tbuckley/cabot-search huggingface dataset:
Evaluation of the prothrombin fragment 1.2 in patients with coronavirus disease 2019 (<scp>COVID</scp>‐19)
Authors: Hanny Al‐Samkari, Fei Song, Elizabeth M. Van Cott, David J. Kuter, Rachel Rosovsky
Journal: American Journal of Hematology (2020)

Coronavirus disease 2019 (COVID-19) may cause a hypercoagulable state. The D-dimer is frequently elevated in COVID-19, but other markers of coagulation activation, including the prothrombin fragment 1.2 (PF1.2) are poorly described. We studied hospitalized adults with COVID-19 and PF1.2 measurements performed at any time during hospitalization. We evaluated the relationship between PF1.2 and synchronously measured D-dimer. We utilized receiver operating characteristic (ROC) analysis to evaluate optimal thresholds for diagnosing thrombosis and multivariable logistic regression to evaluate association with thrombosis. A total of 115 patients were included [110 (95.7%) critically ill]. Both PF1.2 and D-dimer were moderately positively correlated (r = 0.542, P < .001) but significant discordance was observed in elevation of each marker above the laboratory reference range (59.0% elevated PF1.2 vs 98.5% elevated D-dimer). Median PF1.2 levels were higher in patients with thrombosis than those without (611 vs 374 pmol/L, P = .006). In ROC analysis, PF1.2 had superior specificity and conferred a higher positive likelihood ratio in identifying patients with thrombosis than D-dimer (PF1.2 threshold of >523 pmol/L: 69.2% sensitivity, 67.7% specificity; >924 pmol/L: 37.9% sensitivity, 87.8% specificity). In multivariable analysis, a PF1.2 >500 pmol/L was significantly associated with VTE [adjusted odds ratio (OR) 4.26, 95% CI, 1.12-16.21, P = .034] and any thrombotic manifestation (adjusted OR 3.85, 95% CI, 1.39-10.65, P = .010); conversely, synchronously measured D-dimer was not significantly associated with thrombosis. 90.6% of patients with a non-elevated PF1.2 result did not develop VTE. So, PF1.2 may be a useful assay, and potentially more discriminant than D-dimer, in identifying thrombotic manifestations in hospitalized patients with COVID-19.
Osteocyte necrosis triggers osteoclast-mediated bone loss through macrophage-inducible C-type lectin
Authors: Darja Andreev, Mengdan Liu, Daniela Weidner, Katerina Kachler, Maria Faas, Anika Grüneboom, Ursula Schlötzer-Schrehardt, Luis E. Muñoz, Ulrike Steffen, Bettina Grötsch, Barbara Killy, Gerhard Krönke, Andreas M. Luebke, Andreas Niemeier, Falk Wehrhan, Roland Lang, Georg Schett, Aline Bozec
Journal: Journal of Clinical Investigation (2020)

Although the control of bone-resorbing osteoclasts through osteocyte-derived RANKL is well defined, little is known about the regulation of osteoclasts by osteocyte death. Indeed, several skeletal diseases, such as bone fracture, osteonecrosis, and inflammation are characterized by excessive osteocyte death. Herein we show that osteoclasts sense damage-associated molecular patterns (DAMPs) released by necrotic osteocytes via macrophage-inducible C-type lectin (Mincle), which induced their differentiation and triggered bone loss. Osteoclasts showed robust Mincle expression upon exposure to necrotic osteocytes in vitro and in vivo. RNA sequencing and metabolic analyses demonstrated that Mincle activation triggers osteoclastogenesis via ITAM-based calcium signaling pathways, skewing osteoclast metabolism toward oxidative phosphorylation. Deletion of Mincle in vivo effectively blocked the activation of osteoclasts after induction of osteocyte death, improved fracture repair, and attenuated inflammation-mediated bone loss. Furthermore, in patients with osteonecrosis, Mincle was highly expressed at skeletal sites of osteocyte death and correlated with strong osteoclastic activity. Taken together, these data point to what we believe is a novel DAMP-mediated process that allows osteoclast activation and bone loss in the context of osteocyte death.
AB0184 ADHERENCE TO TREATMENT IN AN ITALIAN COHORT OF PATIENTS AFFECTED BY CHRONIC INFLAMMATORY ARTHROPATHIES TREATED WITH BIOLOGIC AGENTS
Authors: M. Colaci, M. L. Aprile, Y. Dal Bosco, C. Schinocca
Journal: Annals of the Rheumatic Diseases (2020)

Background: The lack of adherence to treatment in patients affected by chronic diseases, such as rheumatic diseases, remains a relevant issue. Indeed, “inefficacy” or “intolerance” to therapies prescribed could hide a scarce compliance of a considerable percentage of patients. Objectives: We aimed to evaluate the adherence to treatment in a series of patients affected by chronic inflammatory arthropathies treated with biologic agents. Methods: We recruited 175 consecutive patients (M/F: 56/120; mean age 52.6±12.3 years) affected by rheumatoid arthritis (98), psoriatic arthropathy (45) or ankylosing spondylitis (32) treated with subcutaneous biologic agents. All patients completed the Morisky Medication Adherence Scales (MMAS-8) 1 , in order to estimate their adherence to therapy. Moreover, we achieved from all cases the Patient Global Assessment (PGA), the Visual Analogue Scale (VAS) for articular pain, the Health Assessment Questionnaire (HAQ), and the report of eventual adverse events. Results: Considering MMAS-8, 23/175 (13.1%) patients were low adherent to treatment (score &lt;6), and 59/175 (33.7%) presented medium-grade adherence (score 6-7). Adherence to treatments tended to be higher in males (mean MMAS-8 7.3±1.1 vs. 6.9±1.6; p=0.073), while it was not associated with age, education level, type of articular disease, presence of adverse events, or treatment with the type of traditional or biologic DMARDs. Higher mean levels of PGA (51.3 vs. 38.8; p=0.012), VAS (52.6 vs. 44.3; p=0.08), and HAQ (0.9 vs. 0.5; p=0.001) was reported in low-adherent patients compared with full adherent subjects. Conclusion: Our study confirmed that the percentage of patients showing low adherence to therapy is relevant. Moreover, the association of lower adherence to treatments with higher values of the subjective clinimetric indexes suggests to pay attention to the apparent ineffectiveness or loss of efficacy of therapy. References: [1]Morisky DE et al. J Clin Hypertens 2008; 10:348–354. Disclosure of Interests: None declared
Cellular Stressors Contribute to the Expansion of Multiple Hematopoietic Clones of Varying Leukemic Potential
Authors: Terrence N Wong, Christopher A Miller, Matthew Rm Jotte, Nusayba Bagegni, Jack D Baty, Amy E Schmidt, Amanda F Cashen, Eric J. Duncavage, Nichole M Helton, Mark A. Fiala, Robert S Fulton, Sharon E Heath, Megan Janke, Kierstin Luber, Peter Westervelt, Ravi Vij, John F DiPersio, John S. Welch, Timothy A. Graubert, Matthew J. Walter, Timothy James J Ley, Daniel C. Link
Journal: Blood (2017)
Discovery and validation of surface<i>N</i>-glycoproteins in MM cell lines and patient samples uncovers immunotherapy targets
Authors: Robyn A A Oldham, Mary L Faber, Theodore R Keppel, Amanda R Buchberger, Matthew Waas, Parameswaran Hari, Rebekah L Gundry, Jeffrey A Medin
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Multiple myeloma (MM) is characterized by clonal expansion of malignant plasma cells in the bone marrow. While recent advances in treatment for MM have improved patient outcomes, the 5-year survival rate remains ~50%. A better understanding of the MM cell surface proteome could facilitate development of new directed therapies and assist in stratification and monitoring of patient outcomes. Methods In this study, we first used a mass spectrometry (MS)-based discovery-driven cell surface capture (CSC) approach to map the cell surface N -glycoproteome of MM cell lines. Next, we developed targeted MS assays, and applied these to cell lines and primary patient samples to refine the list of candidate tumor markers. Candidates of interest detected by MS on MM patient samples were further validated using flow cytometry (FCM). Results We identified 696 MM cell surface N -glycoproteins by CSC, and developed 73 targeted MS detection assays. MS-based validation using primary specimens detected 30 proteins with significantly higher abundance in patient MM cells than controls. Nine of these proteins were identified as potential immunotherapeutic targets, including five that were validated by FCM, confirming their expression on the cell surface of primary MM patient cells. Conclusions This MM surface N -glycoproteome will be a valuable resource in the development of biomarkers and therapeutics. Further, we anticipate that our targeted MS assays will have clinical benefit for the diagnosis, stratification, and treatment of MM patients.
SARS-CoV-2 disrupts clinical research: the role of a rare disease-specific trial network
Authors: Silke van Koningsbruggen-Rietschel, Fiona Dunlevy, Veerle Bulteel, Damian G. Downey, Lieven Dupont
Journal: European Respiratory Journal (2020)

<b>Rare disease patients may suffer delayed access to new drugs as SARS-CoV-2 is disrupting clinical trials. This survey demonstrates that the European Cystic Fibrosis Clinical Trials Network is ideally placed to track and address such disruption.</b>https://bit.ly/3hCw5dq
Clarifying the Sweeping Consequences of COVID-19 in Pregnant Women, Newborns, and Children With Existing Cohorts
Authors: Yanhong Jessika Hu, Melissa Wake, Richard Saffery
Journal: JAMA Pediatrics (2020)

This Viewpoint describes needs for defining the outcomes of the coronavirus disease 2019 pandemic on pregnant women, neonates, and children and proposes that fulfilling those needs will require engaging with existing research cohorts.
Results from Ongoing Phase 1/2 Trial of SL-401 in Patients with Myeloproliferative Neoplasms Including Chronic Myelomonocytic Leukemia and Primary Myelofibrosis
Authors: Mrinal M. Patnaik, Vikas Gupta, Gary J. Schiller, Sangmin Lee, Abdulraheem Yacoub, Haris Ali, Moshe Talpaz, Megan Sardone, Halyna Wysowskyj, Shay Shemesh, Janice Chen, Christopher Brooks, Trishna Goswami, Animesh Pardanani, Ayalew Tefferi, Srdan Verstovsek, Joseph David Khoury, Naveen Pemmaraju
Journal: Blood (2017)
Are Hispanic, Black, and Asian Physicians Truly Less Burned Out Than White Physicians?
Authors: Joel C. Cantor, Dawne M. Mouzon
Journal: JAMA Network Open (2020)

Luis C. Garcia, MS; Tait D. Shanafelt, MD; Colin P. West, MD, PhD; Christine A. Sinsky, MD; Mickey T. Trockel, MD, PhD; Laurence Nedelec, PhD; Yvonne A. Maldonado, MD; Michael Tutty, PhD; Liselotte N. Dyrbye, MD, MHPE; Magali Fassiotto, PhD
Abstract 10374: Raphanus Sativus Cv. Sakurajima Daikon as a Functional Food May Improve Vascular Endothelial Function
Authors: Takashi Kajiya, Maho Sasaki, Yoshihiko Atsuchi, Nobuhiko Atsuchi, Katsuko Kajiya
Journal: Circulation (2019)

Introduction: Functional foods deliver additional benefits over their basic nutritional value. The largest radish cultivar, Raphanus sativus cv. Sakurajima Daikon, is known as a functional food. Pr...
Rationally designed rapamycin-encapsulated ZIF-8 nanosystem for overcoming chemotherapy resistance
Authors: Mengran Xu, Yi Hu, Weiping Ding, Fenfen Li, Jun Lin, Min Wu, Jingjing Wu, Long-Ping Wen, Bensheng Qiu, Peng-Fei Wei, Ping Li
Journal: Biomaterials (2020)
COVID-19–Associated Multisystem Inflammatory Syndrome in Children — United States, March–July 2020
Authors: Shana Godfred-Cato, Bobbi Bryant, Jessica Leung, Matthew E. Oster, Laura Conklin, Joseph Abrams, Katherine Roguski, Bailey Wallace, Emily Prezzato, Emilia H. Koumans, Ellen H. Lee, Anita Geevarughese, Maura K. Lash, Kathleen H. Reilly, Wendy P. Pulver, Deepam Thomas, Kenneth A. Feder, Katherine K. Hsu, Nottasorn Plipat, Gillian Richardson, Heather Reid, Sarah Lim, Ann Schmitz, Timmy Pierce, Susan Hrapcak, Deblina Datta, Sapna Bamrah Morris, Kevin Clarke, Ermias Belay
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

In April 2020, during the peak of the coronavirus disease 2019 (COVID-19) pandemic in Europe, a cluster of children with hyperinflammatory shock with features similar to Kawasaki disease and toxic shock syndrome was reported in England* (1). The patients' signs and symptoms were temporally associated with COVID-19 but presumed to have developed 2-4 weeks after acute COVID-19; all children had serologic evidence of infection with SARS-CoV-2, the virus that causes COVID-19 (1). The clinical signs and symptoms present in this first cluster included fever, rash, conjunctivitis, peripheral edema, gastrointestinal symptoms, shock, and elevated markers of inflammation and cardiac damage (1). On May 14, 2020, CDC published an online Health Advisory that summarized the manifestations of reported multisystem inflammatory syndrome in children (MIS-C), outlined a case definition,† and asked clinicians to report suspected U.S. cases to local and state health departments. As of July 29, a total of 570 U.S. MIS-C patients who met the case definition had been reported to CDC. A total of 203 (35.6%) of the patients had a clinical course consistent with previously published MIS-C reports, characterized predominantly by shock, cardiac dysfunction, abdominal pain, and markedly elevated inflammatory markers, and almost all had positive SARS-CoV-2 test results. The remaining 367 (64.4%) of MIS-C patients had manifestations that appeared to overlap with acute COVID-19 (2-4), had a less severe clinical course, or had features of Kawasaki disease.§ Median duration of hospitalization was 6 days; 364 patients (63.9%) required care in an intensive care unit (ICU), and 10 patients (1.8%) died. As the COVID-19 pandemic continues to expand in many jurisdictions, clinicians should be aware of the signs and symptoms of MIS-C and report suspected cases to their state or local health departments; analysis of reported cases can enhance understanding of MIS-C and improve characterization of the illness for early detection and treatment.
Comparison of nt-probnp and galectin-3 levels in end-stage heart failure and 3 months after heart transplantation
Authors: Eduardo Barge Caballero, Marisa Crespo Leiro, Alfonso Castro Beiras, Natalia Suárez Fuentetaja, María Jesús Paniagua Martín, Zulaika Grille Cancela, Raquel Marzoa Rivas, Jorge Pombo Otero, Ignacio Pedro Constanso Conde
Journal: European Journal of Heart Failure (2014)
Reply to: Correspondence on “High rates of 30-day mortality in patients with cirrhosis and COVID-19”
Authors: Massimo Iavarone, Roberta D'Ambrosio, Pietro Lampertico, M. Iavarone, R. D’Ambrosio, A. Rimondi, P. Lampertico, A. Soria, P. Bonfanti, M. Triolo, S. Fagiuoli, N. Pugliese, A. Aghemo, P. Del Poggio, G. Perricone, L.S. Belli, S. Massironi, M. Lucà, P. Invernizzi, A. Spinetti, C. Carriero, E. Buscarini, M. Pedaci, M. Viganò, M.G. Rumi
Journal: Journal of Hepatology (2020)
Impact of diet and the bacterial microbiome on the mucous barrier and immune disorders
Authors: Charlotte A. Alemao, Kurtis F. Budden, Henry M. Gomez, Saima F. Rehman, Jacqueline E. Marshall, Shakti D. Shukla, Chantal Donovan, Samuel C. Forster, Ian A. Yang, Simon Keely, Elizabeth R. Mann, Emad M. El Omar, Gabrielle T. Belz, Philip M. Hansbro
Journal: Allergy (2020)

Abstract The prevalence of chronic immune and metabolic disorders is increasing rapidly. In particular, inflammatory bowel diseases, obesity, diabetes, asthma and chronic obstructive pulmonary disease have become major healthcare and economic burdens worldwide. Recent advances in microbiome research have led to significant discoveries of associative links between alterations in the microbiome and health, as well as these chronic supposedly noncommunicable, immune/metabolic disorders. Importantly, the interplay between diet, microbiome and the mucous barrier in these diseases has gained significant attention. Diet modulates the mucous barrier via alterations in gut microbiota, resulting in either disease onset/exacerbation due to a “poor” diet or protection against disease with a “healthy” diet. In addition, many mucosa‐associated disorders possess a specific gut microbiome fingerprint associated with the composition of the mucous barrier, which is further influenced by host‐microbiome and inter‐microbial interactions, dietary choices, microbe immigration and antimicrobials. Our review focuses on the interactions of diet (macronutrients and micronutrients), gut microbiota and mucous barriers (gastrointestinal and respiratory tract) and their importance in the onset and/or progression of major immune/metabolic disorders. We also highlight the key mechanisms that could be targeted therapeutically to prevent and/or treat these disorders.
Apolipoprotein L1-Specific Antibodies Detect Endogenous APOL1 inside the Endoplasmic Reticulum and on the Plasma Membrane of Podocytes
Authors: Suzie J. Scales, Nidhi Gupta, Ann M. De Mazière, George Posthuma, Cecilia P. Chiu, Andrew A. Pierce, Kathy Hötzel, Jianhua Tao, Oded Foreman, Georgios Koukos, Francesca Oltrabella, Judith Klumperman, WeiYu Lin, Andrew S. Peterson
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement Specific variants of APOL1, G1 and G2, are associated with CKD in the Black population. Overexpression of these variants kills cells, through different proposed mechanisms in different subcellular compartments. The localization of endogenous APOL1 has not been conclusively established because all studies have used antibodies that crossreact with APOL2. Generation and use of APOL1-specific antibodies show that endogenous podocyte APOL1 localizes mainly inside the endoplasmic reticulum, with a few molecules on the cell surface. These findings potentially support the endoplasmic reticulum stress or cell surface cation channel models of cytotoxicity. Background APOL1 is found in human kidney podocytes and endothelia. Variants G1 and G2 of the APOL1 gene account for the high frequency of nondiabetic CKD among African Americans. Proposed mechanisms of kidney podocyte cytotoxicity resulting from APOL1 variant overexpression implicate different subcellular compartments. It is unclear where endogenous podocyte APOL1 resides, because previous immunolocalization studies utilized overexpressed protein or commercially available antibodies that crossreact with APOL2. This study describes and distinguishes the locations of both APOLs. Methods Immunohistochemistry, confocal and immunoelectron microscopy, and podocyte fractionation localized endogenous and transfected APOL1 using a large panel of novel APOL1-specific mouse and rabbit monoclonal antibodies. Results Both endogenous podocyte and transfected APOL1 isoforms vA and vB1 (and a little of isoform vC) localize to the luminal face of the endoplasmic reticulum (ER) and to the cell surface, but not to mitochondria, endosomes, or lipid droplets. In contrast, APOL2, isoform vB3, and most vC of APOL1 localize to the cytoplasmic face of the ER and are consequently absent from the cell surface. APOL1 knockout podocytes do not stain for APOL1, attesting to the APOL1-specificity of the antibodies. Stable re-transfection of knockout podocytes with inducible APOL1-G0 , -G1 , and - G2 showed no differences in localization among variants. Conclusions APOL1 is found in the ER and plasma membrane, consistent with either the ER stress or surface cation channel models of APOL1-mediated cytotoxicity. The surface localization of APOL1 variants potentially opens new therapeutic targeting avenues.
Comorbidities And Initial Severity In Community-Acquired Pneumonia (cap)
Authors: R. Menendez, S. Reyes, B. Montull, R. Zalacain, A. Capelastegui, J. Aspa, L. Borderias, J. J. Martin Villasclaras, S. Bello, I. Alfageme, Felipe Carlos B. Rodríguez De Castro, J. Rello, L. Molinos, J. Ruiz Manzano, A. Torres
Journal: American Journal of Respiratory and Critical Care Medicine (2015)
Decellularization optimizes the inhibitory microenvironment of the optic nerve to support neurite growth
Authors: Jia-Hui Sun, Ge Li, Ting-Ting Wu, Zi-Jing Lin, Jian-Long Zou, Li-Jun Huang, Hao-Yu Xu, Jun-Hua Wang, Yuan-Huan Ma, Yuan-Shan Zeng
Journal: Biomaterials (2020)
Changes in Serum TARC Predict PET Response Among Pediatric Patients with Relapsed or Refractory Hodgkin Lymphoma Treated with Brentuximab Vedotin and Gemcitabine: A Report from the Children's Oncology Group
Authors: Peter D Cole, Menachem Spira, Kathleen M McCarten, Terzah M Horton, Quinglin Pei, Monika Metzger, Richard A Drachtman, Kara M. Kelly
Journal: Blood (2017)
AMPK controls the axonal regenerative ability of dorsal root ganglia sensory neurons after spinal cord injury
Authors: Guiping Kong, Luming Zhou, Elisabeth Serger, Ilaria Palmisano, Francesco De Virgiliis, Thomas H. Hutson, Eilidh Mclachlan, Anja Freiwald, Paolo La Montanara, Kirill Shkura, Radhika Puttagunta, Simone Di Giovanni
Journal: Nature Metabolism (2020)
Characteristics and Diabetes Control in Adults With Type 1 Diabetes Admitted With COVID-19 Infection
Authors: Maria Vamvini, Vasileios-Arsenios Lioutas, Roeland J.W. Middelbeek
Journal: Diabetes Care (2020)

Diabetes has been identified as one of the major risk factors for developing severe forms of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (1). While data show a higher incidence of severe acute respiratory distress syndrome and increased mortality in patients with diabetes, the majority of these patients have type 2 diabetes (2), and less is known about the implications of type 1 diabetes in COVID-19. A report from the U.K. describes the COVID-19 mortality rate as significantly higher in older patients with type 1 diabetes compared with those with type 2 diabetes (3). Among young adults with type 1 diabetes in the U.S., diabetic ketoacidosis (DKA) was commonly encountered in those diagnosed with COVID-19 (4). Little is known about adults with type 1 diabetes and COVID-19 who require hospitalization. The goal of this study was to define the clinical characteristics, outpatient diabetes management and control, and disease course of people with type 1 diabetes who were admitted to a tertiary care center for COVID-19.

We retrospectively reviewed the charts and collected data for all patients with an established diagnosis of …
The EsoCap-system – An innovative platform to drug targeting in the esophagus
Authors: Julius Krause, Christoph Rosenbaum, Michael Grimm, Adrian Rump, Rebecca Keßler, Norbert Hosten, Werner Weitschies
Journal: Journal of Controlled Release (2020)

For the therapy of esophageal diseases such as eosinophilic esophagitis, there are no possibilities of local targeted therapy. This publication describes a novel, innovative drug delivery concept, that enables a targeted, long-lasting administration of drug substances to the esophageal mucosa. In addition to a comprehensive in-vitro characterization of the dosage form, this work includes a proof-of-concept study with healthy volunteers, which shows the functionality and acceptance of this novel drug delivery concept. This novel drug delivery technology enables for the first time a targeted, local and long-lasting therapy of the esophagus.
Author Correction: Clinical validation of smartphone-based activity tracking in peripheral artery disease patients
Authors: Raheel Ata, Neil Gandhi, Hannah Rasmussen, Osama El-Gabalawy, Santiago Gutierrez, Alizeh Ahmad, Siddharth Suresh, Roshini Ravi, Kara Rothenberg, Oliver Aalami
Journal: npj Digital Medicine (2020)

[This corrects the article DOI: 10.1038/s41746-018-0073-x.].