tbuckley/cabot-search huggingface dataset:
Interleukin-4 and interleukin-13 induce different metabolic profiles in microglia and macrophages that relate with divergent outcomes after spinal cord injury
Authors: Jesus Amo-Aparicio, Joana Garcia-Garcia, Isaac Francos-Quijorna, Andrea Urpi, Anna Esteve-Codina, Marta Gut, Albert Quintana, Ruben Lopez-Vales
Journal: Theranostics (2021)

Background: Microglia and macrophages adopt a pro-inflammatory phenotype after spinal cord injury (SCI), what is thought to contribute to secondary tissue degeneration.We previously reported that this is due, in part, to the low levels of anti-inflammatory cytokines, such as IL-4.Since IL-13 and IL-4 share receptors and both cytokines drive microglia and macrophages towards an anti-inflammatory phenotype in vitro, here we studied whether administration of IL-13 and IL-4 after SCI leads to beneficial effects.Methods: We injected mice with recombinant IL-13 or IL-4 at 48 h after SCI and assessed their effects on microglia and macrophage phenotype and functional outcomes.We also performed RNA sequencing analysis of macrophages and microglia sorted from the injured spinal cords of mice treated with IL-13 or IL-4 and evaluated the metabolic state of these cells by using Seahorse technology.Results: We observed that IL-13 induced the expression of anti-inflammatory markers in microglia and macrophages after SCI but, in contrast to IL-4, it failed to mediate functional recovery.We found that these two cytokines induced different gene signatures in microglia and macrophages after SCI and that IL-4, in contrast to IL-13, shifted microglia and macrophage metabolism from glycolytic to oxidative phosphorylation.These findings were further confirmed by measuring the metabolic profile of these cells.Importantly, we also revealed that macrophages stimulated with IL-4 or IL-13 are not deleterious to neurons, but they become cytotoxic when oxidative metabolism is blocked.This suggests that the metabolic shift, from glycolysis to oxidative phosphorylation, is required to minimize the cytotoxic responses of microglia and macrophages.Conclusions: These results reveal that the metabolic fitness of microglia and macrophages after SCI contributes to secondary damage and that strategies aimed at boosting oxidative phosphorylation might be a novel approach to minimize the deleterious actions of microglia and macrophages in neurotrauma.
The Role of Real-Time Health Data and Health Information Technology in Reducing Diabetes Risk and Advancing Population Health
Authors: Elham Hatef
Journal: JAMA Network Open (2021)

Rania Kanchi, MPH; Priscilla Lopez, PhD; Pasquale E. Rummo, PhD; David C. Lee, MD; Samrachana Adhikari, PhD; Mark D. Schwartz, MD; Sanja Avramovic, PhD; Karen R. Siegel, PhD; Deborah B. Rolka, MS; Giuseppina Imperatore, MD, PhD; Brian Elbel, PhD; Lorna E. Thorpe, PhD
Mortality in COVID-19 Patients with CKD with and Without Kidney Replacement Therapy in Western Mexico
Authors: Alejandro Garcia Rivera, Ríos C. Katia yuritzi, Arantxa K. Aguilar, Marcos A. Elias Lopez, Jesús A. Rico sánchez, Luz Yareli Villegas Gutierrez, Mario Valdez Avendaño, Fabiola V. Rios Rios, Mauro G. Montemayor Villacobos, Mónica L. Morales Guillén, Rubén Lara Monterrubio, Roxana Villanueva Macedo, José J. Gutiérrez Hernandez, Ramon A. Soto Rodriguez, Hugo B. Espinoza, Omar H. Sanchez Vazquez, Jorge fernando Topete reyes, Renato Parra Michel, Carolina R. Alvarez
Journal: Journal of the American Society of Nephrology (2021)

Rivera, Alejandro Garcia; Katia yuritzi, Ríos C.; Aguilar, Arantxa K.; Elias Lopez, Marcos A.; Rico sánchez, Jesús A.; Gutierrez, Luz Yareli Villegas; Avendaño, Mario Valdez; Rios Rios, Fabiola V.; Montemayor Villacobos, Mauro G.; Morales Guillén, Mónica L.; Monterrubio, Rubén Lara; Macedo, Roxana Villanueva; Gutiérrez Hernandez, José J.; Soto Rodriguez, Ramon A.; Espinoza, Hugo B.; Sanchez Vazquez, Omar H.; Topete reyes, Jorge fernando; Michel, Renato Parra; Alvarez, Carolina R. Author Information
TCT-486 Age-Stratified Sex-Related Differences in Incidence, Management, and Outcomes of Cardiogenic Shock
Authors: Mohammed Osman, Moinuddin Syed, Babikir Kheiri, Christopher Bianco, Ankur Kalra, Joaquin Cigarroa, Mamas Mamas, J. Dawn Abbott, Cindy Grines, Gregg Fonarow, Sudarshan Balla
Journal: Journal of the American College of Cardiology (2021)
Imagine CRISPR cures
Authors: Fyodor D. Urnov
Journal: Molecular Therapy (2021)

A decade of progress in sequencing and in CRISPR/Cas technologies has created a situation without precedent in the history of medicine. Starting with an individual patient, next-generation sequencing can diagnose, in less than 24 h, the genetic basis of a Mendelian disorder.1 Once the causative mutation is found, CRISPR/Cas, in principle, represents a targeted therapy, a first-pass iteration of which can be designed in silico within minutes thanks to straightforward principles of target locus recognition by Cas9.
Abstract 14651: Advanced Interatrialblock as an Independent Marker of Left Atrial Fibrosis and Intra-Atrial Dyssynchrony: ECG-MRI Correlation
Authors: Luisa C Ciuffo, Henrique Doria De Vasconcellos, Vanesa Bruña, Manuel Martínez-Sellés, Susumu Tao, David D Spragg, Joseph E Marine, Ronald D Berger, Joao A Lima, Hugh G Calkins, Antonio Bayés de Luna, Hiroshi Ashikaga
Journal: Circulation (2019)

Introduction: Advanced interatrial block (IAB) on a 12-lead electrocardiogram (ECG) is a predictor of stroke, incident atrial fibrillation (AF), and AF recurrence after catheter ablation. Hypothesi...
Bidirectional control of infant rat social behavior via dopaminergic innervation of the basolateral amygdala
Authors: Maya Opendak, Charlis Raineki, Rosemarie E Perry, Millie Rincón-Cortés, Soomin C Song, Roseanna M Zanca, Emma Wood, Katherine Packard, Shannon Hu, Joyce Woo, Krissian Martinez, K Yaragudri Vinod, Russell W Brown, Gerald A Deehan, Robert C Froemke, Peter A Serrano, Donald A Wilson, Regina M Sullivan
Journal: Neuron (2021)
TCT-295 Safety and Efficacy of Laser Atherectomy for the Treatment of Complex Stent Failure
Authors: Mordechai Golomb, Barbora Zvarova, Diaa Hakim, Musa Sharkawi, Allison Tsao, Phillip M. Devlin, Brian Bergmark, Kevin Croce
Journal: Journal of the American College of Cardiology (2021)
Cancer-associated fibroblast heterogeneity is associated with organ-specific metastasis in pancreatic ductal adenocarcinoma
Authors: Xingyi Pan, Jiaojiao Zhou, Qian Xiao, Kenji Fujiwara, Mengwen Zhang, Guanglan Mo, Wei Gong, Lei Zheng
Journal: Journal of Hematology & Oncology (2021)

Abstract Background Metastasis occurs in the majority of pancreatic ductal adenocarcinoma (PDAC) patients at diagnosis or following resection. Patients with liver metastasis and those with lung metastasis have significantly different prognosis. Here, we sought to understand how cancer-associated fibroblasts (CAFs) play roles in the development of organ-specific metastasis. Methods PDAC tumor cell lines established from the primary tumors with liver and lung metastasis potentials, respectively, in Kras/p53 mutation conditional knock-in (KPC) mice were co-cultured with matched CAFs or mouse mesenchymal stem cells. CAFs were isolated from metastases and subjected to DNA methylation and whole transcriptomic RNA sequencing analysis. Results The ability of mouse PDAC tumor cell lines in developing liver or lung-specific metastases was demonstrated in orthotopic models. Tumor cells associated with liver metastasis potential, but not those associated with lung metastasis potential, induced the methylation of metabolism genes including NQO1 and ALDH1a3 and subsequent downregulated mRNA expression of a broader group of metabolism genes in CAFs. DNA methylation and downregulation of metabolism genes in CAFs in liver metastasis, but not those in lung metastasis, appeared to be regulated by DNA methyltransferase. Tumor cells associated with liver metastasis potential, but not those associated with lung metastasis potential, induce inflammatory CAF (iCAF) signatures. CAFs from liver metastasis demonstrated a more homogenous iCAF phenotype, whereas CAFs from lung metastasis maintained the heterogeneity. Conclusions PDAC with organ-specific metastatic potentials has different capacities in inducing methylation of metabolism genes in CAFs, modulating CAF phenotypes, and resulting in different levels of heterogeneity of CAFs in different metastatic niches.
TCT-469 Mid-Term Outcomes of Transcatheter Aortic Valve Replacement With the Edwards SAPIEN 3 Valve in Patients With Extremely Large Annuli: A Single-Center Study
Authors: Lauren Curtis, Raymond McKay, Nicole Hoover, Asad Rizvi, Sean McMahon, William Duvall, Jeff Mather, Wael ElMallah, Francis Kiernan
Journal: Journal of the American College of Cardiology (2021)
Covid-19: FDA puts Moderna’s paediatric application on hold to investigate side effects
Authors: Owen Dyer
Journal: BMJ (2021)

The US emergency use authorisation of Moderna’s coronavirus vaccine in people aged 12-17 will be delayed, the company has been told by the Food and Drug Administration (FDA), while the regulator reviews new international data suggesting that the risk of myocarditis and pericarditis, the most problematic side effect of mRNA vaccines, may be higher after vaccination with Moderna’s product than with its Pfizer competitor.

Moderna said it will also delay its application for authorisation in 6-11 year olds. The FDA warned the company that the authorisation in 12-17 year olds could now take until January, Moderna said in a statement.

A possible increase in the rate of myocarditis and pericarditis, which involve inflammation of the muscle tissue around the heart, has been observed in several countries among people who recently received an mRNA vaccine such as Pfizer or Moderna. …
Covid-19: UK stockpiles two unapproved antiviral drugs for treatment at home
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Covid-19: UK stockpiles two unapproved antiviral drugs for treatment at home Elisabeth MahaseThe UK has started stockpiling two antiviral drugs as part of a plan to give people who are staying at home with covid-19 a treatment to reduce symptoms and the spread of the virus.7
Implantation and long-term assessment of the stability and biocompatibility of a novel 98 channel suprachoroidal visual prosthesis in sheep
Authors: Samuel C. Eggenberger, Natalie L. James, Cherry Ho, Steven S. Eamegdool, Veronika Tatarinoff, Naomi A. Craig, Barry S. Gow, Susan Wan, Christopher W.D. Dodds, Donna La Hood, Aaron Gilmour, Shannon L. Donahoe, Mark Krockenberger, Krishna Tumuluri, Melville J. da Cruz, John R. Grigg, Peter McCluskey, Nigel H. Lovell, Michele C. Madigan, Adrian T. Fung, Gregg J. Suaning
Journal: Biomaterials (2021)

Severe visual impairment can result from retinal degenerative diseases such as retinitis pigmentosa, which lead to photoreceptor cell death. These pathologies result in extensive neural and glial remodelling, with survival of excitable retinal neurons that can be electrically stimulated to elicit visual percepts and restore a form of useful vision. The Phoenix99 Bionic Eye is a fully implantable visual prosthesis, designed to stimulate the retina from the suprachoroidal space. In the current study, nine passive devices were implanted in an ovine model from two days to three months. The impact of the intervention and implant stability were assessed using indirect ophthalmoscopy, infrared imaging, and optical coherence tomography to establish the safety profile of the surgery and the device. The biocompatibility of the device was evaluated using histopathological analysis of the tissue surrounding the electrode array, with a focus on the health of the retinal cells required to convey signals to the brain. Appropriate stability of the electrode array was demonstrated, and histological analysis shows that the fibrotic and inflammatory response to the array was mild. Promising evidence of the safety and potential of the Phoenix99 Bionic Eye to restore a sense of vision to the severely visually impaired was obtained.
霊長類進化におけるα-galの損失は,細菌敗血症に対する抗体エフェクター機能および耐性を増強する【JST・京大機械翻訳】
Authors: Singh Sumnima, A Thompson Jessica, Yilmaz Bahtiyar, Li Hai, Weis Sebastian, Sobral Daniel, Truglio Mauro, Aires da Silva Frederico, Aguiar Sandra, Carlos Ana Rita, Rebelo Sofia, Cardoso Silvia, Gjini Erida, Nunez Gabriel, P Soares Miguel
Journal: Cell Host & Microbe (2021)
TCT-483 Impact of Sex on Periprocedural Mortality Among Patients Undergoing Transcatheter Aortic Valve Replacement in the United States
Authors: Aditya Mantha, Daniel Miklin, Travis Martinez, Ksheeraja Ravi, Shawn Shah, Priya Bansal, Anilkumar Mehra
Journal: Journal of the American College of Cardiology (2021)
Misoprostol-Induced Pulmonary Edema in a Pregnant Woman with ESKD Undergoing Induction of Labor Following SARS-CoV-2 Infection
Authors: Kelly H. Beers, Swati Mehta, Geovani Faddoul
Journal: Journal of the American Society of Nephrology (2021)

Journal of the American Society of Nephrology 32(10S):p 849, October 2021. | DOI: 10.1681/ASN.20213210S1849a
Association Between mRNA Vaccination and COVID-19 Hospitalization and Disease Severity
Authors: Mark W. Tenforde, Wesley H. Self, Katherine Adams, Manjusha Gaglani, Adit A. Ginde, Tresa McNeal, Shekhar Ghamande, David J. Douin, H. Keipp Talbot, Jonathan D. Casey, Nicholas M. Mohr, Anne Zepeski, Nathan I. Shapiro, Kevin W. Gibbs, D. Clark Files, David N. Hager, Arber Shehu, Matthew E. Prekker, Heidi L. Erickson, Matthew C. Exline, Michelle N. Gong, Amira Mohamed, Daniel J. Henning, Jay S. Steingrub, Ithan D. Peltan, Samuel M. Brown, Emily T. Martin, Arnold S. Monto, Akram Khan, Catherine L. Hough, Laurence W. Busse, Caitlin C. ten Lohuis, Abhijit Duggal, Jennifer G. Wilson, Alexandra June Gordon, Nida Qadir, Steven Y. Chang, Christopher Mallow, Carolina Rivas, Hilary M. Babcock, Jennie H. Kwon, Natasha Halasa, James D. Chappell, Adam S. Lauring, Carlos G. Grijalva, Todd W. Rice, Ian D. Jones, William B. Stubblefield, Adrienne Baughman, Kelsey N. Womack, Jillian P. Rhoads, Christopher J. Lindsell, Kimberly W. Hart, Yuwei Zhu, Samantha M. Olson, Miwako Kobayashi, Jennifer R. Verani, Manish M. Patel
Journal: JAMA (2021)

A comprehensive understanding of the benefits of COVID-19 vaccination requires consideration of disease attenuation, determined as whether people who develop COVID-19 despite vaccination have lower disease severity than unvaccinated people.
Home based rehabilitation after a knee replacement is as effective as physiotherapy
Authors: Helen Saul, Deniz Gursul
Journal: BMJ (2021)

The studyBarker KL, Room J, Knight R, et al. Outpatient physiotherapy versus home-based rehabilitation for patients at risk of poor outcomes after knee arthroplasty: CORKA RCT. Health Technol Assess 2020;24:1-116.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/knee-replacements-home-based-rehabilitation-as-effective-physiotherapy/.
Validation of International Classification of Diseases Tenth Revision code for prurigo nodularis
Authors: Youkyung Sophie Roh, Melika Marani, Una Choi, Nishadh Sutaria, Varsha Parthasarathy, Junwen Deng, Zachary A. Bordeaux, Matthew T. Taylor, Yevgeniy R. Semenov, Shawn G. Kwatra
Journal: Journal of the American Academy of Dermatology (2021)
Grp78 is over-expressed in head neck cancer and is a potential molecular target for inhibition of oncogenesis
Authors: Chi-Ching Chiu, Ann-Joy Cheng
Journal: Cancer Research (2007)

4282  Grp78 (Glucose-regulated protein 78) is one of the best-characterized endoplasmic reticulum (ER) chaperone protein. Recently, elevation of Grp78 has been reported associated with a variety of cancer, but the exact function is obscure. To identify whether Grp78 associated with HNC, we examined the protein expressions between paired cancer and grossly normal mucosa tissues. Of 56 patients assayed, 34 (61%) had two fold of over-expression, suggesting that this molecule participates in carcinogenesis of HNC. To further characterize the role, the effects of Grp78 knockdown by RNAi was examined in six HNC cell lines, including 2 nasopharyngeal cancers, 2 oral cancers, and 2 pharyngolaryngeal cancers. Consistent with the clinical findings, inhibition of Grp78 significantly reduced cell growth and colony formation to 53% ~ 11% in six HNC cell lines. Use of an in vitro wound healing and Matrigel invasion assays, we found that cell migration and invasive ability were also inhibited to 18% ~ 42% in these cell line tested. Two lines of in vivo xenograft studies showed that administration of Grp78-RNAi plasmid significantly inhibited HNC tumor growth for 2 months in BALB/C nude mice. In conclusion, Grp78 is identified over-expressed in HNC. Inhibition of Grp78 significantly suppresses carcinogenic potential in cellular and in vivo animal studies. These findings suggest that GRP78 is a potential molecular target in the development of adjuvant therapy for HNC.
Acute Treatment Effects on GFR in Randomized Clinical Trials of Kidney Disease Progression
Authors: Brendon L. Neuen, Hocine Tighiouart, Hiddo J.L. Heerspink, Edward F. Vonesh, Juhi Chaudhari, Shiyuan Miao, Tak Mao Chan, Fernando C. Fervenza, Jürgen Floege, Marian Goicoechea, William G. Herrington, Enyu Imai, Tazeen H. Jafar, Julia B. Lewis, Philip Kam-Tao Li, Francesco Locatelli, Bart D. Maes, Ronald D. Perrone, Manuel Praga, Annalisa Perna, Francesco P. Schena, Christoph Wanner, Jack F.M. Wetzels, Mark Woodward, Di Xie, Tom Greene, Lesley A. Inker
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement GFR slope has been proposed as a surrogate endpoint for progression to kidney failure in clinical trials studying patients with CKD. Acute or immediate effects on GFR after treatment initiation may complicate the interpretation of long-term treatment effects. In this large meta-analysis of 53 randomized clinical studies of CKD progression, the authors found the magnitude and nature of acute effects are variable across different interventions and may be larger at a higher baseline GFR. Negative acute effects (such as an acute reduction in GFR) were observed in trials of renin-angiotensin system blockade and BP lowering, whereas positive acute effects were more common in trials of immunosuppressive therapies. Such information can inform the optimal design and analysis plan for randomized clinical trials in CKD. Background Acute changes in GFR can occur after initiation of interventions targeting progression of CKD. These acute changes complicate the interpretation of long-term treatment effects. Methods To assess the magnitude and consistency of acute effects in randomized clinical trials and explore factors that might affect them, we performed a meta-analysis of 53 randomized clinical trials for CKD progression, enrolling 56,413 participants with at least one estimated GFR measurement by 6 months after randomization. We defined acute treatment effects as the mean difference in GFR slope from baseline to 3 months between randomized groups. We performed univariable and multivariable metaregression to assess the effect of intervention type, disease state, baseline GFR, and albuminuria on the magnitude of acute effects. Results The mean acute effect across all studies was −0.21 ml/min per 1.73 m 2 (95% confidence interval, −0.63 to 0.22) over 3 months, with substantial heterogeneity across interventions (95% coverage interval across studies, −2.50 to +2.08 ml/min per 1.73 m 2 ). We observed negative average acute effects in renin angiotensin system blockade, BP lowering, and sodium-glucose cotransporter 2 inhibitor trials, and positive acute effects in trials of immunosuppressive agents. Larger negative acute effects were observed in trials with a higher mean baseline GFR. Conclusion The magnitude and consistency of acute GFR effects vary across different interventions, and are larger at higher baseline GFR. Understanding the nature and magnitude of acute effects can help inform the optimal design of randomized clinical trials evaluating disease progression in CKD.
Programmed death 1 expressing CD8+CXCR5+ follicular T cells constitute effector rather than exhaustive phenotype in patients with chronic hepatitis B
Authors: Arshi Khanam, Lydia S. Y. Tang, Shyam Kottilil
Journal: Hepatology (2021)

Classical CD8 T cells are implicated for protective and pathogenic roles in chronic hepatitis B (CHB) infection. Recently, a subset of CD8 T cells expressing C-X-C chemokine receptor type 5 (CXCR5) and exhibiting features of TFH cells has been identified during chronic viral infections. However, in CHB, knowledge of their roles is limited.We characterized circulating CD8+ CXCR5+/- cells and investigated their association with clinical and viral factors. We found that CHB infection did not influence the overall frequencies of CD8+ CXCR5+ cells whereas CD8+ CXCR5- cells were increased. However, among CHB, CD8+ CXCR5+ cells were higher in patients with low HBsAg and HBV-DNA levels, patients who were HBeAg negative and had high fibrosis scores, and these cells exhibited a significant association with HBsAg and HBV-DNA reduction. Contrarily, CD8+ CXCR5- cells were expanded and positively correlated with patients having high HBsAg, HBV-DNA, and alanine aminotransferase levels. CD8+ CXCR5+ cells express costimulatory molecules ICOS, OX40, CD40 ligand, inhibitory molecule programmed death 1, transcription factors B-cell lymphoma (BCL)-2, BCL-6, and signal transducer and activator of transcription 3, and are enriched in effector and central memory phenotype. Moreover, these cells are heterogeneous in nature given that they constitute different subsets of cytotoxic follicular T cells (TCF), including TCF1, TCF2, TCF17, and TCF22. Despite expressing high PD-1, CD8+ CXCR5+ cells are activated, proliferating, secreting more IFN-γ, IL-21, and IL-22, and have better cytolytic potential than CD8+ CXCR5- cells, which were inhibited after PD-1/PD-L1 blockade. CD8+ CXCR5+ cells are efficient in helping B cells in terms of plasmablasts and plasma cell generation.In conclusion, CD8+ CXCR5+ cells are enriched in effector phenotypes, produce HBV-specific cytokines despite increased PD-1, and are associated with HBsAg and HBV-DNA reduction. These cells competently support B-cell function, required for viral clearance, which may serve as potential therapeutic targets for CHB.
Identification of a Special Cell Type as a Determinant of the Kidney Tropism of SARS-CoV-2
Authors: Hongchun Lin, Xinxin Ma, Yuxiang Sun, Jun Song, Yongjie Li, Hui Peng
Journal: Journal of the American Society of Nephrology (2021)

Lin, Hongchun; Ma, Xinxin; Sun, Yuxiang; Song, Jun; Li, Yongjie; Peng, Hui Author Information
Echocardiographic Findings of Takotsubo Cardiomyopathy: A Single Center Experience
Authors: Kagiyama Nobuyuki, Okura Hiroyuki, Kawamura Ai, Higa Tomitaka, Iino Yuzuru, Tamada Tomoko, Imai Koichiro, Yamada Ryotaro, Kume Teruyoshi, Hayashida Akihiro, Neishi Yoji, Kawamoto Takahiro, Yoshida Kiyoshi
Journal: Circulation (2014)