tbuckley/cabot-search huggingface dataset:
Partial purification of human renin.
Authors: KMurakami, TInagami, EHaas
Journal: Circulation Research (1977)

An affinity gel for the purification of renin was prepared by coupling pepstatin to aminohexylagarose gel. Partially purified human renin (Haas et al., Arch. Biochem. Biophys., 110, 534-543, 1965) was purified further by affinity chromatography on the pepstatin-aminohexyl-agarose gel, gel filtration on a Sephadex G-75 column, and ion exchange chromatography on a DEAE-cellulose column. Separation from a protease permitted further purification without progressive loss of activity. Three peaks of enzymatically active renin were obtained after the DEAE-cellulose chromatography, with specific activities ranging from 206 to 166 and 85 Goldblatt units/mg protein, respectively. The specific activity of 206 GU units/mg represents a 103,000-fold purification compared to the renin present in the first crude extract.
AB0018 TRANSCRIPTOMIC CHARACTERIZATION OF SINGLE PATHOGENIC MEMORY B CELLS IN RHEUMATOID ARTHRITIS
Authors: Deimante Simaite, Linda Slot, Veeranagouda Yaligara, Virginia Savova, Claus Reimertz, Carsten Struebing, Axel Dietrich, Emanuele de Rinaldis, Michel Didier, Matthias Herrmann, Frank Nestle, Hans Ulrich Scherer, Rene Toes
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Autoantigen-specific B lymphocytes are crucial players in the development of rheumatoid arthritis (RA). Despite the fact that ACPA+ autoreactive memory B cells have been observed in the majority of RA patients for a long time, their properties still remain enigmatic. <h3>Objectives</h3> In this study, we aimed to reveal transcriptomic nature of single pathogenic memory B cells from RA patients. <h3>Methods</h3> Single-cell full-length RNAseq data was generated from ACPA+ and control memory B cells from 7 human donors with established rheumatoid arthritis and subjected to transcriptome analyses as well as B cell receptor (BCR) assembly. <h3>Results</h3> Both transcriptome and BCR data was successfully generated from the majority of the sequenced cells. The success rate depended on chosen sequencing parameters as well as on a BCR assembling algorithm that was used. We observed expression of genes defining memory B cell population in our data as well as pathways crucial for their function. <h3>Conclusion</h3> Taken together, gene expression and BCR sequence data obtained from the same single cell can give novel insights into the biology and role of B cells in the development of the disease. <h3>Acknowledgement</h3> This work has received support from the EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking RTCure grant n° 777357. <h3>Disclosure of Interests</h3> Deimante Simaite Employee of: Sanofi, Linda Slot Grant/research support from: Sanofi, Veeranagouda Yaligara Employee of: Sanofi, Virginia Savova Employee of: Sanofi, Claus Reimertz Employee of: Sanofi, Carsten Struebing Employee of: Sanofi, Axel Dietrich Employee of: Sanofi, Emanuele de Rinaldis Employee of: Sanofi, Michel Didier Employee of: Sanofi, Matthias Herrmann Employee of: Sanofi, Frank Nestle Employee of: Sanofi, Hans Ulrich Scherer Grant/research support from: Sanofi, BMS, Rene Toes Grant/research support from: Sanofi
Carotid sinus baroreceptor reflex control and epinephrine. Influence on capacitive and resistive properties of the total pulmonary vascular bed of the dog.
Authors: A AShoukas
Journal: Circulation Research (1982)

To quantify the importance of the carotid sinus baroreceptor reflex and the interaction with epinephrine infusion on total pulmonary vascular capacity and resistance, I have simultaneously measured total pulmonary vascular compliance, changes in pulmonary blood volumes, and changes in resistances in seven sodium pentobarbital-anesthetized dogs. A preparation was used that bypasses the right and left hearts allowing for the simultaneous measurement of the pulmonary as well as the systemic vascular bed parameters. At intrasinus pressures of 50, 125, and 200 mm Hg, without epinephrine infusion, the pulmonary vascular resistance was 0.134, 0.121, and 0.109 mm Hg/(ml per min per kg) and the systemic vascular resistance was 1.21, 0.87, and 0.63 mm Hg/(ml per min per kg). Epinephrine infusion of 1 microgram/min per kg at each intrasinus pressure caused the resistances of both vascular beds to increase. Pulmonary vascular resistance increased to 0.157 mm Hg/(ml per min per kg) and showed no further changes with c...
Unmanipulated haploidentical hematopoietic stem cell transplantation is an excellent option for children and young adult relapsed/refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia after CAR-T-cell therapy
Authors: Guan-Hua Hu, Xiang-Yu Zhao, Ying-Xi Zuo, Ying-Jun Chang, Pan Suo, Jun Wu, Yue-Ping Jia, Ai-Dong Lu, Ying-Chun Li, Yu Wang, Shun-Chang Jiao, Long-Ji Zhang, Jun Kong, Chen-Hua Yan, Lan-Ping Xu, Xiao-Hui Zhang, Kai-Yan Liu, Yi-Fei Cheng, Yu Wang, Le-Ping Zhang, Xiao-Jun Huang
Journal: Leukemia (2021)
Effects of altered site of electrical activation on myocardial performance during inotropic stimulation.
Authors: G RHeyndrickx, J PVilaine, D RKnight, S FVatner
Journal: Circulation (1985)

The effects of altering the site of electrical activation on responses to isoproterenol (ISO) and treadmill exercise were examined in mongrel dogs instrumented for long-term measurement of left ventricular pressure, left ventricular dP/dt, coronary blood flow, cardiac output, left ventricular diameters, and mean arterial pressure and O2 content in the coronary sinus and aorta. During spontaneous rhythm, 0.2 micrograms/kg/min ISO increased heart rate by 90 +/- 7 beats/min, left ventricular dP/dt by 2479 +/- 301 mm Hg/sec, cardiac output by 3.5 +/- 0.9 liters/min, coronary blood flow by 30.4 +/- 3.9 ml/min, and myocardial oxygen consumption (MVO2) by 3.91 +/- 0.84 ml/min. During right atrial pacing at 193 +/- 7 beats/min, the effects of ISO were not different from the effects during spontaneous rhythm, with the exception of a lesser increase in coronary blood flow and lesser reductions in coronary resistance and left ventricular end-diastolic diameter and pressure. During right ventricular pacing at an iden...
Potential role of indolelactate and butyrate in multiple sclerosis revealed by integrated microbiome-metabolome analysis
Authors: Izhak Levi, Michael Gurevich, Gal Perlman, David Magalashvili, Shay Menascu, Noam Bar, Anastasia Godneva, Liron Zahavi, Danyel Chermon, Noa Kosower, Bat Chen Wolf, Gal Malka, Maya Lotan-Pompan, Adina Weinberger, Erez Yirmiya, Daphna Rothschild, Sigal Leviatan, Avishag Tsur, Maria Didkin, Sapir Dreyer, Hen Eizikovitz, Yamit Titngi, Sue Mayost, Polina Sonis, Mark Dolev, Yael Stern, Anat Achiron, Eran Segal
Journal: Cell Reports Medicine (2021)

Multiple sclerosis (MS) is an immune-mediated disease whose precise etiology is unknown. Several studies found alterations in the microbiome of individuals with MS, but the mechanism by which it may affect MS is poorly understood. Here we analyze the microbiome of 129 individuals with MS and find that they harbor distinct microbial patterns compared with controls. To study the functional consequences of these differences, we measure levels of 1,251 serum metabolites in a subgroup of subjects and unravel a distinct metabolite signature that separates affected individuals from controls nearly perfectly (AUC = 0.97). Individuals with MS are found to be depleted in butyrate-producing bacteria and in bacteria that produce indolelactate, an intermediate in generation of the potent neuroprotective antioxidant indolepropionate, which we found to be lower in their serum. We identify microbial and metabolite candidates that may contribute to MS and should be explored further for their causal role and therapeutic potential.
Mechanistic understanding of the combined immunodeficiency in complete human CARD11 deficiency
Authors: Henry Y. Lu, Mehul Sharma, Ashish A. Sharma, Atilano Lacson, Ashley Szpurko, Joanne Luider, Poonam Dharmani-Khan, Afshin Shameli, Peter A. Bell, Gregory M.T. Guilcher, Victor A. Lewis, Marta Rojas Vasquez, Sunil Desai, Lyle McGonigle, Luis Murguia-Favela, Nicola A.M. Wright, Consolato Sergi, Eytan Wine, Christopher M. Overall, Sneha Suresh, Stuart E. Turvey
Journal: Journal of Allergy and Clinical Immunology (2021)
Oral Antiplatelet Therapy After Acute Coronary Syndrome
Authors: Hassan Kamran, Hani Jneid, Waleed T. Kayani, Salim S. Virani, Glenn N. Levine, Vijay Nambi, Umair Khalid
Journal: JAMA (2021)

<h3>Importance</h3> Acute coronary syndrome (ACS) is a major cause of morbidity and mortality in the United States with an annual incidence of approximately 1 million. Dual antiplatelet therapy (DAPT), consisting of aspirin and a P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel) reduces cardiovascular event rates after ACS. <h3>Observations</h3> In 2016, the updated guidelines from the American College of Cardiology/American Heart Association (ACC/AHA) recommended aspirin plus a P2Y12 inhibitor for at least 12 months for patients with ACS. Since these recommendations were published, new randomized clinical trials have studied different regimens and durations of antiplatelet therapy. Recommendations vary according to the risk of bleeding. If bleeding risk is low, prolonged DAPT may be considered, although the optimal duration of prolonged DAPT beyond 1 year is not well established. If bleeding risk is high, shorter duration (ie, 3-6 months) of DAPT may be reasonable. A high risk of bleeding traditionally is defined as a 1-year risk of serious bleeding (either fatal or associated with a ≥3-g/dL drop in hemoglobin) of at least 4% or a risk of an intracranial hemorrhage of at least 1%. Patients at higher risk are 65 years old or older; have low body weight (BMI &lt;18.5), diabetes, or prior bleeding; or take oral anticoagulants. The newest P2Y12 inhibitors, prasugrel and ticagrelor, are more potent, with high on-treatment residual platelet reactivity of about 3% vs 30% to 40% with clopidogrel and act within 30 minutes compared with 2 hours for clopidogrel. Clinicians should avoid prescribing prasugrel to patients with a history of stroke or transient ischemic attack because of an increased risk of cerebrovascular events (6.5% vs 1.2% with clopidogrel,<i>P</i> = .002) and should avoid prescribing it to patients older than 75 years or who weigh less than 60 kg. The ISAR-REACT-5 trial found that prasugrel reduced rates of death, myocardial infarction, or stroke at 1 year compared with ticagrelor among patients with ACS undergoing percutaneous coronary intervention (9.3% vs 6.9%,<i>P</i> = .006) with no significant difference in bleeding. Recent trials suggested that discontinuing aspirin rather than the P2Y12 inhibitor may be associated with better outcomes. <h3>Conclusions and Relevance</h3> Dual antiplatelet therapy reduces rates of cardiovascular events in patients with acute coronary syndrome. Specific combinations and duration of dual antiplatelet therapy should be based on patient characteristics—risk of bleeding myocardial ischemia.
Molecular Diagnosis of Hemophilia B Leyden in Japanese Brothers Reveals Spontaneous Amelioration in Early Childhood with c. -35 G>A Onecut Binding Site Mutation
Authors: Akihiro Tamura, Daiichiro Hasegawa, Sayaka Nakamura, Takahiro Fujiwara, Teppei Tahara, Nobuyuki Yamamoto, Atsuro Saito, Aiko Kozaki, Kenji Kishimoto, Toshiaki Ishida, Keiko Shinozawa, Kagehiro Amano, Katsuyuki Fukutake, Yoshiyuki Kosaka
Journal: Blood (2017)
Clinical Validation of a 3-Dimensional Ultrafast Cardiac Magnetic Resonance Protocol Including Single Breath-Hold 3-Dimensional Sequences
Authors: Sandra Gómez-Talavera, Rodrigo Fernandez-Jimenez, Valentín Fuster, Nils D. Nothnagel, Marc Kouwenhoven, Matthew Clemence, Inés García-Lunar, María C. Gómez-Rubín, Felipe Navarro, Braulio Pérez-Asenjo, Leticia Fernández-Friera, María J. Calero, Miguel Orejas, José A. Cabrera, Manuel Desco, Gonzalo Pizarro, Borja Ibáñez, Javier Sánchez-González
Journal: JACC. Cardiovascular imaging (2021)

This study sought to clinically validate a novel 3-dimensional (3D) ultrafast cardiac magnetic resonance (CMR) protocol including cine (anatomy and function) and late gadolinium enhancement (LGE), each in a single breath-hold.CMR is the reference tool for cardiac imaging but is time-consuming.A protocol comprising isotropic 3D cine (Enhanced sensitivity encoding [SENSE] by Static Outer volume Subtraction [ESSOS]) and isotropic 3D LGE sequences was compared with a standard cine+LGE protocol in a prospective study of 107 patients (age 58 ± 11 years; 24% female). Left ventricular (LV) mass, volumes, and LV and right ventricular (RV) ejection fraction (LVEF, RVEF) were assessed by 3D ESSOS and 2D cine CMR. LGE (% LV) was assessed using 3D and 2D sequences.Three-dimensional and LGE acquisitions lasted 24 and 22 s, respectively. Three-dimensional and LGE images were of good quality and allowed quantification in all cases. Mean LVEF by 3D and 2D CMR were 51 ± 12% and 52 ± 12%, respectively, with excellent intermethod agreement (intraclass correlation coefficient [ICC]: 0.96; 95% confidence interval [CI]: 0.94 to 0.97) and insignificant bias. Mean RVEF 3D and 2D CMR were 60.4 ± 5.4% and 59.7 ± 5.2%, respectively, with acceptable intermethod agreement (ICC: 0.73; 95% CI: 0.63 to 0.81) and insignificant bias. Both 2D and 3D LGE showed excellent agreement, and intraobserver and interobserver agreement were excellent for 3D LGE.ESSOS single breath-hold 3D CMR allows accurate assessment of heart anatomy and function. Combining ESSOS with 3D LGE allows complete cardiac examination in <1 min of acquisition time. This protocol expands the indication for CMR, reduces costs, and increases patient comfort.
Sex dependent glial-specific changes in the chromatin accessibility landscape in late-onset Alzheimer’s disease brains
Authors: Julio Barrera, Lingyun Song, Julia E. Gamache, Melanie E. Garrett, Alexias Safi, Young Yun, Ivana Premasinghe, Daniel Sprague, Danielle Chipman, Jeffrey Li, Hélène Fradin, Karen Soldano, Raluca Gordân, Allison E. Ashley-Koch, Gregory E. Crawford, Ornit Chiba-Falek
Journal: Molecular Neurodegeneration (2021)

Abstract Background In the post-GWAS era, there is an unmet need to decode the underpinning genetic etiologies of late-onset Alzheimer’s disease (LOAD) and translate the associations to causation. Methods We conducted ATAC-seq profiling using NeuN sorted-nuclei from 40 frozen brain tissues to determine LOAD-specific changes in chromatin accessibility landscape in a cell-type specific manner. Results We identified 211 LOAD-specific differential chromatin accessibility sites in neuronal-nuclei, four of which overlapped with LOAD-GWAS regions (±100 kb of SNP). While the non-neuronal nuclei did not show LOAD-specific differences, stratification by sex identified 842 LOAD-specific chromatin accessibility sites in females. Seven of these sex-dependent sites in the non-neuronal samples overlapped LOAD-GWAS regions including APOE . LOAD loci were functionally validated using single-nuclei RNA-seq datasets. Conclusions Using brain sorted-nuclei enabled the identification of sex-dependent cell type-specific LOAD alterations in chromatin structure. These findings enhance the interpretation of LOAD-GWAS discoveries, provide potential pathomechanisms, and suggest novel LOAD-loci. Graphical Abstract
Antioxidant Activity and Toxicity Study of Cerium Oxide Nanoparticles Stabilized with Innovative Functional Copolymers
Authors: Geoffroy Goujon, Victor Baldim, Caroline Roques, Nicolas Bia, Johanne Seguin, Bruno Palmier, Alain Graillot, Cédric Loubat, Nathalie Mignet, Isabelle Margaill, Jean‐François Berret, Virginie Beray‐Berthat
Journal: Advanced Healthcare Materials (2021)

Oxidative stress, which is one of the main harmful mechanisms of pathologies including is-chemic stroke, contributes to both neurons and endothelial cell damages, leading to vascular lesions. Although many antioxidants have been tested in preclinical studies, no treatment is currently available for stroke patients. Since cerium oxide nanoparticles (CNPs) exhibit remarkable antioxidant capacities, our objective is to develop an innovative coating to enhance CNPs biocompatibility without disrupting their antioxidant capacities or enhance their toxicity. This study reports the synthesis and characterization of functional polymers and their impact on the enzyme-like catalytic activity of CNPs. To study the toxicity and the antioxidant properties of CNPs for stroke and particularly endothelial damages, in vitro studies are conducted on a cerebral endothelial cell line (bEnd.3). Despite their internalization in bEnd.3 cells, coated CNPs are devoid of cytotoxicity. Microscopy studies report an intracellular localization of CNPs, more precisely in endosomes. All CNPs reduces glutamate-induced intracellular production of ROS in endothelial cells but one CNP significantly reduces both the production of mitochondrial super-oxide anion and DNA oxidation. In vivo studies report a lack of toxicity in mice. This study there-fore describes and identifies biocompatible CNPs with interesting antioxidant properties for ischemic stroke and related pathologies.
Individualized plasticity autograft mimic with efficient bioactivity inducing osteogenesis
Authors: Yan Wei, Guixin Zhu, Zifan Zhao, Chengcheng Yin, Qin Zhao, Hudi Xu, Jinyang Wang, Jinglun Zhang, Xiaoxin Zhang, Yufeng Zhang, Haibin Xia
Journal: International Journal of Oral Science (2021)

Abstract Mineralized tissue regeneration is an important and challenging part of the field of tissue engineering and regeneration. At present, autograft harvest procedures may cause secondary trauma to patients, while bone scaffold materials lack osteogenic activity, resulting in a limited application. Loaded with osteogenic induction growth factor can improve the osteoinductive performance of bone graft, but the explosive release of growth factor may also cause side effects. In this study, we innovatively used platelet-rich fibrin (PRF)-modified bone scaffolds (Bio-Oss ® ) to replace autograft, and used cytokine (BMP-2) to enhance osteogenesis. Encouragingly, this mixture, which we named “Autograft Mimic (AGM)”, has multiple functions and advantages. (1) The fiber network provided by PRF binds the entire bone scaffold together, thereby shaping the bone grafts and maintaining the space of the defect area. (2) The sustained release of BMP-2 from bone graft promoted bone regeneration continuously. (3) AGM recruited bone marrow mesenchymal stem cells (BMSCs) and promote their proliferation, migration, and osteogenic differentiation. Thus, AGM developed in this study can improve osteogenesis, and provide new guidance for the development of clinical bone grafts.
Evaluation and analysis of incidence and risk factors of lower extremity venous thrombosis after urologic surgeries: A prospective two-center cohort study using LASSO-logistic regression
Authors: Guyu Tang, Lin Qi, Zepeng Sun, Jing Liu, Zhengtong Lv, Lingxiao Chen, Bin Huang, Shuai Zhu, Yao Liu, Yuan Li
Journal: International Journal of Surgery (2021)
Female mice lacking ERβ display excitatory/inhibitory synaptic imbalance to drive the pathogenesis of temporal lobe epilepsy
Authors: Zhongke Wang, Ruxin Xie, Xiaolin Yang, Huachun Yin, Xin Li, Tianyao Liu, Yuanyuan Ma, Junwei Gao, Zhenle Zang, Ruotong Ruan, Yang Li, Kaixuan Huang, Qingbo Chen, Kaifeng Shen, Shengqing Lv, Chunqing Zhang, Hui Yang, Maragret Warner, Jan-Ake Gustafsson, Shiyong Liu, Xiaotang Fan
Journal: Theranostics (2021)

Epilepsy is a highly prevalent and drug-refractory neurological disorder characterized by spontaneous recurrent seizures. Estrogen is identified to be proconvulsant and lowers the seizure threshold of female epilepsy. Estrogen receptor β (ERβ) has been proposed to mediate neuroprotection in epilepsy, although the underlying mechanism remains unknown.
From taxonomy to metabolic output: what factors define gut microbiome health?
Authors: Tomasz Wilmanski, Noa Rappaport, Christian Diener, Sean M. Gibbons, Nathan D. Price
Journal: Gut Microbes (2021)

Many studies link the composition of the human gut microbiome to aberrant health states. However, our understanding of what constitutes a 'healthy' gut ecosystem, and how to effectively monitor and maintain it, are only now emerging. Here, we review current approaches to defining and monitoring gut microbiome health, and outline directions for developing targeted ecological therapeutics. We emphasize the importance of identifying which ecological features of the gut microbiome are most resonant with host molecular phenotypes, and highlight certain gut microbial metabolites as potential biomarkers of gut microbiome health. We further discuss how multi-omic measurements of host phenotypes, dietary information, and gut microbiome profiles can be integrated into increasingly sophisticated host-microbiome mechanistic models that can be leveraged to design personalized interventions. Overall, we summarize current progress on defining microbiome health and highlight a number of paths forward for engineering the ecology of the gut to promote wellness.
Endoscopic ultrasound-guided gastroenterostomy using an oroenteric catheter-assisted technique: a retrospective analysis
Authors: Nam Q. Nguyen, Christopher M. Hamerski, Andrew Nett, Rabindra R. Watson, Morgan Rigopoulos, Kenneth F. Binmoeller
Journal: Endoscopy (2021)

BACKGROUND : This study evaluated an oroenteric catheter (OEC)-assisted technique to distend the enteric loop for endoscopic ultrasound-guided gastroenterostomy (EUS-GE) in patients with gastric outlet obstruction (GOO). METHODS : Patient outcomes were reviewed. Proximal enteric loops were filled with water via an OEC (7 Fr or 8 Fr), providing a target for EUS-GE using a lumen-apposing metal stent (15-mm caliber). Clinical success was defined as toleration of a non-liquid diet by Day 3. RESULTS : 42 patients (mean age 73.1 [SEM 2.8] years; 23 male) underwent EUS-GE for malignant (n = 37) and benign (n = 5) duodenal strictures. EUS-GE creation was successful in 41/42 (98 %), with mean procedure time of 36 (SEM 3) minutes and no serious complications. Clinical success was achieved in 39/42 (93 %) at 5.7 (SEM 2.6) months' follow-up. Of 14 patients who died, 13 (93 %) maintained oral intake until death. EUS-GE provided good symptom relief in all 28 surviving patients until follow-up. CONCLUSIONS : OEC-assisted EUS-GE provided satisfactory relief of GOO symptoms, with high technical success (98 %) and no serious complications.