tbuckley/cabot-search huggingface dataset:
Emotional Correlates of the COVID-19 Pandemic in Individuals With and Without Diabetes
Authors: Barbara A. Myers, Rachel Klingensmith, Mary de Groot
Journal: Diabetes Care (2021)

OBJECTIVE To compare the mental health experiences associated with coronavirus disease 2019 (COVID-19) in adults with and without diabetes. RESEARCH DESIGN AND METHODS Between 29 May 2020 and 30 June 2020, 2,176 U.S. adults completed an online survey including demographics, COVID-19 experiences, depression (eight-item Patient Health Questionnaire) and anxiety (seven-item Generalized Anxiety Disorder) symptoms, perceived stress (10-item Perceived Stress Scale), resilience (Brief Resilience Scale), and diabetes-related distress (in participants with diabetes) (17-item Diabetes Distress Scale). RESULTS Mean age was 49.6 years (SD 16.9); participants were primarily women (80.0%) and White (88.3%), with an annual household income of ≥$60,000 (57.6%). One hundred reported a diagnosis of type 1 diabetes (4.6%), 304 type 2 diabetes (13.9%), and 145 prediabetes (6.6%). Nearly one-third (29.7%) indicated decreases in income attributable to the pandemic. Participants with type 1 diabetes had higher levels of diabetes distress than participants with type 2 diabetes (P &amp;lt; 0.05), with moderate severity in both groups. Participants with type 2 diabetes had significantly more comorbidities and COVID-19 risk factors than all other groups (all P &amp;lt; 0.01). After controlling for covariates, participants with type 2 diabetes reported significantly more depressive symptoms than those without diabetes (P &amp;lt; 0.05) and lower levels of resilience (P &amp;lt; 0.05). Subgroup analyses by sex and age indicated that women and younger adults, particularly those age 18–34 years, reported significantly more depression and anxiety symptoms, stress, and diabetes-related distress and lower levels of resilience than men and adults age ≥51 years. CONCLUSIONS In this naturalistic observational study, participants with type 2 diabetes reported more depression, lower resilience, and significantly more COVID-19 risk factors and medical comorbidities than participants without diabetes. Overall, our participants demonstrated worse depression and anxiety symptoms during compared with before the pandemic.
TCT-222 Intravascular Ultrasound Guided Percutaneous Coronary Intervention Is Associated With a Longer Stented Segment and Less Residual Ischemic Burden in Treating Diffuse Coronary Artery Disease
Authors: Povilas Budrys, Arvydas Baranauskas, Michailas Jerdiakovas, Giedrius Davidavicius
Journal: Journal of the American College of Cardiology (2021)
Past, present and future of therapeutic strategies against amyloid-β peptides in Alzheimer’s disease: a systematic review
Authors: Danko Jeremic, Lydia Jiménez-Díaz, Juan D. Navarro-López
Journal: Ageing Research Reviews (2021)

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in ageing, affecting around 46 million people worldwide but few treatments are currently available. The etiology of AD is still puzzling, and new drugs development and clinical trials have high failure rates. Urgent outline of an integral (multi-target) and effective treatment of AD is needed. Accumulation of amyloid-β (Aβ) peptides is considered one of the fundamental neuropathological pillars of the disease, and its dyshomeostasis has shown a crucial role in AD onset. Therefore, many amyloid-targeted therapies have been investigated. Here, we will systematically review recent (from 2014) investigational, follow-up and review studies focused on anti-amyloid strategies to summarize and analyze their current clinical potential. Combination of anti-Aβ therapies with new developing early detection biomarkers and other therapeutic agents acting on early functional AD changes will be highlighted in this review. Near-term approval seems likely for several drugs acting against Aβ, with recent FDA approval of a monoclonal anti-Aβ oligomers antibody –aducanumab– raising hopes and controversies. We conclude that, development of oligomer-epitope specific Aβ treatment and implementation of multiple improved biomarkers and risk prediction methods allowing early detection, together with therapies acting on other factors such as hyperexcitability in early AD, could be the key to slowing this global pandemic.
Acalabrutinib monotherapy for treatment of chronic lymphocytic leukaemia (ACE-CL-001): analysis of the Richter transformation cohort of an open-label, single-arm, phase 1–2 study
Authors: Toby A Eyre, Anna Schuh, William G Wierda, Jennifer R Brown, Paolo Ghia, John M Pagel, Richard R Furman, Jean Cheung, Ahmed Hamdy, Raquel Izumi, Priti Patel, Min Hui Wang, Yan Xu, John C Byrd, Peter Hillmen
Journal: The Lancet Haematology (2021)
Trends in the Use of Benzodiazepines, Z-Hypnotics, and Serotonergic Drugs Among US Women and Men Before and During the COVID-19 Pandemic
Authors: Sadaf Arefi Milani, Mukaila A. Raji, Lu Chen, Yong-Fang Kuo
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The ongoing COVID-19 pandemic and associated mitigation measures have disrupted access to psychiatric medications, particularly for women. <h3>Objective</h3> To assess the sex differences in trends in the prescribing of benzodiazepines, Z-hypnotics and serotonergic (selective serotonin reuptake inhibitors [SSRIs] and serotonin and norepinephrine reuptake inhibitors [SNRIs]), which are commonly prescribed for anxiety, insomnia, and depression. <h3>Design, Setting, and Participants</h3> This cohort study used data from Clinformatics Data Mart, one of the largest commercial health insurance databases in the US. Enrollees 18 years or older were required to have complete enrollment in a given month during our study period, January 1, 2018, to March 31, 2021, to be included for that month. <h3>Main Outcomes and Measures</h3> Prescription of a benzodiazepine, Z-hypnotic, or SSRI or SNRI. For each month, the percentage of patients with benzodiazepine, Z-hypnotic, or SSRI or SNRI prescriptions by sex was calculated. <h3>Results</h3> The records of 17 255 033 adults (mean [SD] age, 51.7 [19.5] years; 51.3% female) were examined in 2018, 17 340 731 adults (mean [SD] age, 52.5 [19.7] years; 51.6% female) in 2019, 16 916 910 adults (mean [SD] age, 53.7 [19.8] years; 51.9% female) in 2020, and 15 135 998 adults (mean [SD] age, 56.2 [19.8] years; 52.5% female) in 2021. Compared with men, women had a higher rate of prescriptions for all 3 drugs classes and had larger changes in prescription rates over time. Benzodiazepine prescribing decreased from January 2018 (women: 5.61%; 95% CI, 5.60%-5.63%; men: 3.03%; 95% CI, 3.02%-3.04%) to March 2021 (women: 4.91%; 95% CI, 4.90%-4.93%; men: 2.66%; 95% CI, 2.65%-2.67%), except for a slight increase in April 2020 among women. Z-hypnotic prescribing increased from January 2020 for women (1.39%; 95% CI, 1.38%-1.40%) and February 2020 for men (0.97%; 95% CI, 0.96%-0.98%) to October 2020 (women: 1.46%; 95% CI, 1.46%-1.47%; men: 1.00%; 95% CI, 0.99%-1.01%). Prescribing of SSRIs and SNRIs increased from January 2018 (women: 12.77%; 95% CI; 12.75%-12.80%; men: 5.56%; 95% CI, 5.44%-5.58%) to April 2020 for men (6.73%; 95% CI, 6.71%-6.75%) and October 2020 for women (15.18%; 95% CI, 15.16%-15.21%). <h3>Conclusions and Relevance</h3> In this cohort study, coinciding with the COVID-19 pandemic onset was an increase in Z-hypnotic as well as SSRI and SNRI prescriptions in both men and women along with an increase in benzodiazepine prescriptions in women, findings that suggest a substantial mental health impact of COVID-19–associated mitigation measures.
Ultrasound in the Diagnosis of Perinatal Ischemic Strokes (Literature Review with Their Own Clinical Observations)
Authors: Yu. K. Bykova, L. V. Ushakova, E. A. Filippova, A. B. Sugak, K. V. Vatolin, V. G. Bychenko, V. V. Zubkov, A. Suvorov
Journal: Radiology - Practice (2021)

The issues of early diagnosis of perinatal arterial stroke (PAII) continue to be discussed in the domestic and foreign literature. Along with MRI, the ultrasound method allows to identify foci of ischemia of different localization and sizes in newborns. During ultrasound, we identified 29 cases of PAIA of different localization in children of different gestational and postnatal age. Analysis of our own and published data showed that up to 32 weeks of gestational development, AII develops in the lenticular-striar basin, and later in the cortical-subcortical region. Diagnostic capabilities of ultrasound in PAII can be significantly expanded by using ultrasound duplex scanning of brain vessels. Our observations showed that the nature of changes in Doppler parameters depends on the localization of the affected vascular basin and on the duration of cerebrovascular disorders
Efficacy and Safety of Itepekimab in Patients with Moderate-to-Severe Asthma
Authors: Michael E. Wechsler, Marcella K. Ruddy, Ian D. Pavord, Elliot Israel, Klaus F. Rabe, Linda B. Ford, Jorge F. Maspero, Raolat M. Abdulai, Chih-Chi Hu, Renata Martincova, Andreas Jessel, Michael C. Nivens, Nikhil Amin, David M. Weinreich, George D. Yancopoulos, Helene Goulaouic
Journal: New England Journal of Medicine (2021)

Monoclonal antibodies targeting IgE, interleukin-4 and -13, and interleukin-5 are effective in treating severe type 2 asthma, but new targets are needed. Itepekimab is a new monoclonal antibody against the upstream alarmin interleukin-33. The efficacy and safety of itepekimab as monotherapy, as well as in combination with dupilumab, in patients with asthma are unclear.In a phase 2 trial, we randomly assigned, in a 1:1:1:1 ratio, adults with moderate-to-severe asthma receiving inhaled glucocorticoids plus long-acting beta-agonists (LABAs) to receive subcutaneous itepekimab (at a dose of 300 mg), itepekimab plus dupilumab (both at 300 mg; combination therapy), dupilumab (300 mg), or placebo every 2 weeks for 12 weeks. After randomization, LABA was discontinued at week 4, and inhaled glucocorticoids were tapered over weeks 6 through 9. The primary end point was an event indicating a loss of asthma control, assessed in the itepekimab group and the combination group, as compared with the placebo group. Secondary and other end points included lung function, asthma control, quality of life, type 2 biomarkers, and safety.A total of 296 patients underwent randomization. By 12 weeks, an event indicating a loss of asthma control occurred in 22% of the patients in the itepekimab group, 27% of those in the combination group, and 19% of those in the dupilumab group, as compared with 41% of those in the placebo group; the corresponding odds ratios as compared with placebo were as follows: in the itepekimab group, 0.42 (95% confidence interval [CI], 0.20 to 0.88; P = 0.02); in the combination group, 0.52 (95% CI, 0.26 to 1.06; P = 0.07); and in the dupilumab group, 0.33 (95% CI, 0.15 to 0.70). As compared with placebo, the forced expiratory volume in 1 second before bronchodilator use increased with the itepekimab and dupilumab monotherapies but not with the combination therapy. Itepekimab treatment improved asthma control and quality of life, as compared with placebo, and led to a greater reduction in the mean blood eosinophil count. The incidence of adverse events was similar in all four trial groups.Interleukin-33 blockade with itepekimab led to a lower incidence of events indicating a loss of asthma control than placebo and improved lung function in patients with moderate-to-severe asthma. (Funded by Sanofi and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT03387852.).
Medics get on their bikes to fight air pollution
Authors: Alison Shepherd
Journal: BMJ (2021)

Thirty paediatric health workers from across the UK and their supporters line up in King's Cross, London, to start the first leg of an 800 km ride to Glasgow and the start of the United Nations' COP26 climate summit.The cyclists, taking part in the "Ride for their Lives" to raise awareness of air pollution, will be joined on the way by health leaders such as Fiona Godlee, The BMJ's editor in chief, Andrew Goddard, Royal College of Physicians president, and Camilla Kingdon, president of the Royal College of Paediatrics and Child Health.Once in Glasgow they will call on health professionals to communicate better about the seriousness of the problem of polluted air, which particularly harms children.They will also deliver documents showing the need for urgent action on air pollution and the wider climate crisis.
TCT-65 Characteristics of COVID-19 Patients With Thrombosis and Impact on Clinical Outcomes
Authors: Brian Case, Jonathan Abramowitz, Corey Shea, Hank Rappaport, Giorgio Medranda, Charan Yerasi, Chava Chezar-Azerrad, Cheng Zhang, Lowell Satler, Itsik Ben-Dor, Hayder Hashim, Toby Rogers, William Weintraub, Ron Waksman
Journal: Journal of the American College of Cardiology (2021)
3D Printed Dual‐Porosity Scaffolds: The Combined Effect of Stiffness and Porosity in the Modulation of Macrophage Polarization
Authors: Sandra Camarero‐Espinosa, Maria Carlos‐Oliveira, Hong Liu, João F. Mano, Nicole Bouvy, Lorenzo Moroni
Journal: Advanced Healthcare Materials (2021)

Abstract Tissue regeneration evolves toward the biofabrication of sophisticated 3D scaffolds. However, the success of these will be contingent to their capability to integrate within the host. The control of the mechanical or topographical properties of the implant appears as an ideal method to modulate the immune response. However, the interplay between these properties is yet not clear. Dual‐porosity scaffolds with varying mechanical and topographical features are created, and their immunomodulatory properties in rat alveolar macrophages in vitro and in vivo in a rat subcutaneous model are evaluated. Scaffolds are fabricated via additive manufacturing and thermally induced phase separation methods from two copolymers with virtually identical chemistries, but different stiffness. The introduction of porosity enables the modulation of macrophages toward anti‐inflammatory phenotypes, with secretion of IL‐10 and TGF‐ β . Soft scaffolds (&lt;5 kPa) result in a pro‐inflammatory phenotype in contrast to stiffer (&gt;40 kPa) scaffolds of comparable porosities supporting a pro‐healing phenotype, which appears to be related to the surface spread area of cells. In vivo, stiff scaffolds integrate, while softer scaffolds appear encapsulated after three weeks of implantation, resulting in chronic inflammation after six weeks. The results demonstrate the importance of evaluating the interplay between topography and stiffness of candidate scaffolds.
TIGER-1: A Phase 2/3 Study of First Line Rociletinib or Erlotinib in EGFR-Mutant NSCLC
Authors: Ross Camidge, Federico Cappuzzo, Jowell Go, Jeffrey Isaacson, Jason Litten, Keunchil Park, David R. Spigel, Alexander Spira, Alain Vergnenegre, Juergen Wolf, James Chih-Hsin Yang, Tony Mok, 楊志新
Journal: Journal of Thoracic Oncology (2015)
Targeting Higher Intraoperative Blood Pressures Does Not Reduce Adverse Cardiovascular Events Following Noncardiac Surgery
Authors: Patrick M. Wanner, Dirk U. Wulff, Mirjana Djurdjevic, Wolfgang Korte, Thomas W. Schnider, Miodrag Filipovic
Journal: Journal of the American College of Cardiology (2021)

Intraoperative arterial hypotension is strongly associated with postoperative major adverse cardiovascular events (MACE); however, whether targeting higher intraoperative mean arterial blood pressures (MAPs) may prevent adverse events remains unclear.This study sought to determine whether targeting higher intraoperative MAP lowers the incidence of postoperative MACE.This single-center randomized controlled trial assigned adult patients at cardiovascular risk undergoing major noncardiac surgery to an intraoperative MAP target of ≥60 mm Hg (control) or ≥75 mm Hg (MAP ≥75). The primary outcome was acute myocardial injury on postoperative days 0-3 and/or 30-day MACE/acute kidney injury (AKI) (acute coronary syndrome, congestive heart failure, coronary revascularization, stroke, AKI, and all-cause mortality). The secondary outcome was 1-year MACE.In total, 458 patients were randomized (intention-to-treat population: 451). The cumulative intraoperative duration with MAP <65 mm Hg was significantly shorter in the MAP ≥75 group (median 9 minutes [interquartile range: 3 to 24 minutes] vs 23 minutes [interquartile range: 8-49 minutes]; P < 0.001). The primary outcome incidence was 48% for MAP ≥75 and 52% for control (risk difference -4.2%; 95% CI: -13% to +5%), the primary contributor being AKI (incidence 44%). Acute myocardial injury occurred in 15% (MAP ≥75) and 19% (control) of patients. The secondary outcome incidence was 17% for MAP ≥75 and 15% for control (risk difference +2.7; 95% CI: -4% to +9.5%).These findings do not support universally targeting higher intraoperative blood pressures to reduce postoperative complications. Despite a 60% reduction in hypotensive time with MAP <65 mm Hg, no significant reductions in acute myocardial injury or 30-day MACE/AKI could be found. (Biomarkers, Blood Pressure, BIS: Risk Stratification/Management of Patients at Cardiac Risk in Major Noncardiac Surgery [BBB]; NCT02533128).
Right-Based Mental Health Care—Advantages of Tax-Financed Universal Mental Health Care
Authors: Merete Nordentoft, Mette Falkenberg Krantz, Ida Hageman
Journal: JAMA Psychiatry (2021)

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Molecular mechanism of exemestane inhibition of aromatase. A site-directed mutagenesis study
Authors: Yanyan Hong, Shiuan Chen
Journal: Cancer Research (2005)

5774  Aromatase converts androgen to estrogen. Research from our and other laboratories has confirmed that aromatase is expressed at a higher level in breast cancer tissue than in benign tissue. In situ estrogen biosynthesis in tumor tissue has been shown to play both an autocrine and an endocrine role in promoting tumor growth. Aromatase inhibitors have been demonstrated to be important drugs in the treatment of breast cancer in postmenopausal women. Exemestane is an irreversible (Type 1), steroidal aromatase inhibitor. While it is thought that exemestane achieves its inhibition by binding to the active site of aromatase, the molecular nature for the interaction of this compound with the enzyme is not yet determined. During the past ten years, our laboratory has prepared 51 mutants using the CHO cell expression method. The studies have revealed that two regions, the I helix (Cys-299 to Ser-312) and the “hydrophobic” pocket (Ile-474 to His-480), are important parts of the active site and makes significant contributions to the binding of the substrate and conversion of androgen to estrogen. To better understand how exemestane interacts with aromatase, we first performed inhibitory profile analyses on the wild-type enzyme and 10 mutants. Exemestane was found to be significantly less potent in the inhibition of the mutants, E302D (IC50 = 32 nM), D309A (IC50 = 65 nM) and S478T (IC50 = 68 nM), than the wild-type aromatase (IC50 = 24 nM). A time course study of the inhibition of different aromatase mutants by exemestane (at 20 nM) was then performed. A definitive time-dependent inhibition of the wild-type aromatase was observed, as expected for a suicide inhibitor. However, time-dependent inhibition of three mutants could not be demonstrated. Glu-302, Asp-309 and Ser-478 have been previously suggested to play important roles in the binding of the androgen substrate. These recent results indicate that these amino acid residues may participate in the mechanism of the suicide inhibition of aromatase by exemestane. A computer model to illustrate the interaction of exemestane with aromatase has been generated. This information is important for the understanding of the molecular action of exemestane, a third-generation aromatase inhibitor, and for the development of the fourth-generation inhibitors.
Cutaneous epithelioid haemangiomas show somatic mutations in the mitogen‐activated protein kinase pathway
Authors: K. Maurus, C. Kosnopfel, H. Kneitz, S. Appenzeller, D. Schrama, V. Glutsch, S. Roth, E. Gerhard‐Hartmann, M. Rosenfeldt, L. Möhrmann, M. Fröhlich, D. Hübschmann, A. Stenzinger, H. Glimm, S. Fröhling, M. Goebeler, A. Rosenwald, H. Kutzner, B. Schilling
Journal: British Journal of Dermatology (2021)

Background Epithelioid haemangioma (EH) arising from the skin is a benign vascular tumour with marked inflammatory cell infiltration, which exhibits a high tendency to persist and frequently recurs after resection. So far, the underlying pathogenesis is largely elusive. Objectives To identify genetic alterations by next-generation sequencing and/or droplet digital polymerase chain reaction (ddPCR) in cutaneous EH. Methods DNA and RNA from an EH lesion of an index patient were subjected to whole-genome and RNA sequencing. Multiplex PCR-based panel sequencing of genomic DNA isolated from archival formalin-fixed paraffin-embedded tissue of 18 patients with cutaneous EH was performed. ddPCR was used to confirm mutations. Results We identified somatic mutations in genes of the mitogen-activated protein kinase (MAPK) pathway (MAP2K1 and KRAS) in cutaneous EH biopsies. By ddPCR we could confirm the recurrent presence of activating, low-frequency mutations affecting MAP2K1. In total, nine out of 18 patients analysed showed activating MAPK pathway mutations, which were mutually exclusive. Comparative analysis of tissue areas enriched for lymphatic infiltrate or aberrant endothelial cells, respectively, revealed an association of these mutations with the presence of endothelial cells. Conclusions Taken together, our data suggest that EH shows somatic mutations in genes of the MAPK pathway which might contribute to the formation of this benign tumour.
TCT-217 Predictors of Dyspnea in Patients Receiving Ticagrelor After PCI: Insights From the Twilight Trial
Authors: Dominick Angiolillo, Carlo Andrea Pivato, Davide Cao, Vijay Kunadian, Samantha Sartori, Zhongjie Zhang, David Cohen, Timothy Collier, Dariusz Dudek, Robert Gil, Kurt Huber, Ran Kornowski, Shamir Mehta, E. Magnus Ohman, Keith Oldroyd, Gennaro Sardella, Samin Sharma, Richard Shlofmitz, Giora Weisz, Bernhard Witzenbichler, George Dangas, Stuart Pocock, Roxana Mehran
Journal: Journal of the American College of Cardiology (2021)
TCT-191 HighLife Trans-Septal Mitral Valve Replacement (TSMVR) System; Early and Long Term Clinical and Hemodynamic Outcomes of the First 30 Consecutive Cases; The HighLife Feasibility Studies in Europe, Australia, and the US
Authors: Wolfgang Rottbauer, Leonhard Schneider, Georg Nickenig, Zenon huczek, Wojciech Wojakowski, Didier Tchetche, Christophe Dubois, Malek Nasr, Luc Verhees, Martin Rothman, Nicolo Piazza, Jean Buithieu, Wen Loong Yeow, Stephen G. Worthley
Journal: Journal of the American College of Cardiology (2021)
TCT-147 Transcatheter Aortic Valve Replacement in Large Annuli Valves With the Supra-Annular, Self-Expandable Evolut Platform: Insights From the STS/ACC TVT Registry
Authors: Luis Augusto Dallan, Gilbert Tang, Michael Reardon, John Forrest, Wilson Szeto, Susheel Kodali, Ruth Eisenberg, Guilherme Attizzani
Journal: Journal of the American College of Cardiology (2021)