tbuckley/cabot-search huggingface dataset:
Abstract 15601: On the Mechanisms of Accelerated Calcification of Bioprosthetic Heart Valve Biomaterials in Juvenile Animal Models
Authors: Yingfei Xue, Alexander Kossar, Gaetano THIENE, Robert LEVY, Giovanni Ferrari
Journal: Circulation (2020)

Objective: Bioprosthetic heart valves (BHV) are subject to accelerated structural valve degeneration (SVD) in pediatric patients. Prior literature has reported differences in circulating markers of mineralization in pediatric patients compared to adults. Here we test the hypothesis that calcification-related circulating markers are differentially expressed in juvenile vs adult animals, and these markers functionally drive the accelerated SVD in juvenile animals in vitro and in vivo . Methods: Serum calcium (Ca 2+ ), phosphate (PO 4 - ), alkaline phosphatase (ALP), and osteopontin (OPN) levels of juvenile (3 week-old; n=5) and adult (8 month-old; n=5) Sprague-Dawley rats were measured by commercially-available assay kits. Glutaraldehyde-fixed bovine pericardial discs (BP) were incubated in juvenile or adult rat serum in vitro for 4 or 8 weeks. BP were subcutaneously implanted in juvenile or adult rats for 7 or 30 days (4-6 discs/rat). Pericardial transcatheter valves were implanted in juvenile Dorset sheep for 150 days (n=3). Alizarin Red staining, Von Kossa staining, and a quantitative assay were used for calcium analyses. Second harmonic generation imaging visualized collagen structure. Results: Serum Ca 2+ (p&lt;0.05), PO 4 - (p&lt;0.05), ALP (p&lt;0.01), and OPN (p&lt;0.01) were all increased in juvenile rats compared to adult rats. BP incubated in juvenile rat serum resulted in higher calcium deposition (p&lt;0.05) and more disruption to collagen structure as evidenced by reduced alignment coefficient (p&lt;0.01) as compared to those incubated in adult rat serum. Similarly, BP explanted from juvenile rats had higher calcium deposition (p&lt;0.01) and more disrupted collagen structure in terms of collagen alignment and crimp period (p&lt;0.01). Results in progress in juvenile sheep implantation model further confirmed the in vitro and in vivo findings that BHV explants had substantial calcium deposition and collagen disalignment. Conclusion: Calcium accumulates within BHV biomaterials more prominently in juvenile rats; increased serum markers of mineralization may explain the increased susceptibility to SVD in pediatric patients. Future studies will investigate novel strategies for the prevention and mitigation of accelerated SVD in pediatric patients.
Abstract MP55: Red And Processed Meat And Alternative Protein Sources In Relation To Risk Of Fatal Coronary Heart Disease: A Pooled Analysis Of 16 Prospective Cohort Studies
Authors: Laila Al-Shaar, Molin Wang, Walter Willett, Stephanie Smith-Warner
Journal: Circulation (2021)

Background: Red and processed meat intake have been associated with higher risk of fatal coronary heart disease (CHD). However, very few studies have evaluated substitution of alternative protein sources for red and processed meat in relation to fatal CHD risk. Objective: We estimated the associations of substituting other animal and plant protein sources for total red meat, unprocessed red meat, and processed meat in relation to risk of fatal CHD. Methods: This pooled analysis was conducted within the Pooling Project of Prospective Studies of Diet and Cancer and included participants with no prior self-reported history of cardiovascular diseases or cancer. Diet was assessed by cohort-specific food frequency questionnaires collected at baseline. Total red meat included processed meat and unprocessed red meat. Animal protein sources included seafood, poultry, eggs, and low- and high-fat dairy products; plant protein sources included nuts and beans. After adjusting for dietary and non-dietary factors, study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated using Cox proportional hazard models and then pooled using a random effects model. Isocaloric dietary substitution was evaluated by differences in coefficients in models including red meat and all alternative protein sources described above as continuous variables. Results: In preliminary analyses of 16 prospective cohorts including 1,364,211 participants (40% men and mean age of 57 ± 10 years) followed for a maximum of 32 years across studies, we identified 51,176 fatal CHD cases. A 100g/day increment in total red meat intake was associated with a 7% higher risk of fatal CHD, RR=1.07 (95% CI 1.04, 1.10). Substitutions of 200 kcal/day from nuts, low- and high-fat dairy products, and poultry for 200 kcal/d from total red meat were associated with 6-14% lower risks of fatal CHD. These associations were stronger when substituting the alternative protein sources for processed meat, especially among women (n=14,888 cases, 17-24% lower risk). Substituting 200 kcal/day from eggs for 200 kcal/day from total red meat and unprocessed red meat was associated with 8 and 14% higher risk of fatal CHD, respectively; this substitution for processed meat was weaker and not significant (4%). Results were similar after excluding the first 4 years of follow-up. Conclusions: Preliminary results from this international pooled analysis of 16 cohort studies provide more evidence about the risks of red and processed meat consumption. Replacement of red and processed meat with nuts, dairy products, or poultry may reduce the risk of fatal CHD.
Prevalence of Inflammatory Bowel Disease Among Medicare Fee-For-Service Beneficiaries — United States, 2001−2018
Authors: Fang Xu, Susan A. Carlson, Yong Liu, Kurt J. Greenlund
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is characterized by chronic inflammation of the gastrointestinal tract. The number of affected persons worldwide has increased from 3.7 million in 1990 to 6.8 million in 2017 (1). The disease is more prevalent among non-Hispanic White persons than it is among persons in other racial/ethnic groups (2). As the prevalence increases with age group (2), it is important to understand the disease epidemiology among the older population. CDC analyzed 2018 Medicare data among beneficiaries aged ≥67 years to examine differences by demographic characteristics for both diseases and to assess trends of prevalence from 2001 through 2018 both overall and by race and ethnicity. In 2018, 0.40% and 0.64% of 25.1 million Medicare fee-for-service beneficiaries aged ≥67 years had received a diagnosis of either Crohn's disease or ulcerative colitis. Prevalence varied by age, sex, race and ethnicity, urban-rural residency, and state. During 2001-2018, the age-adjusted prevalence of both diseases increased (Crohn's disease annual percentage change [APC] = 3.4%, ulcerative colitis APC = 2.8%). The increase was higher among non-Hispanic Black persons (Crohn's disease APC = 5.0%, ulcerative colitis APC = 3.5%) than it was among non-Hispanic White, Hispanic, and Asian/Pacific Islander (A/PI) persons. Prevalence was consistently highest among non-Hispanic White persons for both diseases and lowest among A/PI persons for Crohn's disease. The study findings of increasing prevalence in all racial/ethnic groups among older adults, especially the higher rate of increase among certain racial/ethnic minority groups, underscore the importance for promoting health equity, guiding efforts to tailor disease management strategies for different populations, and continuing to monitor the temporal trends of the disease.
Long-read sequencing of 3,622 Icelanders provides insight into the role of structural variants in human diseases and other traits
Authors: Doruk Beyter, Helga Ingimundardottir, Asmundur Oddsson, Hannes P. Eggertsson, Eythor Bjornsson, Hakon Jonsson, Bjarni A. Atlason, Snaedis Kristmundsdottir, Svenja Mehringer, Marteinn T. Hardarson, Sigurjon A. Gudjonsson, Droplaug N. Magnusdottir, Aslaug Jonasdottir, Adalbjorg Jonasdottir, Ragnar P. Kristjansson, Sverrir T. Sverrisson, Guillaume Holley, Gunnar Palsson, Olafur A. Stefansson, Gudmundur Eyjolfsson, Isleifur Olafsson, Olof Sigurdardottir, Bjarni Torfason, Gisli Masson, Agnar Helgason, Unnur Thorsteinsdottir, Hilma Holm, Daniel F. Gudbjartsson, Patrick Sulem, Olafur T. Magnusson, Bjarni V. Halldorsson, Kari Stefansson
Journal: Nature Genetics (2021)
In vivo fitness of carbapenem-resistant Acinetobacter baumannii strains in murine infection is associated with treatment failure in human infections
Authors: Amir Nutman, Elizabeth Temkin, Jonathan Lellouche, Nadya Rakovitsky, Amichay Hameir, George Daikos, Emanuele Durante-Mangoni, Ioannis Pavleas, Yael Dishon, Neta Petersiel, Dafna Yahav, Noa Eliakim, Mariano Bernardo, Domenico Iossa, Lena E. Friberg, Ursula Theuretzbacher, Leonard Leibovici, Mical Paul, Yehuda Carmeli, Mical Paul, Yael Dishon Benattar, Yaakov Dickstein, Roni Bitterman, Hiba Zayyad, Fidi Koppel, Yael Zak-Doron, Sergey Altunin, Nizar Andria, Ami Neuberger, Anat Stern, Neta Petersiel, Marina Raines, Amir Karban, Leonard Leibovici, Dafna Yahav, Noa Eliakim-Raz, Oren Zusman, Michal Elbaz, Heyam Atamna, Vered Daitch, Tanya Babich, Yehuda Carmeli, Amir Nutman, Amos Adler, Inbar Levi, George L. Daikos, Anna Skiada, Ioannis Pavleas, Anastasia Antoniadou, Antigoni Kotsaki, Emanuele Durante-Mangoni, Roberto Andini, Domenico Iossa, Mariano Bernardo, Giusi Cavezza, Lorenzo Bertolino, Giuseppe Giuffre, Roberto Giurazza, Giuseppe Ruocco, Maria Galdo, Patrizia Murino, Adriano Cristinziano, Antonio Corcione, Rosa Zampino, Johan Mouton, Lena Friberg, Ursula Theuretzbacher
Journal: Clinical Microbiology and Infection (2021)
Ursolic acid reverses liver fibrosis by inhibiting NOX4/NLRP3 inflammasome pathways and bacterial dysbiosis
Authors: Yuan Nie, Qi Liu, Wang Zhang, Yipeng Wan, Chenkai Huang, Xuan Zhu
Journal: Gut Microbes (2021)

Activation of the NOX4/NLRP3 inflammasome pathway has been associated with fibrosis in other organs. An imbalance in intestinal bacteria is an important driving factor of liver fibrosis through the liver-gut axis. This study aimed to explore whether the effect of ursolic acid (UA) on liver fibrosis was associated with the NOX4/NLRP3 inflammasome pathways and intestinal bacteria. Wild-type (WT), NLRP3−/-, and NOX4−/- mice and AP-treated mice were injected with CCI4 and treated with or without UA. The intestinal contents of the mice were collected and analyzed by 16S rRNA sequencing. UA alleviated liver fibrosis, which manifested as decreases in collagen deposition, liver injury, and the expression of fibrosis-related factors, and the expression of NOX4 and NLRP3 was significantly inhibited by UA treatment. Even after CCI4 injection, liver damage and fibrosis-related factors were significantly decreased in NLRP3−/-, NOX4−/-, and AP-treated mice. Importantly, the expression of NLRP3 was obviously inhibited in NOX4−/- and AP-treated mice. In addition, the diversity of intestinal bacteria and the abundance of probiotics in NLRP3−/- and NOX4−/- mice was significantly higher than those in WT mice, while the abundance of harmful bacteria in NLRP3−/- and NOX4−/- mice was significantly lower than that in WT mice. The NOX4/NLRP3 inflammasome pathway plays a crucial role in liver fibrosis and is closely associated with the beneficial effect of UA. The mechanism by which the NOX4/NLRP3 inflammasome pathway is involved in liver fibrosis may be associated with disordered intestinal bacteria.
Abstract P176: Proportionate Cardiovascular Mortality Patterns Among Patients With Inflammatory Disease In The United States, 1999-2018
Authors: Jacob Groenendyk, Arjun Sinha, Adovich Rivera, Matthew J Feinstein
Journal: Circulation (2021)

Introduction: Novel therapies have changed the clinical course of several chronic viral and inflammatory conditions over the past two decades. As the morbidity burden of these conditions has changed, competing risks for end-organ diseases including cardiovascular diseases (CVDs) may have likewise evolved. We therefore aimed to investigate changes in the relative burden of CVD mortality over the past two decades across several chronic infectious and inflammatory conditions. Hypothesis: Changes in proportionate CVD-related mortality over the past two decades differ across distinct infectious and inflammatory conditions. Methods: We analyzed 1999-2018 Multiple Causes of Death data from the Centers of Disease Control and Prevention. For several chronic infectious and inflammatory conditions, we analyzed patterns in age-adjusted cardiovascular proportionate mortality, defined as the fraction of deaths in a calendar year with CVD as the underlying cause. We compared age-adjusted proportionate CVD mortality, stratified by sex, for systemic lupus erythematosus (SLE), hepatitis C virus (HCV), human immunodeficiency virus (HIV), inflammatory bowel disease (IBD), psoriasis (PSO), rheumatoid arthritis (RA), and systemic sclerosis (SSc). Results: Proportionate CVD mortality in the general population decreased from 40.9% of 2319606 deaths (1999) to 30.6% of 2778169 deaths (2018), whereas it increased for chronic viral conditions (HCV: 7.0% to 10.2%; HIV: 1.9% to 6.7%) and changed little in SLE (15.3% to 14.4%). Patterns of decreasing proportionate CVD mortality over time were similar for IBD and RA as in the general population. Conclusions: Patterns in proportionate CVD mortality over the past 20 years vary considerably for different chronic infectious and inflammatory conditions. The underlying contributions of infectious and inflammatory burden, off-target effects of therapies, and dynamic changes in competing mortality risk merit further study.
43O Pertuzumab/trastuzumab in early stage HER2-positive breast cancer: 5-year and final analysis of the BERENICE trial
Authors: C. Dang, M.S. Ewer, S. Delaloge, J-M. Ferrero, R. Colomer, L. de la Cruz Merino, K. Dadswell, M. Verrill, D. Eiger, S. Sarkar, S. de Haas, E. Restuccia, S.M. Swain
Journal: Annals of Oncology (2021)
Abstract 13862: Testing of a Health-related Quality of Life Model
Authors: Seongkum Heo, Terry A Lennie, Debra K Moser, Sandra B Dunbar, Susan J Pressler,, JinShil Kim
Journal: Circulation (2020)

Introduction: In patients with heart failure (IHF), health-related quality of life (HRQOL) is as important as longer survival. Deaths are inevitable for all human beings, but clinicians may help patients with HF to maintain or improve HRQOL until almost at the end of their lives. Psychological and physical symptoms can impact HRQOL through different pathways, and behavioral factors can indirectly impact HRQOL, but the relationships have not been tested in prior theoretical models. Hypothesis: Sociodemographic (i.e., age), biological/physiological (i.e., comorbidity), psycho-social (i.e., depressive symptoms and social support), physical (i.e., physical symptoms and functional status), and behavioral factors (i.e., dietary adherence) in Heo-Moser model will be associated with HRQOL directly and indirectly in patients with HF through different pathways. Methods: This is a secondary analysis of baseline data from two observational studies in which baseline data were collected using the same instruments (N = 358 patients with HF, mean age: 60.4 years). Structural equation modeling (SEM) was used to test the hypothesis. Results: In the SEM, the analysis showed desirable model fit: Chi-square = 7.710, p = .260, RMSEA = .028 (95% confidence interval = 0.00, 0.078), CFI = 0.998, TLI = 0.989, and SRMR = 0.023. Age, depressive symptoms, physical symptoms, and functional status were directly associated with HRQOL. Age, comorbidity, depressive symptoms, social support, dietary adherence, and physical symptoms were indirectly associated with HRQOL through different pathways (Figure 1). Conclusions: All the factors in the model were directly and/or indirectly associated with HRQOL through different pathways. The pathways of physical symptoms, depressive symptoms, and dietary adherence differed. This model can be used to develop interventions targeting improvement in HRQOL in patients with chronic diseases.
Abstract 14814: By Stanza or Story, the Structure of a Poem
Authors: Timothy F Simpson, Babak Nazer, Punag Divanji
Journal: Circulation (2020)

A 63-year-old male with recent diagnosis of idiopathic pericarditis presented to the hospital with atrial fibrillation and rapid ventricular rates. He reported one week of palpitations and subacute lower extremity weakness. On exam he was hemodynamically stable with evidence of intra- and extravascular fluid overload. Lab analysis showed elevated creatinine, inflammatory markers, and serum protein gap. Chest radiograph showed bilateral pleural effusions and a focal sclerotic thoracic vertebra. TTE revealed mildly reduced biventricular function, elevated RVSP, and moderate pericardial effusion. The presence of pericardial and pleural effusions with elevated inflammatory markers suggest serositis, and a differential of malignant, autoimmune, and infectious etiologies were considered. Hepatosplenomegaly was noted on CT imaging. Blood, pleural, and pericardial cultures revealed no growth and autoimmune serologies were negative. Given these findings- the differential was narrowed to lymphoma, myeloma with or without amyloidosis, and paraneoplastic syndromes. Electrophoresis revealed presence of an M protein, fat pad biopsy was negative for amyloid fibrils. Bone marrow biopsy revealed an abnormal plasma cell population and biopsy of sclerotic vertebra showed no malignancy. Whole body FDG PET showed no focal uptake in the heart nor elsewhere. VEGF levels were significantly elevated. On the basis of the plasma cell dyscrasia, polyneuropathy, sclerotic bone lesion, elevated VEGF level, hepatosplenomegaly, and pericardial effusion the patient was diagnosed with POEMS syndrome- an extremely rare paraneoplastic syndrome with multisystemic end-organ effects. Cardiac manifestations are infrequent, but include pericardial effusion, myocardial edema and dysfunction, pulmonary hypertension, and volume overload. No specific cardiac therapy exists, but involvement may regress with chemotherapy for treatment of the underlying malignancy. This case demonstrates the importance of recognizing cardiac manifestations as the initial or cardinal presentation of underlying systemic disease, where accurate diagnosis may rely on identification of subtle non-cardiac symptoms, laboratory, and imaging findings as demonstrated here.
Molecular ultrasound imaging of neutrophil membrane-derived biomimetic microbubbles for quantitative evaluation of hepatic ischemia-reperfusion injury
Authors: Zheng Zhang, Xiaoyan Miao, Weifeng Yao, Jie Ren, Chaojin Chen, Xiang Li, Jing Yang, Yujia You, Yuejun Lin, Tinghui Yin, Ziqing Hei
Journal: Theranostics (2021)

Rationale: Early diagnosis of hepatic ischemia-reperfusion injury (HIRI), the major cause of early allograft dysfunction or primary non-function, is critical in orthotopic liver transplantation. However, liver biopsy is still the primary method for HIRI evaluation in clinical practice despite its numerous complications and shortcomings such as hemorrhage and inaccuracy. Herein, we aimed to develop a non-invasive, highly accurate, and specific method for detecting HIRI. Methods: We developed a top-down and bottom-up strategy to fabricate neutrophil biomimetic microbubbles (MBneu). Neutrophil membrane was mixed with liposomes at a defined mass ratio by sonication. The air in the vial was exchanged with perfluoropropane, and then the solution was mechanically vibrated to form MBneu. Results: MBneu retained the neutrophil proteins, preferentially targeted inflamed hepatic tissue in a rat model of HIRI, and demonstrated physicochemical properties typical of liposome-based MBs because of its artificial phospholipid content. With MBneu we can quantitively evaluate the severity of HIRI, which is helpful for early diagnosis and the prediction of outcome. In addition, MBneu was shown to be safe and showed no immunogenicity. Conclusion: We demonstrated molecular ultrasound imaging of HIRI with MBneu. This new synthesis strategy may be applied to different clinical scenarios using other cell types in the future.
Arginase II protein regulates Parkin-dependent p32 degradation that contributes to Ca2+-dependent eNOS activation in endothelial cells
Authors: Bon-Hyeock Koo, Moo-Ho Won, Young-Myeong Kim, Sungwoo Ryoo
Journal: Cardiovascular Research (2021)

Abstract Aims Arginase II (ArgII) plays a key role in the regulation of Ca2+ between the cytosol and mitochondria in a p32-dependent manner. p32 contributes to endothelial nitric oxide synthase (eNOS) activation through the Ca2+/CaMKII/AMPK/p38MAPK/Akt signalling cascade. Therefore, we investigated a novel function of ArgII in the regulation of p32 stability. Methods and results mRNA levels were measured by quantitative reverse transcription-PCR, and protein levels and activation were confirmed by western blot analysis. Ca2+ concentrations were measured by FACS analysis and a vascular tension assay was performed. ArgII bound to p32, and ArgII protein knockdown using siArgII facilitated the ubiquitin-dependent proteasomal degradation of p32. β-lactone, a proteasome inhibitor, inhibited the p32 degradation associated with endothelial dysfunction in a Ca2+-dependent manner. The amino acids Lys154, Lys 180, and Lys220 of the p32 protein were identified as putative ubiquitination sites. When these sites were mutated, p32 was resistant to degradation in the presence of siArgII, and endothelial function was impaired. Knockdown of Pink/Parkin as an E3-ubiquitin ligase with siRNAs resulted in increased p32, decreased [Ca2+]c, and attenuated CaMKII-dependent eNOS activation by siArgII. siArgII-dependent Parkin activation was attenuated by KN93, a CaMKII inhibitor. Knockdown of ArgII mRNA and its gene, but not inhibition of its activity, accelerated the interaction between p32 and Parkin and reduced p32 levels. In aortas of ArgII−/− mice, p32 levels were reduced by activated Parkin and inhibition of CaMKII attenuated Parkin-dependent p32 lysis. siParkin blunted the phosphorylation of the activated CaMKII/AMPK/p38MAPK/Akt/eNOS signalling cascade. However, ApoE−/− mice fed a high-cholesterol diet had greater ArgII activity, significantly attenuated phosphorylation of Parkin, and increased p32 levels. Incubation with siArgII augmented p32 ubiquitination through Parkin activation, and induced signalling cascade activation. Conclusion The results suggest a novel function for ArgII protein in Parkin-dependent ubiquitination of p32 that is associated with Ca2+-mediated eNOS activation in endothelial cells.
Expanding CRISPR Genome Editing Strategies in Hematopoietic Stem and Progenitor Cells for the Treatment of Hematologic Diseases
Authors: Edouard deDreuzy, Aditi Chalishazar, Jack Heath, Carrie M Margulies, John Labella, Ramya Viswanathan, Katherine Loveluck, KaiHsin Chang, Hariharan Jayaram, John A Zuris, Vic E Myer, Charlie Albright, Cecilia Cotta-Ramusino, Jennifer L Gori
Journal: Blood (2017)