tbuckley/cabot-search huggingface dataset:
Corneal xenotransplantation: Where are we standing?
Authors: Chang Ho Yoon, Hyuk Jin Choi, Mee Kum Kim
Journal: Progress in Retinal and Eye Research (2020)

The search for alternatives to allotransplants is driven by the shortage of corneal donors and is demanding because of the limitations of the alternatives. Indeed, current progress in genetically engineered (GE) pigs, the introduction of gene-editing technology by clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9, and advanced immunosuppressants have made xenotransplantation a possible option for a human trial. Porcine corneal xenotransplantation is considered applicable because the eye is regarded as an immune-privileged site. Furthermore, recent non-human primate studies have shown long-term survival of porcine xenotransplants in keratoplasty. Herein, corneal immune privilege is briefly introduced, and xenogeneic reactions are compared with allogeneic reactions in corneal transplantation. This review describes the current knowledge on special issues of xenotransplantation, xenogeneic rejection mechanisms, current immunosuppressive regimens of corneal xenotransplantation, preclinical efficacy and safety data of corneal xenotransplantation, and updates of the regulatory framework to conduct a clinical trial on corneal xenotransplantation. We also discuss barriers that might prevent xenotransplantation from becoming common practice, such as ethical dilemmas, public concerns on xenotransplantation, and the possible risk of xenozoonosis. Given that the legal definition of decellularized porcine cornea (DPC) lies somewhere between a medical device and a xenotransplant, the preclinical efficacy and clinical trial data using DPC are included. The review finally provides perspectives on the current standpoint of corneal xenotransplantation in the fields of regenerative medicine.
Driving Nonalcoholic Steatohepatitis Forward Using the FibroScan Aspartate Aminotransferase Score, But Obey the Traffic Lights
Authors: Nabil Noureddin, Naim Alkhouri, Kimberly A. Brown, Mazen Noureddin
Journal: Hepatology (2020)

Noureddin, Nabil M.D.; Alkhouri, Naim M.D.; Brown, Kimberly A. M.D.; Noureddin, Mazen M.D., M.H.Sc.Editor(s): Corey, Kathleen E.5; Malhi, Harmeet6 Author Information
Reply to “CLL and COVID-19 at the Hospital Clinic of Barcelona: an interim report” Analysis of six hematological centers in Lombardy
Authors: Gianluigi Reda, Alessandro Noto, Ramona Cassin, Giulia Zamprogna, Chiara Borella, Lydia Scarfò, Lucia Farina, Alfredo Molteni, Paolo Ghia, Alessandra Tedeschi, Marco Montillo
Journal: Leukemia (2020)

We read with interest the correspondence by Baumann et al.[1], reporting the first attempt to determine the prevalence of COVID-19 in the monocentric cohort of CLL patients at Hospital Clinic of Barcelona.Four patients developed a mild symptomatic COVID-19 infection as of April 15, 2020, with a prevalence of 0.95% (4 of 420 pts).The authors speculated that the CLL-related immunodeficiency, rather than exacerbating the effects of SARS-CoV-2 might prevent them.Moreover they imply a potential role of immunomodulatory agents (e.g.ibrutinib) on the outcome of patients with CLL infected by 3].The authors also refer to the recent recommendations for the management of cancer patients in COVID era published by the EHA Infectious Disease Scientific Working Group Executive Committee.The panel suggested to consider treatment interruption in patients who experience community-acquired respiratory virus (CARV) infections, taking into account the type *
Outcomes to first-line pembrolizumab in patients with PD-L1-high (≥50%) non–small cell lung cancer and a poor performance status
Authors: Joao V Alessi, Biagio Ricciuti, Elizabeth Jiménez-Aguilar, Fangxin Hong, Zihan Wei, Mizuki Nishino, Andrew J Plodkowski, Peter Sawan, Jia Luo, Hira Rizvi, Brett W Carter, John V Heymach, Mehmet Altan, Matthew Hellmann, Mark Awad
Journal: Journal for ImmunoTherapy of Cancer (2020)

Patients with non-small cell lung cancer (NSCLC) and a poor Eastern Cooperative Oncology Group Performance Status (ECOG PS) have been excluded from phase III immunotherapy clinical trials. We sought to evaluate clinical outcomes to first-line pembrolizumab in patients with advanced NSCLC, a PD-L1 Tumor Proportion Score (TPS) of ≥50%, and an ECOG PS of 2.We performed a multicenter retrospective analysis of patients with metastatic NSCLC and a PD-L1 TPS of ≥50% (negative for genomic alterations in EGFR and ALK) who received treatment with first-line pembrolizumab. Clinical outcomes were compared in patients based on ECOG PS.Among the 234 patients, 83.3% (n=195) had an ECOG PS of 0 or 1, and 16.7% (n=39) had an ECOG PS of 2. The baseline clinicopathological characteristics were balanced between the ECOG PS 0-1 vs 2 groups in terms of age, sex, tobacco use, histology, KRAS mutation status, presence of other potentially targetable driver mutations (BRAF, MET, HER2, RET), presence of brain metastases, and PD-L1 TPS distribution. Compared with patients with an ECOG PS of 0 or 1, patients with an ECOG PS of 2 had a significantly lower objective response rate (43.1% vs 25.6%; p=0.04), a numerically shorter median progression-free survival (6.6 months vs 4.0 months; HR 0.70 (95% CI 0.47 to 1.06); p=0.09), and a significantly shorter median overall survival (20.3 months vs 7.4 months; HR 0.42 (95% CI 0.26 to 0.68); p<0.001). On disease progression, patients with an ECOG PS of 2 were significantly less likely to receive second-line systemic therapy compared with patients with an ECOG PS of 0-1 (65% vs 22.2%, p=0.001).A subset of patients with NSCLC and an ECOG PS of 2 can respond to first-line pembrolizumab. However, clinical outcomes in this population are often poor and use of second-line systemic therapy is infrequent.
Native-Valve Infective Endocarditis
Authors: Henry F. Chambers, Arnold S. Bayer
Journal: New England Journal of Medicine (2020)

The diagnosis of infectious endocarditis is based on modified Duke criteria, according to findings on physical examination, echocardiography, microbiologic studies, and imaging of target organs. The selection and duration of antibiotic treatment depend on culture results. Early surgery is indicated in some patients.
Transvalvular Ventricular Unloading Before Reperfusion in Acute Myocardial Infarction
Authors: Lija Swain, Lara Reyelt, Shreyas Bhave, Xiaoying Qiao, Corinne J Thomas, Elric Zweck, Paige Crowley, Courtney Boggins, Michele Esposito, Michael Chin, Richard H Karas, William O'Neill, Navin K Kapur
Journal: Journal of the American College of Cardiology (2020)
Association of Childhood Maltreatment With Suicide Behaviors Among Young People
Authors: Ioannis Angelakis, Jennifer L. Austin, Patricia Gooding
Journal: JAMA Network Open (2020)

Children and young people's reports of experiences of adverse childhood events have increased in recent years, and this trend has been associated with an elevated risk for suicide behaviors. However, a systematic review and meta-analysis is needed to confirm the significance of this association in young people.To quantify the association between core types of childhood maltreatment, including sexual, physical, and emotional abuse and/or neglect and suicide behaviors in children and young adults.Medline, PsychInfo, Embase, Web of Science, and CINAHL (Cumulative Index to Nursing and Allied Health) databases were searched from January 1, 1980, until December 31, 2019. The reference lists of all the included studies were also checked.Quantitative studies that focused on the association between core types of childhood abuse and/or neglect and suicide ideation, plans, and attempts.Data were extracted by 2 independent raters. Publication bias and risk of bias across studies were assessed. Meta-analyses using random-effect models were applied, and heterogeneity was quantified using the I2 statistic. Data were analyzed from January to May 2020 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines.The association between core types of childhood maltreatment and suicide behaviors.Seventy-nine studies with 337 185 young individuals (mean [SD] age, 15.67 [2.11] years; 63.19% female) were included. The findings demonstrated that sexual abuse (odds ratio [OR], 3.41; 95% CI, 2.90-4.00), physical abuse (OR, 2.18; 95% CI, 1.75-2.71), emotional abuse (OR, 2.21; 95% CI, 1.37-3.57), emotional neglect (OR, 1.93; 95% CI, 1.36-2.74), physical neglect (OR, 1.79; 95% CI, 1.27-2.53), and combined abuse (OR, 3.38; 95% CI, 2.09-5.47) were significantly associated with higher rates of suicide attempts. Core types of childhood maltreatment were also associated with as much as 2.5-fold greater odds for suicide ideation, and sexual abuse with a 4.0-fold increase for suicide plans. Studies based on community samples (β [SE] = -1.68 [0.79]; P = .04) or with lower methodological quality (β [SE] = -2.86 [1.30]; P = .03) were associated more strongly with suicide attempts in those reporting experiences of sexual abuse, whereas young age was associated with both suicide attempts (β [SE] = -0.59 [0.27]; P = .03) and ideation (β [SE] = -0.41 [0.18]; P = .03).These findings suggest that policy actions should focus on raising public awareness and offering proactive suicide prevention therapies for children and young adults who have experienced abuse and/or neglect.
Healthcare Reimbursement and Service Utilization for One Year of Post-Allogeneic Hematopoietic Cell Transplantation (alloHCT) Care for Medicare Beneficiaries Ages 65 and Older with Acute Myeloid Leukemia
Authors: Lih-Wen Mau, Christa Lea Meyer, Linda J. Burns, Wael Saber, Patricia Steinert, David Vanness, Jaime Preussler, Alicia Silver, Susan Leppke, Elizabeth Anne Murphy, Ellen Denzen
Journal: Blood (2017)
Diabetes and COVID-19: Moving From News to Knowledge and a Glucose Hypothesis
Authors: Matthew C. Riddle
Journal: Diabetes Care (2020)

Science makes civilization possible. New observations provoke theories as to what they mean. Theories (hypotheses) are tested by systematically gathering and analyzing further information. Support for a theory by these methods (experiments) can lead to a plan of action. Other observations from this process (research) may pose further questions, leading to more experiments. In the past, actionable knowledge accumulated slowly, but digital technology has accelerated everything. Novel observations appear as “news” distributed by electronic, broadcast, and print media. Floods of reports, all apparently equal in significance, compete for attention. The media have insatiable appetites—they demand new material daily. Delivery of news is driven by its power to elicit emotional reactions, and we are all somewhat addicted. But news does not teach us what to do. Some items are valid and reproducible, others confusing, some misleading. Each can be placed in context, verified, and converted into useful knowledge using the scientific method, but this takes time.

Experience with the coronavirus disease 2019 (COVID-19) pandemic and its implications for people with diabetes illustrates this process. Diabetes Care has welcomed early reports on COVID-19, even when the first data sets were unavoidably limited. Special collections of articles appeared in the July and August issues, but most were available online earlier (1). These and articles published elsewhere confirmed the alarming news that people with diabetes are up to three times more likely than others to become severely ill or die of COVID-19. They showed that older age, obesity, and other medical conditions often associated with diabetes are also associated with increased risk. These reports highlighted the need for people with diabetes to take precautions to avoid infection, but they did not provide much guidance on how to treat these patients if they did fall ill. Articles by expert clinicians, based on the evidence and …
Prostaglandin E2 stimulates cAMP signaling and resensitizes human leukemia cells to glucocorticoid-induced cell death
Authors: Justine E. Roderick, Kayleigh M. Gallagher, Leonard C. Murphy, Kevin W. O’Connor, Katherine Tang, Boyao Zhang, Michael A. Brehm, Dale L. Greiner, Jun Yu, Lihua Julie Zhu, Michael R. Green, Michelle A. Kelliher
Journal: Blood (2020)
Predicting Cancer Evolution Using Cell State Dynamics
Authors: Marieke L. Kuijjer
Journal: Cancer Research (2020)

Abstract One of the biggest challenges in cancer is predicting its initiation and course of progression. In this issue of Cancer Research, Rockne and colleagues use state transition theory to predict how peripheral mononuclear blood cells in mice transition from a healthy state to acute myeloid leukemia. They found that critical transcriptomic perturbations could predict initiation and progression of the disease. This is an important step toward accurately predicting cancer evolution, which may eventually facilitate early diagnosis of cancer and disease recurrence, and which could potentially inform on timing of therapeutic interventions. See related article by Rockne et al., 3157
David, Brutus, and Caracalla—A Sculptural Chronology of Anatomical Observation
Authors: Neal Breakey
Journal: JAMA Cardiology (2020)

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Abstract B28: A cross-species enhancer activity analysis approach to identify the Ewing sarcoma cell of origin
Authors: Sarah Grissenberger, Anna Poetsch, Monika Heinzl, Luisa Morelli, Nathan Sheffield, Niko Popitsch, Heinrich Kovar, Martin Distel
Journal: Cancer Research (2020)

Abstract Ewing sarcoma is a malignant bone and soft tissue tumor in children and adolescents. In 85% of all cases the formation of Ewing sarcoma is caused by a chromosomal translocation, leading to the expression of the oncogene EWS-FLI1. This aberrant transcription factor is the main driver of the disease and leads to massive transcriptional dysregulation. Although the genetic mechanism driving Ewing sarcoma is well understood, an animal model adequately mimicking the disease is still lacking. One reason why modeling attempts have remained difficult is the elusive cell of origin in Ewing sarcoma. Several cell types including neural crest progenitor cells and mesenchymal stem cells have been proposed, but none of them has yet been confirmed as cell of origin of Ewing sarcoma. Towards identifying this cell of origin, we are currently following a novel cross-species approach by exploring the use of enhancers, which are specifically active in Ewing sarcoma cells, but were not created de novo by EWS-FLI1. Injection of reporter constructs into zebrafish embryos allows for visualization of cell types with activity of the selected enhancers and provides us with cell-of-origin candidate cell types. To investigate which of these candidate cells are permissive for development of Ewing-like tumors, we will also express EWS-FLI1 in these cells. If successful, this approach will not only reveal the Ewing sarcoma cell of origin but also result in a zebrafish Ewing sarcoma model, which will help to understand tumor initiation and progression and, furthermore, will be a valuable tool to develop novel therapeutic strategies. Citation Format: Sarah Grissenberger, Anna Poetsch, Monika Heinzl, Luisa Morelli, Nathan Sheffield, Niko Popitsch, Heinrich Kovar, Martin Distel. A cross-species enhancer activity analysis approach to identify the Ewing sarcoma cell of origin [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 B28.
Abstract IA29: Developmental and oncogenic programs in pediatric brain tumors dissected by single-cell RNA-sequencing
Authors: Mariella G. Filbin
Journal: Cancer Research (2020)

Abstract During development, the multiple cell types of human brain arise from pluripotent stem cells via progressively more committed progenitor cells. Emerging data suggest that pediatric brain tumors arise from progenitors that have become developmentally stalled. In preliminary studies, our lab used single-cell RNA-seq to display the expression profiles of individual cells within pediatric midline and hemispheric high-grade gliomas. Our data show that these tumors are composed of (i) replicating cells that resemble glial and neural progenitors and (ii) maturing cells resembling astrocytes, oligodendrocytes, or mesenchymal cells. In this presentation I will address how single-cell RNA-sequencing has revolutionized our understanding of the developmental hierarchy and oncogenic programs in pediatric brain tumors. Our recent findings pointing towards potential cells of origin of midline and hemispheric pediatric high-grade gliomas as well as plasticity of different cancer cell states will be discussed. Citation Format: Mariella G. Filbin. Developmental and oncogenic programs in pediatric brain tumors dissected by single-cell RNA-sequencing [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 IA29.
Combination of In Situ Lcn2 pRNA-RNAi Nanotherapeutics and iNSC Transplantation Ameliorates Experimental SCI in Mice
Authors: Alice Braga, Sara Bandiera, Jeroen Verheyen, Regan Hamel, Carola Rutigliani, Frank Edenhofer, Jayden Aaron Smith, Stefano Pluchino
Journal: Molecular Therapy (2020)

Spinal cord injury (SCI) is a debilitating neurological condition characterized by different cellular and molecular mechanisms that interplay in exacerbating the progression of the pathology. No fully restorative therapies are yet available, and it is thus becoming recognized that combinatorial approaches aimed at addressing different aspects of SCI will likely results in greater functional outcomes. Here we employed packaging RNA-mediated RNA interference (pRNA-RNAi) nanotherapeutics to downregulate in situ the expression of lipocalin 2 (Lcn2), a known mediator of neuroinflammation and autocrine mediator of reactive astrogliosis, and to create a more amenable niche for the subsequent transplantation of induced neural stem cells (iNSCs). To our knowledge, this is the first approach that takes advantage of the modular and multifunctional pRNA three-way junction platform in the SCI niche, while also exploiting the therapeutic potential of immune-compatible and feasible iNSC transplants. We show the combination of such treatments in a mouse model of contusion thoracic SCI leads to significant improvement of locomotor function, albeit not better than single pRNA-RNAi treatment, and results in synergistic histopathological effects, such as reduction of glial scar volume, diminished pro-inflammatory response, and promotion of neuronal survival. Our results provide evidence for a novel combinatorial approach for treating SCI.
Abstract 10485: Low Density Lipoprotein Cholesterol (LDL-C) Lowering in a Population Represented in a Meta-Analysis of Major Randomized Trials is Associated with a Positive Health-Economic Benefit
Authors: Irfan Khan, Peter J Neumann, Paul W Radensky
Journal: Circulation (2011)

Introduction: LDL-C is a key target for lipid-lowering therapy and reduction in cardiovascular (CV) event risk. A recent meta-analysis of 26 major randomized trials comprising 170,000 subjects demo...
Abstract A18: Characterization of checkpoint inhibitors in the tumor microenvironment (TME) and peripheral blood in endemic Burkitt Lymphoma
Authors: Priya Saikumar-Lakshmi, Cliff Oduor, Catherine Forconi, Patrick Marsh, John Michael Ong’echa, Jeffrey Bailey, Ann Moormann
Journal: Cancer Research (2020)

Abstract Introduction: The tumor microenvironment and the interaction between immune checkpoint inhibitors (ICIs) and tumor cells are essential to understand for designing future immunotherapy strategies. In this study, we aim to characterize the tumor microenvironment (TME) in children diagnosed with endemic Burkitt lymphoma (eBL), the most common pediatric cancer in Africa. A history of chronic malaria (Plasmodium falciparum) and Epstein-Barr virus (EBV) coinfections are both risk factors in the etiology of eBL. Methods: Using multicolor flow cytometry and single-cell RNA sequencing, we analyzed the expression of immune checkpoint inhibitors in T cells from the tumor microenvironment and from peripheral blood mononuclear cells (PBMC) of eBL patients, along with age-matched controls with different malaria exposure. Additionally, CD8 T-cell infiltration was confirmed by immunohistochemistry. Results: PD-1+ CD4 T cells from eBL PBMCs were increased in number compared to healthy controls from the malaria-endemic area (p=0.03). Both CD4 and CD8 T cells from eBL PBMCs reveal higher frequency of TIGIT expressers compared to healthy controls (non-malaria endemic) (p=0.002, p=0.007 respectively). PD1+ TIGIT+ IFNG- memory CD4 T cells phenotype from eBL PBMCs was increased upon short stimulation with PMA/ionomycin, as well as “naive-like” CD95+ PD1high TIGIT+ CTLA4+ IFNG+ CD8T cells. Tumor samples from 4 eBL patient were used on single-cell analysis; we observed activated T-cells profile that highly upregulated TIGIT within the tumor microenvironment. We also noticed relatively low expression of other ICIs such as PD1, TIM3, LAG3, and CTLA4. Base on all these data, we calculated an exhaustion score that was higher than the cytotoxicity score in our eBL-derived tumor-infiltrating lymphocytes (TILs). In addition, we use immunohistochemistry staining to confirm CD8 T-cell infiltration and ICI expression in eBL tumor fine needle aspirates. Our future directions will employ TIGIT blockade inhibitor studies of CD8 T cells, in order to increase expansion and function of CD8 TILs. Our results will help support future development of ICI therapies in endemic Burkitt lymphoma. Citation Format: Priya Saikumar-Lakshmi, Cliff Oduor, Catherine Forconi, Patrick Marsh, John Michael Ong’echa, Jeffrey Bailey, Ann Moormann. Characterization of checkpoint inhibitors in the tumor microenvironment (TME) and peripheral blood in endemic Burkitt Lymphoma [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 A18.