tbuckley/cabot-search huggingface dataset:
Abstract 84: Remodeling of Repolarization and Arrhythmia Susceptibility in a Myosin Binding Protein C Knockout Mouse Model
Authors: Amir Toib, Sadia Mohsin, Xiaoxiao Zhang, Chen Zhang, Constantine D Troupes, Markus Wallner, Remus M Berretta, Thomas E Sharp, Giulia Borghetti, Danielle M Trappanese, Xiongwen Chen, Steven R Houser
Journal: Circulation Research (2016)

Background: Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease (1:500 in the general population) and amongst the leading causes of sudden cardiac death (SCD) in the young. There is lack of an in-depth understanding of cellular mechanisms leading to SCD in HCM. Prior studies that explored the cellular electrophysiological alterations in HCM, focused on the role of calcium and sodium currents in the development of cardiac hypertrophy and arrhythmia. Repolarizing potassium currents in HCM have not been investigated in detail. Better definition of the cellular substrates for arrhythmias could improve risk stratification and lead to potential novel therapeutic targets for prevention of SCD. Objective: To characterize the arrhythmogenic phenotype, cellular electrophysiological properties and repolarizing potassium currents in Myosin binding Protein C (MyBPC) knockout (KO) mice. Methods and results: MyBPC KO mice demonstrate overt phenotype with severe hypertrophy and cardiac dysfunction compared to wild type (WT) control mice, as evidenced by echocardiography and heart weight/body weight analysis. Telemetric electrocardiographic recordings reveal prolongation of the QTc interval in the KO compared to WT control mice (53.2 ± 7.4 vs 30.5 ± 5 msec, n=4 KO, 4 WT, p&lt; 0.05) with frequent arrhythmias including preexcitation, ventricular and supraventricular tachycardia. Whole cell current and voltage clamp studies, comparing KO to WT mice, demonstrate myocyte hypertrophy (469 ± 44 vs 234 ± 15 pF, n=18 KO,15 WT, p&lt;0.01), action potential prolongation (Action potential duration (APD)50 of 30.4± vs 17.7 msec, APD90 of 125.7± vs 74.7 msec, n=11 KO, 12 WT, p &lt;0.05) and decreased repolarizing potassium currents (n=15 KO, 14 WT): I k Peak (-120 to 60 mV) decrease of 33-39%, I k 1 (-120 to -60 mV) decrease of 16-30%, I ks (20 to 60 mV) decrease 21-23% and I to (0 to 60mV) decrease of 46-61%. Conclusion: MyBPC KO mice demonstrate remodeling of repolarizing potassium currents, action potential and QTc intervals prolongation that could account for the arrhythmia susceptibility.
Association of Annual Intensive Care Unit Sepsis Caseload With Hospital Mortality From Sepsis in the United Kingdom, 2010-2016
Authors: Ritesh Maharaj, Alistair McGuire, Andrew Street
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Sepsis is associated with a high burden of inpatient mortality. Treatment in intensive care units (ICUs) that have more experience treating patients with sepsis may be associated with lower mortality. <h3>Objective</h3> To assess the association between the volume of patients with sepsis receiving care in an ICU and hospital mortality from sepsis in the UK. <h3>Design, Setting, and Participants</h3> This retrospective cohort study used data from adult patients with sepsis from 231 UK ICUs between 2010 and 2016. Demographic and clinical data were extracted from the Intensive Care National Audit &amp; Research Centre (ICNARC) Case Mix Programme database. Data were analyzed from January 1, 2010, to December 31, 2016. <h3>Exposures</h3> Annual sepsis case volume in an ICU in the year of a patient's admission. <h3>Main Outcomes and Measures</h3> Hospital mortality after ICU admission for sepsis assessed using a mixed-effects logistic model in a 3-level hierarchical structure based on the number of individual patients nested in years nested within ICUs. <h3>Results</h3> Among 273 001 patients included in the analysis, the median age was 66 years (interquartile range, 53-76 years), 148 149 (54.3%) were male, and 248 275 (91.0%) were White. The mean ICNARC-2018 illness severity score was 21.0 (95% CI, 20.9-21.0). Septic shock accounted for 19.3% of patient admissions, and 54.3% of patients required mechanical ventilation. The median annual sepsis volume per ICU was 242 cases (interquartile range, 177-334 cases). The study identified a significant association between the volume of sepsis cases in the ICU and mortality from sepsis; in the logistic regression model, hospital mortality was significantly lower among patients admitted to ICUs in the highest quartile of sepsis volume compared with the lowest quartile (odds ratio [OR], 0.89; 95% CI, 0.82-0.96;<i>P</i> = .002). With volume modeled as a restricted cubic spline, treatment in a larger ICU was associated with lower hospital mortality. A lower annual volume threshold of 215 patients above which hospital mortality decreased significantly was found; 38.8% of patients were treated in ICUs below this threshold volume. There was no significant interaction between ICU volume and severity of illness as described by the ICNARC-2018 score (β [SE], –0.00014 [0.00024];<i>P</i> = .57). <h3>Conclusions and Relevance</h3> The findings suggest that patients with sepsis in the UK have higher odds of survival if they are treated in an ICU with a larger sepsis case volume. The benefit of a high sepsis case volume was not associated with the severity of the sepsis episode.
Immunoglobulin light chain amyloidosis: 2020 update on diagnosis, prognosis, and treatment
Authors: Morie A. Gertz
Journal: American Journal of Hematology (2020)

Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and "atypical smoldering multiple myeloma or monoclonal gammopathy undetermined significance (MGUS)."Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required for diagnosis. Invasive organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. The gold standard is laser capture mass spectroscopy.N-terminal pro-brain natriuretic peptide (NT-proBNP), serum troponin T, and difference between involved and uninvolved immunoglobulin free light chain (FLC) values are used to classify patients into four groups of similar size; median survivals are 94.1, 40.3, 14.0, and 5.8 months.All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Stem cell transplant (SCT) is preferred, but only 20% of patients are eligible. Requirements for safe SCT include systolic blood pressure >90 mmHg, troponin T < 0.06 ng/mL and serum creatinine ≤1.7 mg/dL. Nontransplant candidates can be offered cyclophosphamide-bortezomib-dexamethasone or daratumumab-containing regimens as it appears to be highly active in AL amyloidosis.Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end-stage organ failure.
Hodgkin Lymphoma and Female Fertility: A Multicenter Study of Fertility in Women Treated with Doxorubicin, Bleomycin, Vinblastine and Dacarbazine
Authors: Antoine Machet, Cecile Tomowiak, Caroline Poudou, Anthony Levy, Florence Sabirou, Cécile Gruchet, Arthur Bobin, Niels Moya, Thomas Systchenko, Deborah Desmier, Stephanie Noel, Xavier Leleu, Vincent Delwail, Stephanie Guidez
Journal: Blood (2017)
Abstract 15287: Incidence, Prevalence, and Prognostic Implications of Atrial Fibrillation Among Patients Undergoing Non-Cardiac Surgery
Authors: Anirudh Bhargava, Rajat Kalra, Nirav Patel, Vibhu Parcha, Garima Arora, Pankaj Arora
Journal: Circulation (2019)

Introduction: Atrial fibrillation (AF) is a commonly encountered arrhythmia in setting of non-cardiac procedures. However, the estimates of incidence, prevalence, and prognostic implications of thi...
Antibiotics for asthma attacks: masking uncertainty
Authors: Sanjay Ramakrishnan, Simon Couillard
Journal: European Respiratory Journal (2021)

<b>Despite current guidelines advising against, GPs commonly prescribe antibiotics with steroids for asthma attacks. The uncertainty caused by a symptom-based management paradigm probably drives this. A biology-guided management paradigm is needed.</b>https://bit.ly/3iS3CCd
NORMA: The Network Makeup Artist — A Web Tool for Network Annotation Visualization
Authors: Mikaela Koutrouli, Evangelos Karatzas, Katerina Papanikolopoulou, Georgios A. Pavlopoulos
Journal: Genomics Proteomics & Bioinformatics (2021)

The Network Makeup Artist (NORMA) is a web tool for interactive network annotation visualization and topological analysis, able to handle multiple networks and annotations simultaneously. Precalculated annotations (e.g., Gene Ontology, Pathway enrichment, community detection, or clustering results) can be uploaded and visualized in a network, either as colored pie-chart nodes or as color-filled areas in a 2D/3D Venn-diagram-like style. In the case where no annotation exists, algorithms for automated community detection are offered. Users can adjust the network views using standard layout algorithms or allow NORMA to slightly modify them for visually better group separation. Once a network view is set, users can interactively select and highlight any group of interest in order to generate publication-ready figures. Briefly, with NORMA, users can encode three types of information simultaneously. These are 1) the network, 2) the communities or annotations of interest, and 3) node categories or expression values. Finally, NORMA offers basic topological analysis and direct topological comparison across any of the selected networks. NORMA service is available at http://norma.pavlopouloslab.info, whereas the code is available at https://github.com/PavlopoulosLab/NORMA.
Evolving therapeutic landscape in follicular lymphoma: a look at emerging and investigational therapies
Authors: Walter Hanel, Narendranath Epperla
Journal: Journal of Hematology & Oncology (2021)

Abstract Follicular Lymphoma (FL) is the most common subtype of indolent B cell non-Hodgkin lymphoma. The clinical course can be very heterogeneous with some patients being safely observed over many years without ever requiring treatment to other patients having more rapidly progressive disease requiring multiple lines of treatment for disease control. Front-line treatment of advanced FL has historically consisted of chemoimmunotherapy but has extended to immunomodulatory agents such as lenalidomide. In the relapsed setting, several exciting therapies that target the underlying biology and immune microenvironment have emerged, most notable among them include targeted therapies such as phosphoinositide-3 kinase and Enhancer of Zeste 2 Polycomb Repressive Complex 2 inhibitors and cellular therapies including chimeric antigen receptor T cells and bispecific T cell engagers. There are several combination therapies currently in clinical trials that appear promising. These therapies will likely reshape the treatment approach for patients with relapsed and refractory FL in the coming years. In this article, we provide a comprehensive review of the emerging and investigational therapies in FL and discuss how these agents will impact the therapeutic landscape in FL.
A High‐Throughput Distal Lung Air–Blood Barrier Model Enabled By Density‐Driven Underside Epithelium Seeding
Authors: Hannah Viola, Kendra Washington, Cauviya Selva, Jocelyn Grunwell, Rabindra Tirouvanziam, Shuichi Takayama
Journal: Advanced Healthcare Materials (2021)

Abstract High‐throughput tissue barrier models can yield critical insights on how barrier function responds to therapeutics, pathogens, and toxins. However, such models often emphasize multiplexing capability at the expense of physiologic relevance. Particularly, the distal lung's air–blood barrier is typically modeled with epithelial cell monoculture, neglecting the substantial contribution of endothelial cell feedback in the coordination of barrier function. An obstacle to establishing high‐throughput coculture models relevant to the epithelium/endothelium interface is the requirement for underside cell seeding, which is difficult to miniaturize and automate. Therefore, this paper describes a scalable, low‐cost seeding method that eliminates inversion by optimizing medium density to float cells so they attach under the membrane. This method generates a 96‐well model of the distal lung epithelium–endothelium barrier with serum‐free, glucocorticoid‐free air–liquid differentiation. The polarized epithelial–endothelial coculture exhibits mature barrier function, appropriate intercellular junction staining, and epithelial‐to‐endothelial transmission of inflammatory stimuli such as polyinosine:polycytidylic acid (poly(I:C)). Further, exposure to influenza A virus PR8 and human beta‐coronavirus OC43 initiates a dose‐dependent inflammatory response that propagates from the epithelium to endothelium. While this model focuses on the air–blood barrier, the underside seeding method is generalizable to various coculture tissue models for scalable, physiologic screening.
COVID-19 Vaccination Coverage and Intent Among Adults Aged 18–39 Years — United States, March–May 2021
Authors: Brittney N. Baack, Neetu Abad, David Yankey, Katherine E. Kahn, Hilda Razzaghi, Kathryn Brookmeyer, Jessica Kolis, Elisabeth Wilhelm, Kimberly H. Nguyen, James A. Singleton
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Overall, 34% of adults aged 18–39 years reported having received a COVID-19 vaccine. Adults aged 18–24 years, as well as non-Hispanic Black adults and those with less education, no health insurance, and lower household incomes, had the lowest reported vaccination coverage and intent to get vaccinated. Concerns about vaccine safety and effectiveness were commonly cited barriers to vaccination.
Abstract 14011: Indication and Management of Allergy to TYRX Absorbable Antibacterial Envelope
Authors: Emrie Tomaiko, Meenakshi Sridhar, Carla Lockhart, Sharon Kusne, Jonathan Ko, Wilber Su
Journal: Circulation (2019)

Introduction: Medtronic TYRX Absorbable Antibacterial Envelope is a bioabsorbable polymer impregnated with Minocycline and Rifampin used for the purpose of infection prophylaxis. There are no repor...
Surfactant‐Stripped Micelles with Aggregation‐Induced Enhanced Emission for Bimodal Gut Imaging In Vivo and Microbiota Tagging Ex Vivo
Authors: Zhen Jiang, Boyang Sun, Yueqi Wang, Heqi Gao, He Ren, Hao Zhang, Tong Lu, Xiangkui Ren, Wei Wei, Xiaoli Wang, Lei Zhang, Jiao Li, Dan Ding, Jonathan F. Lovell, Yumiao Zhang
Journal: Advanced Healthcare Materials (2021)

Abstract Aggregation‐induced emission luminogens (AIEgens) hold promise for biomedical imaging and new approaches facilitating their aggregation state are desirable for fluorescence enhancement. Herein, a series of surfactant‐stripped AIEgen micelles (SSAMs) with improved fluorescence are developed by a low‐temperature surfactant‐stripping method to encapsulate AIEgens in temperature‐sensitive Pluronic block copolymer. After stripping excessive surfactant, SSAMs exhibit altered optical properties and significantly higher fluorescence quantum yield. Using this method, a library of highly concentrated fluorescent nanoparticles are generated with tunable absorption and emission wavelengths, permitting imaging of deep tissues at different wavelengths. SSAMs remain physiologically stable and can pass safely through gastrointestinal tract (GI) without degradation in the harsh conditions, allowing for fluorescence and photoacoustic imaging of intestine with high resolution. d ‐amino acids (DAA), a natural metabolite for bacteria, can be chemically conjugated on the surface of SSAMs, enabling non‐invasive monitoring of the microbial behavior of ex vivo fluorescently labeled gut microbiota in the GI tract.
Abstract 297: The Oracle™ Device: A New Snare for Removal of Thrombus
Authors: Richard R Heuser
Journal: Circulation Research (2016)

Stroke is a leading cause of serious disability and death worldwide. Randomized trials have shown benefits of mechanical thrombectomy compared to usual cases with intravenous thombolysis. A simple intuitively obvious device for clot removal would be ideal. To deal with thrombus removal, we introduce the ORACLE™ snare. This snare pictured has the ability to be placed through an .014 system to remove thrombus or other foreign material throughout the body (Figure 1). The Oracle Retrieval Device is composed of three primary parts: an outer sheath tube, a core wire, and 4 capture loops. The 180cm device has loop sizes that range from 2 - 6 millimeters in diameter (Figure 2). There is an ABS plastic operating handle on the proximal end which is used to direct the device as well as to lock the capture loops in the expanded and retracted positions. Utilizing the ORACLE™ snare, we have successfully removed thrombus in a canine model (3 out of 3 removed successfully) and bovine model (2 out of 2 removed successfully) with minimal loss of endothelial cells (Figure 3). With the emergence of dedicated thrombus removal devices for stroke care, more challenges have occurred in treating smaller vessels. Simple intuitively obvious devices available in all carotid and stroke centers as well as centers performing coronary interventions would be ideal. The ORACLE™ may be one approach to remove thrombus and can be placed through .014 compatible catheters.
Extrafollicular PD-1highCXCR5–CD4+ T cells participate in local immunoglobulin production in nasal polyps
Authors: Zhi-Chao Wang, Yin Yao, Cai-Ling Chen, Cui-Lian Guo, Hong-Xia Ding, Jia Song, Zhe-Zheng Wang, Nan Wang, Xue-Li Li, Bo Liao, Yang Yang, Di Yu, Zheng Liu
Journal: Journal of Allergy and Clinical Immunology (2021)
5-Year Outcomes with Cobimetinib plus Vemurafenib in <i>BRAF</i>V600 Mutation–Positive Advanced Melanoma: Extended Follow-up of the coBRIM Study
Authors: Paolo A. Ascierto, Brigitte Dréno, James Larkin, Antoni Ribas, Gabriella Liszkay, Michele Maio, Mario Mandalà, Lev Demidov, Daniil Stroyakovskiy, Luc Thomas, Luis de la Cruz-Merino, Victoria Atkinson, Caroline Dutriaux, Claus Garbe, Jessie Hsu, Surai Jones, Haocheng Li, Edward McKenna, Athina Voulgari, Grant A. McArthur
Journal: Clinical Cancer Research (2021)

Abstract Purpose: The randomized phase III coBRIM study (NCT01689519) demonstrated improved progression-free survival (PFS) and overall survival (OS) with addition of cobimetinib to vemurafenib compared with vemurafenib in patients with previously untreated BRAFV600 mutation–positive advanced melanoma. We report long-term follow-up of coBRIM, with at least 5 years since the last patient was randomized. Patients and Methods: Eligible patients were randomized 1:1 to receive either oral cobimetinib (60 mg once daily on days 1–21 in each 28-day cycle) or placebo in combination with oral vemurafenib (960 mg twice daily). Results: 495 patients were randomized to cobimetinib plus vemurafenib (n = 247) or placebo plus vemurafenib (n = 248). Median follow-up was 21.2 months for cobimetinib plus vemurafenib and 16.6 months for placebo plus vemurafenib. Median OS was 22.5 months (95% CI, 20.3–28.8) with cobimetinib plus vemurafenib and 17.4 months (95% CI, 15.0–19.8) with placebo plus vemurafenib; 5-year OS rates were 31% and 26%, respectively. Median PFS was 12.6 months (95% CI, 9.5–14.8) with cobimetinib plus vemurafenib and 7.2 months (95% CI, 5.6–7.5) with placebo plus vemurafenib; 5-year PFS rates were 14% and 10%, respectively. OS and PFS were longest in patients with normal baseline lactate dehydrogenase levels and low tumor burden, and in those achieving complete response. The safety profile remained consistent with previously published reports. Conclusions: Extended follow-up of coBRIM confirms the long-term clinical benefit and safety profile of cobimetinib plus vemurafenib compared with vemurafenib monotherapy in patients with BRAFV600 mutation–positive advanced melanoma.
RUNX1-ETO (RUNX1-RUNX1T1) induces myeloid leukemia in mice in an age-dependent manner
Authors: Mohamed Gaber Abdallah, Akiko Niibori-Nambu, Mariko Morii, Takako Yokomizo, Tomomasa Yokomizo, Takako Ideue, Sho Kubota, Vania Swee Imm Teoh, Michelle Meng Huang Mok, Chelsia Qiuxia Wang, Abdellah Ali Omar, Kenji Tokunaga, Eisaku Iwanaga, Masao Matsuoka, Norio Asou, Naomi Nakagata, Kimi Araki, Mabrouk AboElenin, Sayed Hamada Madboly, Goro Sashida, Motomi Osato
Journal: Leukemia (2021)

t(8;21) is among the most common chromosomal translocations associated with human leukemia [1][2][3][4].The RUNX1-ETO (RUNX1-RUNX1T1, AML1-MTG8) fusion gene, generated by t(8;21), has been extensively investigated in the field; however, its mechanistic basis remains to be fully understood.Clinical features of t(8;21) leukemia include: (1) association with acute myeloid leukemia (AML) M2 subtype in the FAB classification, characterized by granulocytic maturation in morphology, (2) positivity for the following immunophenotypic markers, HLA-DR + , CD117(c-KIT) + , CD34 + , CD38 + , CD13 + , CD33 + , CD19 + , and CD56 + , (3) chloroma, (4) predominant onset in adolescent and young adults (AYA), but not in aged population, (5) higher prevalence in Asia, and (6) requirement of additional genetic abnormalities such as mutations in c-KIT, FLT3, RAS, ASXL1, and ZBTB7A, -9q, or -Y [2, 3].Although a number of attempts have been made to generate its mouse model, RUNX1-ETO induction alone did not induce leukemia in most cases [5][6][7][8][9][10].Even when leukemia developed, the penetrance was low and the latency was 1 year or longer.In addition, leukemia phenotypes did not recapitulate clinical features.As such, no tractable murine models are currently available.We reasoned that the failure in the previous efforts for the generation of RUNX1-ETO mouse model is due to insufficient expression and inappropriate cells of origin.RUNX1-ETO mRNA amount per one single leukemia cell at clinical onset time is shown to be significantly higher than that at remission state [11].To achieve sufficient expression, Rosa26 locus which allows for abundant expression of RUNX1-ETO was employed to generate conditional knock-in (KI) mice carrying a heterozygous floxed allele of Rosa26-LSL-RUNX1-ETO-IRES-EGFP (Fig. 1A, Tables S1 andS2, Supplementary Methods).This mouse line was crossed with eR1-CreER T2 transgenic mice
Challenges in Identifying the Retracted Status of an Article
Authors: Elizabeth M. Suelzer, Jennifer Deal, Karen Hanus, Barbara E. Ruggeri, Elizabeth Witkowski
Journal: JAMA Network Open (2021)

Inadvertent or unacknowledged citations to retracted literature are a persistent problem in scholarly publishing.1,2 Inconsistencies in how retraction information is displayed on publisher websites and bibliographic databases hinder determining whether a paper has been retracted, thus contributing to the cause of this problem. This cross-sectional study examines publisher websites and bibliographic databases to check their accordance with industry standards for documenting retracted publications, highlighting challenges readers face in identifying the retracted status of a publication.