tbuckley/cabot-search huggingface dataset:
What Ultrasound Can and Cannot Do in Implantable Medical Device Communications
Authors: Banafsaj Jaafar, Jeff Neasham, Patrick Degenaar
Journal: IEEE Reviews in Biomedical Engineering (2021)

Modern Active Medical Implantable Devices require communications to transmit information to the outside world or other implantable sub-systems. This can include physiological data, diagnostics, and parameters to optimise the therapeutic protocol. The available options are to use optical, radiofrequency, or ultrasonic communications. However, in all cases, transmission becomes more difficult with deeper transmission through tissue. Challenges include absorption and scattering by tissue, and the need to ensure there are no undesirable heating effects. As such, this paper aims to review research progress in using ultrasound as an alternative for deep tissue communications. We provide an empirical review of the technology and communication protocols that different groups have used, as well as comparing the implications in terms of penetration depth, implant size, and data rate. We conclude that this technique has promise for deeper implants and for intrabody communications between implantable devices (intrabody networks).
Abstract 15530: Single-cell Analysis in Aortic Aneurysmal Tissue From Patients With Marfan Syndrome Reveals Increased Tgf-beta Production but Downregulation of Downstream Canonical Tgf-beta Signaling Pathways
Authors: Ashley Dawson, Yanming Li, Pingping Ren, Hernan Vasquez, Chen Zhang, Richard Appel, Waleed Ageedi, Wei Luo, Lin Zhang, Yang Li, Mary B Sheppard, Hong S Lu, Lisa A Cassis, Joseph S Coselli, Alan Daugherty, Ying H Shen, Scott A Lemaire
Journal: Circulation (2020)

Background: Marfan syndrome (MFS) is caused by mutations in the gene for fibrillin-1 ( FBN1 ); however, the mechanisms by which these mutations cause aortic aneurysms are poorly understood. Although it was hypothesized previously that dysregulation of the complex TGF-β signaling pathway leads to aortic aneurysm formation, FBN1 mutations appear to have a paradoxical effect on TGF-β signaling in MFS. In this study, we evaluated cell-specific TGF-β expression in non-immune cells in MFS aortic tissue. Methods: We performed single-cell RNA sequencing of ascending aortic aneurysm tissues from MFS patients (n=3) undergoing aneurysm repair and age-matched, non-aneurysmal control tissue from cardiac transplant donors and recipients (n=4). Non-immune cells were separated out from the data and analyzed using the Seurat package in R. Differentially expressed genes were identified using edgeR. Results: Conserved gene expression was used to identify populations of smooth muscle cells (SMCs; n=6), fibroblasts (n=3), and endothelial cells (ECs; n=3). We found that TGFB1 was significantly upregulated in quiescent fibroblasts (identified by increased expression of DCN , LUM , and complement factors) with log2FC of 1.30 and FDR 8.25x10 -8 , as well as in activated fibroblasts (identified by increased expression of genes involved in blood vessel repair and healing including ACTA2 , NOTCH3 , THBS2 , and PDGFRB ) with log2FC of 1.25 and FDR 6.15x10 -22 . Despite this increase in TGFB1 , expression of TGF-β receptor genes (predominately TGFBR2 ) as well as downstream SMAD genes was downregulated significantly in the SMC, fibroblast, and endothelial cell clusters. Finally, genes involved in the non-canonical TGF-β pathway, including ERK , JNK, and p38, were not differentially expressed in non-immune cells in MFS compared with control tissues. Conclusion: Increased expression of TGFB1 in non-immune cells in MFS was driven by two clusters of fibroblasts. Despite this, our data do not support associated upregulation of other genes in the canonical or non-canonical TGF-β pathways and in fact support downregulation of canonical TGF-β signaling in non-immune cells of aneurysmal tissues from MFS patients with advanced aortic disease.
CDK4/6 Inhibition Promotes Antitumor Immunity through the Induction of T-cell Memory
Authors: Emily J. Lelliott, Isabella Y. Kong, Magnus Zethoven, Kelly M. Ramsbottom, Luciano G. Martelotto, Deborah Meyran, Joe Jiang Zhu, Matteo Costacurta, Laura Kirby, Jarrod J. Sandow, Lydia Lim, Pilar M. Dominguez, Izabela Todorovski, Nicole M. Haynes, Paul A. Beavis, Paul J. Neeson, Edwin D. Hawkins, Grant A. McArthur, Ian A. Parish, Ricky W. Johnstone, Jane Oliaro, Karen E. Sheppard, Conor J. Kearney, Stephin J. Vervoort
Journal: Cancer Discovery (2021)

Abstract Pharmacologic inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) are an approved treatment for hormone receptor–positive breast cancer and are currently under evaluation across hundreds of clinical trials for other cancer types. The clinical success of these inhibitors is largely attributed to well-defined tumor-intrinsic cytostatic mechanisms, whereas their emerging role as immunomodulatory agents is less understood. Using integrated epigenomic, transcriptomic, and proteomic analyses, we demonstrated a novel action of CDK4/6 inhibitors in promoting the phenotypic and functional acquisition of immunologic T-cell memory. Short-term priming with a CDK4/6 inhibitor promoted long-term endogenous antitumor T-cell immunity in mice, enhanced the persistence and therapeutic efficacy of chimeric antigen receptor T cells, and induced a retinoblastoma-dependent T-cell phenotype supportive of favorable responses to immune checkpoint blockade in patients with melanoma. Together, these mechanistic insights significantly broaden the prospective utility of CDK4/6 inhibitors as clinical tools to boost antitumor T-cell immunity. Significance: Immunologic memory is critical for sustained antitumor immunity. Our discovery that CDK4/6 inhibitors drive T-cell memory fate commitment sheds new light on their clinical activity, which is essential for the design of clinical trial protocols incorporating these agents, particularly in combination with immunotherapy, for the treatment of cancer. This article is highlighted in the In This Issue feature, p. 2355
Collagen/hyaluronan based hydrogels releasing sulfated hyaluronan improve dermal wound healing in diabetic mice via reducing inflammatory macrophage activity
Authors: Sophia Hauck, Paula Zager, Norbert Halfter, Elke Wandel, Marta Torregrossa, Ainur Kakpenova, Sandra Rother, Michelle Ordieres, Susann Räthel, Albrecht Berg, Stephanie Möller, Matthias Schnabelrauch, Jan C. Simon, Vera Hintze, Sandra Franz
Journal: Bioactive Materials (2021)

Sustained inflammation associated with dysregulated macrophage activation prevents tissue formation and healing of chronic wounds. Control of inflammation and immune cell functions thus represents a promising approach in the development of advanced therapeutic strategies. Here we describe immunomodulatory hyaluronan/collagen (HA-AC/coll)-based hydrogels containing high-sulfated hyaluronan (sHA) as immunoregulatory component for the modulation of inflammatory macrophage activities in disturbed wound healing. Solute sHA downregulates inflammatory activities of bone marrow-derived and tissue-resident macrophages in vitro. This further affects macrophage-mediated pro-inflammatory activation of skin cells as shown in skin ex-vivo cultures. In a mouse model of acute skin inflammation, intradermal injection of sHA downregulates the inflammatory processes in the skin. This is associated with the promotion of an anti-inflammatory gene signature in skin macrophages indicating a shift of their activation profile. For in vivo translation, we designed HA-AC/coll hydrogels allowing delivery of sHA into wounds over a period of at least one week. Their immunoregulatory capacity was analyzed in a translational experimental approach in skin wounds of diabetic db/db mice, an established model for disturbed wound healing. The sHA-releasing hydrogels improved defective tissue repair with reduced inflammation, augmented pro-regenerative macrophage activation, increased vascularization, and accelerated new tissue formation and wound closure.
UCP1 governs liver extracellular succinate and inflammatory pathogenesis
Authors: Evanna L. Mills, Cathal Harmon, Mark P. Jedrychowski, Haopeng Xiao, Ryan Garrity, Nhien V. Tran, Gary A. Bradshaw, Accalia Fu, John Szpyt, Anita Reddy, Hannah Prendeville, Nika N. Danial, Steven P. Gygi, Lydia Lynch, Edward T. Chouchani
Journal: Nature Metabolism (2021)
Abstract 15688: Computational Fluid Dynamics Assessment of Exercise in Patients With Successfully Repaired Coarctation of the Aorta
Authors: Jason G Mandell, Seda Aslan, Yue-hin Loke, Paige N Mass, Vincent Cleveland, Narutoshi Hibino, Axel Krieger, Laura J Olivieri
Journal: Circulation (2020)

Introduction: Patients with coarctation of the aorta (CoA) have decreased exercise capacity even after successful repair with no anatomic obstruction. Our previous work demonstrated a robust negative correlation of aorta size mismatch, defined by ascending (AAo) to descending aorta (DAo) diameter ratio (D AAo /D DAo ), and exercise capacity (VO2 max), suggesting geometry alters arch resistance. This study aims to identify the hemodynamic impact of aorta size mismatch with simulations of rest and exercise using computational fluid dynamics (CFD). Methods: An IRB-approved retrospective chart review identified patients with CoA repair who had a cardiac MRI and exercise stress test within 6 months. Each aorta was segmented and scaled to a body surface area of 1 m 2 . CFD was used to simulate rest (3 L/min/m 2 ) and exercise (9 L/min/m 2 ). Outlet resistance was tuned to match patient-specific DAo flow split derived from in vivo MRI and assumed unchanged for exercise. Power loss was calculated between AAo and DAo and correlated with D AAo /D DAo . Results: The patients (ages 12-41 years, mean 26.8±8.6), had a VO2 max ranging from 47 to 126% predicted (mean 92±20%). Power loss had a significant negative correlation with D AAo /D DAo at rest (p=0.001) and exercise (p&lt;0.01). The ratio of power loss in exercise to rest positively correlated with D AAo /D DAo (p&lt;0.05) (Figure). Conclusions: The relationship of power loss with aorta size mismatch is largely driven by altered flow distribution dependent on AAo and DAo size. There is a disproportionate increase in power loss with exercise compared to rest with a larger aorta size mismatch. This suggests arch geometry independently impacts power loss in exercise which is captured by the measurement of aorta size mismatch and can be a target for optimizing aortic arch repair. Figure: Ratio of power loss in exercise to rest correlates with D AAo /D DAo . Example aortic arches are shown with low power loss (green) and high power loss (red) with corresponding VO2.
Abstract 12936: Impact of Mitral Regurgitation on Heart Failure Hospitalization and Mortality in Older Age Adults With a Preserved Ejection Fraction
Authors: Ginger Y Jiang, Warren J Manning, Lawrence Markson, A. R Garan, Marwa A Sabe, Jordan B Strom
Journal: Circulation (2020)

Background: The effect of mitral regurgitation (MR) severity on heart failure (HF) hospitalization and mortality in individuals with a preserved ejection fraction (LVEF) and no prior HF history is uncertain. Methods: Transthoracic echocardiogram (TTE) reports from patients with an LVEF &gt; 50% at our institution were linked to complete Medicare inpatient claims, 2003-2017. Patients with HF hospitalization within the 12 months prior to TTE were excluded. We evaluated the relationship of baseline MR severity and time to the composite of all-cause mortality or HF hospitalization using the Kaplan-Meier technique. Secondary outcomes included the individual components of all-cause mortality and HF hospitalization, adjusting for the competing risk of death with Fine-Gray methods. Results: A total of 18,315 individuals met inclusion criteria (77.6 ±7.7 years, 54.3% female). Over a median follow-up time of 6.5 (IQR 3.0 to 10.2) years, the primary endpoint occurred in 7566 individuals (50.6%) of whom 6,927 (37.8%) died and 1703 (13.9%) were admitted for HF at a median of 1.4 (IQR 0.2 to 4.3) years and 1.6 (IQR 0.2 to 4.3) years respectively ( Figure ). After multivariable adjustment, MR severity was not associated with the primary or secondary outcome at 1-, 3-, 5-, or 10-years after TTE (p &gt; 0.05 for all). Mitral valve prolapse (MVP) was associated with decreased risk of the primary outcome at 1-year and 3-years (interaction p-value = 0.04 for both). Jet eccentricity did not impact the observed relationship (interaction p-value &gt; 0.05). Conclusions: In this large, single institution echocardiographic study of individuals with preserved ejection fraction and no prior history of HF, MR severity was not associated with an increased risk of all-cause mortality or HF hospitalization. Presence of MVP was associated with decreased risk of the primary outcome with increasing MR severity.
Abstract 16574: Short Term Outcomes With Mitraclip in Women Compared With Men: Evidence From a Meta-analysis
Authors: Yaser Khallid, Neethi Dasu, Kirti Dasu
Journal: Circulation (2020)

Introduction: MitraClip is now approved for severe functional mitral regurgitation in high-risk patients with contraindications to surgical mitral valve repair. Previous studies have shown conflicting results with respect to sex differences in outcomes with the MitraClip. This study sought to examine short-term outcomes with transcatheter mitraclip in women versus men. Hypothesis: Female patients will have higher all-cause mortality, major cardiovascular events, and complications than men following MitraClip. Methods: Electronic search was performed until April 2020 for studies reporting outcomes with MitraClip in women versus men. Random effects DerSimonian-Laird odds ratios were calculated. Outcomes included all-cause mortality and major cardiovascular events at short-term follow-up (in hospital or 30 days) as well as complications. Results: Six studies (4 MitraClip registries; 2344 patients; 925 women) were analyzed. Women were older but exhibited fewer comorbidities. At 30 days, men had more strokes (p &lt; 0.0347) and major vascular complications (p &lt; 0.042), without a difference in all-cause and cardiovascular mortality (OR 1.31, 0.67-2.57, p &lt;0.43) compared with men. There was no difference in pericardial effusion/cardiac tamponade (p &lt;0.311) or acute renal failure (p &lt;0.805). The female survival advantage remained consistent across multiple secondary analyses. The risk of stroke, moderate/severe aortic insufficiency, and all-cause mortality seemed to vary based on the type of valve used; however, without significant subgroup interactions. Conclusions: Despite conflicting data, women experience better short-term outcomes with the MitraClip repair.
Putting the spotlight on macrophage-derived cathepsin in the pathophysiology of obliterative bronchiolitis
Authors: Olivier Brugiere, Stijn E. Verleden
Journal: European Respiratory Journal (2021)

<b>New findings for the puzzle of bronchiolitis obliterans syndrome (BOS) are pointing to the role of CatB-procollagen-TGF-β signalling pathways, linked to fibrosis mechanisms and tissue damage control</b>https://bit.ly/3qQPax9
Abstract 16003: Genetic Variation Associated With Favorable Exercise Response in Patients With Systolic Heart Failure: A Hf-action Trial Substudy
Authors: Sara Coles, Stephanie Giamberardino, Carol Haynes, Ruicong She, Hongsheng Gui, William E Kraus, David E Lanfear, Svati H Shah
Journal: Circulation (2020)

Background: Exercise has shown benefit in patients with systolic heart failure, including in the clinical trial Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION). There is heterogeneity in who derives benefit from exercise, and the biologic mechanisms of favorable response to exercise in systolic heart failure are not well understood. Hypothesis: Genetic variation is an underlying factor influencing heterogeneity in response to exercise in patients with systolic heart failure. Methods: The HF-ACTION trial randomized individuals with systolic heart failure (left ventricular ejection fraction &lt;35%) to supervised exercise versus usual care. In this study, we performed a genome wide association study (GWAS) in the HF-ACTION biorepository using the Axiom Biobank1 genotyping array (13,403,591 single nucleotide polymorphisms [SNPs] after quality control on directly genotyped and 1000 genomes imputed data), in N=377 study subjects who completed the supervised exercise arm. Using change in peak VO2 as our outcome, we ran within-ancestry GWASes, modeling SNP effects as both additive and dominant, and conducted across-ancestry meta-analysis within each genetic model. Results: Five loci met genome-wide significance in the European ancestry analyses, 5 loci in the African ancestry, and 8 in the meta-analyses. The two most significantly associated loci across both additive and dominant meta-analysis models were rs111577308 located in the histone acetylation for transcription elongator complex 3 gene ( ELP3, p=1.212x10 -9 ) and rs75444785 located in the phosphodiesterase 4D gene ( PDE4D , p=1.565x10 -9 ). ELP3 is responsible for histone modifications related to DNA transcription factor complexes, and PDE4D is involved in cyclic AMP cell signaling. In silico analysis of these loci showed that they are in linkage with regions associated with skeletal muscle and peripheral vascular disease phenotypes. Conclusions: Using a genome-wide association study in a well-phenotyped clinical trial of exercise in systolic heart failure, we found common genetic variants in genes involved in DNA transcription histone modification and cyclic AMP cell signaling that are associated with a more favorable response to exercise.
Association Between Achieved ω-3 Fatty Acid Levels and Major Adverse Cardiovascular Outcomes in Patients With High Cardiovascular Risk
Authors: Steven E. Nissen, A. Michael Lincoff, Kathy Wolski, Christie M. Ballantyne, John J. P. Kastelein, Paul M. Ridker, Kausik K. Ray, Darren K. McGuire, Dariush Mozaffarian, Wolfgang Koenig, Michael H. Davidson, Michelle Garcia, Brian G. Katona, Anders Himmelmann, Larrye E. Loss, Matthew Poole, Venu Menon, Stephen J. Nicholls
Journal: JAMA Cardiology (2021)

In patients treated with ω-3 fatty acids, it remains uncertain whether achieved levels of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) are associated with cardiovascular outcomes.
Abstract MP08: Whole Exome Sequencing Study Identified A Novel Variant For Kidney Function And Progression Of Chronic Kidney Disease
Authors: Changwei Li, Michael Francis, Adrianna Westbrook, Ruiyuan Zhang, Ye Shen, Kaixiong Ye, Jing Chen, Jiang He, Tanika N Kelly
Journal: Circulation (2021)

Introduction: Most genetic variants for chronic kidney disease (CKD) have been identified in non-coding regions, with functional roles that are difficult to interpret. Hypothesis: A whole exome sequencing study focusing on coding variants will reveal novel mechanisms of kidney function and CKD. Methods: We performed whole exome sequencing analyses of cystatin C among 29,789 UK Biobank (UKB) participants with further confirmation among 4,297 white and 607 African American participants of the Health and Retirement Study (HRS). Conditional analyses for loci achieving exome-wide significance ( P &lt;3.5х10 -7 ) were conducted in UKB using both the exome (n=29,789) and imputed GWAS data (n=295,122). Genomic findings were tested for relevance to baseline estimated glomerular filtration rate (eGFR) and stringently adjudicated CKD progression events among participants of the Chronic Renal Insufficiency Cohort (CRIC) by race and smoking status, using a base model and a full model ( Table ). Results: We identified a common missense variant, CST9 rs2983640, in a previously reported locus ( CST3 intron rs13038305), of which the minor G allele was associated with lower serum cystatin C level (UKB: beta=-0.03 mg/L, P =7.64х10 -92 ; HRS whites: beta=-0.05 mg/L, P =4.71х10 -6 ; HRS African Americans: beta=-0.03 mg/L, P =0.64; and multi-ethnic meta-analysis beta=-0.03 mg/L, P =2.46х10 -91 ). After controlling for the CST3 variant, the G allele was associated with higher cystatin C level (UKB exome: beta=0.003 mg/L, P =0.04; UKB GWAS: beta=0.003 mg/L, P =1.47х10 -10 ). Similar associations were identified in white CRIC participants (direct effect: beta=-0.05 mg/L, P =0.005; conditional effect: beta=0.004 mg/L, P =0.86). The CST9 rs2983640 G allele was associated with lower baseline eGFR (base model beta=-0.33 ml/min/1.73 m 2 , P =1.98х10 -6 ) and higher hazard of developing CKD progression independent of the reported CST3 variant ( Table ). Conclusions: We identified a novel missense variant influencing cystatin C level and CKD progression.
Seroconversion and dynamics of the anti-SARS-CoV-2 antibody response related to a hospital COVID-19 outbreak among pediatric oncology patients
Authors: Nikolay Mayanskiy, Polina Luchkina, Natalia Fedorova, Yuri Lebedin, Natalia Ponomareva
Journal: Leukemia (2021)

Two recent reports published in Leukemia have described the antibody response to SARS-CoV-2 infection in adult patients with chronic lymphocytic leukemia (CLL) [1] and acute leukemia [2] in conjunction with PCR-confirmed COVID-19.These studies have demonstrated that 14/21 (67%) of the examined CLL patients and 7/8 (88%) of the examined acute leukemia patients produced anti-SARS-CoV-2 IgG antibodies.Importantly, 6 out of 7 IgG-positive acute leukemia patients developed virus-neutralizing antibodies [2], assuming a protective immune response.Here we describe the anti-SARS-CoV-2 antibody response in a cohort of pediatric oncology patients with PCR-confirmed COVID-19, who became infected during an outbreak at the hemato-oncology department of the Russian children clinical hospital, Pirogov Russian National Research Medical University, at the end of April, 2020.This study enrolled 18 patients with neoplasms (16 patients with acute lymphoblastic leukemia (ALL) in remission and two patients with a brain tumor) receiving multidrug chemotherapy.The median age was 8.2 years (IQR 7.8).All patients with ALL received consolidation chemotherapy based on the local protocol ALL-MB-2015, which included daunorubicin, L-asparaginase, and methotrexate.All patients were tested SARS-CoV-2 PCR-positive on April
Pathophysiology and Therapeutic Approaches to Acute Decompensated Heart Failure
Authors: Joyce N. Njoroge, John R. Teerlink
Journal: Circulation Research (2021)

Acute decompensated heart failure (ADHF) is one of the leading admission diagnoses worldwide, yet it is an entity with incompletely understood pathophysiology and limited therapeutic options. Patients admitted for ADHF have high in-hospital morbidity and mortality, as well as frequent rehospitalizations and subsequent cardiovascular death. This devastating clinical course is partly due to suboptimal medical management of ADHF with persistent congestion upon hospital discharge and inadequate predischarge initiation of life-saving guideline-directed therapies. While new drugs for the treatment of chronic HF continue to be approved, there has been no new therapy approved for ADHF in decades. This review will focus on the current limited understanding of ADHF pathophysiology, possible therapeutic targets, and current limitations in expanding available therapies in light of the unmet need among these high-risk patients.