tbuckley/cabot-search huggingface dataset:
Abstract 13393: Liraglutide Improves Myocardial Redox State in Humans by Regulating the Adipose Tissue-Derived Long-Chain Ceramides
Authors: Nadia Akawi, Antonio Checa, Ioannis Akoumianakis, Shakil Farid, Vivek Srivastava, George Krasopoulos, Keith M Channon, Craig Wheelock, Signe S Torekov, Charalambos antoniades
Journal: Circulation (2021)

Introduction: A notable reduction in major adverse cardiovascular events and cardiovascular mortality was observed in several cardiovascular studies via treatment with liraglutide, which have been suggested to be mediated through several mechanisms including inhibition of oxidative stress. Hypothesis: We hypothesised that treatment with liraglutide reduces oxidative stress via modulating circulating levels of long-chain ceramides. Methods: We measured vascular superoxide production using lucigenin-enhanced chemiluminescence and levels of circulating ceramides using LC-MS/MS in 633 participants of the Oxford Heart Vessels and Fat (OxHVF) cohort. We also measured 33 sphingolipid species (SPL) in plasma from 32 obese individuals (average BMI 33.5±2.5kg/m 2 at inclusion) participating in a randomized clinical trial (RCT) of low calorie diet and liraglutide. Results: We found a significant association between superoxide production by internal mammary arteries (IMA) and circulating levels of long-chain ceramides (C16:0, C17:0, C18:0, C18:1) (A-D) . In the RCT, all participants adhered to an 8-week low-calorie diet (800 kcal/day) (E) , during which they lost 9.9±6.0 kg of body weight exhibiting a significant reduction in BMI ( p &lt;0.0001), which was paralleled by significant effects on the circulating levels of SPL (F) . Following this initial phase, the patients were randomised to liraglutide treatment (1.2 mg daily) or no treatment, for a period of 52 weeks. Liraglutide treatment differentially affected several SPL species compared to the control group despite no significant changes in BMI in any of the two groups (G-J) . Conclusions: In this study, we observed for the first time in human a regulatory effect of liraglutide on the circulating levels of long-chain ceramides that are shown to be associated with vascular oxidative stress suggesting a promising mechanistic link that justifies further exploration.
Association of Differences in Treatment Intensification, Missed Visits, and Scheduled Follow-up Interval With Racial or Ethnic Disparities in Blood Pressure Control
Authors: Valy Fontil, Lucia Pacca, Brandon K. Bellows, Elaine Khoong, Charles E. McCulloch, Mark Pletcher, Kirsten Bibbins-Domingo
Journal: JAMA Cardiology (2021)

Black patients with hypertension often have the lowest rates of blood pressure (BP) control in clinical settings. It is unknown to what extent variation in health care processes explains this disparity.
Trustworthy Clinical Practice Guidelines of Pharmacological Treatments for Hospitalized Patients With COVID-19—A Scarce Resource
Authors: Karina W. Davidson, Catherine M. Alfano, Felicia Hill-Briggs
Journal: JAMA Network Open (2021)

Karen E. A. Burns, MD, MSc (Epid); Matthew Laird, BMSc; James Stevenson, BSc; Kimia Honarmand, MD; David Granton, MD; Michelle E. Kho, PT, PhD; Deborah Cook, MD; Jan O. Friedrich, MD; Maureen O. Meade, MD; Mark Duffett, PhD; Dipayan Chaudhuri, MD; Kuan Liu, PhD; Frederick D’Aragon, MD; Arnav Agarwal, MD; Neill K. J. Adhikari, MD; Hayle Noh, BSc; Bram Rochwerg, MD; Academy of Critical Care: Development, Evaluation, and Methodology (ACCADEMY); David Lightfoot; Karen Choong; Andrea Lucas; Joanna Dionne; Colungo Lozano; Erick Duan; Emilie Belley-Cote; Melissa Parker; John Basmaji; Vincent Lau; Samantha Arora
A Deep-Learning Approach for Inference of Selective Sweeps from the Ancestral Recombination Graph
Authors: Hussein A Hejase, Ziyi Mo, Leonardo Campagna, Adam Siepel
Journal: Molecular Biology and Evolution (2021)

Detecting signals of selection from genomic data is a central problem in population genetics. Coupling the rich information in the ancestral recombination graph (ARG) with a powerful and scalable deep-learning framework, we developed a novel method to detect and quantify positive selection: Selection Inference using the Ancestral recombination graph (SIA). Built on a Long Short-Term Memory (LSTM) architecture, a particular type of a Recurrent Neural Network (RNN), SIA can be trained to explicitly infer a full range of selection coefficients, as well as the allele frequency trajectory and time of selection onset. We benchmarked SIA extensively on simulations under a European human demographic model, and found that it performs as well or better as some of the best available methods, including state-of-the-art machine-learning and ARG-based methods. In addition, we used SIA to estimate selection coefficients at several loci associated with human phenotypes of interest. SIA detected novel signals of selection particular to the European (CEU) population at the MC1R and ABCC11 loci. In addition, it recapitulated signals of selection at the LCT locus and several pigmentation-related genes. Finally, we reanalyzed polymorphism data of a collection of recently radiated southern capuchino seedeater taxa in the genus Sporophila to quantify the strength of selection and improved the power of our previous methods to detect partial soft sweeps. Overall, SIA uses deep learning to leverage the ARG and thereby provides new insight into how selective sweeps shape genomic diversity.
Unmet need for COVID-19 therapies in community settings
Authors: None The Lancet Infectious Diseases
Journal: The Lancet Infectious Diseases (2021)

There was widespread coverage in the media of Merck and Ridgeback's interim results of their phase 3 trial of the antiviral molnupiravir. According to a press release from Merck on Oct 1, molnupiravir reduced the risk of hospitalisation or death by roughly 50% compared with placebo in non-hospitalised patients with mild-to-moderate COVID-19 and at least one risk factor for disease progression. Despite not yet being peer-reviewed, these data incited excitement, in part because of the oral route of administration of molnupiravir, which means the drug could be easily taken at home and used widely in settings with inadequate health-care infrastructure.
Identification of Drug Transporter Genomic Variants and Inhibitors That Protect Against Doxorubicin-Induced Cardiotoxicity
Authors: Tarek Magdy, Mariam Jouni, Hui-Hsuan Kuo, Carly J. Weddle, Davi Lyra-Leite, Hananeh Fonoudi, Marisol Romero-Tejeda, Mennat Gharib, Hoor Javed, Giovanni Fajardo, Colin J.D. Ross, Bruce C. Carleton, Daniel Bernstein, Paul W. Burridge
Journal: Circulation (2021)

Background: Multiple pharmacogenomic studies have identified the synonymous genomic variant rs7853758 (G &gt; A, L461L) and the intronic variant rs885004 in SLC28A3 (solute carrier family 28 member 3) as statistically associated with a lower incidence of anthracycline-induced cardiotoxicity. However, the true causal variant(s), the cardioprotective mechanism of this locus, the role of SLC28A3 and other solute carrier (SLC) transporters in anthracycline-induced cardiotoxicity, and the suitability of SLC transporters as targets for cardioprotective drugs has not been investigated. Methods: Six well-phenotyped, doxorubicin-treated pediatric patients from the original association study cohort were recruited again, and human induced pluripotent stem cell–derived cardiomyocytes were generated. Patient-specific doxorubicin-induced cardiotoxicity (DIC) was then characterized using assays of cell viability, activated caspase 3/7, and doxorubicin uptake. The role of SLC28A3 in DIC was then queried using overexpression and knockout of SLC28A3 in isogenic human-induced pluripotent stem cell–derived cardiomyocytes using a CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9). Fine-mapping of the SLC28A3 locus was then completed after SLC28A3 resequencing and an extended in silico haplotype and functional analysis. Genome editing of the potential causal variant was done using cytosine base editor. SLC28A3-AS1 overexpression was done using a lentiviral plasmid-based transduction and was validated using stranded RNA-sequencing after ribosomal RNA depletion. Drug screening was done using the Prestwick Chemical Library (n = 1200), followed by in vivo validation in mice. The effect of desipramine on doxorubicin cytotoxicity was also investigated in 8 cancer cell lines. Results: Here, using the most commonly used anthracycline, doxorubicin, we demonstrate that patient-derived cardiomyocytes recapitulate the cardioprotective effect of the SLC28A3 locus and that SLC28A3 expression influences the severity of DIC. Using Nanopore-based fine-mapping and base editing, we identify a novel cardioprotective single nucleotide polymorphism, rs11140490, in the SLC28A3 locus; its effect is exerted via regulation of an antisense long noncoding RNA ( SLC28A3-AS1 ) that overlaps with SLC28A3. Using high-throughput drug screening in patient-derived cardiomyocytes and whole organism validation in mice, we identify the SLC competitive inhibitor desipramine as protective against DIC. Conclusions: This work demonstrates the power of the human induced pluripotent stem cell model to take a single nucleotide polymorphism from a statistical association through to drug discovery, providing human cell-tested data for clinical trials to attenuate DIC.
167TiP AdvanTIG-301: Anti-TIGIT monoclonal antibody (mAb) ociperlimab (OCI) + tislelizumab (TIS) + concurrent chemoradiotherapy (cCRT) followed by OCI + TIS or TIS + cCRT followed by TIS vs cCRT followed by durvalumab (DUR) in previously untreated, locally advanced, unresectable NSCLC
Authors: L. Xing, J. Yu, S. Peters, B. Besse, A. Spira, J. Wang, Y. Yang, H. Wang
Journal: Annals of Oncology (2021)
Hematocrit Self-Testing in Patients with Polycythemia Vera: A Proof-of-Concept Study Assessing the Accuracy of the Statstrip Xpress ® 2 Hb/Hct Device and Its Impact on Patients' Quality of Life in Clinical Practice
Authors: Alicia Rovo, Claudia Baierlein-Leimbach, Cesare Medri, Ioannis Chanias, Loreen Errass, Theresa Fehr, Therese Triemer, Daphne B McCarthy-Pontier, Thomas Lehmann
Journal: Blood (2021)
The Magnetic Field is Not a Health Hazard
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 11759: Survival Among Medicare Beneficiaries After Out-of-Hospital Cardiac Arrest Undergoing Interhospital Transfer
Authors: Ethan Abbott, David Buckler, alexis zebrowski, Benjamin Abella, Brendan G Carr
Journal: Circulation (2021)

Intro: Among individuals treated for out-of-hospital cardiac arrest (OHCA), there is hospital-level variability in mortality, but the relationship between interhospital transfer (IHT) OHCA volume and survival remain unclear. We sought to examine the association of OHCA volume and survival for individuals undergoing IHT. Methods: Utilizing age-eligible Medicare fee-for-service claims, we identified an emergency department treated OHCA cohort using ICD-9/10 diagnosis codes. Hospital OHCA volume was defined as the total number of index (first-treated) OHCA claims during the study period and were binned into quartiles. Each claim was assigned the OHCA volume quartile of the index hospital and the index volume of the receiving hospital. Multiple logistic regression was conducted to assess the association between initial and receiving hospital volume categories and survival to 30 days among IHT patients while controlling for patient-level characteristics (age, sex, race), comorbidity index, urbanicity of index hospital and days to transfer. Results: We identified a cohort of 222,018 claims at 4,461 hospitals between 1/2013-12/2015. Median age was 78 years (IQR 71-85); 44% were female; 11% of the cohort was alive at 30 days. IHT occurred in 12,245 cases (5.5%) and 59% of transfers occurred on the day of admission or day 1. Transfers originated from 3411 index hospitals and 1566 receiving hospitals. Median OHCA hospital index volume was 25 [IQR 9, 67]. Adjusted odds of survival at 30 days was significantly lower at index hospitals with lower OHCA volumes compared to the highest volume category (aOR [95%CI] Q2: 0.71 [0.6, 0.83] p&lt;0.001). Additionally, odds of survival at 30 days was significantly lower at low volume receiving hospitals (aOR [95%CI] Q1: 0.73 [0.55, 0.99] p&lt;0.001), and increased for higher OHCA volume receiving hospitals, but these groups did not achieve statistical significance. Conclusion: For Medicare beneficiaries who suffer an OHCA and undergo IHT, lower index and receiving hospital OHCA volume was significantly associated with decreased adjusted odds of 30-day survival. Further exploration of hospital characteristics, timing, and transfer patterns is needed to understand differences in benefit for OHCA patients undergoing IHT.
Projecting COVID-19 disruption to elective surgery
Authors: Dmitri Nepogodiev, Tom EF Abbott, Adesoji O Ademuyiwa, Ehab AlAmeer, Brittany K Bankhead-Kendall, Bruce M Biccard, Sohini Chakrabortee, Daoud Chaudhry, John G Edwards, Kariem El-Boghdadly, Dhruv Ghosh, James C Glasbey, Rohan R Gujjuri, Ewen M Harrison, Conor S Jones, Haytham MA Kaafarani, Sivesh K Kamarajah, Angelos G Kolias, Ismail Lawani, Elizabeth Li, Harvinder Mann, Ella Marson, Janet Martin, Kenneth A Mclean, Ana Minaya-Bravo, Rachel Moore, Faustin Ntirenganya, Omar M Omar, Peter Pockney, Antonio Ramos-De la Medina, Richard Shaw, Joana FF Simões, Neil J Smart, Sudha Sundar, Stephen Tabiri, Elliott H Taylor, Mary L Venn, Aneel Bhangu
Journal: The Lancet (2021)
Abstract 13945: Central Cannulation During Pediatric Extracorporeal Cardiopulmonary Resuscitation is Faster Than Peripheral Approaches
Authors: Alexandra M Marquez, Mariella Vargas-Gutierrez, Mark Todd, Geraldine Goco, Michael-Alice Moga, Alejandro Floh, Osami Honjo, Christoph Haller, Anne M Guerguerian
Journal: Circulation (2021)

Introduction: Favorable survivorship after pediatric extracorporeal cardiopulmonary resuscitation (ECPR) may be limited by prolonged resuscitations. Surgical cannulation metrics for pediatric ECPR have not been widely reported by centers that use time interval benchmarks with a cardiovascular service responding to different hospital locations. Hypothesis: We hypothesize that survival is associated with resuscitation duration, and cannulation duration differs between peripheral and central approaches. Methods: This was a single-center retrospective study of patients 0-18 years with in-hospital ECPR between January 2015 and December 2020. Primary outcome was survival to hospital discharge. Secondary outcomes were odds of favorable neurologic outcome (dichotomized pediatric cerebral performance category), total resuscitation duration defined as cardiac arrest start to ECMO flow start (CA-ECMO), and cannulation duration. Non-parametric and regression methods were used. Results: Of the 92 events that met ECPR criteria, median weight and age were 4 months (IQR 1 month, 16 years) and 4.4 kg (range 1.9-133 kg). Cannulation occurred in the cardiac intensive care unit (ICU) (66%, 61 of 92), followed by operating room (13%, 12 of 92), pediatric ICU (12%, 11 of 92), and catheterization lab (9%, 8 of 92). Central cannulation was performed in 43% (40 of 92), and 21% (19 of 92) had open chests at the time of the event. Median duration of CA-ECMO was 35 min (IQR 26, 45 min); cannulation duration was 11 min (IQR 5, 16.5 min) for central compared to 18.5 min (IQR 12, 23 min) for peripheral approaches (P=0.01). Survival was 40% (37 of 92), and favorable neurologic outcome occurred in 38% (35 of 92). Survival (adjusted OR, 0.94; 95% CI 0.91-0.99, P=0.018) and favorable neurologic outcome (adjusted OR, 0.95; 95% CI 0.917-1.000, P=0.053) were associated with CA-ECMO duration after adjusting for cannulation approach, location, difficulty, shockable rhythm, and weight. Conclusion: In pediatric in-hospital ECPR, total CA-ECMO duration remains a key metric associated with patient outcomes. Central cannulation is faster than peripheral approaches. Since cannulation strategy alters CPR maneuvers, CPR effectiveness with each approach needs further study.
Survival after COVID-19-associated organ failure among inpatients with systemic lupus erythematosus in France: a nationwide study
Authors: Arthur Mageau, Thomas Papo, Stephane Ruckly, Andrey Strukov, Damien van Gysel, Karim Sacre, Jean-François Timsit
Journal: Annals of the Rheumatic Diseases (2021)

We analysed the incidence of, the specific outcomes and factors associated with COVID-19-associated organ failure (AOF) in patients with systemic lupus erythematosus (SLE) in France.We performed a cohort study using the French national medical/administrative hospital database for the January 2011-November 2020 period. Each patient with SLE diagnosed in a French hospital with a COVID-19-AOF until November 2020 was randomly matched with five non-SLE patients with COVID-19-AOF. We performed an exact matching procedure taking age ±2 years, gender and comorbidities as matching variables. COVID-19-AOF was defined as the combination of at least one code of COVID-19 diagnosis with one code referring to an organ failure diagnosis.From March to November 2020, 127 380 hospital stays in France matched the definition of COVID-19-AOF, out of which 196 corresponded with patients diagnosed with SLE. Based on the presence of comorbidities, we matched 908 non-SLE patients with COVID-19-AOF with 190 SLE patients with COVID-19-AOF. On day 30, 43 in-hospital deaths (22.6%) occurred in SLE patients with COVID-19-AOF vs 198 (21.8%) in matched non-SLE patients with COVID-19-AOF: HR 0.98 (0.71-1.34). Seventy-five patients in the SLE COVID-19-AOF group and 299 in the matched control group were followed up from day 30 to day 90. During this period, 19 in-hospital deaths occurred in the SLE group (25.3%) vs 46 (15.4%) in the matched control group; the HR associated with death occurring after COVID-19-AOF among patients with SLE was 1.83 (1.05-3.20).COVID-19-AOF is associated with a poor late-onset prognosis among patients with SLE.
146P Randomized phase II trial of neoadjuvant chemotherapy with modified FOLFIRINOX versus modified FOLFIRINOX and PD-1 antibody for borderline resectable and locally advanced pancreatic cancer (the CISPD-4 study)
Authors: Y. Chen, C. Guo, X. Li, S. Gao, Y. Shen, M. Zhang, J. Yu, J. Wu, R. Que, A. Zhang, X. Bai, T. Liang
Journal: Annals of Oncology (2021)
A rational explanation for links between the ANS and math
Authors: Melissa E. Libertus, Shirley Duong, Danielle Fox, Leanne Elliott, Rebecca McGregor, Andrew Ribner, Alex M. Silver
Journal: Behavioral and Brain Sciences (2021)

Abstract The proposal by Clarke and Beck offers a new explanation for the association between the approximate number system (ANS) and math. Previous explanations have largely relied on developmental arguments, an underspecified notion of the ANS as an “error detection mechanism,” or affective factors. The proposal that the ANS represents rational numbers suggests that it may directly support a broader range of math skills.
Oncologic Treatment of HIV-Associated Kaposi Sarcoma 40 Years on
Authors: Ramya Ramaswami, Kathryn Lurain, Robert Yarchoan
Journal: Journal of Clinical Oncology (2021)

The observation in 1981 of the emergence of Kaposi sarcoma (KS) among young men who had sex with men was one of the first harbingers of the HIV epidemic. With advances in HIV care, the incidence of HIV-associated KS (HIV+KS) has decreased over time in the United States. However, it remains a persistent malignancy among some HIV-infected populations and is one of the most common tumors in sub-Saharan Africa. Because of the relapsing and remitting nature of this cancer, patients with HIV+KS can experience significant, long-term, morbidity. Patients with severe HIV+KS may also have concurrent lymphoproliferative syndromes, malignancies, and/or infections that can contribute to mortality. Several chemotherapy agents were explored in clinical trials for HIV+KS during the early stage of the epidemic. As HIV+KS emerges with CD4 lymphopenia and immunodysregulation, T-cell-sparing options are important to consider. Here, we explore the pathogenesis of HIV+KS and the current evidence for immunotherapy and therapies that potentially target KS pathogenesis. This review provides the current landscape of therapies for HIV+KS and highlights management issues for patients with HIV and cancer.
Photothermal Conjugated Polymer Nanoparticles for Suppressing Breast Tumor Growth by Regulating TRPA1 Ion Channels
Authors: Boying Li, Shuxi Ren, Dong Gao, Ning Li, Manman Wu, Hongbo Yuan, Mei Zhou, Chengfen Xing
Journal: Advanced Healthcare Materials (2021)

Abstract Cancer cells survive by relying on oxidative stress defense against the accumulation of reactive oxygen species (ROS) during tumor formation. ROS‐sensitive TRPA1 ion channels are overexpressed in breast cancer cells and induce a large influx of Ca 2+ which upregulates the anti‐apoptotic pathway to lead breast cancer cells to produce oxidative stress defense and enhance the resistance to ROS related chemotherapy. Targeting and inhibiting the TRPA1 ion channels are critical for breaking down the oxidative stress defense system and overcoming cellular resistance. Here, near‐infrared (NIR) light‐responsive conjugated polymer nanoparticles are designed and prepared to promote apoptosis of breast cancer cells, reduce cell drug resistance and suppress tumor growth through the remote and precise regulation of TRPA1 ion channels. Upon 808 nm laser irradiation, the nanoparticles block the formation of Ca 2+ /CaM complex and regulate the content of MCL‐1 protein. Especially, the nanoparticles overcome drug resistance of cancer cells, therefore accelerating apoptosis of cancer cells and suppressing tumor growth in mice. Compared with carboplatin, the volume of tumor induced by NPs‐H decreases by 54.1%. This work provides a strategy to disrupt the oxidative stress defense system and downregulate the antiapoptotic signaling pathway in cancer cells.