tbuckley/cabot-search huggingface dataset:
Two-Year Neurodevelopmental Outcomes After Mild Hypoxic Ischemic Encephalopathy in the Era of Therapeutic Hypothermia
Authors: Mikael Finder, Geraldine B. Boylan, Deirdre Twomey, Caroline Ahearne, Deirdre M. Murray, Boubou Hallberg
Journal: JAMA Pediatrics (2019)

Therapeutic hypothermia reduces risk of death and disability in infants with moderate to severe hypoxic ischemic encephalopathy (HIE). Randomized clinical trials of therapeutic hypothermia to date have not included infants with mild HIE because of a perceived good prognosis.To test the hypothesis that children with mild HIE have worse neurodevelopmental outcomes than their healthy peers.Analysis of pooled data from 4 prospective cohort studies in Cork, Ireland, and Stockholm, Sweden, between January 2007 and August 2015. The dates of data analysis were September 2017 to June 2019. Follow-up was performed at age 18 to 42 months. In this multicenter cohort study, all children were born or treated at the tertiary centers of Cork University Maternity Hospital, Cork, Ireland, or Karolinska University Hospital, Stockholm, Sweden. In all, 690 children were eligible for this study.At discharge, all children were categorized into the following 5 groups using a modified Sarnat score: healthy controls, perinatal asphyxia (PA) without HIE, mild HIE, moderate HIE, and severe HIE.Cognitive, language, and motor development were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition (BSITD-III). The BSITD-III scores are standardized to a mean (SD) of 100 (15), with lower scores indicating risk of developmental delay.Of the 690 children eligible for this study, 2-year follow-up data were available in 471 (mean [SD] age at follow-up, 25.6 [5.7] months; 54.8% male), including 152 controls, 185 children with PA without HIE, and 134 children with HIE, of whom 14 had died. Infants with mild HIE (n = 55) had lower cognitive composite scores compared with controls, with a mean (SD) of 97.6 (11.9) vs 103.6 (14.6); the crude mean difference was -6.0 (95% CI, -9.9 to -2.1), and the adjusted mean difference was -5.2 (95% CI, -9.1 to -1.3). There was no significant difference in the mean cognitive composite scores between untreated children (n = 47) with mild HIE and surviving children with moderate HIE (n = 53) treated with therapeutic hypothermia, with a crude mean difference for mild vs moderate of -2.2 (95% CI, -8.1 to 3.7).This study's findings suggest that, at age 2 years, the cognitive composite scores of children with a history of mild HIE may be lower than those of a contemporaneous control group and may not be significantly different from those of survivors of moderate HIE treated with therapeutic hypothermia.
CD34+ Cell Dose Effects on Clinical Outcomes of Patients with Acute Myeloid Leukemia after T-Replete Haploidentical Allogeneic Hematopoietic Stemcell Transplantation Using Peripheral Blood Stem Cells. a Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)
Authors: Enrico Maffini, Myriam Labopin, Didier Blaise, Fabio Ciceri, Zafer Gulbas, Etienne Daguindau, Stephanie Nguyen-Quoc, Patrice Chevallier, Gerard Socie, Mercedes Colorado, Yener Koc, Francesco Lanza, Arnon Nagler, Mohamad Mohty
Journal: Blood (2019)
Durable Responses Observed in Elderly AML Patients Unfit for Intensive Chemotherapy with First-in Class Selective AXL Inhibitor Bemcentinib (BGB324) in Combination with LDAC: Phase II Open-Label Study
Authors: Sonja Loges, Michael Heuser, Jörg Chromik, Carlos Enrique Vigil, Peter Paschka, Francesca Re, Nicola Di Renzo, Roberto Massimo Lemoli, Daniele Giovanni Mattei, Isabel Ben Batalla, Monica Hellesoy, David Micklem, Robert J. Holt, James B. Lorens, Muhammad Shoaib, Hassan Aly, Wouter Hanekom, Walter Fiedler, Jorge E. Cortes, Bjorn T. Gjertsen
Journal: Blood (2019)
Application of transient elastography in nonalcoholic fatty liver disease
Authors: Xinrong Zhang, Grace Lai-Hung Wong, Vincent Wai-Sun Wong
Journal: Clinical and Molecular Hepatology (2019)

Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide. Although it has become one of the leading causes of cirrhosis and hepatocellular carcinoma in the Western world, the proportion of NAFLD patients developing these complications is rather small. Therefore, current guidelines recommend noninvasive tests for the initial assessment of NAFLD. Among the available non-invasive tests, transient elastography by FibroScan® (Echosens, Paris, France) is commonly used by hepatologists in Europe and Asia, and the machine has been introduced to the United States in 2013 with rapid adoption. Transient elastography measures liver stiffness and the controlled attenuation parameter simultaneously and can serve as a one-stop examination for both liver steatosis and fibrosis. Liver stiffness measurement also correlates with clinical outcomes and can be used to select patients for varices screening. Although obesity is a common reason for measurement failures, the development of the XL probe allows successful measurements in the majority of obese patients. This article reviews the performance and limitations of transient elastography in NAFLD and highlights its clinical applications. We also discuss the reliability criteria for transient elastography examination and factors associated with false-positive liver stiffness measurements.
2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Executive Summary
Authors: Donna K. Arnett, Roger S. Blumenthal, Michelle A. Albert, Andrew B. Buroker, Zachary D. Goldberger, Ellen J. Hahn, Cheryl Dennison Himmelfarb, Amit Khera, Donald Lloyd-Jones, J. William McEvoy, Erin D. Michos, Michael D. Miedema, Daniel Muñoz, Sidney C. Smith, Salim S. Virani, Kim A. Williams, Joseph Yeboah, Boback Ziaeian
Journal: Journal of the American College of Cardiology (2019)
CSIG-07. TARGETING CELL POLARITY PROTEINS FROM THE SCRIBBLE COMPLEX DISRUPTS GLIOBLASTOMA STEM CELL VIABILITY AND INVASION IN NEURAL TISSUE
Authors: Somanath Kundu, Mohan Nandhu, Sharon Longo, John Longo, Timothy Richardson, Lawrence Chin, Mariano Viapiano
Journal: Neuro-Oncology (2019)

Abstract Despite their molecular heterogeneity, glioblastomas (GBMs) retain a common phenotypical feature, which is their diffuse invasion through neural tissue that makes complete resection impossible. This invasive ability requires changes in cell polarity for the tumor cells to migrate following cues from their microenvironment. Cytoskeleton-associated proteins of the DLG family are part of the Scribble polarity complex that maintains stable cell-cell junctions; accordingly, these proteins are “tumor suppressors” usually downregulated in solid tumors. However, we have found that one family member, DLG5, is highly upregulated in GBM compared to other solid tumors. Results from Western blot, immunohistochemistry, and RNAseq confirmed that DLG5 is highly expressed in GBM compared to normal brain and is the predominant DLG family member in GBM stem cells (GSCs). DLG5 knockdown reduced cell viability after four days in culture, but had an immediate (24h) negative effect on cell invasion through Matrigel and brain tissue. At the molecular level DLG5 knockdown downregulated components of the Sonic-Hedgehog pathway, including PTCH1 and Gli1, as well as SHH-regulated downstream genes (CCND2, cMYC and CD44). Accordingly, DLG5-deficient GSCs showed reduced Gli1 phosphorylation in response to exogenous SHH and lacked increased invasiveness in presence of SHH compared to control GSCs. Ongoing experiments are evaluating the growth and invasion of DLG5-deficient GSCs in response to signals derived from oligodendrocyte progenitor cells, which are a major source of SHH in the postnatal brain. Taken together, our results describe for the first time the expression of DLG proteins in malignant gliomas and reveal an unexpected pro-tumoral function for the protein DLG5 that differs from its proposed tumor-suppressor role in other solid cancers. Targeting DLG5 could disrupt the ability of GSCs to respond to signals enriched in the neural microenvironment (SHH), contributing to the long-term control of residual tumor after surgical resection.
The most beautiful COPD chart in the world: all together to end COPD!
Authors: Joan B. Soriano, Julio Ancochea, Bartolomé R. Celli
Journal: European Respiratory Journal (2019)

Since its inception in 2002, World COPD Day is celebrated to raise awareness and reduce COPD-related burden. In spite of this global effort, COPD remains poorly recognised. Indeed, Boehm et al . [1], using Google Trends, noted the rather limited global awareness of COPD, which rates eighth within the top 10 causes of disease burden searched. On a positive note, they identified a seasonal trend, with a peak activity in November, that could be related to the increased incidence of acute exacerbations during the winter period, but it may also reflect the "noise" created by initiatives like the COPD Awareness Month and World COPD Day. The 2019 theme for World COPD Day is "All Together to End COPD". Optimistically, recent evidence of projected global COPD mortality rates indicates this theme to actually be more than wishful thinking. All together to end COPD! <http://bit.ly/34C7gId>
A Refractory B-ALL Patient Relapsed with Leukemia Cells Expressing CD19 and Anti-CD19 CAR Gene 14 Days after CR from Anti-CD19 CAR T-Cell Therapy
Authors: Liu Meijing, Rui Cui, Juan Mu, Ji-jun Yuan, Nan Mou, Zhen-xing Yang, Jiang Yan-yu, Meng Juanxia, QI Deng
Journal: Blood (2019)
CBMT-38. THERAPEUTIC INHIBITION OF THE SPLICEOSOME IN GLIOBLASTOMA: CHANGES FORM MINOR TO MAJOR
Authors: Tobias Bonifert, Sonali Arora, Matthew Fitzgibbon, Patrick Paddison
Journal: Neuro-Oncology (2019)

Abstract Chemical or genetic perturbation of the spliceosome function may represent a therapeutic opportunity for Glioblastoma multiforme (GBM) and other cancers. We and others have shown that oncogenic MYC activity causes spliceosome vulnerability and leads to deficits in 3’ splice site recognition upon spliceosome perturbation. Several spliceosome inhibitors in pre-clinical development and in clinical trials target the U2 snRNP subcomplex SF3B, which is essential for 3’ splice site recognition. We showed that knockdown of one of its subunits, PHF5A, causes GBM-specific changes in splicing, including increases in exon skipping, intron retention and activation of alternative 3’ and 5’ splice sites. However, in depth analysis of these events revealed they are disproportionately enriched for “minor” introns. This class of ~800 introns is specifically excised by an alternative splicing pathway which involves the U12-dependent spliceosome. Remarkably, we provide evidence that inhibition of PHF5A in GBM stem-like cells causes increased retention of most minor introns, as well as activation of cryptic and alternative U2 snRNP-dependent splicing sites. We further demonstrate that components of the U12 snRNP complex are differentially required for GSC-specific viability. Our results suggest that regulation of the splicing of U12-type introns may be critically important for GBM tumor cell viability.
IGF1R-IRS1/2 Signaling Pathway Is a Potential Target for FLT3-Mutated Acute Myeloid Leukemia
Authors: Juan L Coelho-Silva, Diego A Pereira-Martins, Virginia Campos Silvestrini, Eduardo M Rego, Vitor Marcel Faca, João Agostinho Machado-Neto, Fabiola Traina
Journal: Blood (2019)
Early Signs of Tolerability and Activity in a Phase 2 Study of Weekly Vincristine Sulfate Liposomal Injection (VSLI, MarqiboÒ) in Adults with Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia (ALL) in Second Relapse or Progressing Following Two Anti-Leukemia Treatment Lines
Authors: Susan O’Brien, Lloyd E. Damon, Melissa L. Larson, Gary Schiller, Wendy Stock, Deborah A Thomas, Biao Lu, Michael S. Imperiale, Hagop M Kantarjian
Journal: Blood (2008)
Concurrent Herpes Zoster and Varicella
Authors: J. J. Manning
Journal: BMJ (1944)

JOURNAL115She was x-rayed again on June 9.This showed a rather large stomach, but no sign of any recurrence of the hernia.She has remained entirely free from gastric symptoms since her discharge from the hospital, and six months after the operation had had no further trouble. COMMENTThe case is interesting on account of the condition found at operation, where the stomach was twisted and enormously distended, and by the rapid recovery of the gastric func- tions in spite of the excessive stretching of the muEcular and mucous wall of the stomach.How the torsion had occurred
Pulmonary Alveolar Microlithiasis
Authors: M. Abdel-Hakim, S. El-Mallah, M. Hashem, S. Abdel-Halim
Journal: Thorax (1959)

Pulmonary alveolar microlithiasis is a rare disease of obscure nature characterized by intra- alveolar calcific deposits that show radiologically as multiple small dots of calcification evenly scattered throughout the lungs.The striking feature about the disease is the diffuse and extensive radiological appearance in contrast to the minimal, or lacking, symptoms and signs early in the disease. INCIDENCEEighteen cases have been reported in the literature, but the diagnosis was established during life in eight cases only.To our knowledge, the two cases we report are the nineteenth and twentieth.Among these 18 cases it has been noticed that 11 were in men and seven in women.The youngest patient reported was 6 years old, but the average age was between 30 and 50 years.Diagnosis was made at necropsy in 10 of the 18 cases, by pulmonary biopsy in four, and radio- logically and clinically in four.A familial incidence has been noticed in some instances.Mikhailov (1954) reported the disease in two brothers and in the son of one of them; the diagnosis was verified by lung biopsy in one on July 15, 2023 by guest.
Tocilizumab for Prophylaxis of Cytokine Release Syndrome after Outpatient-Based Haploidentical T-Cell Replete Peripheral Blood Stem Cell Transplantation
Authors: Oscar Marquez, Andrés Gómez-De León, Perla R. Colunga Pedraza, Cesar O Pezina Cantú, Diana E Garcia-Camarillo, Paola Santana-Hernandez, Cesar Homero Gutierrez-Aguirre, David Gomez-Almaguer
Journal: Blood (2019)
A Phase IB Study of Blinatumomab (blina) in Patients with B Cell Acute Lymphoblastic Leukemia (ALL) and B-Cell Non-Hodgkin Lymphoma (NHL) As Post-Allogeneic Blood or Marrow Transplant (allo-BMT) Remission Maintenance
Authors: Jonathan Webster, Richard F. Ambinder, Richard J. Jones, Nina D. Wagner-Johnston, Gabrielle T. Prince, Audra Shedeck, Amanda Blackford, Leo Luznik, Ivana Gojo
Journal: Blood (2019)
PATH-18. CSF-DERIVED CIRCULATING TUMOR DNA REFLECTS DISEASE COURSE AND CLONAL EVOLUTION IN MEDULLOBLASTOMA
Authors: Anthony P Y Liu, Rahul Kumar, Kyle Smith, Giles Robinson, Amar Gajjar, Paul Northcott
Journal: Neuro-Oncology (2019)

Abstract Medulloblastoma (MB) is the most common malignant brain tumor in young children. A multi-modal approach comprises standard of care, and recent advances in molecular studies have identified clinically relevant subgroups. Nonetheless, 30% of MB patients relapse or progress, conferring dismal prognosis. Such suboptimal outcome is partly due to a lack of sensitive biomarkers for response-adapted personalization of treatment and relapse prediction. Circulating tumor DNA has been shown to correlate with disease status in a variety of adult cancers, but studies in pediatric brain tumors, including medulloblastoma, are scarce. Here, we aim to evaluate the utility of profiling cell-free DNA (cfDNA) derived from longitudinally-banked cerebrospinal fluid (CSF) samples collected from children with MB enrolled in two prospective, multi-center trials (SJMB03 and SJMB12, estimated sample size of 100 patients, including 50 with subsequent progression). cfDNA was extracted, quantified, and analyzed for size distribution from pre-centrifuged CSF serially banked during the course of treatment and follow-up. Low-pass whole genome sequencing (LP-WGS) enabled detection of chromosomal and focal copy number alterations (CNAs). CNAs detected in cfDNA were compared against known somatic changes in corresponding primary tumors. Detectability of tumor-specific CNAs in cfDNA was then correlated with tumor burden and patient outcome. Pilot analysis showed presence of arm level and/or focal CNAs in cfDNA from 80% of CSF samples in 20 children with metastatic MB, and longitudinal assessment revealed correlation with clinical course throughout treatment with radiotherapy and chemotherapy. Further comparison of tumor and longitudinal cfDNA derived CNAs revealed divergent genomic alterations implicating potential oncogenic mechanisms underlying treatment failure and recurrence. Our study performed on a large prospective series of MB trial patients substantiates the utility of CSF derived cfDNA as an actionable biomarker in high-risk MB patients while also facilitating understanding of tumor evolution and heterogeneity.
Abstract 11100: Persistent Atrial Fibrillation as a Dynamic Network of Competing Zones of Control
Authors: Neal K Bhatia, Albert J Rogers, David E Krummen, Mahmood Alhusseini, Nosheen Moosvi, Chad Brodt, Tina Baykaner, Paul J Wang, Wouter-Jan Rappel, Sanjiv M Narayan
Journal: Circulation (2019)

Introduction: Mechanisms for persistent atrial fibrillation (AF) are divergent, yet agree that AF shows organized (high frequency, rotational or focal activity or passive waves) or disorganized (co...
Omission of Staging Bone Marrow Biopsy Does Not Affect Outcomes in Patients with Stage I Extranodal Marginal Zone Lymphoma (EMZL) Treated with Radiation Therapy
Authors: Juan Pablo Alderuccio, Derek Isrow, Isildinha M. Reis, Sunil Iyer, Jessica Meshman, Wei Zhao, Arnold M. Markoe, Izidore S. Lossos
Journal: Blood (2019)
Multiparametric Flow-Cytometry Is a Reliable Tool for Measurable Residual Disease Assessment and Risk-Stratification of FLT3-Mutated AML Patients
Authors: Raffaele Palmieri, Luca Maurillo, Alfonso Piciocchi, Maria Ilaria Del Principe, Valentina Arena, Stefano Soddu, Ambra Di Veroli, Giovangiacinto Paterno, Eleonora De Bellis, Raffaella Cerretti, Gottardo De Angelis, Benedetta Mariotti, Tiziana Ottone, Mariadomenica Divona, Serena Lavorgna, Maria Irno Consalvo, Consuelo Conti, Cristina Attrotto, Daniela Fraboni, William Arcese, Maria Teresa Voso, Adriano Venditti, Francesco Buccisano
Journal: Blood (2019)
CELL-Derived Microparticles and Sickle CELL Disease Chronic Vasculopathy in Sub-Saharan Africa
Authors: Abdoul Karim Dembele, Claudine Lapoumeroulie, Mor Diaw, Oumar Tessougué, Lucile Offredo, Dapa Aly Diallo, Saliou Diop, Jacques Elion, Yves Colin Aronovicz, Pierre Louis Tharaux, Xavier Jouven, Marc Romana, Brigitte Ranque, Caroline Le Van Kim
Journal: Blood (2019)
Bisphosphonate‐Functionalized Scaffolds for Enhanced Bone Regeneration
Authors: Yutao Cui, Tongtong Zhu, Di Li, Zuhao Li, Yi Leng, Xuan Ji, He Liu, Dankai Wu, Jianxun Ding
Journal: Advanced Healthcare Materials (2019)

Abstract The local sustained release of bioactive substances are attracting increasing attention in bone tissue engineering, which is beneficial to bone tissue formation and helps to improve the bone ingrowth ability of a scaffold. Bisphosphonates (BPs), as a representative kind of osteoclast inhibitors, are proven to possess excellent osteogenic induction capability. Accordingly, various physical and chemical strategies are developed to functionalize bone tissue scaffolds with BPs to achieve controlled release profiles. Compared with traditional treatment modalities, local release of BPs from these composite scaffolds will contribute to continuous bone integration without the risk of many complications. This review explores the molecular mechanisms of BPs on bone metabolism and analyzes the appropriate concentrations of BPs that promote bone regeneration. The advanced BP loading strategies, implant modification technologies, and BP‐loaded composite scaffolds based on different matrices are summarized. Finally, the latest advances and the future development of BP‐modified scaffolds for enhanced bone regeneration are discussed. This article provides leading‐edge design strategies of the BP‐functionalized bone engineering scaffolds for improved bone repairability.
Precision Medicine Based on the Achievement of Sustained Undetectable Minimal Residual Disease (MRD) By Next-Generation Flow (NGF) and Imaging Leads to Significant Reduction in Risk of Progression of Patients with Multiple Myeloma (MM)
Authors: Jose Enrique De La Puerta Rueda, Leire Burgos, Garazi Letamendi Madariaga, Cristina Martinez Bilbao, Luis Atutxa Aresti, Jesus Ojanguren Bergaz, Matxalen Olivares Salaverri, Begoña Sancho Garaizabal, Isabel Uriarte, Iñigo Vicente Olabarria, Raquel Pérez Garay, Ana de Juan Arroyo, Itxaso Amarika Ibarrondo, Tomas Carrascosa Vallejo, Amaia Casado Diez, Cristina Cortes Fernández, Ianire Etxeguren Urkixo, Eukene Gainza González, Inés González Vallejo, Javier Goikolea Ugarte, Inmaculada Barredo Santamaría, Alberto Sáiz López, Antonio Vázquez Rodríguez, Eloisa Urrechaga Igartua, Maria José Ereño Ealo, Estibalitz Montejo Rodrigo, Elixabete Pastor Ausin, Alberto Cabrera Zubizarreta, José María Ontañón Garcés, Ibone Saralegui Prieto, Natalia Maruri Machado, Paula Arana Berganza, Mara Celis Alvarez, Ane Aranbarri Larrañaga, Paloma Ibarrondo Chamorro, Bruno Paiva
Journal: Blood (2019)
Medical problems of adults who were sexually abused in childhood
Authors: R. Fry, R. Wallis
Journal: BMJ (1990)

<i>BACKGROUND AND PURPOSE:</i> Many therapeutic techniques have been used for the treatment of symptomatic vertebral hemangiomas (SVH), and each has its own limitations. Our objective was to evaluate the therapeutic efficacy of alcohol ablation for treating these lesions. <i>METHODS:</i> Fourteen patients with SVH were treated by injection of absolute alcohol into the lesion via the percutaneous transpedicular route under CT guidance. Symptoms before treatment included neurologic deficit in 13 patients and debilitating pain in one. All patients underwent preprocedural MR imaging. All patients had clinical and MR imaging follow-up (14 patients at 48–96 hours and 2 months; six at 9–15 months). Results were divided into excellent (resumption of work, alleviation of pain), good (significant improvement), and failure of treatment categories on the basis of subjective assessment of clinical improvement. Clinical improvement/deterioration was correlated with MR-revealed changes. <i>RESULTS:</i> All patients showed transient deterioration of neurologic status after alcohol ablation. Subsequently, excellent results were seen in five patients and eight were in the good category. One patient in whom treatment failed also developed a complication (paravertebral abscess). Four of the eight patients with good results had preprocedural cord changes. Total follow-up ranged from 5 to 31 months, with 11 patients showing stable improvement. One patient developed recurrent hemangioma within a month. Another patient became symptomatic after initial good response, secondary to the collapse of the involved vertebral body. Good correlation was found between clinical improvement and reduction of epidural soft-tissue masses on MR images. Cord signal alteration seen on MR images in four treated patients, however, did not show any change after treatment. <i>CONCLUSION:</i> Alcohol ablation is an effective management option for symptomatic vertebral hemangiomas. Although encouraging results were seen in almost 86% of our patients, a longer follow-up period still is needed to assess the stability of improvement. Potential complications include vertebral collapse and infection.
Trial in Progress: Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Global Study of Fostamatinib for the Treatment of Warm Antibody Autoimmune Hemolytic Anemia
Authors: Nichola Cooper, Isabel Gorham, Ann M. Lowe, Robert P. Numerof, Sandy Tong, David J. Kuter
Journal: Blood (2019)