tbuckley/cabot-search huggingface dataset:
CLEC-2-dependent platelet subendothelial accumulation by flow disturbance contributes to atherogenesis in mice
Authors: Chaojun Tang, Lei Wang, Yulan Sheng, Zhong Zheng, Zhanli Xie, Fan Wu, Tao You, Lijie Ren, Lijun Xia, Changgeng Ruan, Li Zhu
Journal: Theranostics (2021)

Rationale: Platelets play an essential role in atherosclerosis, but the underlying mechanisms remain to be addressed. This study is to investigate the role of platelets in d-flow induced vascular inflammation and the underlying mechanism. Methods: We established a disturbed blood flow (d-flow) model by partial carotid ligation (PCL) surgery using atherosclerosis-susceptible mice and wild-type mice to observe the d-flow induced platelet accumulation in the subendothelium or in the plaque by immunostaining or transmission electron microscopy. The mechanism of platelet subendothelial accumulation was further explored by specific gene knockout mice. Results: We observed presence of platelets in atherosclerotic plaques either in the atheroprone area of aortic arch or in carotid artery with d-flow using Ldlr-/- or ApoE-/- mice on high fat diet. Immunostaining showed the subendothelial accumulation of circulating platelets by d-flow in vivo. Transmission electron microscopy demonstrated the accumulation of platelets associated with monocytes in the subendothelial spaces. The subendothelial accumulation of platelet-monocyte/macrophage aggregates reached peak values at 2 days after PCL. In examining the molecules that may mediate the platelet entry, we found that deletion of platelet C-type lectin-like receptor 2 (CLEC-2) reduced the subendothelial accumulation of platelets and monocytes/macrophages by d-flow, and ameliorated plaque formation in Ldlr-/- mice on high fat diet. Supportively, CLEC-2 deficient platelets diminished their promoting effect on the migration of mouse monocyte/macrophage cell line RAW264.7. Moreover, monocyte podoplanin (PDPN), the only ligand of CLEC-2, was upregulated by d-flow, and the myeloid-specific PDPN deletion mitigated the subendothelial accumulation of platelets and monocytes/macrophages. Conclusions: Our results reveal a new CLEC-2-dependent platelet subendothelial accumulation in response to d-flow to regulate vascular inflammation.
TCT-380 Pressure-Bound Coronary Flow Reserve Correlates With Coronary Flow Reserve by Thermodilution and Detects a Significant Proportion of Fractional Flow Reserve–Negative Patients With Coronary Microvascular Dysfunction and Misdiagnosis
Authors: Edwina McNaughton, Emily Heatley, Shree Venuraju
Journal: Journal of the American College of Cardiology (2021)
Memo to COP26 leaders: abandon your hubris, politics, and pride and see the future through young people’s eyes
Authors: Kamran Abbasi
Journal: BMJ (2021)

Don't let anybody else decide your future," Barack Obama urged young people this week."Imagine a better future and help make it real."In fairness, young people aren't the problem.The future, unfortunately, is controlled by their parents and grandparents, too many of whom see the future as an only slightly less rosy version of the past.Yet the multiverse of crises we face today won't magically disappear with the click of a superhero's fingers.
Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors for Anemia in CKD
Authors: Patrick Parfrey
Journal: New England Journal of Medicine (2021)

The prevalence of anemia increases as chronic kidney disease (CKD) progresses. Ultimately, anemia occurs in most patients who undergo dialysis, as well as in many patients with CKD who do not undergo dialysis. Non–dialysis-dependent CKD (NDD-CKD) and dialysis-dependent CKD (DD-CKD) should be studied separately for three reasons. First, the hemoglobin trajectories differ in NDD-CKD and DD-CKD. Second, the hemodynamic and metabolic milieus differ. Third, the manifestation of cardiovascular disease changes from predominantly atherosclerotic events to an equal prominence of events of cardiac failure linked to nonatherosclerotic processes. In the Trial to Reduce Cardiovascular Events with Aranesp Therapy involving patients who . . .
Ciltacabtagene Autoleucel for Triple-Class Exposed Multiple Myeloma: Adjusted Comparisons of CARTITUDE-1 Patient Outcomes Versus Therapies from Real-World Clinical Practice from the LocoMMotion Prospective Study
Authors: Maria-Victoria Mateos, Katja Weisel, Thomas Martin, Jesús G. Berdeja, Andrzej Jakubowiak, A. Keith Stewart, Sundar Jagannath, Yi Lin, Joris Diels, Francesca Ghilotti, Nolen J Perualila, Jedelyn Cabrieto, Benjamin Haefliger, Nichola Erler-Yates, Clare Hague, Carolyn C. Jackson, Vadim Strulev, Tonia Nesheiwat, Lida Pacaud, Philippe Moreau, Hermann Einsele
Journal: Blood (2021)
Assessment of Nonfatal Myocardial Infarction as a Surrogate for All-Cause and Cardiovascular Mortality in Treatment or Prevention of Coronary Artery Disease
Authors: Kevin O’Fee, Elena Deych, Oriana Ciani, David L. Brown
Journal: JAMA Internal Medicine (2021)

Although nonfatal myocardial infarction (MI) is associated with an increased risk of mortality, evidence validating nonfatal MI as a surrogate end point for all-cause or cardiovascular (CV) mortality is lacking.To examine whether nonfatal MI may be a surrogate for all-cause or CV mortality in patients with or at risk for coronary artery disease.In this meta-analysis, PubMed was searched from inception until December 31, 2020, for randomized clinical trials of interventions to treat or prevent coronary artery disease reporting mortality and nonfatal MI published in 3 leading journals.Randomized clinical trials including at least 1000 patients with 24 months of follow-up.Trial-level correlations between nonfatal MI and all-cause or CV mortality were assessed for surrogacy using the coefficient of determination (R2). The criterion for surrogacy was set at 0.8. Subgroup analyses based on study subject (primary prevention, secondary prevention, mixed primary and secondary prevention, and revascularization), era of trial (before 2000, 2000-2009, and 2010 and after), and follow-up duration (2.0-3.9, 4.0-5.9, and ≥6.0 years) were performed.All-cause or CV mortality and nonfatal MI.A total of 144 articles randomizing 1 211 897 patients met the criteria for inclusion. Nonfatal MI did not meet the threshold for surrogacy for all-cause (R2 = 0.02; 95% CI, 0.00-0.08) or CV (R2 = 0.11; 95% CI, 0.02-0.27) mortality. Nonfatal MI was not a surrogate for all-cause mortality in primary (R2 = 0.01; 95% CI, 0.001-0.26), secondary (R2 = 0.03; 95% CI, 0.00-0.20), mixed primary and secondary prevention (R2 = 0.001; 95% CI, 0.00-0.08), or revascularization trials (R2 = 0.21; 95% CI, 0.002-0.50). For trials enrolling patients before 2000 (R2 = 0.22; 95% CI, 0.08-0.36), between 2000 and 2009 (R2 = 0.02; 95% CI, 0.00-0.17), and from 2010 and after (R2 = 0.01; 95% CI, 0.00-0.09), nonfatal MI was not a surrogate for all-cause mortality. Nonfatal MI was not a surrogate for all-cause mortality in randomized clinical trials with 2.0 to 3.9 (R2 = 0.004; 95% CI, 0.00-0.08), 4.0 to 5.9 (R2 = 0.06; 95% CI, 0.001-0.16), or 6.0 or more years of follow-up (R2 = 0.30; 95% CI, 0.01-0.55).The findings of this meta-analysis do not appear to establish nonfatal MI as a surrogate for all-cause or CV mortality in randomized clinical trials of interventions to treat or prevent coronary artery disease.
E3 ubiquitin ligase ring finger protein 5 protects against hepatic ischemia reperfusion injury by mediating phosphoglycerate mutase family member 5 ubiquitination
Authors: Ming‐Jie Ding, Hao‐Ran Fang, Jia‐Kai Zhang, Ji‐Hua Shi, Xiao Yu, Pei‐Hao Wen, Zhi‐Hui Wang, Sheng‐Li Cao, Yi Zhang, Xiao‐Yi Shi, Hua‐Peng Zhang, Yu‐Ting He, Bing Yan, Hong‐Wei Tang, Dan‐Feng Guo, Jie Gao, Zhen Liu, Li Zhang, Shui‐Jun Zhang, Xiao‐Jing Zhang, Wen‐Zhi Guo
Journal: Hepatology (2021)

Hepatic ischemia-reperfusion (HIR) injury, a common clinical complication of liver transplantation and resection, affects patient prognosis. Ring finger protein 5 (RNF5) is an E3 ubiquitin ligase that plays important roles in endoplasmic reticulum stress, unfolded protein reactions, and inflammatory responses; however, its role in HIR is unclear.RNF5 expression was significantly down-regulated during HIR in mice and hepatocytes. Subsequently, RNF5 knockdown and overexpression of cell lines were subjected to hypoxia-reoxygenation challenge. Results showed that RNF5 knockdown significantly increased hepatocyte inflammation and apoptosis, whereas RNF5 overexpression had the opposite effect. Furthermore, hepatocyte-specific RNF5 knockout and transgenic mice were established and subjected to HIR, and RNF5 deficiency markedly aggravated liver damage and cell apoptosis and activated hepatic inflammatory responses, whereas hepatic RNF5 transgenic mice had the opposite effect compared with RNF5 knockout mice. Mechanistically, RNF5 interacted with phosphoglycerate mutase family member 5 (PGAM5) and mediated the degradation of PGAM5 through K48-linked ubiquitination, thereby inhibiting the activation of apoptosis-regulating kinase 1 (ASK1) and its downstream c-Jun N-terminal kinase (JNK)/p38. This eventually suppresses the inflammatory response and cell apoptosis in HIR.We revealed that RNF5 protected against HIR through its interaction with PGAM5 to inhibit the activation of ASK1 and the downstream JNK/p38 signaling cascade. Our findings indicate that the RNF5-PGAM5 axis may be a promising therapeutic target for HIR.
Photocrosslinkable Col/PCL/Mg composite membrane providing spatiotemporal maintenance and positive osteogenetic effects during guided bone regeneration
Authors: Feilong Wang, Dandan Xia, Siyi Wang, Ranli Gu, Fan Yang, Xiao Zhao, Xuenan Liu, Yuan Zhu, Hao Liu, Yongxiang Xu, Yunsong Liu, Yongsheng Zhou
Journal: Bioactive Materials (2021)

Guided bone regeneration membranes have been effectively applied in oral implantology to repair bone defects. However, typical resorbable membranes composed of collagen (Col) have insufficient mechanical properties and high degradation rate, while non-resorbable membranes need secondary surgery. Herein, we designed a photocrosslinkable collagen/polycaprolactone methacryloyl/magnesium (Col/PCLMA/Mg) composite membrane that provided spatiotemporal support effect after photocrosslinking. Magnesium particles were added to the PCLMA solution and Col/PCLMA and Col/PCLMA/Mg membranes were developed; Col membranes and PCL membranes were used as controls. After photocrosslinking, an interpenetrating polymer network was observed by scanning electron microscopy (SEM) in Col/PCL and Col/PCL/Mg membranes. The elastic modulus, swelling behavior, cytotoxicity, cell attachment, and cell proliferation of the membranes were evaluated. Degradation behavior in vivo and in vitro was monitored according to mass change and by SEM. The membranes were implanted into calvarial bone defects of rats for 8 weeks. The Col/PCL and Col/PCL/Mg membranes displayed much higher elastic modulus (p < 0.05), and a lower swelling rate (p < 0.05), than Col membranes, and there were no differences in cell biocompatibility among groups (p > 0.05). The Col/PCL and Col/PCL/Mg membranes had lower degradation rates than the Col membranes, both in vivo and in vitro (p < 0.05). The Col/PCL/Mg groups showed enhanced osteogenic capability compared with the Col groups at week 8 (p < 0.05). The Col/PCL/Mg composite membrane represents a new strategy to display space maintenance and enhance osteogenic potential, which meets clinical needs.
TCT-459 Impact of Type of Mitral Regurgitation on Outcomes of Mitral Valve Surgery After Edge-to-Edge Transcatheter Mitral Repair: Results From the CUTTING-EDGE Registry
Authors: Syed Zaid, Thomas Modine, Paolo Denti, Vinayak Bapat, Tsuyoshi Kaneko, Gilbert Tang
Journal: Journal of the American College of Cardiology (2021)
Endoscopic line-attached clipping closure with laparoscopic suturing for duodenal defects involving the medial wall post-endoscopic submucosal dissection
Authors: Takaya Shimura, Hiroyasu Iwasaki, Tomotaka Okubo, Naomi Sugimura, Yusuke Okuda, Takahito Katano, Hiromi Kataoka
Journal: Endoscopy (2021)

Duodenal endoscopic submucosal dissection (ESD) is difficult to perform owing to a high incidence of complications, including intra/post-ESD perforation and bleeding. A complete closure of the post-ESD mucosal defect can prevent post-ESD perforation, but the success of a complete endoscopic closure depends on the size and location of the defect [1]. Although laparoscopic seromuscular suturing is the most reliable closing method [2], it cannot be used for duodenal lesions over the medial wall.
High-quality reference genome sequences of two coconut cultivars provide insights into evolution of monocot chromosomes and differentiation of fiber content and plant height
Authors: Shouchuang Wang, Yong Xiao, Zhi-Wei Zhou, Jiaqing Yuan, Hao Guo, Zhuang Yang, Jun Yang, Pengchuan Sun, Lisong Sun, Yuan Deng, Wen-Zhao Xie, Jia-Ming Song, Muhammad Tahir ul Qamar, Wei Xia, Rui Liu, Shufang Gong, Yong Wang, Fuyou Wang, Xianqing Liu, Alisdair R. Fernie, Xiyin Wang, Haikuo Fan, Ling-Ling Chen, Jie Luo
Journal: Genome biology (2021)

Abstract Background Coconut is an important tropical oil and fruit crop whose evolutionary position renders it a fantastic species for the investigation of the evolution of monocot chromosomes and the subsequent differentiation of ancient plants. Results Here, we report the assembly and annotation of reference-grade genomes of Cn. tall and Cn. dwarf , whose genome sizes are 2.40 Gb and 2.39 Gb, respectively. The comparative analysis reveals that the two coconut subspecies diverge about 2–8 Mya while the conserved Arecaceae-specific whole-genome duplication (ω WGD) occurs approximately 47–53 Mya. It additionally allows us to reconstruct the ancestral karyotypes of the ten ancient monocot chromosomes and the evolutionary trajectories of the 16 modern coconut chromosomes. Fiber synthesis genes in Cn. tall , related to lignin and cellulose synthesis, are found at a higher copy number and expression level than dwarf coconuts. Integrated multi-omics analysis reveals that the difference in coconut plant height is the result of altered gibberellin metabolism, with both the GA20ox copy number and a single-nucleotide change in the promoter together leading to the difference in plant height between Cn. tall and Cn. dwarf . Conclusion We provide high-quality coconut genomes and reveal the genetic basis of trait differences between two coconuts through multi-omics analysis. We also reveal that the selection of plant height has been targeted for the same gene for millions of years, not only in natural selection of ancient plant as illustrated in coconut, but also for artificial selection in cultivated crops such as rice and maize.
Ribonuclease recruitment using a small molecule reduced c9ALS/FTD r(G <sub>4</sub> C <sub>2</sub> ) repeat expansion in vitro and in vivo ALS models
Authors: Jessica A. Bush, Haruo Aikawa, Rita Fuerst, Yue Li, Andrei Ursu, Samantha M. Meyer, Raphael I. Benhamou, Jonathan L. Chen, Tanya Khan, Sarah Wagner-Griffin, Montina J. Van Meter, Yuquan Tong, Hailey Olafson, Kendra K. McKee, Jessica L. Childs-Disney, Tania F. Gendron, Yongjie Zhang, Alyssa N. Coyne, Eric T. Wang, Ilyas Yildirim, Kye Won Wang, Leonard Petrucelli, Jeffrey D. Rothstein, Matthew D. Disney
Journal: Science Translational Medicine (2021)

Small-molecule recruitment of an endogenous nuclease rescues pathologies associated with c9ALS/FTD in vivo by targeting an RNA repeat expansion.
Sustainability of a Surgical Quality Improvement Program at Hospitals in Ethiopia
Authors: Nichole Starr, Maia R. Nofal, Natnael Gebeyehu, Jared A. Forrester, Miliard Derbew, Thomas G. Weiser, Tihitena Negussie Mammo
Journal: JAMA Surgery (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
Inhaled gene therapy of preclinical muco-obstructive lung diseases by nanoparticles capable of breaching the airway mucus barrier
Authors: Namho Kim, Gijung Kwak, Jason Rodriguez, Alessandra Livraghi-Butrico, Xinyuan Zuo, Valentina Simon, Eric Han, Siddharth Kaup Shenoy, Nikhil Pandey, Marina Mazur, Susan E Birket, Anthony Kim, Steven M Rowe, Richard Boucher, Justin Hanes, Jung Soo Suk
Journal: Thorax (2021)

Introduction Inhaled gene therapy of muco-obstructive lung diseases requires a strategy to achieve therapeutically relevant gene transfer to airway epithelium covered by particularly dehydrated and condensed mucus gel layer. Here, we introduce a synthetic DNA-loaded mucus-penetrating particle (DNA-MPP) capable of providing safe, widespread and robust transgene expression in in vivo and in vitro models of muco-obstructive lung diseases. Methods We investigated the ability of DNA-MPP to mediate reporter and/or therapeutic transgene expression in lung airways of a transgenic mouse model of muco-obstructive lung diseases (ie, Scnn1b -Tg) and in air–liquid interface cultures of primary human bronchial epithelial cells harvested from an individual with cystic fibrosis. A plasmid designed to silence epithelial sodium channel (ENaC) hyperactivity, which causes airway surface dehydration and mucus stasis, was intratracheally administered via DNA-MPP to evaluate therapeutic effects in vivo with or without pretreatment with hypertonic saline, a clinically used mucus-rehydrating agent. Results DNA-MPP exhibited marked greater reporter transgene expression compared with a mucus-impermeable formulation in in vivo and in vitro models of muco-obstructive lung diseases. DNA-MPP carrying ENaC-silencing plasmids provided efficient downregulation of ENaC and reduction of mucus burden in the lungs of Scnn1b -Tg mice, and synergistic impacts on both gene transfer efficacy and therapeutic effects were achieved when DNA-MPP was adjuvanted with hypertonic saline. Discussion DNA-MPP constitutes one of the rare gene delivery systems providing therapeutically meaningful gene transfer efficacy in highly relevant in vivo and in vitro models of muco-obstructive lung diseases due to its unique ability to efficiently penetrate airway mucus.
TCT-34 Hemoglobin Drop in the Absence of Overt Bleeding After Percutaneous Coronary Intervention is Associated With In-Hospital Mortality
Authors: Ilias Nikolakopoulos, Evangelia Vemmou, Judit Karacsonyi, Santiago Garcia, Timothy Henry, Mario Goessl, Scott Sharkey, M. Nicholas Burke, Paul Sorajja, Jay Traverse, Yale Wang, Michael Mooney, Anil Poulose, Ivan Chavez, Bahadir Simsek, Spyridon Kostantinis, Bavana Rangan, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2021)
Nemolizumab plus topical agents in patients with atopic dermatitis (AD) and moderate‐to‐severe pruritus provide improvement in pruritus and signs of AD for up to 68 weeks: results from two phase III, long‐term studies*
Authors: K. Kabashima, T. Matsumura, H. Komazaki, M. Kawashima
Journal: British Journal of Dermatology (2021)

Interleukin (IL)-31 affects the inflammatory response, is involved in epidermal barrier disruption in atopic dermatitis (AD) and plays a key role in pruritus. Nemolizumab, a humanized monoclonal antibody against IL-31 receptor A, reduced pruritus in patients with AD after a 16-week administration period.To examine the long-term effectiveness and safety of nemolizumab in patients aged ≥ 13 years with AD and inadequately controlled moderate-to-severe pruritus.In two long-term phase III studies, nemolizumab 60 mg every 4 weeks (Q4W) was administered subcutaneously, concomitantly with topical treatments. Study-JP01 patients received double-blind nemolizumab or placebo for 16 weeks, and then entered a 52-week extension period in which all patients received nemolizumab (nemolizumab/nemolizumab and placebo/nemolizumab groups). Study-JP02 patients received nemolizumab for 52 weeks. Both studies included an 8-week follow-up period.Study-JP01 nemolizumab/nemolizumab and placebo/nemolizumab, and Study-JP02 nemolizumab groups comprised 143, 72 and 88 patients, respectively. In the nemolizumab/nemolizumab group, there were clinically meaningful improvements from the start of treatment to week 68 in the pruritus visual analogue scale (66% decrease) and Eczema Area and Severity Index (78% decrease). Quality of life (QoL) indicators improved after the first nemolizumab dose; improvements were maintained during the follow-up period. The long-term safety profile was consistent with previous studies, with no unexpected late-onset adverse events.Nemolizumab 60 mg Q4W with concomitant topical treatments in patients with AD and inadequately controlled moderate-to-severe pruritus produced a continuous improvement in pruritus, signs of AD, and QoL for up to 68 weeks, with a favourable safety profile.
TCT-278 Five-Year Outcomes After Revascularization With the Biodegradable Polymer Ultrathin Strut Sirolimus-Eluting Orsiro Stent or the Biodegradable Polymer Biolimus-Eluting Nobori Stent in Patients With and Without Acute Coronary Syndromes: From the SORT OUT VII Trial
Authors: Manijeh Noori, Evald Christiansen, Bent Raungaard, Anders Junker, Martin Kirk Christensen, Johnny Kahlert, Lars Jakobsen, Phillip Freeman, Kirstine Hansen, Christian Terkelsen, Julia Ellert, Steen Dalby Kristensen, Karsten Veien, Michael Maeng, Henrik Hansen, Lisette Okkels Jensen
Journal: Journal of the American College of Cardiology (2021)
TCT-490 Early Strut Coverage of a Novel Polymer-Free Ultra-Thin-Strut Sirolimus-Eluting Stent Compared With a Biodegradable-Polymer Sirolimus-Eluting Stent, an Intrapatient Randomized Study With OCT: The FRIENDLY-OCT TRIAL
Authors: Imanol Otaegui, Bruno Garcia-Del-Blanco, Ricardo Palma Carbajal, Gerard Marti, Bernat Serra, Jose Luis Molina, Neus Bellera Gotarda, Yassin Belahnech
Journal: Journal of the American College of Cardiology (2021)
Immune cell-mediated features of non-alcoholic steatohepatitis
Authors: Thierry Huby, Emmanuel L. Gautier
Journal: Nature reviews. Immunology (2021)

Non-alcoholic fatty liver disease (NAFLD) includes a range of hepatic manifestations, starting with liver steatosis and potentially evolving towards non-alcoholic steatohepatitis (NASH), cirrhosis or even hepatocellular carcinoma. NAFLD is a major health burden, and its incidence is increasing worldwide. Although it is primarily a disease of disturbed metabolism, NAFLD involves several immune cell-mediated inflammatory processes, particularly when reaching the stage of NASH, at which point inflammation becomes integral to the progression of the disease. The hepatic immune cell landscape is diverse at steady state and it further evolves during NASH with direct consequences for disease severity. In this Review, we discuss current concepts related to the role of immune cells in the onset and progression of NASH. A better understanding of the mechanisms by which immune cells contribute to NASH pathogenesis should aid the design of innovative drugs to target NASH, for which current therapeutic options are limited. Non-alcoholic steatohepatitis (NASH) is a serious chronic liver disorder of increasing prevalence worldwide. Metabolic by nature, the disease also mobilizes the immune system. Here, Huby and Gautier discuss current knowledge regarding how diverse immune cell subsets affect NASH onset and progression.
Correction: Aspirin Suppresses the Growth and Metastasis of Osteosarcoma through the NF-κB Pathway
Authors: Dan Liao, Li Zhong, Tingmei Duan, Ru-Hua Zhang, Xin Wang, Gang Wang, Kaishun Hu, Xiaobin Lv, Tiebang Kang
Journal: Clinical Cancer Research (2021)

In the original version of this article (1), there were three errors in Fig. 6: in Fig. 6A, the GADPH blots were inadvertently duplicated from Fig. 5D; in Fig. 6B, the image for Aspirin/NC was a duplicate of DMSO/sh#2; and in Fig. 6B, the Aspirin/vector image was a duplicate of Aspirin/sh#2. These errors have been corrected in the latest online HTML and PDF versions of the article. The authors regret these errors.