tbuckley/cabot-search huggingface dataset:
Abstract 12684: Transcriptional Features Of Biological Age Maintained In Cultured Cardiac Interstitial Cells
Authors: Oscar E Echeagaray, Taeyong Kim, Alex Casillas, Megan M Monsanto, Mark A Sussman
Journal: Circulation (2021)

Introduction: Ex vivo expansion of cells is necessary in regenerative medicine to generate large populations for therapeutic use. Adaptation to culture conditions prompt an increase in transcriptome diversity and decreased population heterogeneity in cKit+ cardiac interstitial cells (cCICs). Hypothesis: Age and/or condition of origin is impacts the transcriptional phenotype as well as population heterogeneity characteristics of cCICs undergoing in vitro expansion. Methods: cCICs isolated from neonatal and adult cardiac tissue (Left Ventricular Assist Device; LVAD). Single cell libraries from in vitro expanded cells were prepared following five passages. “Transcriptional memory” was surveyed via bioinformatic analysis including unsupervised clustering, differential expression analysis, gene ontology and pathway analysis. Transitional states were assessed through pseudotime analysis. Results: Cell cycle imprint associated with biological age after culture was observed in Neonatal cCICs via upregulation of G2M genes. LVAD derived cCICs retained a widespread senescent profile, in particular high expression of interleukins and elements of the senescence associated secretory phenotype (SASP). Nuclear pore complex TPR and UBC9 and translation initiation factors, displayed age-associated downregulation of elements in the RNA transport and processing pathway. Pathway and co-expression analysis of fibroblast markers Ddr2, Tcf21, Vimentin, Periostin and Collagen deposition markers indicated a primed fibrotic phenotype in senescent cells. A small subset of cCICs exist in a transcriptional continuum between “youthful” phenotype and the damaged microenvironment of adult tissue in which they were embedded. Conclusions: The influence of age, pathology and the cellular stress associated to the in vivo tissue microenvironment persist after culture adaptation, influencing targets of 1) cell cycle, 2) senescence associated secretory phenotype (SASP), 3) RNA transport, and 4) ECM-receptor/fibrosis. The connate transcriptional phenotypes offer fundamental biological insight and highlights cellular input as a consideration in culture expansion and adoptive transfer protocols.
Abstract 11154: Cardioprotective Effects of Mtss1 Reduction Iin Dilated Cardiomyopathy
Authors: dongwook C choe, Jeffrey A Brandimarto, Nataliya Petrenko, Ingrid Marti-pamies, Megan Burke, Wenjian Lv, Sharlene Day, Kiran Musunuru, Xiao Wang, Thomas P Cappola
Journal: Circulation (2021)

Introduction: MTSS1 is an I-BAR protein that interacts with the actin cytoskeleton and the cell membrane and is speculated to play a role in cell motility, tumor metastasis, and cardiogenesis. Enhancer variants that reduce the expression of MTSS1 in the human left ventricle have been associated with cardioprotective traits in genome-wide association studies. However, the effect of MTSS1 downregulation on the development of heart disease has not been studied in experimental models. Here we tested the hypothesis that reduction of MTSS1 protects against dilated cardiomyopathy (DCM) in vitro and in vivo . Methods: We used CRISPR-Cas9 to knock out MTSS1 in induced pluripotent stem cells (iPSCs) harboring pathogenic variants from patients with severe DCM. DCM iPSC lines with and without MTSS1 were then differentiated into cardiomyocytes and phenotyped in vitro . A DCM mouse model containing a TPM1 D230N transgene was crossed with a mouse model heterozygous for Mtss1 knockout. Progeny from this F1 cross were assessed for differences in cardiac structure and function via echocardiography. Results: MTSS1 deletion restored the beta-adrenergic response in DCM iPSC cardiomyocytes. In parallel, Mtss1 deletion partially rescued DCM-associated phenotypes including left ventricular dilation and reduced ejection fraction in mice. Conclusions: Our initial results suggest a causal link between MTSS1 reduction and cardioprotection in DCM. Inhibiting cardiac MTSS1 may hold therapeutic potential for DCM, though the cellular mechanisms through which MTSS1 affects cardiac phenotypes remain under investigation.
Abstract 13147: The Internally Translated Isoform of Connexin 43, GJA1-20k Rescues Cx43 Trafficking and Reduces Arrhythmias in the DSG2 Mutant Model of Arrhythmogenic Cardiomyopathy
Authors: Joseph A Palatinus, Steven Valdez, Claire Whisenant, Andre G Kleber, Jeffrey E Saffitz, Robin M Shaw
Journal: Circulation (2021)

Introduction: Arrhythmogenic cardiomyopathy (ACM) is an inherited condition caused by mutations of junctional proteins resulting in heart rhythm abnormalities, heart failure and sudden cardiac death. ACM subjects exhibit a loss of normal trafficking of the gap junction protein Connexin 43 (Cx43) to the intercalated disk. Our group has previously demonstrated that the Cx43 gene, GJA1, undergoes internal translation to form multiple truncations of the full-length protein. The 20 kilodalton isoform, (GJA1-20k) is required for trafficking of Cx43 gap junction channels, and exogenous expression of GJA1-20k increases trafficking of full length Cx43 to the membranes and the intercalated disk. Here, we hypothesize that GJA1-20K will reduce dysrhythmias by improving trafficking of Cx43 to the intercalated disc in a mouse model of ACM. Methods: Desmoglein 2 (DSG2) homozygous knock-out mice, producing a typical ACM phenotype, were injected with a viral vector containing either GJA1-20K-GFP or GFP alone at four weeks of age along with wild-type littermate controls. Echocardiography was performed every four weeks and Telemetry was recorded at ~18-19 weeks of age to record cardiac electrical activity over a continuous 12 hour period. At 20 weeks, the mice were sacrificed, and hearts were harvested for further analysis. Results: Compared to WT littermates DSG2-KO mice that received a GFP viral vector demonstrated over a 100 fold increase in mean number of PVCs observed over a 12 hour period (2 vs 371 respectively p=0.0005). Mice that received the GJA1-20k viral vector in contrast demonstrated significantly fewer PVCs than their GFP treated littermates 43 vs 371. (analysis of variance of Log(#PVC) p =0.015 N = 6-7 mice/group). Quantitative immunofluorescence analysis of hearts confirmed an increase in Cx43 localization at the intercalated disk (as measured as a percent of N-Cadherin-Cx43 colabeling) in mice treated with GJA1-20k relative to GFP (25% vs 6% respectively N= 7 images/mouse and 3 mice/ group) t-test p=0.0009). Conclusions: Our data indicate that GJA1-20K significantly reduces the number of PVCs and recovers Cx43 trafficking to the intercalated disk in a mouse model of ACM. Our results point to a therapeutic option for the treatment of ACM related arrhythmias.
ジゴキシンは脂肪性肝炎におけるピルビン酸キナーゼM2で促進されたHIF-1αトランス活性化を抑制する【Powered by NICT】
Authors: Ouyang Xinshou, Han Sheng-Na, Zhang Ji-Yuan, Nemeth Balazs Tamas, Pacher Pal, Feng Dechun, Bataller Ramon, Cabezas Joaquin, Staerkel Peter, Caballeria Joan, Pongratz Rebecca LePine, Cai Shi-Ying, Schnabl Bernd, Hoque Rafaz, Chen Yonglin, Yang Wei-hong, Martinez Irma Garcia, Wang Fu-Sheng, Gao Bin, Torok Natalie Julia, Kibbey Richard Glenn, Mehal Wajahat Zafar
Journal: Cell Metabolism (2018)
Effect of Pregnancy on the Clinical Course of ITP Pregnant Women and Their Newborns. Resuts of a Spanish Case Series of 297 Primary ITP Pregnancies
Authors: Tomás José González-López, Pavel Olivera, Isidro Jarque, Jose Maria Bastida, Silvia Bernat, Blanca Sanchez-Gonzalez, Estefanía Bolaños, Gloria Perez-Rus, Ana R. Huerta, Fernando Fernandez-Fuertes, Violeta Martinez-Robles, Maria Paz Martínez-Badas, Rocio Pérez-Montes, Maria Jesus Penarrubia Ponce, Venancio Conesa, Nuria Bermejo, Gonzalo Caballero, Maria Teresa Alvarez Roman, Carmen Fernandez-Miñano, Lucia Guerrero, Shally Marcellini, Magdalena Sierra Pacho, Emilia Pardal, Carmen Pastoriza, Maria Elsa Lopez Ansoar, Erik de Cabo, Gerardo Hermida, Miguel A. Sanz
Journal: Blood (2017)
Abstract 12217: Accurate Prediction of Systolic Peak-to-Peak Gradient in Children With Pulmonary Valve Stenosis
Authors: Salvador A Rodriguez Franco, Jenny E Zablah, Benjamin S Frank, Gareth J Morgan
Journal: Circulation (2021)

Objective: To evaluate the correlation between transthoracic echocardiography (TTE) derived gradients and invasive RV-PA peak-to-peak systolic gradient (iPG) and the predictability of these values in children with pulmonary valve stenosis (PVS). Introduction: Historically, correlations have been found between the Doppler-derived peak echo gradient (ePG), using the modified Bernoulli equation and invasive hemodynamic indices. This has led to the ePG being a widely used estimate of the degree of stenosis and an indicator of timing to consider intervention in children with PVS. However, large disparities observed between these invasive and non-invasive measurements have called into question the reliability of ePG to screen patients for consideration of pulmonary valvoplasty. Methods: We performed a retrospective chart review of 119 children who underwent pulmonary valvoplasty between January 2010 and January 2020 and selected 51 patients who had "simple" PVS in whom a TTE was performed within 6 months prior to the procedure. We evaluated the correlation between TTE parameters [Maximum velocity (Vmax), Mean Gradient (MG), ePG], and iPG. We then used the mathematical functions resulting from the correlation models to predict iPG. Results: All the assessed models were statistically significant and presented a strong correlation. When the differences between echocardiographic parameters and iPG were evaluated, ePG demonstrated the least accuracy in predicting iPG, erroneously estimating the real value by &gt;10mm Hg in 66% of cases. The MG presented a more accurate estimation of iPG, showing a narrower range of variance, with an error of &gt;10mm Hg in less than 30% of cases. We then modeled several mathematical functions of Vmax, MG, and ePG to predict iPG, and found that a derived function of Vmax ( f iPG) distributed by BSA (fiPG =12.7[Vmax]-17.3[BSA]) produced the most accurate results. Conclusions: There is a strong correlation between pre-procedural TTE parameters and iPG, but when ePG is used to estimate iPG, up to two-thirds of cases could be inappropriately characterized. We found that MG was a better predictor and that a mathematical function derived from Vmax and BSA ( f iPG) was the most accurate predictor of iPG.
Unexpected Widespread Bone Metastases from a BRAF K601N Mutated Follicular Thyroid Carcinoma within a Previously Resected Multinodular Goiter
Authors: Andrea Repaci, Nicola Salituro, Valentina Vicennati, Fabio Monari, Ottavio Cavicchi, Dario de Biase, Alessia Ciarrocchi, Giorgia Acquaviva, Antonio De Leo, Elisa Gruppioni, Uberto Pagotto, Giovanni Tallini
Journal: Endocrine Pathology (2021)
In-Hospital Outcomes of Hemolytic Uremic Syndrome: A Perspective from the Last Decade
Authors: Sanjana Mullangi, Bhuvana Tantry, Arjun Narayanan, Elad Eylat, Sanjay Rao Gergal Gopalkrishna Rao, Divya Gavini, Soumya Gupta, Chandrakala Dadeboyina, Achint Patel, Manidhar Reddy Lekkala
Journal: Blood (2021)
Abstract 13682: Remote Hypertension Management During the COVID-19 Pandemic
Authors: Alexander Blood, Kira Chaney, David Zelle, William Gordon, Thomas A Gaziano, Christopher P Cannon, Benjamin M Scirica, Naomi D Fisher
Journal: Circulation (2021)

Introduction: During the COVID-19 pandemic, much of routine chronic disease monitoring and management via outpatient visits was deferred, revealing a disruption in care delivery. We demonstrate that an established remote care delivery program enabled delivery of uninterrupted, effective care. Methods: The team-based Digital Care Transformation (DCT) program remotely manages hypertension via monitoring home blood pressure (BP) readings that are automatically transmitted, using a team of navigators who follow expert-designed titration algorithms. We examined all patients enrolled in this program during the first six months of the health emergency in Boston (3/15- 9/15/2020) to assess outcomes at a cutoff one year into the pandemic (3/15/2021). We also assessed healthcare utilization by analyzing monthly PCP and non-PCP visits, as well as BPs measured, in the year prior to enrollment compared to the study year 3/15/2020 - 3/15/2021. Results: 651 patients were enrolled and transmitted a home baseline BP during the first week. 475 patients (73%) had sustained hypertension according to home BPs. PCP visits decreased by 50% and non-PCP visits by 40% over this period (both p&lt;0.001.) The weekly mean BP at program baseline was 145/84 + 15/9 mmHg, and at program exit was 135/79 + 15/10 mmHg (p&lt;0.001.) Assessing the 240 patients who completed all follow-up, maintenance BP was 125/73 + 7/7 mmHg (p&lt;0.001.) Control was reached with a mean 2.3 medication titrations. While in the program, patients received an average of 8.2 phone calls/month and recorded 32.4 individual BP measurements monthly. Conclusions: While in-person clinical care delivery during the COVID-19 pandemic decreased dramatically, an established remote health delivery program continued to deliver effective BP reduction and achieve clinical targets. Further study is warranted to understand the role remote care can play in hypertension management as we exit the pandemic.
Abstract 9958: Calcium-Phosphorus Product is Associated with Adverse Prognosis in Hospitalized Patients with Heart Failure and Chronic Kidney Disease
Authors: Satoshi Abe, Akiomi Yoshihisa, Ryohei Takeishi, Himika Ohara, Yasuhiro Ichijo, Koichiro Watanabe, Yu Hotsuki, Yu Sato, Yusuke Kimishima, Tomofumi Misaka, Takamasa Sato, Masayoshi Oikawa, ATSUSHI KOBAYASHI, Kazuhiko Nakazato, Yasuchika Takeishi
Journal: Circulation (2021)

Introduction: It has been reported that calcium-phosphorus (Ca-P) product &amp;gt 55 mg 2 /dl 2 is an independent predictor for coronary calcifications, and Ca-P product &amp;gt 80 or &amp;lt 40 is a mortality risk in patients undergoing chronic hemodialysis. However, the association between Ca-P product and prognosis in patients with heart failure (HF) and chronic kidney disease (CKD) remains unclear. We aimed to evaluate the significance of the Ca-P product to predict prognosis of patients with HF and CKD. Methods: We conducted a prospective observational study of 793 patients with decompensated HF and CKD, who had been discharged from our hospital. According to the receiver operating characteristic curve analysis, the accurate cut-off value of Ca-P product in predicting post-discharge all-cause mortality and/or worsening HF was 28 mg 2 /dl 2 . These patients were divided into two groups: the high group (Ca-P product &amp;gt 28, n=594) and the low group (Ca-P product &amp;lt 28, n=199). We compared the patient baseline characteristics and their post-discharge prognosis between the two groups. Results: Age was significantly higher, and the prevalence of male, ischemic etiology and anemia was significantly higher in the low group than in the high group. In contrast, there was no difference in echocardiographic parameters between two groups. Ca-P product was correlated with cardio-ankle vascular index (a marker of arterial stiffness), but not with left ventricular ejection fraction. In the Kaplan-Meier analysis (mean follow-up 1089 days), all-cause mortality and/or worsening HF event rates were higher in the low group than in the high group (Figure, log-rank P=0.001). In the multivariable Cox proportional hazard analysis, the low group was found to be an independent predictor of all-cause mortality and/or worsening HF (hazard ratio 1.218, P=0.048). Conclusions: Lower Ca-P product is associated with arterial stiffness, and predicts adverse prognosis in patients with HF and CKD.
Migraine runs in families ..
Authors: W E Waters
Journal: BMJ (1995)

… but is it inherited?

EDITOR,--Michael Bjorn Russell and Jes Olesen report an increased familial risk of migraine.1 Before migraine is accepted as an inherited disorder, as it is in the heading to the paragraph about the paper on the “This week in BMJ” page, however, all studies and possible biases should be considered.

The paper concentrates on the high prevalence of migraine in first degree relatives of probands with migraine. Surprisingly, however, the figures …
Abstract P496: Exosomes From Brown Adipose Tissue Contain Cardiac Gene-regulatory Elements
Authors: Vikram Shettigar, Sarah Sturgill, Benjamin Hu, Lisa Baer, Carmem Peres Valgas Da Silva, Kriistin Stanford, Mark T Ziolo
Journal: Circulation Research (2021)

Exosomes, extracellular vesicles &lt;150 nm, are vehicles for transporting information (i.e., cargo) allowing tissue to tissue communication. Depending on the cargo, exosomes can have beneficial or detrimental effects. Brown Adipose Tissue (BAT) is a thermogenic organ that modulates metabolism. BAT is also an endocrine organ affecting function of various distant tissue. We have recently shown that BAT is an important modulator of the healthy and diseased heart. Adipose tissue is a large source of circulating exosomes, but the effects of BAT and changing BAT activity on circulating exosome number and cargo are unknown. Identifying the role of BAT in modulating exosome number and cargo is important since the myocardium is highly responsive to exosomes. We used various known approaches that increase BAT activity (cold exposure, BATcold) or decrease BAT activity (BAT removal (BATless), obesity (HFD), aging (old)) and examined the number and content of circulating exosomes. Upon BAT activation via cold exposure, there was a large increase in circulating exosome numbers (see figure). All approaches that results in decreased BAT activity resulted in a decrease in circulating exosome numbers (see figure). We further examined the role of changing BAT activity on the content (i.e., cargo) of the exosomes, specifically focusing on miRNA. Interestingly, changing BAT activity resulted in large changes to the content of the exosomes, with some miRNA increasing levels and other miRNA decreasing levels. Some of these identified miRNA have been shown to exert beneficial effects on the heart and many miRNA having no defined effect on cardiac function. We believe that these BAT activated exosomes have the combination and proportion of circulatory miRNA necessary to enhance and maintain heart function. There is a great need for new strategies and approaches for treatment of cardiovascular disease (CVD). Our data suggest that a novel treatment strategy for CVD can be derived from BAT exosomes.
Abstract 12222: The Role of Metformin in Abdominal Aortic Aneurysm: A Systematic Review and Meta-Analysis
Authors: Raditya Dewangga, Kevin Winston, Lazuardi Gayu Ilhami, Suci Indriani, Taofan Siddiq, Suko Adiarto
Journal: Circulation (2021)

Introduction: Abdominal aortic aneurysm (AAA) is a cardiovascular disease with very high mortality especially due to its tendency to be asymptomatic. Some reports suggest that patients with diabetes, especially those who take metformin, may be negatively associated with AAA, but the association is still unclear. Hence, we aim to conduct a systematic review with meta-analysis on the role of metformin in reducing AAA diameter progression and AAA-related events. Hypothesis: We hypothesized that metformin reduces the growth of AAA diameter and AAA-related events. Methods: A comprehensive search of relevant articles was systematically performed on PubMed, Science Direct, Cochrane, and Scopus for studies comparing metformin with no metformin treatment on patients with AAA. Two reviewers independently assessed the abstracts and full-text articles. The outcome was aortic enlargement progression and AAA-related events such as AAA rupture and mortality. Biases in selected studies were assessed using Newcastle-Ottawa Scale. Data from eligible studies were pooled for effect estimates. Statistical analysis was performed using Review Manager software. Results: A total of 11 articles comprising 110,727 patients were included in the systematic review. Results showed that metformin was associated with reduction of annual AAA diameter progression (weighted mean difference: -0.84 mm; 95%CI: -1.33 to -0.35; p: 0.0007; I 2 : 85%). Metformin treatment may be associated with a decrease in AAA-related events. Funnel plot analysis showed that there was an indication of publication bias. Conclusions: Our results may suggest a potential role for metformin in limiting AAA growth. Further randomized controlled trials are needed to confirm the results.
QOLP-01. EXPERIENCES FROM PATIENT, CAREGIVER, AND PHYSICIAN SURVEYS ON DIAGNOSIS AND TREATMENT OF BRAIN METASTASES
Authors: Albert Kim, Gi-Ming Wang, Kristin Waite, Scott Elder, Avery Fine, Manmeet Ahluwalia, Daniel Brat, Minesh Mehta, Robin Page, Erin Dunbar, Heather Calderone, Debra Robins, Ralph DeVitto, Nicole Willmarth, Jill Barnholtz-Sloan, Priscilla Brastianos
Journal: Neuro-Oncology (2021)

Abstract The development of brain metastases (BM) is one of the most feared complications of cancer due to the substantial neuro-cognitive morbidity and grim prognosis. In the past decade, targeted therapies and checkpoint inhibitors have demonstrated remarkable intracranial response rates for tumors of multiple histologies. As overall survival for these patients improves, there is a growing need to identify issues surrounding patient survivorship and to standardize physician practice patterns for these patients. To date, there has not been an adequate study to specifically explore these questions of survivorship and practice standardization for patients with advanced cancer and BM. Here, we present results from a cross-sectional survey in which we analyze responses from 237 patients, 209 caregivers, and 239 physicians to identify areas of improvement in the clinical care of BM. In comparing physician and patient/caregiver responses, we found a disparity in the perceived discussion of topics pertaining to important aspects of BM clinical care. We identified variability in practice patterns for this patient population between private practice and academic physicians. Many physicians continue to have patients with BM excluded from clinical trials. Finally, we obtained patient/physician recommendations on high-yield areas for federal funding to improve patient quality of life. Therefore, by identifying potential areas of unmet need, we anticipate this wealth of actionable information will translate into tangible benefits for both patients and caregivers. Future studies are needed to validate our findings.