tbuckley/cabot-search huggingface dataset:
Myeloid‐Cell–Specific IL‐6 Signaling Promotes MicroRNA‐223‐Enriched Exosome Production to Attenuate NAFLD‐Associated Fibrosis
Authors: Xin Hou, Shi Yin, Ruixue Ren, Siqi Liu, Liang Yong, Yuxiao Liu, Yu Li, Ming‐Hua Zheng, George Kunos, Bin Gao, Hua Wang
Journal: Hepatology (2020)

Background ands Aims NAFLD is associated with elevation of many cytokines, particularly IL‐6; however, the role of IL‐6 in NAFLD remains obscure. The aim of this study was to examine how myeloid‐specific IL‐6 signaling affects NAFLD by the regulation of antifibrotic microRNA‐223 (miR‐223) in myeloid cells. Approach and Results Patients with NAFLD or NASH and healthy controls were recruited, and serum IL‐6 and soluble IL‐6 receptor α (sIL‐6Rα) were measured. Compared to controls, serum IL‐6 and sIL‐6Rα levels were elevated in NAFLD/NASH patients. IL‐6 levels correlated positively with the number of circulating leukocytes and monocytes. The role of IL‐6 in NAFLD was investigated in Il6 knockout (KO) and Il6 receptor A ( Il6ra ) conditional KO mice after high‐fat diet (HFD) feeding. HFD‐fed Il6 KO mice had worse liver injury and fibrosis, but less inflammation, compared to wild‐type mice. Hepatocyte‐specific Il6ra KO mice had more steatosis and liver injury, whereas myeloid‐specific Il6ra KO mice had a lower number of hepatic infiltrating macrophages (IMs) and neutrophils with increased cell death of these cells, but greater liver fibrosis (LF), than WT mice. Mechanistically, the increased LF in HFD‐fed, myeloid‐specific Il6ra KO mice was attributable to the reduction of antifibrotic miR‐223 and subsequent up‐regulation of the miR‐223 target gene, transcriptional activator with PDZ‐binding motif (TAZ), a well‐known factor to promote NASH fibrosis. In vitro , IL‐6 treatment up‐regulated exosome biogenesis‐related genes and subsequently promoted macrophages to release miR‐223‐enriched exosomes that were able to reduce profibrotic TAZ expression in hepatocytes by exosomal transfer. Finally, serum IL‐6 and miR‐223 levels were elevated and correlated with each other in NAFLD patients. Conclusions Myeloid‐specific IL‐6 signaling inhibits LF through exosomal transfer of antifibrotic miR‐223 into hepatocytes, providing therapeutic targets for NAFLD therapy.
Use of Chimeric Antigen Receptor Modified T Cells With Extensive Leukemic Myocardial Involvement
Authors: Brian Han, Raul Montiel-Esparza, Henry Chubb, Saraswati Kache, Liora M. Schultz, Kara L. Davis, Sneha Ramakrishna, Lillian Su
Journal: JACC CardioOncology (2020)
肺高血圧症(PH)患者におけるC-11酢酸PETによる心筋エネルギー評価に関する強化PH療法の効果
Authors: Yoshinaga Keiichiro, Ohhira Hiroshi, Tsujino Ichizo, Manabe Osamu, Katoh Chietsugu, Kasai Katsuhiko, Tomiyama Yuuki, Satoh Takahiro, Oyama-Manabe Noriko, Nishimura Masaharu, Tamaki Nagara
Journal: Circulation (2014)
Non-surgical and surgical treatments for rotator cuff disease: a pragmatic randomised clinical trial with 2-year follow-up after initial rehabilitation
Authors: Sanna Cederqvist, Tapio Flinkkilä, Markus Sormaala, Jari Ylinen, Hannu Kautiainen, Tero Irmola, Heidi Lehtokangas, Juho Liukkonen, Konsta Pamilo, Tero Ridanpää, Kai Sirniö, Juhana Leppilahti, Ilkka Kiviranta, Juha Paloneva
Journal: Annals of the Rheumatic Diseases (2020)

Background Rotator cuff disease (RCD) causes prolonged shoulder pain and disability in adults. RCD is a continuum ranging from tendinopathy to full-thickness tendon tear. Recent studies have shown that subacromial decompression and non-surgical treatments provide equivalent results in RCD without a full-thickness tendon lesion. However, the importance of surgery for full-thickness tendon tears remains unclear. Methods In a pragmatic, randomised, controlled trial, 417 patients with subacromial pain underwent 3-month initial rehabilitation and MRI arthrography (MRA) for the diagnosis of RCD. Of these, 190 shoulders remained symptomatic and were randomised to non-surgical or surgical treatments. The primary outcomes were the mean changes in the Visual Analogue Scale for pain and the Constant Murley Score for shoulder function at the 2-year follow-up. Results At the 2-year follow-up, both non-surgical and surgical treatments for RCD reduced pain and improved shoulder function. The scores differed between groups by 4 (95% CI −3 to 10, p=0.25) for pain and 3.4 (95% CI −0.4 to 7.1, p=0.077) for function. Among patients with full-thickness ruptures, the reduction in pain (13, 95% CI 5 to 22, p=0.002) and improvement in function (7.0, 95% CI 1.8 to 12.2, p=0.008) favoured surgery. Conclusions Non-surgical and surgical treatments for RCD provided equivalent improvements in pain and function. Therefore, we recommend non-surgical treatment as the primary choice for patients with RCD. However, surgery yielded superior improvement in pain and function for full-thickness rotator cuff rupture. Therefore, rotator cuff repair may be suggested after failed non-surgical treatment. Trial registration details ClinicalTrials.gov, NCT00695981 and NCT00637013 .
Mortality Prediction by Quantitative PET Perfusion Expressed as Coronary Flow Capacity With and Without Revascularization
Authors: K. Lance Gould, Danai Kitkungvan, Nils P. Johnson, Tung Nguyen, Richard Kirkeeide, Linh Bui, Monica B. Patel, Amanda E. Roby, Mohammad Madjid, Hongjian Zhu, Dejian Lai
Journal: JACC. Cardiovascular imaging (2020)

This study sought to determine the relationship between the severity of reduced quantitative perfusion parameters and mortality with and without revascularization.The physiological mechanisms for differential mortality risk of coronary flow reserve (CFR) and coronary flow capacity (CFC) before and after revascularization are unknown.Global and regional rest-stress (ml/min/g), CFR, their regional per-pixel combination as CFC, and relative stress in ml/min/g were measured as percent of LV in all serial routine 5,274 diagnostic PET scans with systematic follow-up over 10 years (mean 4.2 ± 2.5 years) for all-cause mortality with and without revascularization.Severely reduced CFR of 1.0 to 1.5 and stress perfusion ≤1.0 cc/min/g incurred increasing size-dependent risks that were additive because regional severely reduced CFC (CFCsevere) was associated with the highest major adverse cardiac event rate of 80% (p < 0.0001 vs. either alone) and a mortality risk of 14% (vs. 2.3% for no CFCsevere; p = 0.001). Small regions of CFCsevere ≤0.5% predicted high risk (p < 0.0001 vs. no CFCsevere) related to a wave front of border zones at risk around the small most severe center. By receiver-operating characteristic analysis, relative stress topogram maps of stress (ml/min/g) as a fraction of LV defined these border zones at risk or for mildly reduced CFC (area under the curve [AUC]: 0.69) with a reduced relative tomographic subendocardial-to-subepicardial ratio. CFCsevere incurred the highest mortality risk that was reduced by revascularization (p = 0.005 vs. no revascularization) for artery-specific stenosis not defined by global CFR or stress perfusion alone.CFC is associated with the size-dependent highest mortality risk resulting from the additive risk of CFR and stress (ml/min/g) that is significantly reduced after revascularization, a finding not seen for global CFR. Small regions of CFCsevere ≤0.5% of LV also carry a high risk because of the surrounding border zones at risk defined by relative stress perfusion and a reduced relative subendocardial-to-subepicardial ratio.
How Will Patients With Cancer Fare During COVID-19?
Authors: Beth A. Virnig, Sayeh S. Nikpay
Journal: JAMA Oncology (2020)

Andrew Hantel, MD; Jonathan M. Marron, MD, MPH; Michael Casey, APRN-BC, FNP; Sharyn Kurtz, PA-C, MPAS, MA; Emily Magnavita, MPH; Gregory A. Abel, MD, MPH
156P Safety and feasibility of laparoscopic spleen-preserving splenic hilar lymphadenectomy during total gastrectomy for advanced proximal gastric cancer: A randomized clinical trial
Authors: J-X. Lin, J-P. Lin, L-Q. Wang, C-H. Zheng, P. Li, J-W. Xie, J-B. Wang, J. Lu, Q-Y. Chen, L-L. Cao, M. Lin, R-H. Tu, Z-N. Huang, J-L. Lin, H-L. Zheng, C. Huang
Journal: Annals of Oncology (2020)
275P Weekly paclitaxel, carboplatin and cetuximab (PCC) combination followed by nivolumab in platinum-sensitive recurrent and /or metastatic squamous cell carcinoma of head and neck: A double institution retrospective analysis from India
Authors: V. Agarwala, M.V. Chandrakanth, P.K. Mondal, R. Chanana
Journal: Annals of Oncology (2020)
Triglyceride-rich lipoprotein remnant levels and metabolism: Time to adopt these orphan risk factors?**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Eliot A Brinton, M.Nazeem Nanjee, Paul N Hopkins
Journal: Journal of the American College of Cardiology (2004)
Topographic heterogeneity of lung microbiota in end-stage idiopathic pulmonary fibrosis: the Microbiome in Lung Explants-2 (MiLEs-2) study
Authors: Eleanor Valenzi, Haopu Yang, John C Sembrat, Libing Yang, Spencer Winters, Rachel Nettles, Daniel J Kass, Shulin Qin, Xiaohong Wang, Michael M Myerburg, Barbara Methé, Adam Fitch, Jonathan K Alder, Panayiotis V Benos, Bryan J McVerry, Mauricio Rojas, Alison Morris, Georgios D Kitsios
Journal: Thorax (2020)

Background Lung microbiota profiles in patients with early idiopathic pulmonary fibrosis (IPF) have been associated with disease progression; however, the topographic heterogeneity of lung microbiota and their roles in advanced IPF are unknown. Methods We performed a retrospective, case-control study of explanted lung tissue obtained at the time of lung transplantation or rapid autopsy from patients with IPF and other chronic lung diseases (connective tissue disease-associated interstitial lung disease (CTD-ILD), cystic fibrosis (CF), COPD and donor lungs unsuitable for transplant from Center for Organ Recovery and Education (CORE)). We sampled subpleural tissue and airway-based specimens (bronchial washings and airway tissue) and quantified bacterial load and profiled communities by amplification and sequencing of the 16S rRNA gene. Findings Explants from 62 patients with IPF, 15 patients with CTD-ILD, 20 patients with CF, 20 patients with COPD and 20 CORE patients were included. Airway-based samples had higher bacterial load compared with distal parenchymal tissue. IPF basilar tissue had much lower bacterial load compared with CF and CORE lungs (p&lt;0.001). No microbial community differences were found between parenchymal tissue samples from different IPF lobes. Dirichlet multinomial models revealed an IPF cluster (29%) with distinct composition, high bacterial load and low alpha diversity, exhibiting higher odds for acute exacerbation or death. Interpretation IPF explants had low biomass in the distal parenchyma of all three lobes with higher bacterial load in the airways. The discovery of a distinct subgroup of patients with IPF with higher bacterial load and worse clinical outcomes supports investigation of personalised medicine approaches for microbiome-targeted interventions.
Abstract PO-057: Breast cancer cell metabolism: Effect of beta-hydroxybutyrate on glucose deprived breast cancer cells
Authors: Rylee Maldonado, Chloe Adrienna Talana, Kahealani Uehara, Michael Weichhaus
Journal: Cancer Research (2020)

Abstract Ketogenic diets have the potential to lower glucose availability to cancer cells. The effect that the resulting increase in ketone bodies has on cancer cells is not fully understood. Here we explored the effect of beta-hydroxybutyrate (BHB) on glucose deprived MCF-7 and T47D breast cancer cells. Cell proliferation was decreased with lower glucose conditions which could not be rescued by either 10 mM or 25 mM BHB supplementation. Gene expression changes were altered when cells were glucose deprived. Smaller changes were observed when gene expression changes were compared between glucose deprived cells and those treated with BHB. Pathway enrichment analysis demonstrated that glucose deprivation decreased activity of the Hippo-Yap cell signaling pathway in MCF-7 breast cancer cells, while it increased expression of genes of the NRF2-pathawy and genes regulating ferroptosis in T47D breast cancer cells. No significant pathway enrichment was found when glucose deprived cells were treated with BHB. Both cell lines expressed the enzymes (OXCT1/2, BDH1, ACAT1/2) responsible for metabolizing BHB to acetyl-CoA, yet expression of these enzymes does not change with either glucose deprivation or BHB treatment. In the publicly available Cancer Genome Atlas increased expression compared to healthy tissue of enzymes responsible for metabolizing BHB to acetyl-CoA was also observed, however only a small subset of patients showed alterations in these enzymes. This alteration was linked to a significant decrease in overall survival. In conclusion, neither MCF-7 nor T47D breast cancer cells were affected by BHB during glucose deprivation, however screening of the patient’s tumor for activation of ketone bodies metabolizing enzymes may be indicated to identify who will benefit from ketogenic diet interventions. Citation Format: Rylee Maldonado, Chloe Adrienna Talana, Kahealani Uehara, Michael Weichhaus. Breast cancer cell metabolism: Effect of beta-hydroxybutyrate on glucose deprived breast cancer cells [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-057.
Abstract 13915: Lifetime Cardiovascular Surgical and Percutaneous Interventions in Females With Turner Syndrome
Authors: Angela T Yetman, Megan Wilde, Lois Starr, Jennifer Sanmann, Mary Murray, Jonathan W Cramer
Journal: Circulation (2017)

Introduction: The reported prevalence of congenital heart defects (CHD) in females with Turner syndrome (TS) has been largely based on historical reports of patients evaluated prior to the advent o...
Eradication of T-ALL Cells by CD7-targeted Universal CAR-T Cells and Initial Test of Ruxolitinib-based CRS Management
Authors: Shiqi Li, Xinxin Wang, Zhongtao Yuan, Lin Liu, Le Luo, Yu Li, Kun Wu, Jia Liu, Chunhui Yang, Zhimin Li, Duanpeng Wang, Lianjun Shen, Xun Ye, Jiaping He, Cong Han, Youcheng Wang, Dingsong Zhang, Yancheng Dong, Lihua Fang, Yingnian Chen, Martina Sersch, Wei William Cao, Sanbin Wang
Journal: Clinical Cancer Research (2020)

Although chimeric antigen receptor T-cell (CAR-T) therapy development for B-cell malignancies has made significant progress in the last decade, broadening the success to treating T-cell acute lymphoblastic leukemia (T-ALL) has been limited. We conducted two clinical trials to verify the safety and efficacy of GC027, an "off-the-shelf" allogeneic CAR-T product targeting T-cell antigen, CD7. Here, we report 2 patients as case reports with relapsed/refractory T-ALL who were treated with GC027.Both the trials reported here were open-label and single-arm. A single infusion of GC027 was given to each patient after preconditioning therapy.Robust expansion of CAR-T cells along with rapid eradication of CD7+ T lymphoblasts were observed in the peripheral blood, bone marrow, and cerebrospinal fluid. Both patients achieved complete remission with no detectable minimal residual disease. At data cutoff, 30 September 2020, 1 of the 2 patients remains in ongoing remission for over 1 year after CAR T-cell infusion. Grade 3 cytokine release syndrome (CRS) occurred in both patients and was managed by a novel approach with a ruxolitinib-based CRS management. Ruxolitinib showed promising activity in a preclinical study conducted at our center. No graft-versus-host disease was observed.The two case reports demonstrate that a standalone therapy with this novel CD7-targeted "off-the-shelf" allogeneic CAR-T therapy may provide deep and durable responses in select patients with relapsed/refractory T-ALL. GC027 might have a potential to be a promising new approach for treating refractory/relapsed T-ALL. Further studies are warranted.
Abstract PO-019: DNA methylation status in a promoter region of the <i>K-RAS</i> gene in patients with Colorectal Cancer
Authors: Jehison Alirio Herrera-Pulido, Orlando Ricaurte-Guerrero, Jinneth Acosta-Forero, Pablo Moreno-Acosta, María Carolina Sanabria-Salas, Humberto Arboleda-Granados, Gustavo Hernández, Martha Lucía Serrano-López
Journal: Cancer Research (2020)

Abstract Background: DNA methylation plays an important role in colorectal cancer (CRC) carcinogenesis. The mutated K-RAS gene has been reported to be crucial in CRC progression, but it is not known whether the wild-type gene is regulated by methylation and whether or not this mechanism contributes to disease progression. Now, there are not known reports about the methylation status of the distal K-RAS gene promoter in patients diagnosed with CRC. Materials and methods: Fifty-seven formalin-fixed, paraffin-embedded (FFPE) tissue samples from 57 patients diagnosed with CRC, without K-RAS mutation, were analyzed to determine the methylation status of the distal promoter of this gene. The analysis was performed by DNA extraction from laser microdissections, and 2 mm diameter punch, conversion with sodium bisulfite, amplification by nested PCR, and direct sequencing of purified PCR products. Results: Of the 57 cases, in 2 (6.25%) partial methylation was found in island 2 for one of the cases and in islands 1 and 2 for the other. In 30 (93.75%) cases no methylation was found and in the remaining 25 (43.85%) cases methylation could not be determined, probably due to the quantity and quality of DNA extracted from these blocks. Conclusion: The results found from the preliminary analysis of the methylation status of a region of the distal promoter of the K-RAS gene that serves as an anchorage to Sp1, allowed to determine a partial methylation status in 6.25% of the cases studied, concluding that methylation in this region is not a frequent event Citation Format: Jehison Alirio Herrera-Pulido, Orlando Ricaurte-Guerrero, Jinneth Acosta-Forero, Pablo Moreno-Acosta, María Carolina Sanabria-Salas, Humberto Arboleda-Granados, Gustavo Hernández, Martha Lucía Serrano-López. DNA methylation status in a promoter region of the K-RAS gene in patients with Colorectal Cancer [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-019.
ADMAring Endothelial Progenitor Cells: Accident, Association, or Antecedent**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Gajen Kanaganayagam, Michael S. Marber
Journal: Journal of the American College of Cardiology (2005)
COVID-19 Severity Is Tripled in the Diabetes Community: A Prospective Analysis of the Pandemic’s Impact in Type 1 and Type 2 Diabetes
Authors: Justin M. Gregory, James C. Slaughter, Sara H. Duffus, T. Jordan Smith, Lauren M. LeStourgeon, Sarah S. Jaser, Allison B. McCoy, James M. Luther, Erin R. Giovannetti, Schafer Boeder, Jeremy H. Pettus, Daniel J. Moore
Journal: Diabetes Care (2020)

To quantify and contextualize the risk for coronavirus disease 2019 (COVID-19)-related hospitalization and illness severity in type 1 diabetes.
Transcriptomic and Proteomic Analysis of Mannitol-Metabolism-Associated Genes in <i>Saccharina Japonica</i>
Authors: Shan Chi, Guoliang Wang, Tao Liu, Xumin Wang, Cui Liu, Yuemei Jin, Hongxin Yin, Xin Xu, Jun Yu
Journal: Genomics Proteomics & Bioinformatics (2020)

As a carbon-storage compound and osmoprotectant in brown algae, mannitol is synthesized and then accumulated at high levels in Saccharina japonica (Sja); however, the underlying control mechanisms have not been studied. Our analysis of genomic and transcriptomic data from Sja shows that mannitol metabolism is a cyclic pathway composed of four distinct steps. A mannitol-1-phosphate dehydrogenase (M1PDH2) and two mannitol-1-phosphatases (M1Pase1 and MIPase2) work together or in combination to exhibit full enzymatic properties. Based on comprehensive transcriptomic data from different tissues, generations, and sexes as well as under different stress conditions, coupled with droplet digital PCR (ddPCR) and proteomic confirmation, we suggest that SjaM1Pase1 plays a major role in mannitol biosynthesis and that the basic mannitol anabolism and the carbohydrate pool dynamics are responsible for carbon storage and anti-stress mechanism. Our proteomic data indicate that mannitol metabolism remains constant during diurnal cycle in Sja. In addition, we discover that mannitol-metabolism-associated (MMA) genes show differential expression between the multicellular filamentous (gametophyte) and large parenchymal thallus (sporophyte) generations and respond differentially to environmental stresses, such as hyposaline and hyperthermia conditions. Our results indicate that the ecophysiological significance of such differentially expressed genes may be attributable to the evolution of heteromorphic generations (filamentous and thallus) and environmental adaptation of Laminariales.
Predicting drug release and degradation kinetics of long-acting microsphere formulations of tacrolimus for subcutaneous injection
Authors: Ge Fiona Gao, Mukul Ashtikar, Ryo Kojima, Takatsune Yoshida, Masanori Kaihara, Tomokazu Tajiri, Saeed Shanehsazzadeh, Harshvardhan Modh, Matthias G. Wacker
Journal: Journal of Controlled Release (2020)
Poor Survival and Differential Impact of Genetic Features of Black Patients with Acute Myeloid Leukemia
Authors: Bhavana Bhatnagar, Jessica Kohlschmidt, Krzysztof Mrózek, Qiuhong Zhao, James L. Fisher, Deedra Nicolet, Christopher J. Walker, Alice S. Mims, Christopher Oakes, Brian Giacopelli, Shelley Orwick, Isaiah Boateng, James S. Blachly, Sophia E. Maharry, Andrew J. Carroll, Bayard L. Powell, Jonathan E. Kolitz, Richard M. Stone, John C. Byrd, Electra D. Paskett, Albert de la Chapelle, Ramiro Garzon, Ann-Kathrin Eisfeld
Journal: Cancer Discovery (2020)

Clinical outcome of patients with acute myeloid leukemia (AML) is associated with cytogenetic and molecular factors and patient demographics (e.g., age and race). We compared survival of 25,523 non-Hispanic Black and White adults with AML using Surveillance Epidemiology and End Results (SEER) Program data and performed mutational profiling of 1,339 patients with AML treated on frontline Alliance for Clinical Trials in Oncology (Alliance) protocols. Black patients had shorter survival than White patients, both in SEER and in the setting of Alliance clinical trials. The disparity was especially pronounced in Black patients <60 years, after adjustment for socioeconomic (SEER) and molecular (Alliance) factors. Black race was an independent prognosticator of poor survival. Gene mutation profiles showed fewer NPM1 and more IDH2 mutations in younger Black patients. Overall survival of younger Black patients was adversely affected by IDH2 mutations and FLT3-ITD, but, in contrast to White patients, was not improved by NPM1 mutations. SIGNIFICANCE: We show that young Black patients have not benefited as much as White patients from recent progress in AML treatment in the United States. Our data suggest that both socioeconomic factors and differences in disease biology contribute to the survival disparity and need to be urgently addressed.See related commentary by Vyas, p. 540.This article is highlighted in the In This Issue feature, p. 521.
17790 M89, a dermocosmetic combining 89% Vichy mineralizing water and hyaluronic acid, does not modify ex vivo the cutaneous penetration of topical ivermectin
Authors: Jerry Tan, Emilie Raynaud, Noémie Merle, Ingrid Durand, Sebastien Gregoire, Laurène Roussel, Delphine Kerob
Journal: Journal of the American Academy of Dermatology (2020)