tbuckley/cabot-search huggingface dataset:
Mydgf promotes Cardiomyocyte proliferation and Neonatal Heart regeneration
Authors: Yuyao Wang, Yan Li, Jie Feng, Weijing Liu, Yandong Li, Jun Liu, Qianqian Yin, Hong Lian, Lihui Liu, Yu Nie
Journal: Theranostics (2020)

Myeloid-derived growth factor (Mydgf), a paracrine protein secreted by bone marrow-derived monocytes and macrophages, was found to protect against cardiac injury following myocardial infarction (MI) in adult mice. We speculated that Mydgf might improve heart function via myocardial regeneration, which is essential for discovering the target to reverse heart failure. Methods: Two genetic mouse lines were used: global Mydgf knockout (Mydgf-KO) and Mydgf-EGFP mice. Two models of cardiac injury, apical resection was performed in neonatal and MI was performed in adult mice. Quantitative reverse transcription-polymerase chain reaction, western blot and flow cytometry were performed to study the protein expression. Immunofluorescence was performed to detect the proliferation of cardiomyocytes. Heart regeneration and cardiac function were evaluated by Masson's staining and echocardiography, respectively. RNA sequencing was employed to identify the key involved in Mydgf-induced cardiomyocyte proliferation. Mydgf recombinant protein injection was performed as a therapy for cardiac repair post MI in adult mice. Results: Mydgf expression could be significantly induced in neonatal mouse hearts after cardiac injury. Unexpectedly, we found that Mydgf was predominantly expressed by endothelial cells rather than macrophages in injured neonatal hearts. Mydgf deficiency impeded neonatal heart regeneration and injury-induced cardiomyocyte proliferation. Mydgf recombinant protein promoted primary mouse cardiomyocyte proliferation. Employing RNA sequencing and functional verification, we demonstrated that c-Myc/FoxM1 pathway mediated Mydgf-induced cardiomyocyte expansion. Mydgf recombinant protein improved cardiac function in adult mice after MI injury with inducing cardiomyocyte proliferation. Conclusion: Mydgf promotes cardiomyocyte proliferation by activating c-Myc/FoxM1 pathway and improves heart regeneration both in neonatal and adult mice after cardiac injury, providing a potential target to reverse cardiac remodeling and heart failure.
Cancer and Leukemia Group B 90203 (Alliance): Radical Prostatectomy With or Without Neoadjuvant Chemohormonal Therapy in Localized, High-Risk Prostate Cancer
Authors: James A. Eastham, Glenn Heller, Susan Halabi, J. Paul Monk, Himisha Beltran, Martin Gleave, Christopher P. Evans, Steven K. Clinton, Russell Z. Szmulewitz, Jonathan Coleman, David W. Hillman, Colleen R. Watt, Saby George, Martin G. Sanda, Olwen M. Hahn, Mary-Ellen Taplin, J. Kellogg Parsons, James L. Mohler, Eric J. Small, Michael J. Morris
Journal: Journal of Clinical Oncology (2020)

PURPOSE Radical prostatectomy (RP) alone is often inadequate in curing men with clinically localized, high-risk prostate cancer (PC). We hypothesized that chemohormonal therapy (CHT) with androgen-deprivation therapy plus docetaxel before RP would improve biochemical progression–free survival (BPFS) over RP alone. PATIENTS AND METHODS Men with clinically localized, high-risk PC were assigned to RP alone or neoadjuvant CHT with androgen deprivation plus docetaxel (75 mg/m 2 body surface area every 3 weeks for 6 cycles) and RP. The primary end point was 3-year BPFS. Biochemical failure was defined as a serum prostate-specific antigen level &gt; 0.2 ng/mL that increased on 2 consecutive occasions that were at least 3 months apart. Secondary end points included 5-year BPFS, overall BPFS, local recurrence, metastasis-free survival (MFS), PC-specific mortality, and overall survival (OS). RESULTS In total, 788 men were randomly assigned. Median follow-up time was 6.1 years. The overall rates of grade 3 and 4 adverse events during chemotherapy were 26% and 19%, respectively. No difference was seen in 3-year BPFS between neoadjuvant CHT plus RP and RP alone (0.89 v 0.84, respectively; 95% CI for the difference, −0.01 to 0.11; P = .11). Neoadjuvant CHT was associated with improved overall BPFS (hazard ratio [HR], 0.69; 95% CI, 0.48 to 0.99), improved MFS (HR, 0.70; 95% CI, 0.51 to 0.95), and improved OS (HR, 0.61; 95% CI, 0.40 to 0.94) compared with RP alone. CONCLUSION The primary study end point, 3-year BPFS, was not met. Although some improvement was seen in secondary end points, any potential benefit must be weighed against toxicity. Our data do not support the routine use of neoadjuvant CHT and RP in patients with clinically localized, high-risk PC at this time.
EZH2-mediated Epigenetic Silencing of miR-29/miR-30 targets LOXL4 and contributes to Tumorigenesis, Metastasis, and Immune Microenvironment Remodeling in Breast Cancer
Authors: Huilong Yin, Yidi Wang, Ye Wu, Xiang Zhang, Xiaofang Zhang, Jun Liu, Ting Wang, Jing Fan, Jianyong Sun, Angang Yang, Rui Zhang
Journal: Theranostics (2020)

Enhancer of Zeste Homolog 2 (EZH2), a key epigenetic regulator, is involved in breast cancer progression and metastasis. LOXL4 is increasingly recognized as an important player in cancer progression. To date, how EZH2 regulates LOXL4 in the progression of breast cancer remains unclear. Methods: We evaluated the association between LOX family proteins and EZH2 in invasive breast carcinoma through the starBase v2.0 analysis, and its correlation with breast tumorigenesis using the Oncomine dataset. We then applied miRcode data combined with gene expression omnibus (GEO) data to screen candidate miRNAs mediating the regulation of LOXL4 by EZH2. We explored the regulatory mechanism of EZH2, miR-29b/miR-30d, and LOXL4 in breast cancer cells by qRT-PCR, Western blotting, cell proliferation, colony formation, and wound healing assays, xenograft experiments, dual-luciferase reporter assay, and chromatin immunoprecipitation. All statistical tests were two-sided. Results: Inhibition of EZH2 or LOXL4, or miR-29b/miR-30d overexpression, decreased breast cancer cell proliferation, migration, and metastasis in vitro and in vivo. LOXL4 was identified as a direct target of miR-29b and miR-30d. EZH2 inhibition enhanced miR-30d and miR-29b transcription via promoter binding activity, leading to the reduced expression of LOXL4. Immunohistochemical analysis of human breast cancer specimens and flow cytometry analysis of tumor-infiltrating macrophages in mice showed a positive association of EZH2 with LOXL4 expression and macrophage infiltration. Conclusions: Our findings identified EZH2-miR-29b/miR-30d-LOXL4 signaling pathway was involved in breast tumorigenesis, and suggested that the epigenetic modulation represents a potential therapeutic target for breast cancer by controlling macrophage activation.
Psychopathological Networks in Cognitive-Behavioral Treatments for Binge-Eating Disorder
Authors: Anja Hilbert, Stephan Herpertz, Stephan Zipfel, Brunna Tuschen-Caffier, Hans-Christoph Friederich, Andreas Mayr, Martina de Zwaan
Journal: Psychotherapy and Psychosomatics (2020)

Network approaches to psychopathology posit that mental disorders emerge from interrelated symptoms, and thus connectivity among symptoms are assumed to negatively predict the treatment response and decrease with efficacious treatment.This study uniquely sought to elucidate the network structure, its change, and its predictive value in cognitive-behavioral therapy (CBT) for binge-eating disorder (BED).In a multicenter randomized trial of face-to-face and Internet-based guided self-help CBT, 178 individuals with full syndrome and subsyndromal BED, eating disorder and general psychopathology, and body mass index (BMI) were subjected to Gaussian Graphical Network and Exploratory Graph Analyses before and after treatment and at 6-month follow-up.At pretreatment, 3 network communities of: eating disorder psychopathology; general psychopathology; and restraint and BMI were identified, with the latter community included in the first thereafter. Eating disorder-related impairment and self-esteem were the most central symptoms, while BMI and binge eating had the lowest centrality. Network connectivity significantly increased from pre- to posttreatment, with the greatest increases in strength centrality found in binge eating and shape concern, but it did not predict remission from binge eating.With decreasing symptom severity, CBT resulted in a greater integration and connectivity of the psychopathology network in BED, suggesting an increased patient understanding of relations between binge eating and other symptoms. Network connectivity was not a negative prognostic indicator of treatment outcome. These results indicate a need for further research on the predictive value of network variables in the explanation of therapeutic change for patients with BED.
Abstract 10326: Outcomes in Adults With Heterotaxy Syndrome and Congenital Heart Disease: A Single Center Experience
Authors: Christopher R Broda, Katherine Salciccioli, Keila M Lopez, Peter R Ermis, Douglas S Moodie, Heather A Dickerson
Journal: Circulation (2018)

Introduction: Heterotaxy syndrome (HTX), a condition where the thoraco-abdominal organs demonstrate abnormal lateral arrangement, is typically associated with congenital heart disease (CHD). Data r...
Eukaryote-Conserved Methylarginine Is Absent in Diplomonads and Functionally Compensated in <i>Giardia</i>
Authors: Samantha J Emery-Corbin, Joshua J Hamey, Brendan R E Ansell, Balu Balan, Swapnil Tichkule, Andreas J Stroehlein, Crystal Cooper, Bernie V McInerney, Soroor Hediyeh-Zadeh, Daniel Vuong, Andrew Crombie, Ernest Lacey, Melissa J Davis, Marc R Wilkins, Melanie Bahlo, Staffan G Svärd, Robin B Gasser, Aaron R Jex
Journal: Molecular Biology and Evolution (2020)

Abstract Methylation is a common posttranslational modification of arginine and lysine in eukaryotic proteins. Methylproteomes are best characterized for higher eukaryotes, where they are functionally expanded and evolved complex regulation. However, this is not the case for protist species evolved from the earliest eukaryotic lineages. Here, we integrated bioinformatic, proteomic, and drug-screening data sets to comprehensively explore the methylproteome of Giardia duodenalis—a deeply branching parasitic protist. We demonstrate that Giardia and related diplomonads lack arginine-methyltransferases and have remodeled conserved RGG/RG motifs targeted by these enzymes. We also provide experimental evidence for methylarginine absence in proteomes of Giardia but readily detect methyllysine. We bioinformatically infer 11 lysine-methyltransferases in Giardia, including highly diverged Su(var)3-9, Enhancer-of-zeste and Trithorax proteins with reduced domain architectures, and novel annotations demonstrating conserved methyllysine regulation of eukaryotic elongation factor 1 alpha. Using mass spectrometry, we identify more than 200 methyllysine sites in Giardia, including in species-specific gene families involved in cytoskeletal regulation, enriched in coiled-coil features. Finally, we use known methylation inhibitors to show that methylation plays key roles in replication and cyst formation in this parasite. This study highlights reduced methylation enzymes, sites, and functions early in eukaryote evolution, including absent methylarginine networks in the Diplomonadida. These results challenge the view that arginine methylation is eukaryote conserved and demonstrate that functional compensation of methylarginine was possible preceding expansion and diversification of these key networks in higher eukaryotes.
Response to: ‘Clinical features of patients with rheumatic diseases and COVID-19 infection in Sarawak, Malaysia’ by Wan<i>et al</i>
Authors: Jixin Zhong, Lingli Dong
Journal: Annals of the Rheumatic Diseases (2020)

We thank Dr. Wan and colleagues for their comments on our manuscript reporting the clinical features of COVID-19 pneumonia in patients with rheumatic disease.1 Wan et al analysed 569 cases of COVID-19 in Sarawak, Malaysia and found 4 patients with rheumatic diseases (2 systemic lupus erythematosus, 1 dermatomyositis, and 1 scleroderma). Among these four patients with COVID-19 and rheumatic disease, they noted one case requiring ventilation (25%, 1/4) and one case developing an SLE flare at admission (25%, 1/4). These were in agreement with our findings that respiratory failure was more common in patients with COVID-19 with rheumatic disease (38% vs 10%, p<0.001) and some patients with COVID-19 and rheumatic disease may experience a flare of …
Self-assembly of stem cell membrane-camouflaged nanocomplex for microRNA-mediated repair of myocardial infarction injury
Authors: Chi Yao, Weijian Wu, Han Tang, Xuemei Jia, Jianpu Tang, Xinhua Ruan, Feng Li, David Tai Leong, Dan Luo, Dayong Yang
Journal: Biomaterials (2020)
Mitochondrial Sirtuin 3: New emerging biological function and therapeutic target
Authors: Jin Zhang, Honggang Xiang, Jie Liu, Yi Chen, Rong-Rong He, Bo Liu
Journal: Theranostics (2020)

Sirtuin 3 (SIRT3) is one of the most prominent deacetylases that can regulate acetylation levels in mitochondria, which are essential for eukaryotic life and inextricably linked to the metabolism of multiple organs. Hitherto, SIRT3 has been substantiated to be involved in almost all aspects of mitochondrial metabolism and homeostasis, protecting mitochondria from a variety of damage. Accumulating evidence has recently documented that SIRT3 is associated with many types of human diseases, including age-related diseases, cancer, heart disease and metabolic diseases, indicating that SIRT3 can be a potential therapeutic target. Here we focus on summarizing the intricate mechanisms of SIRT3 in human diseases, and recent notable advances in the field of small-molecule activators or inhibitors targeting SIRT3 as well as their potential therapeutic applications for future drug discovery.
Early peripheral blast cell clearance predicts minimal residual disease status and refines disease prognosis in <scp>acute myeloid leukemia</scp>
Authors: Francesco Mannelli, Giacomo Gianfaldoni, Sara Bencini, Matteo Piccini, Ilaria Cutini, Maria Ida Bonetti, Barbara Scappini, Fabiana Pancani, Vanessa Ponziani, Marco Chiarini, Erika Borlenghi, Renato Bassan, Giuseppe Rossi, Alberto Bosi
Journal: American Journal of Hematology (2020)

Minimal residual disease (MRD) assessment in acute myeloid leukemia (AML) is increasingly used in risk stratification. However, several issues around this use are unresolved, including, among others, the most suitable time-point(s) for its application. Overall, late assessments appear more effective at distinguishing outcome but, in some studies, the early evaluations were already highly informative, anticipating the value of later ones. Our work integrated MRD with peripheral blast clearance (PBC), a treatment-related biomarker previously demonstrated to be a powerful predictor of response. From 2007 to 2014, we have studied 120 patients treated according to the NILG 02-06 trial and who achieved CR after induction. Patients in PBC-defined categories (separated by a 1.5-log threshold) showed significantly different probabilities of attaining MRD negativity, after either induction (MRD1) or consolidation (MRD2). Peripheral blast clearance combined with MRD1 largely anticipated MRD2-related information: when both biomarkers predicted chemosensitive disease (PBChigh /MRD1neg ), the rate of MRD2-negativity was 90%, and DFS and OS estimates were 68% and 76% at 3 years, respectively. When both markers were unfavorable (PBClow /MRD1pos ), rates of MRD2 negativity, DFS, and OS were 20%, 34%, and 24%, respectively, at 3 years. In fact, MRD2 added prognostic value only in cases with discordant PBC/MRD1 data. Our data support a reasoned timing for MRD-based therapeutic decisions, modulated on individual chemosensitivity, an approach we have implemented in a forthcoming prospective multi-center trial by Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA).
Letter to the editor: Generation interval for COVID-19 based on symptom onset data
Authors: Sergio Bacallado, Qingyuan Zhao, Nianqiao Ju
Journal: Eurosurveillance (2020)

Preview this article: Letter to the editor: Generation interval for COVID-19 based on symptom onset data, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/25/29/eurosurv-25-29-3-1.gif
Abstract IA23: Lessons from a rare childhood cancer syndrome on replication repair deficiency and hypermutation
Authors: Uri Y. Tabori
Journal: Cancer Research (2020)

Abstract In order to divide, cells need to replicate their DNA. Replication is done by DNA polymerase epsilon and delta (POLE and POLD1) and creates thousands of mistakes per each replication cycle. The major components safeguarding our genome against such mutations are the proofreading capacity of both polymerases and the mismatch repair (MMR) genes. Germline mutations in either POLE or the MMR genes result in the most aggressive childhood cancer syndromes with high penetrance of cancers during childhood with the hallmark of extreme hypermutation. Data from the International Replication Repair Deficiency (RRD) Consortium reveal that this phenomenon is not restricted to the rare cancer syndrome and affects 5% of childhood cancers throughout many tissues. Hypermutation is observed in up to 10% of recurrent childhood cancers and 20% of adult cancers. Recent data reveal that there are a variety of mutational signatures that are associated with each cause of RRD and hypermutation. These mutations can be traced to the germline or previous therapy. Furthermore, signatures are not restricted to SNV but can be observed by insertions and deletions in microsatellites. Animal models of RRD shed new light on the process of tumorigenesis and mutation progression in RRD cancers and their impact on inter- and intratumoral heterogeneity. Together, these data provide an Achilles heel to these tumors where immunotherapy and combinations can improve survival for patients with germline RRD and children with RRD hypermutant cancers. Novel biomarkers of response to immunotherapy provide insight into the patterns of immune and tumor interactions in these patients. Citation Format: Uri Y. Tabori. Lessons from a rare childhood cancer syndrome on replication repair deficiency and hypermutation [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr IA23.
Guidewire-assisted method to achieve hemostasis in colonic diverticular bleeding in the ascending colon
Authors: Eisuke Akamine, Satoshi Asai, Hitomi Jimbo, Kotaro Takeshita, Takumi Ichinona, Naoki Fujimoto
Journal: Endoscopy (2020)

A 61-year-old man was admitted because of colonic diverticular bleeding. Despite having achieved hemostasis at the cecum using five clips on the second day of admission, he re-bled on the third day, so we again performed a colonoscopy. During this colonoscopy, we removed the previously placed clips and, after placing a 0.035-inch biliary guidewire and withdrawing the colonoscope ([Fig. 1]), we attached an over-the-scope (OTS) clip (Ovesco Endoscopy AG, Tübingen, Germany) to the tip of the scope. We then re-inserted it into the cecum following the guidewire. Hemostasis was achieved using the OTS clip ([Fig. 2]; [Video 1]). The patient’s condition improved after this intervention, and he was discharged from hospital on the ninth day of admission.
Day 5 Peripheral Blood Blasts and Day 14 Bone Marrow Studies As Predictors for Response to Therapy in Acute Myeloid Leukemia (AML): An Experience from Indian Subcontinent
Authors: Shilpa Prabhu, Nataraj Ks, Sharat Damodar, Swasti Sinha, Sunil Bhat, Shoba Badiger, Vellaichamy Annapandian
Journal: Blood (2017)
Aichi virus 3C protease modulates LC3- and SQSTM1/p62-involved antiviral response
Authors: Ming-Hsiang Kung, You-Sheng Lin, Tsung-Hsien Chang
Journal: Theranostics (2020)

Rationale: Autophagy is an essential, homeostatic process by which cells break down their own components, it also contributes to restricting bacterial infection in host defense systems; yet, how autophagy regulates viral infection remains inconclusive. Aichi virus (AiV), belonging to the genus Kobuvirus in the Picornaviridae family, causes acute gastroenteritis in human. The role of autophagy-mediated anti-viral activity on AiV infection was investigated in this study. Methods: The effect of autophagy-associated molecules in retinoic acid-inducible gene-I (RIG-I)-like receptor (RLR) antiviral signal axis was analyzed in AiV infected cells by using biochemistry and pharmacologic approaches. In addition, the AiV viral protein regulating autophagy-associated RLR activity was also evaluated. Results: In AiV-infected cells, autophagic flux including the formation of autophagic vacuoles, as well as degradation of microtubule-associated protein light chain 3 (LC3) and sequestosome-1 (SQSTM1/p62) were observed. Ectopic overexpression of LC3 and p62, but not Atg proteins, contributed to RLR antiviral signal axis, shRNA knockdown of LC3 and p62 led to a downregulation of antiviral inflammation. Moreover, AiV infection inhibited double-stranded RNA (dsRNA)-activated RLR activity by the viral protein 3C protease but not H42D, C143S protease dead mutants. AiV 3C protease caused the degradation of LC3 and p62, and also RLR signal proteins. Conclusion: This study reveals a possible mechanism of autophagy-associated proteins regulating virus replication. Maintaining a cellular level of LC3 and p62 during the viral infection period might help restrict virus replication. Although, AiV 3C protease dampens the LC3 and p62-mediated host antiviral machinery for AiV replication. Results obtained provide a better understanding of the molecular pathogenesis of AiV for developing methods of prevention and treatment.
Endoscopy and central reading in inflammatory bowel disease clinical trials: achievements, challenges and future developments
Authors: Klaus Gottlieb, Marco Daperno, Keith Usiskin, Bruce E Sands, Harris Ahmad, Colin W Howden, William Karnes, Young S Oh, Irene Modesto, Colleen Marano, Ryan William Stidham, Walter Reinisch
Journal: Gut (2020)

Central reading, that is, independent, off-site, blinded review or reading of imaging endpoints, has been identified as a crucial component in the conduct and analysis of inflammatory bowel disease clinical trials. Central reading is the final step in a workflow that has many parts, all of which can be improved. Furthermore, the best reading algorithm and the most intensive central reader training cannot make up for deficiencies in the acquisition stage (clinical trial endoscopy) or improve on the limitations of the underlying score (outcome instrument). In this review, academic and industry experts review scoring systems, and propose a theoretical framework for central reading that predicts when improvements in statistical power, affecting trial size and chances of success, can be expected: Multireader models can be conceptualised as statistical or non-statistical (social). Important organisational and operational factors, such as training and retraining of readers, optimal bowel preparation for colonoscopy, video quality, optimal or at least acceptable read duration times and other quality control matters, are addressed as well. The theory and practice of central reading and the conduct of endoscopy in clinical trials are interdisciplinary topics that should be of interest to many, regulators, clinical trial experts, gastroenterology societies and those in the academic community who endeavour to develop new scoring systems using traditional and machine learning approaches.