tbuckley/cabot-search huggingface dataset:
Reduced Relapse and Improved Survival in Chemosensitive Hodgkin Lymphoma Patients Undergoing Haploidentical Related Donor Compared to HLA-Identical Donor Transplantation
Authors: Luca Castagna, Stefania Bramanti, Alessandro Busca, Michele Malagola, Fabio Ciceri, William Arcese, Daniele Vallisa, Francesca Patriarca, Giorgina Specchia, Roberto Raimondi, Raynier Devillier, Sabine Furst, Laura Giordano, Barbara Sarina, Lucio Morabito, Jacopo Mariotti, Angela Granata, Reda Bouabdallah, Carmelo Carlo-Stella, Alessandro Rambaldi, Armando Santoro, Andrea Bacigalupo, Paolo Corradini, Francesca Bonifazi, Didier Blaise
Journal: Blood (2017)
Mechanical Properties of Bioengineered Corneal Stroma
Authors: Nello Formisano, Cas van der Putten, Rhiannon Grant, Gozde Sahin, Roman K. Truckenmüller, Carlijn V. C. Bouten, Nicholas A. Kurniawan, Stefan Giselbrecht
Journal: Advanced Healthcare Materials (2021)

Abstract For the majority of patients with severe corneal injury or disease, corneal transplantation is the only suitable treatment option. Unfortunately, the demand for donor corneas greatly exceeds the availability. To overcome shortage issues, a myriad of bioengineered constructs have been developed as mimetics of the corneal stroma over the last few decades. Despite the sheer number of bioengineered stromas developed , these implants fail clinical trials exhibiting poor tissue integration and adverse effects in vivo. Such shortcomings can partially be ascribed to poor biomechanical performance. In this review, existing approaches for bioengineering corneal stromal constructs and their mechanical properties are described. The information collected in this review can be used to critically analyze the biomechanical properties of future stromal constructs, which are often overlooked, but can determine the failure or success of corresponding implants.
変性大動脈外科的生体弁パートナー2Valve in Valveレジストリにおける経カテーテル大動脈弁移植【Powered by NICT】
Authors: G Webb John, J Mack Michael, M White Jonathon, Dvir Danny, Blanke Philipp, C Herrmann Howard, Leipsic Jonathon, K Kodali Susheel, Makkar Raj, Miller D. Craig, Pibarot Philippe, Pichard Augusto, F Satler Lowell, Svensson Lars, C Alu Maria, M Suri Rakesh, B Leon Martin
Journal: Journal of the American College of Cardiology (2017)
Abstract 8279: Avoiding Cerebral Embolism during Ablation of Atrial Fibrillation by the Use of Radiofrequency Hot Balloon Catheter
Authors: Yoshio Yamaguchi, Hiroshi Sohara, Hiroshi Takeda, Hideki Ueno, Syutaro Satake
Journal: Circulation (2011)

Background Cerebral Embolism (CE) is a serious complication associated with conventional radiofrequency (RF) catheter ablation of atrial fibrillation (AF). It is partly because of non-uniform heating of the tissue due to direct resistive heating by RF current under regional cooling by changeable blood flow or irrigation, resulting in thrombus formation. To avoid non-uniform heating, we have developed a RF hot balloon catheter system. Methods and Results In this RF hot balloon catheter system, the balloon could be uniformly heated at the target temperature between 60 and 65°C, as the inner fluid of the balloon was heated by RF current (1.8 MHz), and agitated by a specially designed vibration generator (Fig). The tissue in contact with the hot balloon was ablated by heat conduction, where the lesion depth was determined by the temperature of the balloon and the delivery time of RF energy. We experimentally performed pulmonary vein (PV) isolation in 10 pigs and histological examination of serial sections of the atrial lesions and the brain after ablation. There was no thrombus formation at ablated lesion and no cerebral infarction in all 10 pigs. We treated 445 patients with AF (Paroxysmal AF (PAF), n=270; Persistent AF (Per-AF), n=77; Long persistent AF (Long-AF), n=98) by PV antral isolation or box isolation ( isolation of PV and left posterior atrium) using this system and randomly performed magnetic resonance imaging (MRI) of brains in 120 patients after ablation. Within 12 months after ablation, we have no new symptom of cerebral infarction in all patients, and no CE lesion detected by Brain MRI in 120 patients. During 12 months follow up, no AF episodes were detected without anti-arrhythmic drugs in 346 patients (PAF, n=238 (88%); Per-AF, n=53 (69%); Long-AF, n=55 (56%)). Conclusion PV antral isolation or box isolation using a RF hot balloon catheter system could be performed without complication of CE and successfully treat most of the patients with AF.
Irregular distribution of grid cell firing fields in rats exploring a 3D volumetric space
Authors: Roddy M. Grieves, Selim Jedidi-Ayoub, Karyna Mishchanchuk, Anyi Liu, Sophie Renaudineau, Éléonore Duvelle, Kate J. Jeffery
Journal: Nature Neuroscience (2021)

We investigated how entorhinal grid cells encode volumetric space. On a horizontal surface, grid cells usually produce multiple, spatially focal, approximately circular firing fields that are evenly sized and spaced to form a regular, close-packed, hexagonal array. This spatial regularity has been suggested to underlie navigational computations. In three dimensions, theoretically the equivalent firing pattern would be a regular, hexagonal close packing of evenly sized spherical fields. In the present study, we report that, in rats foraging in a cubic lattice, grid cells maintained normal temporal firing characteristics and produced spatially stable firing fields. However, although most grid fields were ellipsoid, they were sparser, larger, more variably sized and irregularly arranged, even when only fields abutting the lower surface (equivalent to the floor) were considered. Thus, grid self-organization is shaped by the environment's structure and/or movement affordances, and grids may not need to be regular to support spatial computations.
Dual targeting of CTLA-4 and CD47 on T <sub>reg</sub> cells promotes immunity against solid tumors
Authors: Anli Zhang, Zhenhua Ren, Kuo-Fu Tseng, Xiaojuan Liu, Huiyu Li, Changzheng Lu, Yueqi Cai, John D. Minna, Yang-Xin Fu
Journal: Science Translational Medicine (2021)

Blockade of CD47, the "do not eat me" signal, has limited effects in solid tumors despite its potent antitumor effects in hematopoietic malignancies. Taking advantage of the high expression of cytotoxic T lymphocyte-associated protein 4 (CTLA-4) on Treg cells and abundant Fc receptor-expressing active phagocytes inside the tumor microenvironment (TME), we designed and tested a heterodimer combining an anti-CTLA-4 antibody, which targets Treg cells, with the CD47 ligand, signal regulatory protein α (SIRPα), to selectively block CD47 on intratumoral Treg cells. We hypothesized that heterodimer treatment would increase antibody-dependent cellular phagocytosis of the targeted Treg cells. We found that anti-CTLA-4×SIRPα preferentially depleted ICOShigh immunosuppressive Treg cells in the TME and enhanced immunity against solid tumors, including MC38 and CT26 murine colon cancers. Mechanistically, we found that CD47 expression on Treg cells limited anti-CTLA-4-mediated depletion and Fc on the heterodimer-enhanced depletion. Furthermore, anti-human CTLA-4×SIRPα depleted tumor Treg cells and exhibits less toxicity than anti-human CTLA-4 in a humanized mouse model. Collectively, these results demonstrate that simultaneously modulating both "eat me" and do not eat me signals induces Treg cell depletion inside the TME and may be an effective strategy for treating solid tumors.
Multifunctional Hybrid Hydrogel Enhanced Antitumor Therapy through Multiple Destroying DNA Functions by a Triple‐Combination Synergistic Therapy
Authors: Jiamin Zhang, Lijun Yang, Fan Huang, Cuicui Zhao, Jinjian Liu, Yumin Zhang, Jianfeng Liu
Journal: Advanced Healthcare Materials (2021)

Brachytherapy, as an effective setting for precise cancer therapy in clinic, can lead to serious DNA damage. However, its therapeutic efficacy is always limited by the DNA self-repair property, tumor hypoxia-associated radiation resistance as well as inhomogeneous distribution of the radioactive material. Herein, a multifunctional hybrid hydrogel (131 I-hydrogel/DOX/GNPs aggregates) is developed by loading gold nanoparticle aggregates (GNPs aggregates) and DOX into a radionuclide iodine-131 (131 I) labelled polymeric hydrogels (131 I-PEG-P(Tyr)8 ) for tumor destruction by completely damaging DNA self-repair functions. This hybrid hydrogel exhibits excellent photothermal/radiolabel stability, biocompatibility, and fluorescence/photothermal /SPECT imaging properties. After local injection, the sustained releasing DOX within tumor greatly inhibits the DNA replication. Meanwhile, GNPs aggregates as a radiosensitizer and photosensitizer show a significant improvement of brachytherapeutic efficacy and cause serious DNA damage. Simultaneously, GNPs aggregates induce mild photothermal therapy under 808 nm laser irradiation, which not only inhibits self-repair of the damaged DNA but also effectively relieves tumor hypoxic condition to enhance the therapeutic effects of brachytherapy, leading to a triple-synergistic destruction of DNA functions. Therefore, this study provides a highly efficient tumor synergistic therapy platform and insight into the synergistic antitumor mechanism in DNA level.
<i>Notes from the Field</i>: Delays in Identification and Treatment of a Case of Septicemic Plague — Navajo County, Arizona, 2020
Authors: Ariella P. Dale, Melissa Kretschmer, Irene Ruberto, David M. Wagner, Cathy Solomon, Kenneth Komatsu, Heather Venkat
Journal: MMWR Morbidity and Mortality Weekly Report (2021)
Abstract 18521: Donor Pulmonary Capillary Wedge Pressure is Associated With Survival After Heart Transplantation
Authors: Jonathan Buggey, Sadeer G Al-Kindi, Guilherme H Oliveira
Journal: Circulation (2017)

Objectives: To investigate the association between invasive hemodynamic measurements of cardiac donors and post-transplantation mortality of recipients. Methods: We queried the United Network for O...
4-hydroxy(phenyl)retinamide induced death in cell lines of the Ewing’s sarcoma family of tumours (ESFT)
Authors: Stephen S. Myatt, Sue A. Burchill
Journal: Cancer Research (2004)

4875   4-hydroxy(phenyl)retinamide (4-HPR or fenretinide) is a retinamide capable of inducing apoptosis in some cancer cells. The effects of 4-HPR have been investigated in ESFT cells lines. Treatment with 4-HPR (0.75–10 μM) decreased viable cell number of all 6 ESFT cell lines studied, in a dose dependent manner. The IC50 for the ESFT cell line TC32 was 0.95μM, compared to 5.3 μM for the neuroblastoma cell line SY5Y. The greater sensitivity of TC-32 cells to 4-HPR-induced death compared to the neuroblastoma SY5Y cells suggests a novel mechanism of action. The decrease in ESFT viable cell number reflects 4-HPR-induced apoptosis, demonstrated by an increase in annexin V and propidium iodide positive cells after 10h, and was analysed by FACs. Furthermore, PARP cleavage, evaluated by western blot was identified after 10h treatment with 4-HPR (1.5μM). The reactive oxygen species (ROS) responsive dye CM-H 2 DCFDA was used to measure ROS levels in TC-32 cells before and after treatment with 4-HPR, fluorescence was analysed by FACs. A 6.5-fold increase in ROS was evident within 1h exposure of TC-32 cells to 4-HPR (1.5 μM). To assess the functional consequence of ROS accumulation TC-32 cells were pre-treated with the anti-oxidant ascorbic acid (100 μM, 1 h). This resulted in the rescue of TC-32 cells from 4-HPR-induced cell death and inhibited the accumulation of ROS. These results suggest that ROS is an essential component of 4-HPR-induced cell death in TC-32 cells, consistent with previous studies in other cancer cell types. Interestingly, pre-treatment of TC-32 cells with the p38-inhibitor SB202190 (6.7 μM, 1h) rescued TC-32 cells from 4-HPR-induced death (1.5μM; 48h), demonstrated by decreased apoptosis and increased viable cell number. Treatment with SB202190 also prevented PARP cleavage induced by 4-HPR (1.5μM, 24h). These data suggest that 4-HPR mediates apoptosis through a ROS-dependent mechanism in TC-32 cells. This may directly or indirectly activate the p38 stress-activated kinase pathway leading to PARP cleavage and induction of ESFT cell death. The activation of p38 may in part be responsible for the increased sensitivity of ESFT cells to 4HPR-induced death compared to neuroblastoma cells.
Zooming in on T cell clones: Are we heading to personalized treatment of allergy?
Authors: Netali Ben-Baruch Morgenstern, Mark Rochman, Marc E. Rothenberg
Journal: Science Immunology (2021)

Single-cell RNA and TCR sequencing of peripheral blood and esophageal cells of human eosinophilic esophagitis uncovers antigen-restricted TH2 cells.
Long-term Use of Hydroxyurea for Sickle Cell Anemia—Reply
Authors: Joep Killestein, Bernard M. J. Uitdehaag, Chris H. Polman
Journal: JAMA (2003)

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Comparison of Antiviral Agents for Seasonal Influenza Outcomes in Healthy Adults and Children
Authors: Jen-Wei Liu, Shen-Hua Lin, Lin-Chien Wang, Hsiao-Yean Chiu, Jen-Ai Lee
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Antiviral treatment of influenza is recommended for patients with influenza-like illness during periods of community cocirculation of influenza viruses and SARS-CoV-2; however, questions remain about which treatment is associated with the best outcomes and fewest adverse events. <h3>Objective</h3> To compare the efficacy and safety of neuraminidase inhibitors and the endonuclease inhibitor for the treatment of seasonal influenza among healthy adults and children. <h3>Data Sources</h3> Medline, Embase, and the Cochrane Register of Clinical Trials were searched from inception to January 2020 (the last search was updated in October 2020). <h3>Study Selection</h3> Included studies were randomized clinical trials conducted among patients of all ages with influenza treated with neuraminidase inhibitors (ie, oseltamivir, peramivir, zanamivir, or laninamivir) or an endonuclease inhibitor (ie, baloxavir) compared with other active agents or placebo. <h3>Data Extraction and Synthesis</h3> Two investigators identified studies and independently abstracted data. Frequentist network meta-analyses were performed; relative ranking of agents was conducted using P-score probabilities. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations criteria. Data were analyzed in October 2020. <h3>Main Outcomes and Measures</h3> The time to alleviation of influenza symptoms (TTAS), complications of influenza, and adverse events (total adverse events, nausea, and vomiting). <h3>Results</h3> A total of 26 trials were identified that investigated antiviral drugs at high or low doses; these trials included 11 897 participants, among whom 6294 (52.9%) were men and the mean (SD) age was 32.5 (16.9) years. Of all treatments comparing with placebo in efficacy outcomes, high-quality evidence indicated that zanamivir was associated with the shortest TTAS (hazard ratio, 0.67; 95% CI, 0.58-0.77), while baloxavir was associated with the lowest risk of influenza-related complications (risk ratio [RR], 0.51; 95% CI, 0.32-0.80) based on moderate-quality evidence. In safety outcomes, baloxavir was associated with the lowest risk of total adverse events (RR, 0.84; 95% CI, 0.74-0.96) compared with placebo based on moderate-quality evidence. There was no strong evidence of associations with risk of nausea or vomiting among all comparisons, except for 75 mg oseltamivir, which was associated with greater occurrence of nausea (RR, 1.82; 95% CI, 1.38-2.41) and vomiting (RR, 1.88; 95% CI, 1.47-2.41). <h3>Conclusions and Relevance</h3> In this systematic review and network meta-analysis, all 4 antiviral agents assessed were associated with shortening TTAS; zanamivir was associated with the shortest TTAS, and baloxavir was associated with reduced rate of influenza-related complications.
Change in Saliva RT-PCR Sensitivity Over the Course of SARS-CoV-2 Infection
Authors: Zion Congrave-Wilson, Yesun Lee, Jaycee Jumarang, Stephanie Perez, Jeffrey M. Bender, Jennifer Dien Bard, Pia S. Pannaraj
Journal: JAMA (2021)

Lan Lan, MD; Dan Xu, MD; Guangming Ye, MD; Chen Xia, MS; Shaokang Wang, MS; Yirong Li, MD, PhD; Haibo Xu, MD, PhD
Abstract P137: Walking Impairment and Vitamin D Deficiency in the Elderly, National Health and Nutrition Examination Survey 2001 to 2004
Authors: Lea Moukarzel, Danlin Mao, Luis H Eraso
Journal: Circulation (2013)

Introduction: Vitamin D deficiency has been reported in 36% of otherwise healthy adults and 57% of inpatients in the US. Vitamin D deficiency (&lt; 15 ng/ml) is linked to increased muscle weakenss, cardiovascular disease and abnormal bone mineral metabolism. The elderly are more prone to vitamin D deficiency because of decrease dietary intake, diminished sunlight exposure and reduced skin thickness among other risk factors. We hypothesized that walking impairment in subjects older than 60 years old is associated to abnormal serum levels of 25-hydroxyvitaminD levels independent of traditional cardiovascular risk factors. Methods: A multivariable adjustment was performed using the National Health and Nutrition Examination Survey database and a graded association was present between serum 25-hydroxyvitaminD levels and walking impairment. We analyzed data from 2,322 participants of the NHANES 2001-2004 survey ages 60 years or older who responded to the walking impairment (WI) questionnaire and had serum 25-hydroxyvitamin D levels measured. Walking impairment was defined as an affirmative answer to the question: “have you had pain in either leg while walking?” A 25 hydroxyvitamin D deficiency level was defined as a serum level of 15ng/dl or less. PAD was defined as an ABI of less than 0.9 in either leg. Results: The prevalence of individuals 60 year or older with walking impairment due to leg pain in the United States is 25 % (S.E, 1.3). Mexican Americans (31.43%) had a higher prevalence of WI than Whites (24.28%) or African Americans (28.67%). Walking impairment was also statistically significant among those with a history of diabetes mellitus, cardiovascular disease, and peripheral arterial disease. Results also showed that C-reactive protein and alkaline phosphates were higher among those with walking impairment. A multivariable adjustment was performed and a graded association was present between serum 25-hydroxyvitaminD levels and walking impairment. An odds ratio of 1.526186(p= 0.013) for walking impairment was present among vitamin D deficient subjects after adjusting for age, gender, and race-ethnicity. The association remained after further adjusting for C-reactive protein, chronic kidney disease, smoking, history of diabetes, PAD, and history of cardiovascular disease (O.R. =1.416255, p=0.045). Conclusion: Walking impairment is associated with 25-hydroxyvitaminD deficiency in the elderly independent of traditional cardiovascular risk factors. These results warrant further studies to determine if vitamin D supplementation improves functional capacity and reduces cardiovascular disease in the elderly.
Suppressor CD4<sup>+</sup>T cells expressing HLA-G are expanded in the peripheral blood from patients with acute decompensation of cirrhosis
Authors: Wafa Khamri, Cathrin Gudd, Tong Liu, Rooshi Nathwani, Marigona Krasniqi, Sofia Azam, Thomas Barbera, Francesca M Trovato, Lucia Possamai, Evangelos Triantafyllou, Rocio Castro Seoane, Fanny Lebosse, Arjuna Singanayagam, Naveenta Kumar, Christine Bernsmeier, Sujit Mukherjee, Mark McPhail, Chris J Weston, Charalambos Gustav Antoniades, Mark R Thursz
Journal: Gut (2021)

Objective Identifying components of immuneparesis, a hallmark of chronic liver failure, is crucial for our understanding of complications in cirrhosis. Various suppressor CD4 + T cells have been established as potent inhibitors of systemic immune activation. Here, we establish the presence, regulation and mechanism of action of a suppressive CD4 + T cell subset expressing human leucocyte antigen G (HLA-G) in patients with acute decompensation of cirrhosis (AD). Design Flow cytometry was used to determine the proportion and immunophenotype of CD4 + HLA-G + T cells from peripheral blood of 20 healthy controls (HCs) and 98 patients with cirrhosis (28 with stable cirrhosis (SC), 20 with chronic decompensated cirrhosis (CD) and 50 with AD). Transcriptional and functional signatures of cell-sorted CD4 + HLA-G + cells were delineated by NanoString technology and suppression assays, respectively. The role of immunosuppressive cytokine interleukin (IL)-35 in inducing this population was investigated through in vitro blockade experiments. Immunohistochemistry (IHC) and cultures of primary human Kupffer cells (KCs) were performed to assess cellular sources of IL-35. HLA-G-mediated T cell suppression was explored using neutralising antibodies targeting co-inhibitory pathways. Results Patients with AD were distinguished by an expansion of a CD4 + HLA-G + CTLA-4 + IL-35 + immunosuppressive population associated with disease severity, clinical course of AD, infectious complications and poor outcome. Transcriptomic analyses excluded the possibility that these were thymic-derived regulatory T cells. IHC analyses and in vitro cultures demonstrate that KCs represent a potent source of IL-35 which can induce the observed HLA-G + phenotype. These exert cytotoxic T lymphocyte antigen-4-mediated impaired responses in T cells paralleled by an HLA-G-driven downregulation of T helper 17-related cytokines. Conclusion We have identified a cytokine-driven peripherally derived suppressive population that may contribute to immuneparesis in AD.