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1. Projects by Concept, Economic Education Awards.

Author: Joint Council on Economic Education, New York, NY., Palmer, George E., and Meihsner, Joey A.
Abstract: Over 200 economics units submitted to the annual National Awards Program for Teaching Economics are described. Projects are arranged by academic level (primary, intermediate, junior high, senior high, and college and university) and subdivided by economic concept. Concepts covered include: economic wants, scarcity and choices, economic systems, specialization and division of labor, interdependence, government regulation, supply and demand, market structure, income distribution, monetary policy, and savings and investment. Each project citation includes title, author, grade level, and abstract. Entries are indexed by entrant and title. (LP)
Published: 1982

2. Economic Education Projects: Abstracts from the 1979-80 Competition.

Author: Joint Council on Economic Education, New York, NY. and Palmer, George E.
Abstract: Over 175 economics education projects submitted to the 1979-1980 National Awards Program for Teaching Economics are abstracted. The aim of this annual competition is to discover outstanding classroom teaching practices while encouraging teachers to include and improve economics instruction in the classroom. Citations are contained in separate sections on primary grades, intermediate grades, junior high schools, senior high schools, and colleges and universities. Each project abstract is preceded by title, entrant's name and school affiliation, specific grade level, and list of economic concepts covered. Examples of projects, which range from weeklong units to yearlong activities, include creating a miniature town, holding an arts and crafts festival, and studying the economic factors involved in endangered species protection (primary level); operating a school store, simulating a corporation, and developing and marketing a product (intermediate level); making economic interpretations of American history and American literature, and studying the economics of law enforcement (junior high level); learning economics through cartoons, studying local utilities, and playing a collective bargaining game (senior high school); and making a student macroeconomics model and studying the financing of a public school (college level). Projects are indexed by title and entrant. A separate index lists award winners. (LP)
Published: 1981

3. Economic Education Projects: Abstracts from the 1980-81 Competition.

Author: Joint Council on Economic Education, New York, NY. and Palmer, George E.
Abstract: Abstracts of innovative and imaginative economics units are provided in this annotated listing of economic education projects submitted to the 1980-81 National Awards Program for Teaching Economics. Over 200 abstracts are contained in separate sections covering materials for primary grades, intermediate grades, junior high schools, senior high schools, and colleges and universities. Each project abstract is preceded by a listing of title, entrant's name and school affiliation, specific grade level, and economic concepts covered. The units vary from weeklong elementary activities to yearlong interdisciplinary projects. Examples are working an economics puzzle, baking and marketing cookies, and holding a consumer fair (primary grades); opening a checking account, marketing Christmas ornaments, and buying stocks (intermediate grades); studying food scarcity and creating an in-class economic system (junior high school); simulating a job hunt, investing in commodities, and studying the economics of recycling (high school level); and developing a computer simulation and an inservice teacher program (college level). Projects are indexed by title and entrant. A separate index lists award winners. (LP)
Published: 1982

4. Business and Law Respondents: What Is Ethical Behavior?

Author: Stevens, George E.
Abstract: In a survey of 97 business managers, 141 business students, 46 attorneys, and 98 law students, all groups were consistent in rating their own and peers' ethical beliefs; they perceived peers to have lower ethical values and were aware of competitive market pressures. The idea that new workplace entrants represent a new wave of ethical values was not supported. (SK)
Published: 1993

5. Members Thoughts on PPBE Reform

Author: Harker, Tom, Kovatch, George E., Maxwell, Mike, and Rhode, Marisa
Subjects: United States. Department of Defense -- Political activity, Financial management -- Political aspects, Business, Military and naval science
Abstract: This year's PDI in St. Louis was a resounding success. Not just because of the record numbers of participants, but because of all the emphasis and participation focused on the [...]
Published: 2023

6. Joint Labor-Management Training: A Case Study

Author: Garvey, Michael and O'Connell, George E.
Abstract: Discusses a joint labor-management training program designed to explore possibilities of improving postnegotiation relationships between the two. Planning, design, implementation, and results of the program are described. (WL)
Published: 1976

7. Women in Business: The View of Future Male and Female Managers.

Author: Stevens, George E.
Abstract: Discusses the integration of women into management positions in business. Found that women and men appear to be shedding the stereotype of traditional female roles and that men are more traditional than women in their attitudes toward women in management. (JOW)
Published: 1984

8. Exemptions from Unrelated Business Tax--Rental Income

Author: Reed, George E.
Abstract: Section 512(b) of the Internal Revenue Code contains several categorical exemptions from the unrelated business tax including rental income. Application of this exemption to church-owned property is examined. (LBH)
Published: 1975

9. De-Globalization, Welfare State Reforms and Labor Market Outcomes

Author: Molana, Hassan, Montagna, Catia, and Onwordi, George E.
Subjects: Economic reform -- Evaluation, Labor market -- Laws, regulations and rules, Globalization -- Economic aspects, Welfare state -- Laws, regulations and rules, Government regulation, Banking, finance and accounting industries, Business, Business, international
Abstract: Within an open economy framework characterized by vertical linkages in production, and search frictions with two-sided heterogeneity in the labor market, raising trade barriers is shown to increase unemployment across skill levels and to reduce labor market participation and aggregate income. These effects are not necessarily moderated by maintaining frictionless mobility of capital across borders. We find that a flexicurity reform of a liberal welfare state can dampen the adverse effects of de-globalization. JEL Classification F16 * F6, 1 Introduction The perception that international trade has been a source of economic dislocations with adverse effects on labor market outcomes, above all in industrial economies, is arguably one of [...]
Published: 2021
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10. Online Fundraising: Waiting for guidance from California, prepare for implementing

Author: Constantine, George E. and Vessels, Cristina I.
Subjects: Amendments (Parliamentary practice) -- Laws, regulations and rules, Government regulation, Business
Abstract: If your nonprofit organization fundraises online, and reaches donors in California in doing so, you might be wondering how to comply with the state's amended charitable solicitation law while its [...]
Published: 2023

11. Low-Dose Lung Radiation Therapy for COVID-19 Lung Disease: A Preclinical Efficacy Study in a Bleomycin Model of Pneumonitis

Author: Charles McSharry, Megan K. L. MacLeod, Rodrigo Gutierrez-Quintana, Emer Curley, Karin Williams, Sandeep K. Chahal, Karen Strathdee, George E. Finney, Evarest Onwubiko, Angie Rupp, Katrina Stevenson, Mark R. Jackson, and Anthony J. Chalmers
Subjects: Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Context (language use), Lung injury, Bleomycin, Effective dose (radiation), Gastroenterology, Mice, chemistry.chemical_compound, Internal medicine, Weight Loss, medicine, Animals, Humans, Radiology, Nuclear Medicine and imaging, Lung volumes, Lung, Pneumonitis, Radiation, Radiotherapy, business.industry, COVID-19, Pneumonia, respiratory system, medicine.disease, respiratory tract diseases, Mice, Inbred C57BL, Radiation therapy, Disease Models, Animal, Biology Contribution, medicine.anatomical_structure, Oncology, chemistry, Female, business
Abstract: Purpose:\ud Low-dose whole lung radiotherapy (LDLR) has been proposed as a treatment for patients with acute respiratory distress syndrome associated with SARS-CoV-2 infection and clinical trials are underway. There is an urgent need for preclinical evidence to justify this approach and inform dose, scheduling and mechanisms of action.\ud \ud Materials and methods:\ud Female C57BL/6 mice were treated with intranasal bleomycin sulphate (7.5 or 11.25 units/kg, day 0), then exposed to whole lung radiation therapy (0.5, 1.0, 1.5 Gy or sham, day 3). Bodyweight was measured daily and lung tissue harvested for histology and flow cytometry on day 10. Computed tomography (CT) lung imaging was performed pre-radiation (day 3) and pre-endpoint (day 10).\ud \ud Results:\ud Bleomycin caused pneumonitis of variable severity which correlated with weight loss. LDLR at 1.0 Gy was associated with a significant increase in the proportion of mice recovering to 98% of initial bodyweight and a proportion of these mice exhibited less severe histopathological lung changes. Mice experiencing moderate initial weight loss were more likely to respond to LDLR than those experiencing severe initial weight loss. Additionally, LDLR (1.0 Gy) significantly reduced bleomycin-induced increases in interstitial macrophages, CD103+ dendritic cells and neutrophil-DC hybrids. Overall, bleomycin-treated mice exhibited significantly higher percentages of non-aerated lung in left than right lungs and LDLR (1.0 Gy) limited further reductions in aerated lung volume in right but not left lungs. LDLR at 0.5 and 1.5 Gy did not improve bodyweight, flow cytometric or radiological readouts of bleomycin-induced pneumonitis.\ud \ud Conclusions:\ud Our data support the concept that LDLR can ameliorate acute inflammatory lung injury, identify 1.0 Gy as the most effective dose and provide evidence that it is more effective in the context of moderate than severe pneumonitis. Mechanistically, LDLR at 1.0 Gy significantly suppressed bleomycin-induced accumulation of pulmonary interstitial macrophages, CD103+ dendritic cells and neutrophil-DC hybrids.
Published: 2022
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12. Burden of Chronic Conditions Among Persons with HIV/AIDS and Psychiatric Comorbidity

Author: George E. Woody, Ravishankar Jayadevappa, Sumedha Chhatre, and David S. Metzger
Subjects: medicine.medical_specialty, Substance-Related Disorders, HIV Infections, Comorbidity, Disease, Article, Quality of life, Acquired immunodeficiency syndrome (AIDS), Virology, Survivorship curve, Internal medicine, mental disorders, Humans, Medicine, Acquired Immunodeficiency Syndrome, business.industry, virus diseases, medicine.disease, Mental health, Cross-Sectional Studies, Infectious Diseases, Cardiovascular Diseases, Chronic Disease, Cohort, Quality of Life, business, Medical Expenditure Panel Survey
Abstract: Background: Improved survivorship among persons living with HIV translates into a higher risk of medical comorbidities. Objective : We assessed the association between the intersection of physical (HIV) and mental health (psychiatric) conditions and intermediate outcomes. Methods: This was a cross-sectional study of the Medical Expenditure Panel Survey (MEPS)- Household Component between 1996 and 2016. We created four groups for persons aged ≥18: (1) HIV + psychiatric comorbidity, (2) HIV, (3) psychiatric comorbidity, and (4) no-HIV/no-psychiatric comorbidity. We compared the burden of medical comorbidities (metabolic disorders, cardiovascular disease, cancers, infectious diseases, pain, and substance use) among groups using chisquare tests. We used logistic regression to determine the association between group status and medical comorbidity. Results: Of 218,133,630 (weighted) persons aged ≥18, 0.18% were HIV-positive. Forty-three percent of the HIV group and 19% of the no-HIV group had psychiatric comorbidities. Half of the HIV+ psychiatric disorder group had at least one medical comorbidity. Compared to the no- HIV/no-psychiatric comorbidity group, the HIV + psychiatric comorbidity group had the highest odds of medical comorbidity (OR= 3.69, 95% CI = 2.99, 4.52). Conclusion: Persons presenting with HIV + psychiatric comorbidity had higher odds of medical comorbidities of pain, cancer, cardiovascular disease, substance use, metabolic disorders and infectious diseases, beyond that experienced by persons with HIV infection or psychiatric disorders, independently. Future research will focus on the mediating effects of social determinants and biological factors on outcomes such as the quality of life, cost and mortality. This will facilitate a shift away from the single-disease framework and compress morbidity of the aging cohort of HIV-infected persons.
Published: 2021
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13. A Softwarized Intrusion Detection System for the RPL-based Internet of Things networks

Author: Lefteris Mamatas, Sophia G. Petridou, George E. Violettas, and George Simoglou
Subjects: Computer Networks and Communications, business.industry, Computer science, Intrusion detection system, Computer security, computer.software_genre, Asset (computer security), Identification (information), Broadcasting (networking), Workflow, Hardware and Architecture, Overhead (computing), The Internet, business, Protocol (object-oriented programming), computer, Software
Abstract: Internet of Things (IoT) constitutes a pivotal contributor to the Industry 4.0 (I 4.0) vision, technologically transforming production and societies. It enables novel services through the seamless integration of devices, such as motes carrying sensors, with the Internet. However, the broad adoption of IoT technologies is facing security issues due to the direct access to the devices from the Internet, the broadcasting nature of the wireless media, and the potential unattended operation of relevant deployments. In particular, the Routing over Low Power and Lossy Networks (RPL) protocol, a prominent IoT solution, is vulnerable to a large number of attacks, both of general-purpose and RPL-specific nature, while the resource-constraints of the corresponding devices are making attack mitigation even more challenging, e.g., in terms of involved control overhead and detection accuracy. In this paper, we introduce ASSET, a novel Intrusion Detection System (IDS) for RPL with diverse profiles to tackle the above issues that mitigate at least 13 attacks. At the same time, other solutions go up to eight. ASSET, inspired by the network softwarization paradigm, supports a novel, extendable workflow, bringing together three anomaly-detection and four RPL specification-based mechanisms, a novel attacker identification process, as well as multiple attack mitigation strategies. Our IDS also supports an adaptable control & monitoring protocol, trading overhead for accuracy, depending on the network conditions. The proof-of-concept experiments show that ASSET entails a low overhead for the different modes of operation it supports (i.e., 6.28 percent on average) compared to other solutions reaching up to 30 percent. At the same time, it also keeps the power consumption at acceptable levels (from 0.18 up to 1.54 percent more). Moreover, it provides 100 percent accuracy for specific attacks and can identify the attacker in far more attacks than any other similar solution.
Published: 2021
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14. Τechno-economic assessment of industrially-captured CO2 upgrade to synthetic natural gas by means of renewable hydrogen

Author: Dimitris Ipsakis, Athanasios Lampropoulos, Spiros Papaefthimiou, Michalis Konsolakis, George E. Marnellos, and Georgios Varvoutis
Subjects: Substitute natural gas, Electrolysis of water, Renewable Energy, Sustainability and the Environment, business.industry, Cement plant, RES powered electrolytic hydrogen, Renewable energy, CO hydrogenation for synthetic natural gas production, Lead (geology), Upgrade, Work (electrical), Circular economy approach, Production (economics), Environmental science, Electricity, CO capture and utilization, Process engineering, business, Feasibility assessment
Abstract: Summarization: The present work assesses the feasibility of a circular approach towards a carbon-neutral process that leads to the production of 500 ktn/yr of synthetic natural gas (SNG). Overall, three main systems were sized, simulated and heat/energy coupled under a realistic scenario that ensures an autonomous and economically feasible operation: a) cement-based CO2 capture with amines, b) H2 production through combined solar/wind powered water electrolysis and c) CO2 catalytic hydrogenation. The economic analysis revealed a min-to-max break-even price of 500–1550 €/tn of SNG, taking also into account the potential sales of the high-purity O2 (from water electrolysis) and the excess electricity produced via renewable energy sources (RES). The ranges for the SNG prices correspond to the screening of CO2 penalty fees (25–100 €/tn) along with the option to subsidy the RES-H2 system up to 36 %. Two further critical issues were also revealed: a highly feasible operating circular scheme is achieved only when SNG is recycled to the cement industry (to satisfy heat/energy requirements), whereas RES-powered H2 is more competitive than electricity grid, as long as electricity prices are higher than 0.02 €/kWh. The proposed process proves that a combination of novel technologies and renewables can lead in a circular approach towards added-value products. Presented on: Renewable Energy
Published: 2021
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15. Injuries and risk factors in professional football players during four consecutive seasons

Author: Christos Mourikis, Christos Theos, Emmanouil Smpokos, George E. Manolarakis, and Manolis Linardakis
Subjects: Football players, business.industry, Medicine, Orthopedics and Sports Medicine, business, Demography
Published: 2021
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16. A Systematic Review of Cyberstalking Victimization and Offending Behaviors

Author: George E. Higgins and Catherine D. Marcum
Subjects: Categorization, business.industry, Electronic surveillance, Inclusion and exclusion criteria, Cyberstalking, The Internet, Social media, Interpersonal communication, business, Psychology, Law, Clinical psychology, Criminal justice
Abstract: A systematic review of literature investigating cyberstalking offending and victimization was conducted, considering multiple key words and phrases used to label the behavior: cyberstalking, cyber dating abuse, cybervictimization, Internet, interpersonal electronic surveillance, and victimization. The following electronic databases, with the indication of peer-reviewed journal articles as a requirement, were searched: Academic Search Complete, Criminal Justice Database (ProQuest), Google, JSTOR and PsychInfo. After sorting through the studies using the inclusion and exclusion criteria, 31 studies remained for review. Correlates of the behaviors were discussed for each categorization, with main themes including negative characteristics of relationship behaviors, and social media and online use as main predictors of victimization and offending. There is a strong need for further research utilizing older age groups and individuals who are married, as well as a need for longitudinal research.
Published: 2021
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17. Risk of Developing Breast Reconstruction Complications: A Machine-Learning Nomogram for Individualized Risk Estimation with and without Postmastectomy Radiation Therapy

Author: Laura Salama, Amy S. Colwell, Alice Y. Ho, Jonathan M. Winograd, Saveli Goldberg, Amy Shui, Waleed Arafat, George E. Naoum, Alphonse G. Taghian, and Barbara L. Smith
Subjects: Adult, Mammaplasty, medicine.medical_treatment, Breast Neoplasms, Machine learning, computer.software_genre, Risk Assessment, Machine Learning, Young Adult, Postoperative Complications, Breast cancer, medicine, Humans, Mastectomy, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Incidence, Implant failure, Capsular contracture, Middle Aged, Nomogram, medicine.disease, Combined Modality Therapy, United States, Radiation therapy, Nomograms, Female, Surgery, Artificial intelligence, Implant, business, Breast reconstruction, computer, Follow-Up Studies, Forecasting
Abstract: BACKGROUND The authors' purpose was to create a nomogram using machine learning models predicting risk of breast reconstruction complications with or without postmastectomy radiation therapy. METHODS Between 1997 and 2017, 1617 breast cancer patients undergoing mastectomy and breast reconstruction were analyzed. Those with autologous, tissue expander/implant, and single-stage direct-to-implant reconstruction were included. Postmastectomy radiation therapy was delivered either with three-dimensional conformal photon or proton therapy. Complication endpoints were defined based on surgical reintervention operative notes as infection/necrosis requiring debridement. For implant-based patients, the authors studied capsular contracture requiring capsulotomy and implant failure. For each complication endpoint, least absolute shrinkage and selection operator-penalized regression was used to select the subset of predictors associated with the smallest prediction error from 10-fold cross-validation. Nomograms were built using the least absolute shrinkage and selection operator-selected predictors, and internal validation using cross-validation was performed. RESULTS Median follow-up was 6.6 years. Among 1617 patients, 23 percent underwent autologous reconstruction, 39 percent underwent direct-to-implant reconstruction, and 37 percent underwent tissue expander/implant reconstruction. Among 759 patients who received postmastectomy radiation therapy, 8.3 percent received proton-therapy to the chest wall and nodes and 43 percent received chest wall boost. Internal validation for each model showed an area under the receiver operating characteristic curve of 73 percent for infection, 75 percent for capsular contracture, 76 percent for absolute implant failure, and 68 percent for overall implant failure. Periareolar incisions and complete implant muscle coverage were found to be important predictors for infection and capsular contracture, respectively. In a multivariable analysis, we found that protons compared to no postmastectomy radiation therapy significantly increased capsular contracture risk (OR, 15.3; p < 0.001). This was higher than the effect of photons with electron boost versus no postmastectomy radiation therapy (OR, 2.5; p = 0.01). CONCLUSION Using machine learning, these nomograms provided prediction of postmastectomy breast reconstruction complications with and without radiation therapy. CLINICAL QUESTION/LEVEL OF EVIDENCE Risk, III.
Published: 2021
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18. A simple method for mitigating error in the fixed-offset of a double-crystal monochromator

Author: Steve M. Heald and George E. Sterbinsky
Subjects: Nuclear and High Energy Physics, Radiation, Offset (computer science), Materials science, business.industry, Physics::Optics, Rotation, Translation (geometry), Synchrotron, law.invention, Crystal, Optics, law, Condensed Matter::Superconductivity, Physics::Accelerator Physics, Monochromatic color, business, Instrumentation, Beam (structure), Monochromator
Abstract: In order to maintain a constant monochromatic synchrotron X-ray beam height for all energies, the separation between the crystals of a double-crystal monochromator is typically adjusted, via translation of the second crystal, while X-ray energy is varied, via rotation of the crystal pair. The ability to accurately translate the second crystal requires precise knowledge of the separation between the two crystals and, when present, crystal miscuts. Here, a simple method for calibrating the crystal gap from measured variation in the X-ray beam height that eliminates error in the fixed beam offset is provided.
Published: 2021
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19. Hybrid imaging of neuroendocrine tumors in the heart: Union is strength

Author: Alexandros P. Patrianakos, Nikolaos Kapsoritakis, Sophia Koukouraki, Fragiskos I. Parthenakis, Stelios Zervakis, Olga Bourogianni, George E. Kochiadakis, Sophia Papadaki, Maria E. Marketou, and A Plevritaki
Subjects: Hormonal activity, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, Neuroendocrine tumors, medicine.disease, Positron emission tomography, medicine, Effective treatment, Radiology, Nuclear Medicine and imaging, Radiology, Cardiology and Cardiovascular Medicine, Anatomic Location, Prospective cohort study, business, Emission computed tomography
Abstract: Cardiac neuroendocrine tumors (NETs) are particularly rare tumors that can lead to a very poor clinical outcome, partly because of metastases but mainly because of manifestations of the hormonal activity they exhibit. Prompt diagnosis is important in order to start the most effective treatment for their removal or management, with the fewest complications. They are often difficult to diagnose, especially in their early stages. One of the reasons for this is that the heart is an organ with a high rate of metabolism and is located in close proximity to other high-metabolism organs. In addition, the anatomic location and their small size render their diagnosis extremely challenging. In recent years, hybrid imaging methods have revolutionized the diagnostic approach to oncology patients and have established a place in the diagnosis of cardiac NETs, because they provide both anatomical and functional information at the same time. Positron emission tomography/computed tomography (PET/CT), PET/magnetic resonance imaging (PET/MRI) and single-photon emission computed tomography/CT (SPECT/CT) are widely used in clinical practice because of the very important metabolic information, the high sensitivity and specificity. However, prospective studies are needed to confirm the true clinical and prognostic value of various hybrid imaging diagnostic techniques in cardiac NETs.
Published: 2021
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20. Evidence of acrolein in synovial fluid of dogs with osteoarthritis as a potential inflammatory biomarker

Author: Riyi Shi, Seth A. Herr, George E. Moore, Sarah Malek, Jeff C. Ko, and Mark C. Rochat
Subjects: medicine.medical_specialty, Pathology, Inflammation, Osteoarthritis, Diseases of the musculoskeletal system, Matrix metalloproteinase, chemistry.chemical_compound, Dogs, Rheumatology, Western blot, Internal medicine, medicine, Animals, Synovial fluid, Orthopedics and Sports Medicine, Acrolein, medicine.diagnostic_test, business.industry, Research, medicine.disease, chemistry, RC925-935, Matrix Metalloproteinase 2, medicine.symptom, business, Inflammatory biomarker, FDP-lysine, acrolein-lysine adduct, MMP2, Biomarkers
Abstract: Background Acrolein is a known pro-inflammatory toxic aldehyde, propagating cellular damage and tissue inflammation in humans and animal models of various diseases. Osteoarthritis (OA) has a significant inflammatory component; however, presence of acrolein in synovial fluid of joints with OA has not been previously reported. The first aim of this study was to evaluate evidence of acrolein in the synovial fluid of dogs with OA as well as in Control joints. The second aim was to determine if evidence of acrolein can be detected in synovial fluid samples that have been in a frozen state for long periods of time. Methods In this pilot clinical study, synovial fluid samples were prospectively collected (i.e., New samples) from a single joint of both clinically healthy (New Control, n = 5) and dogs with OA (New OA, n = 16) and frozen until the time of analysis. Additionally, frozen synovial fluid samples from a biobank (i.e., Old samples) were used to evaluate ability to detect evidence of acrolein in long-term stored samples (median of 4.89 years) in Old Control (n = 5) and Old OA (n = 5) samples. Measurements of acrolein in all synovial fluid samples was based on detection of its major protein adduct, N ε - (3-formyl-3, 4-dehydropiperidino)lysine (FDP-lysine), using the western blot method. Synovial fluid matrix metalloproteinase 2 (MMP2) was measured in all samples using the western blot method as a positive control of OA inflammation. Results Acrolein-lysine adduct was detected in both Control (n = 10) and OA (n = 21) groups in both Old and New samples. Acrolein-lysine adduct and MMP2 were detectable at a lower level in the Old compared to New synovial fluid samples; however, the differences were not statistically significant (p > 0.1). The measured MMP2 levels were significantly higher in the OA compared to Control group samples (p = 0.033), but not for acrolein-lysine adduct (p = 0.30). Conclusions This study confirmed evidence of acrolein in canine synovial fluid of both OA and Control groups. Freezing of synovial fluid for up to 5 years does not appear to significantly affect the ability to detect acrolein-lysine adduct and MMP2 in these samples.
Published: 2021

21. The early effect of dapagliflozin on strain and tissue Doppler parameters of diastolic function in diabetic patients with heart failure with reduced ejection fraction

Author: Labrini Tsigkriki, Fragkiskos Parthenakis, Vasiliki Katsi, Alexandros P. Patrianakos, Maria Mamaloukaki, Spyridon Maragkoudakis, George E. Kochiadakis, Kostas Tsioufis, and Maria Marketou
Subjects: medicine.medical_specialty, Ejection fraction, strain and tissue Doppler parameters, business.industry, diastolic function, Diastole, General Medicine, dapagliflozin, medicine.disease, Sacubitril, chemistry.chemical_compound, chemistry, Valsartan, Clinical Research, Internal medicine, Heart failure, Cardiology, Medicine, Enalapril, Dapagliflozin, business, Prospective cohort study, medicine.drug
Abstract: IntroductionHeart failure (HF) with reduced ejection fraction (HFrEF) remains a challenging problem due to its high mortality rate. The PARADIGM HF trial and a new class of drugs – angiotensin receptor–neprilysin inhibitors (ARNIs) – managed to change the current perception of HF treatment by reducing cardiovascular mortality and morbidity as well as HF hospitalizations compared with enalapril and have emerged as an evidence-based therapy for HFrEF. Another novelty in HF therapy is dapagliflozin, a sodium-glucose transporter-2 inhibitor (SGLT2i) which decreased the rates of cardiac death and worsening of HF in the DAPA-HF trial, when added in other guideline recommended therapy. A recent study evaluated the potency of dapagliflozin in terms of mortality and deterioration of HF, in patients taking sacubitril/valsartan and in patients who were naive.Material and methodsA prospective cohort study of 30 symptomatic HF patients with EF < 35% (aged 65 ±10 years) was conducted. Diabetic (2TDM) patients of NYHA status II–III, previously treated with ARNI, -blocker, and mineralocorticoid receptor antagonists (MRA) were included. Dapagliflozin was added to their therapy.ResultsEchocardiographic evaluation revealed improvement of both conventional tissue Doppler and diastolic strain parameters by dapagliflozin addition on HF therapy.ConclusionsDapagliflozin impact on diastolic function may explain the symptom amelioration and the improvement of quality of life. And more specifically, the ratio of early diastolic transmitral flow velocity to global strain rate at the early filling phase of diastole (E/SRE)may be considered a reliable index of HF therapy responders.
Published: 2021

22. The role for JAK inhibitors in the treatment of immune-mediated rheumatic and related conditions

Author: James Brock, George E Fragoulis, Neil Basu, Iain B. McInnes, and Stefan Siebert
Subjects: business.industry, medicine.medical_treatment, Immunology, Inflammatory Bowel Diseases, medicine.disease, Bioinformatics, Inflammatory bowel disease, Biologic Disease-Modifying Antirheumatic Drug, Proinflammatory cytokine, Targeted therapy, Arthritis, Rheumatoid, Psoriatic arthritis, Psoriasis, Rheumatoid arthritis, medicine, Animals, Humans, Janus Kinase Inhibitors, Immunology and Allergy, Spondylitis, Ankylosing, Disease-modifying antirheumatic drug, business
Abstract: JAK inhibitors (JAKIs) are a new class of targeted therapy that have entered clinical practice for the treatment of immune-mediated rheumatic conditions. JAKIs can block the signaling activity of a variety of proinflammatory cytokines and therefore have the potential to mediate therapeutic benefits across a wide range of immune-mediated conditions. Several JAKIs are licensed, and many more are undergoing clinical trials. Here we provide a narrative review of the current and upcoming JAKIs for adult immune-mediated rheumatic and related conditions, with a specific focus on efficacy in rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, psoriasis, and inflammatory bowel disease. The overall safety profile of JAKIs appears largely comparable to that of existing biologic cytokine-targeting agents, particularly, TNF inhibitors, apart from risk of herpes zoster, which is increased for JAKIs. Importantly however, unresolved safety concerns remain, particularly relating to increased venous thromboembolism.
Published: 2021
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23. Initial Invasive or Conservative Strategy for Stable Coronary Disease

Author: Maron D. J., Hochman J. S., Reynolds H. R., Bangalore S., O'Brien S. M., Boden W. E., Chaitman B. R., Senior R., Lopez-Sendon J., Alexander K. P., Lopes R. D., Shaw L. J., Berger J. S., Newman J. D., Sidhu M. S., Goodman S. G., Ruzyllo W., Gosselin G., Maggioni A. P., White H. D., Bhargava B., Min J. K., John Mancini G. B., Berman D. S., Picard M. H., Kwong R. Y., Ali Z. A., Mark D. B., Spertus J. A., Krishnan M. N., Elghamaz A., Moorthy N., Hueb W. A., Demkow M., Mavromatis K., Bockeria O., Peteiro J., Miller T. D., Szwed H., Doerr R., Keltai M., Selvanayagam J. B., Gabriel Steg P., Held C., Kohsaka S., Mavromichalis S., Kirby R., Jeffries N. O., Harrell F. E., Rockhold F. W., Broderick S., Bruce Ferguson T., Williams D. O., Harrington R. A., Stone G. W., Rosenberg Y, ISCHEMIA Research Group: Joseph Ricci, A Tello Montoliu, A I Robero Aniorte, Abbey Mulder, Abhay A Laddu, Abhinav Goyal, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Abraham Oomman, Adam J Jaskowiak, Adam Kolodziej, Adam Witkowski, Adnan Hameed, Adriana Anesini, Afshan Hussain, Agne Juceviciene, Agne Urboniene, Agnes Jakal, Agnieszka Szramowska, Ahmad Khairuddin, Ahmed Abdel-Latif, Ahmed Adel, Ahmed Aljzeeri, Ahmed Kamal, Ahmed Talaat, Aimee Mann, Aira Contreras, Ajit Kumar, V K Kumar, Akemi Furukawa, Akshay Bagai, Akvile Smigelskaite, Alain Furber, Alain Rheault, Alaine Melanie Loehr, Alan Rosen, Albert Varga, Albertina Qelaj, Alberto Barioli, Aldo Russo, Alec Moorman, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alena Kuleshova, Alessandro Sionis, Alexander A Sirker, Alexander M Chernyavskiy, Alexandra Craft, Alexandra Vazquez, Alexandre Ciappina Hueb, Alexandre S Colafranseschi, Alexandre Schaan de Quadros, Alexandre Tognon, Ali Alghamdi, Alice Manica Muller, Aline Nogueira Rabaça, Aline Peixoto Deiro, Alison Hallam, Allegra Stone, Allison Schley, Almudena Castro, Alvaro Rabelo Ales, Amanda Germann, Amanda O'Malley, Amar Uxa, Amarachi Ojajuni, Amarino C Oliveira Jr, Amber B Hull, Ambuj Roy, Amer Zarka, Amir Janmohamed, Ammani Brown, Ammy Malinay, Amparo Martinez Monzonis, Amy J Richards, Amy Iskandrian, Amy Ollinger, Ana D Djordjevic-Dikic, Ana Fernández Martínez, Ana Gomes Almeida, Ana Paula Batista, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anam Siddiqui, Anastasia M Kuzmina-Krutetskaya, Andras Vertes, Andre S Sousa, Andre Gabriel, André Schmidt, Andrea M Lundeen, Andrea Bartykowszki, Andrea Lorimer, Andrea Mortara, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew G Howarth, Andrew J Moriarty, Andrew Docherty, Andrew Starovoytov, Andrew Zurick, Andrzej Łabyk, Andrzej Swiatkowski, Andy Lam, Anelise Kawakami, Angela Hoye, Angela Kim, Angelique Smit, Angelo Nobre, Anil V Shah, Anja Ljubez, Anjali Anand, Ankush Sachdeva, Ann Greenberg, Ann Luyten, Ann Ostrander, Anna Di Donato, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Proietti, Anna Teresinska, Anne Marie Webb, Anne Cartwright, Anne Heath, Anne Mackin, Anong Amaritakomol, Anong Chaiyasri, Anoop Chauhan, Anoop Mathew, Anthony Gemignani, Anto Luigi Andres, Antonia Vega, Antonietta Hansen, Antonino Ginel Iglesias, Antonio Carlos Carvalho, Antonio Di Chiara, Antonio Serra Peñaranda, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anupama Rao, Aquiles Valdespino-Estrada, Araceli Boan, Areef Ishani, Ariel Diaz, Arijit Ghosh, Arintaya Prommintikul, Arline Roberts, Arnold H Seto, Arnold P Good, Arshed Quyyumi, Arthur J Labovitz, Arthur Kerner, Arturo S Campos-Santaolalla, Arunima Misra, Ashok Mukherjee, Ashok Seth, Ashraf Seedhom, Asim N Cheema, Asker Ahmed, Atul Mathur, Atul Verma, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Baljeet Kaur, Bandula Guruge, Barbara Brzezińska, Barbara Nardi, Bartosz Czarniak, Bebek Singh, Begoña Igual, Bela Merkely, Belen Cid Alvarez, Benjamin J Spooner, Benjamin J W Chow, Benjamin Cheong, Benoy N Shah, Bernard de Bruyne, Bernardas Valecka, Bernhard Jäger, Beth A Archer, Beth Abramson, Beth Jorgenson, Bethany Harvey, Betsy O'Neal, Bev Atkinson, Bev Bozek, Bevin Lang, Bijulal Sasidharan, Bin Yang, Bin Zhang, Binoy Mannekkattukudy Kurian, Bjoern Goebel, Bob Hu, Bogdan A Popescu, Bogdan Crnokrak, Bolin Zhu, Bonnie J Kirby, Brandi D Zimbelman, Brandy Starks, Branko D Beleslin, Brenda Hart, Brian P Shapiro, Brian McCandless, Brianna Wisniewski, Brigham R Smith, Brooks Mirrer, Bruce McManus, Bruce Rutkin, Bruna Edilena Paulino, Bruna Maria Ascoli, Bryn Smith, Byron J Allen, C Michael Gibson, C Noel Bairey Merz, Calin Pop, Cameron Hague, Camila Thais de Ormundo, Candace Gopaul, Candice P Edillo, Carísi A Polanczyk, Carita Krannila, Carla Vicente, Carl-Éric Gagné, Carlo Briguori, Carlos Peña Gil, Carlos Alvarez, Carly Ohmart, Carmen C Beladan, Carmen Ginghina, Carol M Kartje, Caroline Alsweiler, Caroline Brown, Caroline Callison, Caroline Pinheiro, Caroline Rodgers, Caroline Spindler, Carolyn Corbett, Carrie Drum, Casey Riedberger, Catherine Bone, Catherine Fleming, Catherine Gordon, Catherine Jahrsdorfer, Catherine Lemay, Catherine Weick, Cathrine Patten, Cecilia Goletto, Cezary Kepka, Chandini Suvarna, Chang Xu, Chantale Mercure, Charle A Viljoen, Charlene Wiyarand, Charles Jia-Yin Hou, Charles Y Lui, Charles Cannan, Charles Cornet, Charlotte Pirro, Chataroon Rimsukcharoenchai, Chen Wang, Cheng-Ting Tsai, Chen-Yen Chien, Cheryl A Allardyce, Chester M Hedgepeth, Chetan Patel, Chiara Attanasio, Chih-Hsuan Yen, Chi-Ming Chow, Ching Min Er, Ching-Ching Ong, Cholenahally Nanjappa Manjunath, Chris Beck, Chris Buller, Christel Vassaliere, Christian Hamm, Christiano Caldeira, Christie Ballantyne, Christina Björklund, Christine R Hinton, Christine Bergeron, Christine Masson, Christine Roraff, Christine Shelley, Christophe Laure, Christophe Thuaire, Christopher Kinsey, Christopher McFarren, Christopher Spizzieri, Christopher Travill, Chun-Chieh Liu, Chung-Lieh Hung, Chunguang Li, Chun-Ho Yun, Chunli Xia, Ciarra Heard, Cidney Schultz, Clare Venn-Edmonds, Claudia P Hochberg, Claudia Wegmayr, Claudia Cortés, Claudia Escobar, Cláudia Freixo, Claudio T Mesquita, Clemens T Kadalie, Colin Berry, Constance Philander, Corine Thobois, Costantino Costantini, Courtney Page, Craig Atkinson, Craig Barr, Craig Paterson, Cristina Bare, Cynthia Baumann, Cynthia Burman, Dalisa Espinosa, Damien Collison, Dan Deleanu, Dan Elian, Dan Gao, Dana Oliver, Daniel P Vezina, Daniel O'Rourke, Daniele Komar, Danielle Schade, Darrel P Francis, Dastan Malaev, David A Bull, David E Winchester, David P Faxon, David Booth, David Cohen, David DeMets, David Foo, David Schlichting, David Taggart, David Waters, David Wohns, Davis Vo, Dawid Teodorczyk, Dawn Shelstad, Dawn Turnbull, Dayuan Li, Dean Kereiakes, Deborah O'Neill, Deborah Yip, Debra K Johnson, Debra Dees, Deepak L Bhatt, Deepika Gopal, Deepti Kumar, Deirdre Mattina, Deirdre Murphy, Delano R Small, Delsa K Rose, Dengke Jiang, Denis Carl Phaneuf, Denise Braganza, Denise Fine, Derek Cyr, Desiree Tobin, Diana Cukali, Diana Parra, Diane Camara, Diane Minshall Liu, Diego Adrián Vences, Diego Franca de Cunha, Dimitrios Stournaras, Dipti Patel, Dongze Li, Donna Exley, Dorit Grahl, Dragana Stanojevic, Duarte Cacela, Dwayne S G Conway, E Pinar Bermudez, Eapen Punnoose, Edgar L Tay, Edgar Karanjah, Edoardo Verna, Eduardo Hernandez-Rangel, Edward D Nicol, Edward O McFalls, Edward T Martin, Edyta Kaczmarska, Ekaterina I Lubinskaya, Elena A Demchenko, Elena Refoyo Salicio, Eli Feen, Elihú Durán-Cortés, Elisabeth M Janzen, Elise L Hannemann, Elise van Dongen, Elissa Restelli Piloto, Eliza Kaplan, Elizabeta Srbinovska Kostovska, Elizabeth Capasso-Gulve, Elizabeth Congdon, Elizabeth Ferguson, Elizaveta V Zbyshevskaya, Ellen Magedanz, Ellie Fridell, Ellis W Lader, Elvin Kedhi, Emanuela Racca, Emilie Tachot, Emily DeRosa, Encarnación Alonso-Álvarez, Eric Nicollet, Eric Peterson, Erick Alexánderson Rosas, Erick Donato Morales, Erin Orvis, Ermina Moga, Estelle Montpetit, Estevao Figueiredo, Eugene Passamani, Eugenia Nikolsky, Eunice Yeoh, Evgeniy I Kretov, Ewa Szczerba, Ewelina Wojtala, Expedito Eustáquio Ribeiro Silva, F Marin Ortuño, Fabio R Farias, Fabio Fimiani, Fabrizio Rolfo, Fa-Chang Yu, Fadi Hage, Fadi Matar, Fahim Haider Jafary, Fang Feng, Fang Liu, Fatima Ranjbaran, Fatima Rodriguez, Fausto J Pinto, Fauzia Rashid, Federica Ramani, Fei Wang, Fernanda Igansi, Filipa Silva, Filippo Ottani, Fiona Haines, Firas Al Solaiman, Flávia Egydio, Flavio Lyra, Florian Egger, Fran Farquharson, Frances Laube, Francesc Carreras Costa, Francesca de Micco, Francesca Bianchini, Francesca Pezzetta, Francesca Pietrucci, Francesco Orso, Francesco Pisano, Francis Burt, Francisca Patuleia Figueiras, Francisco Fernandez-Aviles, Francois Pierre Mongeon, Frans Van de Werf, Franziska Guenther, Fraser N Witherow, Fred Mohr, Frederico Dall'Orto, Fumiyuki Otsuka, G De La Morena, G Karthikeyan, Gabor Dekany, Gabor Kerecsen, Gabriel Galeote, Gabriel Grossmann, Gabriel Vorobiof, Gabriela Sanchez de Souza, Gabriela Guzman, Gabriela Zeballos, Gabriele Gabrielli, Gabriele Jakl-Kotauschek, Gail A Shammas, Gail Brandt, Gang Chen, Gary E Lane, Gary J Luckasen, Gautam Sharma, Gelmina Mikolaitiene, Gennie Yee, Georg Nickenig, George E Revtyak, George J Juang, Gerald Fletcher, Gerald Leonard, Gerard Patrick Devlin, Gerard Esposito, Gergely Ágoston, Gervasio Lamas, Geza Fontos, Ghada Mikhail, Gia Cobb, Gian Piero Perna, Gianpiero Leone, Giles Roditi, Gilles Barone-Rochette, Girish Mishra, Giuseppe Tarantini, Glenda Wong, Glenn S Hamroff, Glenn Rayos, Gong Cheng, Gonzalo Barge-Caballero, Goran Davidović, Goran Stankovic, Gordana Stevanovic, Grace Jingyan Wang, Grace M Young, Graceanne Wayser, Graciela Scaro, Graham S Hillis, Graham Wong, Grazyna Anna Szulczyk, Gregor Simonis, Gregory Kumkumian, Gretchen Ann Peichel, Grzegorz Gajos, Gudrun Steinmaurer, Guilherme G Rucatti, Guilherme Portugal, Guilhermina Cantinho Lopes, Guillem Pons Lladó, Gunnar Frostfelt, Gurpreet S Wander, Gurpreet Gulati, Gustavo Pucci, Hafidz Abd Hadi, Haibo Zhang, Haitao Wang, Halina Marciniak, Han Chen, Hanan Kerr, Hani Najm, Hanna Douglas, Hannah Phillips, Hao Dai, Haojian Dong, Haqeel Jamil, Harikrishnan Sivadasanpillai, Harry Suryapranata, Hassan Reda, Hayley Pomeroy, Heather Barrentine, Heather Golden, Heather Hurlburt, Heidi Wilson, Helen C Tucker, Helene Abergel, Hemalata Siddaram, Hermine Osseni, Herwig Schuchlenz, Hesong Zeng, Hicham Skali, Hilda Solomon, Hollie Horton, Holly Hetrick, Holly Little, Holly Park, Hongjie Chi, Hossam Mahrous, Howard A Levite, Hristo Pejkov, Huajun Li, Hugo Bloise-Adames, Hugo Marques, Hui Zhong, Hui-Min Zhang, Humayrah Hashim, Hung-I Yeh, Hussien El Fishawy, Ian Webb, Iftikhar Kullo, Igor O Grazhdankin, Ihab Hamzeh, Ikraam Hassan, Ikuko Ueda, Ileana L Pina, Ilona Tamasauskiene, Ilse Bouwhuis, Imran Arif, Ina Wenzelburger, Inês Zimbarra Cabrita, Ines Rodrigues, Inga H Robbins, Inga Soveri, Ingela Schnittger, Iqbal Karimullah, Ira M Dauber, Iram Rehman, Irena Peovska Mitevska, Irene Marthe Lang, Irina Subbotina, Irma Kalibataite-Rutkauskiene, Irni Yusnida, Isabel Estela Carvajal, Isabella C Palazzo, Isabelle Hogan, Isabelle Roy, Ishba Syed, Ishita Tejani, Ivan A Naryshkin, Ivana Jankovic, Iwona Niedzwiecka, J David Knight, Jacek Kusmierek, Jackie M White, Jackie Chow, Jacob Udell, Jacqueline E Tamis-Holland, Jacqueline Fannon, Jacquelyn A Quin, Jacquelyn Do, Jaekyeong Heo, Jakub Maksym, James E Davies, James H O'Keefe Jr, James J Jang, James Cha, James Harrison, James Hirsch, James Stafford, James Tatoulis, Jamie Rankin, Jan Henzel, Jan Orga, Jana Tancredi, Janaina Oliveira, Jane Burton, Jane Eckstein, Jane Marucci, Janet P Knight, Janet Blount, Janet Halliday, Janetta Kourzenkova, Janitha Raj, Jan-Malte Sinning, Jaqueline Pozzibon, Jaroslaw Drozdz, Jaroslaw Karwowski, Jason D Glover, Jason Loh Kwok, Jason T Call, Jason Linefsky, Jassira Gomes, Jati Anumpa, Javier J Garcia, Javier Courtis, Jay Meisner, K Jayakumar, Jayne Scales, Jean E Denaro, Jean Michel Juliard, Jean Ho, Jeanette K Stansborough, Jean-Michel Juliard, Jeanne Russo, Jeannette J M Schoep, Jeet Thambyrajah, Jeff Leimberger, Jeffery A Breall, Jeffrey A Kohn, Jeffrey C Milliken, Jeffrey Anderson, Jeffrey Blume, Jeffrey Kanters, Jeffrey Lorin, Jeffrey Moses, Jelena J Stepanovic, Jelena Celutkiene, Jelena Djokic, Jelena Stojkovic, Jenne M Jose, Jenne Manchery, Jennifer A Mull, Jennifer H Czerniak, Jennifer L Stanford, Jennifer Gillis, Jennifer Horst, Jennifer Isaacs, Jennifer Langdon, Jennifer Thomson, Jennifer Tomfohr, Jennifer White, Jen-Yuan Kuo, Jeremy Rautureau, Jerome Fleg, Jessica Berg, Jessica Rodriguez, Jessica Waldron, Jhina Patro, Jia Li, Jiajia Mao, Jiamin Liu, Jian'an Wang, Jianhua Li, Jianxin Zhang, Jie Qi, Jihyun Lyo, Jill Marcus, Jim Blankenship, Jing Zhang, Jingjing Liu, Jing-Yao Fan, Jiun-Yi Li, Jiwan Pradhan, Jiyan Chen, J M Rivera Caravaca, Jo Evans, Joan Garcia Picart, Joan Hecht, Joanna Jaroch, Joanna Zalewska, Joanne Kelly, Joanne Taaffe, João Reynaldo Abbud, João V Vitola, Joaquín V Peñafiel, Jocelyne Benatar, Jody Bindeman, Joe Sabik, Joel Klitch, Johann Christopher, Johannes Aspberg, John D Friedman, John F Beltrame, John F Heitner, John Joseph Graham, John R Davies, John Doan, John Kotter, John Kurian, John Mukai, John Pownall, Jolanta Sobolewska, Jon Kobashigawa, Jonathan L Goldberg, Jonathan W Bazeley, Jonathan Byrne, Jonathan Himmelfarb, Jonathan Leipsic, Jonean Thorsen, Jorge F Trejo Gutierrez, Jorge Escobedo, Jorik Timmer, José A Ortega-Ramírez, José Antonio Marin-Neto, Jose D Salas, Jose Enrique Castillo, Jose Francisco Saraiva, José J Cuenca-Castillo, Jose L Diez, José Luis Narro Villanueva, José Luiz da Vieira, José M Flores-Palacios, Jose Ramon Gonzalez, Jose Seijas Amigo, Jose Fragata, Josep Maria Padró, Josheph F X McGarvey Jr, Joseph Hannan, Joseph Sacco, Joseph Sweeny, Joseph Wiesel, Josephine D Abraham, Joshua P Loh, Joy Burkhardt, Joyce R White, Joyce Riestenberg-Smith, Judit Sebo, Judith L Meadows, Judith Wright, Judy Mae Foltz, Judy Hung, Judy Otis, Juergen Stumpf, Jui-Peng Tsai, Julia S Dionne, Julia de Aveiro Morata, Julie Bunke, Julie Morrow, Julio César Figal, Jun Fujita, Jun Jiang, Junhua Li, Junqing Yang, Juntima Euathrongchit, Jyotsna Garg, K Manjula Rani, K Preethi, Kaatje Goetschalckx, Kai Eggers, Kamalakar Surineni, Kanae Hirase, T R Kapilamoorthy, Karen Calfas, Karen Gratrix, Karen Hallett, Karen Hultberg, Karen Nugent, Karen Petrosyan, Karen Swan, Karolina Kryczka, Karolina Wojtczak-Soska, Karolina Wojtera, Karsten Lenk, Karthik Ramasamy, Katarzyna Łuczak, Katarzyna Malinowska, Kate Pointon, Kate Robb, Katherine Martin, Kathleen Claes, Kathryn Carruthers, Kathy E Siegel, Katia Drouin, Katie Fowler-Lehman, Kavita Rawat, Kay Rowe, Keiichi Fukuda, Keith A A Fox, Ken Mahaffey, Kendra Unterbrink, Kenneth Giedd, Kerrie Van Loo, Kerry Lee, Kerstin Bonin, Kevin R Bainey, Kevin T Harley, Kevin Anstrom, Kevin Chan, Kevin Croce, Kevin Landolfo, Kevin Marzo, Keyur Patel, Khaled Abdul-Nour, Khaled Alfakih, Khaled Dajani, Khaled Ziada, Khaula Baloch, Khrystyna Kushniriuk, Kian-Keong Poh, Kim F Ireland, Kim Holland, Kimberly Ann Byrne, Kimberly E Halverson, Kimberly Elmore, Kimberly Miller-Cox, Kiran Reddy, Kirsten J Quiles, Kirsty Abercrombie, Klaus Matschke, Konrad Szymczyk, Koo Hui Chan, Kotiboinna Preethi, Kozhaya Sokhon, Krissada Meemuk, Kristian Thygesen, Kristin M Salmi, Kristin Newby, Kristina Wippler, Kristine Arges, Kristine Teoh, Krystal Etherington, Krystyna Łoboz-Grudzień, Krzysztof W Reczuch, Krzysztof Bury, Krzysztof Drzymalski, Krzysztof Kukuła, Kuo-Tzu Sung, Kurt Huber, Ladda Douangvila, Lance Sullenberger, Larissa Miranda Trama, Laszlone Matics, Laura Drew, Laura Flint, Laura Keinaite, Laura Sarti, Laurel Kolakaluri, Lawrence M Phillips, Lawrence Friedman, Lawrence Phillips, Lazar Velicki, Leah Howell, Leandro C Maranan, Leanne Cox, Ledjalem Daba, Lei Zhang, Lekshmi Dharmarajan, Leo Bockeria, Leonardo Pizzol Caetano, Leonardo Bridi, Leonid L Bershtein, Leszek Sokalski, Li Hai Yan, Li Li, Lia Nijmeijer, Lidia Sousa, Lihong Xu, Lihua Zhang, Lili Zhang, Lilia Schiavi, Lilian Mazza Barbosa, Lillian L Khor, Lina Felix-Stern, Linda L Hall, Linda M Hollenweger, Linda Arcand, Linda Davidson-Ray, Linda Schwarz, Lindsey N Sikora, Lingping Chi, Lino Patricio, Liping Zhang, Lisa Chaytor, Lisa Hatch, Lisa McCloy, Lisa Wong, Liselotte Persson, Lixin Jiang, Liz Low, Ljiljana Pupic, Loïc Bière, Lorenzo Monti, Lori Christensen, Lori Pritchard, Loriane Black, Lori-Ann Desimone, Lori-Ann Larmand, Lorraine McGregor, Louise Morby, Louise Thomson, Luc Harvey, Luciana de Pádua Baptista, Lucilla Garcia, Ludivine Eliahou, Ludmila Helmer, Luis F Smidt, Luis Bernanrdes, Luis Guzman, Luiz A Carvalho, Luyang Xiong, Lynette L Teo, Lynn M Neeson, Lynne Winstanley, M Barbara Srichai-Parsia, M Quintana Giner, M Sowjanya Reddy, M Valdés Chávarri, M Grazia Rossi, Maarten Simoons, Maayan Konigstein, Maciej Lesiak, Maciej Olsowka, Mafalda Selas, Magalie Corfias, Magdalena Madero Rovalo, Magdalena Łanocha, Magdalena Miller, Magdalena Misztal-Teodorczyk, Magdalena Rantinella, Magdy Abdelhamid, Magnolia Jimenez, Mahboob Alam, Mahevamma Mylarappa, Mahfouz El Shahawy, Mahmoud Mohamed, Mahmud Al-Bustami, Majo X Joseph, Malgorzata Frach, Małgorzta Celińska-Spodar, Malte Helm, Manas Chacko, Mandy Murphy, Manitha Vinod, Manjula Rani, Manu Dhawan, Manuela Mombelli, Marcel Weber, Marcello Galvani, Marcelo Jamus Rodrigues, Marcia F Dubin, Marcia F Werner Bayer, Marcin Szkopiak, Marco Antonio Monsalve, Marco Bizzaro Santos, Marco Magnoni, Marco Marini, Marco Sicuro, Marco Zenati, Marcos Valério Coimbra Resende, Marek Roik, Margalit Bentzvi, Margaret Gilsenan, Margaret Iraola, Margot C Quinn, Maria A Alfonso, Maria Antonieta Pereira Moraes, María Dolores Martínez-Ruíz, María Fernanda Canales, Maria Inês Caetano, Maria P Corral, Maria Pérez García, Maria Victoria Actis, Maria Aguirre, Maria Andreasson, Maria Aprile, Maria Colton, Maria Eugenia Martin, Maria Lasala, Maria Lorenzo, Maria Posada, Maria Shier, Maria Thottam, Mariana V Furtado, Mariana Yumi Okada, Marianna D A Dracoulakis, Marianne De Andrade, Mariano Rubio, Marie Essermark, Marielle Scherrer-Crosbie, Marija T Petrovic, Marija Zdravkovic, Marilyn Black, Marina Garcia, Mario J Garcia, Mariola Szulik, Marisa Orgera, Mark A de Belder, Mark Harbinson, Mark Hyun, Mark Peterson, Mark Xavier, Marlowe Mosley, Marta Capinha, Marta Marcinkiewicz-Siemion, Marta Swiderek, Martha Meyer, Martina Ceseri, Martina Tricoli, Marvin Kronenberg, Mary Williams, Mary Ann Champagne, Mary Colleen Rogge, Mary R Soltau, Mary Streif, Massimo Villella, Massoud Leesar, Matei Claudia, Mateusz Solecki, Matías Nicolás Mungo, Matthew Wall Jr, Matthew Budoff, Matthew Jezior, Matthew Luckie, Matthias Friedrich, Mauren P Haeffner, Maximilian Tscharre, Max-Paul Winter, Mayana Almeida, Mayil S Krishnam, Mayuri Patel, Meenakshi Mishra, Megan Manocchia, Meghana Kakade, Melanie J Munro, Melissa D Chaplin, Melissa LeFevre, Mervyn Andiapen, Michael A Gibson, Michael B Rubens, Michael C Turner, Michael D Shapiro, Michael W Lee, Michael Berlowitz, Michael Davidson, Michael Mack, Michael McDaniel, Michael Mumma, Michal Wlodarczyk, Michel G Khouri, Michel S Slama, Michele Rawlins, Michelle M Bonner, Michelle M Seib, Michelle Chang, Michelle Crowder, Michelle Dixon, Michelle Mayon, Michelle McEvoy, Michelle Yee, Miguel M Fernandes, Miguel Nobre Menezes, Miguel Souto Bayarri, Miguel Barrero, Mikhail T Torosoff, Milan R Dobric, Milan Dobric, Milica Nikola Dekleva, Milind Avdhoot Gadkari, Millie Gomez, Min Tun Kyaw, Miriam Brooks, Miroslav Stevo Martinovic, Mitchel B Lustre, Mohammad Tariq Vakani, Mohammad El-Hajjar, Mohammed Al-Amoodi, 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Paula García-González, Paulo Cury Rezende, Paulo Ricardo Caramori, Pavel S Kozlov, Pedro Canas Silva, Pedro Gabriel Melo Barros E Silva, Pedro Píccaro de Oliveira, Pedro Carvalho, Pedro Modas, Pedro Rio, Peeyush Jain, Peiyu He, Peter A McCullough, Peter H Stone, Peter M Pollak, Peter Douglass, Peter Henriksen, Peter OKane, Peter Ong, Philip Jones, Philip Rogal, Philippe Généreux, Philippe Menasche, Philippe Rheault, Phoebe Goold, Pierre Gervais, Pierre Michaud, Pilar Calvillo, Ping Chai, Piotr Jakubowski, Piotr Pruszczyk, Piotr Slomka, Piyamitr Sritara, Poay-Huan Loh, Poonam Sonawane, Pouneh Samadi, Pragnesh P Parikh, Prakash Deedwania, Pranav M Patel, Praneeth Polamuri, Pratiksha Sharma, Precilia Vasquez, Preeti Kamath, Prince Thomas, Priyadarshani Arambam, Puja K Mehta, Purvez Grant, Pushpa Naik, Qi Zhong, Qian Zhao, Qiang Zhou, Qianqian Yuan, Qin Yu, Qingxian Li, Qiulan Xie, Qiutang Zeng, R J Vindhya, R James Gerlach, Rachel King, Rada Vučić, Radmila Lyubarova, Radoslaw Pracon, 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Jeffrey Kanters, Jeffrey Lorin, Jeffrey Moses, Jelena J Stepanovic, Jelena Celutkiene, Jelena Djokic, Jelena Stojkovic, Jenne M Jose, Jenne Manchery, Jennifer A Mull, Jennifer H Czerniak, Jennifer L Stanford, Jennifer Gillis, Jennifer Horst, Jennifer Isaacs, Jennifer Langdon, Jennifer Thomson, Jennifer Tomfohr, Jennifer White, Jen-Yuan Kuo, Jeremy Rautureau, Jerome Fleg, Jessica Berg, Jessica Rodriguez, Jessica Waldron, Jhina Patro, Jia Li, Jiajia Mao, Jiamin Liu, Jian'an Wang, Jianhua Li, Jianxin Zhang, Jie Qi, Jihyun Lyo, Jill Marcus, Jim Blankenship, Jing Zhang, Jingjing Liu, Jing-Yao Fan, Jiun-Yi Li, Jiwan Pradhan, Jiyan Chen, J M Rivera Caravaca, Jo Evans, Joan Garcia Picart, Joan Hecht, Joanna Jaroch, Joanna Zalewska, Joanne Kelly, Joanne Taaffe, João Reynaldo Abbud, João V Vitola, Joaquín V Peñafiel, Jocelyne Benatar, Jody Bindeman, Joe Sabik, Joel Klitch, Johann Christopher, Johannes Aspberg, John D Friedman, John F Beltrame, John F Heitner, John Joseph Graham, John R Davies, John Doan, John Kotter, John Kurian, John Mukai, John Pownall, Jolanta Sobolewska, Jon Kobashigawa, Jonathan L Goldberg, Jonathan W Bazeley, Jonathan Byrne, Jonathan Himmelfarb, Jonathan Leipsic, Jonean Thorsen, Jorge F Trejo Gutierrez, Jorge Escobedo, Jorik Timmer, José A Ortega-Ramírez, José Antonio Marin-Neto, Jose D Salas, Jose Enrique Castillo, Jose Francisco Saraiva, José J Cuenca-Castillo, Jose L Diez, José Luis Narro Villanueva, José Luiz da Vieira, José M Flores-Palacios, Jose Ramon Gonzalez, Jose Seijas Amigo, Jose Fragata, Josep Maria Padró, Josheph F X McGarvey Jr, Joseph Hannan, Joseph Sacco, Joseph Sweeny, Joseph Wiesel, Josephine D Abraham, Joshua P Loh, Joy Burkhardt, Joyce R White, Joyce Riestenberg-Smith, Judit Sebo, Judith L Meadows, Judith Wright, Judy Mae Foltz, Judy Hung, Judy Otis, Juergen Stumpf, Jui-Peng Tsai, Julia S Dionne, Julia de Aveiro Morata, Julie Bunke, Julie Morrow, Julio César Figal, Jun Fujita, Jun Jiang, Junhua Li, Junqing Yang, Juntima Euathrongchit, Jyotsna Garg, K Manjula Rani, K Preethi, Kaatje Goetschalckx, Kai Eggers, Kamalakar Surineni, Kanae Hirase, T R Kapilamoorthy, Karen Calfas, Karen Gratrix, Karen Hallett, Karen Hultberg, Karen Nugent, Karen Petrosyan, Karen Swan, Karolina Kryczka, Karolina Wojtczak-Soska, Karolina Wojtera, Karsten Lenk, Karthik Ramasamy, Katarzyna Łuczak, Katarzyna Malinowska, Kate Pointon, Kate Robb, Katherine Martin, Kathleen Claes, Kathryn Carruthers, Kathy E Siegel, Katia Drouin, Katie Fowler-Lehman, Kavita Rawat, Kay Rowe, Keiichi Fukuda, Keith A A Fox, Ken Mahaffey, Kendra Unterbrink, Kenneth Giedd, Kerrie Van Loo, Kerry Lee, Kerstin Bonin, Kevin R Bainey, Kevin T Harley, Kevin Anstrom, Kevin Chan, Kevin Croce, Kevin Landolfo, Kevin Marzo, Keyur Patel, Khaled Abdul-Nour, Khaled Alfakih, Khaled Dajani, Khaled Ziada, Khaula Baloch, Khrystyna Kushniriuk, Kian-Keong Poh, Kim F Ireland, Kim Holland, Kimberly Ann Byrne, Kimberly E Halverson, Kimberly Elmore, Kimberly Miller-Cox, Kiran Reddy, Kirsten J Quiles, Kirsty Abercrombie, Klaus Matschke, Konrad Szymczyk, Koo Hui Chan, Kotiboinna Preethi, Kozhaya Sokhon, Krissada Meemuk, Kristian Thygesen, Kristin M Salmi, Kristin Newby, Kristina Wippler, Kristine Arges, Kristine Teoh, Krystal Etherington, Krystyna Łoboz-Grudzień, Krzysztof W Reczuch, Krzysztof Bury, Krzysztof Drzymalski, Krzysztof Kukuła, Kuo-Tzu Sung, Kurt Huber, Ladda Douangvila, Lance Sullenberger, Larissa Miranda Trama, Laszlone Matics, Laura Drew, Laura Flint, Laura Keinaite, Laura Sarti, Laurel Kolakaluri, Lawrence M Phillips, Lawrence Friedman, Lawrence Phillips, Lazar Velicki, Leah Howell, Leandro C Maranan, Leanne Cox, Ledjalem Daba, Lei Zhang, Lekshmi Dharmarajan, Leo Bockeria, Leonardo Pizzol Caetano, Leonardo Bridi, Leonid L Bershtein, Leszek Sokalski, Li Hai Yan, Li Li, Lia Nijmeijer, Lidia Sousa, Lihong Xu, Lihua Zhang, Lili Zhang, Lilia Schiavi, Lilian Mazza Barbosa, Lillian L Khor, Lina Felix-Stern, Linda L Hall, Linda M Hollenweger, Linda Arcand, Linda Davidson-Ray, Linda Schwarz, Lindsey N Sikora, Lingping Chi, Lino Patricio, Liping Zhang, Lisa Chaytor, Lisa Hatch, Lisa McCloy, Lisa Wong, Liselotte Persson, Lixin Jiang, Liz Low, Ljiljana Pupic, Loïc Bière, Lorenzo Monti, Lori Christensen, Lori Pritchard, Loriane Black, Lori-Ann Desimone, Lori-Ann Larmand, Lorraine McGregor, Louise Morby, Louise Thomson, Luc Harvey, Luciana de Pádua Baptista, Lucilla Garcia, Ludivine Eliahou, Ludmila Helmer, Luis F Smidt, Luis Bernanrdes, Luis Guzman, Luiz A Carvalho, Luyang Xiong, Lynette L Teo, Lynn M Neeson, Lynne Winstanley, M Barbara Srichai-Parsia, M Quintana Giner, M Sowjanya Reddy, M Valdés Chávarri, M Grazia Rossi, Maarten Simoons, Maayan Konigstein, Maciej Lesiak, Maciej Olsowka, Mafalda Selas, Magalie Corfias, Magdalena Madero Rovalo, Magdalena Łanocha, Magdalena Miller, Magdalena Misztal-Teodorczyk, Magdalena Rantinella, Magdy Abdelhamid, Magnolia Jimenez, Mahboob Alam, Mahevamma Mylarappa, Mahfouz El Shahawy, Mahmoud Mohamed, Mahmud Al-Bustami, Majo X Joseph, Malgorzata Frach, Małgorzta Celińska-Spodar, Malte Helm, Manas Chacko, Mandy Murphy, Manitha Vinod, Manjula Rani, Manu Dhawan, Manuela Mombelli, Marcel Weber, Marcello Galvani, Marcelo Jamus Rodrigues, Marcia F Dubin, Marcia F Werner Bayer, Marcin Szkopiak, Marco Antonio Monsalve, Marco Bizzaro Santos, Marco Magnoni, Marco Marini, Marco Sicuro, Marco Zenati, Marcos Valério Coimbra Resende, Marek Roik, Margalit Bentzvi, Margaret Gilsenan, Margaret Iraola, Margot C Quinn, Maria A Alfonso, Maria Antonieta Pereira Moraes, María Dolores Martínez-Ruíz, María Fernanda Canales, Maria Inês Caetano, Maria P Corral, Maria Pérez García, Maria Victoria Actis, Maria Aguirre, Maria Andreasson, Maria Aprile, Maria Colton, Maria Eugenia Martin, Maria Lasala, Maria Lorenzo, Maria Posada, Maria Shier, Maria Thottam, Mariana V Furtado, Mariana Yumi Okada, Marianna D A Dracoulakis, Marianne De Andrade, Mariano Rubio, Marie Essermark, Marielle Scherrer-Crosbie, Marija T Petrovic, Marija Zdravkovic, Marilyn Black, Marina Garcia, Mario J Garcia, Mariola Szulik, Marisa Orgera, Mark A de Belder, Mark Harbinson, Mark Hyun, Mark Peterson, Mark Xavier, Marlowe Mosley, Marta Capinha, Marta Marcinkiewicz-Siemion, Marta Swiderek, Martha Meyer, Martina Ceseri, Martina Tricoli, Marvin Kronenberg, Mary Williams, Mary Ann Champagne, Mary Colleen Rogge, Mary R Soltau, Mary Streif, Massimo Villella, Massoud Leesar, Matei Claudia, Mateusz Solecki, Matías Nicolás Mungo, Matthew Wall Jr, Matthew Budoff, Matthew Jezior, Matthew Luckie, Matthias Friedrich, Mauren P Haeffner, Maximilian Tscharre, Max-Paul Winter, Mayana Almeida, Mayil S Krishnam, Mayuri Patel, Meenakshi Mishra, Megan Manocchia, Meghana Kakade, Melanie J Munro, Melissa D Chaplin, Melissa LeFevre, Mervyn Andiapen, Michael A Gibson, Michael B Rubens, Michael C Turner, Michael D Shapiro, Michael W Lee, Michael Berlowitz, Michael Davidson, Michael Mack, Michael McDaniel, Michael Mumma, Michal Wlodarczyk, Michel G Khouri, Michel S Slama, Michele Rawlins, Michelle M Bonner, Michelle M Seib, Michelle Chang, Michelle Crowder, Michelle Dixon, Michelle Mayon, Michelle McEvoy, Michelle Yee, Miguel M Fernandes, Miguel Nobre Menezes, Miguel Souto Bayarri, Miguel Barrero, Mikhail T Torosoff, Milan R Dobric, Milan Dobric, Milica Nikola Dekleva, Milind Avdhoot Gadkari, Millie Gomez, Min Tun Kyaw, Miriam Brooks, Miroslav Stevo Martinovic, Mitchel B Lustre, Mohammad Tariq Vakani, Mohammad El-Hajjar, Mohammed Al-Amoodi, Mohammed Hussain, Mohammed Saleem, Moisés Blanco-Calvo, Moisés Jiménez-Santos, Mona Bhatia, Monica Rosca, Monika Laukyte, Montserrat Gracida Blanca, Montserrat Vila Perales, Mouaz H Al-Mallah, Moysés de Oliveira Filho, Mpiko Ntsekhe, Muhamed Saric, Mulei Chen, Myriam Brousseau, Myrthes Emy Takiuti, Nada Cemerlic-Adjic, Nadia Asif, Nadia Gakou, Nafisa Hussain, Nana O Katamadze, Nancy L Clapp, Nancy Aedy, Nandita Nataraj, Nanette K Wenger, Naomi Uchida, Nasrul Ismail, Natalia S Oliveira, Natalia de Carvalho Maffei, Natalie Spitzer, Natasha C Putnam, Naved Aslam, Neamat Mowafy, Neeraj Pandit, Neeraj Parakh, Nevena Garcevic, Ngaire Meadows, Nhi N Tran, Nicholas Danchin, Nicki Lakeman, Nicola Johnston, Nicolas W Shammas, Nicole Saint Vrestil, Nicole Deming, Nier Zhong, Niket Patel, Nikola N Boskovic, Nikolaos Karogiannis, Nikos Werner, Nina Johnston, Ning Zhang, Ning Zhou, Niree Hindoyan, Nirmal Kumar, Nitika Chadha, Nitish Naik, Nodira Aripova, Noloyiso Mtana, Nona A Eskelson, Noor Syamira Mokhtar, Noppon Taksaudom, Nor Asiah Basri, Nora Marchelletta, Norma Hogg, Nungshi Jungla, Nuno Ferreira, Oksana A Lubyanaya, Olga B Nikolaeva, Olga Cañavate, Olga Sobrino, Olga Walesiak, Olga Walter, Olga Zdończyk, Olivia J Lim, Olivia Anaya, Olivia Mancilla, Olivier Dubourg, Olugbenga Bello, Omar Almousalli, Omar Thompson, Oni Olurinde, Or Harel, Osama Raheem, Oscar Méndiz, Óscar Prada-Delgado, Oz Shapira, P Christian Schulze, Pachara Panpunuan, Pal Maurovich-Horvat, Pallav Garg, Paloma Moraga, Pam Singh, Pamela Julian, Pamela Ouyang, Pamela Sigel, Pamela Woodard, Panpan Zhou, Paola Emanuela Poggio, Paola Smanio, Paolo Calabro, Paramjit Jeetley, Pascal Goube, Patricia K Nguyen, Patricia Alarie, Patricia Arakelian, Patricia Arsenault, Patricia Blaise, Patricia Brito, Patricia Cowper, Patricia Endsley, Patricia Mieses, Patrick B Alexander, Patrick Donnelly, Patrick Wilmot, Patrycja Lebioda, Paul C Gordon, Paul Der Mesropian, Paul Galiwango, Paul Hauptman, Paul Kennedy, Paula Beardsley, Paula García-González, Paulo Cury Rezende, Paulo Ricardo Caramori, Pavel S Kozlov, Pedro Canas Silva, Pedro Gabriel Melo Barros E Silva, Pedro Píccaro de Oliveira, Pedro Carvalho, Pedro Modas, Pedro Rio, Peeyush Jain, Peiyu He, Peter A McCullough, Peter H Stone, Peter M Pollak, Peter Douglass, Peter Henriksen, Peter OKane, Peter Ong, Philip Jones, Philip Rogal, Philippe Généreux, Philippe Menasche, Philippe Rheault, Phoebe Goold, Pierre Gervais, Pierre Michaud, Pilar Calvillo, Ping Chai, Piotr Jakubowski, Piotr Pruszczyk, Piotr Slomka, Piyamitr Sritara, Poay-Huan Loh, Poonam Sonawane, Pouneh Samadi, Pragnesh P Parikh, Prakash Deedwania, Pranav M Patel, Praneeth Polamuri, Pratiksha Sharma, Precilia Vasquez, Preeti Kamath, Prince Thomas, Priyadarshani Arambam, Puja K Mehta, Purvez Grant, Pushpa Naik, Qi Zhong, Qian Zhao, Qiang Zhou, Qianqian Yuan, Qin Yu, Qingxian Li, Qiulan Xie, Qiutang Zeng, R J Vindhya, R James Gerlach, Rachel King, Rada Vučić, Radmila Lyubarova, Radoslaw Pracon, Raewyn Fisher, Rafael Beyar, Rafael Diaz, Rafael Selgas, Raffaele Bugiardini, Raffaele Fanelli, Raisa Kavalakkat, V S Rajalekshmi, Rajat S Barua, Rajeev Menon, Rajesh Gopalan Nair, Rajesh Francis, Rajiv Narang, Rakesh Yadav, Ralph Alan Huston, T Ramakrishnan, Ramesh de Silva, Rami El Mahmoud, Ramiro Carvalho, Ramon de Jesús-Pérez, Ramona Stevens, Ran Leng, Ranjan Kachru, Ranjit Kumar Nath, Raquel Sanchez, Raven R Dwyer, Raven Lee, Ray Wyman, Raymond C Wong, Raymond W Little, Raymundo Ocaranza Sanchez, Rebecca J Wimmer, Rebecca Bariciano, Rebecca Otis, Rebekah R Herrmann, Reem Yunis, Reinette Hampson, Renato Abdala Karam, Renee C Hessian, Renee Kaneshiro, Reshma Ravindran, Reto Andreas Gamma, Reyna Bhandari, Reza Arsanjani, Ricardo L Lopes, Ricardo Mendes Oliveira, Ricardo Costa, Richa Bhatt, Richard F Davies, Richard H J Trimlett, Richard Goldweit, Rik Hermanides, Rine Nakanishi, Rinu R Sidh, Risha Patel, Rita Coram, Rizwan A Siddiqui, Rob S Beanlands, Robert J Hamburger, Robert K Riezebos, Robert M Donnino, Robert Bojar, Robert Chilton, Robert Guyton, Robert Henderson, Robert Kornberg, Robert Leber, Robert Mao, Robert Stenberg, Roberta P Santos, Roberto René Favaloro, Roberto Amati, Rodolfo G S D Lima, Rodrigo J Cerci, Rogerio Tumelero, Rohit Tandon, Roma Tewari, Romalisa Miranda-Peats, Ron Wald, Ronald A Mastouri, Ronald G Morford, Ronald G Schwartz, Ronald P Pedalino, Rongrong Hu, Ronnell A Hansen, Ronny A Cohen, Rory Hachamovitch, Rosa Homem, Rosa Sandonato, Rosane Laimer, Rosann Gans, Roxanne Yost, Roy Mathew, Rubén Baleón-Espinosa, Ruben Ramos, Rubine Gevorgyan, Rui Ferreira, Rui Jing, Ruth Pérez-Fernández, S K Dwivedi, S Ramakrishnan, Saadat Khan, Sabahat Bokhari, Sabu Thomas, Sadath Lubna, Sajeeda Parveen Khan, Sajeev Chakanalil Govindan, Saket Girotra, Saleem Kassam, Sallie Canada, Salvador Cruz-Flores, Samaa Mohamed, Samantha Ly, Sameh El Kaffas, Samia Massalha, Sampoornima Setty, Samuel Nwosu, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandra M Rivest, Sandra S Zier, Sandra Ahoud, Sandy Carr, Sanjay Ganapathi, Sanjay Shetty, Sanjeev Sharma, Santa Jimenez, Santhosh Satheesh, Santiago A Garcia, Sara Fernandez, Sara Karlsson, Sara Salkind, Sara Temiyasathit, Sarah Medina Rodriguez, Sarah Beaudry, Sarah Hadjih, Sarah Williams, Sarah Zahrani, Sarju Ralhan, Sasa Hinic, Sasko Kedev, Satinder Singh, Satoshi Yasuda, Satvic Cholenahally Manjunath, Sau Lee, Scott M Kaczkowski, Scott Kinlay, Sean W Hayes, Sebastian Sobczak, Senait Asier, Sergey A Sayganov, Seth I Sokol, Shaheen Pandie, Shaiful Azmi Yahaya, Shamir Mehta, Shao-Ping Nie, Sharad Chandra, Sharder Islam, Sharon Tai, Sheetal Rupesh Karwa, Sheri Ussery, Sheromani Bajaj, Sherron C Crook, Shigeyuki Nishimura, Shintaro Nakano, Shirin Heydari, Shiv Kumar Choudhary, Shivali Patel, Shobana Ganesan, Shruti Pandey, Shuyang Zhang, Shweta Hande, Siddharth Gadage, Sik-Yin V Tan, Silvia Zottis Poletti, Silvia Riera, Silvia Valbuena, Simon Walsh, Simona Maspoli, Simone Savaris, Si-Ting Feng, So Yang Cho, Solomon Yakubov, Songlin Zhu, Songtao Wang, Sonia Guerrero, Sonika Gupta, Sonja Salinger Martinovic, Sonya Brons, Sorin Brener, Sothinathan Gurunathan, Souheil Saba, Soundarya Nayak, Sowjanya Reddy, Srinivasa Potluri, Sriram Sudarshan, Srun Kuanprasert, Stacie Van Oosterhout, Stamatios Lerakis, Stanley E Cobos, Stefan C Bertog, Stefan M Simović, Stefan Weikl, Stefano Di Marco, Stefano Provasoli, Stephanie A Tirado, Stephanie C Boer, Stephanie M Lane, Stephanie Ferket, Stephanie Kelly, Stephanie Wasmiller, Stephen H McKellar, Stephen P Hoole, Stephen Fremes, Stephen Preston, Steve Leung, Steven A Fein, Steven J Lindsay, Steven P Sedlis, Steven Giovannone, Steven Michael, Steven Weitz, Stijn van Vugt, Subhash Banerjee, Sudhir Naik, Suellen Hosino, Sukie Desire, Sukit Yamwong, Suku T Thambar, Sulagna Mookherjee, Suman Singh, Sundeep Mishra, Sunil Kumar Verma, Supap Kulthawong, Supatchara Khwakhong, Surendra Naik, Suresh Babu, Surin Woragidpoonpol, Suryaprakash Narayanappa, Susan Derbyshire, Susan Gent, Susan Mathus, Susan Milbrandt, Susan Moore, Susan Regan, Susan Stinson, Susan Webber, Susana Silva, Susanna Stevens, Susanne Gruensfelder, Suthara Aramcharoen, Suvarna Kolhe, Suzana Tavares, Suzanne Arnold, Suzanne Welsh, Svetlana Apostolovic, Swapna Kunhunny, Ta-Chuan Hung, Taissa Zappernick, Tali Sharir, Talita Silva, Tamara Colaiácovo Soares, Tapan Umesh Pillay, Tarun K Mittal, Tatiana Trifonova, Tauane Bello Duarte, Tauqir Huk, Téodora Dutoiu, Terrance Chua, Terry Weyand, Thabitha Charles, Theodoros Kofidis, Theresa McCreary, Thierry Lefevre, Thippeekaa Arumairajah, Thitipong Tepsuwan, Thomas J Mulhearn, Thomas M Meyer, Thomas P Rocco, Thomas R Downes, Thomas Crain, Thomas Haldis, Thomas Mathew, Thomas Redick, Thounaojam Indira Devi, Thuraia Nageh, Tia Cauthren, Tiago Silva, Tiffany Little, Tijana Andric, Tina Harding, Titus Lau, Tiziana Formisano, Tiziano Moccetti, Tomasz Ciurus, Tomasz Mazurek, Tomasz Tarchalski, Toshiyuki Nagai, Tri Tran, Tricia Youn, Trish Tucker, Trudie Milner, Tuhina Bose, Tushar Kotecha, Udo Sechtem, Uma S Valeti, Umberto Cucchini, Umesh Badami, Upendra Kaul, V K Bahl, V S Narain, Valentina Casali, Valeria Godoy, Valerie Robesyn, Vamshi P Priya, Vandana Yadav, Vera McKinney, Veronica De Lenges, Veronica Tinnirello, Vicente Miro, Victor Navarro, Victoria Gumerova, Victoria Hernandez, Vidya Seeratan, Vijay Kumar, Vikentiy Y Kozulin, Viktoria Bulkley, Vilmar Veiga Jr, Vincent Setang, C P Vineeth, Virginai Pubull Nuñez, Virginia Fernández-Figares, Vitor Gomes, Viviana Gabriel, Viviane Dos Santos, Viviane Almeida, Vlad A Iliescu, Vladan Mudrenovic, Vladimir Dzavik, Vojislav L Giga, Walter Enrique Mogrovejo, Wan Xian Chan, Wanda C Marfori, Wanda Parker, Warangkana Mekara, Wassim Nona, Wayne Old, Wayne Pennachi, Weerachai Nawarawong, Wei Chen, Wei Su, Weibing Xing, Wei-Ren Lan, Wenda Crawford, Wendy L Stewart, Wendy Drewes, Wenhua Lin, William B Abernethy, William D Salerno, William F Fearon, William Vergoni, William Weintraub, Winnie C Sia, Wlodzimierz J Musial, Xacobe Flores-Ríos, Xavier Garcia-Moll Marimon, Xi Su, Xiang Ma, Xiangqiong Gu, Xiao Wang, Xiaomei Li, Xiaowei Yao, Xin Fu, Xin Su, Xin Zeng, Xinchun Yang, Xiuhong Li, Xuehua Fang, Xutong Wang, Yaming Geng, Yan Yan, Yanek Pépin-Dubois, Yanfu Wang, Yang Wang, Yanmeng Tian, Yaping Huang, Yechen Han, Yesenia Zambrano, Yi-Hsuan Yang, Ying Tung Sia, Yining Yang, Yitong Ma, Yolayfi Peralta, Yongjian Wu, Yu Kunwu, Yu Zhao, Yudong Peng, Yueh-Hung Lin, Yulan Zhao, Yumei Dong, Yunhai Zhao, Yutthaphan Wannasopha, Yvonne Taul, Zakir Sahul, Zalina Kudzoeva, Zbigniew Kalarus, Zeljko Z Markovic, Zhen Huang, Zheng Ji, Zhenyu Liu, Zhou Yue, Zhulin Zhang, Zhuxi Li, Zile Singh Meharwal, Ziliang Bai, Zixiang Yu, Zohra Huda, Zoltan Davidovits
Subjects: Male, Cardiac Catheterization, Computed Tomography Angiography, medicine.medical_treatment, Myocardial Ischemia, Coronary Disease, Coronary Artery Disease, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Coronary Angiography, ISCHEMIA Research Group, law.invention, Angina, Coronary artery disease, 0302 clinical medicine, Randomized controlled trial, law, Cardiovascular Disease, Myocardial Revascularization, 030212 general & internal medicine, Coronary Artery Bypass, 11 Medical and Health Sciences, Cardiac catheterization, General Medicine, Middle Aged, humanities, Cardiovascular Diseases, Cardiology, Female, Human, medicine.medical_specialty, Ischemia, Article, 03 medical and health sciences, Geriatric cardiology, Percutaneous Coronary Intervention, General & Internal Medicine, Internal medicine, medicine, Humans, Angina, Unstable, Aged, business.industry, Coronary Artery Bypa, Percutaneous coronary intervention, Bayes Theorem, medicine.disease, Heart failure, Quality of Life, business
Abstract: BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).
Published: 2020
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24. Treatment Response and GWAS Risk Allele rs2514218 (C) of the Dopamine D2 Receptor Gene in Inpatients with Schizophrenia

Author: Tatyana Lezheiko, Sergey S. Potanin, Vera Golimbet, Allan G. Beniashvili, George E. Rupchev, Margarita A. Morozova, Denis S. Burminskiy, and Taissia A. Lepilkina
Subjects: Adult, Male, Psychosis, medicine.medical_specialty, Locus (genetics), Genome-wide association study, Polymorphism (computer science), Internal medicine, Dopamine receptor D2, medicine, Humans, Genotyping, Alleles, Biological Psychiatry, Inpatients, Receptors, Dopamine D2, business.industry, medicine.disease, Pathophysiology, Psychiatry and Mental health, Neuropsychology and Physiological Psychology, Schizophrenia, Female, business, Antipsychotic Agents, Genome-Wide Association Study
Abstract: Introduction: The pathophysiological mechanisms of acute schizophrenia are largely unknown, but it is widely accepted that dopamine D2 receptors (DRD2s) are involved in psychosis treatments for schizophrenic patients. We suggest that genetic variation in these receptors may play a role in patients’ responses to commonly used antipsychotics, particularly D2-blockers. Methods: This study included adult patients with ICD-10 diagnoses of schizophrenia and current acute psychosis who were treated with antipsychotics. All patients underwent genotyping for DRD2 rs2514218 polymorphism. The definition of overall treatment response was based on changes in treatment scheme: no changes indicated a good response, and changes indicated a limited response. Results: There were 275 inpatients (38.1% of whom were female; mean age = 32.7 years, SD = 11.1 years) who met the inclusion criteria. Of the participants, 99 were good responders (34% of whom were female), and 176 were limited responders (40% of whom were female). No differences in demographic, premorbid, or disease characteristics were found. The number of patients that were homozygous for the risk allele was significantly greater in the limited response group than in the good response group. Conclusion: Our findings suggest that the risk variant at the DRD2 locus can be used as an indicator for patients’ responses to antipsychotics without direct DRD2-blocking, thereby shortening the time needed for drug selection.
Published: 2021
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25. Elevated Prevalence of Adverse Childhood Experiences in Severe Gambling Disorder: A Pilot Study in U.S. Veterans

Author: Toby Chen, Heather Chapman, P. Eric Konicki, Peijun Chen, and George E. Jaskiw
Subjects: Psychiatry and Mental health, Clinical Psychology, business.industry, Lower prevalence, Medicine, Gambling disorder, business, Adverse Childhood Experiences, Demography
Abstract: Gambling disorder (GD) is associated with a higher prevalence of adverse childhood experiences (ACEs). Whether this applies to groups such as U.S. veterans, who already have elevated ACEs, is not known. In this pilot study, we extracted ACEs from the charts of a random sample (n = 19) male veterans in residential GD treatment and compared them to those from a general veteran sample (n =154, 30 females, 124 males). The GD group had an elevated prevalence (79% vs. 37%) of three or more ACEs and a lower prevalence (5% vs. 49%) of one or fewer ACEs. Within groups with elevated ACEs, higher ACE load may still confer a higher risk of adult GD.
Published: 2021
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26. Long-term exposure of Pacu (Piaractus mesopotamicus) fish to dietary aflatoxin B1: residues in tissues and performance

Author: Ricardo Luiz Moro de Sousa, L. C. S. Carrion, Carolina M. Bedoya-Serna, George Shigueki Yasui, Silvia Helena Seraphin de Godoy, Juliana Cristina Baldin, Andrezza Maria Fernandes, George E. Rottinghaus, César Gonçalves de Lima, and Euder Cesar Michelin
Subjects: 0106 biological sciences, Aflatoxin, biology, business.industry, 010604 marine biology & hydrobiology, Public Health, Environmental and Occupational Health, 04 agricultural and veterinary sciences, Toxicology, biology.organism_classification, 01 natural sciences, Pacu, Piaractus mesopotamicus, chemistry.chemical_compound, chemistry, Aquaculture, 040102 fisheries, 0401 agriculture, forestry, and fisheries, %22">Fish , Food science, Mycotoxin, business, Food Science
Abstract: The objective of this work was to evaluate the aflatoxins residues on tissues of Pacu (Piaractus mesopotamicus) fish chronically exposed to dietary aflatoxins, also evaluating the effects on fish performance. Aflatoxins were incorporated into the extruded fish feed and the concentrations were confirmed by high performance liquid chromatography (HPLC). The experimental design comprised the following treatments: Control – feed without toxin; Treatment A: feed + 10 μg aflatoxin B1 (AFB1)/kg; Treatment B: feed + 20 μg AFB1/kg and Treatment C: feed + 50 μg AFB1/kg. Pacu juvenile were allocated in tanks with density of one fish per litter. The experiment lasted 180 days with monthly sampling, and approximately ten fish per treatment were used to compose a sample. Biometric surveys were performed every 30 days, including standard weight and length. Aflatoxins were detected and quantified in fish muscle and liver by HPLC, using immunoafinity columns. Results showed AFB1 deposition in the liver throughout the experiment in all treatments, but only treatment C differed significantly (P1 residues at low levels in liver and only a slight amount in fish muscle, it should be noted that accumulation is possible in the Pacu species. The diets contaminated with AFB1 negatively interfered in weight and length of fish when compared to control. Therefore, it can be concluded that long-term exposure of Pacu to dietary AFB1 can cause losses to producers.
Published: 2021
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27. The role of sexting and related behaviors to victimization via nonconsensual pornography: an exploratory analysisof university students

Author: Catherine D. Marcum, Barbara H. Zaitzow, and George E. Higgins
Subjects: Cybercrime, Health (social science), Sociology and Political Science, Social Psychology, business.industry, Pornography, The Internet, Criminology, business, Psychology, Law
Abstract: Purpose The purpose of this study is to explore the experiences of university students with nonconsensual pornography. The focus of the present work is on nonconsensual pornography – the nonconsensual distribution of intimate images and sexual extortion – that are becoming common experiences for many people. While the forms of nonconsensual pornography may vary, each case has one thing in common: the offender has shared a private image of the victim without the victim’s consent. Design/methodology/approach The data for this study was collected from student participants at a southeastern university. The stratified sample of university students was sent a link to an online survey and the responses of those who chose to respond were used in subsequent analyses (n = 300). Findings The findings of this exploratory study show low self-control as a significant predictor of sexting. Significant predictors of victimization via nonconsensual pornography included participation in sexting and use of dating apps. Originality/value While not generalizable, the descriptive data provide an important landscape for consideration of policy and legal recommendations to protect potential victims as well as would-be perpetrators beyond a university setting.
Published: 2021
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28. Comparisons of 3-Dimensional Conformal and Intensity-Modulated Neutron Therapy for Head and Neck Cancers

Author: Natalie Viscariello, George E. Laramore, Matthew D. Greer, Robert D. Stewart, Jay J. Liao, and Upendra Parvathaneni
Subjects: Larynx, treatment planning, business.industry, medicine.medical_treatment, R895-920, Original Articles, QC770-798, Atomic and Molecular Physics, and Optics, Neutron therapy, Intensity (physics), fast neutron therapy, Medical physics. Medical radiology. Nuclear medicine, Therapeutic index, medicine.anatomical_structure, Nuclear and particle physics. Atomic energy. Radioactivity, Medicine, Dosimetry, Radiology, Nuclear Medicine and imaging, business, Head and neck, Radiation treatment planning, Nuclear medicine, Fast neutron therapy
Abstract: Purpose Neutron therapy is a high linear energy transfer modality that is useful for the treatment of radioresistant head and neck (H&N) cancers. It has been limited to 3-dimensioanal conformal-based fast-neutron therapy (3DCNT), but recent technical advances have enabled the clinical implementation of intensity-modulated neutron therapy (IMNT). This study evaluated the comparative dosimetry of IMNT and 3DCNT plans for the treatment of H&N cancers. Materials and Methods Seven H&N IMNT plans were retrospectively created for patients previously treated with 3DCNT at the University of Washington (Seattle). A custom RayStation model with neutron-specific scattering kernels was used for inverse planning. Organ-at-risk (OAR) objectives from the original 3DCNT plan were initially used and were then systematically reduced to investigate the feasibility of improving a therapeutic ratio, defined as the ratio of the mean tumor to OAR dose. The IMNT and 3DCNT plan quality was evaluated using the therapeutic ratio, isodose contours, and dose volume histograms. Results When compared with the 3DCNT plans, IMNT reduces the OAR dose for the equivalent tumor coverage. Moreover, IMNT is most advantageous for OARs in close spatial proximity to the target. For the 7 patients with H&N cancers examined, the therapeutic ratio for IMNT increased by an average of 56% when compared with the 3DCNT. The maximum OAR dose was reduced by an average of 20.5% and 20.7% for the spinal cord and temporal lobe, respectively. The mean dose to the larynx decreased by an average of 80%. Conclusion The IMNT significantly decreases the OAR doses compared with 3DCNT and provides comparable tumor coverage. Improvements in the therapeutic ratio with IMNT are especially significant for dose-limiting OARs near tumor targets. Moreover, IMNT provides superior sparing of healthy tissues and creates significant new opportunities to improve the care of patients with H&N cancers treated with neutron therapy.
Published: 2021
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29. Exercise Intolerance in Older Adults With Heart Failure With Preserved Ejection Fraction

Author: Jingzhone Ding, Alain G. Bertoni, Anthony J.A. Molina, Javed Butler, Jamie N. Justice, George E. Taffet, Scott L. Hummel, Daniel E. Forman, Flora Sam, Bret H. Goodpaster, Julio A. Chirinos, Ambarish Pandey, Barry A. Borlaug, Robert J. Mentz, Mark J. Haykowsky, Gregory D. Lewis, Marc A. Simon, Sanjiv J. Shah, Nathan K. LeBrasseur, Iraklis I. Pipinos, Dalane W. Kitzman, Dean L. Kellogg, James P. White, Roger A. Fielding, and Elena Volpi
Subjects: medicine.medical_specialty, Geroscience, business.industry, Exercise intolerance, State of the art review, Disease, medicine.disease, Heart failure, medicine, medicine.symptom, Cardiology and Cardiovascular Medicine, Intensive care medicine, business, Heart failure with preserved ejection fraction
Abstract: Exercise intolerance (EI) is the primary manifestation of chronic heart failure with preserved ejection fraction (HFpEF), the most common form of heart failure among older individuals. The recent recognition that HFpEF is likely a systemic, multiorgan disorder that shares characteristics with other common, difficult-to-treat, aging-related disorders suggests that novel insights may be gained from combining knowledge and concepts from aging and cardiovascular disease disciplines. This state-of-the-art review is based on the outcomes of a National Institute of Aging-sponsored working group meeting on aging and EI in HFpEF. We discuss aging-related and extracardiac contributors to EI in HFpEF and provide the rationale for a transdisciplinary, "gero-centric" approach to advance our understanding of EI in HFpEF and identify promising new therapeutic targets. We also provide a framework for prioritizing future research, including developing a uniform, comprehensive approach to phenotypic characterization of HFpEF, elucidating key geroscience targets for treatment, and conducting proof-of-concept trials to modify these targets.
Published: 2021
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30. A prospective, randomized, placebo-controlled, double-blinded clinical trial comparing the incidence and severity of gastrointestinal adverse events in dogs with cancer treated with piroxicam alone or in combination with omeprazole or famotidine

Author: George E. Moore, Christopher M. Fulkerson, and Marejka H Shaevitz
Subjects: medicine.medical_specialty, Piroxicam, Placebo, Gastroenterology, law.invention, Dogs, Randomized controlled trial, law, Neoplasms, Internal medicine, medicine, Animals, Dog Diseases, Prospective Studies, Prospective cohort study, Adverse effect, Omeprazole, General Veterinary, business.industry, Incidence, Famotidine, Clinical trial, business, medicine.drug
Abstract: OBJECTIVE To assess the impact of prophylactic omeprazole and famotidine on the incidence and severity of gastrointestinal (GI) adverse events (AEs) in dogs with cancer treated with single agent piroxicam. ANIMALS 39 dogs with a cytologic or histologic diagnosis of cancer with no history of GI disease and received piroxicam. PROCEDURES A prospective, randomized, placebo-controlled, double-blinded clinical trial was performed. All dogs received piroxicam (0.3 mg/kg [0.14 mg/lb], PO, q 24 h) and either omeprazole (1 mg/kg [0.45 mg/lb], PO, q 12 h), famoti-dine (1 mg/kg, PO, q 12 h), or placebo (lactose; PO, q 12 h). Monthly assessments of GI AEs were performed and scored by using the Veterinary Comparative Oncology Group's Common Terminology Criteria for Adverse Events (version 1.1). RESULTS Compared with dogs in the placebo group, more dogs in the omeprazole group (84.6% vs 36.4%) and famotidine group (80.0% vs 36.4%) experienced GI AEs by day 56. The severity of GI AEs was higher in the omeprazole group, compared with the placebo group. CONCLUSIONS AND CLINICAL RELEVANCE Omeprazole was not helpful in reducing the frequency or severity of GI AEs and was associated with more frequent and severer GI AEs in dogs with cancer treated with single agent piroxicam. Proton-pump inhibitors and H2-receptor antagonists should not be prescribed as prophylaxis with NSAIDs for dogs with cancer. (J Am Vet Med Assoc 2021;259:385-391)
Published: 2021
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31. Does Age Matter in Psoriatic Arthritis? A Narrative Review

Author: Elena Nikiphorou, George E Fragoulis, Stefan Siebert, and Iain B. McInnes
Subjects: medicine.medical_specialty, education.field_of_study, business.industry, Arthritis, Psoriatic, Immunology, Population, Comorbidity, medicine.disease, Affect (psychology), Psoriatic arthritis, Rheumatology, Ageing, Psoriasis, Relative risk, Internal medicine, Humans, Immunology and Allergy, Medicine, Social determinants of health, business, education, Depression (differential diagnoses)
Abstract: Psoriatic arthritis (PsA) affects about 0.8% of the general population. Together with psoriasis is termed psoriatic disease. Comorbidities play an important role in the clinical expression and treatment of psoriatic disease. Ageing adds another level of complexity, partly because age directly accrues increasing risk of comorbidities, but also due to its complex interactions with several factors such as depression and social determinants. Ageing seems to have a "paradoxical association" with cardiovascular comorbidities for which the relative risk is more pronounced in younger patients with psoriatic disease and also to affect treatment decisions and response in patients with psoriatic disease. Finally, there is convincing evidence that there are clinical, genetic and histopathological differences between young- and late- onset PsA and psoriasis. Herein, we review the effect of age in patients with psoriatic disease, with a focus on PsA, highlighting the need to consider this feature in routine clinical practice as well as in the research domain.
Published: 2021
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32. Astrocytes and Inflammasome: A Possible Crosstalk in Neurological Diseases

Author: George E. Barreto, Morgayn I. Read, Amirhossein Sahebkar, and Fahimeh Nourbakhsh
Subjects: Inflammasomes, Inflammation, Disease, Biochemistry, Neurological Damage, Glial Fibrillary Acidic Protein, Drug Discovery, medicine, Humans, Neuroinflammation, Pharmacology, Glial fibrillary acidic protein, biology, business.industry, Organic Chemistry, Inflammasome, medicine.disease, Astrogliosis, Crosstalk (biology), Astrocytes, biology.protein, Molecular Medicine, Nervous System Diseases, medicine.symptom, business, Neuroscience, medicine.drug
Abstract: Inflammasome research has primarily focused on neurological tissue, particularly on damaged tissue. Most current neurological literature involves in vivo and in vitro studies utilizing astroglia, as astroglia express the cytoskeletal glial fibrillary acidic protein (GFAP), which is used as a hallmark of neuropathological disorders. Research suggests that astrocytes respond to all forms of neurological damage or disease through reactive astrogliosis. Additionally, there is a consensus among scientists that inflammasomes play an important role in neuroinflammation. This review focuses on the latest developments in inflammasome biology, describing the current understanding of how inflammasomes can be triggered in the brain and summarizing the literature on the relevance of inflammasome NLR in prevalent neurological diseases.
Published: 2021
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33. Percutaneous Tracheostomy in Respiratory Failure Due to COVID-19

Author: Samuel Cohen, Philip K Ng, Oren A Friedman, Angelena R Lopez, and George E Chaux
Subjects: Pulmonary and Respiratory Medicine, Mechanical ventilation, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), SARS-CoV-2, business.industry, medicine.medical_treatment, COVID-19, Apnea, Context (language use), Single Center, Surgery, Tracheostomy, Respiratory failure, medicine, Humans, Respiratory virus, medicine.symptom, Respiratory Insufficiency, business, Body mass index, Retrospective Studies
Abstract: Background Coronavirus disease 2019 (COVID-19) can lead to hypoxemic respiratory failure resulting in prolonged mechanical ventilation. Typically, tracheostomy is considered in patients who remain ventilator dependent beyond 2 weeks. However, in the setting of this novel respiratory virus, the safety and benefits of tracheostomy are not well-defined. Our aim is to describe our experience with percutaneous tracheostomy in patients with COVID-19. Materials and methods This is a single center retrospective descriptive study. We reviewed comorbidities and outcomes in patients with respiratory failure due to COVID-19 who underwent percutaneous tracheostomy at our institution from April 2020 to September 2020. In addition, we provide details of our attempt to minimize aerosolization by using a modified protocol with brief periods of planned apnea. Results A total of 24 patients underwent percutaneous tracheostomy during the study. The average body mass index was 33.0±10.0. At 30 days posttracheostomy 17 (71%) patients still had the tracheostomy tube and 14 (58%) remained ventilator dependent. There were 3 (13%) who died within 30 days. At the time of data analysis in November 2020, 9 (38%) patients had died and 7 (29%) had been decannulated. None of the providers who participated in the procedure experienced signs or symptoms of COVID-19 infection. Conclusion Percutaneous tracheostomy in prolonged respiratory failure due to COVID-19 appears to be safe to perform at the bedside for both the patient and health care providers in the appropriate clinical context. Morbid obesity did not limit the ability to perform percutaneous tracheostomy in COVID-19 patients.
Published: 2021
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34. A combination of multi-scale calculations with machine learning for investigating hydrogen storage in metal organic frameworks

Author: Emmanuel Tylianakis, George E. Froudakis, Marco Di Gennaro, Rafaela Maria Giappa, and Konstantinos Gkagkas
Subjects: Materials science, Hydrogen, Binding energy, Energy Engineering and Power Technology, chemistry.chemical_element, 02 engineering and technology, 010402 general chemistry, Machine learning, computer.software_genre, 01 natural sciences, chemistry.chemical_compound, Hydrogen storage, Benzene, Renewable Energy, Sustainability and the Environment, business.industry, 021001 nanoscience & nanotechnology, Condensed Matter Physics, 0104 chemical sciences, Fuel Technology, chemistry, Proof of concept, Surface modification, Metal-organic framework, Artificial intelligence, 0210 nano-technology, Porous medium, business, computer
Abstract: Combining multi-scale calculations with machine learning, we investigate how the ligand functionalization affects the hydrogen storage profile of Metal Organic Frameworks. The binding energy of hydrogen with 58 strategically selected functionalized benzenes was calculated with accurate ab-initio methods. Our results show that many functional groups (e.g. -OPO3H2, –OCONH2) increase the interaction strength up to 15–25% compared to benzene while –OSO3H holds the most promise with an enhancement up to 80%. Grand Canonical Monte-Carlo calculations with interatomic potentials derived from the ab-initio calculations, verify the trend obtained from the meticulous screening. In addition, a proof of principle Machine Learning analysis is performed on the ab-initio results showing a good prediction of the H2 binding energies even with a limited amount of data. The results from our bottom-up approach lead us to conclude that this functionalization strategy can be applied to various porous materials in order to enhance their hydrogen storage performance.
Published: 2021
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35. Inclusivity and diversity: Integrating international perspectives on stem cell challenges and potential

Author: Andrés Caicedo, Patrick Chingo-Ho Hsieh, Consuelo Macias Abraham, Giulio Cossu, Jillian Cornish, Patrice Debré, Mamun Al Mahtab, Hidenori Akutsu, Michael S. Pepper, Antonio Carlos Campos de Carvalho, Lara Theresa Alentajan-Aleta, Geoffrey Dierckxsens, Romaldas Mačiulaitis, Nagwa El-Badri, Fergal J. O'Brien, George E. Griffin, Pradeep Kumar, Robin Fears, Maneesha S. Inamdar, Miodrag Čolić, and Volker ter Meulen
Subjects: Biomedical Research, Internationality, media_common.quotation_subject, Population, Cell- and Tissue-Based Therapy, regenerative medicine, biomedical policy, Biology, Biochemistry, Genetics, Animals, Humans, Good practice, education, media_common, Pace, education.field_of_study, Information Dissemination, business.industry, Stem Cells, Authorization, Cell Biology, Public relations, global, Transformative learning, Action (philosophy), Research Design, General partnership, Commentary, business, Developmental Biology, Diversity (politics)
Abstract: Summary Regenerative medicine has great potential. The pace of scientific advance is exciting and the medical opportunities for regeneration and repair may be transformative. However, concerns continue to grow, relating to problems caused both by unscrupulous private clinics offering unregulated therapies based on little or no evidence and by premature regulatory approval on the basis of insufficient scientific rationale and clinical evidence. An initiative by the InterAcademy Partnership convened experts worldwide to identify opportunities and challenges, with a focus on stem cells. This was designed to be inclusive and consensus outputs reflected the diversity of the global research population. Among issues addressed for supporting research and innovation while protecting patients were ethical assessment; pre-clinical and clinical research; regulatory authorization and medicines access; and engagement with patients, policy makers, and the public. The InterAcademy Partnership (IAP) identified options for action for sharing good practice and building collaboration within the scientific community and with other stakeholders worldwide., Highlights • An inclusive IAP study examined global stem cell opportunities and challenges • Great potential leads to concerns for evidence base in unregulated clinics • Also concerns for premature regulatory approval without sufficient evidence • Recommendations for responsible research and innovation and collaborations, In this article, Fears and colleagues describe an inclusive global initiative by the InterAcademy Partnership examining stem cell opportunities and challenges. Great therapeutic potential brings concerns about the inadequate evidence base used by unregulated clinics. Concerns are also expressed about premature regulatory approval without sufficient evidence. Recommendations cover ethical assessment; pre-clinical and clinical research; regulatory authorization and medicines access; and engagement with patients, policy makers, and the public.
Published: 2021
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36. Inter-laboratory automation of the in vitro micronucleus assay using imaging flow cytometry and deep learning

Author: John W. Wills, Ruby Buckley, Catherine A. Thornton, Claire M. Barnes, Paul Rees, George E. Johnson, Julia Kenny, Rachel E. Hewitt, Danielle S.G. Harte, Anne E. Carpenter, James G. Cronin, Minh Doan, Huw D. Summers, Andrew Filby, Benjamin J. Rees, Rachel E. Barnes, Jatin R. Verma, Qiellor Haxhiraj, Matthew A. Rodrigues, Anthony M. Lynch, Wills, John W. [0000-0002-4347-5394], Apollo - University of Cambridge Repository, and Wills, John W [0000-0002-4347-5394]
Subjects: 0301 basic medicine, Imaging flow cytometry, Computer science, Health, Toxicology and Mutagenesis, Genotoxicity and Carcinogenicity, Image analysis, Toxicology, Cell Line, 03 medical and health sciences, Deep Learning, 0302 clinical medicine, Micronucleus test, Machine learning, High throughput, Humans, Inter-laboratory, Safety testing, Cytokinesis, Automation, Laboratory, Micronucleus Tests, Dose-Response Relationship, Drug, Contextual image classification, business.industry, Deep learning, Pattern recognition, General Medicine, Flow Cytometry, Methyl Methanesulfonate, Automation, Compound screening, 030104 developmental biology, 030220 oncology & carcinogenesis, Benzimidazoles, Genetic toxicology, Carbamates, Artificial intelligence, business, Micronucleus, DNA Damage, Mutagens
Abstract: The in vitro micronucleus assay is a globally significant method for DNA damage quantification used for regulatory compound safety testing in addition to inter-individual monitoring of environmental, lifestyle and occupational factors. However, it relies on time-consuming and user-subjective manual scoring. Here we show that imaging flow cytometry and deep learning image classification represents a capable platform for automated, inter-laboratory operation. Images were captured for the cytokinesis-block micronucleus (CBMN) assay across three laboratories using methyl methanesulphonate (1.25–5.0 μg/mL) and/or carbendazim (0.8–1.6 μg/mL) exposures to TK6 cells. Human-scored image sets were assembled and used to train and test the classification abilities of the “DeepFlow” neural network in both intra- and inter-laboratory contexts. Harnessing image diversity across laboratories yielded a network able to score unseen data from an entirely new laboratory without any user configuration. Image classification accuracies of 98%, 95%, 82% and 85% were achieved for ‘mononucleates’, ‘binucleates’, ‘mononucleates with MN’ and ‘binucleates with MN’, respectively. Successful classifications of ‘trinucleates’ (90%) and ‘tetranucleates’ (88%) in addition to ‘other or unscorable’ phenotypes (96%) were also achieved. Attempts to classify extremely rare, tri- and tetranucleated cells with micronuclei into their own categories were less successful (≤ 57%). Benchmark dose analyses of human or automatically scored micronucleus frequency data yielded quantitation of the same equipotent concentration regardless of scoring method. We conclude that this automated approach offers significant potential to broaden the practical utility of the CBMN method across industry, research and clinical domains. We share our strategy using openly-accessible frameworks. Supplementary Information The online version contains supplementary material available at 10.1007/s00204-021-03113-0.
Published: 2021
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37. Circulating Rotavirus Genotypes among Children Younger than 5 Years with Acute Gastroenteritis in Zaria, Northwestern Nigeria

Author: Maria Ahuoiza Garba, Adebola Olayinka, Mukhtar Idris, Hassan Muktar, George E. Armah, Belinda Lartey, Fatima J Giwa, Abdulaziz Mukhtar, Modupeola Omotara Samaila, and Susan Damanka
Subjects: 0301 basic medicine, medicine.medical_specialty, Veterinary medicine, business.industry, Acute gastroenteritis, medicine.disease_cause, Group A, law.invention, 03 medical and health sciences, Rotavirus G, 030104 developmental biology, 0302 clinical medicine, Infectious Diseases, law, Rotavirus, Pediatrics, Perinatology and Child Health, Genotype, Epidemiology, medicine, 030212 general & internal medicine, business, Polymerase chain reaction, Mixed infection
Abstract: Objective This study aimed to determine the circulating rotavirus genotypes among children 0 to 59 months with acute gastroenteritis in Zaria, Northwestern Nigeria. Methods A cross-sectional hospital-based study was performed from November 2015 to April 2017 on 415 stool samples of children 0 to 59 months with acute gastroenteritis presenting at the pediatric clinics in five selected health care facilities in Zaria, Northwestern Nigeria. The stool samples were tested for group A rotavirus antigen by enzyme-linked immunosorbent assay (ELISA) using the ProSpecT™ Rotavirus Microplate Assay (Thermo Scientific Oxoid, United Kingdom). Rotavirus-positive strains were further characterized using seminested multiplex reverse transcriptase polymerase chain reaction. Results Of the 415 diarrheal stool samples collected from children with acute gastroenteritis, 12.3% (n = 51) tested positive by ELISA. Five rotavirus G genotypes (G1, G2, G3, G9, and G12) and three P genotypes (P[4], P[6], and P[8]) were detected. Eight genotype combinations were detected with G1P[8], G12P[8], and G3P[6] being the most prevalent (9.8% each) followed by G1P[6], G2P[4], and G9P[8] (5.9% each). G/P mix types representing 25.5% (n = 13) of strains were detected during the study period. Conclusion This study found a high diversity of rotavirus strains with emerging unusual rotavirus genotypes and a concurrent high proportion of mixed infections. This increased antigenic diversity of rotavirus strains may impact on vaccine effectiveness and rotavirus epidemiology and highlights the importance of continuous surveillance.
Published: 2021
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38. Haploinsufficiency of PRR12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities

Author: Tugce B. Balci, Paul R. Mark, Sedlácek Z, Krista Sondergaard Schatz, Tadashi Kaname, Christiane Zweier, Hidenori Ohnishi, Ingrid M. Wentzensen, Solveig Heide, Weimin Bi, A. Baxova, Antje Wiesener, Nancy J. Cox, Devon Haynes, David Rodriguez-Buritica, Sarka Bendova, Nobuhiko Okamoto, Tomoko Uehara, Oana Caluseriu, Koichi Kawakami, Victoria Mok Siu, Alfredo Brusco, Boris Keren, Jennifer M. Lemons, David J. Amor, Patrick Rump, Marie T. McDonald, George E. Hoganson, Miroslava Hancarova, Gina M. Morley, Maria A. Magriña, Sarah Montgomery, Lei Wang, Seema R. Lalani, Kazuo Kubota, Mohammed Al-raqad, Patricia G Wheeler, Haley Streff, Fuad Chowdhury, Elisa Biamino, Meral Gunay-Aygun, Tawfiq Froukh, Kenjiro Kosaki, and Jagdeep S. Walia
Subjects: 0301 basic medicine, Haploinsufficiency/genetics, Pathology, medicine.medical_specialty, Mutation, Missense, Haploinsufficiency, 030105 genetics & heredity, Microphthalmia, Frameshift mutation, Intellectual Disability, PRR12, neurodevelopmental disorder, Mice, 03 medical and health sciences, Neurodevelopmental disorder, medicine, Animals, Humans, Missense mutation, Genetics (clinical), Anophthalmia, business.industry, medicine.disease, Intellectual Disability/genetics, Hypotonia, Phenotype, 030104 developmental biology, Mutation, Muscle Hypotonia, Missense, medicine.symptom, business, Kidney disease
Abstract: Purpose: Proline Rich 12 (PRR12) is a gene of unknown function with suspected DNA-binding activity, expressed in developing mice and human brains. Predicted loss-of-function variants in this gene are extremely rare, indicating high intolerance of haploinsufficiency. Methods: Three individuals with intellectual disability and iris anomalies and truncating de novo PRR12 variants were described previously. We add 21 individuals with similar PRR12 variants identified via matchmaking platforms, bringing the total number to 24. Results: We observed 12 frameshift, 6 nonsense, 1 splice-site, and 2 missense variants and one patient with a gross deletion involving PRR12. Three individuals had additional genetic findings, possibly confounding the phenotype. All patients had developmental impairment. Variable structural eye defects were observed in 12/24 individuals (50%) including anophthalmia, microphthalmia, colobomas, optic nerve and iris abnormalities. Additional common features included hypotonia (61%), heart defects (52%), growth failure (54%), and kidney anomalies (35%). PrediXcan analysis showed that phecodes most strongly associated with reduced predicted PRR12 expression were enriched for eye- (7/30) and kidney- (4/30) phenotypes, such as wet macular degeneration and chronic kidney disease. Conclusion: These findings support PRR12 haploinsufficiency as a cause for a novel disorder with a wide clinical spectrum marked chiefly by neurodevelopmental and eye abnormalities. Graphic Abstract: [Figure not available: see fulltext.]
Published: 2021
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39. Biomechanical Evaluation of a Novel Barbed Suture Pattern with Epitendinous Suture Augmentation in a Canine Flexor Tendon Model

Author: Matthew B. Fisher, Yi-Jen Chang, George E. Moore, and Daniel J. Duffy
Subjects: medicine.medical_specialty, 040301 veterinary sciences, medicine.medical_treatment, Tenotomy, 0403 veterinary science, Tendons, 03 medical and health sciences, 0302 clinical medicine, Dogs, Suture (anatomy), Tendon Injuries, Tensile Strength, Forelimb, medicine, Cadaver, Animals, Dog Diseases, General Veterinary, Flexor tendon, Sutures, business.industry, Suture Techniques, 04 agricultural and veterinary sciences, Repair site, Plastic Surgery Procedures, Surgery, Biomechanical Phenomena, Knot tying, Barbed suture, 030220 oncology & carcinogenesis, Monofilament suture, Cadaveric spasm, business
Abstract: OBJECTIVE To determine the effect of a novel barbed suture pattern (NBSP) compared to a three-loop-pulley (3LP) with and without epitendinous suture (ES) augmentation on the biomechanical strength and gap formation of repaired canine tendons. STUDY DESIGN Ex vivo, cadaveric, randomized, experimental study. SAMPLE POPULATION Forty, adult superficial digital flexor tendons (SDFT). METHODS SDFT were randomly assigned to one of four groups (n = 10/group). Sharp tenotomy was performed and repaired with 3LP, NBSP, 3LP + ES, and NBSP + ES. Constructs were tested to failure while evaluating yield, peak, and failure loads, loads at 1 and 3 mm gap formation, and failure mode. RESULTS Constructs augmented with ES sustained 80% greater yield (p
Published: 2022
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40. Investigation of the Effects of Two-, Four-, Six- and Eight-Strand Suture Repairs on the Biomechanical Properties of Canine Gastrocnemius Tenorrhaphy Constructs

Author: Yi-Jen Chang, George E. Moore, and Daniel J. Duffy
Subjects: Orthodontics, Polypropylene suture, Sutures, General Veterinary, business.industry, medicine.medical_treatment, Suture Techniques, Tenotomy, General Medicine, Repair site, Tendon, Tendons, Dogs, medicine.anatomical_structure, Suture (anatomy), Animals, Medicine, Blood supply, Gastrocnemius tendon, Cadaveric spasm, business
Abstract: OBJECTIVE To determine the effects of 2-, 4-, 6- and 8-strand suture repairs on the biomechanical properties of canine gastrocnemius tenorrhaphy constructs in an ex vivo model. SAMPLE 56 cadaveric gastrocnemius musculotendinous units from 28 adult large-breed dogs. PROCEDURES Tendons were randomly assigned to 4 repair groups (2-, 4-, 6- or 8-strand suture technique; n = 14/group). Following tenotomy, repairs were performed with the assigned number of strands of 2-0 polypropylene suture in a simple interrupted pattern. Biomechanical testing was performed. Yield, peak, and failure loads, the incidence of 1- and 3-mm gap formation, forces associated with gap formation, and failure modes were compared among groups. RESULTS Yield, peak, and failure forces differed significantly among groups, with significantly greater force required as the number of suture strands used for tendon repair increased. The force required to create a 1- or 3-mm gap between tendon ends also differed among groups and increased significantly with number of strands used. All constructs failed by mode of suture pull-through. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that increasing the number of suture strands crossing the repair site significantly increases the tensile strength of canine gastrocnemius tendon repair constructs and their resistance to gap formation. Future studies are needed to assess the effects of multistrand suture patterns on tendon glide function, blood supply, healing, and long-term clinical function in dogs to inform clinical decision-making.
Published: 2022
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41. Urinary Pharmacokinetic Profile of Cannabidiol (CBD), Δ9-Tetrahydrocannabinol (THC) and Their Metabolites following Oral and Vaporized CBD and Vaporized CBD-Dominant Cannabis Administration

Author: Ruth E. Winecker, Elia Goffi, George E. Bigelow, Ryan Vandrey, John M. Mitchell, Ronald Flegel, Edward J. Cone, David J. Kuntz, Tory R. Spindle, and Dennis J. Sholler
Subjects: Adult, Health, Toxicology and Mutagenesis, Urinary system, Cmax, Administration, Oral, Urine, Pharmacology, Toxicology, digestive system, Article, Analytical Chemistry, Excretion, 03 medical and health sciences, Route of administration, 0302 clinical medicine, Pharmacokinetics, Oral administration, medicine, Cannabidiol, Humans, Environmental Chemistry, Dronabinol, 030212 general & internal medicine, Cannabis, Analgesics, Chemical Health and Safety, Cannabinoids, business.industry, digestive system diseases, surgical procedures, operative, Hallucinogens, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: The market for products containing cannabidiol (CBD) is booming globally. However, the pharmacokinetics of CBD in different oral formulations and the impact of CBD use on urine drug testing outcomes for cannabis (e.g., 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (Δ9-THCCOOH)) are understudied. This study characterized the urinary pharmacokinetics of CBD (100 mg) following vaporization or oral administration (including three formulations: gelcap, pharmacy-grade syrup and or Epidiolex) as well as vaporized CBD-dominant cannabis (containing 100 mg CBD and 3.7 mg Δ9-THC) in healthy adults (n = 18). A subset of participants (n = 6) orally administered CBD syrup following overnight fasting (versus low-fat breakfast). Urine specimens were collected before and for 58 h after dosing on a residential research unit. Immunoassay (IA) screening (cutoffs: 20, 50 and 100 ng/mL) for Δ9-THCCOOH was performed, and quantitation of cannabinoids was completed via LC–MS-MS. Urinary CBD concentrations (ng/mL) were higher after oral (mean Cmax: 734; mean Tmax: 4.7 h, n = 18) versus vaporized CBD (mean Cmax: 240; mean Tmax: 1.3 h, n = 18), and oral dose formulation significantly impacted mean Cmax (Epidiolex = 1,274 ng/mL, capsule = 776 ng/mL, syrup = 151 ng/mL, n = 6/group) with little difference in Tmax. Overnight fasting had limited impact on CBD excretion in urine, and there was no evidence of CBD conversion to Δ8- or Δ9-THC in any route or formulation in which pure CBD was administered. Following acute administration of vaporized CBD-dominant cannabis, 3 of 18 participants provided a total of six urine samples in which Δ9-THCCOOH concentrations ≥15 ng/mL. All six specimens screened positive at a 20 ng/mL IA cutoff, and two of six screened positive at a 50 ng/mL cutoff. These data show that absorption/elimination of CBD is impacted by drug formulation, route of administration and gastric contents. Although pure CBD is unlikely to impact drug testing, it is possible that hemp products containing low amounts of Δ9-THC may produce a cannabis-positive urine drug test.
Published: 2021
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42. The Curse of the Original: How and When Heritage Branding Reduces Consumer Evaluations of Enhanced Products

Author: Ravi Dhar, Rosanna Smith, Minju Han, and George E. Newman
Subjects: Marketing, Economics and Econometrics, Curse, Arts and Humanities (miscellaneous), Anthropology, 0502 economics and business, 05 social sciences, 050211 marketing, Advertising, Business, Business and International Management, 050203 business & management
Abstract: Heritage branding is a common marketing strategy that has been shown to increase product appeal. Here, we find that certain forms of heritage branding can also have potentially negative consequences by leading consumers to react negatively to changes made to the brand’s original, flagship product—even if those changes objectively improve it. We demonstrate that when firms engage in heritage branding that emphasizes a brand’s longevity, consumers evaluate enhanced products less favorably than the original versions of those same products due to decreased perceptions of continuity authenticity. We demonstrate this effect across a variety of product domains (e.g., cosmetics, cookware, and food products), using online experiments as well as in-person product trials. Moreover, we provide a framework that distinguishes between types of heritage branding cues that lead to negative evaluations of enhanced products versus those that do not. Finally, beyond identifying an important boundary condition based on specific aspects of heritage branding, we further show how the negative evaluations of enhanced products can be attenuated if brands reframe product changes as continuous with the brand’s origins. Together, these studies contribute to existing theory regarding heritage branding and authenticity, while also providing a number of practical recommendations for heritage brands.
Published: 2021
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43. Tolerability of risk: A commentary on the nitrosamine contamination issue

Author: David J. Snodin, David P. Elder, and George E. Johnson
Subjects: medicine.medical_specialty, Nitrosamines, business.industry, Pharmaceutical Science, 02 engineering and technology, 021001 nanoscience & nanotechnology, Risk Assessment, 030226 pharmacology & pharmacy, Drug standards, Highly sensitive, Discontinuation, 03 medical and health sciences, 0302 clinical medicine, Genomic mutation, Tolerability, False positive paradox, Humans, Valsartan, Medicine, Daily exposure, Drug Contamination, 0210 nano-technology, business, Intensive care medicine, Angiotensin II Type 1 Receptor Blockers
Abstract: For decades, regulators have grappled with different approaches to address the issue of control of impurities. Safety-based limits, such as permissible daily exposure (PDE), acceptable intake (AI), threshold of toxicological concern (TTC) and less than lifetime limits (LTL) have all been used. For many years these safety-based limits have been recognized as virtually safe doses (VSDs). Recently, however, many regulatory agencies are seeking to impose limits for N-nitrosamine impurities, which are significantly below the VSD. This commentary will discuss the evolution of safety-based limits for impurities, provide an overview of the valsartan N-nitrosamine contamination issue and review the toxicology of N-nitrosamines. The outcome of a lessons-learned exercise on sartan medications undertaken by the European Medicines Agency (EMA) will also be discussed. The review will also highlight the many analytical challenges inherent with controlling impurities to ppb-based limits. The use of highly sensitive, low ppb limits, methods may lead to future issues of batch rejection, based on false positives. Regulators initially viewed the N-nitrosamine risk as being insufficient to prompt immediate product discontinuation and patients were specifically advised to continue using their affected medication. Patients were also informed that exposure to N-nitrosamines is extremely common via food and drinking water.
Published: 2021
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44. Near Complete Pathologic Response to PD-1 Inhibitor and Radiotherapy in a Patient with Locally Advanced Pancreatic Ductal Adenocarcinoma

Author: Matthew J. Rendo, Guy T. Clifton, Anne E O'Shea, Alexandra M Adams, Timothy J. Vreeland, Joshua L. Fenderson, Patrick M. McCarthy, Daniel W. Nelson, Katherine M Cebe, Robert W Krell, George E. Peoples, and Matthew D Uy
Subjects: PD-L1, 0301 basic medicine, Oncology, medicine.medical_specialty, Pancreatic ductal adenocarcinoma, endocrine system diseases, medicine.medical_treatment, pancreatic cancer, Locally advanced, immune checkpoint inhibitor, Case Report, Pembrolizumab, complete response, 03 medical and health sciences, 0302 clinical medicine, locally advanced, Pancreatic cancer, Internal medicine, medicine, Pharmacology (medical), biology, business.industry, Cancer, Immunotherapy, medicine.disease, digestive system diseases, Radiation therapy, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, pembrolizumab, business
Abstract: Pancreatic ductal adenocarcinoma (PDAC) remains deadly despite advances in systemic therapies and surgical techniques. While there is increasing utilization of immune therapies across diverse cancer types, PDAC remains generally resistant to these treatments. We report a case of locally advanced PDAC treated with preoperative radiation and anti-PD-1 immunotherapy guided by preoperative PD-L1 tumor analysis. After 4 months of preoperative therapy, the patient was submitted to resection, demonstrating a near-complete pathologic response on final tumor analysis. We will discuss the relevant literature and current state of immunotherapeutics for PDAC.
Published: 2021
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45. Effect of epitendinous suture caliber on the tensile strength of repaired canine flexor tendons

Author: Yi-Jen Chang, George E. Moore, Aidan R Chambers, Matthew B. Fisher, and Daniel J. Duffy
Subjects: musculoskeletal diseases, Tendons, Dogs, Suture (anatomy), Tendon Injuries, Cadaver, Tensile Strength, Ultimate tensile strength, Animals, Medicine, Dog Diseases, Sutures, General Veterinary, Flexor tendon, business.industry, Suture Techniques, General Medicine, Anatomy, musculoskeletal system, Biomechanical Phenomena, body regions, surgical procedures, operative, Caliber, Cadaveric spasm, business
Abstract: OBJECTIVE To determine the effect of epitendinous suture (ES) caliber on the tensile strength of flexor tendon repairs in cadaveric specimens from dogs. SAMPLE 60 cadaveric superficial digital flexor tendons (SDFTs) from 30 skeletally mature dogs. PROCEDURES Specimens were randomly assigned to 5 suture caliber groups (n = 12 SDFTs/group). After sharp transection, SDFTs were repaired by placement of a simple continuous circumferential ES created with size-0, 2-0, 3-0, 4-0, or 5-0 polypropylene suture. Constructs were preloaded to 2 N and load tested to failure. Loads at yield, peak, and failure and mode of failure were compared among groups by statistical methods. RESULTS Yield, peak, and failure loads for SDFT repair constructs were positively correlated with ES caliber and did not differ between the size-0 and 2-0 groups on pairwise comparisons. Yield load was significantly greater for size-0, 2-0, and 3-0 groups than for the 4-0 and 5-0 groups. Peak and failure loads were significantly greater for the size-0 and 2-0 groups than for the remaining groups. Most size-0 (12/12), 2-0 (12/12), and 3-0 (10/12) group constructs failed because of ES pull-through; several constructs in the 4-0 group (5/12) and most in the 5-0 group (11/12) failed because of ES breakage. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested size-0 and 2-0 sutures should be considered when placing an ES for flexor tendon repairs in dogs. However, in vivo studies are needed determine the effects of increasing ES caliber on clinical outcomes for dogs undergoing these procedures.
Published: 2021
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46. Efonidipine Exerts Cerebroprotective Effect by Down-regulation of TGF-β/SMAD-2-Dependent Signaling Pathway in Diabetic Rats

Author: Ghulam Md Ashraf, Vishal Chavda, George E. Barreto, Snehal S. Patel, and Rashmi Rajput
Subjects: 0301 basic medicine, medicine.medical_specialty, medicine.drug_class, Efonidipine, Calcium channel blocker, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Diabetes mellitus, Internal medicine, medicine, Stroke, Voltage-dependent calcium channel, business.industry, Calcium channel, General Medicine, Streptozotocin, medicine.disease, Malondialdehyde, 030104 developmental biology, Endocrinology, chemistry, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Calcium overload and hyperglycemia are risks of stroke onset in diabetics. Our study was designed to elucidate the beneficial role of calcium channel blockers by targeting voltage-gated calcium channels in diabetes-associated cerebrovascular complications. Diabetes was induced using the neonatal streptozotocin rat model. After confirmation of diabetes, middle cerebral artery occlusion (MCAO) was carried out. The pre-treatment with 1 mg/kg/day efonidipine was administered for the period of 4 weeks. After 24 h of ischemic induction surgery, the neurological score was determined, and blood was collected for determination of biochemical parameters. Treatment with efonidipine showed a significant reduction in post-ischemic brain infract volume, brain hemisphere weight difference, neurological score, Na+-K+ ATPase activity, serum CK-MB, and LDH levels in normoglycemic and hyperglycemic MCAO-induced animals. While no significant changes in glucose and lipid levels were observed by treatment, efonidipine significantly decreased the levels of malondialdehyde, acetylcholine esterase, and nitrite levels and increased the levels of antioxidant markers in both normoglycemic and hyperglycemic MCAO animals. TGF-β and VEGF were found to be down-regulated after treatment with efonidipine in gene expression study. In conclusion, the study data supports the cerebroprotective role of efonidipine in diabetic animals possibly through TGF-β/SMAD-2 signaling pathway.
Published: 2021
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47. Constraints in Clinical Cardiology and Personalized Medicine: Interrelated Concepts in Clinical Cardiology

Author: Katerina G. Lourida and George E. Louridas
Subjects: 0301 basic medicine, Computer science, Systems biology, Disease, Downward causation, computer.software_genre, complex cardiovascular diseases, Field (computer science), 03 medical and health sciences, 0302 clinical medicine, Health care, Diseases of the circulatory (Cardiovascular) system, 030212 general & internal medicine, data integration, Constraint (mathematics), General Environmental Science, Management science, business.industry, systems biology, personalized medicine, taxonomic revision, 030104 developmental biology, RC666-701, General Earth and Planetary Sciences, Personalized medicine, constraints, business, computer, Data integration
Abstract: Systems biology is established as an integrative computational analysis methodology with practical and theoretical applications in clinical cardiology. The integration of genetic and molecular components of a disease produces interacting networks, modules and phenotypes with clinical applications in complex cardiovascular entities. With the holistic principle of systems biology, some of the features of complexity and natural progression of cardiac diseases are approached and explained. Two important interrelated holistic concepts of systems biology are described; the emerging field of personalized medicine and the constraint-based thinking with downward causation. Constraints in cardiovascular diseases embrace three scientific fields related to clinical cardiology: biological and medical constraints; constraints due to limitations of current technology; and constraints of general resources for better medical coverage. Systems healthcare and personalized medicine are connected to the related scientific fields of: ethics and legal status; data integration; taxonomic revisions; policy decisions; and organization of human genomic data.
Published: 2021
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48. Social arrangements, technical designs and impacts of energy communities: A review

Author: George E. Georghiou, Snezana Cundeva, and Vladimir Gjorgievski
Subjects: Value (ethics), 060102 archaeology, Relation (database), Renewable Energy, Sustainability and the Environment, business.industry, 020209 energy, Energy (esotericism), Field (Bourdieu), 06 humanities and the arts, 02 engineering and technology, Environmental economics, Critical discussion, Distributed generation, 0202 electrical engineering, electronic engineering, information engineering, 0601 history and archaeology, business, Engineering design process, Efficient energy use
Abstract: Due to the potential for deploying distributed generation, improving energy efficiency and adopting sustainable energy-related practices, consumers provide significant value in the energy sector transformation. If their interests and goals are similar, they can group together and form energy communities. Energy communities enable consumers to jointly pursue their individual and collective economic, environmental and social goals, while simultaneously contributing to the decarbonisation of the energy system. Considering the growing interest in this field, this paper aims to enhance the understanding of the social arrangements, the technical designs and the impacts of energy communities. The social arrangements of energy communities are discussed in relation to the different actors, their roles and interactions. Then, the paper reviews the technical aspects of designing various local energy systems, while taking into account the goals of energy community members and outside actors. The reviewed literature is benchmarked with respect to the methods, modelling objectives and the constraints used in the design process. Finally, the paper quantifies the economic, environmental, technical and social impacts of energy communities, reviews the numerical indicators used to quantify these impacts and provides a critical discussion of the findings. Based on the findings, future research directions are highlighted.
Published: 2021
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49. Current Status of Training and Certification for Congenital Heart Surgery Around the World: Proceedings of the Meetings of the Global Council on Education for Congenital Heart Surgery of the World Society for Pediatric and Congenital Heart Surgery

Author: Morten Helvind, Bohdan Maruszewski, Emile A. Bacha, Kisaburo Sakamoto, Christo I. Tchervenkov, Susan Vosloo, Cheul Lee, James S. Tweddell, Christian Kreutzer, Attilio A. Lotto, Hani K. Najm, Giovanni Stellin, Nguyen Ly Thinh Truong, Piya Samankatiwat, Jeffrey P. Jacobs, Joseph A. Dearani, Drissi Boumzebra, Miguel Arboleda, Krishna S Iyer, Pedro Becker, Tae-Gook Jun, James D St Louis, Valdano Manuel, Claudia Herbst, Bistra Zheleva, George E. Sarris, Richard A. Jonas, Frank Edwin, Kirsten Finucane, Sivakumar Sivalingam, Hafil B Abdulgani, Hao Zhang, David M. Overman, Marcelo B. Jatene, Vladimiro L. Vida, David J. Barron, Zohair Al-Halees, José Fragata, Adel Elgamal, Budi Rahmat, Elizabeth H. Stephens, Jorge Cervantes, Nestor Sandoval, Darshan Reddy, James K. Kirklin, and Justin T. Tretter
Subjects: Heart Defects, Congenital, Nonprofit organization, medicine.medical_specialty, Certification, Heart disease, education, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Cardiac Surgical Procedures, Quality of care, Child, Societies, Medical, business.industry, Thoracic Surgery, General Medicine, medicine.disease, Surgery, Cardiac surgery, 030228 respiratory system, Cardiothoracic surgery, Pediatrics, Perinatology and Child Health, Cardiology and Cardiovascular Medicine, business
Abstract: The optimal training of the highly specialized congenital heart surgeon is a long and complex process, which is a significant challenge in most parts of the world. The World Society for Pediatric and Congenital Heart Surgery (WSPCHS) has established the Global Council on Education for Congenital Heart Surgery as a nonprofit organization with the goal of assessing current training and certification and ultimately establishing standardized criteria for the training, evaluation, and certification of congenital heart surgeons around the world. The Global Council and the WSPCHS have reviewed the present status of training and certification for congenital cardiac surgery around the world. There is currently lack of consensus and standardized criteria for training in congenital heart surgery, with significant disparity between continents and countries. This represents significant obstacles to international job mobility of competent congenital heart surgeons and to the efforts to improve the quality of care for patients with Congenital Heart Disease worldwide. The purpose of this article is to summarize and document the present state of training and certification in congenital heart surgery around the world.
Published: 2021
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50. Effect of Biologics on Cardiovascular Inflammation: Mechanistic Insights and Risk Reduction

Author: Petros P. Sfikakis, Stergios Soulaidopoulos, Theodoros Dimitroulas, George D. Kitas, and George E Fragoulis
Subjects: 0301 basic medicine, ARDS, biologic agents, Immunology, Review, Disease, Bioinformatics, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, Randomized controlled trial, cardiovascular disease, law, Immunology and Allergy, Medicine, medicine.diagnostic_test, business.industry, Abatacept, medicine.disease, interleukins, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Rheumatoid arthritis, Rituximab, atherosclerosis, inflammatory disorders, business, Lipid profile, medicine.drug
Abstract: It is increasingly recognized that atherosclerosis and consequently cardiovascular disease (CVD) are closely linked with inflammatory processes. The latter is in the center of the pathogenic mechanism underlying autoimmune rheumatic diseases (ARD). It follows then, that optimal control of inflammation in ARDs may lead to a decrease of the accompanied CVD risk. Major trials (eg, CANTOS, CIRT), aimed at examining the possible benefits of immunomodulatory treatments in CVD, demonstrated conflicting results. On the other hand, substantial evidence is accumulating about the possible beneficial effects of biologic disease modifying antirheumatic drugs (bDMARDs) in patients with ARDs, particularly those with rheumatoid arthritis (RA). It seems that bDMARDs (some more than others) alter the lipid profile in RA patients but do not adversely affect, in most cases, the TC/HDL ratio. Favorable effects are noted for arterial stiffness and endothelial function. This is reflected in the lower risk for CVD events, seen in observational studies of RA patients treated with bDMARDs. It should be stressed that more data exist for the TNF-inhibitors than for other bDMARDs, such as tocilizumab, abatacept and rituximab. As regards the spondyloarthropathies (SpA), data are less robust. For TNF-inhibitors, effects appear to be on par with those seen in RA but no conclusions can be drawn for newer biologic drugs used in SpA (eg, IL-17 blockers). Finally, there is accumulating evidence for a beneficial effect of immunosuppressive treatment in cardiac inflammation and function in several ARDs. Introduction of newer therapeutic options in clinical practice seem to have a positive impact on CVD in the setting of ARD. This is probably due to better control of inflammation, but direct improvement in vascular pathology is also a valid hypothesis. Most data are derived from observational studies and, therefore, randomized controlled trials are needed to assess the possible favorable effect of bDMARDs on CVD outcomes.
Published: 2021
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