tbuckley/cabot-search huggingface dataset:
Unravelling the risk of (intermediate) antitrypsin deficiency
Authors: Mark Quinn, Alice Margaret Turner, Ravi Mahadeva
Journal: Thorax (2020)

The seminal observation of severe deficiency of alpha-1-antitrypsin (AAT) with premature emphysema over 50 years ago led to the elastase–antielastase hypothesis of lung disease. Subsequent research identified alpha-1-antitrypsin deficiency (AATD) as an inherited metabolic genetic condition caused by mutations on the SERPINA1 gene, resulting in a reduction in the serum concentration of AAT.1 The role of AAT is to act as an inhibitor to the enzyme neutrophil elastase, and it is crucial in the homeostasis of elastase–antielastase activity, with an imbalance in this activity causing lung disease via a cycle of inflammation and proteolytic damage leading to premature emphysema, disability and death. There are over 100 mutations of SERPINA1 described in the literature, some of which are associated with AATD. The normal genotype is designated PiMM; the most common genotype resulting in severe deficiency is designated PiZZ. AATD is an autosomal codominant condition so heterozygosity can also create in genotypes resulting in mild and intermediate deficiency, such as PiMZ and PiSZ. The prevalence of AATD worldwide is estimated between 0.02% and 0.05%. Normal AAT serum concentration would be in the range 20–53 µmol/L, while deficient genotypes express varying levels, from 55% for PiMZ to 40% for PiSZ and <15% for PiZZ. While the risk of developing premature emphysema in PiZZ is beyond doubt, there has been considerable debate regarding the risk of SZ genotype (intermediate deficiency) and emphysema severity.2 

The study carried out by Franciosi et al 3 in this journal is a welcome addition to the area aiming to further understand the PiSZ genotype and its effect on lung disease. Their results imply that …
Prevalence of SARS-CoV-2 IgG antibodies in a large prospective cohort study of elite football players in Germany (May–June 2020): implications for a testing protocol in asymptomatic individuals and estimation of the rate of undetected cases
Authors: Dietrich Mack, Barbara Christine Gärtner, Annika Rössler, Janine Kimpel, Katrin Donde, Oliver Harzer, Werner Krutsch, Dorothee von Laer, Tim Meyer
Journal: Clinical Microbiology and Infection (2020)
437P Long-term efficacy and toxicity outcome of adjuvant external beam radiotherapy for medullary thyroid cancer: A single institution cohort study
Authors: K.M. Cheung, G.T.C. Cheung, J.C.H. Chow, T.Y.M. Tsui, H.L. Leung, T.Y. Lee, J. Chik, K.H. Wong, C.K. Kwan, K.H. Au
Journal: Annals of Oncology (2020)
Family Caregiving for Those With and Without Dementia in the Last 10 Years of Life
Authors: Jennifer M. Reckrey, Evan Bollens-Lund, Mohammed Husain, Katherine A. Ornstein, Amy S. Kelley
Journal: JAMA Internal Medicine (2020)

delivery at a hospital with a neonatal care unit should be recommended.Given the risks of these medications and the high rate of unintended pregnancy, we recommend that pregnancy be considered a possibility in all individuals of reproductive age who may be prescribed a potential teratogen.To avoid major congenital malformations associated with modafinil and armodafinil, these medications should be avoided or offered along with a reliable contraceptive to individuals who could become pregnant.
Elongated neutrophil-derived structures are blood-borne microparticles formed by rolling neutrophils during sepsis
Authors: Alex Marki, Konrad Buscher, Cristina Lorenzini, Matthew Meyer, Ryosuke Saigusa, Zhichao Fan, Yi-Ting Yeh, Nadine Hartmann, Jennifer M. Dan, William B. Kiosses, Gregory J. Golden, Rajee Ganesan, Holger Winkels, Marco Orecchioni, Sara McArdle, Zbigniew Mikulski, Yoav Altman, Jack Bui, Mitchell Kronenberg, Shu Chien, Jeffrey D. Esko, Victor Nizet, David Smalley, Johannes Roth, Klaus Ley
Journal: The Journal of Experimental Medicine (2020)

Rolling neutrophils form tethers with submicron diameters. Here, we report that these tethers detach, forming elongated neutrophil-derived structures (ENDS) in the vessel lumen. We studied ENDS formation in mice and humans in vitro and in vivo. ENDS do not contain mitochondria, endoplasmic reticulum, or DNA, but are enriched for S100A8, S100A9, and 57 other proteins. Within hours of formation, ENDS round up, and some of them begin to present phosphatidylserine on their surface (detected by annexin-5 binding) and release S100A8–S100A9 complex, a damage-associated molecular pattern protein that is a known biomarker of neutrophilic inflammation. ENDS appear in blood plasma of mice upon induction of septic shock. Compared with healthy donors, ENDS are 10–100-fold elevated in blood plasma of septic patients. Unlike neutrophil-derived extracellular vesicles, most ENDS are negative for the tetraspanins CD9, CD63, and CD81. We conclude that ENDS are a new class of bloodborne submicron particles with a formation mechanism linked to neutrophil rolling on the vessel wall.
Letter by Mehmood Regarding Article, “Cardiac Energetics in Patients With Aortic Stenosis and Preserved Versus Reduced Ejection Fraction”
Authors: Muddassir Mehmood
Journal: Circulation (2020)

Peterzan and colleagues 1 eloquently delineated myocardial energetics in aortic stenosis (AS) by using 31 P magnetic resonance spectroscopy coupled with left ventricular (LV) biopsies.Significant energetic impairment was already established in moderate AS but was not a necessary correlate of systolic failure as assessed by LV ejection fraction (LVEF). 1 It would be pertinent to discuss the evolving role of LV strain imaging in AS.Cardiac magnetic resonance-derived LV circumferential strain correlates with impaired myocardial energetics in AS, 2 whereas echocardiographic Doppler strain imaging has been shown to reflect changes in high-energy phosphate metabolism in acute myocardial ischemia. 3Data regarding the prognostic value of LV global longitudinal strain (GLS) in AS have been accumulating. 4,5n a meta-analysis of 10 studies of asymptomatic patients with AS and normal LVEF, impaired GLS was associated with reduced survival with a GLS cutoff value of 14.7% yielding the best sensitivity and specificity. 2In patients with AS and New York Heart Association class I to IV, LV GLS was independently associated with mortality. 3Survival in patients with severe AS with normal LVEF but GLS > -14% was similar to survival with severe AS and impaired LVEF. 2 Peterzan and colleagues showed that myocardial energetics assessed by the phosphocreatine to adenosine triphosphate ratio were lower in severe AS with reduced LVEF than in the non-pressure-loaded heart, but they were not different than severe AS with preserved LVEF. 1 Randomized investigation of aortic valve replacement in asymptomatic patients with AS guided by late gadolinium enhancement is underway (URL: https://www.clinicaltrials.gov;Unique identifier: NCT03042104).Investigation of a myocardial energetics-based approach to evaluating and managing AS would be physiologically more intuitive.Peterzan and colleagues should consider correlating 2-dimensional speckle tracking echocardiography-derived LV GLS with myocardial energetics in AS.Adding credence to the pathophysiologic underpinnings of an accessible imaging technique may facilitate the investigation and translation of an energeticsbased approach to AS.
Abstract PO-053: Investigating intra-tumour metabolic heterogeneity in triple-negative breast cancer
Authors: Marina Fukano, Geneviève Deblois, Dongmei Zuo, Constanza Martinez, Yang Yang, Ioannis Ragoussis, Claudia Kleinman, Morag Park
Journal: Cancer Research (2020)

Abstract Intra-tumour heterogeneity is a great challenge in cancer treatment. Cancer cells presenting different metabolic profiles can mutually support each other through metabolic symbiosis mechanism, which contributes to tumour proliferation, metastasis, and therapeutic resistance. Triple-negative breast cancer (TNBC) shows poor clinical outcomes due to a high level of heterogeneity and a lack of targeted therapies. Through multiplex immunofluorescence tissue section staining of TNBC patient-derived xenografts (PDX), we identified two mutually exclusive and metabolically distinct cell populations within a TNBC tumour. One cancer cell population expresses glucose transporter 1 (GLUT1) and is located in hypoxic areas, whereas another specifically expresses glutamine synthetase (GS) and is located near vasculatures. Single-cell RNA sequencing data from a TNBC PDX with mutually exclusive GLUT1- and GS-positive cells shows that GLUT1-positive cells are enriched for hypoxic and glycolytic gene signatures, while GS-positive cells are associated with glutathione, pyrimidine and purine metabolism. Importantly, our data suggest that GLUT1- and GS-positive cells exchange glutamate and lactate metabolites as part of metabolic symbiosis and targeting this mechanism could successfully impair the growth of TNBC. Citation Format: Marina Fukano, Geneviève Deblois, Dongmei Zuo, Constanza Martinez, Yang Yang, Ioannis Ragoussis, Claudia Kleinman, Morag Park. Investigating intra-tumour metabolic heterogeneity in triple-negative breast cancer [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-053.
Response by Li to Letter Regarding Article, “Autoantibody Signature in Cardiac Arrest”
Authors: Jin Li
Journal: Circulation (2020)

In Response:We appreciate the interest by Lazzerini et al regarding our recent publication 1 and their thoughts on the anti-Ca v 1.2 autoantibody we discovered and identified as a biomarker of idiopathic cardiac arrest.The anti-Ca v 1.2 autoantibody inhibits the L-type Ca 2+ current and shortens the action potential duration in human induced pluripotent stem cell-derived cardiomyocytes.Although we could have expected a shortened QT interval on ECG on the basis of the action potential duration shortening, our cohort of patients with anti-Ca v 1.2 autoantibodies presented a normal QT length (see the Table in reference 1 ).After heart rate correction, the QTc value of patients with idiopathic cardiac arrest is slightly longer compared with that of the healthy controls, but still within the normal range (see the Table in reference 1 ).Statistical significance is only found when using the Bazett formula, an equation well-known to have limitations despite its wide use. 2 Lazzerini et al claim that our newly identified anti-Ca v 1.2 autoantibodies are actually anti-Ro/SSA autoantibodies.This hypothesis cannot be supported for several reasons.Anti-Ro/SSA autoantibodies target a cytoplasmic linker between domains II and III of the α 1c subunit of Ca v 1.2 channels, 3,4 whereas our anti-Ca v 1.2 autoantibody targets an extracellular sequence of domain III between the transmembrane segments S5 and S6 (DFDNVLAAMMALFTVSTFEG); ie, the pore-forming part of Ca v 1.2 channels.Also, because anti-Ro/SSA (particularly 52 kD) cross-reacts with the extracellular pore domain of the hERG (human ether-a-go-go-related gene) channel, 5 our microarray assay would have detected immunoglobulin G responses specific to this sequence (DSRIGWLHNLGDQIGKPYNS), which is not the case.We therefore can exclude the presence of anti-Ro/SSA autoantibodies in the study patients.In this context, because our anti-Ca v 1.2 immunoglobulin G was purified from patient plasma using affinity chromatography (matrix coupled to the DFDNVLAAMMALFTVSTFEG peptide), the action potential duration shortening recorded in human induced pluripotent stem cell-derived cardiomyocytes cannot be the result of an anti-Ro/SSA-mediated inhibition of Ca v 1.2 and hERG channels as suggested by Lazzerini et al.
158P A phase II study of trastuzumab with S-1 plus oxaliplatin for HER2-positive advanced gastric cancer (HIGHSOX study): Final report
Authors: A. Takashima, K. Chin, K. Minashi, S. Kadowaki, T. Nishina, N. Izawa, K. Amagai, N. Machida, M. Goto, K. Taku, N. Ishizuka, D. Takahari
Journal: Annals of Oncology (2020)
Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents: A Science Advisory From the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, With Representation From the American College of Physicians⁎⁎Representation does not imply endorsement by the American College of Physicians.
Authors: Cindy L. Grines, Robert O. Bonow, Donald E. Casey, Timothy J. Gardner, Peter B. Lockhart, David J. Moliterno, Patrick O'Gara, Patrick Whitlow
Journal: Journal of the American College of Cardiology (2007)
Polymer-lipid hybrid nanovesicle-enabled combination of immunogenic chemotherapy and RNAi-mediated PD-L1 knockdown elicits antitumor immunity against melanoma
Authors: Changrong Wang, Xiaoguang Shi, Huijuan Song, Chuangnian Zhang, Xiaoli Wang, Pingsheng Huang, Anjie Dong, Yumin Zhang, Deling Kong, Weiwei Wang
Journal: Biomaterials (2020)
Learning to Walk Before We Run: The Mechanics of Medical Intervention for Peripheral Arterial Disease⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Mitchell W. Krucoff, W. Schuyler Jones, Manesh R. Patel
Journal: Journal of the American College of Cardiology (2011)
Abstract 12239: Enhanced Roles of Cholesterol Efflux Capacity in Coronary Atheroma Regression in Patients Achieving Targets for Cardiovascular Risk
Authors: Kohei Takata, Jordan Andrews, Gijo Thomas, Julie Butters, Daisuke Shishikura, Giuseppe Di Giovanni, Stephen Nicholls
Journal: Circulation (2019)

Introduction: While high-density lipoprotein (HDL) has attracted attentions for its atheroprotective properties and associations of cardiovascular disease, HDL-targeted therapies have been reconsid...
Abstract IA16: COVID-19 pandemic and its effect on the psychological status of cancer patients and oncologists
Authors: Gabriella Pravettoni
Journal: Clinical Cancer Research (2020)

Abstract On the 11th of March, the Word Health Organization declared COVID-19 a pandemic. This unprecedented emergency caused some unexpected effects on the health care system. During the pandemic, the attention focused on keeping cancer patients safe from COVID-19. This infection could have a detrimental effect on the physical and mental health of cancer patients; patients who have a suspension of cancer care suffer more from anxiety and/or depression. One of the worst side effects of COVID-19 is the fact that family members could not visit patients; social support in cancer patients is an important factor for a healthy mental condition. With no social support, their normal coping strategies have to adapt and the feeling of helplessness is overwhelming. These aspects are highlighted by a case report of a European Institute of Oncology patient. After a surgical intervention due to oral tongue cancer, he was diagnosed with COVID-19 infection and this caused anxiety and depression symptoms. During the pandemic, health care professionals’ (HCP) role has been pivotal: HCP had to cope with a stressful working environment, facing physical and psychological challenges. Oncologists, in particular, in their daily practice are at risk of developing burnout symptoms and post-traumatic stress disorder symptoms and this could be exacerbated by the pandemic. During pandemic phase 1, we evaluated emotional distress and mental health of oncologists all over the world. Our results showed a low mental health status and distress regarding emotional status; oncologists revealed that fear is one of the most diffuse emotions during pandemic. They are afraid for their patients during the hospital hours, and, when they leave the hospital ward, they feel fear for their family members and cohabitants, in a never-ending feeling of dread. This condition, if prolonged, could be a stressor that could lead to burnout syndrome and post-traumatic stress disorder. For these reasons, it is important to care for the oncologists who had cared for their patients, often prioritizing it over their own well-being. In these particular times, new technologies can help both patients and oncologists. In this complex scenario, the role of the oncologists becomes more and more important; new technologies’ output must be interpreted and technologies have to be at the service of humans, not vice versa. This should help oncologists to perform the integration of a big amount of diverse data otherwise impossible to put together meaningfully. Citation Format: Gabriella Pravettoni. COVID-19 pandemic and its effect on the psychological status of cancer patients and oncologists [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr IA16.
254TiP ENGOT-cx11/KEYNOTE-A18: A phase III, randomized, double-blind study of pembrolizumab with chemoradiotherapy in patients with high-risk locally advanced cervical cancer
Authors: D. Lorusso, Y. Xiang, N. Colombo, R. Coleman, L. Randall, L. Duska, K. Hasegawa, A. Nogueira-Rodrigues, D. Cibula, M.R. Mirza, B. You, A. Oaknin, M. Christiaens, C. Taskiran, J. Sehouli, J. Korach, C. Marth, S. Keefe, M. Puglisi, S. Pignata
Journal: Annals of Oncology (2020)
14410 Impact of mirikizumab maintenance dosing at week 104 on health-related quality of life in patients who had less than PASI 90 response at week 16: A phase 2 study analysis
Authors: Jerry Bagel, Kristian Reich, Phoebe Rich, Robert Bissonnette, Chika Ohata, Kim Alexander Papp, Dipak R. Patel, Baojin Zhu, Emily Edson-Heredia, Melinda Gooderham
Journal: Journal of the American Academy of Dermatology (2020)
18408 A combined clinicopathologic and gene expression model (CP-GEP) identifies primary cutaneous melanoma patients who can safely forgo sentinel lymph node biopsy
Authors: Alexander Meves, Suzette Arias-Mejias, Alina G. Bridges, Julia S. Lehman, Mark R. Pittelkow, Mark A. Cappel, Charles Perniciaro, Martin H. van Vliet, Jvalini Dwarkasing, Domenico Bellomo
Journal: Journal of the American Academy of Dermatology (2020)
Association of Missense Mutation in FOLH1 With Decreased NAAG Levels and Impaired Working Memory Circuitry and Cognition
Authors: Caroline F. Zink, Peter B. Barker, Akira Sawa, Daniel R. Weinberger, Min Wang, Henry Quillian, William S. Ulrich, Qiang Chen, Andrew E. Jaffe, Joel E. Kleinman, Thomas M. Hyde, Greer E. Prettyman, Mellissa Giegerich, Kayla Carta, Marcus van Ginkel, Kristin L. Bigos
Journal: American Journal of Psychiatry (2020)

Altering the metabotropic glutamate receptor 3 (mGluR3) by pharmacology or genetics is associated with differences in learning and memory in animals and humans. GRM3 (the gene coding for mGluR3) is also genome-wide associated with risk for schizophrenia. The neurotransmitter N-acetyl-aspartyl-glutamate (NAAG) is the selective endogenous agonist of mGluR3, and increasing NAAG may improve cognition. Glutamate carboxypeptidase II (GCPII), coded by the gene folate hydrolase 1 (FOLH1), regulates the amount of NAAG in the synapse. The goal of this study was to determine the relationship between FOLH1, NAAG levels, measures of human cognition, and neural activity associated with cognition.The effects of genetic variation in FOLH1 on mRNA expression in human brain and NAAG levels using 7-T magnetic resonance spectroscopy (MRS) were measured. NAAG levels and FOLH1 genetic variation were correlated with measures of cognition in subjects with psychosis and unaffected subjects. Additionally, FOLH1 genetic variation was correlated with neural activity during working memory, as measured by functional MRI (fMRI).A missense mutation in FOLH1 (rs202676 G allele) was associated with increased FOLH1 mRNA in the dorsolateral prefrontal cortex of brains from unaffected subjects and schizophrenia patients. This FOLH1 variant was associated with decreased NAAG levels in unaffected subjects and patients with psychosis. NAAG levels were positively correlated with visual memory performance. Carriers of the FOLH1 variant associated with lower NAAG levels had lower IQ scores. Carriers of this FOLH1 variant had less efficient cortical activity during working memory.These data show that higher NAAG levels are associated with better cognition, suggesting that increasing NAAG levels through FOLH1/GCPII inhibition may improve cognition. Additionally, NAAG levels measured by MRS and cortical efficiency during working memory measured by fMRI have the potential to be neuroimaging biomarkers for future clinical trials.
Facile synthesis of insulin fusion derivatives through sortase A ligation
Authors: Maria M. Disotuar, Jake A. Smith, Jinze Li, Steve Alam, Nai-Pin Lin, Danny Hung-Chieh Chou
Journal: Acta Pharmaceutica Sinica B (2020)

Insulin derivatives such as insulin detemir and insulin degludec are U.S. Food and Drug Administration (FDA)-approved long-acting insulin currently used by millions of people with diabetes. These derivatives are modified in C-terminal B29 lysine to retain insulin bioactivity. New and efficient methods for facile synthesis of insulin derivatives may lead to new discovery of therapeutic insulin. Herein, we report a new method using sortase A (SrtA)-mediated ligation for the synthesis of insulin derivatives with high efficiency and functional group tolerance in the C-terminal B chain. This new insulin molecule (Ins-SA) with an SrtA-recognizing motif can be conjugated to diverse groups with N-terminal oligoglycines to generate new insulin derivatives. We further demonstrated that a new insulin derivative synthesized by this SrtA-mediated ligation shows strong cellular and in vivo bioactivity. This enzymatic method can therefore be used for future insulin design and development.
18292 Fibrosis-4 index in psoriasis patients treated with methotrexate before cosentyx: A descriptive study
Authors: Vania Lukoviek, María Arteaga Henríquez, José María Ramírez Conchas, Judit Algarra Sahuquillo, Marcella Markthaler, Marta García Bustinduy
Journal: Journal of the American Academy of Dermatology (2020)
Abstract 19903: Incidence and Outcomes of Acute Myocardial Infarction in Patients Admitted With Diabetic Ketoacidosis
Authors: Fahad Alqahtani, Sami Aljohani, Tatiana Busu, Ahmad Almustafa, Ali Hama Amin, Almoutassim Trabulsi, Chalak Berzingi, Mohamad Adnan Alkhouli
Journal: Circulation (2017)

Introduction: Single center suggested that acute myocardial infarction (AMI) in patients admitted with diabetic ketoacidosis (DKA) are associated with high morbidity and mortality and prolonged hos...
Effect of Empagliflozin on Hemodynamics in Patients With Heart Failure and Reduced Ejection Fraction
Authors: Massar Omar, Jesper Jensen, Peter H. Frederiksen, Caroline Kistorp, Lars Videbæk, Mikael Kjær Poulsen, Sören Möller, Mulham Ali, Finn Gustafsson, Lars Køber, Barry A. Borlaug, Morten Schou, Jacob Eifer Møller
Journal: Journal of the American College of Cardiology (2020)
17555 A systematic search and literature review of knowledge, attitudes, beliefs, and practices regarding skin cancer among population in Gulf countries
Authors: Daniel Zieman, Pooya Zardoost, Shirley Payson, Iram Aman, Amanda Wilkerson, Syed Quadri, Fahimeh Bagheri, Marcelle Savoy, Vinayak K. Nahar
Journal: Journal of the American Academy of Dermatology (2020)
Adolescent participation in HIV research: consortium experience in low and middle-income countries and scoping review
Authors: Suzanne Day, Bill G Kapogiannis, Seema K Shah, Erin C Wilson, Theodore D Ruel, Donaldson F Conserve, Ann Strode, Geri R Donenberg, Pamela Kohler, Catherine Slack, Oliver Ezechi, Joseph D Tucker
Journal: The Lancet HIV (2020)
22P Correlation of muscle strength and quality of life in Indonesian breast cancer patients who underwent chemotherapy
Authors: D.A. Halim, A. Kurniawan, R.D. Hatma, A. Adisasmita, N. Sutandyo, S.S. Panigoro, D.S. Rivami, F.I. Witjaksono, T.Z. Tamin, R. Sumantri, C. Jodhinata, W.M. Rafaello, F. Wijovi, H. Putri, O.A. Saroso, F. Dharmaraja, N.P.H. Lugito, C. Cindy, A. Tancherla, B.A. Hariyoga
Journal: Annals of Oncology (2020)