tbuckley/cabot-search huggingface dataset:
Novel mechanisms of action contributing to benralizumab's potent anti-eosinophilic activity
Authors: Rania Dagher, Varsha Kumar, Alan M. Copenhaver, Sandra Gallagher, Mahboobe Ghaedi, Jonathan Boyd, Paul Newbold, Alison A. Humbles, Roland Kolbeck
Journal: European Respiratory Journal (2021)

Background Benralizumab is a humanised, anti-interleukin-5 receptor α monoclonal antibody with anti-eosinophilic activity. Lack of fucose (afucosylation) increases its affinity to CD16a and significantly enhances antibody-dependent cell-mediated cytotoxicity by natural killer (NK) cells. Although benralizumab proved clinically efficacious in clinical trials for patients with severe asthma and hypereosinophilic syndrome, in-depth characterisation of its anti-eosinophilic mechanisms of action remains elusive. Methods Here, we further investigated the mechanisms involved in benralizumab's anti-eosinophilic activities by employing relevant primary human autologous cell co-cultures and real-time-lapse imaging combined with flow cytometry. Results In the presence of NK cells, benralizumab induced potent eosinophil apoptosis as demonstrated by the upstream induction of Caspase-3/7 and upregulation of cytochrome c . In addition, we uncovered a previously unrecognised mechanism whereby benralizumab can induce eosinophil phagocytosis/efferocytosis by macrophages, a process called antibody-dependent cellular phagocytosis. Using live cell imaging, we unravelled the stepwise processes leading to eosinophil apoptosis and uptake by activated macrophages. Through careful observations of cellular co-culture assays, we identified a novel role for macrophage-derived tumour necrosis factor (TNF) to further enhance benralizumab-mediated eosinophil apoptosis through activation of TNF receptor 1 on eosinophils. TNF-induced eosinophil apoptosis was associated with cytochrome c upregulation, mitochondrial membrane depolarisation and increased Caspase-3/7 activity. Moreover, activated NK cells were found to amplify this axis through the secretion of interferon-γ, subsequently driving TNF expression by macrophages. Conclusions Our data provide deeper insights into the timely appearance of events leading to benralizumab-induced eosinophil apoptosis and suggest that additional mechanisms may contribute to the potent anti-eosinophilic activity of benralizumab in vivo . Importantly, afucosylation of benralizumab strongly enhanced its potency for all mechanisms investigated.
von Willebrand Factor Proteolysis Is Deficient in Classic, but not in Bone Marrow Transplantation–Associated, Thrombotic Thrombocytopenic Purpura
Authors: R. Martijn van der Plas, Marion E. Schiphorst, Eric G. Huizinga, Ronald J. Hené, Leo F. Verdonck, Jan J. Sixma, Rob Fijnheer
Journal: Blood (1999)
P15-9 Factors correlated to muscle strength in breast cancer patients before chemotherapy
Authors: Devina A. Halim, Andree Kurniawan, Ratna D. Hatma, Asri Adisasmita, Sonar S. Panigoro, Noorwati Sutandyo, Fiastuti Witjaksono, Dwi S. Rivami, Rachmat Sumantri, Tirza Z. Tamin, Wilson M. Raffaello, Olivia J.D.A. Saroso, Julang Fahman, Felix Wijovi, Helenia Putri, Claudia Jodhinata, Angeline Tancherla, Fernando Dharmaraja
Journal: Annals of Oncology (2021)
Baricitinib prevents GvHD by increasing Tregs via JAK3 and treats established GvHD by promoting intestinal tissue repair via EGFR
Authors: Sena Kim, Kidist Ashami, Sora Lim, Karl Staser, Kiran Vij, Srikanth Santhanam, Julie Ritchey, Sarah Peterson, Feng Gao, Matthew A. Ciorba, Matthew L. Cooper, John F. DiPersio, Jaebok Choi
Journal: Leukemia (2021)
Central sleep apnoea in heart failure: one size does not fit all
Authors: Winfried J Randerath, Michael Arzt
Journal: Thorax (2021)

Over the last decade, results from cluster analyses have offered new insights into pathophysiological endotypes of obstructive sleep apnoea (OSA), opening the possibility to developing a more personalised approach to OSA treatment. In contrast, therapeutic approach to patients with heart failure (HF) and central sleep apnoea (CSA) remains quite undifferentiated. If optimisation of the underlying HF fails to improve CSA, continuous positive airway pressure might be offered in the majority of symptomatic patients. While adaptive servoventilation (ASV) has been developed suppressing CSA and Cheyne-Stokes respiration/periodic breathing, its use is limited to patients without HF or to those with preserved left ventricular ejection fraction of >45%. The data of the French Cohort Study of Chronic Heart Failure Patients With Central Sleep Apnoea Eligible for Adaptive Servo-Ventilation (FACE) trial1 add important puzzle pieces to our understanding of the outcome of patients with HF with CSA, thus fostering a more differentiated perspective to treatment and supporting the concepts of tailoring treatment to individual patients:

1.  FACE includes patients who are typically excluded from randomised controlled trials due to their characteristics.

2.  It raises the question of specific phenotypes with unfavourable outcome.

The Treatment of Predominant Central Sleep Apnoea by Adaptive Servo Ventilation in Patients With Heart Failure (SERVE-HF) trial2 studied a specific HF population with predominant CSA and left ventricular ejection fraction ≤45%. The FACE trial, which enrolled patients from 2009 to 2018,1 included patients who were prescribed ASV before and after publication of the SERVE-HF …
PARIS farnesylation prevents neurodegeneration in models of Parkinson’s disease
Authors: Areum Jo, Yunjong Lee, Tae-In Kam, Sung-Ung Kang, Stewart Neifert, Senthilkumar S. Karuppagounder, Rin Khang, Hojin Kang, Hyejin Park, Shih-Ching Chou, Sungtaek Oh, Haisong Jiang, Deborah A. Swing, Sangwoo Ham, Sheila Pirooznia, George K. E. Umanah, Xiaobo Mao, Manoj Kumar, Han Seok Ko, Ho Chul Kang, Byoung Dae Lee, Yun-Il Lee, Shaida A. Andrabi, Chi-Hu Park, Ji-Yeong Lee, Hanna Kim, Hyein Kim, Hyojung Kim, Jin Whan Cho, Sun Ha Paek, Chan Hyun Na, Lino Tessarollo, Valina L. Dawson, Ted M. Dawson, Joo-Ho Shin
Journal: Science Translational Medicine (2021)

Farnesol enhances the amounts of farnesylated PARIS and PGC-1α, preventing dopaminergic neuronal loss in Parkinson’s disease models.
A Roadmap to the Structure-Related Metabolism Pathways of Per- and Polyfluoroalkyl Substances in the Early Life Stages of Zebrafish ( <i>Danio rerio</i> )
Authors: Jiajun Han, Wen Gu, Holly Barrett, Diwen Yang, Song Tang, Jianxian Sun, Jiabao Liu, Henry M. Krause, Keith A. Houck, Hui Peng
Journal: Environmental Health Perspectives (2021)

Background: Thousands of per- and polyfluoroalkyl substances (PFAS) with diverse structures have been detected in the ambient environment. Apart from a few well-studied PFAS, the structure-related toxicokinetics of a broader set of PFAS remain unclear. Objectives: To understand the toxicokinetics of PFAS, we attempted to characterize the metabolism pathways of 74 structurally diverse PFAS samples from the U.S. Environmental Protection Agency's PFAS screening library. Methods: Using the early life stages of zebrafish (Danio rerio) as a model, we determined the bioconcentration factors and phenotypic toxicities of 74 PFAS. Then, we applied high-resolution mass spectrometry–based nontargeted analysis to identify metabolites of PFAS in zebrafish larvae after 5 d of exposure by incorporating retention time and mass spectra. In vitro enzymatic activity experiments with human recombinant liver carboxylesterase (hCES1) were employed to validate the structure-related hydrolysis of 11 selected PFAS. Results: Our findings identified five structural categories of PFAS prone to metabolism. The metabolism pathways of PFAS were highly related to their structures as exemplified by fluorotelomer alcohols that the predominance of β-oxidation or taurine conjugation pathways were primarily determined by the number of hydrocarbons. Hydrolysis was identified as a major metabolism pathway for diverse PFAS, and perfluoroalkyl carboxamides showed the highest in vivo hydrolysis rates, followed by carboxyesters and sulfonamides. The hydrolysis of PFAS was verified with recombinant hCES1, with strong substrate preferences toward perfluoroalkyl carboxamides. Conclusions: We suggest that the roadmap of the structure-related metabolism pathways of PFAS established in this study would provide a starting point to inform the potential health risks of other PFAS. https://doi.org/10.1289/EHP7169
Finding a Place for Candidate Gene Studies in a Genome-Wide Association Study World
Authors: David K. Menon, Jonathan Rosand
Journal: JAMA Network Open (2021)

Ruchira M. Jha, MD, MSc; Benjamin E. Zusman, MD, MSc; Ava M. Puccio, PhD; David O. Okonkwo, MD, PhD; Matthew Pease, MD; Shashvat M. Desai, MBBS; Matthew Leach, MD; Yvette P. Conley, PhD; Patrick M. Kochanek, MD
Metabolic reprogramming of cancer-associated fibroblasts and its effect on cancer cell reprogramming
Authors: Zhenzhen Li, Chanjun Sun, Zhihai Qin
Journal: Theranostics (2021)

Cancer cells are well-known for adapting their metabolism to maintain high proliferation rates and survive in unfavorable environments with low oxygen and nutritional deficiency.Metabolic reprogramming most commonly arises from the tumor microenvironment (TME).The events of metabolic pathways include the Warburg effect, shift in Krebs cycle metabolites, and increase rate of oxidative phosphorylation that provides the energy for the development and invasion of cancer cells.The TME and shift in tumor metabolism shows a close relationship through bidirectional signaling pathways between the stromal and tumor cells.Cancer-associated fibroblasts (CAFs) are the main type of stromal cells in the TME and consist of a heterogeneous and plastic population that play key roles in tumor growth and metastatic capacity.Emerging evidence suggests that CAFs act as major regulators in shaping tumor metabolism especially through the dysregulation of several metabolic pathways, including glucose, amino acid, and lipid metabolism.The arrangement of these metabolic switches is believed to shape distinct CAF behavior and change tumor cell behavior by the CAFs.The crosstalk between cancer cells and CAFs is associated with cell metabolic reprogramming that contributes to cancer cell growth, progression, and evasion from cancer therapies.But the mechanism and process of this interaction remain unclear.This review aimed to highlight the metabolic couplings between tumor cells and CAFs.We reviewed the recent literature supporting an important role of CAFs in the regulation of cancer cell metabolism, and the relevant pathways, which may serve as targets for therapeutic interventions.
MO4-1 EGFR inhibitor upregulates HER3 expression and enhances the efficacy of anti-HER3 antibody drug conjugate U3-1402
Authors: Kimio Yonesaka, Junko Tanizaki, Osamu Maenishi, Hisato Kawakami, Kaoru Tanaka, Hidetoshi Hayashi, Masayuki Takeda, Kazuko Sakai, Maki Kobayashi, Ryoto Yoshimoto, Hiroki Goto, Masanori Funabashi, Yuuri Hashimoto, Kenji Hirotani, Takashi Kagari, Kazuto Nishio, Kazuhiko Nakagawa
Journal: Annals of Oncology (2021)
Race-Free Equations for eGFR: Comparing Effects on CKD Classification
Authors: James A. Diao, Neil R. Powe, Arjun K. Manrai
Journal: Journal of the American Society of Nephrology (2021)

Medical centers nationwide are considering race-free equations to improve the reporting of eGFR.[1][1] Numerous alternatives[2][2] have been proposed and implemented—including removal of the coefficient for Black race—with substantial implications for guideline-recommended care.[3][3] Race-free
Coil Occlusion of Patent Ductus Arteriosus : Impact of 0.052-Inch Gianturco Coil Without Amplatzer Duct Occluder
Authors: Hideshi Tomita, Motoki Takamuro, Shigeto Fuse, Norihisa Horita, Kinya Hatakeyama, Hiroyuki Tsutsumi, Satoshi Yazaki, Shigeyuki Echigo, Kohji Kimura
Journal: Circulation (2005)
Radiation Resistance of C57Bl/6 Mouse Bone Marrow Stromal Cell Lines Induced By Apoptosis Inhibitor JP4-039 or Necroptosis Inhibitor Necrostatin-1, but Not By Simultaneous Administration of Both Mitigators
Authors: Zhiyang Wei, Michael Epperly, Donna Shields, Wen Hou, Darcy Franicola, Xichen Zhang, Renee Fisher, Hulya Bayir, Peter Wipf, Joel S. Greenberger
Journal: Blood (2017)
Extra-Corporeal Photopheresis Plus Low-Dose Interleukin-2 for Steroid-Refractory Chronic Graft-Vs.-Host Disease: Efficacy, Safety and Immune Correlates
Authors: John Koreth, Haesook T Kim, Roger Belizaire, Samuel J Poryanda, Carol Reynolds, Jennifer Whangbo, Sarah Nikiforow, Edwin Alyea, Philippe Armand, Corey Cutler, Vincent T Ho, Bruce Blazar, Joseph H. Antin, Jerome Ritz, Robert J. Soiffer
Journal: Blood (2017)
Circulating microfibrillar-associated protein 4 is an independent predictor of transplant-free survival in compensated and decompensated cirrhosis
Authors: Nikolaj Torp, Mads Israelsen, Ditlev Nytoft Rasmussen, Bjørn Stæhr Madsen, Maria Kjærgaard, Philipp Lutz, Christian Strassburg, Christian Mortensen, Anne Wilkens Knudsen, Grith Sorensen, Uffe Holmskov, Anders Schlosser, Maja Thiele, Jonel Trebicka, Aleksander Krag
Journal: Journal of Hepatology (2020)
O14-3 End-of-life decision-making among the AYA cancer patients
Authors: Emi Kubo, Hiroto Ishiki, Miho Yamada, Takashi Kawaguchi, Sayaka Arakawa, Sayuri Yokota, Daisuke Kiuchi, Koji Amano, Eriko Satomi
Journal: Annals of Oncology (2021)
Prediction of progression in Barrett’s esophagus: does inflammation hold the key?
Authors: Prasad G. Iyer
Journal: Endoscopy (2021)

The clinical significance of Barrett’s esophagus (BE) lies in it being the only known precursor to esophageal adenocarcinoma (EAC), which occurs via the development of dysplasia. As endoscopic therapy of dysplasia can prevent EAC, surveillance is recommended to detect dysplasia. Endoscopic surveillance is recommended every 3–5 years in those without dysplasia (NDBE). Most gastrointestinal society guidelines do not personalize surveillance intervals on the basis of patient or BE characteristics [1]. Unfortunately, endoscopic surveillance as currently performed is only modestly effective in reducing EAC mortality [2]. Hence, risk prediction algorithms to tailor surveillance and management on the basis of progression risk is highly appealing.
68Ga-PSMA PET/CT to Distinguish Brain Metastasis of Renal Cell Carcinoma From Radiation Necrosis After Stereotactic Radiosurgery
Authors: Nuh Filizoglu, Ilknur Alsan Cetin, Tugba Nergiz Kissa, Khanim Niftaliyeva, Tunc Ones
Journal: Clinical Nuclear Medicine (2021)

Abstract Renal cell carcinoma (RCC) is the most common primary malignancy of the kidney. Approximately 35% of patients of RCC presents with distant metastasis at initial evaluation. CT and MRI are the mainstay imaging modalities. Distinguishing radiation necrosis from tumor progression after stereotactic radiosurgery is challenging. Herein, we present a case of a 43-year-old man with RCC who was treated with stereotactic radiosurgery for brain metastases. We want to emphasize the potential value of 68 Ga-PSMA PET/CT imaging in the differential diagnosis and follow-up of tumor progression from radiation necrosis in RCC patients.
Novel Insights into Mechanisms of Intestinal Phosphate Absorption in Patients with Chronic Kidney Disease
Authors: Kittrawee Kritmetapak, Rajiv Kumar
Journal: Journal of the American Society of Nephrology (2021)

CKD associates with phosphate retention, contributing to an increased risk of secondary hyperparathyroidism, vascular calcification, and cardiovascular mortality. Hyperphosphatemia is generally not evident until the eGFR falls below 30 ml/min per 1.73 m,[1][1] due to a compensatory reduction in
Abstract 14438: A Factor Xa Inhibitor Antidote (Andexanet Alfa) is Capable of Neutralizing the Anticoagulant Effects of Unfractionated Heparin of Bovine, Ovine and Porcine Origin in a Comparable Manner as Protamine Sulfate
Authors: Debra Hoppensteadt, Fakiha Siddiqui, Alfonso J Tafur, Emily Bontekoe, Omer Iqbal, Walter Jeske, Ahmed Kouta, Kambiz Zorriasateyn, Eduardo Ramacciotti, Jawed Fareed, Bruce Lewis
Journal: Circulation (2019)

Introduction: Andexanet alfa is an approved antidote for such factor Xa inhibitors as apixaban and rivaroxaban. Unfractionated heparin (UFH) is commonly used for therapeutic, interventional and sur...
Overcoming the Dependence on Animal Models for Osteoarthritis Therapeutics – The Promises and Prospects of In Vitro Models
Authors: Yogendra Pratap Singh, Joseph Christakiran Moses, Nandana Bhardwaj, Biman B. Mandal
Journal: Advanced Healthcare Materials (2021)

Abstract Osteoarthritis (OA) is a musculoskeletal disease characterized by progressive degeneration of osteochondral tissues. Current treatment is restricted to the reduction of pain and loss of function of the joint. To better comprehend the OA pathophysiological conditions, several models are employed, however; there is no consensus on a suitable model. In this review, different in vitro models being developed for possible therapeutic intervention of OA are outlined. Herein, various in vitro OA models starting from 2D model, co‐culture model, 3D models, dynamic culture model to advanced technologies‐based models such as 3D bioprinting, bioassembly, organoids, and organ‐on‐chip‐based models are discussed with their advantages and disadvantages. Besides, different growth factors, cytokines, and chemicals being utilized for induction of OA condition are reviewed in detail. Furthermore, there is focus on scrutinizing different molecular and possible therapeutic targets for better understanding the mechanisms and OA therapeutics. Finally, the underlying challenges associated with in vitro models are discussed followed by future prospective. Taken together, a comprehensive overview of in vitro OA models, factors to induce OA‐like conditions, and intricate molecular targets with the potential to develop personalized osteoarthritis therapeutics in the future with clinical translation is provided.
Recognizing Intersectionality—The Association of Gender, Gender Identity, Sexual Orientation, and Race With Social Experience
Authors: Kelli N. Patterson, Amalia Cochran
Journal: JAMA Surgery (2021)

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Multiple inducers of endothelial <scp>NOS</scp> (<scp>eNOS</scp>) dysfunction in sickle cell disease
Authors: Robert P. Hebbel, Gregory M. Vercellotti
Journal: American Journal of Hematology (2021)

A characteristic aspect of the robust, systemic inflammatory state in sickle cell disease is dysfunction of endothelial nitric oxide synthase (eNOS). We identify 10 aberrant endothelial cell inputs, present in the specific sickle context, that are known to have the ability to cause eNOS dysfunction. These are: endothelial arginase depletion, asymmetric dimethylarginine, complement activation, endothelial glycocalyx degradation, free fatty acids, inflammatory mediators, microparticles, oxidized low density lipoproteins, reactive oxygen species, and Toll-like receptor 4 signaling ligands. The effect of true eNOS dysfunction on clinical testing using flow-mediated dilation can be simulated by two known examples of endothelial dysfunction mimicry (hemoglobin consumption of NO; and oxidation of smooth muscle cell soluble guanylate cyclase). This lends ambiguity to interpretation of such clinical testing. The presence of these multiple perturbing factors argues that a therapeutic approach targeting only a single injurious endothelial input (or either example of mimicry) would not be sufficiently efficacious. This would seem to argue for identifying therapeutics that directly protect eNOS function or application of multiple therapeutic approaches.
Norman Bruce Bennett
Authors: Peter N Bennett, Audrey A Dawson, John G Simpson
Journal: BMJ (2021)

Norman Bruce Bennett (“Bruce”) was educated at Brechin High School, Angus, Scotland where he achieved dux of the junior and then the senior school, giving early indication of his academic capability. His father was initially hesitant to support his desire to study medicine, so he won a competitive bursary and duly enrolled at the University of Aberdeen.

He embarked on a clinical academic career in the Department of Medicine, investigating inhibition of the fibrinolytic enzyme system in collaboration with Derek Ogston and graduating MD (Hons) …
The Power of Nursing
Authors: Molly A. Uhlenhake
Journal: Annals of Internal Medicine (2021)

Ad LibitumJuly 2021The Power of NursingMolly A. Uhlenhake, DOMolly A. Uhlenhake, DOThe University of Missouri–Kansas City Kansas City, MissouriSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-6130 Audio Reading - “The Power of Nursing” Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads “The Power of Nursing” by Molly A. Uhlenhake, DO Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Your body moves up and down with my ... Author, Article, and Disclosure InformationAffiliations: The University of Missouri–Kansas City Kansas City, MissouriCurrent Author Address: Molly A. Uhlenhake, DO, 2301 Holmes Street, Kansas City, MO 64108; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “The Power of Nursing” Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads “The Power of Nursing” by Molly A. Uhlenhake, DO Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics July 2021Volume 174, Issue 7Page: 1019 ePublished: 20 July 2021 Issue Published: July 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...