tbuckley/cabot-search huggingface dataset:
Comprehensive Genomic Analysis of Flow-Sorted Hodgkin Reed Sternberg Cells Reveals Additional Genetic Bases of Immune Evasion
Authors: Kirsty Wienand, Bjoern Chapuy, Chip Stewart, Andrew Dunford, David Wu, Jaegil Kim, Atanas Kamburov, Fathima Zumla Cader, Matthew D. Ducar, Aaron R. Thorner, Alexander T Heubeck, Michael J Buonopane, Philippe Armand, Scott J Rodig, Jonathan R. Fromm, Gad Getz, Margaret A. Shipp
Journal: Blood (2018)
In vitro detection of drug-induced granzyme B, interferon-gamma, and interleukin-22 releasing cells in different phenotypes of severe cutaneous adverse reactions
Authors: Jettanong Klaewsongkram, Supranee Buranapraditkun, Pattarawat Thantiworasit, Nithikan Suthumcha, Pawinee Rerknimitr, Papapit Tuchinda, Leena Chularojanamontri, Yuttana Srinoulprasert, Ticha Rerkpattanapipat, Kumutnart Chanprapaph, Wareeporn Disphanurat, Panlop Chakkavittumrong, Chonlaphat Sukasem, Napatra Tovanabutra, Chutika Srisuttiyakorn
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 2446: 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) attenuates gemcitabine-induced neutrophil extravasation
Authors: Jinseon Jeong, Yong Jae Kim, Su-Hyun Shin, Do Young Lee, Byoung-Gon Moon, Ki-Young Sohn, Sun Young Yoon, Jae Wha Kim
Journal: Cancer Research (2018)

Abstract Neutrophils are the most abundant leukocyte in circulation and are the first responder to foreign particles and/or injury. Some chemotherapeutics are known to induce depletion of blood neutrophils as its high cytotoxicity. However, it is also possible that circulating neutrophils undergo extravasation in response to chemotactic gradients induced by anticancer agents. Here, we found that 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) attenuates gemcitabine-induced neutrophil extravasation via the inhibition of neutrophil-attracting chemokine expression in macrophages using in vivo and in vitro approaches. First, we observed that there were increased neutrophils infiltrated into the peritoneal cavity following gemcitabine treatment in 4T1 tumor-bearing mice. In addition, gemcitabine increased MIP-2 mRNA expression in the peritoneal cells as well as in other tissues of the mice. Likewise, gemcitabine induced the migration of circulating neutrophils into the peritoneal cavity in normal mice, and PLAG effectively decreased neutrophil migration by inhibiting the expression of adhesion molecules. Inhibition of CXCR2 by its antagonist, reparixin, abrogated gemcitabine-induced neutrophil migration, indicating that chemokines produced by gemcitabine mainly support neutrophil activation. In vitro experiments demonstrated that PLAG inhibited NADPH oxidase (NOX)-mediated reactive oxygen species production induced by gemcitabine, which is upstream of MIP-2 and/or CXCL8. Importantly, PLAG downregulated gemcitabine-induced membrane translocation of the cytosolic NOX subunit, Rac1, and phosphorylation of p47phox. We also demonstrated that 1-palmitoyl-2-linoleic-3-hydroxyl-rac-glycerol (PLH), the natural form of diacylglycerol, has no effects on gemcitabine-induced CXCL8 production and dHL-60 migration, suggesting that an acetyl group at the third position of the glycerol backbone may have a key role in the regulation of neutrophil activation. Altogether, this study suggests the potential of PLAG as a therapeutic strategy to modulate chemotherapy-induced neutrophil activation for cancer patients undergoing chemotherapeutic treatment. Citation Format: Jinseon Jeong, Yong Jae Kim, Su-Hyun Shin, Do Young Lee, Byoung-Gon Moon, Ki-Young Sohn, Sun Young Yoon, Jae Wha Kim. 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) attenuates gemcitabine-induced neutrophil extravasation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2446.
Evolving and expanding scope of lupus-inducing drugs
Authors: Robert L Rubin
Journal: Annals of the Rheumatic Diseases (2019)

Drug-induced lupus (DIL) is a side effect of long-term treatment with various medications, an idiosyncratic adverse drug reaction (ADR) that has been documented for some seven decades. While symptoms can be severe, DIL, unlike systemic lupus erythematosus (SLE), is fully reversible simply by discontinuation of the inducing medication, although full recovery can take several months. However, as with SLE, diagnosis of DIL is often missed or delayed in part because onset of symptoms can be gradual and variable and because the temporal link to the implicated drug is often not apparent. DIL typically develops after many months or years of largely symptom-free continuous drug use. While bonafide SLE or other idiopathic autoimmune disease would naturally be included in the differential diagnosis of someone who develops lupus-like symptoms, awareness that symptoms could be iatrogenic due to chronic medication can be the most important factor in making a correct and prompt diagnosis. Failure to do this often results in prolonged and worsening symptoms and unnecessary or ineffective anti-inflammatory/immunosuppressive treatment.

The literature is replete with well-documented case reports of DIL due to some 70 different drugs as well as numerous reviews on this subject that list reported lupus-inducing drugs and their relative risk of causing this adverse side effect. However, because many drugs have a low or very low risk of causing lupus-like symptoms, it can be challenging to recognise DIL as the underlying cause of symptom development. In addition, increased use of new medications and/or the absence of publications of full case reports raise the possibility that other drugs exist with a DIL propensity. Gratefully, with the creation of VigiBase by the WHO in 1967,1 a mechanism for reporting potential lupus-inducing drugs has been facilitated without the formality of fully documented case reports. This Individual Case Safety Reports (ICSR) database now …
Lack of GDF11 Does Not Ameliorate Erythropoiesis in β-Thalassemia and Does Not Prevent the Activity of the Trap-Ligand RAP-536
Authors: Amaliris Guerra, Rea Oikonomidou, Sinha Gonzalez, Jianbing Zhang, Vania Lo Presti, Callum R Hamilton, Laura Breda, Carla Casu, Mark D. Fleming, Pedro Martinez, Rajasekhar Suragani, Ravi Kumar, Stefano Rivella
Journal: Blood (2018)
External Validation of the MEESSI Acute Heart Failure Risk Score
Authors: Desiree Wussler, Nikola Kozhuharov, Zaid Sabti, Joan Walter, Ivo Strebel, Letizia Scholl, Oscar Miró, Xavier Rossello, Francisco Javier Martín-Sánchez, Stuart J. Pocock, Albina Nowak, Patrick Badertscher, Raphael Twerenbold, Karin Wildi, Christian Puelacher, Jeanne du Fay de Lavallaz, Samyut Shrestha, Olivia Strauch, Dayana Flores, Thomas Nestelberger, Jasper Boeddinghaus, Carmela Schumacher, Assen Goudev, Otmar Pfister, Tobias Breidthardt, Christian Mueller
Journal: Annals of Internal Medicine (2019)

Background: The MEESSI-AHF (Multiple Estimation of risk based on the Emergency department Spanish Score In patients with AHF) score was developed to predict 30-day mortality in patients presenting with acute heart failure (AHF) to emergency departments (EDs) in Spain. Whether it performs well in other countries is unknown. Objective: To externally validate the MEESSI-AHF score in another country. Design: Prospective cohort study. (ClinicalTrials.gov: NCT01831115). Setting: Multicenter recruitment of dyspneic patients presenting to the ED. Participants: The external validation cohort included 1572 patients with AHF. Measurements: Calculation of the MEESSI-AHF score using an established model containing 12 independent risk factors. Results: Among 1572 patients with adjudicated AHF, 1247 had complete data that allowed calculation of the MEESSI-AHF score. Of these, 102 (8.2%) died within 30 days. The score predicted 30-day mortality with excellent discrimination (c-statistic, 0.80). Assessment of cumulative mortality showed a steep gradient in 30-day mortality over 6 predefined risk groups (0 patients in the lowest-risk group vs. 35 [28.5%] in the highest-risk group). Risk was overestimated in the high-risk groups, resulting in a Hosmer–Lemeshow P value of 0.022. However, after adjustment of the intercept, the model showed good concordance between predicted risks and observed outcomes (P = 0.23). Findings were confirmed in sensitivity analyses that used multiple imputation for missing values in the overall cohort of 1572 patients. Limitations: External validation was done using a reduced model. Findings are specific to patients with AHF who present to the ED and are clinically stable enough to provide informed consent. Performance in patients with terminal kidney failure who are receiving long-term dialysis cannot be commented on. Conclusion: External validation of the MEESSI-AHF risk score showed excellent discrimination. Recalibration may be needed when the score is introduced to new populations. Primary Funding Source: The European Union, the Swiss National Science Foundation, the Swiss Heart Foundation, the Cardiovascular Research Foundation Basel, the University of Basel, and University Hospital Basel.
Abnormal mTORC1 signaling leads to retinal pigment epithelium degeneration
Authors: Jiancheng Huang, Shun Gu, Meng Chen, Shu-jie Zhang, Zhichun Jiang, Xue Chen, Chao Jiang, Guohua Liu, Roxana A Radu, Xiantao Sun, Douglas Vollrath, Jianhai Du, Biao Yan, Chen Zhao
Journal: Theranostics (2019)

Retinal pigment epithelial (RPE) degeneration is potentially involved in the pathogenesis of several retinal degenerative diseases.mTORC1 signaling is shown as a crucial regulator of many biological processes and disease progression.In this study, we aimed at investigating the role of mTORC1 signaling in RPE degeneration.Methods: Western blots were conducted to detect mTORC1 expression pattern during RPE degeneration.Cre-loxP system was used to generate RPE-specific mTORC1 activation mice.Fundus, immunofluorescence staining, transmission electron microscopy, and targeted metabolomic analysis were conducted to determine the effects of mTORC1 activation on RPE degeneration in vivo.Electroretinography, spectral-domain optical coherence tomography, and histological experiments were conducted to determine the effects of mTORC1 activation on choroidal and retinal function in vivo.Results: RPE-specific activation of mTORC1 led to RPE degeneration as shown by the loss of RPE-specific marker, compromised cell junction integrity, and intracellular accumulation of lipid droplets.RPE degeneration further led to abnormal choroidal and retinal function.The inhibition of mTORC1 signaling with rapamycin could partially reverse RPE degeneration.Targeted metabolomics analysis further revealed that mTORC1 activation affected the metabolism of purine, carboxylic acid, and niacin in RPE. Conclusion:This study revealed that abnormal activation of mTORC1 signaling leads to RPE degeneration, which could provide a promising target for the treatment of RPE dysfunction-related diseases.
Adjuvant Doxycycline to Enhance Anti-Amyloid Effects: Results from the DUAL (Doxycycline to Upgrade response in AL amyloidosis) Study
Authors: Anita D'Souza, Kathryn E Flynn, Binod Dhakal, Saurabh Chhabra, Marcelo C Pasquini, Parameswaran Hari
Journal: Blood (2018)
Acute Myeloid Leukemia with Plasmacytoid Dendritic Cell Differentiation: Predominantly Secondary AML, Enriched for RUNX1 Mutations, Frequent Cross-Lineage Antigen Expression and Poor Prognosis
Authors: Wenbin Xiao, Aaron D Goldberg, Christopher Famulare, Jeeyeon Baik, Qi Gao, Martin S. Tallman, Yanming Zhang, Maria E Arcila, Mikhail Roshal
Journal: Blood (2018)
Definitive EMP and Pre-HSC Emerge in Myb-Null Murine Embryos and Retain Macrophage Potential
Authors: Kathleen E. McGrath, Jenna M Frame, Katherine H Fegan, Emanuele Azzoni, Paul D. Kingsley, Anne D Koniski, Seana C Catherman, Marella De Bruijn, James Palis
Journal: Blood (2018)
Development of a CRISPR/Cas9-based therapy for Hutchinson–Gilford progeria syndrome
Authors: Olaya Santiago-Fernández, Fernando G. Osorio, Víctor Quesada, Francisco Rodríguez, Sammy Basso, Daniel Maeso, Loïc Rolas, Anna Barkaway, Sussan Nourshargh, Alicia R. Folgueras, José M. P. Freije, Carlos López-Otín
Journal: Nature Medicine (2019)
The novel roles of circRNAs in human cancer
Authors: Qingfeng Shang, Zhi Yang, Renbing Jia, Shengfang Ge
Journal: Molecular Cancer (2019)

Covalently closed single-stranded circular RNAs (circRNAs) consist of introns or exons and are widely present in eukaryotic cells. CircRNAs generally have low expression levels and relatively stable structures compared with messenger RNAs (mRNAs), most of which are located in the cytoplasm and often act in cell type and tissue-specific manners, indicating that they may serve as novel biomarkers. In recent years, circRNAs have gradually become a hotspot in the field of RNA and cancer research, but the functions of most circRNAs have not yet been discovered. Known circRNAs can affect the biogenesis of cancers in diverse ways, such as functioning as a microRNA (miRNA) sponges, combining with RNA binding proteins (RBPs), working as a transcription factor and translation of proteins. In this review, we summarize the characteristics and types of circRNAs, introduce the biogenesis of circRNAs, discuss the emerging functions and databases on circRNAs and present the current challenges of circRNAs studies.
SOX17 Regulates Cholangiocyte Differentiation and Acts as a Tumour Suppressor in Cholangiocarcinoma
Authors: M. Merino-Azpitarte, E. Lozano, M.J. Perugorria, O. Erice, A. Santos-Laso, R. Jiménez-Agüero, A. LaCasta, N. Jalan-Sakrikar, R.C. Huebert, K.M. Thelen, S. Gradilone, A.M. Aransay, J.L. Lavín, M.G. Fernández-Barrena, M. Marzioni, G.J. Gores, L. Bujanda, J.J. Marín, J.M. Banales
Journal: Journal of Hepatology (2016)
Abstract 18621: Clinical Non-Responders to Left Ventricular Assist Device Have Persistently Higher Levels of Plasma β-Adrenergic Receptor Kinase-1 Compared With Clinical Responders
Authors: Quin E Denfeld, Christopher S Lee, James O Mudd, Jill M Gelow, Shirin O Hiatt, William R Woodward, Beth A Habecker
Journal: Circulation (2017)

Introduction: Clinical response to left ventricular assist devices (LVAD), as measured by health-related quality of life, varies among patients following implantation. It is unknown how markers of ...
Is There Difference between the Survival Rate and Treatment Related Complications between Peripheral Blood Stem Cell Transplantation and Bone Marrow Transplantation for Pediatric Hematological Malignancy?: Systematic Review and Meta-Analysis
Authors: Yuko Shimosato-Wada, Reo Tanoshima, Shinichi Tujimoto, Masanobu Takeuchi, Norio Shiba, Tohru Kobayashi, Shuichi Ito
Journal: Blood (2018)
Aberrant Super‐Enhancer Landscape in Human Hepatocellular Carcinoma
Authors: Felice Ho‐Ching Tsang, Cheuk‐Ting Law, Tsz‐Ching Chloe Tang, Carol Lai‐Hung Cheng, Don Wai‐Ching Chin, Wing‐Sum Vincy Tam, Lai Wei, Carmen Chak‐Lui Wong, Irene Oi‐Lin Ng, Chun‐Ming Wong
Journal: Hepatology (2019)

Hepatocellular carcinoma (HCC) cells exploit an aberrant transcriptional program to sustain their infinite growth and progression. Emerging evidence indicates that the continuous and robust transcription of oncogenes in cancer cells is often driven by super‐enhancers (SEs). In this study, we systematically compared the SE landscapes between normal liver and HCC cells and revealed that the cis ‐acting SE landscape was extensively reprogrammed during liver carcinogenesis. HCC cells acquired SEs at multiple prominent oncogenes to drive their vigorous expression. We identified sphingosine kinase 1 (SPHK1) as an SE‐associated oncogene, and we used this gene as an example to illustrate the impact of SEs on the activation of oncogenes in HCC. Concurrently, we also showed that the critical components of the trans ‐acting SE complex, namely, cyclin‐dependent kinase 7 (CDK7), bromodomain‐containing protein 4 (BRD4), E1A binding protein P300 (EP300), and mediator complex subunit 1 (MED1), were frequently overexpressed in human HCCs and were associated with the poor prognosis of patients with HCC. Using the CRISPR/Cas9 gene‐editing system and specific small‐molecule inhibitors, we further demonstrated that HCC cells were highly sensitive to perturbations of the SE complex. The inactivation of CDK7, BRD4, EP300, and MED1 selectively repressed the expression of SE‐associated oncogenes in HCC. Finally, we demonstrated that THZ1, which is a small‐molecule inhibitor of CDK7, exerted a prominent anticancer effect in both in vitro and in vivo HCC models. Conclusion : The SE landscape and machinery were significantly altered in human HCCs. HCC cells are highly susceptible to perturbations of the SE complex due to the resulting selective suppression of SE‐associated oncogenes. Our results suggest that targeting SE complex is a promising therapeutic strategy for HCC treatment.
Primary Common Iliac Artery Angiosarcoma With Multiple Bone Metastases Revealed by Dual-Time Point FDG PET/CT Imaging
Authors: Renjie Wang, Xueju Wang, Bin Ji, Qingtao Guan, Bin Chen
Journal: Clinical Nuclear Medicine (2019)

Iliac artery angiosarcoma is rare, and bone metastasis as its presenting initial symptom is extremely rare. A 67-year-old man with a history of low back pain presented with multiple MRI-identified lumbar and sacrum lesions highly suggestive of bone metastasis. On subsequent PET/CT scan, in addition to multiple vertebrae and pelvis hypermetabolism, a lesion with intense focal uptake was discovered within the lumen of left common iliac artery. Dual-time point quantitative analysis revealed that the lesion-to-liver ratio of SUVmax was significantly increased in the delayed phase. Biopsy confirmed the lesion as a primary iliac artery angiosarcoma.
Comments Regarding Nutrition Study Among Preschool Children—Reply
Authors: Emily M. Melnick, Meng Li
Journal: JAMA Pediatrics (2019)

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 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 Pediatrics journal
Abstract P145: Association Between Birth Weight and Childhood and Maternal Cardiovascular Disease Risk Factors in Full Term Birth Infants
Authors: Amna Umer, Candice Hamilton, Cris Britton, Lesley Cottrell, Peter Giacobbi, George Kelley, Kim Innes, Collin John, William Neal, Christa Lilly
Journal: Circulation (2017)

Introduction: Reported associations between birth weight (BTW) and childhood cardiovascular disease (CVD) risk factors have been inconsistent. The relationship between infants’ BTW and later maternal CVD is also a more recent and active area of research. We aimed to examine the association between BTW and subsequent childhood and maternal CVD risk factors 11 years post-partum. Methods: The study used longitudinally linked data from three cross-sectional datasets in West Virginia (N=19,583). The outcome variables included blood pressure for children and lipid levels for both mothers and children. The exposure was BTW of the infants born full-term. The role of the child’s current body mass index (BMI) was assessed as a potential mediator. Results: Unadjusted analyses showed a positive association between BTW and the child’s systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein cholesterol (HDL), and a negative association with triglycerides (TGs). When adjusted for the child’s BMI, the association became non-significant for SBP and DBP but remained significant for HDL [β= 0.14 mg/dL (95% CI: 0.11, 0.18) per1000g increase in BTW] and TGs [β= -0.007 mg/dL (-0.008, -0.005) per 1000g increase in BTW]. Low-density lipoprotein cholesterol (LDL) and non-HDL became significant and negatively associated with BTW in the adjusted analysis [LDL (β = -0.1 mg/dL (-0.19, - 0.16) per 1000 g increase in BTW; non-HDL (b = - 0.18 mg/dL (-0.28, -0.09) per 1000 g increase in BTW]. There was a positive association between infant’s birth weight and maternal total cholesterol (TC) levels, which became non-significant in the adjusted analysis [β = 0.4 (95% CI: -0.01, 0.90) mg/dL per1000g increase in birth weight]. None of the other maternal lipids levels (LDL, HDL, and TG) were significant in the unadjusted or the adjusted analysis. Conclusion: Low BTW was associated with higher LDL, non-HDL, and TGs, and lower HDL levels in fifth grade children independent of the current weight status. As childhood CVD risk factors persist and are often amplified over time, these small effect sizes can have potential unfavorable consequences on lipid levels in later adulthood.
Abstract 18717: Heart Repair by CRISPR-Induced Cardiovascular Progenitor Cells
Authors: Lin Jiang, Jialiang Liang, Wei Huang, Wenfeng Cai, Christian Paul, Yigang Wang
Journal: Circulation (2017)

Background and Objective: Reprogramming of somatic fibroblasts into induced cardiac progenitor cells (iCPCs) has provided a promising therapeutic paradigm for cardiac repair. This study aims to gen...
Reply
Authors: Angels Escorsell, Jaime Bosch
Journal: Hepatology (2017)

Potential conflict of interest: Dr. Escorsell received grants from Vital Therapies. We sincerely thank Sonambekar and Desai for their letter. We agree that it is possible that the stiff guide wire used for stent deployment could explain the gastric perforation in their patient. The stiff guide wire included in the procedure pack is considered suitable for guiding the introduction of the delivery system into the stomach after being passed through the working channel of the endoscope. As stated in our article,1 we implanted all the stents without radiological or endoscopic assistance and without using stiff wire for positioning the delivery system preloaded with the stent. Therefore, we have no experience with the use of the wire. Also, from our contacts with other groups, we are not aware of any other case of such severe complication. The observation of Sonambekar and Desai is opportune and should be considered when using the guide wire provided by the manufacturers.Moreover, this observation also strengthens the need to perform a plain chest x‐ray after the procedure for an early recognition of this and other potential complications.