tbuckley/cabot-search huggingface dataset:
Volume-Outcome Association of Mitral Valve Surgery in the United States
Authors: Vinay Badhwar, Sreekanth Vemulapalli, Michael A. Mack, A. Marc Gillinov, Joanna Chikwe, Joseph A. Dearani, Maria V. Grau-Sepulveda, Robert Habib, J. Scott Rankin, Jeffrey P. Jacobs, Patrick M. McCarthy, Jordan P. Bloom, Paul A. Kurlansky, Moritz C. Wyler von Ballmoos, Vinod H. Thourani, James R. Edgerton, Christina M. Vassileva, James S. Gammie, David M. Shahian
Journal: JAMA Cardiology (2020)

Early surgery for severe primary degenerative mitral regurgitation is recommended, provided optimal outcomes are achievable. Contemporary national data defining mitral valve surgery volume and outcomes are lacking.To assess national 30-day and 1-year outcomes of mitral valve surgery and define the hospital- and surgeon-level volume-outcome association with mitral valve repair or replacement (MVRR) in patients with primary mitral regurgitation.This multicenter cross-sectional observational study used the Society of Thoracic Surgeons Adult Cardiac Surgery Database to identify patients undergoing isolated MVRR for primary mitral regurgitation in the United States. Operative data were collected from July 1, 2011, to December 31, 2016, and analyzed from March 1 to July 1, 2019, with data linked to the Centers for Medicare and Medicaid Services.The primary outcome was 30-day in-hospital operative mortality after isolated MVRR for primary mitral regurgitation. Secondary outcomes were 30-day composite mortality plus morbidity (any occurrence of bleeding, stroke, prolonged ventilation, renal failure, or deep wound infection), rate of successful mitral valve repair of primary mitral regurgitation (residual mitral regurgitation of mild [1+] or better), and 1-year mortality, reoperation, and rehospitalization for heart failure.A total of 55 311 patients, 1094 hospitals, and 2410 surgeons were identified. Increasing hospital and surgeon volumes were associated with lower risk-adjusted 30-day mortality, lower 30-day composite mortality plus morbidity, and higher rate of successful repair. The lowest vs highest hospital volume quartile had higher 1-year risk-adjusted mortality (hazard ratio [HR], 1.61, 95% CI, 1.31-1.98), but not mitral reoperation (odds ratio [OR], 1.51; 95% CI, 0.81-2.78) or hospitalization for heart failure (HR, 1.25; 95% CI, 0.96-1.64). The surgeon-level 1-year volume-outcome associations were similar for mortality (HR, 1.60; 95% CI, 1.32-1.94) but not significant for mitral reoperation (HR, 1.14; 95% CI, 0.60-2.18) or hospitalization for heart failure (HR, 1.17; 95% CI, 0.91-1.50).National hospital- and surgeon-level inverse volume-outcome associations were observed for 30-day and 1-year mortality after mitral valve surgery for primary mitral regurgitation. These findings may help to define access to experienced centers and surgeons for the management of primary mitral regurgitation.
Intracellular aggregation of peptide-reprogrammed small molecule nanoassemblies enhances cancer chemotherapy and combinatorial immunotherapy
Authors: Jinrong Peng, Yao Xiao, Qian Yang, Qingya Liu, Yu Chen, Kun Shi, Ying Hao, Ruxia Han, Zhiyong Qian
Journal: Acta Pharmaceutica Sinica B (2020)

The intracellular retention of nanotherapeutics is essential for their therapeutic activity. The immobilization of nanotherapeutics inside target cell types can regulate various cell behaviors. However, strategies for the intracellular immobilization of nanoparticles are limited. Herein, a cisplatin prodrug was synthesized and utilized as a glutathione (GSH)-activated linker to induce aggregation of the cisplatin prodrug/IR820/docetaxel nanoassembly. The nanoassembly has been reprogrammed with peptide-containing moieties for tumor-targeting and PD-1/PD-L1 blockade. The aggregation of the nanoassemblies is dependent on GSH concentration. Evaluations in vitro and in vivo revealed that GSH-induced intracellular aggregation of the nanoassemblies enhances therapeutic activity in primary tumors by enhancing the accumulation and prolonging the retention of the chemotherapeutics in the tumor site and inducing reactive oxygen species (ROS) generation and immunogenic cell death. Moreover, the nanoassemblies reinvigorate the immunocytes, especially the systemic immunocytes, and thereby alleviate pulmonary metastasis, even though the population of immunocytes in the primary tumor site is suppressed due to the enhanced accumulation of chemotherapeutics. This strategy provides a promising option for the intracellular immobilization of nanoparticles in vitro and in vivo.
Case 22-2020: A 62-Year-Old Woman with Early Breast Cancer during the Covid-19 Pandemic
Authors: Laura M. Spring, Michelle C. Specht, Rachel B. Jimenez, Steven J. Isakoff, Gary X. Wang, Amy Ly, Jennifer A. Shin, Aditya Bardia, Beverly Moy
Journal: New England Journal of Medicine (2020)

A Woman with Early Breast Cancer during the Covid-19 Pandemic A 62-year-old woman was evaluated for a mass that had been identified in the left breast during the Covid-19 pandemic. Mammography reve...
Letter to the Editor: Additional Factors to Consider When Studying Liver Injury Indicators and Mortality in COVID‐19 Patients
Authors: Yanqing Liu
Journal: Hepatology (2020)

Potential conflict of interest: Nothing to report. TO THE EDITOR: In a recent issue of Hepatology, Lei et al.(1) conducted a multicenter retrospective cohort study that included 5,771 adult patients with coronavirus disease 2019 (COVID‐19) pneumonia in Hubei Province. The purpose of the study was to evaluate the relationships between liver injury indicators (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase, and total bilirubin) and mortality in patients with COVID‐19. The authors considered the possibility that elevated liver injury indicators, particularly AST, are strongly associated with mortality risk. However, the association between liver injury indicators and mortality in patients with COVID‐19 should be interpreted cautiously in light of the following issues. Hepatitis B virus (HBV) is a common epidemic virus in the Chinese population, especially in adults. HBV infection can cause severe liver damage, including elevated serum enzymes ALT and AST. HBV infection also has a strong correlation with the development of cirrhosis and hepatocellular carcinoma (HCC).(2) Similar to HBV, hepatitis C virus (HCV) infection is on the rise and is also associated with the development of HCC.(3) However, whether patients have HBV and/or HCV infection is not discussed in the article. In addition, inspired by the AASLD Expert Panel Consensus Statement,(4) lactate dehydrogenase (LDH) is an important indicator in liver injury. Several studies have reported that LDH might be a risk factor for the progression of patients infected with COVID‐19.(5) However, I did not find any data about LDH in this paper. It is my recommendation that LDH should be considered as an independent and/or joint indicator to assess the relationships between liver injury indicators and mortality in patients with COVID‐19.
Human antibodies neutralize enterovirus D68 and protect against infection and paralytic disease
Authors: Matthew R. Vogt, Jianing Fu, Nurgun Kose, Lauren E. Williamson, Robin Bombardi, Ian Setliff, Ivelin S. Georgiev, Thomas Klose, Michael G. Rossmann, Brett L. Hurst, E. Bart Tarbet, Yury A. Bochkov, James E. Gern, Richard J. Kuhn, James E. Crowe
Journal: Science Immunology (2020)

A human monoclonal antibody shows potential to prevent or treat acute flaccid myelitis associated with enterovirus D68 infection.
Risankizumab: A Review in Moderate to Severe Plaque Psoriasis
Authors: Hannah A. Blair
Journal: Drugs (2020)

Risankizumab (Skyrizi®; risankizumab-rzaa) is a humanized immunoglobulin (Ig) G1 monoclonal antibody that specifically targets the p19 subunit of interleukin (IL)-23, thereby inhibiting IL-23-dependent cell signaling. Subcutaneous risankizumab is approved for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy (in the EU), those who are candidates for systemic therapy or phototherapy (in the USA) and those who have an inadequate response to conventional therapies (in Japan). In pivotal phase III trials (UltIMMa-1, UltIMMa-2, IMMvent and IMMhance), risankizumab was more effective than placebo, ustekinumab and adalimumab with regard to the proportion of patients achieving ≥ 90% improvement from baseline in Psoriasis Area and Severity Index score (PASI 90) and a static Physician's Global Assessment score of 0 or 1 at week 16, with these benefits maintained over the longer term. In supportive head-to-head trials, risankizumab was also superior to secukinumab and fumaric acid esters in terms of PASI 90 response rate. In an ongoing open-label extension study (LIMMitless), risankizumab was associated with durable and improved efficacy after switching from ustekinumab or adalimumab, as well as durable maintenance of efficacy through > 2.5 years of continuous exposure. Treatment with risankizumab improved health-related quality of life and was generally well tolerated, both in the short- and longer-term. In conclusion, risankizumab represents a useful new treatment option for patients with moderate to severe plaque psoriasis.
CHARACTERISATION OF MR DERIVED BIOMARKERS OF LIVER HEALTH IN A EUROPEAN COHORT WITH METABOLIC SYNDROME AND NAFLD: PRELIMINARY ANALYSIS OF AN ONGOING PROSPECTIVE TRIAL (RADIcAL1)
Authors: H Thomaides-Brears, E Shumbayawonda, S Mouchti, M Castelo-Branco, F C Alves, M J Coenraad, H J Lamb, M Beer, J J Schaapman, T Costa, M Kelly, S Rymell, L Herdman, T Waddell, S Neubauer, R Banerjee, M M Dollinger
Journal: Hepatology (2019)
Abstract 11886: The Level of Function Mobility Scale for Nurse-driven Early Mobilization in Patients With Acute Cardiovascular Disease
Authors: Diana Dima, Joelle Berube-Dufour, Michael Goldfarb
Journal: Circulation (2019)

Background: There are currently no validated tools that are reliable and easy to use for nurses to assess mobility in people with acute cardiovascular disease. Methods: A multidisciplinary team at ...
骨肉腫:BCOR-CCNB3遺伝子融合で定義される骨肉腫の新しいサブタイプ | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Pierron Gaeelle, Reynaud Stephanie, Ballet Stelly, Delattre Olivier, Tirode Franck, Lucchesi Carlo, Cohen-Gogo Sarah, Perrin Virginie, Coindre Jean-Michel
Journal: Nature Genetics (2012)
The global meningitis genome partnership
Authors: Elizabeth Rodgers, Stephen D. Bentley, Ray Borrow, Holly B. Bratcher, Sylvain Brisse, Angela B. Brueggemann, Dominique A. Caugant, Jamie Findlow, LeAnne Fox, Linda Glennie, Lee H. Harrison, Odile B. Harrison, Robert S. Heyderman, Melissa Jansen van Rensburg, Keith A. Jolley, Brenda Kwambana-Adams, Shamez Ladhani, Marc LaForce, Michael Levin, Jay Lucidarme, Neil MacAlasdair, Jenny Maclennan, Martin C.J. Maiden, Laura Maynard-Smith, Alessandro Muzzi, Philipp Oster, Charlene M.C. Rodrigues, Olivier Ronveaux, Laura Serino, Vinny Smith, Arie van der Ende, Julio Vázquez, Xin Wang, Saber Yezli, James M. Stuart
Journal: Journal of Infection (2020)

Genomic surveillance of bacterial meningitis pathogens is essential for effective disease control globally, enabling identification of emerging and expanding strains and consequent public health interventions. While there has been a rise in the use of whole genome sequencing, this has been driven predominately by a subset of countries with adequate capacity and resources. Global capacity to participate in surveillance needs to be expanded, particularly in low and middle-income countries with high disease burdens. In light of this, the WHO-led collaboration, Defeating Meningitis by 2030 Global Roadmap, has called for the establishment of a Global Meningitis Genome Partnership that links resources for: N. meningitidis (Nm), S. pneumoniae (Sp), H. influenzae (Hi) and S. agalactiae (Sa) to improve worldwide co-ordination of strain identification and tracking. Existing platforms containing relevant genomes include: PubMLST: Nm (31,622), Sp (15,132), Hi (1935), Sa (9026); The Wellcome Sanger Institute: Nm (13,711), Sp (> 24,000), Sa (6200), Hi (1738); and BMGAP: Nm (8785), Hi (2030). A steering group is being established to coordinate the initiative and encourage high-quality data curation. Next steps include: developing guidelines on open-access sharing of genomic data; defining a core set of metadata; and facilitating development of user-friendly interfaces that represent publicly available data.
MiR‐125b Loss Activated HIF1α/pAKT Loop, Leading to Transarterial Chemoembolization Resistance in Hepatocellular Carcinoma
Authors: Xiyang Wei, Lei Zhao, Ruizhe Ren, Fubo Ji, Shuting Xue, Jianjuan Zhang, Zhaogang Liu, Zhao Ma, Xin W. Wang, Linda Wong, Niya Liu, Jiong Shi, Xing Guo, Stephanie Roessler, Xin Zheng, Junfang Ji
Journal: Hepatology (2020)

Background and Aims Transarterial chemoembolization (TACE) is a standard locoregional therapy for patients with hepatocellular carcinoma (HCC) patients with a variable overall response in efficacy. We aimed to identify key molecular signatures and related pathways leading to HCC resistance to TACE, with the hope of developing effective approaches in preselecting patients with survival benefit from TACE. Approach and Results Four independent HCC cohorts with 680 patients were used. MicroRNA (miRNA) transcriptome analysis in patients with HCC revealed a 41‐miRNA signature related to HCC recurrence after adjuvant TACE, and miR‐125b was the top reduced miRNA in patients with HCC recurrence. Consistently, patients with HCC with low miR‐125b expression in tumor had significantly shorter time to recurrence following adjuvant TACE in two independent cohorts. Loss of miR‐125b in HCC noticeably activated the hypoxia inducible factor 1 alpha subunit (HIF1α)/pAKT loop in vitro and in vivo . miR‐125b directly attenuated HIF1α translation through binding to HIF1A internal ribosome entry site region and targeting YB‐1, and blocked an autocrine HIF1α/platelet‐derived growth factor β (PDGFβ)/pAKT/HIF1α loop of HIF1α translation by targeting the PDGFβ receptor. The miR‐125b‐loss/HIF1α axis induced the expression of CD24 and erythropoietin (EPO) and enriched a TACE‐resistant CD24‐positive cancer stem cell population. Consistently, patients with high CD24 or EPO in HCC had poor prognosis following adjuvant TACE therapy. Additionally, in patients with HCC having TACE as their first‐line therapy, high EPO in blood before TACE was also noticeably related to poor response to TACE. Conclusions MiR‐125b loss activated the HIF1α/pAKT loop, contributing to HCC resistance to TACE and the key nodes in this axis hold the potential in assisting patients with HCC to choose TACE therapy.
Selenium detoxification is required for cancer-cell survival
Authors: Anne E. Carlisle, Namgyu Lee, Asia N. Matthew-Onabanjo, Meghan E. Spears, Sung Jin Park, Daniel Youkana, Mihir B. Doshi, Austin Peppers, Rui Li, Alexander B. Joseph, Miles Smith, Karl Simin, Lihua Julie Zhu, Paul L. Greer, Leslie M. Shaw, Dohoon Kim
Journal: Nature Metabolism (2020)
Extended clinical and immunological phenotype and transplant outcome in CD27 and CD70 deficiency
Authors: Sujal Ghosh, Sevgi Köstel Bal, Emily S. J. Edwards, Bethany Pillay, Raúl Jiménez Heredia, Funda Erol Cipe, Geetha Rao, Elisabeth Salzer, Samaneh Zoghi, Hassan Abolhassani, Tooba Momen, Emma Gostick, David A. Price, Yu Zhang, Andrew J. Oler, Claudia Gonzaga-Jauregui, Baran Erman, Ayse Metin, Inci Ilhan, Sule Haskologlu, Candan Islamoglu, Kubra Baskin, Serdar Ceylaner, Ebru Yilmaz, Ekrem Unal, Musa Karakukcu, Dagmar Berghuis, Theresa Cole, Aditya K. Gupta, Fabian Hauck, Hubert Kogler, Andy I. M. Hoepelman, Safa Baris, Elif Karakoc-Aydiner, Ahmet Ozen, Leo Kager, Dirk Holzinger, Michael Paulussen, Renate Krüger, Roland Meisel, Prasad T. Oommen, Emma Morris, Benedicte Neven, Austen Worth, Joris van Montfrans, Pieter L. A. Fraaij, Sharon Choo, Figen Dogu, E. Graham Davies, Siobhan Burns, Gregor Dückers, Ruy Perez Becker, Horst von Bernuth, Sylvain Latour, Maura Faraci, Marco Gattorno, Helen C. Su, Qiang Pan-Hammarström, Lennart Hammarström, Michael J. Lenardo, Cindy S. Ma, Tim Niehues, Asghar Aghamohammadi, Nima Rezaei, Aydan Ikinciogullari, Stuart G. Tangye, Arjan C. Lankester, Kaan Boztug
Journal: Blood (2020)
IGF-1C hydrogel improves the therapeutic effects of MSCs on colitis in mice through PGE<sub>2</sub>-mediated M2 macrophage polarization
Authors: Xiaocang Cao, Liyun Duan, Huixing Hou, Yue Liu, Shang Chen, Shuaiqiang Zhang, Yuanyuan Liu, Chen Wang, Xin Qi, Na Liu, Zhibo Han, Dekui Zhang, Zhong-Chao Han, Zhikun Guo, Qiang Zhao, Zongjin Li
Journal: Theranostics (2020)

Background: Mesenchymal stem cell (MSC)-based therapies hold great promise for the treatment of inflammatory bowel disease (IBD). In order to optimize and maximize the therapeutic benefits of MSCs, we investigated whether cotransplantation of a chitosan (CS)-based injectable hydrogel with immobilized IGF-1 C domain peptide (CS-IGF-1C) and human placenta-derived MSCs (hP-MSCs) could ameliorate colitis in mice. Methods: IGF-1C hydrogel was generated by immobilizing IGF-1C to CS hydrogel. Colitis was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice. We initially applied hP-MSCs and CS-IGF-1C hydrogel for the treatment of colitis by in situ injection, and molecular imaging methods were used for real-time imaging of reactive oxygen species (ROS) and tracking of transplanted hP-MSCs by bioluminescence imaging (BLI). Furthermore, the effects of CS-IGF-1C hydrogel on prostaglandin E2 (PGE2) secretion of hP-MSCs and polarization of M2 macrophages were investigated as well. Results: The CS-IGF-1C hydrogel significantly increased hP-MSC proliferation and promoted the production of PGE2 from hP-MSCs in vitro. Moreover, in vivo studies indicated that the CS-IGF-1C hydrogel promoted hP-MSC survival as visualized by BLI and markedly alleviated mouse colitis, which was possibly mediated by hP-MSC production of PGE2 and interleukin-10 (IL-10) production by polarized M2 macrophages. Conclusions: The CS-IGF-1C hydrogel improved the engraftment of transplanted hP-MSCs, ameliorated inflammatory responses, and further promoted the functional and structural recovery of colitis through PGE2-mediated M2 macrophage polarization. Molecular imaging approaches and therapeutic strategies for hydrogel application provide a versatile platform for exploring the promising therapeutic potential of MSCs in the treatment of IBD.
Substrate stiffness modulates bone marrow-derived macrophage polarization through NF-κB signaling pathway
Authors: Mimi Chen, Yu Zhang, Pinghui Zhou, Xingzhi Liu, Huan Zhao, Xichao Zhou, Qiaoli Gu, Bin Li, Xuesong Zhu, Qin Shi
Journal: Bioactive Materials (2020)

The stiffness of the extracellular matrix (ECM) plays an important role in regulating the cellular programming. However, the mechanical characteristics of ECM affecting cell differentiation are still under investigated. Herein, we aimed to study the effect of ECM substrate stiffness on macrophage polarization. We prepared polyacrylamide hydrogels with different substrate stiffness, respectively. After the hydrogels were confirmed to have a good biocompatibility, the bone marrow-derived macrophages (BMMs) from mice were incubated on the hydrogels. With simulated by the low substrate stiffness, BMMs displayed an enhanced expression of CD86 on the cell surface and production of reactive oxygen species (ROS) in cells, and secreted more IL-1β and TNF-α in the supernatant. On the contrary, stressed by the medium stiffness, BMMs expressed more CD206, produced less ROS, and secreted more IL-4 and TGF-β. In vivo study by delivered the hydrogels subcutaneously in mice, more CD68
Fasting Serum Fructose Levels Are Associated With Risk of Incident Type 2 Diabetes in Middle-Aged and Older Chinese Population
Authors: Ying Chen, Huandong Lin, Li Qin, Youli Lu, Lin Zhao, Mingfeng Xia, Jingjing Jiang, Xiaomu Li, Chen Yu, Geng Zong, Yan Zheng, Xin Gao, Qing Su, Xiaoying Li
Journal: Diabetes Care (2020)

OBJECTIVE We investigated the relationship between fasting serum fructose levels and the risk of incident type 2 diabetes in a prospective Chinese cohort. RESEARCH DESIGN AND METHODS Among 949 community-based participants aged ≥40 years without diabetes at baseline, fasting serum fructose levels were measured using liquid chromatography–tandem mass spectrometry. The participants were followed up for the occurrence of diabetes. Cox regression models were performed to analyze the effect of fasting serum fructose levels on risk of incident diabetes. RESULTS During a median of 3.5 years’ follow-up, 179 of 949 (18.9%) participants developed type 2 diabetes. Elevated fasting serum fructose levels were associated with an increased risk of incident diabetes in a dose-response manner. After adjustment for age, sex, BMI, lipid profiles, blood pressure, liver function, smoking and drinking status, baseline glucose level, and sugar-sweetened beverage consumption, a 1-SD increased fasting fructose level was associated with a 35% (95% CI 1.08–1.67) increased risk of developing diabetes. After further adjustment for serum uric acid and estimated glomerular filtration rate, the association was partially attenuated (hazard ratio 1.33 [95% CI 1.07–1.65]). The association was similar by age, prediabetes status, BMI, and family history of diabetes but attenuated in women (P for heterogeneity = 0.037). CONCLUSIONS Elevated fasting serum fructose levels were independently associated with increased risk of incident type 2 diabetes in a middle-aged and older Chinese population. Our data suggest that higher fasting serum fructose levels might serve as a biomarker and/or a contributor to incident diabetes.
99mTc-MDP Bone Scan Findings in Fibrodysplasia Ossificans Progressiva
Authors: Nitin Gupta, Ritu Verma, Ethel Shangne Belho, Sudip Dey
Journal: Clinical Nuclear Medicine (2020)

Abstract Fibrodysplasia ossificans progressiva is a rare debilitating, connective tissue disease characterized by progressive extraosseous ossification with abnormal great toes. Clinical (hallux valgus), radiological, and classical bone scan findings help to reach diagnosis and prevent patient from unnecessary surgical interventions for fibrodysplasia ossificans progressiva lesions and radiotherapy cycles. Here we present a case where a child presented with multiple swellings over the body and hallux valgus, and further bone scan findings helped to reach the diagnosis. The progressive nature of disease is difficult to halt, but early diagnosis can help in the delay of the disease process, by preventing trauma and giving disease-modifying agents.
Abstract 10931: Hepatocyte Growth Factor Predicts Heart Failure in Patients With a Fontan Circulation
Authors: Takuro Kojima, Naokata Sumitomo, Shigeki Yoshiba, Toshiki Kobayashi
Journal: Circulation (2018)

Introduction: Plasma Hepatocyte growth factor (HGF) concentrations are reported to be increased in cardiovascular diseases, such as congestive heart failure, acute myocardial infarctions, and hyper...