tbuckley/cabot-search huggingface dataset:
Abstract 12989: Long-term Prognostic Value of Fibrosis-4 Index and Albumin-bilirubin Score in Patients Admitted for Acute Decompensated Heart Failure
Authors: Takahisa Yamada, Tetsuya Watanabe, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Masato Kawasaki, Atsushi Kikuchi, Tsutomu Kawai, Masahiro Seo, Jun Nakamura, Kiyomi Kayama, Masatsugu Kawahira, Kumpei Ueda, Takanari Kimura, Daisuke Sakamoto, Masatake Fukunami
Journal: Circulation (2020)

Backgrounds: Cardiohepatic interactions have been a focus of attention among heart failure (HF). It was reported that liver stiffness assessed by non-invasive fibrosis marker such as Fibrosis-4(FIB4) index provide prognostic information in HF patients. Furthermore, the albumin-bilirubin (ALBI) score has recently been proposed as a validated index of liver dysfunction. We sought to investigate the long-term prognostic values of the combination of FIB4 index and ALBI score in patients admitted for acute decompensated heart failure (ADHF). Methods and Results: We studied 299 ADHF pts with survival discharge. FIB4 index was calculated by the formula: age(yrs) х AST[U/L]/(platelets [10 3 /μL] х (ALT[U/L]) 1/2 ). The ALBI was calculated using the formula: log 10 (total bilirubin) х 0.66 + albuminх-0.085. During a follow-up period of 4.3±3.3 yrs, 94 patients died. At multivariate Cox analysis, FIB4 index and ALBI score were significantly associated with total mortality, independently of prior HF hospitalization and body mass index after adjustment with systolic blood pressure, left ventricular end-diastolic dimension and left atrial dimension indexes. Patients with both greater FIB4 index (&gt;3.608: top tertile) and ALBI score (&gt;-2.076:top tertile) had a significantly higher risk of total mortality than those with either or none of them (46% vs 34% vs 25%, respectively, p=0.002). Conclusion: The combination of FIB4 index and ALBI score might identify higher risk subset for total mortality in ADHF patients.
Abstract 16130: Plasma Proteomic Analysis of Association Between Atrial Fibrillation, Coronary Microvascular Disease and Heart Failure
Authors: Cevher Ozcan, GUNJAN DIXIT, John Blair
Journal: Circulation (2020)

Introduction: Atrial fibrillation (AF) commonly occurs in patients with heart failure with preserved ejection fraction (HFpEF). Recent studies showed a high prevalence of coronary microvascular dysfunction (CMD) in patients with HFpEF and a likely association with AF. Yet, the biomarkers and mechanisms of their association have not been characterized. Hypothesis: Plasma proteomic analysis can identify novel biomarkers of the association between AF, CMD and HFpEF, and mechanistic pathways of their association. Methods: We studied the plasma samples from the patients with AF, CMD and/or HFpEF. Liquid chromatography-mass spectrometry based untargeted and label-free quantification proteomic analysis was performed. Circulating plasma proteins were screened to determine candidate biomarkers and the mutual mechanistic pathways in these disease processes. Results: We identified 130 dysregulated proteins across the groups with the independent patient replicates. Discovery-based untargeted plasma proteomic analysis identified 35 proteins in association with AF, CMD and HFpEF candidate biomarkers of their association (Fig). SAA1, LRG1 and APOC3 were significantly elevated in the coexistence of AF, CMD and HFpEF. LCP1, PON1 and C1S were markedly downregulated in their associations. Combined downregulation of PON1 and C1S was a marker of the HFpEF and CMD. Low PON1 was associated with HFpEF. Low C1S was a marker of CMD. Reduced levels of LCP1, KLKB1 and C4A were associated with AF in patients with CMD and HFpEF. These dysregulated proteins are associated with inflammatory processes, coagulation pathways, oxidative stress, metabolism, complement system and extracellular matrix remodeling. Conclusions: Plasma proteomic profile provides biomarkers and mechanistic insight into the association of AF, CMD and HFpEF. Circulation dysregulated proteins can be clinically useful for risk stratification.
Abstract 13147: Non-invasive Identification of Carditis in Acute Rheumatic Fever and Rheumatic Heart Disease
Authors: Sarah J Gutman, Benedict T Costello, Melissa G van Leeuwen, Jessica O'Brien, Seeba E Varghese, Leah Wright, Stephen Brady, Christopher Wong, Graeme Maguire, Thomas H Marwick, Andrew J Taylor
Journal: Circulation (2020)

Background: The pathogenesis of acute rheumatic fever (ARF) and its evolution into rheumatic heart disease (RHD) is poorly understood. We aimed to identify carditis in patients with ARF and RHD using cardiac magnetic resonance (CMR) tissue characterisation with T1 mapping. We hypothesised that prolonged native T1 time on CMR, would be present in ARF and RHD patients. Methods: We prospectively recruited 62 patients. We recruited 16 patients fulfilling the Jones Criteria for the diagnosis of ARF, 15 controls with an inflammatory condition and 10 healthy controls. We also recruited 11 patients with echocardiographic evidence of RHD and 10 matched controls. All patients underwent CMR with assessment of non-contrast myocardial T1 mapping. The myocardial T1 time, as an index of myocardial inflammation from carditis, was compared between the groups. All T1 times were converted to Z-scores, to enable comparison with different CMR systems. Findings: Patients with ARF had evidence of carditis demonstrated by markedly elevated mean myocardial T1 times. The mean Z score was 2.76(95% CI 1.34-4.17) for patients with ARF compared to 0.32(95% CI -0.25-0.88) for those with non-cardiac inflammatory conditions and 0.00(95% CI -0.72-0.72) for healthy controls, P=0.004. A myocardial T1 Z score greater than 1.4 showed excellent diagnostic performance as a single test for the diagnosis of ARF (AUC = 0.85[0.67-0.99], P=0.001, sensitivity = 82 %, specificity = 92%, Youden’s J = 0.74). Patients with RHD also demonstrated significantly elevated native T1 time compared to matched controls. The mean Z score for RHD patients was 2.79(95% CI 1.3-4.3) compared to 0.00(95% CI -0.72-0.72) in controls, P=0.002. Interpretation: Patients with ARF and RHD have markedly elevated myocardial T1 Z-scores on CMR, consistent with carditis. Incorporating CMR T1 mapping into the diagnostic algorithm for ARF may improve diagnostic certainty and lead to more effective delivery of secondary penicillin prophylaxis.
Abstract 15523: Dynamic Protein S-palmitoylation Contributes to Cardiac Remodeling During Aging With Chronic Hypertension
Authors: Madeleine R Miles, John Seo, Zachary Wilson, Min Jiang, Gea-ny Tseng
Journal: Circulation (2020)

Introduction: More that 10% of human proteins can be S-palmitoylated, a post-translational modification (PTM) whereby palmitoyl chains are covalently linked to cysteine thiol groups. S-palmitoylation influences protein trafficking, distribution and function. There is no information on the scope of protein S-palmitoylation in the heart, or how this enzyme-mediated reversible PTM is regulated. Hypothesis: S-palmitoylation occurs to a wide spectrum of proteins in cardiomyocytes, and is coordinated by membrane-embedded palmitoylating (DHHC) enzymes. DHHC enzymes are subject to remodeling during chronic hypertension. Methods: We used resin-assisted capture to purify S-palmitoylated proteins from ventricular myocardium of 3 species: human, dog, and rat. We used global unbiased proteomic search to identify S-palmitoylated proteins. We validated DHHC antibodies and used them to monitor protein level and subcellular distribution of native DHHC enzymes in ventricular myocytes. Results: We built a 'composite' cardiac palmitome composed of 462 S-palmitoylatable proteins identified in ≥ 2 species-specific cardiac palmitomes. Enrichment analysis based on GO term 'cellular component' indicated that they are mainly involved in cell-cell and cell-substrate associations, sarcolemma and sarcomere organization, vesicular trafficking, G-protein function, ATP-dependent transmembrane transport, and mitochondria inner and outer membrane organization. Among the 23 DHHC enzymes, we detected ten in hearts across species. In ventricular myocytes with well-defined subcellular compartments, DHHC enzymes exhibited distinct distribution patterns: peripheral sarcolemma (DHHC1), M-lines (DHHC2), Z-lines (DHHC5), vesicles (DHHC7) and intercalated disc (DHHC9). In aging spontaneously hypertensive rats (a model of chronic hypertension, some in heart failure), seven DHHC enzymes were upregulated in the heart, accompanied by a higher degree of S-palmitoylation of CaMK II, caveolin3, Na/Ca exchanger, and Na/K pump α-subunit. Conclusion: S-palmitoylation is involved in most, if not all, aspects of cardiomyocyte function. Palmitoylation dysregulation may contribute to pathological progression in hypertrophy leading to heart failure.
Gaza: Israeli airstrikes kill doctors and damage healthcare facilities
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Israeli airstrikes in the Palestinian territory of Gaza have damaged six hospitals, nine primary health care centres, and a desalination plant that supplies clean water to 250 000 people, the United Nations has reported.1

Gaza’s main covid-19 laboratory and the Palestinian Ministry of Health offices have also been hit,2 and at least two prominent doctors, the internal medicine consultant Ayman Abu Alouf, who was leading the covid-19 team at Al Shifa hospital, and the health ministry neurologist Moeen Al-Aloul, have been killed.

The latest escalation in violence was the result of unrest in the West Bank, as pro-settler organisations have been attempting to force Palestinian families from their homes in the Sheikh Jarrah neighbourhood of East Jerusalem, in a move that the United Nations warned could amount to “war crimes.”3

Since the unrest began on 7 May at least 212 Palestinians, including 61 children, have been killed in …
Rotavirus Vaccines—Going Strong After 15 Years
Authors: David I. Bernstein
Journal: JAMA Pediatrics (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 JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Abstract 13169: Depression and Heart Rate Variability in Adults With Cyanotic Congenital Heart Disease
Authors: Ju Ryoung Moon, June Huh, Jinyoung Song, I-Seok Kang, Ji-Hyuk Yang, Tae-Gook Jun, Sung-A Chang, Seung Woo Park
Journal: Circulation (2019)

Introduction: Depression has been shown to have an increased risk for morbidity and mortality in patients with congenital heart disease (CHD). Reduced heart rate variability (HRV) has been investig...
An alternatingly amphiphilic, resistance-resistant antimicrobial oligoguanidine with dual mechanisms of action
Authors: Zhiyong Chen, Cailing Zhou, Yangfan Xu, Kang Wen, Junfeng Song, Silei Bai, Chenxuan Wu, Wei Huang, Qingyun Cai, Kai Zhou, Hui Wang, Yingjie Wang, Xinxin Feng, Yugang Bai
Journal: Biomaterials (2021)
Integrated Environmental and Genomic Analysis Reveals the Drivers of Local Adaptation in African Indigenous Chickens
Authors: Almas A Gheyas, Adriana Vallejo-Trujillo, Adebabay Kebede, Maria Lozano-Jaramillo, Tadelle Dessie, Jacqueline Smith, Olivier Hanotte
Journal: Molecular Biology and Evolution (2021)

Abstract Breeding for climate resilience is currently an important goal for sustainable livestock production. Local adaptations exhibited by indigenous livestock allow investigating the genetic control of this resilience. Ecological niche modeling (ENM) provides a powerful avenue to identify the main environmental drivers of selection. Here, we applied an integrative approach combining ENM with genome-wide selection signature analyses (XPEHH and Fst) and genotype−environment association (redundancy analysis), with the aim of identifying the genomic signatures of adaptation in African village chickens. By dissecting 34 agro-climatic variables from the ecosystems of 25 Ethiopian village chicken populations, ENM identified six key drivers of environmental challenges: One temperature variable—strongly correlated with elevation, three precipitation variables as proxies for water availability, and two soil/land cover variables as proxies of food availability for foraging chickens. Genome analyses based on whole-genome sequencing (n = 245), identified a few strongly supported genomic regions under selection for environmental challenges related to altitude, temperature, water scarcity, and food availability. These regions harbor several gene clusters including regulatory genes, suggesting a predominantly oligogenic control of environmental adaptation. Few candidate genes detected in relation to heat-stress, indicates likely epigenetic regulation of thermo-tolerance for a domestic species originating from a tropical Asian wild ancestor. These results provide possible explanations for the rapid past adaptation of chickens to diverse African agro-ecologies, while also representing new landmarks for sustainable breeding improvement for climate resilience. We show that the pre-identification of key environmental drivers, followed by genomic investigation, provides a powerful new approach for elucidating adaptation in domestic animals.
<i>Bifidobacterium dentium</i>-derived y-glutamylcysteine suppresses ER-mediated goblet cell stress and reduces TNBS-driven colonic inflammation
Authors: Melinda A. Engevik, Beatrice Herrmann, Wenly Ruan, Amy C. Engevik, Kristen A. Engevik, Faith Ihekweazu, Zhongcheng Shi, Berkley Luck, Alexandra L. Chang-Graham, Magdalena Esparza, Susan Venable, Thomas D. Horvath, Sigmund J. Haidacher, Kathleen M. Hoch, Anthony M. Haag, Deborah A. Schady, Joseph M. Hyser, Jennifer K. Spinler, James Versalovic
Journal: Gut Microbes (2021)

Endoplasmic reticulum (ER) stress compromises the secretion of MUC2 from goblet cells and has been linked with inflammatory bowel disease (IBD). Although Bifidobacterium can beneficially modulate mucin production, little work has been done investigating the effects of Bifidobacterium on goblet cell ER stress. We hypothesized that secreted factors from Bifidobacterium dentium downregulate ER stress genes and modulates the unfolded protein response (UPR) to promote MUC2 secretion. We identified by mass spectrometry that B. dentium secretes the antioxidant γ-glutamylcysteine, which we speculate dampens ER stress-mediated ROS and minimizes ER stress phenotypes. B. dentium cell-free supernatant and γ-glutamylcysteine were taken up by human colonic T84 cells, increased glutathione levels, and reduced ROS generated by the ER-stressors thapsigargin and tunicamycin. Moreover, B. dentium supernatant and γ-glutamylcysteine were able to suppress NF-kB activation and IL-8 secretion. We found that B. dentium supernatant, γ-glutamylcysteine, and the positive control IL-10 attenuated the induction of UPR genes GRP78, CHOP, and sXBP1. To examine ER stress in vivo, we first examined mono-association of B. dentium in germ-free mice which increased MUC2 and IL-10 levels compared to germ-free controls. However, no changes were observed in ER stress-related genes, indicating that B. dentium can promote mucus secretion without inducing ER stress. In a TNBS-mediated ER stress model, we observed increased levels of UPR genes and pro-inflammatory cytokines in TNBS treated mice, which were reduced with addition of live B. dentium or γ-glutamylcysteine. We also observed increased colonic and serum levels of IL-10 in B. dentium- and γ-glutamylcysteine-treated mice compared to vehicle control. Immunostaining revealed retention of goblet cells and mucus secretion in both B. dentium- and γ-glutamylcysteine-treated animals. Collectively, these data demonstrate positive modulation of the UPR and MUC2 production by B. dentium-secreted compounds.
A Chromosome-Level Assembly of Blunt Snout Bream (<i>Megalobrama amblycephala</i>) Genome Reveals an Expansion of Olfactory Receptor Genes in Freshwater Fish
Authors: Han Liu, Chunhai Chen, Maolin Lv, Ning Liu, Yafei Hu, Hailin Zhang, Erik D Enbody, Zexia Gao, Leif Andersson, Weimin Wang
Journal: Molecular Biology and Evolution (2021)

Abstract The number of olfactory receptor genes (ORs), which are responsible for detecting diverse odor molecules varies extensively among mammals as a result of frequent gene gains and losses that contribute to olfactory specialization. However, how OR expansions/contractions in fish are influenced by habitat and feeding habit and which OR subfamilies are important in each ecological niche is unknown. Here, we report a major OR expansion in a freshwater herbivorous fish, Megalobrama amblycephala, using a highly contiguous, chromosome-level assembly. We evaluate the possible contribution of OR expansion to habitat and feeding specialization by comparing the OR repertoire in 28 phylogenetically and ecologically diverse teleosts. In total, we analyzed &amp;gt; 4,000 ORs including 3,253 intact, 122 truncated, and 913 pseudogenes. The number of intact ORs is highly variable ranging from 20 to 279. We estimate that the most recent common ancestor of Osteichthyes had 62 intact ORs, which declined in most lineages except the freshwater Otophysa clade that has a substantial expansion in subfamily β and ε ORs. Across teleosts, we found a strong association between duplications of β and ε ORs and freshwater habitat. Nearly, all ORs were expressed in the olfactory epithelium (OE) in three tested fish species. Specifically, all the expanded β and ε ORs were highly expressed in OE of M. amblycephala. Together, we provide molecular and functional evidence for how OR repertoires in fish have undergone gain and loss with respect to ecological factors and highlight the role of β and ε OR in freshwater adaptation.
CD200 Limits Monopoiesis and Monocyte Recruitment in Atherosclerosis
Authors: Christina Kassiteridi, Jennifer E. Cole, Thibault Griseri, Mika Falck-Hansen, Michael E. Goddard, Anusha N. Seneviratne, Patricia A. Green, Inhye Park, Annelie G. Shami, Tanyaporn Pattarabanjird, Aditi Upadhye, Angela M. Taylor, Ashok Handa, Keith M. Channon, Esther Lutgens, Coleen A. McNamara, Richard O. Williams, Claudia Monaco
Journal: Circulation Research (2021)

Rationale: Inflammation is a basic component of the pathogenesis of atherosclerosis. CD200 is an immune checkpoint known to control macrophage activation. CD200 recently emerged in the Framingham Heart Study and 2 other cohorts as being potentially relevant in cardiovascular disease. The role of this pathway in cardiovascular disease is unknown. Objective: We sought to examine the role of CD200 in atherosclerosis. Methods and Results: Using hypercholesterolemic apolipoprotein-E deficient mice, we demonstrate that whole-body CD200 deficiency augments atherosclerotic lesion formation and vulnerability. Administration of a CD200-Fusion protein reduces neointima formation. Our data show that the CD200-CD200R pathway restrains activation of CD200R+ lesional macrophages, their production of CCR2 ligands, and monocyte recruitment in vitro and in vivo in an air pouch model. Loss of CD200 leads to an excessive accumulation of classical Ly6C hi monocytes and CCR2 + macrophages within the atherosclerotic aorta, as assessed by mass cytometry. Moreover, we uncover a previously uncharacterized effect of the CD200/CD200R pathway in limiting dysregulated monopoiesis and Ly6C hi monocytosis in hypercholesterolemic mice. Bone marrow chimera experiments demonstrate that the CD200-CD20R pathway enables 2 complementary and tissue-dependent strategies to limit atherogenesis: CD200 expression by bone marrow–derived cells limits systemic monocytosis, while CD200 expression by nonhematopoietic cells, for example, endothelial cells, prevents local plaque growth. We show that CD200R signaling controls monopoiesis and macrophage activation through inhibiting phosphorylation of STAT1 (signal transducer and activator of transcription 1). Finally, CD200R expression on classical monocytes in peripheral blood of patients with coronary artery disease is associated with a lower burden of coronary artery disease and a more favorable Virtual Histology plaque profile. Conclusions: The CD200 checkpoint is a key-limiting factor for monopoiesis, monocyte-macrophage activation, and recruitment in atherosclerosis with conserved features in human and mouse. It thus offers a novel potential therapeutic pathway to treat cardiovascular disease.
Endothelial cells promote metastatic melanoma cell invasion via alpha(v)beta(3) integrin
Authors: Yukihiko Kato, L. U. Zhang, Roberto Pili
Journal: Cancer Research (2005)

3771  Extravasation of tumor cells through endothelial cells and basement membrane is a critical step in the metastatic process. Melanoma is the most aggressive form of skin cancer. To determine the role of endothelial cell-tumor cell interaction a co-culture dual chamber system was established. Human umbilical vein endothelial cells (HUVECs) were seeded in trans-well inserts (upper chamber) and incubated with melanoma cells. The migration and invasion of metastatic melanoma A2058 cells, a cell line isolated from lymph node metastasis, through HUVECs and matrigel was increased 5-folds as compared to A2058 cells alone (p
Abstract 17415: Mitochondrial Ca2+/Calmodulin-Dependent Kinase II Inhibition Changes the Calcium Homeostasis in the Endothelium and Decreases the Vascular Relaxation in Mesenteric Arteries
Authors: Celio Damacena De Angelis, Daniel W Nuno, Olha Koval, Kathryn G Lamping, Isabella M Grumbach
Journal: Circulation (2020)

Introduction: The Ca2+/Calmodulin-dependent Kinase II (CaMKII) is present in mitochondria and cytosol. In mitochondria, it regulates the mitochondrial Ca 2+ uptake via the mitochondrial Ca2+ uniporter. Since endothelial nitric oxide synthase activity is regulated by intracellular [Ca2+], we hypothesized that it affects cytosolic Ca2+, NO production and ACh-dependent vasodilation. Hypothesis: Inhibition of mitochondrial CaMKII in endothelium increases the cytosolic [Ca2+], and decreases vasorelaxation by Acetylcholine. Methods: CaMKII in mitochondria was inhibited through expression of the mitochondria-targeted CaMKII inhibitor peptide (mito-CaMKIIN) in a novel transgenic mouse model (endo-mtCaMKIIN) in endothelial cells only or delivered by adenoviral transduction (Ad-mtCaMKIIN) in human Aortic Endothelium cells (HAEC). In HAEC, cytosolic Ca2+ levels (by FURA-2 AM), eNOS activation and NOx levels were measured. Results: The basal Ca2+ levels were higher in the cytosol of mitoCaMKIIN cells (1.08 ± 0.02 Fura-2 ratio normalized by control, p&lt;0.05). Thapsigargin-induced ER Ca 2+ release was significantly higher with mitoCaMKIIN (AUC 0.252 ± 0.027 versus 0.112 ± 0.01275, p&lt;0.05), whereas cytosolic Ca 2+ levels after ACh were reduced (AUC 0.191 ± 0.025 versus 0.435 ± 0.054). Higher levels of phosphorylation of eNOS at Ser1177 and Thr495 sites were seen at baseline. The concentration-response curve of vascular relaxation to acetylcholine and SNP shifted to the right (p&lt;0.05) in mesenteric resistance artery of mitoCaMKIIN mice. Conclusions: The inhibition of mitochondrial CaMKII in the endothelium increases the cytosolic levels, endoplasmic reticulum storage of calcium and eNOS phosphorylation. However, there are lower calcium release and lower sensitivity to acetylcholine and SNP.