tbuckley/cabot-search huggingface dataset:
Abstract 461: Microrna-126 Overexpression Rescues Impaired Efferocytosis in Diabetes
Authors: Sahana Suresh Babu, Rajarajan A Thandavarayan, Darukeshwara Joladarashi, Prince Jeyabal, Shashirekha Krishnamurthy, Arvind Bhimaraj, Keith A Youker, Prasanna Krishnamurthy*
Journal: Circulation Research (2016)

Cardiac healing after myocardial ischemia requires accumulation of macrophages at the site of injury for the clearance of apoptotic/dead cardiomyocytes, a process known as efferocytosis. Effective clearance of apoptotic cells in turn results in inflammation resolution during cardiac regeneration. Diabetes accompanied by hyperglycemia is known to compromise the function of macrophages leading to impaired inflammation resolution during cardiac regeneration, wound healing, atherosclerosis and auto-immune disorders. However, the effect of diabetes on macrophage efferocytosis and molecular mechanisms involved have not been understood so far. We found miR-126 is essential for the macrophage efferocytosis of apoptotic myocytes in high glucose conditions (HG). In-vivo, miR-126 expression was reduced and, a corresponding increase in A Disintegrin And Metalloprotease 9 (ADAM9) expression was observed in human diabetic heart failure tissues compared with the normal counterparts. In-vitro, macrophages efferocytosis was reduced in HG compared to normal glucose. Over-expression of miR-126 increased the efferocytosis in HG. Mechanistically, reduced miR-126 leads to increased expression of human ADAM9. ADAM9 in turn cleaves Mer tyrosine receptor kinase (MerTK), a proto-oncogene that plays a role in efferocytosis, leading to the formation of soluble-Mer that reduces the macrophage efferocytosis in HG conditions. This, we term as “not ready to eat” signal of the macrophages, which could be rescued by overexpressing miR-126 and termed as “ready to eat” signal of the macrophages.
Myocardial Infarction and Evolocumab
Authors: Mohammad Alkhalil
Journal: JAMA Cardiology (2021)

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GMC to appeal tribunal decision that found case against urologist was racist
Authors: Clare Dyer
Journal: BMJ (2021)

The General Medical Council is to appeal against a “flawed” employment tribunal decision that the regulator discriminated against a consultant urologist on the ground of his race.

Reading employment tribunal made the finding this month in the case of Omer Karim, the first doctor to succeed in a race discrimination claim against the GMC.1

Karim, who is of Sudanese and Irish heritage, was referred to the GMC by his employers in 2014. Interim conditions were placed on his registration in 2015, then lifted later that year. When his case was finally heard in 2018, he was cleared of misconduct.

The employment tribunal held that he was treated differently from a white doctor who was …
Structural basis for the constitutive activity and immunomodulatory properties of the Epstein-Barr virus-encoded G protein-coupled receptor BILF1
Authors: Naotaka Tsutsumi, Qianhui Qu, Maša Mavri, Maibritt S. Baggesen, Shoji Maeda, Deepa Waghray, Christian Berg, Brian K. Kobilka, Mette M. Rosenkilde, Georgios Skiniotis, K. Christopher Garcia
Journal: Immunity (2021)
Optimising antimicrobial use in humans – review of current evidence and an interdisciplinary consensus on key priorities for research
Authors: Esmita Charani, Martin McKee, Raheelah Ahmad, Manica Balasegaram, Candice Bonaconsa, Gemma Buckland Merrett, Reinhard Busse, Vanessa Carter, Enrique Castro-Sanchez, Bryony D Franklin, Pantelis Georgiou, Kerri Hill-Cawthorne, William Hope, Yuichi Imanaka, Andrew Kambugu, Andrew JM Leather, Oluchi Mbamalu, M McLeod, Marc Mendelson, Mirfin Mpundu, Timothy M Rawson, Walter Ricciardi, Jesus Rodriguez-Manzano, Sanjeev Singh, Constantinos Tsioutis, Chibuzor Uchea, Nina Zhu, Alison H Holmes
Journal: The Lancet Regional Health - Europe (2021)

Addressing the silent pandemic of antimicrobial resistance (AMR) is a focus of the 2021 G7 meeting. A major driver of AMR and poor clinical outcomes is suboptimal antimicrobial use. Current research in AMR is inequitably focused on new drug development. To achieve antimicrobial security we need to balance AMR research efforts between development of new agents and strategies to preserve the efficacy and maximise effectiveness of existing agents. Combining a review of current evidence and multistage engagement with diverse international stakeholders (including those in healthcare, public health, research, patient advocacy and policy) we identified research priorities for optimising antimicrobial use in humans across four broad themes: policy and strategic planning; medicines management and prescribing systems; technology to optimise prescribing; and context, culture and behaviours. Sustainable progress depends on: developing economic and contextually appropriate interventions; facilitating better use of data and prescribing systems across healthcare settings; supporting appropriate and scalable technological innovation. Implementing this strategy for AMR research on the optimisation of antimicrobial use in humans could contribute to equitable global health security.
Abstract 242: Priming for Action: Interventions That Promote IKs-Channel Opening Restore Defective cAMP-Dependent Upregulation in Long-QT1 Syndrome
Authors: Paul G Volders, Roel L Spätjens, Sandrine R Seyen, Gabriele Menini, Cristina Moreno Vadillo
Journal: Circulation Research (2016)

Introduction: Patients with the KCNQ1 mutation A341V show a high incidence of sympathetically-triggered ventricular tachyarrhythmias and sudden cardiac death. A341V decreases basal IKs and disrupts cAMP-dependent upregulation. The latter can be rescued by the phosphomimetic substitution KCNQ1 S27D. We hypothesize that A341V imposes a different conformational state of the IKs channel, which prevents full phosphorylation of KCNQ1 S27 and therefore loss of upregulation. We have now examined whether different strategies that promote channel opening can rescue cAMP-dependent upregulation. Methods: Chinese hamster ovary cells were transfected with wild type (WT) and heterozygous KCNQ1 A341V, with KCNE1 and Yotiao. In the absence and presence of cAMP/okadaic acid (OA), we examined IKs responses to (1) the KCNQ1 I346-K358 short peptide (shown to unlock the closed state of IKs through its binding to the endogenous S4-S5L of KCNQ1), (2) the double mutant A341V/L353K (L353K was previously shown to promote constitutive current), and (3) the channel activator ML277 (1 μmol/L). Results: As previously shown, WT but not A341V IKs was upregulated by intrapipette cAMP/OA. The unlocking effect of the I346-K358 peptide and the constitutive conduction by the co-presence of L353K facilitated mutant IKs enhancement by cAMP/OA (+61% and +71%, respectively), along with a -10 mV shift of the IV curve. Similar results were found for the IKs activator ML277. In baseline conditions, ML277 increased both WT and A341V IKs by approximately 60%. The IKs response to ML277 in cells stimulated with cAMP/OA was amplified more than twofold in WT, but strikingly also in A341V channels. This larger ML277 effect is thus likely explained by an augmented cAMP-dependent regulation of A341V IKs. Conclusions: Pharmacological and molecular interventions that promote IKs-channel opening rescue (at least partly) from defective cAMP-dependent upregulation by the hot spot mutation A341V. Our results suggest novel therapeutic strategies to restore the beta-adrenergic control of repolarization in long-QT1 syndrome.
Catalase, a therapeutic target in the reversal of estrogen-mediated aging
Authors: Sharon J. Elliot, Paola Catanuto, Simone Pereira-Simon, Xiaomei Xia, Irena Pastar, Seth Thaller, Cheyanne R. Head, Olivera Stojadinovic, Marjana Tomic-Canic, Marilyn K. Glassberg
Journal: Molecular Therapy (2021)

Despite increasing interest in the reversal of age-related processes, there is a paucity of data regarding the effects of post-menopausal-associated estrogen loss on cellular function. We studied human adipose-derived mesenchymal stem cells (hASCs) isolated from women younger than 45 years old (pre-menopause, pre-hASC) or older than 55 years old (post-menopause, post-hASC). In this study, we provide proof of concept that the age-related ineffective functionality of ASCs can be reversed to improve their ability in promoting tissue repair. We found reduced estrogen receptor expression, decreased estrogen receptor activation, and reduced sensitivity to 17β-estradiol in post-hASCs. This correlated with decreased antioxidants (catalase and superoxide dismutase [SOD] expression) and increased oxidative stress compared with pre-hASCs. Increasing catalase expression in post-hASCs restored estrogen receptor (ER) expression and their functional capacity to promote tissue repair as shown in human skin ex vivo wound healing and in vivo mouse model of lung injury. Our results suggest that the consequences of 17β-estradiol decline on the function of hASCs may be reversible by changing the oxidative stress/antioxidant composition.
The m <sup>6</sup> A reader IMP2 directs autoimmune inflammation through an IL-17– and TNFα-dependent C/EBP transcription factor axis
Authors: Rami Bechara, Nilesh Amatya, Rachel D. Bailey, Yang Li, Felix E. Y. Aggor, De-Dong Li, Chetan V. Jawale, Bianca M. Coleman, Ning Dai, Nandan S. Gokhale, Tiffany C. Taylor, Stacy M. Horner, Amanda C. Poholek, Anita Bansal, Partha S. Biswas, Sarah L. Gaffen
Journal: Science Immunology (2021)

The m6A “reader” IMP2 promotes cytokine-induced kidney autoimmunity by posttranscriptional control of C/EBPβ/δ transcription factors.
Differences of Human Cytomegalovirus Strains in Recipients of Allogeneic Hematopoietic Stem Cells before and after Transplantation
Authors: Michael V Demin, Dmitry S. Tikhomirov, Bella V. Biderman, Olga A. Glinshchikova, Tatiana A. Tupoleva, Andrey Sudarikov, Feliks F. Filatov, Tatiana V. Gaponova, Elena N. Parovichnikova, Valery G. Savchenko
Journal: Blood (2017)
Calcium phosphate microcrystals in the renal tubular fluid accelerate chronic kidney disease progression
Authors: Kazuhiro Shiizaki, Asako Tsubouchi, Yutaka Miura, Kinya Seo, Takahiro Kuchimaru, Hirosaka Hayashi, Yoshitaka Iwazu, Marina Miura, Batpurev Battulga, Nobuhiko Ohno, Toru Hara, Rina Kunishige, Mamiko Masutani, Keita Negishi, Kazuomi Kario, Kazuhiko Kotani, Toshiyuki Yamada, Daisuke Nagata, Issei Komuro, Hiroshi Itoh, Hiroshi Kurosu, Masayuki Murata, Makoto Kuro-o
Journal: Journal of Clinical Investigation (2021)

The Western pattern diet is rich not only in fat and calories but also in phosphate. The negative effects of excessive fat and calorie intake on health are widely known, but the potential harms of excessive phosphate intake are poorly recognized. Here, we show the mechanism by which dietary phosphate damages the kidney. When phosphate intake was excessive relative to the number of functioning nephrons, circulating levels of FGF23, a hormone that increases the excretion of phosphate per nephron, were increased to maintain phosphate homeostasis. FGF23 suppressed phosphate reabsorption in renal tubules and thus raised the phosphate concentration in the tubule fluid. Once it exceeded a threshold, microscopic particles containing calcium phosphate crystals appeared in the tubule lumen, which damaged tubule cells through binding to the TLR4 expressed on them. Persistent tubule damage induced interstitial fibrosis, reduced the number of nephrons, and further boosted FGF23 to trigger a deterioration spiral leading to progressive nephron loss. In humans, the progression of chronic kidney disease (CKD) ensued when serum FGF23 levels exceeded 53 pg/mL. The present study identified calcium phosphate particles in the renal tubular fluid as an effective therapeutic target to decelerate nephron loss during the course of aging and CKD progression.
BET Inhibitors in Chronic Lymphocytic Leukemia: JQ1 Synergizes with Venetoclax in Promoting Apoptosis
Authors: Giovanna Carrà, Cristina Panuzzo, Deborah Morena, Marcello Francesco Lingua, Cristina Fantino, Mara Brancaccio, Giuseppe Saglio, Angelo Guerrasio, Riccardo Taulli, Alessandro Morotti
Journal: Blood (2017)
Cell of Origin and Genomic Profile of Primary Central Nervous System Lymphoma Determined Using the Nanostring Lst Assay and Ultra Deep Targeted Next Generation Sequencing
Authors: Csaba Bödör, Donát Alpár, Dóra Marosvári, Hajnalka Rajnai, Bianka Dudela, Béla Kajtár, Beáta Deák, Andras Matolcsy, Sebastian Brandner, James Storhoff, Nadeem Ghali, Lilla Reiniger
Journal: Blood (2017)
Abstract 448: Impact of Novel Healthcare Facility First Responder Training on Resuscitation Task Self-Efficacy Measures
Authors: Les R Becker, Cheryl Camacho, Sheryl J Titus, Janet L Thorne, Munish Goyal
Journal: Circulation (2019)

Introduction: When sudden cardiac arrest occurs in non-resuscitation focused care settings, bedside clinicians may not intervene prior to dedicated resuscitation team arrival. As perceived self-efficacy (SE) contributes to cognitive functioning, facilitating effective intervention, we developed and evaluated a mock code training approach, First Five (FF) , to enhance bedside responders’ resuscitation task SE using an entity’s defibrillator and manikin. Self-efficacy is knowing that one can perform actions in principle and envision performing the steps to reach a goal. Hypotheses: Participants’ resuscitation SE will improve after FF training; 2) Inpatient (IP) and Ambulatory Care Center (ACC) providers will differ in their pre-SE and post-SE in response to FF training. Methods: Participants enrolled from ACCs and medical-surgical IP units at a large, urban tertiary care hospital from May 2018 to April 2019 completed a de-identified 10-point Likert-scale SE survey before and after they were trained to perform initial bedside resuscitation tasks (Figure 1 x-axis labels). Matched, complete, pre/post data for 85 in-hospital and 107 ACC participants were analyzed via repeated measures multivariate analysis of variance. Results: Patterns of reported change in the seven resuscitation task SE measures of IP personnel differed significantly from those of ACC personnel [Pillai’s Trace = .222, F(7,184)=7.483, p=.0005, partial η 2 = .222]. In both settings, post-session SE measures increased significantly from pre-session SE measures [Pillai’s Trace = .588, F(7,184)=37.438, p=.0005, partial η 2 = .588]. Moreover, though ACC providers consistently reported lower pre-training SE resuscitation task scores, post-training scores from both settings were comparable (Figure 1). Conclusions: First Five training is effective in enhancing resuscitation task SE among inpatient and ambulatory care setting providers that are not resuscitation-focused.
Genetic Admixture in the Culturally Unique Peranakan Chinese Population in Southeast Asia
Authors: Degang Wu, Peter Yiqing Li, Bangfen Pan, Zenia Tiang, Jinzhuang Dou, Ivanna Williantarra, Amadeus Yeremia Pribowo, Rizky Nurdiansyah, Roger S Y Foo, Chaolong Wang
Journal: Molecular Biology and Evolution (2021)

Abstract The Peranakan Chinese are culturally unique descendants of immigrants from China who settled in the Malay Archipelago ∼300–500 years ago. Today, among large communities in Southeast Asia, the Peranakans have preserved Chinese traditions with strong influence from the local indigenous Malays. Yet, whether or to what extent genetic admixture co-occurred with the cultural mixture has been a topic of ongoing debate. We performed whole-genome sequencing (WGS) on 177 Singapore (SG) Peranakans and analyzed the data jointly with WGS data of Asian and European populations. We estimated that Peranakan Chinese inherited ∼5.62% (95% confidence interval [CI]: 4.76–6.49%) Malay ancestry, much higher than that in SG Chinese (1.08%, 0.65–1.51%), southern Chinese (0.86%, 0.50–1.23%), and northern Chinese (0.25%, 0.18–0.32%). A sex-biased admixture history, in which the Malay ancestry was contributed primarily by females, was supported by X chromosomal variants, and mitochondrial (MT) and Y haplogroups. Finally, we identified an ancient admixture event shared by Peranakan Chinese and SG Chinese ∼1,612 (95% CI: 1,345–1,923) years ago, coinciding with the settlement history of Han Chinese in southern China, apart from the recent admixture event with Malays unique to Peranakan Chinese ∼190 (159–213) years ago. These findings greatly advance our understanding of the dispersal history of Chinese and their interaction with indigenous populations in Southeast Asia.
Staphylococcus aureusロイコシジンはマウスにおける致死性を引き起こす内皮DARCを標的とする【JST・京大機械翻訳】
Authors: Lubkin Ashira, L Lee Warren, Alonzo Francis, Wang Changsen, Aligo Jason, Keller Matthew, M Girgis Natasha, Reyes-Robles Tamara, Chan Rita, O’Malley Aidan, Buckley Peter, Vozhilla Nikollaq, T Vasquez Marilyn, Su Johnny, Sugiyama Michael, T Yeung Stephen, Coffre Maryaline, Bajwa Sofia, Chen Eric, Martin Patricia, Y Kim Sang, Loomis Cynthia, Worthen G. Scott, Shopsin Bo, M Khanna Kamal, Weinstock Daniel, Lynch Anthony Simon, B Koralov Sergei, Loke P’ng, Cadwell Ken, J Torres Victor
Journal: Cell Host & Microbe (2019)
Abstract 399: CPR in Chicago Public Schools; A Survey for Implementation of Sudden Cardiac Arrest Education in Schools
Authors: Alyssa Vermeulen, Marina Del Rios, Teri Campbell, Hoang Nguyen
Journal: Circulation (2019)

Introduction: There is variability on CPR and AED training requirements and mandates in schools; some states require teachers to be certified in CPR while others, such as Illinois, only require students to be taught CPR prior to graduation. However, even when required, implementation is not always successful. Most US schools do not establish protocols for sudden cardiac arrest. Identification of barriers to implementation of such protocols and school-wide CPR and AED training are needed for safety of students and staff. Hypothesis: To survey Chicago Public Schools (CPS) staff on knowledge and barriers to training in CPR, AED, and sudden cardiac arrest. Methods: A 20-question anonymous survey was distributed to adult Chicago Public School staff. Questions included on knowledge of CPR, AED, and sudden cardiac arrest, knowledge of the schools’ preparedness, barriers to CPR, AED training, and desire of staff to improve CPR, AED knowledge. Results: Of 95 respondents, 53% were teachers. 66% had previously participated in CPR training, but 60% had not taken it in the last 2 years and. 41% did not know how to operate an AED and 30% had learned but were not confident they would be able to use it. 90% said they would like more education on sudden cardiac arrest, but only 3.2% had CPR training available to them through the school. When asked about future training, 42% would sign up regardless of cost, 51% said they would sign up only if free of cost. 21% provided cost as the only barrier and 45% of respondents selected both cost and time as the main barriers. Conclusions: Our survey demonstrates a lack of knowledge in CPR, AED and sudden cardiac arrest. Despite strong interest, barriers such as availability, time, and cost stand in the way of increasing preparedness. Through community organizations and volunteers, free basic training programs for schools can be created addressing the issue of cost, time and comfort with CPR and AED use can be created; in teaching staff, we can increase safety and the availability of persons to train students.
BOLD asynchrony elucidates tumor burden in IDH-mutated gliomas
Authors: Petros D Petridis, Craig I Horenstein, Brianna Pereira, Peter B Wu, Jorge Samanamud, Tamara Marie, Deborah Boyett, Tejaswi D Sudhakar, Sameer A Sheth, Guy M McKhann, Michael B Sisti, Jeffrey N Bruce, Peter Canoll, Jack Grinband
Journal: Neuro-Oncology (2021)

Gliomas comprise the most common type of primary brain tumor, are highly invasive, and often fatal. IDH-mutated gliomas are particularly challenging to image and there is currently no clinically accepted method for identifying the extent of tumor burden in these neoplasms. This uncertainty poses a challenge to clinicians who must balance the need to treat the tumor while sparing healthy brain from iatrogenic damage. The purpose of this study was to investigate the feasibility of using resting-state blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to detect glioma-related asynchrony in vascular dynamics for distinguishing tumor from healthy brain.Twenty-four stereotactically localized biopsies were obtained during open surgical resection from ten treatment-naïve patients with IDH-mutated gliomas who received standard-of-care preoperative imaging as well as echo-planar resting-state BOLD fMRI. Signal intensity for BOLD asynchrony and standard-of-care imaging was compared to cell counts of total cellularity (H&E), tumor density (IDH1 & Sox2), cellular proliferation (Ki67), and neuronal density (NeuN), for each corresponding sample.BOLD asynchrony was directly related to total cellularity (H&E, P = 4 × 10-5), tumor density (IDH1, P = 4 × 10-5; Sox2, P = 3 × 10-5), cellular proliferation (Ki67, P = .002), and inversely related to neuronal density (NeuN, P = 1 × 10-4).Asynchrony in vascular dynamics, as measured by resting-state BOLD fMRI, correlates with tumor burden and provides a radiographic delineation of tumor boundaries in IDH-mutated gliomas.
Combined effects of plasma von Willebrand factor and platelet measures on the risk of incident venous thromboembolism
Authors: Magnus S. Edvardsen, Ellen-Sofie Hansen, Kristian Hindberg, Vânia M. Morelli, Thor Ueland, Pål Aukrust, Sigrid K. Brækkan, Line H. Evensen, John-Bjarne Hansen
Journal: Blood (2021)
Serum Leucine-Rich α2 Glycoprotein: A Novel Biomarker For Small Bowel Mucosal Activity in Crohn’s Disease
Authors: Ami Kawamoto, Kento Takenaka, Shuji Hibiya, Kazuo Ohtsuka, Ryuichi Okamoto, Mamoru Watanabe
Journal: Clinical Gastroenterology and Hepatology (2021)