tbuckley/cabot-search huggingface dataset:
Abstract 13681: Single-cell Gene Profiling Revealed Heterogeneity of Human Skeletal Muscle Derived Stem Cells and Their Paracrine Factors
Authors: Hiroko Iseoka, Shigeru Miyagawa, Kosuke Torigata, Yoshiki Sawa
Journal: Circulation (2020)

Background: Transplantation of sheet-shaped autologous skeletal muscle-derived cells (SMDCs) has been shown to produce therapeutic effects via paracrine factors in ischemic cardiomyopathy. SMDCs are heterogeneous cell population consist of myoblasts and non-myogenic cells, and their detailed characteristic and paracrine factors has not been fully analyzed. We herein applied single-cell RNA sequencing (scRNA-seq) to profile the population and paracrine factors of SMDCs. Methods and Results: Primary SMDCs of human origin were subjected to scRNA-seq and divided into 5 populations, expressing myogenic markers differently. These included four myogenic populations with higher expression of MYF5 (myoblasts), myogenin (early differentiated cells), mitosis-related gene (proliferating cells), and MYL3 (moderately differentiated cells) and non-myogenic population with lower expression of myogenic genes. On the other hand, PAX7 , quiescent satellite cell marker, and MYH4 , terminally differentiated marker, were not expressed in any populations. Furthermore, regarding the expression of key angiogenic factors, VEGF and HGF were highly expressed in the non-myogenic population and HMGB1 was expressed in both populations. Moreover, analysis of the gene expression of angiogenic factors differentially expressed in each population indicated that myoblast population highly expressed PDGFA and CCN (Cellular communication network factor) 1 , and early differentiated population highly expressed CCN2 . Although these factors were expressed in other populations, their expression tended to be lower in the moderately differentiated cell population. Conclusion: Analysis of SMDCs using scRNA-seq revealed that they are heterogeneous cells consisting of multiple myogenic populations with different degrees of differentiation and cytokine production, suggesting that single-cell gene profiling may be useful for the evaluation on characters of effector cells.
Safety and immunogenicity of a synthetic carbohydrate conjugate vaccine against Shigella flexneri 2a in healthy adult volunteers: a phase 1, dose-escalating, single-blind, randomised, placebo-controlled study
Authors: Dani Cohen, Jacob Atsmon, Cécile Artaud, Shiri Meron-Sudai, Marie-Lise Gougeon, Anya Bialik, Sophy Goren, Valeria Asato, Ortal Ariel-Cohen, Arava Reizis, Alexandra Dorman, Carla W G Hoitink, Janny Westdijk, Shai Ashkenazi, Philippe Sansonetti, Laurence A Mulard, Armelle Phalipon
Journal: The Lancet Infectious Diseases (2020)
Abstract 303: Optic Nerve Sheath Diameter Differences by Sex, Rhythm, and Neurological Outcome After Out-of-hospital Cardiac Arrest
Authors: Pavitra Kotini-Shah, Richard Gordon, Benjamin Karfunkle, Jing Li, Hajwa Kim, Pei-Shan Yen, Misha Granado, Pratik B Doshi, Henry E Wang, Terry L Vanden Hoek
Journal: Circulation (2020)

Introduction: Neurologically guided resuscitation after out-of-hospital cardiac arrest (OHCA) to improve survival has been limited due to knowledge gaps in cerebral edema changes. Point-of-care ultrasound (POCUS) for the assessment of optic nerve sheath diameter (ONSD) is an established modality to characterize the extent of cerebral edema. We aimed to describe ONSD differences by sex, rhythm type, neurological outcome using cerebral performance category (CPC), and overall survival status. Methods: We studied adult OHCA treated at an urban academic ED with return of spontaneous circulation (ROSC) from May 2018 to May 2020. After ROSC, trained emergency physicians obtained bilateral ONSD measurements at 1, 6, 24, 48, and 72 hours, in the transverse, oblique, and sagittal planes for each eye. All the ONSD measurements were averaged for each time point and comparisons were made between each predictor’s categories. To compare the mean at each time point between groups, t-test or ANOVA was used. The trend comparison was done using generalized estimating equations. Statistical analysis was performed using SAS 9.4 under the significance level of 0.05. Results: Out of 62 eligible patients, 35 (56%) were male and 27 (44%) were female, 33 (59%) had a shockable rhythm and 23 (41%) had non-shockable rhythm. At 72 hr, 6 (10%) had a CPC of 1-2 and 57 (90%) had CPC of 3-5. Overall, there were 37 (61%) survivors and 24 (39%) non-survivors. There was a notable sex difference in the mean ONSD across all time points between males and females (p = 0.031), with males showing higher ONSD, and between shockable and non-shockable (p= 0.035), with the shockable group having relatively lower ONSD. There is a statistically significant difference of mean ONSD between CPC 1-2 and CPC 3-5 groups at 6hr, 48hr, and at 72hr, with higher means in the CPC 3-5 group. Across all times, the trend line was statistically significant between non-survivors and survivors (p= 0.015), with non-survivors having higher ONSD. Conclusion: Males, patients with non-shockable rhythm, CPC 3-5 at 72 hr, and non-survivors had higher ONSD. Understanding cerebral edema dynamics during resuscitation will allow for future work to potentially tailor interventions to individual patient cerebral injury patterns.
Acupuncture and Knee Osteoarthritis: Does Dose Matter?
Authors: David J. Hunter, Richard E. Harris
Journal: Arthritis & Rheumatology (2020)

Osteoarthritis (OA) is an extraordinarily prevalent and disabling disease (1).Current management options for pain and functional limitation are constrained by modest efficacy or a range of unwanted side effects.Our society is being impacted through underemployment and the opioid epidemic, and our health care systems are overstretched, as a consequence of the trajectory of increasing joint replacement requirements (2).In this context, development of new treatments or identification of the efficacy of existing therapies to address the huge unmet need of pain management are strongly desired.Acupuncture is a component of traditional East Asian medicine and has been used as a healing practice for many centuries (3).Acupuncture is generally thought to have arisen in China with documented clinical practice in the Huangdi Neijing "Yellow Emperor's Inner Classic" more than 2,000 years ago.However, ancient Chinese burial sites have uncovered acupuncture tools (Bian stones) that predate this period.Following its development in ancient China, acupuncture spread throughout Southeast Asia and Europe, and is becoming increasingly popular in North and South America.Acupuncture typically involves the insertion of thin (32-36-gauge) solid needles into specific points in the body (acupoints).Once needles are inserted, they may be stimulated mechanically, electrically, or thermally.Needles are then retained in the body for 20-30 minutes during a single session.When provided as a course of treatment, acupuncture is performed during multiple sessions spread over a number of weeks.The efficacy of acupuncture in the context of pain, and knee OA more specifically, is a subject of controversy.The initial literature struggled to consistently demonstrate efficacy of acupuncture over and above sham treatment.However, the Acupuncture Trialist Collaborative showed, in an individual participant meta-analysis (n = 20,827 patients; 39 trials), that acupuncture was superior to sham acupuncture for multiple pain conditions: OA had an effect
Abstract 358: Out-of-hospital Cardiac Arrest and Community First Response: Building Evidence for Policy and Practice
Authors: Eithne Heffernan, Andrew Murphy, Cathal O'Donnell, Jacqueline Egan, Siobhán Masterson
Journal: Circulation (2020)

Introduction: Out-of-hospital cardiac arrest (OHCA) is a leading cause of mortality globally. Community First Response (CFR) is an important component of OHCA management in many countries. It entails the mobilisation of volunteers by the Emergency Medical Services to respond to OHCAs in their locality. These volunteers include lay-people and professionals (e.g. nurses, physicians). CFR can increase rates of cardiopulmonary resuscitation or defibrillation performed prior to the Emergency Medical Services’ arrival, though its impact on survival and cognitive function requires further study. This research aimed to improve our understanding of CFR, including volunteers’ motives and activities, the association between volunteer location and social fragmentation/deprivation, and the outcomes that should be measured for this intervention. Methods: This mixed-methods project comprises several key stages: systematic review of the CFR literature, interviews with CFR experts from a range of countries (e.g. USA, Canada, UK, Australia, Singapore), a survey of volunteers, and an analysis of Irish ambulance service records. Results: Various factors affect volunteer motivation, such as personality, family history, legislation, and psychological support. Volunteers undertake many activities in addition to responding to OHCAs, including responding to other emergencies (e.g. stroke), raising awareness of OHCA, providing CPR training, and supporting patients’ relatives. Barriers to responding include problems with technology and recruitment. Volunteer location in Ireland does not appear to be influenced by social fragmentation/deprivation. Outcomes that are measured for CFR include response times and survival. Other potentially important outcomes can prove difficult to measure, particularly the benefits for patients’ relatives and communities. Conclusions: This project has implications for CFR research and practice, especially recruiting and supporting volunteers and measuring outcomes. Improving these processes could help to optimise and build evidence for this intervention. Funding has been obtained to extend this project so that the impact of the coronavirus disease 2019 (COVID-19) pandemic on the CFR evidence base can be examined.
Abstract 274: Drugs and Cardiac Arrest: Suffocate the Brain, Spare the Body?
Authors: Anezi Uzendu, Mark McIntyre, Habeeb Suara, Alisha Alabre, Emmanuel Boateng, Lawrence Charles, Edvard Gumbs, Patrick Ruz, Uzoma Anaba, Rebecca Carter, Henry Okafor, Cameron Dezfulian, Avirup Guha, Daniel Addison
Journal: Circulation (2020)

Background: Nearly 70,000 people die of a drug overdose every year. Yet, how drug induced cardiac arrests differ from presumed cardiac etiology cardiac arrests is not well described. In animal models, asphyxial arrests resemble drug induced arrests, demonstrating better hemodynamic profiles yet worse neurologic recovery. Theoretically, this is caused by hypoxemic but preserved perfusion prior to ultimate arrest. But, this has not been studied in humans. We hypothesize that drug induced cardiac arrests will have higher incidence of return of spontaneous circulation (ROSC) in all comers, yet worse neurologic recovery among hospitalized patients. Methods: From a large institutional dataset capturing all patients with out-of-hospital cardiac arrests admitted from 2011 to 2019, we assess the prevalence and outcomes of cardiac arrests, by drug-use status. Patients were excluded if the arrest was trauma induced, occurred in an extended care facility/nursing home, or if treatment was initiated at another medical center. The primary outcome was ROSC in all comers, and the secondary outcome was favorable neurologic function among those surviving to admission. Multivariable logistic regression was used to assess factors associated with differences in outcomes, accounting for traditional cardiac risk factors and arrest characteristics. Results: In total, 436 patients (57±10 years, 31.7% female, 58.5% non-white, 49.3% hypertensive, 28.4% diabetics, and 21.1% preceding coronary disease) were identified, including 94 (21.6%) with drug induced cardiac arrest. Of that total group 101 (23.2%) survived, to admission, 26.6% of the drug induced group and 22.2% of the presumed cardiac cohort, demonstrating no difference in ROSC (P=0.32). Among those that survived to admission, 8% (2/25) of the drug induced group had a favorable neurologic outcome, compared to 29.0% (22/76) of the cardiac induced group (P= 0.03). Following adjustment, the presence of presenting drug induced cardiac arrest remained associated with lower rates of neurologic recovery [OR 7.3 (1.03-51.6) P= 0.04]. There was no difference in survival to discharge. Conclusion: Drug induced cardiac arrest is associated with worse neurologic outcomes than presumed cardiac etiology cardiac arrests.
In chronic plaque psoriasis, roflumilast cream safely increased likelihood of clear or almost clear state at 6 weeks
Authors: Satveer K. Mahil, Catherine H. Smith
Journal: Annals of Internal Medicine (2020)

Lebwohl MG, Papp KA, Stein Gold L, et al. Trial of roflumilast cream for chronic plaque psoriasis. N Engl J Med. 2020;383:229-39. 32668113.
Abstract 12817: Comparison of New York Heart Association Classification and Patient-reported Outcomes Among Heart Failure Patients in U.S. Clinical Practice: CHAMP-HF
Authors: Stephen J Greene, Javed Butler, John Spertus, Muthiah Vaduganathan, Anne Hellkamp, Adam D Devore, J Herbert H Patterson, Nancy M Albert, Carol Duffy, Fredonia Williams, Laine E Thomas, Adrian F Hernandez, Gregg C Fonarow
Journal: Circulation (2020)

Introduction: How the New York Heart Association classification system compares with patient-reported outcomes for HF patients in contemporary U.S. clinical practice is unclear. Methods: Among 2,872 U.S. outpatients with chronic HF with reduced ejection fraction (HFrEF) in the CHAMP-HF registry with complete NYHA class and Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS) data at baseline and 12 months, longitudinal changes in the 2 measures and their correlation with each other were examined. Multivariable models landmarked at 12 months separately evaluated associations between improvement in NYHA and KCCQ-OS from baseline to 12 months with clinical outcomes occurring from months 12 through 24. Results: At 12-month follow-up, 65% of patients had no change in NYHA class, 18% had 1 class improvement, and 13% had 1 class worsening. For KCCQ-OS, 25% had no significant change (i.e., &lt;5 point improvement or worsening), 48% had ≥5 point improvement, and 27% a ≥5 point worsening (Figure, Panel A) . NYHA class and KCCQ-OS showed modest correlation at baseline (r=0.33, p&lt;0.01) and 12 months (r=0.33, p&lt;0.01). After adjustment, improvement in NYHA class was not associated with 1-year mortality or composite mortality/ HF hospitalization ( Figure, Panel B) . For KCCQ-OS, ≥5-point improvement was independently associated with a 41% lower risk of mortality and a 27% lower risk of mortality/ HF hospitalization. Conclusions: In this contemporary U.S. outpatient HFrEF registry, as compared with NYHA class, the KCCQ-OS was substantially more likely to show meaningful change over 12-month follow-up and these changes had strong prognostic implications. These data support the advantages and relative importance of patient-reported outcomes for HFrEF, as compared with traditional clinician-reported functional assessments.
Gs/Gq signaling switch in β cells defines incretin effectiveness in diabetes
Authors: Okechi S. Oduori, Naoya Murao, Kenju Shimomura, Harumi Takahashi, Quan Zhang, Haiqiang Dou, Shihomi Sakai, Kohtaro Minami, Belen Chanclon, Claudia Guida, Lakshmi Kothegala, Johan Tolö, Yuko Maejima, Norihide Yokoi, Yasuhiro Minami, Takashi Miki, Patrik Rorsman, Susumu Seino
Journal: Journal of Clinical Investigation (2020)

By restoring glucose-regulated insulin secretion, glucagon-like peptide-1–based (GLP-1–based) therapies are becoming increasingly important in diabetes care. Normally, the incretins GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) jointly maintain normal blood glucose levels by stimulation of insulin secretion in pancreatic β cells. However, the reason why only GLP-1–based drugs are effective in improving insulin secretion after presentation of diabetes has not been resolved. ATP-sensitive K+ (KATP) channels play a crucial role in coupling the systemic metabolic status to β cell electrical activity for insulin secretion. Here, we have shown that persistent membrane depolarization of β cells due to genetic (β cell–specific Kcnj11–/– mice) or pharmacological (long-term exposure to sulfonylureas) inhibition of the KATP channel led to a switch from Gs to Gq in a major amplifying pathway of insulin secretion. The switch determined the relative insulinotropic effectiveness of GLP-1 and GIP, as GLP-1 can activate both Gq and Gs, while GIP only activates Gs. The findings were corroborated in other models of persistent depolarization: a spontaneous diabetic KK-Ay mouse and nondiabetic human and mouse β cells of pancreatic islets chronically treated with high glucose. Thus, a Gs/Gq signaling switch in β cells exposed to chronic hyperglycemia underlies the differential insulinotropic potential of incretins in diabetes.
慢性腎臓疾患の定義と分類:腎臓疾患からの位置記載:全体的な転帰(KDIGO)の改善
Authors: Levey As, Eckardt Ku, Tsukamoto Y, Levin A, Coresh J, Rossert J, De Zeeuw D, Hostetter Th, Lameire N, Eknoyan G
Journal: Kidney International (2005)
Use UK aid to train doctors in developing countries, says MP
Authors: Abi Rimmer
Journal: BMJ (2020)

The UK should train more doctors and nurses rather than recruiting staff from developing countries, an MP has said.

Speaking in the House of Commons on 17 November, former international development secretary Andrew Mitchell said it was immoral and selfish of Britain to poach doctors from the developing world.

Data from the General Medical Council show that between 2015 and …
Abstract 16406: Epigenetic Regulation of Myofibroblast Differentiation and Persistence is Mediated by Enhanced Glutaminolysis
Authors: Andrew A Gibb, Emma K Murray, Anh T Huynh, Alyssa A Lombardi, Pawel K Lorkiewicz, Devin W Kolmetzky, Michael P Lazaropoulos, Zolt P Arany, Daniel P Kelly, Kenneth B Margulies, Bradford G Hill, John W Elrod
Journal: Circulation (2020)

Cardiac fibrosis is mediated by the activation and differentiation of resident cardiac fibroblasts. While initially reparative, chronic activation leads to progressive cardiac dysfunction. Associated with myofibroblast formation are changes in metabolites directly linked to the activity of epigenetic-modifying enzymes. To define the signaling linking fibroblast activation with changes to the epigenetic landscape, we treated primary adult murine cardiac fibroblasts (CFs) with the pro-fibrotic agonist, TGFβ, and subjected them to next-gen sequencing techniques (RNA-seq, ATAC-seq). Following activation, we observed alterations in chromatin accessibility corresponding to the transcriptional activation and suppression of key fibrotic genes. Intriguingly, increased chromatin accessibility was strongly associated with both transcriptional activation and suppression, while decreased accessibility correlated with neither transcriptional repression or activation. Regions of increased accessibility were enriched for canonical fibrotic TF binding motifs (e.g. SMADs, NFAT). We recently reported that αKG-dependent lysine demethylases may be required for myofibroblast formation, so we made correlative comparisons between chromatin remodeling and the synthesis and utilization of metabolites critical for (de)methylation by applying unbiased, stable isotope metabolomics. These studies indicated enhanced glutaminolysis as the driver of increased αKG abundance. In the presence of TGFβ, pharmacologic inhibition (CB-839) or genetic deletion ( Gls1 -/- ) of glutaminolysis prevented myofibroblast formation as indicated by αSMA positivity, fibrotic gene program activation, and collagen contraction assays. Following myofibroblast formation, inhibition of glutaminolysis was sufficient to revert activated myofibroblasts to a non-fibrotic phenotype, during sustained stress. Remarkably, these results were recapitulated in CFs from human heart failure patients. Collectively, these findings suggest that metabolic remodeling is necessary for the epigenetic modifications that underlie myofibroblast formation and persistence, providing substantial rationale to evaluate several new therapeutic targets to treat fibrosis.
Soft Electronics Based on Stretchable and Conductive Nanocomposites for Biomedical Applications
Authors: Byron Llerena Zambrano, Aline F. Renz, Tobias Ruff, Samuel Lienemann, Klas Tybrandt, János Vörös, Jaehong Lee
Journal: Advanced Healthcare Materials (2020)

Abstract Research on the field of implantable electronic devices that can be directly applied in the body with various functionalities is increasingly intensifying due to its great potential for various therapeutic applications. While conventional implantable electronics generally include rigid and hard conductive materials, their surrounding biological objects are soft and dynamic. The mechanical mismatch between implanted devices and biological environments induces damages in the body especially for long‐term applications. Stretchable electronics with outstanding mechanical compliance with biological objects effectively improve such limitations of existing rigid implantable electronics. In this article, the recent progress of implantable soft electronics based on various conductive nanocomposites is systematically described. In particular, representative fabrication approaches of conductive and stretchable nanocomposites for implantable soft electronics and various in vivo applications of implantable soft electronics are focused on. To conclude, challenges and perspectives of current implantable soft electronics that should be considered for further advances are discussed.
Abstract 17114: Whose Work is It? Patient Perspectives on Challenges in Heart Failure Self-Management
Authors: Renee Leverty, Leslie Chang, Jose Barcenas, James James Campbell, Kirsten Dahlgren, William Piltzer, Clayburn Rich, Judy Roark, Barry Sude, Fredonia Williams, Adam D Devore, Adrian F Hernandez, Bradi B Granger
Journal: Circulation (2020)

Introduction: The importance of self-care behaviors in successful heart failure (HF) management is widely recognized. And yet, patient perspectives on strategies to effective carry out the work of behavior change remain relatively unexplored. Methods: From March 2017 to May 2017, we conducted semi-structured, in-depth interviews with 8 HF patients involved in the CONNECT-HF clinical trial and 7 of their respective caregivers. Interviews were audio-recorded and transcriptions were imported to NVivo 11 (Version 11.4.0) for coding and analysis. We used content analysis and a mixed inductive and deductive approach for interpretation of coded text. Results: Patients (n=8) and caregivers (n=7) reported numerous strategies (n=28) for each guideline-based self-care behavior. The over-arching theme contributing to successful, effective behavior change was the value of social support and social interactions in the work of “sticking with it.” Predominant sub-themes included the idea that “knowledge is necessary but not sufficient” for behavior change, and “ building a routine” was critical for life-long self-care to be effective (Table 1). Conclusions: Many of the behavior change barriers and strategies proposed by patients are concepts that are consistent with findings in the field of behavioral economics and have the potential to inform development of effective behavior change tools.