tbuckley/cabot-search huggingface dataset:
Prmt1 upregulated by Hdc deficiency aggravates acute myocardial infarction via NETosis
Authors: Zhiwei Zhang, Suling Ding, Zhe Wang, Xiaowei Zhu, Zheliang Zhou, Weiwei Zhang, Xiangdong Yang, Junbo Ge
Journal: Acta Pharmaceutica Sinica B (2021)

Neutrophils are mobilized and recruited to the injured heart after myocardial infarction, and neutrophil count has been clinically implicated to be associated with coronary disease severity. Histidine decarboxylase (HDC) has been implicated in regulating reactive oxidative species (ROS) and the differentiation of myeloid cells. However, the effect of HDC on neutrophils after myocardial infarction remains unclear. Here, we found that neutrophils were disorderly recruited into the ischemic injured area of the myocardium of Hdc deficiency (Hdc-/-) mice. Moreover, Hdc deficiency led to attenuated adhesion but enhanced migration and augmented ROS/neutrophil extracellular traps (NETs) production in neutrophils. Hdc-/- mouse-derived NETs promoted cardiomyocyte death and cardiac fibroblast proliferation/migration. Furthermore, protein arginine methyltransferase 1 (PRMT1) was increased in Hdc-/- mouse-derived neutrophils but decreased with exogenous histamine treatment. Its expression could be rescued by blocking histamine receptor 1 (H1R), inhibiting ATP synthesis or reducing SWItch/sucrose non fermentable (SWI/SNF) chromatin remodeling complex. Accordingly, histamine or MS023 treatment could decrease ROS and NETs ex vivo, and ameliorated cardiac function and fibrosis, along with the reduced NETs in plasma in vivo. Together, our findings unveil the role of HDC in NETosis by histamine-H1R-ATP-SWI/SNF-PRMT1-ROS signaling and provide new biomarkers and targets for identifying and tuning the detrimental immune state in cardiovascular disease.
The Impact of Racial and Ethnic Health Disparities in Diabetes Management on Clinical Outcomes: A Reinforcement Learning Analysis of Health Inequity Among Youth and Young Adults in the SEARCH for Diabetes in Youth Study
Authors: Anna R. Kahkoska, Teeranan Pokaprakarn, G. Rumay Alexander, Tessa L. Crume, Dana Dabelea, Jasmin Divers, Lawrence M. Dolan, Elizabeth T. Jensen, Jean M. Lawrence, Santica Marcovina, Amy K. Mottl, Catherine Pihoker, Sharon H. Saydah, Michael R. Kosorok, Elizabeth J. Mayer-Davis
Journal: Diabetes Care (2021)

OBJECTIVE To estimate difference in population-level glycemic control and the emergence of diabetes complications given a theoretical scenario in which non-White youth and young adults (YYA) with type 1 diabetes (T1D) receive and follow an equivalent distribution of diabetes treatment regimens as non-Hispanic White YYA. RESEARCH DESIGN AND METHODS Longitudinal data from YYA diagnosed 2002–2005 in the SEARCH for Diabetes in Youth Study were analyzed. Based on self-reported race/ethnicity, YYA were classified as non-White race or Hispanic ethnicity (non-White subgroup) versus non-Hispanic White race (White subgroup). In the White versus non-White subgroups, the propensity score models estimated treatment regimens, including patterns of insulin modality, self-monitored glucose frequency, and continuous glucose monitoring use. An analysis based on policy evaluation techniques in reinforcement learning estimated the effect of each treatment regimen on mean hemoglobin A1c (HbA1c) and the prevalence of diabetes complications for non-White YYA. RESULTS The study included 978 YYA. The sample was 47.5% female and 77.5% non-Hispanic White, with a mean age of 12.8 ± 2.4 years at diagnosis. The estimated population mean of longitudinal average HbA1c over visits was 9.2% and 8.2% for the non-White and White subgroup, respectively (difference of 0.9%). Within the non-White subgroup, mean HbA1c across visits was estimated to decrease by 0.33% (95% CI −0.45, −0.21) if these YYA received the distribution of diabetes treatment regimens of the White subgroup, explaining ∼35% of the estimated difference between the two subgroups. The non-White subgroup was also estimated to have a lower risk of developing diabetic retinopathy, diabetic kidney disease, and peripheral neuropathy with the White youth treatment regimen distribution (P &amp;lt; 0.05), although the low proportion of YYA who developed complications limited statistical power for risk estimations. CONCLUSIONS Mathematically modeling an equalized distribution of T1D self-management tools and technology accounted for part of but not all disparities in glycemic control between non-White and White YYA, underscoring the complexity of race and ethnicity-based health inequity.
Characterization of myeloid neoplasms following allogeneic hematopoietic cell transplantation
Authors: Masatomo Kuno, Satoshi Yamasaki, Nobuharu Fujii, Yasushi Ishida, Takahiro Fukuda, Keisuke Kataoka, Naoyuki Uchida, Yuta Katayama, Maho Sato, Daishi Onai, Toshihiro Miyamoto, Shuichi Ota, Satoshi Yoshioka, Takahide Ara, Akira Hangaishi, Yoshiko Hashii, Makoto Onizuka, Tatsuo Ichinohe, Yoshiko Atsuta, Yoshihiro Inamoto
Journal: American Journal of Hematology (2021)

We compared characteristics of myeloid neoplasms (MNs) following allogeneic hematopoietic cell transplantation (HCT) versus autologous HCT using a Japanese HCT registry database. Among 43 788 patients who underwent allogeneic (n = 18 874) or autologous HCT (n = 24 914) for non-myeloid malignancies or non-malignant diseases, 352 developed MNs. The cumulative incidence of MNs was lower after allogeneic HCT than after autologous HCT (0.3% vs. 1.8% at 10 years, respectively, p < .001). Compared with autologous HCT, MNs following allogeneic HCT developed in younger patients (median, 42 vs. 57 years old, respectively) and sooner after HCT (median, 16 vs. 33 months, respectively). Approximately half of MNs following allogeneic HCT were donor-derived and occurred later than recipient-derived MNs (median, 26 vs. 6 months, respectively, p = .003). In multivariate analysis, reduced-intensity conditioning and cord blood transplantation were associated with MN development after allogeneic HCT. Overall survival was similar in patients who developed MNs following allogeneic versus autologous HCT (18% vs. 22% at 5 years, respectively, p = .48). Patient age ≥ 55 years, the presence of previous HCT, AML subtype, and chromosome 5 or 7 abnormalities were adverse factors for overall survival after MN diagnosis. Further research is warranted to elucidate the mechanisms of MN development following allogeneic HCT.
Rationale and design of the Dapagliflozin after Transcatheter Aortic Valve Implantation (<scp>DapaTAVI</scp>) randomized trial
Authors: Ignacio J. Amat‐Santos, Juan P. Sánchez‐Luna, Emad Abu‐Assi, María Melendo‐Viu, Ignacio Cruz‐Gonzalez, Luis Nombela‐Franco, Antonio J. Muñoz‐Garcí, Sergio G. Blas, Jose M. de la Torre Hernandez, Rafael Romaguera, Ángel Sánchez‐Recalde, José L. Diez‐Gil, Diego Lopez‐Otero, Livia Gheorge, Borja Ibáñez, Andrés Iñiguez‐Romo, Sergio Raposeiras‐Roubín
Journal: European Journal of Heart Failure (2021)
Abstract 15068: Neurofibromin 2 Regulates Metabolism in the Heart
Authors: Yu Zhang, Wataru Mizushima, Peiyong Zhai, Dominic P Del Re
Journal: Circulation (2018)

Introduction: Neurofibromin 2 (NF2) is a tumor suppressor that modulates cell proliferation and survival. We previously demonstrated that NF2 mediates cardiomyocyte apoptosis and injury caused by a...
Barnase*Barstar-guided two-step targeting approach for drug delivery to tumor cells in vivo
Authors: E.I. Shramova, M.V. Shilova, A.V. Ryabova, D.S. Dzhalilova, N.A. Zolotova, G.B. Telegin, S.M. Deyev, G.M. Proshkina
Journal: Journal of Controlled Release (2021)
Closed-loop enhancement and neural decoding of cognitive control in humans
Authors: Ishita Basu, Ali Yousefi, Britni Crocker, Rina Zelmann, Angelique C. Paulk, Noam Peled, Kristen K. Ellard, Daniel S. Weisholtz, G. Rees Cosgrove, Thilo Deckersbach, Uri T. Eden, Emad N. Eskandar, Darin D. Dougherty, Sydney S. Cash, Alik S. Widge
Journal: Nature Biomedical Engineering (2021)
Reply
Authors: David Simon, Filippo Fagni, Koray Tascilar, Georg Schett
Journal: Arthritis & Rheumatology (2021)

We appreciate the comments from Dr. Evangelatos and colleagues on our study of SARS–CoV-2 vaccine responses in RTX-treated patients. The authors briefly reviewed current evidence on the reduced rates of response to SARS–CoV-2 vaccines among patients undergoing B cell depletion therapy with RTX and provided novel data on this topic. In a series of 11 patients with immune-mediated inflammatory diseases treated with RTX, only 2 patients developed detectable levels of IgG antibodies against SARS–CoV-2 spike protein after vaccination with the BNT162b2 mRNA SARS–CoV-2 vaccine. This finding supports observations from other studies (1, 2), including our own, in which we showed that humoral but not T cell–mediated responses to SARS–CoV-2 vaccination are reduced in patients treated with RTX. These findings are highly relevant to the estimated 700,000 patients with hematologic malignancies (3) and 900,000 patients with immune-mediated inflammatory diseases (4) treated with RTX worldwide. Of note, RTX-treated patients show an increased risk of severe COVID-19 (5). Therefore, in light of the impaired humoral immune response to SARS–CoV-2 vaccination, new vaccination strategies and careful monitoring of vaccine efficacy are needed for this patient population, as urged by Evangelatos et al. For RTX-treated patients who have not been vaccinated, RTX therapy and vaccination regimens should be aligned. Thus, RTX administration can be time-adjusted, as also recommended in the American College of Rheumatology guidelines (vaccination 4 weeks before RTX administration [6]), or it could be administered depending on the grade of repopulation of peripheral B cells. The latter approach is reasonable, since adequate humoral immune responses are more likely if at least some B cells are detectable in the peripheral blood (1). However, further studies are needed to determine the effect of B cell repopulation and the best timing of vaccination. Of note, T cell responses to SARS–CoV-2 vaccination have been shown to be intact in RTX-treated patients, and they have also been shown to support defense against infection and the development of severe COVID-19 (1). Therefore, patients treated with RTX should receive SARS–CoV-2 vaccination even in the absence of B cells. Furthermore, humoral immune responses should be assessed in RTX-treated patients who have received a full SARS–CoV-2 vaccination regimen. Fully vaccinated individuals who do not respond could benefit from additional boosters to achieve a protective humoral response (7). In this context, the observation that SARS–CoV-2 infection can mobilize tissue B cells and trigger protective antibody formation in RTX-treated patients without peripheral B cells is interesting and may support the use of booster vaccinations. When the standard vaccination regimen has failed, a humoral immune response may be mobilized by the timely administration of booster vaccines and by cross-vaccinating with different vaccine agents.
BRD4 Regulates Transcription Factor ΔNp63α to Drive a Cancer Stem Cell Phenotype in Squamous Cell Carcinomas
Authors: Matthew L. Fisher, Seamus Balinth, Yon Hwangbo, Caizhi Wu, Carlos Ballon, John E. Wilkinson, Gary L. Goldberg, Alea A. Mills
Journal: Cancer Research (2021)

Abstract Bromodomain containing protein 4 (BRD4) plays a critical role in controlling the expression of genes involved in development and cancer. Inactivation of BRD4 inhibits cancer growth, making it a promising anticancer drug target. The cancer stem cell (CSC) population is a key driver of recurrence and metastasis in patients with cancer. Here we show that cancer stem-like cells can be enriched from squamous cell carcinomas (SCC), and that these cells display an aggressive phenotype with enhanced stem cell marker expression, migration, invasion, and tumor growth. BRD4 is highly elevated in this aggressive subpopulation of cells, and its function is critical for these CSC-like properties. Moreover, BRD4 regulates ΔNp63α, a key transcription factor that is essential for epithelial stem cell function that is often overexpressed in cancers. BRD4 regulates an EZH2/STAT3 complex that leads to increased ΔNp63α-mediated transcription. Targeting BRD4 in human SCC reduces ΔNp63α, leading to inhibition of spheroid formation, migration, invasion, and tumor growth. These studies identify a novel BRD4-regulated signaling network in a subpopulation of cancer stem-like cells, elucidating a possible avenue for effective therapeutic intervention. Significance: This study identifies a signaling cascade driven by BRD4 that upregulates ΔNp63α to promote cancer stem-like properties, which has potential therapeutic implications for the treatment of squamous cell carcinomas.
Prevalence of <i>BRAF</i>V600 in glioma and use of <i>BRAF</i> Inhibitors in patients with <i>BRAF</i>V600 mutation-positive glioma: systematic review
Authors: Lily J Andrews, Zak A Thornton, Saanwalshah S Saincher, Ian Y Yao, Sarah Dawson, Luke A McGuinness, Hayley E Jones, Sarah Jefferies, Susan C Short, Hung-Yuan Cheng, Alexandra McAleenan, Julian P T Higgins, Kathreena M Kurian
Journal: Neuro-Oncology (2021)

Detailed prevalence estimates of BRAFV600 mutations and BRAF inhibitor (BRAFi) treatment responses in V600-mutant glioma will inform trial development.
Supervised versus unsupervised primaquine radical cure for the treatment of falciparum and vivax malaria in Papua, Indonesia: a cluster-randomised, controlled, open-label superiority trial
Authors: Jeanne Rini Poespoprodjo, Faustina Helena Burdam, Freis Candrawati, Benedikt Ley, Niamh Meagher, Enny Kenangalem, Ratni Indrawanti, Leily Trianty, Kamala Thriemer, David J Price, Julie A Simpson, Ric N Price
Journal: The Lancet Infectious Diseases (2021)
Melanoma Screening—Time for a Reset?
Authors: Allan C. Halpern, Michael A. Marchetti
Journal: JAMA Dermatology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Anti‐BCMA Immuno‐NanoPET Radiotracers for Improved Detection of Multiple Myeloma
Authors: Eloise Thomas, Clélia Mathieu, Patricia Moreno‐Gaona, Vincent Mittelheisser, François Lux, Olivier Tillement, Xavier Pivot, Paiman Peter Ghoroghchian, Alexandre Detappe
Journal: Advanced Healthcare Materials (2021)

Abstract Current clinical imaging modalities for the sensitive and specific detection of multiple myeloma (MM) rely on nonspecific imaging contrast agents based on gadolinium chelates for magnetic resonance imaging (MRI) or for 18 F‐FDG‐directed and combined positron emission tomography (PET) and computed tomography (CT) scans. These tracers are not, however, able to detect minute plasma cell populations in the tumor niche, leading to false negative results. Here, a novel PET‐based anti‐BCMA nanoplatform labeled with 64 Cu is developed to improve the monitoring of these cells in both the spine and femur and to compare its sensitivity and specificity to more conventional immunoPET ( 64 Cu labeled anti‐BCMA antibody) and passively targeted PET radiotracers ( 64 CuCl 2 and 18 F‐FDG). This proof‐of‐concept preclinical study confirmed that by conjugating up to four times more radioisotopes per antibody with the immuno‐nanoPET platform, an improvement in the sensitivity and in the specificity of PET to detect tumor cells in an orthotopic model of MM is observed when compared to the traditional immunoPET approach. It is anticipated that when combined with tumor biopsy, this immuno‐nanoPET platform may improve the management of patients with MM.
Aberrant Expression and Subcellular Localization of ECT2 Drives Colorectal Cancer Progression and Growth
Authors: Danielle R. Cook, Melissa Kang, Timothy D. Martin, Joseph A. Galanko, Gabriela H. Loeza, Dimitri G. Trembath, Verline Justilien, Karen A. Pickering, David F. Vincent, Armin Jarosch, Philipp Jurmeister, Andrew M. Waters, Priya S. Hibshman, Andrew D. Campbell, Catriona A. Ford, Temitope O. Keku, Jen Jen Yeh, Michael S. Lee, Adrienne D. Cox, Alan P. Fields, Robert S. Sandler, Owen J. Sansom, Christine Sers, Antje Schaefer, Channing J. Der
Journal: Cancer Research (2021)

Abstract ECT2 is an activator of RHO GTPases that is essential for cytokinesis. In addition, ECT2 was identified as an oncoprotein when expressed ectopically in NIH/3T3 fibroblasts. However, oncogenic activation of ECT2 resulted from N-terminal truncation, and such truncated ECT2 proteins have not been found in patients with cancer. In this study, we observed elevated expression of full-length ECT2 protein in preneoplastic colon adenomas, driven by increased ECT2 mRNA abundance and associated with APC tumor-suppressor loss. Elevated ECT2 levels were detected in the cytoplasm and nucleus of colorectal cancer tissue, suggesting cytoplasmic mislocalization as one mechanism of early oncogenic ECT2 activation. Importantly, elevated nuclear ECT2 correlated with poorly differentiated tumors, and a low cytoplasmic:nuclear ratio of ECT2 protein correlated with poor patient survival, suggesting that nuclear and cytoplasmic ECT2 play distinct roles in colorectal cancer. Depletion of ECT2 reduced anchorage-independent cancer cell growth and invasion independent of its function in cytokinesis, and loss of Ect2 extended survival in a KrasG12D Apc-null colon cancer mouse model. Expression of ECT2 variants with impaired nuclear localization or guanine nucleotide exchange catalytic activity failed to restore cancer cell growth or invasion, indicating that active, nuclear ECT2 is required to support tumor progression. Nuclear ECT2 promoted ribosomal DNA transcription and ribosome biogenesis in colorectal cancer. These results support a driver role for both cytoplasmic and nuclear ECT2 overexpression in colorectal cancer and emphasize the critical role of precise subcellular localization in dictating ECT2 function in neoplastic cells. Significance: ECT2 overexpression and mislocalization support its role as a driver in colon cancer that is independent from its function in normal cell cytokinesis.
Application or function of citric acid in drug delivery platforms
Authors: Malihe Pooresmaeil, Siamak Javanbakht, Hassan Namazi, Ahmad Shaabani
Journal: Medicinal Research Reviews (2021)

Abstract Nontoxic materials with natural origin are promising materials in the designing and preparation of the new drug delivery systems (DDSs). Today's, citric acid (CA) has attracted a great deal of attention because of its special features; green nature, biocompatibility, low price, biodegradability, and commercially available property. So, CA has been employed in the preparation of the various platforms to induce a suitable property on their structure. Recently, several research groups investigated the CA‐based platforms in different forms like tablets, dendrimers, hyperbranched polymers, (co)polymer, hydrogels, and nanoparticles as efficient DDSs. By considering an increasing amount of published articles in this field, for the first time, in this review, an overview of the published works regarding CA applications in the design of various DDSs is presented with a detailed and insightful discussion.
GATA‐3 and T‐bet as diagnostic markers of non‐esophageal eosinophilic gastrointestinal disease
Authors: Joseph L. Neely, Annika Reimers, Steve Taylor, Shipra Garg, Mia Y. Masuda, Shauna Schroeder, Benjamin L. Wright, Alfred D. Doyle
Journal: Allergy (2021)

Dr. Schroeder has received research funding from Allakos, Regeneron, and Takeda. Dr. Wright has received research funding from Allakos. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Minimal Residual Disease Dynamics after Venetoclax-Obinutuzumab Treatment: Extended Off-Treatment Follow-up From the Randomized CLL14 Study
Authors: Othman Al-Sawaf, Can Zhang, Tong Lu, Michael Z. Liao, Anesh Panchal, Sandra Robrecht, Travers Ching, Maneesh Tandon, Anna-Maria Fink, Eugen Tausch, Christof Schneider, Matthias Ritgen, Sebastian Böttcher, Karl-Anton Kreuzer, Brenda Chyla, Dale Miles, Clemens-Martin Wendtner, Barbara Eichhorst, Stephan Stilgenbauer, Yanwen Jiang, Michael Hallek, Kirsten Fischer
Journal: Journal of Clinical Oncology (2021)

The CLL14 study has established one-year fixed-duration treatment of venetoclax and obinutuzumab (Ven-Obi) for patients with previously untreated chronic lymphocytic leukemia. With all patients off treatment for at least three years, we report a detailed analysis of minimal residual disease (MRD) kinetics and long-term outcome of patients treated in the CLL14 study.Patients were randomly assigned to receive six cycles of obinutuzumab with 12 cycles of venetoclax or 12 cycles of chlorambucil (Clb-Obi). Progression-free survival (PFS) was the primary end point. Key secondary end points included rates of undetectable MRD and overall survival. To analyze MRD kinetics, a population-based growth model with nonlinear mixed effects approach was developed.Of 432 patients, 216 were assigned to Ven-Obi and 216 to Clb-Obi. Three months after treatment completion, 40% of patients in the Ven-Obi arm (7% in the Clb-Obi arm) had undetectable MRD levels < 10-6 by next-generation sequencing in peripheral blood. Median MRD doubling time was longer after Ven-Obi than Clb-Obi therapy (median 80 v 69 days). At a median follow-up of 52.4 months, a sustained significant PFS improvement was observed in the Ven-Obi arm compared with Clb-Obi (median not reached v 36.4 months; hazard ratio 0.33; 95% CI, 0.25 to 0.45; P < .0001). The estimated 4-year PFS rate was 74.0% in the Ven-Obi and 35.4% in the Clb-Obi arm. No difference in overall survival was observed (hazard ratio 0.85; 95% CI, 0.54 to 1.35; P = .49). No new safety signals occurred.Appearance of MRD after Ven-Obi is significantly slower than that after Clb-Obi with more effective MRD reduction. These findings translate into a superior long-term efficacy with the majority of Ven-Obi-treated patients remaining in remission.