tbuckley/cabot-search huggingface dataset:
E4BP4-mediated inhibition of T follicular helper cell differentiation is compromised in autoimmune diseases
Authors: Zijun Wang, Ming Zhao, Jinghua Yin, Limin Liu, Longyuan Hu, Yi Huang, Aiyun Liu, Jiajun Ouyang, Xiaoli Min, Shijia Rao, Wenhui Zhou, Haijing Wu, Akihiko Yoshimura, Qianjin Lu
Journal: Journal of Clinical Investigation (2020)

T follicular helper (Tfh) cells are indispensable for the formation of germinal center (GC) reactions, whereas T follicular regulatory (Tfr) cells inhibit Tfh-mediated GC responses. Aberrant activation of Tfh cells contributes substantially to the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE). Nonetheless, the molecular mechanisms mitigating excessive Tfh cell differentiation are not fully understood. Herein we demonstrate that the adenovirus E4 promoter-binding protein (E4BP4) mediates a feedback loop and acts as a transcriptional brake to inhibit Tfh cell differentiation. Furthermore, we show that such an immunological mechanism is compromised in patients with SLE. Establishing mice with either conditional knockout (cKO) or knockin (cKI) of the E4bp4 gene in T cells reveals that E4BP4 strongly inhibits Tfh cell differentiation. Mechanistically, E4BP4 regulates Bcl6 transcription by recruiting the repressive epigenetic modifiers HDAC1 and EZH2. E4BP4 phosphorylation site mutants have limited capability with regard to inhibiting Tfh cell differentiation. In SLE, we detected impaired phosphorylation of E4BP4, finding that this compromised transcription factor is positively correlated with disease activity. These findings unveiled molecular mechanisms by which E4BP4 restrains Tfh cell differentiation, whose compromised function is associated with uncontrolled autoimmune reactions in SLE.
Nuclear localization of the androgen receptor in prostate cancer circulating tumor cells from men who have failed androgen deprivation therapy.
Authors: Joshua Michael Lang, Benjamin Pun Casavant, Scott Michael Berry, Lindsay Nicole Strotman, Stephanie Margaret Thiede, Jamie Sperger, Glenn Liu, David J. Beebe
Journal: Journal of Clinical Oncology (2013)

e22141 Background: Prostate cancer (PRCA) is driven by the Androgen Receptor (AR), a cytoplasmic protein that translocates to the nucleus to activate a transcriptional program critical to PRCA tumorigenesis. The AR is the major therapeutic target in PRCA, with multiple drugs that improve survival and quality of life for men with advanced PRCA. However, few biomarkers can assay for AR activity to identify those most likely to benefit from AR-targeting therapies. Methods: Utilizing a novel microfluidic technology known as the VERSA (Vertical Exclusion-based Rare Sample Analysis) platform, CTCs were captured and purified from men with advanced PRCA who had failed androgen deprivation therapy. CTCs were then stained and imaged via epiflourescent microscopy for EpCAM, AR, Hoechst and CD45. The enhanced optical imaging of the VERSA platform enabled subcellular localization of the AR and calculation of the relative amount of AR localized to the nucleus as a biomarker of resistance to AR-targeting therapies. Results: CTCs were prospectively collected and analyzed for AR nuclear localization. Significant heterogeneity in AR localization was found between patients who had failed androgen deprivation therapy with the mean nuclear AR ranging from 20-57% of total AR. Significant intra-patient heterogeneity was also identified with the percentage of AR localized to the nucleus ranging from 11-77% of total AR. DNA and mRNA have been isolated from these cells to analyze for underlying mechanisms of nuclear localization. Conclusions: The VERSA platform is able to analyze subcellular localization of proteins in CTCs followed by total nucleic acid extraction. We show that among men whose disease has progressed through androgen deprivation, a significant portion of the AR is localized to the nucleus as a possible biomarker of resistance to AR targeting therapies. We also identify significant heterogeneity in AR localization among CTCs, suggesting resistant PRCA clones that have greater proliferative potential.
A COMPOSITE ECHOCARDIOGRAPHIC SCORE TO PREDICT LONG-TERM SURVIVAL FOLLOWING MYOCARDIAL INFARCTION
Authors: Anish Krishnan, Sandhir B. Prasad, Kristyan B. Guppy-Coles, Christopher Hammett, Gillian Whalley, David Holland, Thomas Liza, John Atherton
Journal: Journal of the American College of Cardiology (2020)
NATIVE T1 MAPPING USING CMR ADENOSINE STRESS PROTOCOL IS ASSOCIATED WITH TROPONIN LEVELS IN PATIENTS WITH CHEST PAIN AND DETECTABLE TROPONINS: SUB-ANALYSIS OF THE CMR-IMPACT TRIAL
Authors: Carolyn Park, Jennifer Jordan, Subha V. Raman, Michael Hall, W. Hundley, Chadwick Miller
Journal: Journal of the American College of Cardiology (2020)
ASSOCIATION OF LOW-DENSITY LIPOPROTEIN TRIGLYCERIDES (LDL-TG) AND REMNANT-LIKE PROTEIN CHOLESTEROL (RLP-C) WITH CARDIOVASCULAR EVENTS IN THE ELDERLY: THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY
Authors: Aliza Hussain, Wensheng Sun, Elizabeth Selvin, Vijay Nambi, Josef Coresh, Adrienne Tin, Xiaoming Jia, Christie M. Ballantyne, Ron Hoogeveen
Journal: Journal of the American College of Cardiology (2020)
Role of non-coding RNA networks in leukemia progression, metastasis and drug resistance
Authors: Ajaz A. Bhat, Salma N. Younes, Syed Shadab Raza, Lubna Zarif, Sabah Nisar, Ikhlak Ahmed, Rashid Mir, Sachin Kumar, Surender K. Sharawat, Sheema Hashem, Imadeldin Elfaki, Michal Kulinski, Shilpa Kuttikrishnan, Kirti S. Prabhu, Abdul Q. Khan, Santosh K. Yadav, Wael El-Rifai, Mohammad A. Zargar, Hatem Zayed, Mohammad Haris, Shahab Uddin
Journal: Molecular Cancer (2020)

Abstract Early-stage detection of leukemia is a critical determinant for successful treatment of the disease and can increase the survival rate of leukemia patients. The factors limiting the current screening approaches to leukemia include low sensitivity and specificity, high costs, and a low participation rate. An approach based on novel and innovative biomarkers with high accuracy from peripheral blood offers a comfortable and appealing alternative to patients, potentially leading to a higher participation rate. Recently, non-coding RNAs due to their involvement in vital oncogenic processes such as differentiation, proliferation, migration, angiogenesis and apoptosis have attracted much attention as potential diagnostic and prognostic biomarkers in leukemia. Emerging lines of evidence have shown that the mutational spectrum and dysregulated expression of non-coding RNA genes are closely associated with the development and progression of various cancers, including leukemia. In this review, we highlight the expression and functional roles of different types of non-coding RNAs in leukemia and discuss their potential clinical applications as diagnostic or prognostic biomarkers and therapeutic targets.
Annals Graphic Medicine - Progress Notes: Common Fears
Authors: Michael Natter
Journal: Annals of Internal Medicine (2020)

Web Exclusives17 March 2020Annals Graphic Medicine - Progress Notes: Common FearsFREEMichael Natter, MDMichael Natter, MDNYU School of Medicine, New York, New York (M.N.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G20-0007 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: NYU School of Medicine, New York, New York (M.N.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G19-0002.Author/Illustrator Information: Michael Natter, MD, is a current internal medicine resident at NYU School of Medicine and a graduate of Sidney Kimmel Medical College of Thomas Jefferson University in Philadelphia. His artwork is inspired by his medical training, patient encounters, and the human condition. A type 1 diabetic, Dr. Natter views himself as a patient as well as a doctor and plans to pursue a fellowship in endocrinology to help others who also share his disease. You can find more of his illustrations, stories, and comics on Instagram (www.instagram.com/mike.natter) and Twitter (@mike_natter).About Progress Notes: Progress Notes explores the everyday emotional, clinical, humorous, and ethical challenges of the medical residency training process. As implied by the title of the series, these pieces act as a visual bildungsroman, graphically dissecting the subtext of what it means to be a young doctor in today's medical world. Progress Notes appears monthly in Annals Graphic Medicine at Annals.org. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 17 March 2020Volume 172, Issue 6Page: W80-W81KeywordsConflicts of interestDisclosureEmotionsEndocrinologyFearFellowshipsGraduate medical educationResidency ePublished: 17 March 2020 Issue Published: 17 March 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
THROMBOEMBOLIC RISK IN ATRIAL FIBRILLATION PATIENTS WITH LEFT ATRIAL SCAR RESULTING FROM EXTENSIVE ABLATION
Authors: Sanghamitra Mohanty, Chintan Trivedi, Domenico Della Rocca, Carola Gianni, Anu Salwan, Alisara Anannab, Bryan Macdonald, Angel Mayedo, Mohamed Bassiouny, Gerald Gallinghouse, John Burkhardt, Rodney Horton, Luigi Di Biase, Amin Al-Ahmad, Andrea Natale
Journal: Journal of the American College of Cardiology (2020)
Prognosis of melanoma in Peru: An analysis of 410 cases.
Authors: Natalia Coras, Domingo Morales, Alejandro Yabar, Brady Ernesto Beltran
Journal: Journal of Clinical Oncology (2013)

e20023 Background: Little is known of the status of melanoma in developing countries. Our retrospective study was performed to determine the clinical characteristics and outcome of patients with melanoma in Peru. Methods: All cases with a pathological diagnosis of malignant melanoma from our institution between January 2002 and December 2011 were identified. Clinical data were extracted through retrospective chart review. Patients’ characteristics are presented using descriptive statistics. Survival curves were estimated using the Kaplan-Meier method. Univariate and multivariate analyses were evaluated using log-rank and Cox proportional-hazard regression tests, respectively. Results: A total of 410 cases were evaluated. The median age at presentation was 66 years (range 4-97 years) with a male-to-female ratio was 1.1:1. There were 146 cases (35.6%) of acral lentiginous melanoma, 67 (16.3%) of nodular melanoma, 54 (16.3%) of mucosal melanoma, 39 (9.5%) of superficial spreading melanoma, 55 (13.4%) were lentigo maligno and 49 (12.0%) were unclassifiable. Melanoma of unknown primary occurred in 34 (8.3%) of cases. The proportion of patients with stage I, II, III and IV disease were 24.2%, 24.8%, 21.9% and 7.8%, respectively. Ulceration status of 320 cases of cutaneous melanoma was recorded and 138 (45.1%) had ulceration. The 5-year survival rate of 409 patients was 58.4% with a median survival time of 7.6 years. The 5-year survival rates of patients with stage I, II, III and IV disease were 88.2%, 67.8%, 39.3% and 17.8% respectively (p&lt;0.001). Univariate analysis showed age &gt;65 years (p=0.003), male sex (p=0.0001), stage (p&lt;0.001), nodular histology type (p&lt;0.001), ulceration (p&lt;0.001), Breslow thickness (p&lt;0.001), Clark level (p&lt;0.001) and localization (mucosal vs. cutaneous) (p&lt;0.001) were associated with survival. In the multivariate analysis, stage was associated with worst prognosis (p=0.01), while other factors had no statistical correlation with survival. Conclusions: Based on our report, acral lentiginous melanoma is the most common type of malignant melanoma in Peruvian patients, and clinical stage was the only independent prognostic factor associated with survival.
THE ASSOCIATION BETWEEN HEALTHFUL AND UNHEALTHFUL PLANT BASED DIETARY PATTERNS AND 10-YEAR CARDIOVASCULAR DISEASE INCIDENCE IN APPARENTLY HEALTHY MEN AND WOMEN: HIGHLIGHTS FROM THE ATTICA PROSPECTIVE (2002-2012) STUDY
Authors: Demosthenes Panagiotakos, Matina Kouvari, Christina Chrysohoou, Ekavi Georgousopoulou, Dimitrios Tousoulis, Christos Pitsavos
Journal: Journal of the American College of Cardiology (2020)
Effect of Sonic hedgehog activation on CXCR7 expression and CXCR4 signaling in medulloblastoma.
Authors: Stacey Anne Ward, Rajarshi Sengupta, Joshua Rubin
Journal: Journal of Clinical Oncology (2013)

e13537 Background: Stratification of pediatric medullolastoma into molecular subtypes elevates hopes that subtype-specific therapy can be more efficacious and less toxic. To realize this goal, the molecular targets that distinguish each subtype must be defined. We found that Sonic hedgehog (Shh)-subtype medulloblastoma can be further divided by CXCR4 expression and that CXCR4 inhibition has potent anti-tumor effects. Here we present data that Shh regulates CXCR4 activity through CXCR7, whose differential expression between normal granule cells and medulloblastoma cells makes its function an ideal therapeutic target. Methods: Single-cell suspensions were plated with or without Shh or cyclopamine followed by treatment with CXCL12. SmoA1 brain tumors were dissociated into single cells and transplanted into nude mice and treated with vehicle, AMD3100, GDC-0449, or both. Tumors were measured and harvested at the conclusion of treatment. Results: Using primary cultures of Shh-driven medulloblastoma we found that Shh activation enhances CXCR4 surface localization and promotes CXCL12-induced signaling, similar to effects of Shh on normal granule cells. We evaluated expression of CXCR4 internalization regulators and found that Shh activation altered the levels of GRKs, arrestins and CXCR7. Among these, CXCR7 expression exhibited the greatest differential response to Shh pathway activation between normal cells and medulloblastoma: CXCR7 expression was highly expressed in normal cells despite Shh effects, but almost completely absent in tumor cells. Conclusions: We conclude that activation of the Shh pathway in medulloblastomas promotes CXCR4 surface localization through inhibition of internalization mediators. This cross-talk is also evident in developing GPCs but with one notable difference: CXCR7 expression (high in normal cells, absent in tumor cells). This distinction suggests that CXCR7 antagonists, which are moving towards clinical trials, may be detrimental to normal cerebellar development and inactive against medulloblastoma. We propose that restoring CXCR7 activity would have negligible effects on granule cells and potently block CXCR4 function in medulloblastoma.
Uterine Patterning, Endometrial Gland Development, and Implantation Failure in Mice Exposed Neonatally to Genistein
Authors: Wendy N. Jefferson, Elizabeth Padilla-Banks, Alisa A. Suen, Lindsey J. Royer, Sharon M. Zeldin, Ripla Arora, Carmen J. Williams
Journal: Environmental Health Perspectives (2020)

Embryo implantation relies on precise hormonal regulation, associated gene expression changes, and appropriate female reproductive tract tissue architecture. Female mice exposed neonatally to the phytoestrogen genistein (GEN) at doses similar to those in infants consuming soy-based infant formulas are infertile due in part to uterine implantation defects.
DEVELOPMENT AND VALIDATION OF A DEEP LEARNING SYSTEM WITH MULTI-INPUT CONVOLUTIONAL NEURAL NETWORK FOR IDENTIFYING HYPERTROPHIC CARDIOMYOPATHY IN CARDIAC MAGNETIC RESONANCE IMAGES
Authors: Yutaro Miyoshi, Shuichiro Kaji, Toshiaki Toyota, Kitae Kim, Takeshi Kitai, Atsushi Kobori, Natsuhiko Ehara, Makoto Kinoshita, Yutaka Furukawa
Journal: Journal of the American College of Cardiology (2020)
LONG-TERM OUTCOMES AMONG PATIENTS WITH MEDIASTINAL RADIATION-INDUCED CORONARY ARTERY DISEASE UNDERGOING PERCUTANEOUS CORONARY INTERVENTION VERSUS CORONARY ARTERY BYPASS GRAFTING
Authors: Aaron Dunn, Eoin Donnellan, Alaa Alashi, Douglas Johnston, Christine Louise Jellis, Gosta Pettersson, Lars G. Svensson, Grant W. Reed, Stephen Ellis, Brian P. Griffin, Milind Desai
Journal: Journal of the American College of Cardiology (2020)
MANIFESTATION OF TROUSSEAU SYNDROME AS INTRA CARDIAC THROMBUS DETECTED BY ECHOCARDIOGRAM IN PATIENT WITH OCCULT MALIGNANCY
Authors: Oluwateniola Olatunde, Ajay Uprety, Vijay Raj, Oluwakanyinsola Adenusi, Tamas Szombathy
Journal: Journal of the American College of Cardiology (2020)
Comparison of doxorubicin cardiotoxicity in pediatric patients when given with dexrazoxane versus a continuous infusion
Authors: C. E. Herzog, W. Huh, N. Jaffe, J. Durand
Journal: Journal of Clinical Oncology (2006)

9044 Background: Despite the effectiveness of doxorubicin (D) in sarcomas, its use is limited by cardiotoxicity. Both delivery by continuous infusion (CI) and use of the cardioprotectant dexrazoxane (Z) have been used to reduce cardiotoxicity. Since 1998 patients with Ewing’s sarcoma seen at MDACC have been treated with a total of 540 mg/m 2 D given with Z (ZD). During this period patients with osteosarcoma have been treated with 360–540 mg/m 2 D given as a 48-hour infusion (CID). Methods: To compare the cardiotoxicity of ZD versus CID, we did a retrospective review of patients seen on the pediatric service at MDACC since 1998. Patients included needed to have had 1) planned therapy of at least 360 mg/m 2 D, given either as ZD or CID; 2) measurement of ejection fraction (EF) prior to any D; and 3) routine monitoring of cardiotoxicity with EF. Patients were recorded as having cardiotoxicity for any EF&lt;50% or clinical symptoms. Groups were compared by 2-sided t-test and Fisher’s Exact test. Results: A total of 64 patients were treated with ZD or DCI, 52 of which are evaluable. Comparison of ZD to CID showed no significant difference in age or male:female ratio. Total D dose was higher in ZD. Cardiotoxicity was higher in DCI as determined by number of patients with cardiotoxicity and EF on worst Echo. Conclusions: Despite the higher total dose of D, patients treated with ZD had less cardiotoxicity. Whether this is due to giving a cardioprotectant or other factors, such as, higher degree of electrolyte abnormalities or greater degree of anemia in patients treated with CID needs to be investigated. [Table: see text] No significant financial relationships to disclose.
Percutaneous hepatic perfusion (PHP or ChemoSat) with melphalan versus best alternative care (BAC) in patients (pts) with hepatic metastases from melanoma: A post hoc analysis of PHP-randomized versus BAC-to-PHP crossover versus BAC-only pts.
Authors: H. Richard Alexander
Journal: Journal of Clinical Oncology (2012)

8570 Background: PHP (Chemosat, Delcath Systems Inc, New York, NY) allows repeated delivery of high dose chemotherapy to the liver while limiting unwanted systemic exposure by extracorporeal filtration of hepatic venous blood. A prospective randomized multicenter study compared melphalan PHP versus BAC in pts with unresectable hepatic metastases from ocular or cutaneous melanoma and showed a highly significant advantage for PHP in terms of the primary endpoint, hepatic PFS, and multiple secondary endpoints. We present an exploratory post-hoc analysis of pts assigned to BAC who crossed over to PHP after disease progression (BAC-to-PHP crossover) versus those who did not (BAC-only) versus PHP-randomized pts. Methods: 93 pts were randomized to PHP (n=44) or BAC (n=49). In the BAC group, crossover to PHP with melphalan was permitted after hepatic disease progression. Up to 6 PHP treatments with melphalan 3.0 mg/kg ideal body weight were given every 4–8 weeks. Results: In the BAC group, 28 of 49 pts crossed over to PHP. Updated efficacy findings (investigator) as of 31 March 2011 are shown in the table. Independent Review Committee results were similar to investigator-assessed efficacy. Safety in BAC-to-PHP crossover pts was similar to that seen in PHP-randomized pts. The most common toxicities in BAC-to-PHP crossover pts were hematological: peri-procedural thrombocytopenia (71%) and anemia (57%), and melphalan-related neutropenia (82%) and thrombocytopenia (79%). Conclusions: Efficacy of melphalan PHP in BAC-to-PHP crossover pts was consistent with that seen in PHP-randomized pts with hepatic metastases from melanoma. Crossover from BAC to PHP after hepatic disease progression led to a median 11-month survival advantage vs BAC alone. [Table: see text]
THE IMPACT OF AORTIC VALVE VELOCITY AND MEAN GRADIENT ON THE INCIDENCE AND SEVERITY OF PROSTHESIS PATIENT MISMATCH FOLLOWING TAVR
Authors: Amr E. Abbas, Ramy Mando, Julien Ternacle, Philippe Pibarot, Josep Rodes-Cabau, Leonardo Guimaraes, George S. Hanzel, Priscilla Sigua-Arce, Robert D. Safian, Wei Lau, Francis Shannon
Journal: Journal of the American College of Cardiology (2020)
RISK-adapted treatment of Burkitt’s lymphomas in childern
Authors: T. Z. Mohran, E. N. Ebeed
Journal: Journal of Clinical Oncology (2006)

9034 Background and Purpose: Various treatment regimens have been implemented in an attempt to improveDFS of children with B cell lymphoma. We evaluates the treatment results of children with stage I, II III Burkitt’s lymphoma at 2 centers in Egypt. Patients and Methods: Patient recruitment in this open non-randomized study occurred from July 1998 to Dec 2002 . 97 patients with pathologically proven Burkitt’s lymphoma stage I to III were diagnosed . All patients were subjected to history, clinical examination, CSF, bone marrow and radiological evaluation. Patients with stage IV were excluded from. Patients with stage I and II received 4 cycles of (A→B→A→B), while patients with stage III received 8 cycles of (A→B→A→B→A→B→A→B). Intrathecals were given during the first 4 cycles. Cycle A was formed of cyclophosphamide, adriamycin, vincristine, cytosine arabinoside, plus intrathecal MTX and cytosine arabinoside. Cycle B was formed of ifosfamide, vepeside, methotrexate, vincristine and intrathecal cytosine arabinoside and mtx. Results: Patients was 97, their age ranged between 2 and 18, theirmean age was 8.6 and median was 8 years.The male to female ratio was 3.8:1. The primary site was the abdomen in 49 patients (50%), peripheral lymph node enlargement was encountered in 38 patients (39.1%). Jaw involvement occurred in 7 patients (7.2%). Two patients (2%) presented with Tonsilar mass and only one patient presented with mass at inner canthus (1%). Patients were staged according to St. Jude staging system. Patient distribution was as follows: Stage I, 18 (18.6%); stage II, 31 (32%); stage III, 48 (49.5%). In August 2003, 90 patients were in continuous complete remission with a follow up period ranged between 8 months and 53 months and a median 39 months. The projected 3 years DFS for the whole group was 93.8%±2.5%. Correlation between DFS and LDH was significant (P=0.01) while correlation with age, sex and stage was insignificant. Conclusions: Treatment result with the prescribed protocol is extremely good. The outcome of non advanced Burkitt’s lymphoma in rural areas of Egypt is comparable to all studies in developed countries. High dose methotrexate is not a must to improve survival of stage I-III Burkitt’s lymphoma. Initial serum LDH level is an important prognostic factor. Key words: Childhood, Burkitt’s lymph. No significant financial relationships to disclose.