic and mitochondrial proteins (16 of 27 identified proteins), in particular electron transport chain proteins. Sarcomeric (myosin) and cytoskeletal proteins (desmin, tubulin) also underwent 4HNE adduction. RV failure showed lower oxidative phosphorylation (moderate RV hypertrophy, 287.6±19.75 versus RV failure, 137.8±11.57 pmol/[sec×mL]; P =0.0004), and mitochondrial structural damage. Using a cell model, we show that 4HNE decreases cell number and oxidative phosphorylation (control, 388.1±23.54 versus 4HNE, 143.7±11.64 pmol/[sec×mL]; P &lt;0.0001). Carvedilol, a known antioxidant did not decrease 4HNE adduction of metabolic and mitochondrial proteins and did not improve oxidative phosphorylation. Conclusions: Metabolic, mitochondrial, sarcomeric, and cytoskeletal proteins are susceptible to 4HNE-adduction in patients with RV failure. 4HNE decreases mitochondrial oxygen consumption by inhibiting electron transport chain complexes. Carvedilol did not improve the 4HNE-mediated decrease in oxygen consumption. Strategies to decrease lipid peroxidation could improve mitochondrial energy generation and cardiomyocyte survival and improve RV failure in patients with congenital heart disease.