tbuckley/cabot-search huggingface dataset:
Abstract 17059: Ocrelizumab Induced Kounis Syndrome
Authors: Mian Tanveer Ud Din, Kushani Gajjar, Valentyna Ivanova
Journal: Circulation (2021)

Kounis syndrome(KS), first described in 1991, is defined as concurrence of acute coronary syndrome and anaphylactic events. Primary mechanism of KS is interaction of mast cells with T-lymphocytes and macrophages via multidirectional stimuli leading to platelets activation. Case presentation: A 35 y.o. tennis coach with multiple sclerosis is admitted to the medical ICU with anaphylaxis after receiving Ocrelizumab infusion. Vital signs on presentation are significant for hypotension with blood pressure of 69/30 mm Hg, sinus tachycardia to 110 bpm and hypoxia with SatO2 88% on room air. Other investigations including chest x-ray, EKG and blood work are unrevealing for secondary pathological process outside of anaphylaxis. She undergoes fluid resuscitation followed by epinephrine drip for persistent hypotension. In addition methylprednisolone, famotidine and diphenhydramine are administered. She requires escalating doses of epinephrine and subsequently develops chest pain with troponin elevation to 0.29 ng/ml and EKG concerning for new ST depression and T wave inversion in II, III, aVF, V2 - V6 leads. Urgent echocardiography revealed normal biventricular function with no wall motion abnormalities and is only significant for moderate MR. Given excellent underlying functional capacity and no underlying cardiac risk factors, she was treated for Kounis syndrome by treating underlying anaphylaxis and weaning epinephrine as able with additional fluid resuscitation. Her chest pain resolved and EKG normalized with eventual discontinuation of epinephrine. Repeat echocardiography revealed preserved left ventricular (LV) function and mild MR. Discussion: KS is not a rare disease but easily overlooked and infrequently diagnosed. Our patient had the type I variant: endothelial dysfunction or microvascular angina in absence of cardiac risk factors. Inflammatory mediators can cause vasospasm and catecholamines used for treatment may potentiate it therefore requiring thoughtful dosing and appropriate duration of treatment. Prompt recognition is crucial for appropriate management of anaphylatic shock followed by that of ACS if LV function declines or risk factors for cardiac disease are present.
Plasma biomarkers of hemoglobin loss in <i>Plasmodium falciparum–</i>infected children identified by quantitative proteomics
Authors: Almahamoudou Mahamar, Patricia A. Gonzales Hurtado, Robert Morrison, Rachel Boone, Oumar Attaher, Bacary S. Diarra, Santara Gaoussou, Djibrilla Issiaka, Alassane Dicko, Patrick E. Duffy, Michal Fried
Journal: Blood (2021)
Safety of Early Discontinuation of Antiseizure Medication After Acute Symptomatic Neonatal Seizures—Reply
Authors: Hannah C. Glass, Renée A. Shellhaas
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Eurosurveillance: 25 years of public health impact
Journal: Eurosurveillance (2021)

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Loss of myeloid cell-specific SIRPα, but not CD47, attenuates inflammation and suppresses atherosclerosis
Authors: Bhupesh Singla, Hui-Ping Lin, WonMo Ahn, Jiean Xu, Qian Ma, Moses Sghayyer, Kunzhe Dong, Mary Cherian-Shaw, Jiliang Zhou, Yuqing Huo, Joseph White, Gábor Csányi
Journal: Cardiovascular Research (2021)

Inhibitors of the anti-phagocytic CD47-SIRPα immune checkpoint are currently in clinical development for a variety of haematological and solid tumours. Application of immune checkpoint inhibitors to the cardiovascular field is limited by the lack of preclinical studies using genetic models of CD47 and SIRPα inhibition. In this study, we comprehensively analysed the effects of global and cell-specific SIRPα and CD47 deletion on atherosclerosis development.Here, we show that both SIRPα and CD47 expression are increased in human atherosclerotic arteries and primarily co-localize to CD68+ areas in the plaque region. Hypercholesterolaemic mice homozygous for a Sirpa mutant lacking the signalling cytoplasmic region (Sirpamut/mut) and myeloid cell-specific Sirpa-knockout mice are protected from atherosclerosis. Further, global Cd47-/- mice are protected from atherosclerosis but myeloid cell-specific deletion of Cd47 increased atherosclerosis development. Using a combination of techniques, we show that loss of SIRPα signalling in macrophages stimulates efferocytosis, reduces cholesterol accumulation, promotes lipid efflux, and attenuates oxidized LDL-induced inflammation in vitro and induces M2 macrophage phenotype and inhibits necrotic core formation in the arterial wall in vivo. Conversely, loss of myeloid cell CD47 inhibited efferocytosis, impaired cholesterol efflux, augmented cellular inflammation, stimulated M1 polarization, and failed to decrease necrotic core area in atherosclerotic vessels. Finally, comprehensive blood cell analysis demonstrated lower haemoglobin and erythrocyte levels in Cd47-/- mice compared with wild-type and Sirpamut/mut mice.Taken together, these findings identify SIRPα as a potential target in atherosclerosis and suggest the importance of cell-specific CD47 inhibition as a future therapeutic strategy.
Regulation of Iron Homeostasis and Efficacy of Rusfertide Analog Peptide in a Mouse Model for Polycythemia Vera
Authors: Roopa Taranath, Li Zhao, Jayanthi Vengalam, Lawrence Lee, Tenny Tang, Celino Dion, Ahu Su, James Tovera, Ashok Bhandari, Xiaoli Cheng, Larry Mattheakis, David Y Liu
Journal: Blood (2021)
Covid-19: CDC shortens isolation period as US cases hit record high
Authors: Janice Hopkins Tanne
Journal: BMJ (2021)

Covid-19: CDC shortens isolation period as US cases hit record high Janice Hopkins Tanne US cases of covid-19 hit a record daily average of 265 000 cases on 28 December, the highest number since the pandemic began two years ago, according to Johns Hopkins University. 1 There were about 1.8 million cases last week, a 69% increase over the week before.1
Vorinostat and isotretinoin with chemotherapy in young children with embryonal brain tumors: A report from the Pediatric Brain Tumor Consortium (PBTC-026)
Authors: Sarah E S Leary, Lindsay Kilburn, J Russell Geyer, Mehmet Kocak, Jie Huang, Kyle S Smith, Jennifer Hadley, Ralph Ermoian, Tobey J MacDonald, Stewart Goldman, Peter Phillips, Tina Young Poussaint, James M Olson, David W Ellison, Ira J Dunkel, Maryam Fouladi, Arzu Onar-Thomas, Paul A Northcott
Journal: Neuro-Oncology (2021)

Embryonal tumors of the CNS are the most common malignant tumors occurring in the first years of life. This study evaluated the feasibility and safety of incorporating novel non-cytotoxic therapy with vorinostat and isotretinoin to an intensive cytotoxic chemotherapy backbone.PBTC-026 was a prospective multi-institutional clinical trial for children <48 months of age with newly diagnosed embryonal tumors of the CNS. Treatment included three 21-day cycles of induction therapy with vorinostat and isotretinoin, cisplatin, vincristine, cyclophosphamide, and etoposide; three 28-day cycles of consolidation therapy with carboplatin and thiotepa followed by stem cell rescue; and twelve 28-day cycles of maintenance therapy with vorinostat and isotretinoin. Patients with M0 medulloblastoma (MB) received focal radiation following consolidation therapy. Molecular classification was by DNA methylation array.Thirty-one patients with median age of 26 months (range 6-46) received treatment on study; 19 (61%) were male. Diagnosis was MB in 20 and supratentorial CNS embryonal tumor in 11. 24/31 patients completed induction therapy within a pre-specified feasibility window of 98 days. Five-year progression-free survival (PFS) and overall survival (OS) for all 31 patients were 55 ± 15 and 61 ± 13, respectively. Five-year PFS was 42 ± 13 for group 3 MB (n = 12); 80 ± 25 for SHH MB (n = 5); 33 ± 19 for embryonal tumor with multilayered rosettes (ETMR, n = 6).It was safe and feasible to incorporate vorinostat and isotretinoin into an intensive chemotherapy regimen. Further study to define efficacy in this high-risk group of patients is warranted.
Tunicate‐Inspired Photoactivatable Proteinic Nanobombs for Tumor‐Adhesive Multimodal Therapy (Adv. Healthcare Mater. 23/2021)
Authors: Yeonsu Jeong, Yun Kee Jo, Mou Seung Kim, Kye Il Joo, Hyung Joon Cha
Journal: Advanced Healthcare Materials (2021)

NIR-Responsive Nanotherapeutics In article number 2101212, Hyung Joon Cha and co-workers develop NIR-activatable tumoradhesive proteinic nanoparticles by using tunicate-inspired bioinorganic chemistry to realize effective photothermal activity with high bioavailability and achieve multimodal tumor-specific therapy. The vanadium ion-doped adhesive nanoparticles exhibit a remarkable photothermal capability, on-demand NO gas, and anticancer drug release in a “bomb-like” manner, and robust retention of multiple therapeutics within tumors, thereby leading to excellent anticancer responses.
Large-scale analysis of longitudinal skin gene expression in systemic sclerosis reveals relationships of immune cell and fibroblast activity with skin thickness and a trend towards normalisation over time
Authors: Brian Skaug, Marka A Lyons, William R Swindell, Gloria A Salazar, Minghua Wu, Tuan M Tran, Julio Charles, Connor P Vershel, Maureen D Mayes, Shervin Assassi
Journal: Annals of the Rheumatic Diseases (2021)

Objectives Determine relationships between skin gene expression and systemic sclerosis (SSc) clinical disease features, and changes in skin gene expression over time. Methods A total of 339 forearm skin biopsies were obtained from 113 SSc patients and 44 matched healthy controls. 105 SSc patients had a second biopsy, and 76 had a third biopsy. Global gene expression profiling was performed, and differentially expressed genes and cell type-specific signatures in SSc were evaluated for relationships to modified Rodnan Skin Score (mRSS) and other clinical variables. Changes in skin gene expression over time were analysed by mixed effects models and principal component analysis. Immunohistochemical staining was performed to validate conclusions. Results Gene expression dysregulation was greater in SSc patients with affected skin than in those with unaffected skin. Immune cell and fibroblast signatures positively correlated with mRSS. High baseline immune cell and fibroblast signatures predicted higher mRSS over time, but were not independently predictive of longitudinal mRSS after adjustment for baseline mRSS. In early diffuse cutaneous SSc, immune cell and fibroblast signatures declined over time, and overall skin gene expression trended towards normalisation. On immunohistochemical staining, most early diffuse cutaneous SSc patients with high baseline T cell and macrophage numbers had declines in these numbers at follow-up. Conclusions Skin thickness in SSc is related to dysregulated immune cell and fibroblast gene expression. Skin gene expression changes over time in early diffuse SSc, with a tendency towards normalisation. These observations are relevant for understanding SSc pathogenesis and could inform treatment strategies and clinical trial design.
Dose-Response Relationship in Selective Serotonin and Norepinephrine Reuptake Inhibitors in the Treatment of Major Depressive Disorder: A Meta-Analysis and Network Meta-Analysis of Randomized Controlled Trials
Authors: Lena Rink, Anne Adams, Cora Braun, Tom Bschor, Kathrin Kuhr, Christopher Baethge
Journal: Psychotherapy and Psychosomatics (2021)

Introduction: Selective serotonin and norepinephrine reuptake inhibitors (SNRI) are among the most prescribed antidepressants, and dose escalation is a frequently applied strategy after non-response to an initially prescribed dose. Objective: This meta-analysis aimed to find evidence of a dose-response relationship or to the contrary in direct comparisons of different SNRI doses in patients with major depressive disorder. Methods: A systematic literature search for RCTs comparing at least two doses of SNRIs was carried out in CENTRAL, PubMed, PsycINFO, and EMBASE. Doses were classified as high, medium, and low according to manufacturers’ product monographs and analyses at the level of SNRIs as a group and for single substances, accompanied by sensitivity network meta-analyses (Prospero CRD42018081031). Results: From 2,070 studies screened, we included 26 studies with a total of 10,242 patients. Comparisons of medium versus low and high versus medium doses resulted in clinically and statistically non-significant standardized mean differences of –0.06 (–0.16 to 0.04) and –0.06 (–0.16 to 0.03) in favor of higher doses. In the analyses of single substances, no statistically significant results emerged, and many contrasts yielded very small effect sizes. Dropouts due to side effects tended to be more frequent with higher doses. Heterogeneity was low. Network meta-analyses of direct comparisons supported the findings, as did a risk of bias analysis. Conclusion: Based on the lack of positive evidence for a dose-response relationship in SNRIs as a group and in single SNRIs, we recommend prescribing medium doses. In case of insufficient response, we do not recommend increasing the dose of SNRIs.
2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines
Authors: Jennifer S. Lawton, Jacqueline E. Tamis-Holland, Sripal Bangalore, Eric R. Bates, Theresa M. Beckie, James M. Bischoff, John A. Bittl, Mauricio G. Cohen, J. Michael DiMaio, Creighton W. Don, Stephen E. Fremes, Mario F. Gaudino, Zachary D. Goldberger, Michael C. Grant, Jang B. Jaswal, Paul A. Kurlansky, Roxana Mehran, Thomas S. Metkus, Lorraine C. Nnacheta, Sunil V. Rao, Frank W. Sellke, Garima Sharma, Celina M. Yong, Brittany A. Zwischenberger
Journal: Circulation (2021)

The executive summary of the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions coronary artery revascularization guideline provides the top 10 items readers should know about the guideline. In the full guideline, the recommendations replace the 2011 coronary artery bypass graft surgery guideline and the 2011 and 2015 percutaneous coronary intervention guidelines. This summary offers a patient-centric approach to guide clinicians in the treatment of patients with significant coronary artery disease undergoing coronary revascularization, as well as the supporting documentation to encourage their use.A comprehensive literature search was conducted from May 2019 to September 2019, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, CINHL Complete, and other relevant databases. Additional relevant studies, published through May 2021, were also considered. Structure: Recommendations from the earlier percutaneous coronary intervention and coronary artery bypass graft surgery guidelines have been updated with new evidence to guide clinicians in caring for patients undergoing coronary revascularization. This summary includes recommendations, tables, and figures from the full guideline that relate to the top 10 take-home messages. The reader is referred to the full guideline for graphical flow charts, supportive text, and tables with additional details about the rationale for and implementation of each recommendation, and the evidence tables detailing the data considered in the development of this guideline.
Targeting DNA2 Overcomes Myeloma Cells' Metabolic Reprogramming in Response to DNA Damage
Authors: Natthakan Thongon, Andrea Santoni, Jintan Liu, Natalia Baran, Feiyang Ma, Christopher Jackson, Pamela Lockyer, Irene Ganan-Gomez, Vera Adema, Ashley Rose, Matteo Marchesini, Yun Qing, Min Jin Ha, Caleb Class, Matteo Pellegrini, Lin Tan, Philip Lorenzi, Marina Konopleva, Simona Colla
Journal: Blood (2021)
ITVT-02. Elucidating the pleiotropic effects of verteporfin photodynamic therapy in preclinical glioblastoma models
Authors: Gabrielle Price, Maria Anastasiadou, Sweta Sudhir, Alexandros Bouras, Nadejda Tsankova, Constantinos Hadjipanayis
Journal: Neuro-Oncology (2021)

Abstract Glioblastoma (GBM) ranks the highest in mortality rate, incidence, and aggressiveness of primary brain tumor types. The highly malignant nature of GBM makes it difficult for mainstay treatments to have an effect beyond stabilizing the disease. Deregulation of receptor tyrosine kinase (RTKs), such as EGFR and PI3K, have been implicated in GBM tumorigenesis. The expression of EGFR has been linked to hippo pathway transcriptional co-activators YAP and TAZ that bind to TEAD co-factors to drive the transcription of target genes. The convergence of EGFR signaling and the hippo pathway regulates stem cell programs, including proliferation, survival, and self-renewal. Verteporfin (VP), an FDA-approved macular degeneration therapy, has antitumor effects in in vitro and in vivo GBM preclinical models and phase I/II clinical trials for patients with EGFR mutated/amplified GBM by abrogating YAP/TAZ-TEAD interactions. As a porphyrin derivative, VP can exert therapeutic and photodynamic effects in the presence of 689 nm light; however, the efficacy of VP-PDT has not been explored in GBM. Our results indicate that VP-PDT reduces cell viability to a greater extent than solitary VP treatment (viability — 0.7 uM VP: 97%, 0.7 uM VP-PDT: 46%). The antitumor effects of VP-PDT are two pronged involving 1) inhibition of live cell dynamics, including migration and intravasation, by downregulating hippo pathway constituents YAP, TAZ and TEAD and transcriptional target EGFR and 2) induction of programmed cell death by reactive oxygen species. Our results suggest that VP-PDT can be a potential avenue for treating these incurable tumors.
Wheeze trajectories: Determinants and outcomes in the CHILD Cohort Study
Authors: Ruixue Dai, Kozeta Miliku, Sirisha Gaddipati, Jihoon Choi, Amirthagowri Ambalavanan, Maxwell M Tran, Myrtha Reyna, Hind Sbihi, Wendy Lou, Paula Parvulescu, Diana L Lefebvre, Allan B Becker, Meghan B Azad, Piush J Mandhane, Stuart E Turvey, Qingling Duan, Theo J Moraes, Malcolm R Sears, Padmaja Subbarao
Journal: Journal of Allergy and Clinical Immunology (2021)
Interferon inducible pseudouridine modification in human mRNA by quantitative nanopore profiling
Authors: Sihao Huang, Wen Zhang, Christopher D. Katanski, Devin Dersh, Qing Dai, Karen Lolans, Jonathan Yewdell, A. Murat Eren, Tao Pan
Journal: Genome biology (2021)

Abstract Pseudouridine (Ψ) is an abundant mRNA modification in mammalian transcriptome, but its functions have remained elusive due to the difficulty of transcriptome-wide mapping. We develop a nanopore native RNA sequencing method for quantitative Ψ prediction (NanoPsu) that utilizes native content training, machine learning modeling, and single-read linkage analysis. Biologically, we find interferon inducible Ψ modifications in interferon-stimulated gene transcripts which are consistent with a role of Ψ in enabling efficacy of mRNA vaccines.
Clinical Trial Endpoints in Metastatic Cancer: Using Individual Participant Data to Inform Future Trials Methodology
Authors: Richard M Goldberg, Richard Adams, Marc Buyse, Cathy Eng, Axel Grothey, Thierry André, Alberto F Sobrero, Stuart M Lichtman, Al B Benson, Cornelis J A Punt, Tim Maughan, Tomasz Burzykowski, Dirkje Sommeijer, Everardo D Saad, Qian Shi, Elisabeth Coart, Benoist Chibaudel, Miriam Koopman, Hans-Joachim Schmoll, Takayuki Yoshino, Julien Taieb, Niall C Tebbutt, John Zalcberg, Josep Tabernero, Eric Van Cutsem, Alastair Matheson, Aimery de Gramont
Journal: JNCI Journal of the National Cancer Institute (2021)

Meta-analysis based on individual participant data (IPD) is a powerful methodology for synthesizing evidence by combining information drawn from multiple trials. Hitherto, its principal application has been in questions of clinical management, but an increasingly important use is in clarifying trials methodology, for instance in the selection of endpoints, as discussed in this review. In oncology, the Aide et Recherche en Cancérologie Digestive (ARCAD) Metastatic Colorectal Cancer Database is a leader in the use of IPD-based meta-analysis in methodological research. The ARCAD database contains IPD from more than 38 000 patients enrolled in 46 studies and continues to collect phase III trial data. Here, we review the principal findings of the ARCAD project in respect of endpoint selection and examine their implications for cancer trials. Analysis of the database has confirmed that progression-free survival (PFS) is no longer a valid surrogate endpoint predictive of overall survival in the first-line treatment of colorectal cancer. Nonetheless, PFS remains an endpoint of choice for most first-line trials in metastatic colorectal cancer and other solid tumors. Only substantial PFS effects are likely to translate into clinically meaningful benefits, and accordingly, we advocate an oncology research model designed to identify highly effective treatments in carefully defined patient groups. We also review the use of the ARCAD database in assessing clinical response including novel response metrics and prognostic markers. These studies demonstrate the value of IPD as a tool for methodological studies and provide a reference point for the expansion of this approach within clinical cancer research.
Apatinib vs Placebo in Patients With Locally Advanced or Metastatic, Radioactive Iodine–Refractory Differentiated Thyroid Cancer
Authors: Yansong Lin, Shukui Qin, Zhiyong Li, Hui Yang, Wei Fu, Shaohua Li, Wenxin Chen, Zairong Gao, Weibing Miao, Huiqin Xu, Qing Zhang, Xinming Zhao, Jiandong Bao, Linfa Li, Yuan Ren, Chenghe Lin, Shanghua Jing, Qingjie Ma, Jun Liang, Guang Chen, Hong Zhang, Yifan Zhang, Xianfeng Zhou, Yaxiong Sang, Zhiguo Hou
Journal: JAMA Oncology (2021)

Patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) have a poor prognosis and limited treatment options.
SPARC-mediated long-term retention of nab-paclitaxel in pediatric sarcomas
Authors: Guillem Pascual-Pasto, Helena Castillo-Ecija, Nora Unceta, Rosario Aschero, Claudia Resa-Pares, Alberto Gómez-Caballero, Monica Vila-Ubach, Oscar Muñoz-Aznar, Mariona Suñol, Victor Burgueño, Soledad Gomez-Gonzalez, Alejandro Sosnik, Manuel Ibarra, Paula Schaiquevich, Enrique de Álava, Oscar M. Tirado, Jaume Mora, Angel M. Carcaboso
Journal: Journal of Controlled Release (2021)