tbuckley/cabot-search huggingface dataset:
Cardiovascular Effects of Intravenous Triiodothyronine in Patients Undergoing Coronary Artery Bypass Graft Surgery
Authors: Elliott Bennett-Guerrero
Journal: JAMA (1996)

<h3>Objective.</h3> —To test the hypothesis that triiodothyronine (T<sub>3</sub>) administration improves hemodynamic variables and decreases inotropic drug requirements in cardiac surgery patients. <h3>Design.</h3> —Prospective, randomized, double-blind, placebo-controlled trial. <h3>Setting.</h3> —Tertiary care medical center. <h3>Patients.</h3> —A total of 211 patients undergoing coronary artery surgery at high risk for requiring inotropic drug support. <h3>Intervention.</h3> —At release of aortic cross-clamp, patients were randomized to an intravenous infusion of T<sub>3</sub>(0.8 μg/kg followed by 0.12 μg·kg<sup>-1</sup>·h<sup>-1</sup>for 6 hours), dopamine (positive control, 5 μg·kg<sup>-1</sup>·min<sup>-1</sup>for 6 hours), or placebo. <h3>Main Outcome Measures.</h3> —Perioperative hemodynamic variables, inotropic support requirements, and serum T<sub>3</sub>concentrations. <h3>Results.</h3> —Mean±SEM free T<sub>3</sub>serum concentrations decreased significantly during cardiopulmonary bypass in all groups (from 0.0035±0.0001 nmol/L [0.23±0.01 ng/dL] to 0.001±0.0001 nmol/L [0.07±0.00 ng/dL];<i>P</i>=001) and increased to 0.0133±0.0004 nmol/L [0.87±0.03 ng/dL] (twice normal range;<i>P</i>&lt;.001) following initiation of intravenous T<sub>3</sub>. Intravenous T<sub>3</sub>did not change hemodynamic variables or inotropic drug requirements; however, heart rate increased (<i>P</i>&lt;.001), and a trend toward decreased use of inotropic agents was demonstrated in the dopamine group. <h3>Conclusions.</h3> —Triiodothyronine administration prevents decreases in serum thyroid hormone concentrations associated with cardiopulmonary bypass. Intravenous T<sub>3</sub>does not have dramatic effects on hemodynamic variables in this setting as has been previously suggested. Although mild effects on myocardial performance may exist, we cannot recommend at this time the routine use of intravenous T<sub>3</sub>as an inotropic agent in patients undergoing coronary artery bypass graft surgery. (<i>JAMA</i>. 1996;275:687-692)
Erosive Hand Osteoarthritis: Incidence and Predictive Characteristics Among Participants in the Osteoarthritis Initiative
Authors: Timothy E. McAlindon, Jeffrey B. Driban, Mary B. Roberts, Jeffrey Duryea, Ida K. Haugen, Lena F. Schaefer, Stacy E. Smith, Alexander Mathiessen, Charles Eaton
Journal: Arthritis & Rheumatology (2021)

To evaluate age, sex, race, osteoarthritis (OA) severity, metabolic factors, and bone health as risk factors for erosive hand OA at baseline and its incidence over a 48-month period.This was a longitudinal cohort study that included participants from the Osteoarthritis Initiative (OAI) with complete hand radiographs from baseline and 48-month visits who were eligible at baseline for incident erosive hand OA (i.e., had or were at risk for knee OA [criterion for OAI inclusion] and did not currently have erosive hand OA). Individuals were classified as having erosive hand OA if the Kellgren/Lawrence (K/L) grade was ≥2 in at least 1 interphalangeal joint on 2 different fingers and central erosion was present in at least 1 joint.Of the 3,365 individuals without prevalent erosive hand OA at baseline, 86 (2.6%) developed erosive hand OA during the 48-month period. Risk factors included older age (relative risk [RR] per SD 1.63 [95% confidence interval 1.35-1.97]), female sex (RR 2.47 [95% confidence interval 1.52-4.02]), greater OA severity (sum K/L grade 13.9 versus 5.3; P < 0.001), and less cortical width (1.38 mm versus 1.52 mm; P < 0.001). After 48 months, subjects who had developed erosive hand OA were characterized by greater progression of radiographic OA (i.e., joint space narrowing, K/L grade progression [RR 1.35], and loss of cortical thickness [RR 1.23]), adjusted for age, sex, race, body mass index, and baseline OA severity (sum K/L grade).These findings demonstrate that erosive hand OA is more common in older women and is strongly associated with severity of articular structural damage and its progression. Individuals who develop erosive hand OA have thinner bones prior to erosive hand OA development and as it progresses, suggesting that erosive hand OA is a disorder of skeletal frailty.
Rectal organoid morphology analysis (ROMA) as a promising diagnostic tool in cystic fibrosis
Authors: Senne Cuyx, Anabela Santo Ramalho, Nikky Corthout, Steffen Fieuws, Eva Fürstová, Kaline Arnauts, Marc Ferrante, Catherine Verfaillie, Sebastian Munck, Mieke Boon, Marijke Proesmans, Lieven Dupont, Kris De Boeck, François Vermeulen
Journal: Thorax (2021)

Diagnosing cystic fibrosis (CF) when sweat chloride is not in the CF range and less than 2 disease-causing CFTR mutations are found requires physiological CFTR assays, which are not always feasible or available. We developed a new physiological CFTR assay based on the morphological differences between rectal organoids from subjects with and without CF. In organoids from 167 subjects with and 22 without CF, two parameters derived from a semi-automated image analysis protocol (rectal organoid morphology analysis, ROMA) fully discriminated CF subjects with two disease-causing mutations from non-CF subjects (p&lt;0.001). ROMA, feasible at all ages, can be centralised to improve standardisation.
KSHV reactivation in post-transplant Kaposi sarcoma (multiple letters)
Authors: Carlo Parravicini, Chiara Scalamogna, Sara Calattini, Francesca Poli, Mario Scalamogna, Massimo Galli, Mauro Moroni, Mario Corbellino, Mario Luppi, Patrizia Barozzi, Fabio Facchetti, Thomas F. Schulz, Giuseppe Torelli
Journal: Nature Medicine (2003)
RB/E2F1 as a Master Regulator of Cancer Cell Metabolism in Advanced Disease
Authors: Amy C. Mandigo, Wei Yuan, Kexin Xu, Peter Gallagher, Angel Pang, Yi Fang Guan, Ayesha A. Shafi, Chellappagounder Thangavel, Beshara Sheehan, Denisa Bogdan, Alec Paschalis, Jennifer J. McCann, Talya S. Laufer, Nicolas Gordon, Irina A. Vasilevskaya, Emanuela Dylgjeri, Saswati N. Chand, Matthew J. Schiewer, Josep Domingo-Domenech, Robert B. Den, Jeff Holst, Peter A. McCue, Johann S. de Bono, Christopher McNair, Karen E. Knudsen
Journal: Cancer Discovery (2021)

Abstract Loss of the retinoblastoma (RB) tumor suppressor protein is a critical step in reprogramming biological networks that drive cancer progression, although mechanistic insight has been largely limited to the impact of RB loss on cell-cycle regulation. Here, isogenic modeling of RB loss identified disease stage–specific rewiring of E2F1 function, providing the first-in-field mapping of the E2F1 cistrome and transcriptome after RB loss across disease progression. Biochemical and functional assessment using both in vitro and in vivo models identified an unexpected, prominent role for E2F1 in regulation of redox metabolism after RB loss, driving an increase in the synthesis of the antioxidant glutathione, specific to advanced disease. These E2F1-dependent events resulted in protection from reactive oxygen species in response to therapeutic intervention. On balance, these findings reveal novel pathways through which RB loss promotes cancer progression and highlight potentially new nodes of intervention for treating RB-deficient cancers. Significance: This study identifies stage-specific consequences of RB loss across cancer progression that have a direct impact on tumor response to clinically utilized therapeutics. The study herein is the first to investigate the effect of RB loss on global metabolic regulation and link RB/E2F1 to redox control in multiple advanced diseases. This article is highlighted in the In This Issue feature, p. 2113
Abstract 16172: Cardiac Stim1 Silencing Prevents Physiological Cardiac Hypertrophy and Promotes Pathological Remodeling in Exercised Mice
Authors: Ingrid M Bonilla, Stephen Baine, Andriy Belevych, Sandor Gyorke
Journal: Circulation (2019)

Stromal interaction molecule 1 (STIM1) is a mediator of store-operated Ca entry (SOCE) involved in pathological hypertrophic growth of cardiac myocytes. However, it is unknown whether STIM1 promote...
ICOS signaling limits regulatory T cell accumulation and function in visceral adipose tissue
Authors: Kristen L. Mittelsteadt, Erika T. Hayes, Daniel J. Campbell
Journal: The Journal of Experimental Medicine (2021)

A unique population of Foxp3+ regulatory T cells (TRs) resides in visceral adipose tissue (VAT) that regulates adipose inflammation and helps preserve insulin sensitivity. Inducible T cell co-stimulator (ICOS) is highly expressed on effector (e)TRs that migrate to nonlymphoid tissues, and contributes to their maintenance and function in models of autoimmunity. In this study, we report an unexpected cell-intrinsic role for ICOS expression and downstream phosphoinositide 3-kinase (PI3K) signaling in limiting the abundance, VAT-associated phenotype, and function of TRs specifically in VAT. Icos−/− mice and mice expressing a knock-in form of ICOS that cannot activate PI3K had increased VAT-TR abundance and elevated expression of canonical VAT-TR markers. Loss of ICOS signaling facilitated enhanced accumulation of TRs to VAT associated with elevated CCR3 expression, and resulted in reduced adipose inflammation and heightened insulin sensitivity in the context of a high-fat diet. Thus, we have uncovered a new and surprising molecular pathway that regulates VAT-TR accumulation and function.
원저 : 만성 B 형 간염에서 HBsAg 및 HBcAg 의 간세포 내 발현양상과 병리조직학적 소견과의 상관관계
Authors: 조광범(Kwang Bum Cho), 손정호(Jung Ho Sohn), 박경식(Kyung Sik Park), 권두영(Du Young Kwon), 황재석(Jae Seok Hwang), 허정욱(Jung Wook Hur), 안성훈(Sung Hoon Ahn), 박승국(Soong Kuk Park), 김상표(Sang Pyo Kim)
Journal: Clinical and Molecular Hepatology (2001)

Background / Aims : The purpose of this study was to assess the correlation between histologic activity and fibrosis and the distribution of intrahepatic hepatitis B core antigen(HBcAg) and surface antigen(HBcAg ) inpatients with chronic hepatitis B . Methods : 141 patients(M:F=141:27) with biopsy-proven chronic hepatitis B ,abnormal liver function, and a positive HBV viral marker(serum HBeAg , serum HBV DNA) were enrolled. Results : HBcAg was expressed in 96 of 141 patoents(68.1%), n HBcAg in 23(16.3%), c HBcAg in 58(41.25), and n-c HBcAg in 15(10.6%). In the cases of HBsAg, 114 of 141 patients(80.9%) were expressed as c HBsAg, 2(1.4%) as m HBsAg, and 16(11,3%) as m-c HBsAg. The presence of intrahepatic HBcAg and HBsAg according to gudat`s calssification was not correlated with activity and fibrosis. But the groups with nuckear expression of HBcAg revealed less inflammatory activity (grade, p=0.003), and less fibrotic stage(p=0.002) than with cytoplasmic or no expression of HBcAg. HBsAg was not. Conclusion : These observations suggest that inflammatory activity and fibrosis of chronic hepatitis B are related to the presence of HBcAg in hepatocytes and the expression of HBcAg. This is a very important finding in hepatocytolysis.
Early Comprehensive Cardiovascular Magnetic Resonance Imaging in Patients With Myocardial Infarction With Nonobstructive Coronary Arteries
Authors: Peder Sörensson, Christina Ekenbäck, Magnus Lundin, Stefan Agewall, Elin Bacsovics Brolin, Kenneth Caidahl, Kerstin Cederlund, Olov Collste, Maria Daniel, Jens Jensen, Shams Y-Hassan, Loghman Henareh, Claes Hofman-Bang, Patrik Lyngå, Eva Maret, Nondita Sarkar, Jonas Spaak, Oscar Winnberg, Martin Ugander, Per Tornvall
Journal: JACC. Cardiovascular imaging (2021)

The objective of the SMINC-2 (Stockholm Myocardial Infarction With Normal Coronaries 2) study was to determine if more than 70% of patients with myocardial infarction with nonobstructed coronary arteries (MINOCA), investigated early with comprehensive cardiovascular magnetic resonance (CMR), could receive a diagnosis entirely by imaging.The etiology of MINOCA is heterogeneous, including coronary, cardiac, and noncardiac causes. Patients with MINOCA, therefore, represent a diagnostic challenge where CMR is increasingly used.The SMINC-2 study was a prospective study of 148 patients with MINOCA imaged with 1.5-T CMR with T1 and extracellular volume mapping early after hospital admission, compared to 150 patients with MINOCA imaged using 1.5-T CMR without mapping techniques from the SMINC-1 study as historic controls.CMR was performed at a median of 3 (SMINC-2) versus 12 (SMINC-1) days after hospital admission. In total, 77% of patients received a diagnosis with CMR imaging in the SMINC-2 study compared to 47% in the SMINC-1 study (p < 0.001). Compared to SMINC-1, CMR in SMINC-2 detected higher proportions of myocarditis (17% vs. 7%; p = 0.01) and takotsubo syndrome (35% vs. 19%; p = 0.002) but similar proportions of myocardial infarction (22% vs. 19%; p = 0.56) and other cardiomyopathies (3% vs. 2%; p = 0.46).The results of the SMINC-2 study show that 77% of all patients with MINOCA received a diagnosis when imaged early with CMR, including advanced tissue characterization, which was a considerable improvement in comparison to the SMINC-1 study. This supports the use of early CMR imaging as a diagnostic tool in the investigation of patients with MINOCA. (Stockholm Myocardial Infarction With Normal Coronaries [SMINC]-2 Study on Diagnosis Made by Cardiac MRI [SCMINC-2]; NCT02318498).
Not all COVID-19 pandemic waves are alike
Authors: Pere Domingo, Virgina Pomar, Isabel Mur, Ivan Castellví, Héctor Corominas, Natividad de Benito
Journal: Clinical Microbiology and Infection (2021)

ObjectiveWe aimed to assess differences in patients' profiles in the first two surges of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Barcelona, Spain.MethodsWe prospectively collected data from all adult patients with SARS-CoV-2 infection diagnosed at the Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. All the patients were diagnosed through nasopharyngeal swab PCR. The first surge spanned from 1st March to 13th August 2020, while surge two spanned from 14th August to 8th December 2020.ResultsThere were 2479 and 852 patients with microbiologically proven SARS-CoV-2 infection in surges one and two, respectively. Patients from surge two were significantly younger (median age 52 (IQR 35) versus 59 (40) years, respectively, p < 0.001), had fewer comorbidities (379/852, 44.5% versus 1237/2479, 49.9%, p 0.007), and there was a shorter interval between onset of symptoms and diagnosis (median 3 (5) versus 4 (5) days, p < 0.001). All-cause in-hospital mortality significantly decreased for both the whole population (24/852, 2.8% versus 218/2479, 8.8%, p < 0.001) and hospitalized patients (20/302, 6.6% versus 206/1570, 13.1%, p 0.012). At adjusted logistic regression analysis, predictors of in-hospital mortality were older age (per year, adjusted odds ratio (aOR) 1.079, 95%CI 1.063–1.094), male sex (aOR 1.476, 95%CI 1.079–2.018), having comorbidities (aOR 1.414, 95%CI 0.934–2.141), ICU admission (aOR 3.812, 95%CI 1.875–7.751), mechanical ventilation (aOR 2.076, 95%CI 0.968–4.454), and coronavirus disease 2019 (COVID-19) during surge one (with respect to surge two) (aOR 2.176, 95%CI 1.286–3.680).ConclusionsFirst-wave SARS-CoV-2-infected patients had a more than two-fold higher in-hospital mortality than second-wave patients. The causes are likely multifactorial.
Hypoxia compromises the mitochondrial metabolism of Alzheimer’s disease microglia via HIF1
Authors: Rosana March-Diaz, Nieves Lara-Ureña, Carmen Romero-Molina, Antonio Heras-Garvin, Clara Ortega-de San Luis, Maria I. Alvarez-Vergara, Manuel A. Sanchez-Garcia, Elisabeth Sanchez-Mejias, Jose C. Davila, Alicia E. Rosales-Nieves, Cristina Forja, Victoria Navarro, Angela Gomez-Arboledas, Maria V. Sanchez-Mico, Adrian Viehweger, Almudena Gerpe, Emma J. Hodson, Marisa Vizuete, Tammie Bishop, Alberto Serrano-Pozo, Jose Lopez-Barneo, Edurne Berra, Antonia Gutierrez, Javier Vitorica, Alberto Pascual
Journal: Nature Aging (2021)
Engrafted Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes Undergo Clonal Expansion In Vivo
Authors: Danny El-Nachef, Darrian Bugg, Kevin M. Beussman, Sonette Steczina, Amy M. Martinson, Charles E. Murry, Nathan J. Sniadecki, Jennifer Davis
Journal: Circulation (2021)
Providing Data to Empower Pregnant Patients to Make Evidence-Based Choices
Authors: Kathryn J. Gray
Journal: JAMA Network Open (2021)

Colin R. Dormuth, ScD; Brandace Winquist, PhD; Anat Fisher, MD, PhD; Fangyun Wu, MSc; Pauline Reynier, MSc; Samy Suissa, PhD; Matthew Dahl, BSc; Zhihai Ma, MSc; Xinya Lu, MPH; Jianguo Zhang, MSc; Colette B. Raymond, PharmD; Kristian B. Filion, PhD; Robert W. Platt, PhD; Carolina Moriello, MSc; J. Michael Paterson, MSc; Canadian Network for Observational Drug Effect Studies (CNODES) Investigators
Understanding Risk Factors for Persistent Opioid Use Among Youths
Authors: Maria H. Rahmandar, Faith Summersett Williams, Lisa M. Kuhns
Journal: JAMA Network Open (2021)

J. Deanna Wilson, MD, MPH; Kaleab Z. Abebe, PhD; Kevin Kraemer, MD, MSc; Jane Liebschutz, MD, MPH; Jessica Merlin, MD, PhD, MBA; Elizabeth Miller, MD, PhD; David Kelley, MD; Julie Donohue, PhD
Abstract 13980: Epidemiological Trends in Hospitalizations of Patients With Marfan Syndrome From 2001 Through 2016
Authors: Ala Mohsen, John Conner, Alhuneafat Laith, Ahmed M Altibi, Ahmad Masri
Journal: Circulation (2019)

Introduction: Marfan syndrome is frequently encountered cause of acute aortic syndromes with worse cardiovascular outcomes and reduced survival. Aim: to determine epidemiological trends in hospital...
Effect of Early Recombinant Human Erythropoietin on Neurodevelopmental Outcomes at Age 5 Years
Authors: Hannelore Ehrenreich, Achim-Peter Neubauer, Kamilla Miskowiak
Journal: JAMA (2021)

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Abstract 16294: Maladaptive Hemodynamic Responses to Sympathetic Activation Play a Pivotal Role in the Pathogenesis of Acute Decompensated Heart Failure
Authors: Takafumi Sakamoto, Keita Saku, Kenji Sunagawa, Hiroyuki Tsutsui
Journal: Circulation (2019)

Introduction: Despite the recent progress in cardiovascular research, the mortality rate of acute decompensated heart failure (ADHF) remains high. Furthermore, the mechanism responsible for the hig...
Emerging genetic complexity and rare genetic variants in neurodegenerative brain diseases
Authors: Federica Perrone, Rita Cacace, Julie van der Zee, Christine Van Broeckhoven
Journal: Genome Medicine (2021)

Abstract Knowledge of the molecular etiology of neurodegenerative brain diseases (NBD) has substantially increased over the past three decades. Early genetic studies of NBD families identified rare and highly penetrant deleterious mutations in causal genes that segregate with disease. Large genome-wide association studies uncovered common genetic variants that influenced disease risk. Major developments in next-generation sequencing (NGS) technologies accelerated gene discoveries at an unprecedented rate and revealed novel pathways underlying NBD pathogenesis. NGS technology exposed large numbers of rare genetic variants of uncertain significance (VUS) in coding regions, highlighting the genetic complexity of NBD. Since experimental studies of these coding rare VUS are largely lacking, the potential contributions of VUS to NBD etiology remain unknown. In this review, we summarize novel findings in NBD genetic etiology driven by NGS and the impact of rare VUS on NBD etiology. We consider different mechanisms by which rare VUS can act and influence NBD pathophysiology and discuss why a better understanding of rare VUS is instrumental for deriving novel insights into the molecular complexity and heterogeneity of NBD. New knowledge might open avenues for effective personalized therapies.
"CAN CAP GUIDELINE ADHERENCE IMPROVE PATIENT OUTCOME IN INTERNAL MEDICINE DEPARTMENTS?". F. BLASI, I. IORI, A. BULFONI, S. CORRAO, S. COSTANTINO AND D. LEGNANI. EUR RESPIR J 2008; 32: 902-910.
Journal: European Respiratory Journal (2008)

Unfortunately, the therapy information presented on the left-hand side of figure 3 was incomplete; this specifically concerned the therapy
Abstract IA-009: TGFβ regulation of DNA repair across cancer types predicts response to genotoxic therapies
Authors: Mary Helen Barcellos-Hoff
Journal: Clinical Cancer Research (2021)

Abstract Transforming growth factor β (TGFβ) has a long-standing but poorly understood role in DNA repair and genomic stability. We recently showed that inhibition or loss of TGFβ signaling decreases homologous recombination and increases use of alternative end-joining (alt-EJ), an error-prone DNA repair process (Liu et al. Clin. Ca. Res. 2018). New experimental studies show that TGFβ actively suppresses genes involved in alt-EJ. Because many cancers have compromised TGFβ signaling, we determined the mechanistic implications of the relationship between TGFβ and alt-EJ using gene expression signatures by analyzing their association with outcomes in the Cancer Genome Atlas (TCGA). These studies show that the anti-correlation of TGFβ and alt-EJ regardless of tumor type is significantly associated with survival in patients treated with radiotherapy or chemoradiation. Prospective identification of patients in which TGFβ opposes effective genotoxic therapy will expand the potential therapeutic scope of TGFβ inhibitors. Citation Format: Mary Helen Barcellos-Hoff. TGFβ regulation of DNA repair across cancer types predicts response to genotoxic therapies [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr IA-009.
Left Atrial Remodeling Assessed by Serial Longitudinal Cardiac MRI in MESA
Authors: Bharath Ambale-Venkatesh, Seo Young Hong, Mohammadali Habibi, Daniel Lim, Enpei Wu, Neal Jorgensen, W. Gregory Hundley, Steven Shea, Kiang Liu, Antoinette S. Gomes, Susan R. Heckbert, Wendy S. Post, David Bluemke, João A.C. Lima
Journal: JACC. Cardiovascular imaging (2021)