tbuckley/cabot-search huggingface dataset:
Transcriptomic organization of the human brain in post-traumatic stress disorder
Authors: Matthew J. Girgenti, Jiawei Wang, Dingjue Ji, Dianne A. Cruz, Murray B. Stein, Joel Gelernter, Keith A. Young, Bertrand R. Huber, Douglas E. Williamson, Matthew J. Friedman, John H. Krystal, Hongyu Zhao, Ronald S. Duman
Journal: Nature Neuroscience (2020)
Abstract 3061: Optimal Left Atrial Volume Reduction Surgery (LA-VR) with the Cox-Maze Procedure (MAZE) for Better Postoperative LA Global Function
Authors: Akira Marui, Takeshi Nishina, Yoshiaki Saji, Kazuhiro Yamazaki, Tadashi Ikeda, Masashi Komeda
Journal: Circulation (2007)

Background: LA-VR with MAZE has been reported to facilitate sinus rhythm recovery even in patients with refractory atrial fibrillation (AF) with LA enlargement; however, optimal extent of LA volume...
Abstract 17597: Elevated Gut Microbiota Dependent Metabolite Trimethylamine N-Oxide (TMAO) is Associated With Subclinical Myocardial Dysfunction and Necrosis in Stable Cardiac Patients
Authors: W. H. Wilson Tang, Zeneng Wang, Xinmin S Li, Yiying Fan, Yuping Wu, Stanley L Hazen
Journal: Circulation (2017)

Background: Recent studies identify trimethylamine N-oxide (TMAO) as a gut microbiota-generated proatherogenic and prothrombotic metabolite that contributes to the development and progression of ca...
Evolutionary conservation of human ketodeoxynonulosonic acid production is independent of sialoglycan biosynthesis
Authors: Kunio Kawanishi, Sudeshna Saha, Sandra Diaz, Michael Vaill, Aniruddha Sasmal, Shoib S. Siddiqui, Biswa Choudhury, Kumar Sharma, Xi Chen, Ian C. Schoenhofen, Chihiro Sato, Ken Kitajima, Hudson H. Freeze, Anja Münster-Kühnel, Ajit Varki
Journal: Journal of Clinical Investigation (2020)

Human metabolic incorporation of nonhuman sialic acid (Sia) N-glycolylneuraminic acid into endogenous glycans generates inflammation via preexisting antibodies, which likely contributes to red meat–induced atherosclerosis acceleration. Exploring whether this mechanism affects atherosclerosis in end-stage renal disease (ESRD), we instead found serum accumulation of 2-keto-3-deoxy-d-glycero-d-galacto-2-nonulosonic acid (Kdn), a Sia prominently expressed in cold-blooded vertebrates. In patients with ESRD, levels of the Kdn precursor mannose also increased, but within a normal range. Mannose ingestion by healthy volunteers raised the levels of urinary mannose and Kdn. Kdn production pathways remained conserved in mammals but were diminished by an M42T substitution in a key biosynthetic enzyme, N-acetylneuraminate synthase. Remarkably, reversion to the ancestral methionine then occurred independently in 2 lineages, including humans. However, mammalian glycan databases contain no Kdn-glycans. We hypothesize that the potential toxicity of excess mannose in mammals is partly buffered by conversion to free Kdn. Thus, mammals probably conserve Kdn biosynthesis and modulate it in a lineage-specific manner, not for glycosylation, but to control physiological mannose intermediates and metabolites. However, human cells can be forced to express Kdn-glycans via genetic mutations enhancing Kdn utilization, or by transfection with fish enzymes producing cytidine monophosphate–Kdn (CMP-Kdn). Antibodies against Kdn-glycans occur in pooled human immunoglobulins. Pathological conditions that elevate Kdn levels could therefore result in antibody-mediated inflammatory pathologies.
Pulmonary embolism in COVID-19: D-dimer threshold selection should not be based on maximising Youden's index
Authors: Daniël A. Korevaar, Josien van Es
Journal: European Respiratory Journal (2020)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised new challenges in the diagnosis of pulmonary embolism (PE) [1]. Patients with coronavirus disease 2019 (COVID-19) are at increased risk of developing venous thromboembolism, but symptoms of COVID-19 and PE may overlap, which makes it difficult to identify those with a higher likelihood of PE. Simple and minimally invasive diagnostic algorithms that can safely rule-out PE in patients with COVID-19 are urgently needed. Therefore, we read with interest the recent paper by Mouhat et al. [2] in the European Respiratory Journal . D-dimer thresholds for ruling-out pulmonary embolism should not be selected based on the "optimal" Youden's index <https://bit.ly/2Mfp4on>
COVID-19 in Kidney Transplant Recipients at New England’s Largest Safety-Net Hospital
Authors: Hassan Mahmoud, Sandeep Ghai, Jean M. Francis
Journal: Journal of the American Society of Nephrology (2020)

Journal of the American Society of Nephrology 31(10S):p 281-282, October 2020. | DOI: 10.1681/ASN.20203110S1281c
KEYNOTE-022 part 3: a randomized, double-blind, phase 2 study of pembrolizumab, dabrafenib, and trametinib in <i>BRAF</i>-mutant melanoma
Authors: Pier Francesco Ferrucci, Anna Maria Di Giacomo, Michele Del Vecchio, Victoria Atkinson, Henrik Schmidt, Jacob Schachter, Paola Queirolo, Georgina V Long, Rosalie Stephens, Inge Marie Svane, Michal Lotem, Mahmoud Abu-Amna, Eduard Gasal, Razi Ghori, Scott J Diede, Elizabeth S Croydon, Antoni Ribas, Paolo Antonio Ascierto
Journal: Journal for ImmunoTherapy of Cancer (2020)

In the KEYNOTE-022 study, pembrolizumab with dabrafenib and trametinib (triplet) improved progression-free survival (PFS) versus placebo with dabrafenib and trametinib (doublet) without reaching statistical significance. Mature results on PFS, duration of response (DOR), and overall survival (OS) are reported.The double-blind, phase 2 part of KEYNOTE-022 enrolled patients with previously untreated BRAFV600E/K-mutated advanced melanoma from 22 sites in seven countries. Patients were randomly assigned 1:1 to intravenous pembrolizumab (200 mg every 3 weeks) or placebo plus dabrafenib (150 mg orally two times per day) and trametinib (2 mg orally one time a day). Primary endpoint was PFS. Secondary endpoints were objective response rate, DOR, and OS. Efficacy was assessed in the intention-to-treat population, and safety was assessed in all patients who received at least one dose of study drug. This analysis was not specified in the protocol.Between November 30, 2015 and April 24, 2017, 120 patients were randomly assigned to triplet (n=60) or doublet (n=60) therapy. With 36.6 months of follow-up, median PFS was 16.9 months (95% CI 11.3 to 27.9) with triplet and 10.7 months (95% CI 7.2 to 16.8) with doublet (HR 0.53; 95% CI 0.34 to 0.83). With triplet and doublet, respectively, PFS at 24 months was 41.0% (95% CI 27.4% to 54.2%) and 16.3% (95% CI 8.1% to 27.1%); median DOR was 25.1 months (95% CI 14.1 to not reached) and 12.1 months (95% CI 6.0 to 15.7), respectively. Median OS was not reached with triplet and was 26.3 months with doublet (HR 0.64; 95% CI 0.38 to 1.06). With triplet and doublet, respectively, OS at 24 months was 63.0% (95% CI 49.4% to 73.9%) and 51.7% (95% CI 38.4% to 63.4%). Grade 3-5 treatment-related adverse events (TRAEs) occurred in 35 patients (58%, including one death) receiving triplet and 15 patients (25%) receiving doublet.In BRAFV600E/K-mutant advanced melanoma, pembrolizumab plus dabrafenib and trametinib substantially improved PFS, DOR, and OS with a higher incidence of TRAEs. Interpretation of these results is limited by the post hoc nature of the analysis.
Downloaded From : by a University Of Connecticut Health Center User on 07 / 27 / 2018
Authors: John Zic, Jami Miller, H Alan Arbuckle, Linnea Hemphill, Mayumi Fujita, David Norris, Preethi Ramaswamy, Jennifer Nevas, Caroline H Rao, Allen J Gifford, Kelly A Asher, Rambi G Cardones, Angela F Richardson, Carmen Adams, Ryan E Ferguson, Soe Soe Thwin
Journal: JAMA Dermatology (2018)
Cardiopulmonary exercise testing might be helpful for interpretation of impaired pulmonary function in recovered COVID-19 patients
Authors: Yi Gao, Ruchong Chen, Qian Geng, Xiaoneng Mo, Chen Zhan, Wenhua Jian, Shiyue Li, Jinping Zheng
Journal: European Respiratory Journal (2020)

We are grateful to have the opportunity for an in-depth discussion with Nusair [1] and D.G. Chapman and co-workers. We sincerely appreciate their insightful comments on our study about the impaired pulmonary function in coronavirus disease 2019 (COVID-19) patients [2, 3], which helps to interpret the parameters of abnormal lung diffusion capacity more accurately. Besides the impaired lung diffusion capacity, impairment of exercise endurance in recovered patients with COVID-19 should also be considered <https://bit.ly/3qrzPDY>
Нестероидные противовоспалительные средства: современное представление о механизмах повреждения пищеварительного тракта, минусы препаратов патогенетического лечения и перспективы биологической терапии НПВС-индуцированной эзофагогастроэнтероколонопатии
Authors: F.V. Hladkykh, M.O. Chyzh
Journal: GASTROENTEROLOGY (2020)

Актуальность. Нестероидные противовоспалительные средства (НПВС) ежедневно применяют более чем 30 млн человек, а их арсенал насчитывает свыше 80 препаратов и около 1000 созданных на их основе лекарственных форм. Они широко используются во многих сферах медицины и являются одной из наиболее клинически значимых групп лекарственных средств. Однако при использовании НПВС достаточно часто могут возникать побочные реакции, наиболее распространенными из них являются повреждения желудочно-кишечного тракта. Цель: охарактеризовать со­временное представление о механизмах повреждения пищеварительного тракта НПВС, оценить недостатки существующих препаратов патогенетического лечения и перспективы биологической терапии НПВС-индуцированной эзофагогастроэнтероколонопатии криоконсервированным экстрактом плаценты человека. Материалы и методы. Проведен анализ работ, опубликованных в 2010–2020 гг., в которых освещались сведения об эпидемиологии, патогенезе, диагностике и тактике лечения поражений пищевода и желудочно-кишечного тракта, индуцированных НПВС, а также биологические свойства криоконсервированного экстракта плаценты человека как средства биологической терапии. Результаты. Лечение НПВС-индуцированной эзофагогастроэнтероколонопатии классически направлено на кислотосупрессивную терапию (ингибиторы протонной помпы, Н2-гистаминоблокаторы и др.), применение гастроцитопротекторов (де-нол, сукральфат и др.) и препаратов, восстанавливающих содержание простагландинов в слизистой оболочке (мизопростол, ребамипид и др.). Однако все указанные группы лекарственных средств недостаточно удовлетворяют клиницистов, поскольку направлены преимущественно на лечение НПВС-гастропатии и имеют побочные эффекты. Новым перспективным направлением повышения безопасности НПВС на сегодняшний день является применение средств биологической терапии, источниками которых выступают микроорганизмы, органы и ткани растительного или животного происхождения, клетки или жидкости (в том числе кровь и плазма) человеческого или животного происхождения и биотехнологические клеточные конструкции. Выводы. Использование НПВС значительно ограничивается присущими им побочными эффектами, наи­более распространенными являются нарушения со стороны желудочно-кишечного тракта. Криоконсервированный экстракт плаценты человека является перспективным средством биологической терапии ульцерогенных повреждений желудочно-кишечного тракта, индуцированных НПВС.
Mouse Models of Human Proprotein Convertase Insufficiency
Authors: Manita Shakya, Iris Lindberg
Journal: Endocrine Reviews (2020)

Abstract The kexin-like proprotein convertases perform the initial proteolytic cleavages that ultimately generate a variety of different mature peptide and proteins, ranging from brain neuropeptides to endocrine peptide hormones, to structural proteins, among others. In this review, we present a general introduction to proprotein convertase structure and biochemistry, followed by a comprehensive discussion of each member of the kexin-like subfamily of proprotein convertases. We summarize current knowledge of human proprotein convertase insufficiency syndromes, including genome-wide analyses of convertase polymorphisms, and compare these to convertase null and mutant mouse models. These mouse models have illuminated our understanding of the roles specific convertases play in human disease and have led to the identification of convertase-specific substrates; for example, the identification of procorin as a specific PACE4 substrate in the heart. We also discuss the limitations of mouse null models in interpreting human disease, such as differential precursor cleavage due to species-specific sequence differences, and the challenges presented by functional redundancy among convertases in attempting to assign specific cleavages and/or physiological roles. However, in most cases, knockout mouse models have added substantively both to our knowledge of diseases caused by human proprotein convertase insufficiency and to our appreciation of their normal physiological roles, as clearly seen in the case of the furin, proprotein convertase 1/3, and proprotein convertase 5/6 mouse models. The creation of more sophisticated mouse models with tissue- or temporally-restricted expression of specific convertases will improve our understanding of human proprotein convertase insufficiency and potentially provide support for the emerging concept of therapeutic inhibition of convertases.
Klotho Deficiency Causes Heart Aging via Impairing the Nrf2-GR Pathway
Authors: Kai Chen, Shirley Wang, Qiwei Wilton Sun, Bo Zhang, Mujib Ullah, Zhongjie Sun
Journal: Circulation Research (2020)

Rationale: Cardiac aging is an important contributing factor for heart failure, which affects a large population but remains poorly understood. Objective: The purpose of this study is to investigate whether Klotho plays a role in cardiac aging. Methods and Results: Heart function declined in old mice (24 months), as evidenced by decreases in fractional shortening, ejection fraction, and cardiac output. Heart size and weight, cardiomyocyte size, and cardiac fibrosis were increased in old mice, indicating that aging causes cardiac hypertrophy and remodeling. Circulating Klotho levels were dramatically decreased in old mice, which prompted us to investigate whether the Klotho decline may cause heart aging. We found that Klotho gene mutation (KL−/−) largely decreased serum klotho levels and impaired heart function. Interestingly, supplement of exogenous secreted Klotho prevented heart failure, hypertrophy, and remodeling in both old mice and KL (−/−) mice. Secreted Klotho treatment inhibited excessive cardiac oxidative stress, senescence and apoptosis in old mice and KL (−/−) mice. Serum phosphate levels in KL (−/−) mice were kept in the normal range, suggesting that Klotho deficiency-induced heart aging is independent of phosphate metabolism. Mechanistically, Klotho deficiency suppressed GR (glutathione reductase) expression and activity in the heart via inhibition of transcription factor Nrf2 (nuclear factor-erythroid 2 p45-related factor 2). Furthermore, cardiac-specific overexpression of GR prevented excessive oxidative stress, apoptosis, and heart failure in both old and KL (−/−) mice. Conclusions: Klotho deficiency causes cardiac aging via impairing the Nrf2-GR pathway. Supplement of exogenous secreted Klotho represents a promising therapeutic strategy for aging-associated cardiomyopathy and heart failure.
Recombinant human epidermal growth factor combined with vacuum sealing drainage for wound healing in Bama pigs
Authors: Shuai Wei, Wei Wang, Li Li, Hao-Ye Meng, Chun-Zhen Feng, Yu-Ying Dong, Xi-Chi Fang, Qi-Qiang Dong, Wen Jiang, Hai-Li Xin, Zhan-Zhen Li, Xin Wang
Journal: Military Medical Research (2021)

Abstract Background Vacuum sealing drainage (VSD) and epidermal growth factor (EGF) both play an important role in the treatment of wounds. This study aims to explore the effects of the combination of VSD and EGF on wound healing and the optimal concentration and time of EGF. Methods We tested the proliferation and migration capacity of HaCaT and L929 cells at different EGF concentrations (0, 1, 5, 10, and 100 ng/ml) and different EGF action times (2, 10, and 30 min). A full-thickness skin defect model was established using male, 30-week-old Bama pigs. The experiment included groups as follows: routine dressing change after covering with sterile auxiliary material (Control), continuous negative pressure drainage of the wound (VSD), continuous negative pressure drainage of the wound and injection of EGF 10 min followed by removal by continuous lavage (V + E 10 min), and continuous negative pressure drainage of the wound and injection of EGF 30 min followed by removal by continuous lavage (V + E 30 min). The wound healing rate, histological repair effect and collagen deposition were compared among the four groups. Results An EGF concentration of 10 ng/ml and an action time of 10 min had optimal effects on the proliferation and migration capacities of HaCaT and L929 cells. The drug dispersion effect was better than drug infusion after bolus injection effect, and the contact surface was wider. Compared with other groups, the V + E 10 min group promoted wound healing to the greatest extent and obtained the best histological score. Conclusions A recombinant human epidermal growth factor (rhEGF) concentration of 10 ng/ml can promote the proliferation and migration of epithelial cells and fibroblasts to the greatest extent in vitro. VSD combined with rhEGF kept in place for 10 min and then washed, can promote wound healing better than the other treatments in vivo.
AKI Is Related to Mortality in COVID-19 Patients Without Underlying Kidney Disease
Authors: Yue Yu, Huipeng Ge, Xiufen Wang, Lijian Tao, Zhangzhe Peng, Xiangcheng Xiao
Journal: Journal of the American Society of Nephrology (2020)

Yu, Yue; Ge, Huipeng; Wang, Xiufen; Tao, Lijian; Peng, Zhangzhe; Xiao, Xiangcheng Author Information
Response to: ‘Correspondence on ‘Critical role of neutrophil extracellular traps (NETs) in patients with Behcet’s disease’’ by Chen<i>et al</i>
Authors: Alexandre Le Joncour, David Saadoun, Yacine Boulaftali
Journal: Annals of the Rheumatic Diseases (2020)

<b>Objective.</b> To investigate students9 use and views on social networking sites and assess differences in attitudes between genders and years in the program. <b>Methods.</b> All pharmacy undergraduate students were invited via e-mail to complete an electronic questionnaire consisting of 21 questions relating to social networking. <b>Results.</b> Most (91.8%) of the 377 respondents reported using social networking Web sites, with 98.6% using Facebook and 33.7% using Twitter. Female students were more likely than male students to agree that they had been made sufficiently aware of the professional behavior expected of them when using social networking sites (76.6% vs 58.1% <i>p</i>=0.002) and to agree that students should have the same professional standards whether on placement or using social networking sites (76.3% vs 61.6%; <i>p</i>&lt;0.001). <b>Conclusions.</b> A high level of social networking use and potentially inappropriate attitudes towards professionalism were found among pharmacy students. Further training may be useful to ensure pharmacy students are aware of how to apply codes of conduct when using social networking sites.
Clinical Outcomes of Patients with ESKD Hospitalized with COVID-19
Authors: Aldo E. Torres Ortiz, Muner Mohamed, Vernelle T. Mitchell, Juan Carlos Q. Velez
Journal: Journal of the American Society of Nephrology (2020)

Torres Ortiz, Aldo E.; Mohamed, Muner; Mitchell, Vernelle T.; Velez, Juan Carlos Q.; Ochsner Nephrology Author Information
Supported Decision Making With People at the Margins of Autonomy
Authors: Andrew Peterson, Jason Karlawish, Emily Largent
Journal: The American Journal of Bioethics (2020)

This article argues that supported decision making is ideal for people with dynamic cognitive and functional impairments that place them at the margins of autonomy. First, we argue that guardianship and similar surrogate decision-making frameworks may be inappropriate for people with dynamic impairments. Second, we provide a conceptual foundation for supported decision making for individuals with dynamic impairments, which integrates the social model of disability with relational accounts of autonomy. Third, we propose a three-step model that specifies the necessary conditions of supported decision making: identifying domains for support; identifying kinds of supports; and reaching a mutually acceptable and formal agreement. Finally, we identify a series of challenges for supported decision making, provide preliminary responses, and highlight avenues for future bioethics research.
ARIA‐EAACI statement on severe allergic reactions to COVID‐19 vaccines – An EAACI‐ARIA Position Paper
Authors: Ludger Klimek, Marek Jutel, Cezmi A. Akdis, Jean Bousquet, Mübeccel Akdis, Maria J Torres, Ioana Agache, G. Walter Canonica, Stefano Del Giacco, Liam O'Mahony, Mohamed H. Shamji, Jürgen Schwarze, Eva Untersmayr, Johannes Ring, Anna Bedbrook, Margitta Worm, Torsten Zuberbier, Edward Knol, Karin Hoffmann‐Sommergruber, Tomás Chivato
Journal: Allergy (2020)

Abstract Further to the approval of the Coronavirus disease 2019 (COVID‐19) vaccine BNT162b2, several severe anaphylaxis cases occured within the first few days of public vaccination. An investigation is taking place to understand the cases and their triggers. The vaccine will be administered to a large number of individuals worldwide and there are raising concerns that severe adverse events might occur. With the current information, the European Academy of Allergy and Clinical Immunology (EAACI) states its position for the following preliminary recommendations that are to be revised as soon as more data emerge. To minimize the risk of severe allergic reactions in vaccinated individuals, it is urgently required to understand the specific nature of the reported severe allergic reactions, including the background medical history of the individuals affected and the mechanisms involved. To achieve this goal, all clinical and laboratory information should be collected and reported. Mild and moderate allergic patients should not be excluded from the vaccine as this could have a significant impact on reaching the goal of population immunity. Healthcare practitioners vaccinating against COVID‐19 are required to be sufficiently prepared to recognize and treat anaphylaxis properly with the ability to administer adrenaline. Further to vaccine administration, a mandatory observation period of at least 15 minutes should be followed for all individuals. The current data have not shown any higher risk for patients suffering from allergic rhinitis or asthma, and this message should be clearly stated by physicians to enable our patients to trust the vaccine. More than 30% of the population suffers from allergic diseases and the benefit of the vaccination clearly outweighs the risk of severe COVID‐19 development.
Benchmarking as a Public Health Strategy for Creating Healthy Food Environments: An Evaluation of the INFORMAS Initiative (2012–2020)
Authors: Gary Sacks, Janelle Kwon, Stefanie Vandevijvere, Boyd Swinburn
Journal: Annual Review of Public Health (2020)

Diet-related noncommunicable diseases (NCDs) and obesity are the leading contributors to poor health worldwide. Efforts to improve population diets need to focus on creating healthy food environments. INFORMAS, established in 2012, is an international network that monitors and benchmarks food environments and related policies. By 2020, INFORMAS was active in 58 countries; national government policies were the most frequent aspect benchmarked. INFORMAS has resulted in the development and widespread application of standardized methods for assessing the characteristics of food environments. The activities of INFORMAS have contributed substantially to capacity building, advocacy, stakeholder engagement, and policy evaluation in relation to creating healthy food environments. Future efforts to benchmark food environments need to incorporate measurements related to environmental sustainability. For sustained impact, INFORMAS activities will need to be embedded within other existing monitoring initiatives. The most value will come from repeated assessments that help drive increased accountability for improving food environments.