tbuckley/cabot-search huggingface dataset:
Abstract 283: Efficacy of a Novel Artificial Oxygen Carrier (LHb) on Ameliorating Lethal Arrhythmogenetic Property in Hemorrhagic Shock Heart: Optical Mapping Analysis
Authors: Bonpei Takase, Yoshihiro Tanaka, Hidemi Hattori, Takanobu Ishizuka, Shinichi Kaneda, Makoto Kikuchi, Masayuki Ishihara
Journal: Circulation (2011)

Irreversible heart dysfunction despites restoring normal systemic circulation in shock, that is so called “Shock Syndrome”, is caused by prolonged low mean systemic blood pressure (BP) &lt; 40 mmHg, and this heart dysfunction frequently associates with lethal arrhythmias leading to adverse prognosis in the hemorrhagic shock patients. To investigate if a novel artificial oxygen carrier (LHb) is effective to improve arrhythmogenetic property in hemorrhagic shock heart, we performed optical mapping analysis (OM) and electrophysiological study (EPS) in rat's heart obtained from 30% hemorrhagic shock model with repetitive bleedings, where sustained lower mean BP &lt; 40 mmHg was kept for more than 30 min. Hemorrhagic shock was induced in Sprague-Dawley rats (n=32). Rats were resuscitated by LHb, washed red bold cell (wRBC), normal saline (NS) and 5% albumin (5%alb). Hearts were excised, perfused with Tyrode solution and stained with fluorescent dye. Ventricular fibrillation (VF) was induced by burst pacing stimulus to multiple sites in the left ventricle (LV) and OM was performed. VF was induced in all rats resuscitated by NS and 5%alb and their OM showed conduction delay and impaired action potential duration (APD) dispersion (APDd), defined as APDd = maximum APD - minimum APD, in LV. However, all rats rescued by LHb and wRBC had normal OM findings and no VF was induced. Conclusions; LHb can improve deteriorated electrophysiological property in LV of hemorrhagic shock heart and prevent lethal arrhythmias compatible with wRBC. LHb possibly and comparably ameliorates prognosis in massive hemorrhagic shock patients through reducing shock-related lethal arrhythmias with wRBC.
Genomic surveillance to combat COVID-19: challenges and opportunities
Authors: Janet D Robishaw, Scott M Alter, Joshua J Solano, Richard D Shih, David L DeMets, Dennis G Maki, Charles H Hennekens
Journal: The Lancet Microbe (2021)

Although the development and increasingly widespread availability of effective and safe vaccines provides the greatest hope for the future recovery from the increasingly devastating COVID-19 pandemic, there are other preventive efforts that offer an immediate route to decreasing morbidity and mortality. Genomic surveillance is emerging as a vital necessity to achieve effective mitigation and containment. Since SARS-CoV-2 variants have already been detected, it is crucial to obtain reliable evidence about whether they are more contagious, virulent, or more resistant to the available COVID-19 vaccines well before they spread throughout the world. Genomic surveillance leverages applications of next-generation sequencing, creates the availability of whole genome data, and advances phylogenetic methods. These methods offer novel means to detect variants that are phenotypically or antigenically different. Genomic surveillance will facilitate greater early anticipation as well as initiation of effective strategies to mitigate and contain outbreaks of SARS-CoV-2 variants and other novel viruses.
Mdm2 inhibition synergises with endocrine therapy or cdk4/6 inhibition for the treatment of estrogen receptor-positive breast cancer
Authors: Neil Portman, Heloisa Milioli, Sarah Alexandrou, Rhiannon Coulson, Aliza Yong, Kristine Fernandez, KeeMing Chia, Ensar Halilovic, Davendra Segara, Andrew Parker, Sue Haupt, Ygal Haupt, Wayne Tilley, Alex Swarbrick, Liz Caldon, Elgene Lim
Journal: Cancer Research (2021)
Thermal-triggered packing of lipophilic NIR dye IR780 in hepatitis B core at critical ionic strength and cargo-host ratio for improved stability and enhanced cancer phototherapy
Authors: Fengying Lu, Zhengjun Li, Yanan Sheng, Yanyan Ma, Yanli Yang, Ying Ren, Zhiguo Su, Rong Yu, Songping Zhang
Journal: Biomaterials (2021)
Current‐Driven Organic Electrochemical Transistors for Monitoring Cell Layer Integrity with Enhanced Sensitivity
Authors: Katharina Lieberth, Paolo Romele, Fabrizio Torricelli, Dimitrios A. Koutsouras, Maximilian Brückner, Volker Mailänder, Paschalis Gkoupidenis, Paul W. M. Blom
Journal: Advanced Healthcare Materials (2021)

Abstract In this progress report an overview is given on the use of the organic electrochemical transistor (OECT) as a biosensor for impedance sensing of cell layers. The transient OECT current can be used to detect changes in the impedance of the cell layer, as shown by Jimison et al. To circumvent the application of a high gate bias and preventing electrolysis of the electrolyte, in case of small impedance variations, an alternative measuring technique based on an OECT in a current‐driven configuration is developed. The ion‐sensitivity is larger than 1200 mV V ‐1 dec ‐1 at low operating voltage. It can be even further enhanced using an OECT based complementary amplifier, which consists of a p‐type and an n‐type OECT connected in series, as known from digital electronics. The monitoring of cell layer integrity and irreversible disruption of barrier function with the current‐driven OECT is demonstrated for an epithelial Caco‐2 cell layer, showing the enhanced ion‐sensitivity as compared to the standard OECT configuration. As a state‐of‐the‐art application of the current‐driven OECT, the in situ monitoring of reversible tight junction modulation under the effect of drug additives, like poly‐ l ‐lysine, is discussed. This shows its potential for in vitro and even in vivo toxicological and drug delivery studies.
Abstract 10826: Crucial Role of Hypoxia in Epigenetic Changes of Pulmonary Artery SMCs From PAH With Bmpr2 Mutation
Authors: Kazufumi Nakamura, Satoshi Akagi, Yukihiro Saito, Kentaro Ejiri, Toru Miyoshi, Masashi Yoshida, Satoshi Hirohata, Hiroshi Ito
Journal: Circulation (2019)

Introduction: Mutations of the BMPR2 gene are implicated in the pathogenesis of pulmonary arterial hypertension(PAH). Because mutant alleles are typically of low penetrance, multiple hits by geneti...
PGD2 and CRTH2 counteract Type 2 cytokine–elicited intestinal epithelial responses during helminth infection
Authors: Oyebola O. Oyesola, Michael T. Shanahan, Matt Kanke, Bridget M. Mooney, Lauren M. Webb, Shuchi Smita, Macy K. Matheson, Pamela Campioli, Duc Pham, Simon P. Früh, John W. McGinty, Madeline J. Churchill, Jordan L. Cahoon, Pavithra Sundaravaradan, Becca A. Flitter, Karthik Mouli, Marija S. Nadjsombati, Elena Kamynina, Seth A. Peng, Rebecca L. Cubitt, Karsten Gronert, James D. Lord, Isabella Rauch, Jakob von Moltke, Praveen Sethupathy, Elia D. Tait Wojno
Journal: The Journal of Experimental Medicine (2021)

Type 2 inflammation is associated with epithelial cell responses, including goblet cell hyperplasia, that promote worm expulsion during intestinal helminth infection. How these epithelial responses are regulated remains incompletely understood. Here, we show that mice deficient in the prostaglandin D2 (PGD2) receptor CRTH2 and mice with CRTH2 deficiency only in nonhematopoietic cells exhibited enhanced worm clearance and intestinal goblet cell hyperplasia following infection with the helminth Nippostrongylus brasiliensis. Small intestinal stem, goblet, and tuft cells expressed CRTH2. CRTH2-deficient small intestinal organoids showed enhanced budding and terminal differentiation to the goblet cell lineage. During helminth infection or in organoids, PGD2 and CRTH2 down-regulated intestinal epithelial Il13ra1 expression and reversed Type 2 cytokine–mediated suppression of epithelial cell proliferation and promotion of goblet cell accumulation. These data show that the PGD2–CRTH2 pathway negatively regulates the Type 2 cytokine–driven epithelial program, revealing a mechanism that can temper the highly inflammatory effects of the anti-helminth response.
Targeting<i>EGFR</i>Exon 20 Insertions in Non–Small Cell Lung Cancer: Recent Advances and Clinical Updates
Authors: Catherine B. Meador, Lecia V. Sequist, Zofia Piotrowska
Journal: Cancer Discovery (2021)

Approximately 10% of EGFR-activating mutations occur as in-frame insertion mutations in exon 20 of the EGFR kinase domain (EGFR ins20). EGFR ins20 mutations have not demonstrated the same sensitivity to early generations of EGFR tyrosine kinase inhibitors (TKI) as canonical activating EGFR mutations such as del19 and L858R. Development of effective therapies for this subset of patients has been challenging, but recent years have seen more rapid progress in these efforts. In this review, we describe the molecular and clinicopathologic features of EGFR ins20 mutations and summarize recent data on emerging therapies for patients with this subtype of EGFR-mutant non-small cell lung cancer (NSCLC). SIGNIFICANCE: When activating mutations in EGFR were first discovered in lung cancer, the lack of sensitivity of tumors harboring EGFR ins20 mutations to early-generation EGFR TKIs resulted in this subset of EGFR-mutant tumors being initially classified as an untargetable or intrinsically resistant subpopulation. In addition, the diversity of mutations within EGFR exon 20 and resultant challenges identifying them on routine clinical genotyping tests led to underestimation of their frequency. However, recent scientific progress in targeting EGFR ins20 mutations as well as more effective identification of this clinical cohort has enhanced our ability to develop effective therapies for patients with this subtype of EGFR-mutant NSCLC.
Aiding and Abetting Anhedonia: Impact of Inflammation on the Brain and Pharmacological Implications
Authors: Michael J. Lucido, Mandy Bekhbat, David R. Goldsmith, Michael T. Treadway, Ebrahim Haroon, Jennifer C. Felger, Andrew H. Miller
Journal: Pharmacological Reviews (2021)

Exogenous administration of inflammatory stimuli to humans and laboratory animals and chronic endogenous inflammatory states lead to motivational deficits and ultimately anhedonia, a core and disabling symptom of depression present in multiple other psychiatric disorders. Inflammation impacts neurotransmitter systems and neurocircuits in subcortical brain regions including the ventral striatum, which serves as an integration point for reward processing and motivational decision-making. Many mechanisms contribute to these effects of inflammation, including decreased synthesis, release and reuptake of dopamine, increased synaptic and extrasynaptic glutamate, and activation of kynurenine pathway metabolites including quinolinic acid. Neuroimaging data indicate that these inflammation-induced neurotransmitter effects manifest as decreased activation of ventral striatum and decreased functional connectivity in reward circuitry involving ventral striatum and ventromedial prefrontal cortex. Neurocircuitry changes in turn mediate nuanced effects on motivation that include decreased willingness to expend effort for reward while maintaining the ability to experience reward. Taken together, the data reveal an inflammation-induced pathophysiologic phenotype that is agnostic to diagnosis. Given the many mechanisms involved, this phenotype represents an opportunity for development of novel and/or repurposed pharmacological strategies that target inflammation and associated cellular and systemic immunometabolic changes and their downstream effects on the brain. To date, clinical trials have failed to capitalize on the unique nature of this transdiagnostic phenotype, leaving the field bereft of interpretable data for meaningful clinical application. However, novel trial designs incorporating established targets in the brain and/or periphery using relevant outcome variables (e.g., anhedonia) are the future of targeted therapy in psychiatry. SIGNIFICANCE STATEMENT: Emerging understanding of mechanisms by which peripheral inflammation can affect the brain and behavior has created unprecedented opportunities for development of pharmacological strategies to treat deficits in motivation including anhedonia, a core and disabling symptom of depression well represented in multiple psychiatric disorders. Mechanisms include inflammation and cellular and systemic immunometabolism and alterations in dopamine, glutamate, and kynurenine metabolites, revealing a target-rich environment that nevertheless has yet to be fully exploited by current clinical trial designs and drugs employed.
Preliminary Data Show Heterogenous Patterns of 18f-FDG PET/CT When Assessing the Inflammatory Component of Primary or Secondary Myelofibrosis
Authors: Mario Ojeda-Uribe, Christophe Schohn, Olivier Morel, Nathalie Mac Dougall, Xavier Malezieux, Atteka Chabanse, Andrien Norosoa, Laurent Mauvieux, Hatem Boulahdour, Edmond Rust
Journal: Blood (2017)
Electroconvulsive Therapy and the Risk of Suicide in Hospitalized Patients With Major Depressive Disorder
Authors: Ida Rönnqvist, Fredrik K. Nilsson, Axel Nordenskjöld
Journal: JAMA Network Open (2021)

Electroconvulsive therapy (ECT) is indicated for severe depression, including depression with psychosis, catatonia, and/or an elevated suicide risk. However, the association of ECT with suicide risk is uncertain.
Short Androgen Suppression and Radiation Dose Escalation in Prostate Cancer: 12-Year Results of EORTC Trial 22991 in Patients With Localized Intermediate-Risk Disease
Authors: Michel Bolla, Anouk Neven, Philippe Maingon, Christian Carrie, Ana Boladeras, Demetrios Andreopoulos, Antoine Engelen, Santhanam Sundar, Elzbieta M. van der Steen-Banasik, John Armstrong, Karine Peignaux-Casasnovas, Jihane Boustani, Fernanda G. Herrera, Bradley R. Pieters, Annerie Slot, Amit Bahl, Christopher D. Scrase, David Azria, Jan Jansa, Joe M. O'Sullivan, Alphonsus C. M. Van Den Bergh, Laurence Collette
Journal: Journal of Clinical Oncology (2021)

The European Organisation for Research and Treatment of Cancer (EORTC) trial 22991 (NCT00021450) showed that 6 months of concomitant and adjuvant androgen suppression (AS) improves event- (EFS, Phoenix) and clinical disease-free survival (DFS) of intermediate- and high-risk localized prostatic carcinoma, treated by external-beam radiotherapy (EBRT) at 70-78 Gy. We report the long-term results in intermediate-risk patients treated with 74 or 78 Gy EBRT, as per current guidelines.Of 819 patients randomly assigned between EBRT or EBRT plus AS started on day 1 of EBRT, 481 entered with intermediate risk (International Union Against Cancer TNM 1997 cT1b-c or T2a with prostate-specific antigen (PSA) ≥ 10 ng/mL or Gleason ≤ 7 and PSA ≤ 20 ng/mL, N0M0) and had EBRT planned at 74 (342 patients, 71.1%) or 78 Gy (139 patients, 28.9%). We report the trial primary end point EFS, DFS, distant metastasis-free survival (DMFS), and overall survival (OS) by intention-to-treat stratified by EBRT dose at two-sided α = 5%.At a median follow-up of 12.2 years, 92 of 245 patients and 132 of 236 had EFS events in the EBRT plus AS and EBRT arm, respectively, mostly PSA relapse (48.7%) or death (45.1%). EBRT plus AS improved EFS and DFS (hazard ratio [HR] = 0.53; CI, 0.41 to 0.70; P < .001 and HR = 0.67; CI, 0.49 to 0.90; P = .008). At 10 years, DMFS was 79.3% (CI, 73.4 to 84.0) with EBRT plus AS and 72.7% (CI, 66.2 to 78.2) with EBRT (HR = 0.74; CI, 0.53 to 1.02; P = .065). With 140 deaths (EBRT plus AS: 64; EBRT: 76), 10-year OS was 80.0% (CI, 74.1 to 84.7) with EBRT plus AS and 74.3% (CI, 67.8 to 79.7) with EBRT, but not statistically significantly different (HR = 0.74; CI, 0.53 to 1.04; P = .082).Six months of concomitant and adjuvant AS statistically significantly improves EFS and DFS in intermediate-risk prostatic carcinoma, treated by irradiation at 74 or 78 Gy. The effects on OS and DMFS did not reach statistical significance.
Abstract 16924: Multimodality Imaging Reveals Decreased Creatine-Kinase Flux and Systolic Strain in Patients with Hypertrophic Cardiomyopathy and Preserved LVEF
Authors: M Roselle R Abraham, Paul Bottomley, Veronica L Dimaano, Aurelio Pinheiro, Thomas Traill, Theodore P Abraham, Robert Weiss
Journal: Circulation (2011)

Background/Objectives: We investigated in vivo cardiac creatine kinase (CK) ATP supply and function in a family with HCM who carry an extensively characterized point mutation (R403Q) in the cardiac β-myosin heavy chain gene. Methods: Quantitative phosphorus ( 31 P) saturation transfer MRS was used to noninvasively measure cardiac CK energy transfer-the forward CK flux and the CK rate constant, k f -and CK metabolite concentrations (phosphocreatine, [PCr], and [ATP]) in patients with HCM (n=10), and in age-matched healthy controls (n=15). Systolic strain, LV ejection fraction (EF), diastolic function and cardiac morphology were assessed by echocardiography in HCM patients (n=11) and a second group of healthy controls (n=10). Results: LV mass was higher in HCM patients than controls (307.21 ± 12.37 vs 167.63 ± 42.53; p=0.0037). [PCr] was significantly decreased by 22% in HCM patients (7.36 ± 2.29µmol/g wet weight) as compared to controls (9.41 ± 1.2µmol/g; p=0.005), but PCr/ATP ratio was not significantly altered (1.54 ± 0.4 in HCM vs. 1.69 ± 0.29, p=0.26). The pseudo-first-order rate-constant for the CK reaction, k f was reduced by 26% (0.266 ± 0.14 vs. 0.36 ± 0.08, p&lt;0.04) and the forward CK flux was reduced by 43% (1.94 ± 1.27 vs 3.39 ± 0.96, p&lt;0.003) in HCM patients when compared to controls. Diastolic function (E/A) was impaired (0.90 ± 0.31 in HCM vs 1.48 ± 0.27 controls; p=0.0003) and peak systolic strain (longitudinal; εL) was significantly decreased in HCM patients (-13.40 ± 5.32 vs -18.93 ± 2.46; p=0.0076). Peak longitudinal strain and diastolic function (E/A) correlated with NYHA class (R²=0.50; p =0.0007); E/A &lt;1 correlated with NYHA class progression over 5 years of follow up (R 2 =0.6, p=0.024). Conclusions: PCr, k for and CK flux are significantly reduced in patients compared to age-matched healthy control subjects, indicating impaired CK ATP energy supply even at rest, consistent with prior work on a HCM (R403Q) mouse model. However, only systolic strain and diastolic function were correlated with NYHA class and progression respectively, suggesting that while bioenergetic alterations are associated with the underlying mutation, other downstream molecular effects contribute to the severity of dysfunction and clinical status of these patients.
Novel percutaneous access to the large intestine using a double-balloon endoluminal platform for excision of a large polyp
Authors: Shinya Urakawa, Daniel Joseph Holzwanger, Teijiro Hirashita, Lea Lowenfeld, Kelly A. Garrett, Bradley B. Pua, Jeffrey W. Milsom
Journal: Endoscopy (2021)

Endoluminal therapies (e. g. tumor excision, hemostasis, closure of intestinal defects) can be complex [1]. There are reports of successful percutaneous access to treat upper gastrointestinal (GI) lesions [2]; however, percutaneous access has not been established yet in the treatment of lower GI conditions [3]. We here report a novel method of percutaneous access to the colon for excision of a large polyp.
High penetrance of inferior vena cava system atresia in severe thrombophilia caused by homozygous antithrombin Budapest 3 variant: Description of a new syndrome
Authors: María E. de la Morena‐Barrio, Réka Gindele, Carlos Bravo‐Pérez, Péter Ilonczai, Isabel Zuazu, Marianna Speker, Zsolt Oláh, Juan J. Rodríguez‐Sevilla, Laura Entrena, Maria S. Infante, Belén de la Morena‐Barrio, José M. García, Ágota Schlammadinger, Rosa Cifuentes‐Riquelme, Asunción Mora‐Casado, Antonia Miñano, Jose Padilla, Vicente Vicente, Javier Corral, Zsuzsanna Bereczky
Journal: American Journal of Hematology (2021)

Atresia of inferior vena cava (IVC) is a rare congenital malformation associated with high risk of venous thrombosis that still has unknown etiology, although intrauterine IVC thrombosis has been suggested to be involved. The identification of IVC atresia in a case with early idiopathic venous thrombosis and antithrombin deficiency caused by the homozygous SERPINC1 c.391C > T variant (p.Leu131Phe; antithrombin Budapest 3) encouraged us to evaluate the role of this severe thrombophilia in this vascular abnormality. We have done a cross-sectional study in previously identified cohorts of patients homozygous for the Budapest 3 variant (N = 61) selected from 1118 patients with congenital antithrombin deficiency identified in two different populations: Spain (N = 692) and Hungary (N = 426). Image analysis included computed tomography and phlebography. Atresia of the IVC system was observed in 17/24 cases (70.8%, 95% confidence interval [CI]: 48.9%-87.3%) homozygous for antithrombin Budapest 3 with available computed tomography (5/8 and 12/16 in the Spanish and Hungarian cohorts, respectively), 16 had an absence of infrarenal IVC and one had atresia of the left common iliac vein. All cases with vascular defects had compensatory mechanisms, azygos-hemiazygos continuation or double IVC, and seven also had other congenital anomalies. Short tandem repeat analysis supported the specific association of the IVC system atresia with SERPINC1. We show the first evidence of the association of a severe thrombophilia with IVC system atresia, supporting the possibility that a thrombosis in the developing fetal vessels is the reason for this anomaly. Our hypothesis-generating results encourage further studies to investigate severe thrombophilic states in patients with atresia of IVC.
Patterns of therapy initiation during the first decade for patients with follicular lymphoma who were observed at diagnosis in the rituximab era
Authors: None Arushi Khurana, Raphael Mwangi, Stephen M. Ansell, Thomas M. Habermann, James R. Cerhan, Christopher Strouse, Brian K. Link, Yucai Wang, Rebecca L. King, William R. Macon, J. C. Villasboas, Thomas E. Witzig, Matthew J. Maurer, Grzegorz S. Nowakowski
Journal: Blood Cancer Journal (2021)

Abstract Immediate treatment for asymptomatic, low-tumor burden follicular lymphoma (FL) has not shown an overall survival benefit over “watch and wait” (W/W) strategy. We estimated incidence of treatment initiation at specific time points and assessed its association with the presence of any criteria such as GELF, BNLI, GITMO at diagnosis. FL patients managed by W/W strategy were identified from the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma SPORE between 2002 and 2015. Cumulative incidence estimates of treatment initiation were calculated using transformation (as the first event) and death as competing risks. 401 FL patients were identified on W/W strategy. At a median follow-up of 8 years, 256 (64%) initiated treatment. For patients on the W/W strategy for 5 years, the likelihood of treatment initiation in the next 5 years was 12% compared to 43% at diagnosis unlike transformation rates which remained steady. Patients with any of popular treatment criteria at diagnosis did not have increased therapy initiation rates (44% vs. 42%) during the first 5 years or lymphoma-related death rates at 10 years (6% vs. 7%). Identifying biological differences in patients with early vs. late or no progression is a critical next step in understanding outcomes in W/W patients.
Abstract 14596: The Preferable Anatomical Location of the Rotational Reentrant Circuit in Patients With Atrial Fibrillation: Analysis by the Non-Contact Mapping
Authors: Tadashi Hoshiyama, Hiroshige Yamabe, Junjiroh Koyama, Hisanori Kanazawa, Miwa Ito, Hisao Ogawa
Journal: Circulation (2013)

Background: It has been suggested that the rotational reentry may exist and maintain the atrial fibrillation (AF). However, it remains unclear whether the rotational reentry exists at the stable lo...