tbuckley/cabot-search huggingface dataset:
A BMP/activin A chimera is superior to native BMPs and induces bone repair in nonhuman primates when delivered in a composite matrix
Authors: Howard J. Seeherman, Stephen P. Berasi, Christopher T. Brown, Robert X. Martinez, Z. Sean Juo, Scott Jelinsky, Michael J. Cain, Jaclyn Grode, Kathleen E. Tumelty, Marc Bohner, Orly Grinberg, Nadav Orr, Oded Shoseyov, Jeroen Eyckmans, Christopher Chen, Pablo R. Morales, Christopher G. Wilson, Eric J. Vanderploeg, John M. Wozney
Journal: Science Translational Medicine (2019)

BV-265, a BMP-2/BMP-6/activin A chimera, delivered in a composite matrix generates bone repair in nonhuman primates at lower concentrations than BMP-2.
Measles: low uptake blamed on “incredulity and hostility” towards doctors
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Around 169 million of the world’ children did not receive their first dose of measles vaccine between 2010 and 2017, an average of 21.1 million a year, shows the latest report from Unicef.1

Of the world’s high income countries, the US topped the list for the number of children who were not vaccinated in that time, with 2 593 000 missing out. France came second with 608 000, then the UK with 527 000.

In low and middle income countries the situation was much worse, the report said. In 2017 nearly four million children under the age of 12 months missed out on the vaccine in Nigeria—the highest number worldwide—then 2.9 million in India, 1.2 million each …
Pulmonary Vascular Efficiency Worsening And Cardiac Energy Wasting During Early Stages Of Experimental Acute Respiratory Distress Syndrome
Authors: Arnoldo Santos, M. Monge-Garcia, João Batista Borges, E. Gomez-Penalver, J. Retamal, L. Lucchetta, Göran Hedenstierna, Anders Larsson, Fernando Suarez-Sipmann
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Pulmonary Vascular Efficiency Worsening And Cardiac Energy Wasting During Early Stages Of Experimental Acute Respiratory Distress Syndrome
Bone Regeneration: A Novel Bone Substitute with High Bioactivity, Strength, and Porosity for Repairing Large and Load‐Bearing Bone Defects (Adv. Healthcare Mater. 8/2019)
Authors: Jiao Jiao Li, Colin R. Dunstan, Ali Entezari, Qing Li, Roland Steck, Siamak Saifzadeh, Ameneh Sadeghpour, John R. Field, Austin Akey, Martin Vielreicher, Oliver Friedrich, Seyed‐Iman Roohani‐Esfahani, Hala Zreiqat
Journal: Advanced Healthcare Materials (2019)

In article number 1801298, Hala Zreiqat and co-workers showcase a Sr-HT-Gahnite bone substitute implanted in a sheep tibial segmental defect for one year. Focused ion beam scanning electron microscopy (FIB-SEM) cross-section of the implant-bone interface shows nanoscale detail of the scaffold (top) and loose connective tissue (bottom), between which is a disrupted zone of ceramic degradation and tissue infiltration.
Novel Therapies for an Aging Population
Authors: Jerry H. Gurwitz, Steven D. Pearson
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Childhood Oral Infections and Subclinical Atherosclerosis in Adulthood
Authors: Anwar T. Merchant, Salim S. Virani
Journal: JAMA Network Open (2019)

Pirkko J. Pussinen, PhD; Susanna Paju, DDS, PhD; Jaana Koponen, BDS; Jorma S. A. Viikari, MD, PhD; Leena Taittonen, MD, PhD; Tomi Laitinen, MD, PhD; David P. Burgner, MD, PhD; Mika Kähönen, MD, PhD; Nina Hutri-Kähönen, MD, PhD; Olli T. Raitakari, MD, PhD; Markus Juonala, MD, PhD
High-throughput Screening of Human Tumor Antigen–specific CD4 T Cells, Including Neoantigen-reactive T Cells
Authors: Carla Costa-Nunes, Amélie Cachot, Sara Bobisse, Marion Arnaud, Raphael Genolet, Petra Baumgaertner, Daniel E. Speiser, Pedro M. Sousa Alves, Federico Sandoval, Olivier Adotévi, Walter Reith, Maria Pia Protti, George Coukos, Alexandre Harari, Pedro Romero, Camilla Jandus
Journal: Clinical Cancer Research (2019)

Characterization of tumor antigen-specific CD4 T-cell responses in healthy donors and malignant melanoma patients using an in vitro amplified T-cell library screening procedure.A high-throughput, human leukocyte antigen (HLA)-independent approach was used to estimate at unprecedented high sensitivity level precursor frequencies of tumor antigen- and neoantigen-specific CD4 T cells in healthy donors and patients with cancer. Frequency estimation was combined with isolation and functional characterization of identified tumor-reactive CD4 T-cell clones.In healthy donors, we report frequencies of naïve tumor-associated antigen (TAA)-specific CD4 T cells comparable with those of CD4 T cells specific for infectious agents (Tetanus toxoid). Interestingly, we also identified low, but consistent numbers of memory CD4 T cells specific for several TAAs. In patients with melanoma, low frequencies of circulating TAA-specific CD4 T cells were detected that increased after peptide-based immunotherapy. Such antitumor TAA-specific CD4 T-cell responses were also detectable within the tumor-infiltrated tissues. TAA-specific CD4 T cells in patients displayed a highly polyfunctional state, with partial skewing to Type-2 polarization. Finally, we report the applicability of this approach to the detection and amplification of neoantigen-specific CD4 T cells.This simple, noninvasive, high-throughput screening of tumor- and neoantigen-specific CD4 T cells requires little biologic material, is HLA class II independent and allows the concomitant screening for a large number of tumor antigens of interest, including neoantigens. This approach will facilitate the immunomonitoring of preexisting and therapy-induced CD4 T-cell responses, and accelerate the development of CD4 T-cell-based therapies.
Abstract 19511: Spatiotemporal Variations in Intracardiac Shear Stress Differentially Modulate Trabeculation for Developmental Contractile Function
Authors: Juhyun Lee, Vijay Vedula, Yichen Ding, Junjie Chen, Alison Marsden, Tzung Hsiai
Journal: Circulation (2017)

Hemodynamic shear forces modulate cardiac development, and wall shear stress (WSS) promotes the initiation of endocardiac trabeculation. Whether special (∂τ/∂x) and temporal (∂τ/∂t) variations in s...
Abstract 11441: Musclin, a Novel Skeletal Muscle Derived Myokine, Attenuates LV Dysfunction and Myocardial Fibrosis During Cardiac Cachexia
Authors: Badder Kattih, Malgorzata Szaroszyk, Mortimer Korf-Klingebiel, Andrea Grund, Natali Froese, Michael Wagner, Thomas Thum, Viacheslav Nikolaev, Oliver J Müller, Hugo A Katus, Ali El-Armouche, Kai C Wollert, Johann Bauersachs, Joerg Heineke
Journal: Circulation (2018)

Introduction: Cardiac cachexia is a strong independent risk factor for mortality in patients with chronic heart failure. However, the mechanism how skeletal muscle wasting adversely affects the cou...
HGG-14. PEDIATRIC BITHALAMIC DIFFUSE GLIOMAS ARE DISTINGUISHED FROM THEIR UNILATERAL COUNTERPARTS BY FREQUENT EGFR EXON 20 INSERTIONS AND RARE HISTONE H3 MUTATIONS
Authors: Julieann Lee, Sean Ferris, Emily Sloan, Jeff Hofmann, David Samuel, David Scharnhorst, Aleli Siongco, Rong Li, Lee-way Jin, Reuben Antony, Mouied Alashari, Samuel Cheshier, Nicholas Whipple, Carol Bruggers, Corey Raffel, Nalin Gupta, Cassie Kline, Alyssa Reddy, Anu Banerjee, Ziad Khatib, Ossama Maher, Carole Brathwaite, Melike Pekmezci, Andrew Bollen, Tarik Tihan, Arie Perry, David Solomon
Journal: Neuro-Oncology (2019)

Though diffuse gliomas arising in the thalamus of children frequently harbor K27M mutation in the histone H3 genes H3F3A or HIST1H3B, children with diffuse gliomas involving the bilateral thalami at presentation often lack histone H3 mutations (Broniscer et al, Brain Pathology 2018). In order to investigate the molecular pathogenesis of pediatric bithalamic diffuse gliomas, we performed comprehensive genetic profiling of seven cases (ages 3–11 years). Six tumors (86%) harbored mutations in the EGFR oncogene in the absence of accompanying EGFR amplification. Four of these EGFR mutations were small in-frame insertions/duplications within exon 20 that encodes a portion of the intracellular tyrosine kinase domain, where mutations are common in lung adenocarcinoma and fibrous hamartoma of infancy but are not typically present in gliomas. The other two cases with EGFR mutations were located in the extracellular ligand-binding domain, where mutations and rearrangements are common in IDH-wildtype glioblastomas in the cerebral hemispheres of adults. Additional pathogenic alterations included TP53 mutation (n=4 cases), CDKN2A homozygous deletion (1), CDK6 amplification (1), CDKN2C mutation (1), TERT promoter mutation (1), HIST1H3B K27M mutation (1), and truncating mutations involving the BCOR (1), BCORL1 (2), LZTR1 (1), and CREBBP (1) transcriptional regulatory genes. No tumors harbored pathogenic alterations involving the H3F3A, HIST1H3C, SETD2, PDGFRA, MET, PPM1D, ACVR1, FGFR1, BRAF, PTPN11, IDH1, IDH2, MYB, and MYBL1 genes. In comparison, EGFR mutations are rare (<1% of 982 cases) in pediatric high-grade gliomas in general (Mackay et al, Cancer Cell 2017). Together, these findings identify pediatric bithalamic diffuse gliomas as a unique subtype of IDH-wildtype and mostly histone H3-wildtype high-grade glioma characterized by frequent EGFR kinase domain mutations, with implications for precision medicine treatment using small molecule kinase inhibitors such as poziotinib, a CNS-penetrant agent with selective activity against exon 20 mutant EGFR.
Amygdala NPY Circuits Promote the Development of Accelerated Obesity under Chronic Stress Conditions
Authors: Chi Kin Ip, Lei Zhang, Aitak Farzi, Yue Qi, Ireni Clarke, Felicia Reed, Yan-Chuan Shi, Ronaldo Enriquez, Chris Dayas, Bret Graham, Denovan Begg, Jens C. Brüning, Nicola J. Lee, Diana Hernandez-Sanchez, Gopana Gopalasingam, Julia Koller, Ramon Tasan, Günther Sperk, Herbert Herzog
Journal: Cell Metabolism (2019)
PAC‐14028 cream for atopic dermatitis
Authors: Y.W. Lee, C.‐H. Won, K. Jung, H.‐J. Nam, G. Choi, Y.‐H. Park, M. Park, B. Kim
Journal: British Journal of Dermatology (2019)

This research, from Korea, showed that a non‐steroid containing cream, called PAC‐14028, can be as effective in treating eczema symptoms as current creams on the market but with fewer side‐effects. Eczema is one of the most common skin diseases. Available topical (applied to the skin) treatments can be very effective in treating eczema symptoms. However, they can also cause negative side‐effects such as itching and burning, which can result in patients discontinuing their treatment. The research was conducted with 194 adults with mild to moderate eczema. Participants were split into four groups and treated with either a control cream or the new treatment, PAC‐14028 cream, at one of three different concentrations (0.1%, 0.3% or 1.0%). Participants applied the cream twice daily for eight weeks. The results were primarily measured using the Investigator's Global Assessment (IGA). This is a visual scale for assessing the severity of eczema in a patient based upon typical symptoms. After eight weeks, 57.5 percent of patients in the group who received the highest concentration PAC‐14028 cream, had an IGA score indicating that their symptoms of eczema were completely eradicated or reduced to an almost‐clear level. IGA success rates at week eight were 15 percent for the control cream, compared to 43 percent for PAC‐14028 cream at 0.1%, 38 percent for 0.3% and 57 percent 1.0%. The efficacy of PAC‐14028 cream was similar to a commonly used non‐steroidal cream called pimecrolimus but with a far lower incidence of unwanted side‐effects.
The Liver as an Endocrine Organ—Linking NAFLD and Insulin Resistance
Authors: Matthew J Watt, Paula M Miotto, William De Nardo, Magdalene K Montgomery
Journal: Endocrine Reviews (2019)

The liver is a dynamic organ that plays critical roles in many physiological processes, including the regulation of systemic glucose and lipid metabolism. Dysfunctional hepatic lipid metabolism is a cause of nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disorder worldwide, and is closely associated with insulin resistance and type 2 diabetes. Through the use of advanced mass spectrometry "omics" approaches and detailed experimentation in cells, mice, and humans, we now understand that the liver secretes a wide array of proteins, metabolites, and noncoding RNAs (miRNAs) and that many of these secreted factors exert powerful effects on metabolic processes both in the liver and in peripheral tissues. In this review, we summarize the rapidly evolving field of "hepatokine" biology with a particular focus on delineating previously unappreciated communication between the liver and other tissues in the body. We describe the NAFLD-induced changes in secretion of liver proteins, lipids, other metabolites, and miRNAs, and how these molecules alter metabolism in liver, muscle, adipose tissue, and pancreas to induce insulin resistance. We also synthesize the limited information that indicates that extracellular vesicles, and in particular exosomes, may be an important mechanism for intertissue communication in normal physiology and in promoting metabolic dysregulation in NAFLD.
Sustained long‐term efficacy and safety of adalimumab in paediatric patients with severe chronic plaque psoriasis from a randomized, double‐blind, phase <scp>III</scp> study
Authors: D. Thaçi, K. Papp, D. Marcoux, L. Weibel, A. Pinter, P.‐D. Ghislain, I. Landells, P.H. Hoeger, K. Unnebrink, M.M.B. Seyger, D.A. Williams, S. Rubant, S. Philipp
Journal: British Journal of Dermatology (2019)

Adalimumab (ADA) (Humira® , AbbVie Inc., U.S.A.) is approved by the European Medicines Agency for children aged ≥ 4 years with severe plaque psoriasis.To evaluate the long-term efficacy and safety of ADA in children with severe plaque psoriasis.Results are presented from the 52-week long-term extension (LTE) of the randomized, double-blind, double-dummy, phase III trial, in children with severe plaque psoriasis (results from prior periods have been published). Patients aged ≥ 4 and < 18 years were randomized 1 : 1 : 1 to ADA 0·8 mg kg-1 (40 mg maximum) or 0·4 mg kg-1 (20 mg maximum) every other week or to methotrexate (MTX) 0·1-0·4 mg kg-1 (25 mg maximum) weekly. The 16-week initial treatment (IT) period was followed by a 36-week withdrawal period and a 16-week retreatment period. Patients could enter the LTE at prespecified time points to receive ADA 0·8 mg kg-1 (blinded or open label) or ADA 0·4 mg kg-1 (blinded), or to remain off treatment. Efficacy is reported for patient groups according to doses received in the IT and LTE periods.Of the 114 patients randomized in the IT period, 108 entered the LTE (n = 36 in each group); 93 received ADA 0·8 mg kg-1 . Efficacy (≥ 75% improvement from baseline in Psoriasis Area and Severity Index) was maintained or improved from entry to the end of the LTE: MTX(IT)/ADA 0·8(LTE) 31-86% of patients; ADA 0·4(IT)/0·4 or 0·8(LTE) 28-47%; ADA 0·8(IT)/0·8(LTE) 50-72%. No serious infections occurred in the LTE.After 52 weeks of long-term ADA treatment in children aged 4-18 years with severe plaque psoriasis, disease severity was reduced and maintained or further improved, as demonstrated by efficacy outcomes. No new safety risks were identified. What's already known about this topic? The results from the first three periods of this phase III trial in children aged 4-18 years with severe plaque psoriasis suggest that adalimumab is a safe and efficacious treatment option in this population. What does this study add? This is the first study to evaluate long-term treatment of adalimumab in children with severe psoriasis, and the first to evaluate switching from methotrexate to adalimumab in this population.
DIPG-13. A NOVEL MOUSE MODEL REVEALS UNEXPECTED MECHANISMS OF ACTION OF ACVR1 MUTATIONS IN DIFFUSE INTRINSIC PONTINE GLIOMA
Authors: Jerome Fortin, Ruxiao Tian, Ida Zarrabi, Graham Hill, Eleanor Williams, Gonzalo Sanchez-Duffhues, Midory Thorikay, Parameswaran Ramachandran, Robert Siddaway, Jong Wong, Jillian Haight, Annick You-Ten, Bryan Snow, Andrew Wakeham, Daniel Schramek, Alex Bullock, Peter ten Dijke, Cynthia Hawkins, Tak Mak
Journal: Neuro-Oncology (2019)

Diffuse Intrinsic Pontine Gliomas (DIPGs) are aggressive pediatric brain tumors for which there is currently no effective treatment. Most DIPGs are driven by mutations in histone H3-encoding genes, and a subset of these tumors also carry gain-of-function mutations in ACVR1, which encodes a BMP type I receptor. The oncogenic mechanisms of action of these ACVR1 mutations are currently unknown. Here, we generate a novel conditional knock-in mouse model of the most common ACVR1 mutation driving DIPG (Acvr1G328V). Glial cells carrying the mutation hyperactivate BMP signaling, exhibit enhanced proliferation, and expand throughout the brainstem in vivo. Unexpectedly, we observe that the Acvr1G328V mutation is sufficient to trigger an arrest in the differentiation of oligodendroglial lineage cells, a hallmark event in the formation of many types of gliomas including DIPGs. Mechanistically, this differentiation block is associated with upregulation of transcription factors that control the development of glial progenitors. Inactivation of these factors, which are highly expressed in human DIPGs, impairs the growth of patient-derived DIPG cells and enhances their sensitivity to treatment with a novel ACVR1 inhibitor. Collectively, our results describe a potential oncogenic mechanism of action for ACVR1 mutations, and suggest new therapeutic strategies for the treatment of DIPG.
Abstract 19061: Cardiac Stress Results Forecast Adverse Cardiovascular Events in High Risk Asymptomatic Middle and Older Aged Men: Identification of Silent Myocardial Ischemia in the Elderly
Authors: Richard B Stacey, Jennifer Jordan, Matthew Whitlock, Michael E Hall, Sujethra Vasu, Craig Hamilton, Dalane Kitzman, William G Hundley
Journal: Circulation (2017)

Background: Current guidelines for assessing the risk of experiencing a hospitalized CV event discourage stress testing of asymptomatic individuals; however, these recommendations are based on evidence gathered primarily from those aged  55 years without CV-related symptoms, but otherwise at increased risk for a future CV event due to pre-existing coronary artery disease (CAD), hypertension or diabetes mellitus. After testing, personnel blinded to the stress test results contacted participants at 4-month intervals for the next 5 years to determine and verify the incidence of post-stress testing hospitalized CV events. After accounting for the Framingham risk score, log-rank test and Cox proportional hazards models were used to determine...
LGG-12. TRAMETINIB FOR THE TREATMENT OF RECURRENT/PROGRESSIVE PEDIATRIC LOW GRADE GLIOMA: A SINGLE INSTITUTION EXPERIENCE
Authors: Neevika Manoharan, Jungwhan Choi, Christine Chordas, Mary Ann Zimmerman, Jacqueline Scully, Jessica Clymer, Nicole J Ullrich, Mariella Filbin, Pratiti Bandopadhayay, Susan Chi, Kee Kiat Yeo
Journal: Neuro-Oncology (2019)

INTRODUCTION: Pediatric low-grade gliomas (pLGGs) are the most common CNS tumor of childhood and comprise a heterogenous group of tumors. Children with progressive pLGG typically require numerous regimens of therapy including surgical resection, chemotherapy and rarely, radiation therapy. The presence of frequent genetic alterations activating the mitogen-activated-protein-kinase (MAPK) signaling pathway has recently led to a more targeted therapeutic approach. We describe our institutional experience using trametinib, an FDA-approved MEK inhibitor for recurrent/progressive pLGGs. METHODS: We performed a retrospective, IRB approved, chart review of all patients with recurrent/progressive pLGGs treated with trametinib off-study at Dana-Farber / Boston’s Children’s Cancer and Blood Disorder Center between 2016–2018. RESULTS: Eleven patients were identified, with ten evaluable for response. Median age at commencement of trametinib treatment was 14.7 years old (range 7.3–25.9 years; 6 male: 5 female). Molecular status included KIAA 1549-BRAF fusion (n=3), NF1 (n=4), FGFR mutation and heterozygous CDKN2A loss (n=1 each), unknown mutational status (n=2). Median number of prior treatment regimens was 5 (range 1–7). Median duration on treatment with trametinib was 13.4 months (range 1.5–24.8 months). Based on RANO criteria, responses included partial (n=1), minor response (n=1) and stable disease (n=5) as best response. Four patients remain on therapy with trametinib (range 1.5–24.8 months) with two patients having discontinued therapy secondary to disease progression. The most common toxicities were skin rash, fatigue and gastrointestinal disturbance. Five patients required dose reduction for toxicities. Two patients experienced intracranial hemorrhage (ICH) while on trametinib (at 5 and 498 days). While it is unclear whether ICH was directly attributable to trametinib, therapy was discontinued. CONCLUSION: Trametinib appears to be an effective treatment for patients with recurrent/progressive pLGG. The toxicities of this therapy warrant further investigation, particularly the potential risk for intracranial hemorrhage. Early phase clinical trials are underway.