tbuckley/cabot-search huggingface dataset:
Abstract 10978: <i>Ecklonia Stolonifera</i> Okamura Extract Suppresses Cardiac Hypertrophy and Systolic Dysfunction Through P300-HAT Inhibition
Authors: Takahiro Katagiri, Masafumi Funamoto, Kana Shimizu, Satoshi Shimizu, Yoichi Sunagawa, Yasufumi Katanasaka, Yusuke Miyazaki, Koji Hasegawa, Tatsuya Morimoto
Journal: Circulation (2021)

Introduction: Heart failure is the leading cause of death in the world. Cardiomyocyte hypertrophy is observed during the development of heart failure, suggesting that its inhibition is a potential target for the prevention and treatment of heart failure. In this study, we screened a natural compound library using cultured cardiomyocytes and found that Ecklonia stolonifera Okamura extract (ESE) suppressed cardiomyocyte hypertrophy. Hypothesis: ESE, a perennial brown alga, has been reported to have various bioactive effects, such as antioxidant and anti-inflammatory activity, but its effect on heart failure is still unclear. Therefore, we investigated whether ESE has an inhibitory effect on cardiomyocyte hypertrophic response and on the progression of heart failure in post-myocardial infarction (MI) rats. Methods and Results: First, primary cultured cardiomyocytes from neonatal rats were treated with ESE and then stimulated with phenylephrine (PE) for 48 hours. ESE (1000 μg/mL) significantly suppressed PE-induced increases in cardiomyocyte surface area, hypertrophic response gene transcription, and acetylation of histone H3K9. An in vitro p300-HAT assay indicated that ESE directly inhibited p300-HAT activity (IC50: 505 μg/mL). Next, one week after the ligation of the left anterior descending artery, rats with moderate MI (left ventricular fractioning shorting (LVFS) &lt;40%) were randomly assigned to three groups: vehicle (saline) (n=9), ESE (0.3 g/kg) (n=10), or ESE (1 g/kg) (n=10). Daily oral administration was repeated for 8 weeks. After treatment, LVFS was significantly higher in the ESE (1 g/kg) group (23.3 ± 0.7%, p&lt;0.05) than in the vehicle group (16.6 ± 1.3%). ESE treatment significantly suppressed MI-induced increases both in myocardial cell diameter and in the mRNA levels of hypertrophic response genes. ESE also inhibited MI-induced perivascular fibrosis and the acetylation of histone H3K9. Conclusion: These results suggest that ESE suppresses both hypertrophic responses in cardiomyocytes and the development of heart failure by inhibiting p300-HAT activity. Further studies are needed to clarify the effectiveness of ESE for heart failure therapy.
Human intestinal bitter taste receptors regulate innate immune responses and metabolic regulators in obesity
Authors: Kathrin I. Liszt, Qiaoling Wang, Mona Farhadipour, Anneleen Segers, Theo Thijs, Linda Nys, Ellen Deleus, Bart Van der Schueren, Christopher Gerner, Benjamin Neuditschko, Laurens J. Ceulemans, Matthias Lannoo, Jan Tack, Inge Depoortere
Journal: Journal of Clinical Investigation (2021)

Bitter taste receptors (taste 2 receptors, TAS2Rs) serve as warning sensors in the lingual system against the ingestion of potentially poisonous food. Here, we investigated the functional role of TAS2Rs in the human gut and focused on their potential to trigger an additional host defense pathway in the intestine. Human jejunal crypts, especially those from individuals with obesity, responded to bitter agonists by inducing the release of antimicrobial peptides (α-defensin 5 and regenerating islet–derived protein 3 α [REG3A]) but also regulated the expression of other innate immune factors (mucins, chemokines) that affected E. coli growth. We found that the effect of aloin on E. coli growth and on the release of the mucus glycoprotein CLCA1, identified via proteomics, was affected by TAS2R43 deletion polymorphisms and thus confirmed a role for TAS2R43. RNA-Seq revealed that denatonium benzoate induced an NRF2-mediated nutrient stress response and an unfolded protein response that increased the expression of the mitokine GDF15 but also ADM2 and LDLR, genes that are involved in anorectic signaling and lipid homeostasis. In conclusion, TAS2Rs in the intestine constitute a promising target for treating diseases that involve disturbances in the innate immune system and body weight control. TAS2R polymorphisms may be valuable genetic markers to predict therapeutic responses.
Effect of preventive chemotherapy with praziquantel on schistosomiasis among school-aged children in sub-Saharan Africa: a spatiotemporal modelling study
Authors: Christos Kokaliaris, Amadou Garba, Martin Matuska, Rachel N Bronzan, Daniel G Colley, Ameyo M Dorkenoo, Uwem F Ekpo, Fiona M Fleming, Michael D French, Achille Kabore, Jean B Mbonigaba, Nicholas Midzi, Pauline N M Mwinzi, Eliézer K N'Goran, Maria Rebollo Polo, Moussa Sacko, Louis-Albert Tchuem Tchuenté, Edridah M Tukahebwa, Pitchouna A Uvon, Guojing Yang, Lisa Wiesner, Yaobi Zhang, Jürg Utzinger, Penelope Vounatsou
Journal: The Lancet Infectious Diseases (2021)
Unusual Increased Blood Pool Activity on 68Ga-DOTATATE PET/CT in a Patient With Metastatic Neuroendocrine Disease
Authors: Akash Sharma, Anem J. Navaz, Mukesh K. Pandey, Ephraim E. Parent
Journal: Clinical Nuclear Medicine (2021)

Abstract 68 Ga-DOTATATE is a well-established, positron-emitting, somatostatin receptor–binding radiopharmaceutical. We present an unusual case of transiently increased blood pool uptake of 68 Ga-DOTATATE in a patient with well-differentiated stage IV neuroendocrine tumor, with Ki-67 &lt;2% (WHO grade 1) maintained on lanreotide. During serial 68 Ga-DOTATATE PET/CT examinations, increased blood pool accumulation of presumably unbound 68 Ga was demonstrated, which could impact the Kenning score and lead to a false treatment response assessment.
Abstract P048: Feasibility Of A Remotely Delivered Mobile Health Exercise Intervention For Cardiometabolic Health: A Pilot Trial
Authors: Jacqueline K Dawson, Alison Ede, Madeleine Phan, Alec Sequeira, Hsiang-Ling Teng, Ayla Donlin
Journal: Circulation (2022)

Introduction: Lifestyle interventions incorporating exercise and nutrition can help prevent and manage cardiometabolic disease. However, not all interventions readily reach individuals who are most in need. A mobile health (mHealth) exercise program could be a cost-effective approach to broadening accessibility and providing support for physical activity behavior change. We tested the feasibility and acceptability of a mHealth exercise intervention in this 8-week pilot study. Hypothesis: A remotely delivered mHealth lifestyle program involving a wearable sensor, mobile application and social support is feasible and acceptable in sedentary adults. Methods: A total of 84 sedentary (&lt; 30 min/week of exercise) adults (females 31.5 ± 11.3 yr, males 34.1 ± 28.9 yr, mean ± SD) were randomized (1:1:1) to 8 weeks of increasing physical activity behavioral support: Level 1 (wellness education, n=26), Level 2 (wellness education + pre-recorded exercise videos, n=30), or Level 3 (wellness education + livestream group exercise, n=28). Participants used a chest strap sensor (Myzone MZ-3) during exercise and a mobile application for interaction. A weekly email was used to deliver wellness education and encourage physical activity. Level 2 exercise videos and Level 3 livestream (Zoom) group classes were 35 min long, instructor-led, delivered 3x/wk and designed to meet national guidelines for weekly physical activity. Participants were surveyed at baseline and 8 weeks. Feasibility was defined through accrual and attrition; acceptability through sensor use (3x/wk encouraged) and survey data. Results: Between August 2020 and August 2021, 204 adults were screened for eligibility. Out of 135 eligible participants, 84 (62%) enrolled in the study. Preliminary analysis indicated 65% retention at 8-week follow-up. Participants were primarily Hispanic/Latinx (47%), 71% had 2-year college or more education, 45% reported income below federal poverty thresholds, and 36% reported qualifying for public assistance. Program acceptability varied by group with weekly median sensor use of 1 day/wk (Level 1), 2 days/wk (Level 2) and 3 days/wk (Level 3). Good-to-high program enjoyment was reported by 90% of Level 3 and 83% of Level 2 participants. Conclusions: This pilot study demonstrates that a livestream group-based or video-based exercise program is feasible and acceptable in sedentary adults. A randomized controlled trial investigating health-related outcomes using this mHealth program is warranted.
Cancer Needs a Robust “Metadata Supply Chain” to Realize the Promise of Artificial Intelligence
Authors: Caroline Chung, David A. Jaffray
Journal: Cancer Research (2021)

Abstract Profound advances in computational methods, including artificial intelligence (AI), present the opportunity to use the exponentially growing volume and complexity of available cancer measurements toward data-driven personalized care. While exciting, this opportunity has highlighted the disconnect between the promise of compute and the supply of high-quality data. The current paradigm of ad-hoc aggregation and curation of data needs to be replaced with a “metadata supply chain” that provides robust data in context with known provenance, that is, lineage and comprehensive data governance that will allow the promise of AI technology to be realized to its full potential in clinical practice.
Afatinib and Pembrolizumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (ALPHA Study): A Phase II Study with Biomarker Analysis
Authors: Hsiang-Fong Kao, Bin-Chi Liao, Yen-Lin Huang, Huai-Cheng Huang, Chun-Nan Chen, Tseng-Cheng Chen, Yuan-Jing Hong, Ching-Yi Chan, Jean-San Chia, Ruey-Long Hong
Journal: Clinical Cancer Research (2022)

Abstract Purpose: EGFR pathway inhibition may promote anti–programmed cell death protein 1 (PD-1) responses in preclinical models, but how EGFR inhibition affects tumor antigen presentation during anti–PD-1 monotherapy in humans remain unknown. We hypothesized that afatinib, an irreversible EGFR tyrosine kinase inhibitor, would improve outcomes in patients treated with pembrolizumab for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) by promoting antigen presentation and immune activation in the tumor microenvironment. Patients and Methods: The ALPHA study (NCT03695510) was a single-arm, Phase II study with Simon's 2-stage design. Afatinib and pembrolizumab were administered to patients with platinum-refractory, recurrent, or metastatic HNSCC. The primary endpoint was the objective response rate (ORR). The study applied gene expression analysis using a NanoString PanCancer Immune Profiling Panel and next-generation sequencing using FoundationOne CDx. Results: From January 2019 to March 2020, the study enrolled 29 eligible patients. Common treatment-related adverse events were skin rash (75.9%), diarrhea (58.6%), and paronychia (44.8%). Twelve patients (41.4%) had an objective partial response to treatment. The median progression-free survival was 4.1 months, and the median overall survival was 8.9 months. In a paired tissue analysis, afatinib–pembrolizumab were found to upregulate genes involved in antigen presentation, immune activation, and natural killer cell–mediated cytotoxicity. Unaltered methylthioadenosine phosphorylase and EGFR amplification may predict the clinical response to the therapy. Conclusions: Afatinib may augment pembrolizumab therapy and improve the ORR in patients with HNSCC. Bioinformatics analysis suggested the enhancement of antigen presentation machinery in the tumor microenvironment.
Abstract 048: Changes In Bile Acid Metabolism, Circulating MicroRNA-34a, And Improvements In Lipid Profiles In Response To Weight-loss Diets: The Pounds Lost Trial
Authors: Yoriko Heianza, Qiaochu Xue, Jennifer Rood, Clary Clish, George Bray, Frank Sacks, Lu Qi
Journal: Circulation (2022)

Background: Bile acids are synthesized from cholesterol in the liver and play pivotal roles in nutrient absorption and metabolic regulation. Altered bile acid metabolism is related to dyslipidemia, and microRNA-34a (miR-34a) may play a pivotal role in the treatment of lipid homeostasis by regulating the bile acid biosynthesis. Hypothesis: We investigated whether weight-loss diet-induced changes in primary and secondary bile acids were associated with the improvements in lipid profiles. We also tested the role of circulating miR-34a in the altered bile acid metabolism in adults with overweight and obesity. Methods: A total of 520 participants of a weight-loss dietary intervention (the POUNDS Lost trial) with data on bile acids and miR-34a were included in the present analysis. Circulating levels of miR-34a and bile acid subtypes (primary and secondary unconjugated bile acids and their taurine-/glycine-conjugates) were measured at baseline and 6 months after the intervention. Outcome measurements were improvements in lipids (triglycerides and cholesterol) in response to the interventions. Results: At baseline, higher levels of primary bile acids (chenodeoxycholate (CDCA), glycocholate (GCA), taurocholate (TCA), and glycochenodeoxycholate (GCDCA) were associated with elevated levels of triglycerides ( P FDR &lt;0.05). Greater decreases in the primary bile acid subtypes (CDCA, GCA, TCA, GCDCA, and taurochenodeoxycholate [TCDCA]) in response to the interventions were significantly associated with larger reductions of triglycerides at 6 months ( P FDR &lt;0.05 for all). Decreases in secondary bile acids (deoxycholate and its conjugated forms) also showed significant associations with decreases in triglycerides. Similarly, reductions of total cholesterol at 6 months were associated with decreases in the primary (such as GCA, GCDCA, TCDCA) and secondary bile acid subtypes. We found that greater levels of miR-34a at baseline were related to higher levels of triglycerides at baseline (p=0.038) and higher levels of primary bile acids (such as CA, CDCA, GCA, and TCA [PFDR &lt;0.05 for all]) but not with the secondary bile acids at baseline. Further, weight-loss diet-induced changes in miR-34a were positively correlated with changes in the primary bile acid subtypes (CDCA, GCA, and GCDCA). Conclusions: Changes in the specific primary and secondary bile acid subtypes were related to the improvements in lipid profiles in response to weight-loss diet interventions. Circulating miR-34a might in part contribute to the alterations in the primary bile acid subtypes in obese adults.
Phase II Trial of Ixazomib and Dexamethasone Versus Ixazomib, Dexamethasone and Lenalidomide, Randomized with NFKB2 Rearrangement. (Proteasome Inhibitor NFKB2 Rearrangement Driven Trial, PINR)
Authors: Leon Bernal-Mizrachi, Ajay K. Nooka, Leonard Heffner, Craig E. Cole, Jing C. Ye, Ravi Vij, Craig C. Hofmeister, John Rushton, Zhengjia Chen, Subir Goyal, Jeffrey M. Switchenko, Sagar Lonial, Jonathan L. Kaufman
Journal: Blood (2021)
The HIV-1 proviral landscape reveals that Nef contributes to HIV-1 persistence in effector memory CD4+ T cells
Authors: Gabriel Duette, Bonnie Hiener, Hannah Morgan, Fernando G. Mazur, Vennila Mathivanan, Bethany A. Horsburgh, Katie Fisher, Orion Tong, Eunok Lee, Haelee Ahn, Ansari Shaik, Rémi Fromentin, Rebecca Hoh, Charline Bacchus-Souffan, Najla Nasr, Anthony L. Cunningham, Peter W. Hunt, Nicolas Chomont, Stuart G. Turville, Steven G. Deeks, Anthony D. Kelleher, Timothy E. Schlub, Sarah Palmer
Journal: Journal of Clinical Investigation (2022)

Despite long-term antiretroviral therapy (ART), HIV-1 persists within a reservoir of CD4+ T cells that contribute to viral rebound if treatment is interrupted. Identifying the cellular populations that contribute to the HIV-1 reservoir and understanding the mechanisms of viral persistence are necessary to achieve an effective cure. In this regard, through Full-Length Individual Proviral Sequencing, we observed that the HIV-1 proviral landscape was different and changed with time on ART across naive and memory CD4+ T cell subsets isolated from 24 participants. We found that the proportion of genetically intact HIV-1 proviruses was higher and persisted over time in effector memory CD4+ T cells when compared with naive, central, and transitional memory CD4+ T cells. Interestingly, we found that escape mutations remained stable over time within effector memory T cells during therapy. Finally, we provided evidence that Nef plays a role in the persistence of genetically intact HIV-1. These findings posit effector memory T cells as a key component of the HIV-1 reservoir and suggest Nef as an attractive therapeutic target.
Abstract P222: The Psychological Predictors Of Recovery After Acute Cardiac Events Study: Rationale And Design
Authors: Danielle A Rojas, Michelle A David, Gaspar J Cruz, Alexandra M Sullivan, Cara L McMurry, Jeffrey Birk, Sachin Agarwal
Journal: Circulation (2022)

Objective: To estimate the prospective association of cardiac anxiety at cardiac arrest (CA) discharge with subsequent risk for cardiovascular disease (CVD)/mortality after adjusting for general psychological distress and test its independent association with health-related quality of life (HRQoL). Our second objective is to test whether cardiac anxiety after CA is associated with low physical activity (PA) and/or short sleep shortly after discharge. Our third objective will test if low PA and/or short sleep mediate the association between cardiac anxiety and 12-month CVD/mortality post-discharge for CA. Further, the study will test the associations of general psychological distress with cardiac vagal control assessed by activity-adjusted heart rate variability. Background: Survivorship after CA is on the rise. However, survivors remain at markedly elevated risk for CVD, and many report poor HRQoL in the year after CA. Cardiac anxiety (i.e., cardiac specific-fear, avoidance behavior, and excessive cardiac symptom monitoring) has been shown in non-CA CVD patients to be associated with higher rates of psychological distress, avoidance of PA and poor sleep, patient-reported disability, and poor perceived health. Further, despite the association of low PA and poor sleep in CVD risk, no study has assessed those health behaviors in CA survivors. Design/Methods: This observational cohort study (anticipated n = 246) will evaluate CVD prognosis, HRQoL in the first year of survivorship of neurologically intact CA survivors admitted to New York Presbyterian Hospital between May 2021 and April 2026. At hospital discharge, 1, 6, and 12 months, study participants will be assessed for cardiac anxiety, and general psychological distress (screening measures for depression, posttraumatic stress, generalized anxiety symptoms), positive psychological factors (optimism, positive affect, purpose in life), functional (modified Rankin Scale) and telephone-based cognitive assessments. For 1-week post-discharge, and 1 week at 6-months post-discharge we will assess the level of PA and sleep duration using wrist-worn actigraphy, daily psychological factors using mobile ecological momentary assessment, and heart rate/heart rate variability using chest-worn patches. Results: Of the 21 patients enrolled to date (mean age 57 years, 10 women). The presentation will describe patterns of physical activity, sleep, both negative and positive psychological factors at 1-month post-discharge relative to discharge status. Conclusions: This is the first major prospective cohort study of CA survivorship, and the first to objectively assess health behaviors. By identifying malleable intervention targets for improving both CVD/mortality risk and post-CA HRQoL, this study could ignite the development of the first generation of CA survivorship interventions.
Inhibitor screening using microarray identifies the high capacity of neutralizing antibodies to Spike variants in SARS-CoV-2 infection and vaccination
Authors: Xiaomei Zhang, Mei Zheng, Hongye Wang, Haijian Zhou, Te Liang, Jiahui Zhang, Jing Ren, Huoying Peng, Siping Li, Haodong Bian, Chundi Wei, Shangqi Yin, Chaonan He, Ying Han, Minghui Li, Xuexin Hou, Jie Zhang, Liangzhi Xie, Jing Lv, Biao Kan, Yajie Wang, Xiaobo Yu
Journal: Theranostics (2022)

Rationale: Mutations of SARS-CoV-2, which is responsible for coronavirus disease 2019 (COVID-19), could impede drug development and reduce the efficacy of COVID-19 vaccines.Here, we developed a multiplexed Spike-ACE2 Inhibitor Screening (mSAIS) assay that can measure the neutralizing effect of antibodies across numerous variants of the coronavirus's Spike (S) protein simultaneously.Methods: The SARS-CoV-2 spike variant protein microarrays were prepared by printing 72 S variants onto a chemically-modified glass slides.The neutralization potential of purified anti-S antibodies and serum from convalescent COVID-19 patients and vaccinees to S variants were assessed with the mSAIS assay. Results:We identified new S mutations that are sensitive and resistant to neutralization.Serum from both infected and vaccinated groups with a high titer of neutralizing antibodies (NAbs) displayed a broader capacity to neutralize S variants than serum with low titer NAbs.These data were validated using serum from a large vaccinated cohort (n = 104) with a tiled S peptide microarray.In addition, similar results were obtained using a SARS-CoV-2 pseudovirus neutralization assay specific for wild-type S and five prevalent S variants (D614G, B.1.1.7,B.1.351,P.1, B.1.617.2),thus demonstrating that high antibody diversity is associated with high NAb titers.Conclusions: Our results demonstrate the utility of the mSAIS platform in screening NAbs.Moreover, we show that heterogeneous antibody populations provide a more protective effect against S variants, which may help direct COVID-19 vaccine and drug development.
Population Immunity and Covid-19 Severity with Omicron Variant in South Africa
Authors: Shabir A. Madhi, Gaurav Kwatra, Jonathan E. Myers, Waasila Jassat, Nisha Dhar, Christian K. Mukendi, Amit J. Nana, Lucille Blumberg, Richard Welch, Nicoletta Ngorima-Mabhena, Portia C. Mutevedzi
Journal: New England Journal of Medicine (2022)

The B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified on November 25, 2021, in Gauteng province, South Africa. Data regarding the seroprevalence of SARS-CoV-2 IgG in Gauteng before the fourth wave of coronavirus disease 2019 (Covid-19), in which the omicron variant was dominant, are needed.
The potential and challenges of radiomics in uncovering prognostic and molecular differences in interstitial lung disease associated with systemic sclerosis
Authors: Lu Zhang, Jieling Zheng, Zhe Jin, Qiuying Chen, Shuyi Liu, Bin Zhang
Journal: European Respiratory Journal (2022)

<b>The radiomic risk score is promising but challenging in the evaluation of prognostic and molecular differences in interstitial lung disease associated with systemic sclerosis.</b>https://bit.ly/3oWg4UO