tbuckley/cabot-search huggingface dataset:
Abstract 18291: Vascular Smooth Muscle Cell Stiffness as a Novel Mechanism for the Increased Aortic Stiffness in Aging and Hypertension, Which is Augmented in Aging Hypertensive Animals
Authors: Nancy L Sehgel, Yi Zhu, Zhe Sun, William C Hunter, Jerome P Trzeciakowski, Dorothy E Vatner, Gerald A Meininger, Stephen F Vatner
Journal: Circulation (2013)

It is generally recognized that increased aortic stiffness occurs in hypertension and aging. However, less is known about their combined influence on aortic stiffness. Furthermore, most prior studies have attributed increased aortic stiffness to changes in the extracellular matrix, whereas the hypothesis of this investigation is that a significant component of vascular stiffness resides at the level of the vascular smooth muscle cells (VSMCs), and that the contribution of this mechanism would be enhanced when aging is superimposed on hypertension. Testing of this hypothesis was made possible by examining VSMC the mechanical properties of isolated VSMCs using atomic force microscopy (AFM). We examined aortic stiffness in young (16 wks) and old (64 wks) spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) wild-type controls and tested the hypothesis that the additional increase in aortic stiffness with combined aging and hypertension is mediated, in part, at the level of VSMCs. Systolic aortic pressure, measured by Millar micromanometer catheter, was significantly increased in the old compared to young SHR (191 ± 8 mmHg versus 148 ± 5 mmHg, p&lt;0.01), but not in WKY (old, 101 ± 10 mmHg versus young, 120 ± 8 mmHg). Excised aortic ring segments were subjected to physiological levels of mechanical stretch ex vivo, and the wall stress in these ring segments was greater in older SHR than WKY (p&lt;0.05). VSMCs were isolated from the thoracic aorta, and the stiffness of individual VSMCs was measured by an AFM nano-indentation technique. Isolated VSMC stiffness was 43 ± 8% greater, p&lt;0.05, in old SHR compared to young SHR (27 ± 4 kPa). VSMC stiffness was also increased, p&lt;0.05, in young SHR versus young WKY (14 ± 2 kPa), but this increase (92 ± 15%) was less, p&lt;0.05, than that observed between old SHR versus old WKY (131 ± 2%). Thus, increased VSMC stiffness is a significant component of the increased aortic stiffness of hypertension, but this increase is augmented in aging hypertensive rats.
TCT-448 Early Recruitable Coronary Collateral Vessels Preserve Myocardial Viability in Late-Presentation Infarctions
Authors: Dolores Cañadas, William Delgado-Nava, Livia L. Gheorghe, Sergio Gamaza, Enrique Diaz-Retamino, German Calle Perez, Alejandro Gutierrez-Barrios
Journal: Journal of the American College of Cardiology (2021)
Control of osteoblast arrangement by osteocyte mechanoresponse through prostaglandin E2 signaling under oscillatory fluid flow stimuli
Authors: Tadaaki Matsuzaka, Aira Matsugaki, Takayoshi Nakano
Journal: Biomaterials (2021)

Anisotropic collagen/apatite microstructure is a prominent determinant of bone tissue functionalization; in particular, bone matrix modulates its anisotropic microstructure depending on the surrounding mechanical condition. Although mechanotransduction in bones is governed by osteocyte function, the precise mechanisms linking mechanical stimuli and anisotropic formation of collagen/apatite microstructure are poorly understood. Here we developed a novel anisotropic mechano-coculture system which enables the understanding of the biological mechanisms regulating the oriented bone matrix formation, which is constructed by aligned osteoblasts. The developed model provides bone-mimetic coculture platform that enables simultaneous control of mechanical condition and osteoblast-osteocyte communication with an anisotropic culture scaffold. The engineered coculture device helps in understanding the relationship between osteocyte mechanoresponses and osteoblast arrangement, which is a significant contributor to anisotropic organization of bone tissue. Our study showed that osteocyte responses to oscillatory flow stimuli regulated osteoblast arrangement through soluble molecular interactions. Importantly, we found that prostaglandin E2 is a novel determinant for oriented collagen/apatite organization of bone matrix, through controlling osteoblast arrangement.
HLA informs risk predictions after haploidentical stem cell transplantation with posttransplantation cyclophosphamide
Authors: Ephraim J. Fuchs, Shannon R. McCurdy, Scott R. Solomon, Tao Wang, Megan R. Herr, Dipenkumar Modi, Michael R. Grunwald, Taiga Nishihori, Michelle Kuxhausen, Stephanie Fingerson, Caroline McKallor, Asad Bashey, Yvette L. Kasamon, Yung-Tsi Bolon, Ayman Saad, Joseph McGuirk, Sophie Paczesny, Shahinaz M. Gadalla, Steven G. E. Marsh, Bronwen E. Shaw, Stephen R. Spellman, Stephanie J. Lee, Effie W. Petersdorf
Journal: Blood (2021)
Reduction of Disease Burden With Early Sirolimus Treatment in a Child With Proteus Syndrome
Authors: Lisa Weibel, Martin Theiler, Ralph Gnannt, Kathrin Neuhaus, Jan Schellenberg Han, Hanspeter Huber, Thierry M. Nordmann
Journal: JAMA Dermatology (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
TCT-158 Resting Pd/Pa and the Instantaneous Wave-Free Ratio Are Not Immune to Hemodynamic Interdependence (“Crosstalk”) in the Presence of Serial Coronary Stenoses
Authors: Jung-Min Ahn, Takehiro Hashikata, Takaharu Nakayoshi, Kuninobu Kashiyama, Hiroyuki Arashi, Jihoon Kweon, William Fearon
Journal: Journal of the American College of Cardiology (2021)
TCT-96 Trends and Readmissions Rates After Left Atrial Appendage Occlusion According to Frailty
Authors: Aaqib Malik, Jayakumar Sreenivasan, Alexandros Briasoulis, Wilbert Aronow, Syed Zaid, Srikanth Yandrapalli, Syed Haidry, Ryan Kaple, Gilbert Tang, Hasan Ahmad
Journal: Journal of the American College of Cardiology (2021)
Mitochondrial metabolism coordinates stage-specific repair processes in macrophages during wound healing
Authors: Sebastian Willenborg, David E. Sanin, Alexander Jais, Xiaolei Ding, Thomas Ulas, Julian Nüchel, Milica Popović, Thomas MacVicar, Thomas Langer, Joachim L. Schultze, Alexander Gerbaulet, Axel Roers, Edward J. Pearce, Jens C. Brüning, Aleksandra Trifunovic, Sabine A. Eming
Journal: Cell Metabolism (2021)

Wound healing is a coordinated process that initially relies on pro-inflammatory macrophages, followed by a pro-resolution function of these cells. Changes in cellular metabolism likely dictate these distinct activities, but the nature of these changes has been unclear. Here, we profiled early- versus late-stage skin wound macrophages in mice at both the transcriptional and functional levels. We found that glycolytic metabolism in the early phase is not sufficient to ensure productive repair. Instead, by combining conditional disruption of the electron transport chain with deletion of mitochondrial aspartyl-tRNA synthetase, followed by single-cell sequencing analysis, we found that a subpopulation of early-stage wound macrophages are marked by mitochondrial ROS (mtROS) production and HIF1α stabilization, which ultimately drives a pro-angiogenic program essential for timely healing. In contrast, late-phase, pro-resolving wound macrophages are marked by IL-4Rα-mediated mitochondrial respiration and mitohormesis. Collectively, we identify changes in mitochondrial metabolism as a critical control mechanism for macrophage effector functions during wound healing.
TCT-282 IVUS Assessment of De Novo Ostial RCA Lesion Morphology
Authors: Kei Yamamoto, Takao Sato, Mitsuaki Matsumura, Khady Fall, Ajay Kirtane, Tamim Nazif, Sanjum Sethi, Sahil Parikh, Torsten Vahl, Ziad Ali, Dimitri Karmpaliotis, Leroy Rabbani, Martin Leon, Jeffrey Moses, Gary Mintz, Akiko Maehara
Journal: Journal of the American College of Cardiology (2021)
PHQ-8 scores and estimation of depression prevalence – Author's reply
Authors: Jorge Arias-de la Torre, Gemma Vilagut, Amy Ronaldson, Antoni Serrano-Blanco, Jordi Alonso
Journal: The Lancet Public Health (2021)

We thank Brooke Levis and colleagues for their interest in our work and for suggesting that we might have overestimated the prevalence of depression by using the eight-item Patient Health Questionnaire (PHQ-8) in our study.1 Although we acknowledged the limitations associated with the use of the PHQ-8, we believe that further discussion is required.
Sequential Defects in Cardiac Lineage Commitment and Maturation Cause Hypoplastic Left Heart Syndrome
Authors: Markus Krane, Martina Dreßen, Gianluca Santamaria, Ilaria My, Christine M. Schneider, Tatjana Dorn, Svenja Laue, Elisa Mastantuono, Riccardo Berutti, Hilansi Rawat, Ralf Gilsbach, Pedro Schneider, Harald Lahm, Sascha Schwarz, Stefanie A. Doppler, Sharon Paige, Nazan Puluca, Sophia Doll, Irina Neb, Thomas Brade, Zhong Zhang, Claudia Abou-Ajram, Bernd Northoff, Lesca M. Holdt, Stefanie Sudhop, Makoto Sahara, Alexander Goedel, Andreas Dendorfer, Fleur V.Y. Tjong, Maria E. Rijlaarsdam, Julie Cleuziou, Nora Lang, Christian Kupatt, Connie Bezzina, Rüdiger Lange, Neil E. Bowles, Matthias Mann, Bruce D. Gelb, Lia Crotti, Lutz Hein, Thomas Meitinger, Sean Wu, Daniel Sinnecker, Peter J. Gruber, Karl-Ludwig Laugwitz, Alessandra Moretti
Journal: Circulation (2021)

Complex molecular programs in specific cell lineages govern human heart development. Hypoplastic left heart syndrome (HLHS) is the most common and severe manifestation within the spectrum of left ventricular outflow tract obstruction defects occurring in association with ventricular hypoplasia. The pathogenesis of HLHS is unknown, but hemodynamic disturbances are assumed to play a prominent role. To identify perturbations in gene programs controlling ventricular muscle lineage development in HLHS, we performed whole-exome sequencing of 87 HLHS parent-offspring trios, nuclear transcriptomics of cardiomyocytes from ventricles of 4 patients with HLHS and 15 controls at different stages of heart development, single cell RNA sequencing, and 3D modeling in induced pluripotent stem cells from 3 patients with HLHS and 3 controls. Gene set enrichment and protein network analyses of damaging de novo mutations and dysregulated genes from ventricles of patients with HLHS suggested alterations in specific gene programs and cellular processes critical during fetal ventricular cardiogenesis, including cell cycle and cardiomyocyte maturation. Single-cell and 3D modeling with induced pluripotent stem cells demonstrated intrinsic defects in the cell cycle/unfolded protein response/autophagy hub resulting in disrupted differentiation of early cardiac progenitor lineages leading to defective cardiomyocyte subtype differentiation/maturation in HLHS. Premature cell cycle exit of ventricular cardiomyocytes from patients with HLHS prevented normal tissue responses to developmental signals for growth, leading to multinucleation/polyploidy, accumulation of DNA damage, and exacerbated apoptosis, all potential drivers of left ventricular hypoplasia in absence of hemodynamic cues. Our results highlight that despite genetic heterogeneity in HLHS, many mutations converge on sequential cellular processes primarily driving cardiac myogenesis, suggesting novel therapeutic approaches.
TCT-426 Electrocardiographically Gated Intravascular Image Segmentation Enables More Reproducible Volumetric Analysis of Atheroma Burden
Authors: Emrah Erdogan, Xingru Huang, Jackie Cooper, Ajay Jain, Anantharaman Ramasamy, Retesh Bajaj, Ryo Torii, James Moon, Andrew Deaner, Christos Costa, Hector Manel Garcia-Garcia, Vincenzo Tufaro, Patrick Serruys, Francesca Pugliese, Anthony Mathur, Jouke Dijkstra, Andreas Baumbach, Qianni Zhang, Christos Bourantas
Journal: Journal of the American College of Cardiology (2021)
Association of Expanded Health Care Networks With Utilization Among Veterans Affairs Enrollees
Authors: Liam Rose, Marion Aouad, Laura Graham, Lena Schoemaker, Todd Wagner
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Health insurers alter the size of their networks, offering lower premiums in exchange for a more limited set of care choices. However, little is known about the association of network size with health care utilization and outcomes, particularly outside of the context of private insurance plans. <h3>Objective</h3> To evaluate changes in health care utilization after an expansion in the Veterans Affairs Health Care System (VA) health care network. <h3>Design, Setting, and Participants</h3> This cross-sectional study included individuals enrolled in the VA from 2015 to 2018. Considering that the health care network expansion only affected a portion of enrollees, only those who lived between 20 and 60 miles from a VA facility were included. Data analysis was conducted from September 2020 to February 2021. <h3>Exposures</h3> Individuals who lived 40 or more miles away from a VA facility were automatically eligible for an expanded health care network through non-VA practitioners (VA community care); those living less than 40 miles away from a VA facility were not automatically eligible. <h3>Main Outcomes and Measures</h3> A regression discontinuity analysis of individuals who became eligible for an expanded network based on geographic residence was performed. Inpatient and outpatient utilization rates per VA enrollee during the study period, with utilization differentiated by whether services were provided by a VA or non-VA practitioner, were calculated. <h3>Results</h3> The study included more than 2.7 million unique individuals whose characteristics largely reflected the demographic characteristics of the VA system (mean [SD] age, 62 [17] years; 2 589 252 [90%] men; 282 168 [10%] Black; 2 203 352 [77%] White). Patient characteristics (age, race, and comorbidities) did not vary significantly by eligibility status. Outpatient utilization was 3.2% higher (95% CI, 1.0% to 5.3%) among those with access to an expanded network. Increased utilization was most pronounced among those with a higher VA disability rating (3.1%; 95% CI, 0.5% to 5.7%) and among younger individuals without service-connected disabilities (7.0%, 95% CI, 1.7% to 12.3%). There was no evidence of changes to inpatient utilization (1.2%; 95% CI. –2.5% to 4.9%;<i>P</i> = .37) for those with access to the expanded network. <h3>Conclusions and Relevance</h3> In this study, expanded network access was associated with increased total health care utilization among affected enrollees in the VA. Understanding how network size affects utilization is immediately informative for the VA, but it can also help to guide policies for insurance markets.
Response-Adapted Postinduction Strategy in Patients With Advanced-Stage Follicular Lymphoma: The FOLL12 Study
Authors: Stefano Luminari, Martina Manni, Sara Galimberti, Annibale Versari, Alessandra Tucci, Carola Boccomini, Lucia Farina, Jacopo Olivieri, Luigi Marcheselli, Luca Guerra, Simone Ferrero, Luca Arcaini, Federica Cavallo, Sofya Kovalchuk, Tetiana Skrypets, Ilaria del Giudice, Stephane Chauvie, Caterina Patti, Caterina Stelitano, Francesca Ricci, Antonello Pinto, Gloria Margiotta Casaluci, Vittorio R. Zilioli, Anna Merli, Marco Ladetto, Silvia Bolis, Vincenzo Pavone, Annalisa Chiarenza, Annalisa Arcari, Antonella Anastasia, Alessandra Dondi, Donato Mannina, Massimo Federico
Journal: Journal of Clinical Oncology (2021)

PURPOSE We compared 2 years of rituximab maintenance (RM) with a response-adapted postinduction approach in patients with follicular lymphoma who responded to induction immunochemotherapy. METHODS We randomly assigned treatment-naïve, advanced-stage, high-tumor burden follicular lymphoma patients to receive standard RM or a response-adapted postinduction approach on the basis of metabolic response and molecular assessment of minimal residual disease (MRD). The experimental arm used three types of postinduction therapies: for complete metabolic response (CMR) and MRD-negative patients, observation; for CMR and MRD-positive (end of induction or follow-up) patients, four doses of rituximab (one per week, maximum three courses) until MRD-negative; and for non-CMR patients, one dose of ibritumomab tiuxetan followed by standard RM. The study was designed as noninferiority trial with progression-free survival (PFS) as the primary end point. RESULTS Overall, 807 patients were randomly assigned. After a median follow-up of 53 months (range, 1-92 months), patients in the standard arm had a significantly better PFS than those in the experimental arm (3-year PFS 86% v 72%; P &lt; .001). The better PFS of the standard versus experimental arm was confirmed in all the study subgroups except non-CMR patients (n = 65; P = .274). The 3-year overall survival was 98% (95% CI, 96 to 99) and 97% (95% CI, 95 to 99) in the reference and experimental arms, respectively ( P = .238). CONCLUSION A metabolic and molecular response-adapted therapy as assessed in the FOLL12 study was associated with significantly inferior PFS compared with 2-year RM. The better efficacy of standard RM was confirmed in the subgroup analysis and particularly for patients achieving both CMR and MRD-negative.
2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines
Authors: Martha Gulati, Phillip D. Levy, Debabrata Mukherjee, Ezra Amsterdam, Deepak L. Bhatt, Kim K. Birtcher, Ron Blankstein, Jack Boyd, Renee P. Bullock-Palmer, Theresa Conejo, Deborah B. Diercks, Federico Gentile, John P. Greenwood, Erik P. Hess, Steven M. Hollenberg, Wael A. Jaber, Hani Jneid, José A. Joglar, David A. Morrow, Robert E. O’Connor, Michael A. Ross, Leslee J. Shaw
Journal: Circulation (2021)

Aim: This clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients. Methods: A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing randomized and nonrandomized trials, observational studies, registries, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered. Structure: Chest pain is a frequent cause for emergency department visits in the United States. The “2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain” provides recommendations based on contemporary evidence on the assessment and evaluation of chest pain. This guideline presents an evidence-based approach to risk stratification and the diagnostic workup for the evaluation of chest pain. Cost-value considerations in diagnostic testing have been incorporated, and shared decision-making with patients is recommended.
High expression of peroxiredoxins in prostate cancer cells
Authors: Anamika Basu, Shannalee Martinez, Lauren Melendez, Melanie Mediavilla-Varela, Carlos Casiano
Journal: Cancer Research (2007)

2911  The peroxiredoxins (PRDXs), an anti-oxidant protein family composed of six isoforms, called PRDX1-PRDX6, are thought to offer protection to tumor cells in an environment of increased oxidative stress. PRDX6, also known as antioxidant protein 2, is transcriptionally activated by the stress regulated transcription co-activator lens epithelium-derived growth factor (LEDGF/p75). LEDGF/p75 is upregulated in prostate cancer (PCa) and is likely to promote prostate tumor survival by transcriptionally activating stress and anti-oxidant genes. We hypothesized that because PRDX6 is upregulated by LEDGF/p75, the PRDXs might also be upregulated in PCa cells and promote protection against oxidative stress-induced cell damage. We analyzed by immunoblotting the protein levels of LEDGF/p75 and PRDXs in a panel of prostate cell lines in order to establish a correlation in the expression levels of these proteins. Cell lines included tumor, transformed tumor, transformed non-tumor, benign prostatic hyperplasia and primary prostate. Total protein from cell lines was separated by 4-12% SDS-PAGE, followed by transfer onto PVDF membranes. Protein expressions were detected using specific antibodies to the individual proteins. Similarly, we also analyzed the expression of PRDXs in PC3 prostate tumor cells with small inhibitory RNA (siRNA) mediated LEDGF/p75 knockdown. Additionally expression levels of LEDGF/p75 and PRDX6 was quantified in commercially available PCa tissue micro-arrays. We observed that the PRDXs are expressed at very high levels in the prostate tumor cell lines, as compared to normal or non-tumor transformed cells. Preliminary immunohistochemical analysis of PRDX6 in human prostate tumor tissue arrays revealed high expression of this protein in prostate tumor tissues compared to adjacent normal prostate tissue. However, there was little correlation between the expression levels of LEDGF/p75 and PRDXs in the different prostate cell lines. This was confirmed by the observation that knockdown of LEDGF/p75 in PC3 cells, using siRNA oligos, did not decrease the expression levels of PRDXs. We conclude that while LEDGF/p75 might contribute to the regulation of PRDXs, it may not be essential for controlling their expression in prostate cells. The high PRDX expression in prostate cancer cells may provide a protective mechanism against the augmented state of cellular oxidative stress (ASCOS) in prostate tumors. PRDXs could be attractive targets for novel therapeutic strategies in the treatment of advanced PCa.
Interim Analysis of the COSA Registry: COVID-19 Patients Treated with the Seraph® 100 Microbind® Affinity Filter
Authors: Julius Schmidt, Michael Schmitz, Jan T. Kielstein
Journal: Journal of the American Society of Nephrology (2021)

Background: How the COVID-19 pandemic altered ESKD incidence, dialysis initiation, and preemptive kidney transplantation is unknown. Methods: Using Centers for Medicare & Medicaid Services data, we investigated the incidence of ESKD, dialysis initiation, and preemptive kidney transplantation by week during the first half of 2020. Using Poisson regression, we compared findings in 2020 to a forecast of 2020, had 2017-2019 historical trends continued, overall and by strata of age and race. Results: Mean weekly counts of patients with new ESKD are shown in the Figure. Incidence of ESKD dropped dramatically in 2020 compared with the expected incidence, particularly during epidemiologic weeks 15-18 (April;incidence rate ratio [IRR] 0.75, 95% CI 0.73-0.78), before approaching pre-pandemic levels in weeks 23-26 (June;IRR 0.93, 0.90-0.95). Across age groups, the decrease was most pronounced during weeks 15-18 among individuals aged ≥75 years (IRR 0.69, 0.66-0.73, compared with individuals aged 45-64 years, IRR 0.80, 0.77-0.84). In terms of race, the decrease was least notable among non-Hispanic Blacks (IRR 0.85, 0.81-0.89) and was most pronounced in non-Hispanic Whites (IRR 0.72, 0.69-0.74) and Hispanics (IRR 0.73, 0.69-0.78). Dialysis initiation reached a nadir during weeks 15-18 (IRR 0.76, 0.74-0.78), and preemptive kidney transplantation decreased even more strikingly during this period (IRR 0.56, 0.46-0.67). Conclusions: During the first wave of the COVID-19 pandemic in 2020, the number of patients starting treatment for ESKD fell to a level not observed since 2011. Changes in ESKD incidence and utilization of treatment modalities may reflect differential access to care.