tbuckley/cabot-search huggingface dataset:
A host signature based on TRAIL, IP-10, and CRP for reducing antibiotic overuse in children by differentiating bacterial from viral infections: a prospective, multicentre cohort study
Authors: Cihan Papan, Alberto Argentiero, Marian Porwoll, Ummaya Hakim, Edoardo Farinelli, Ilaria Testa, Maria Bruna Pasticci, Daniele Mezzetti, Katia Perruccio, Liat Etshtein, Niv Mastboim, Einat Moscoviz, Tahel Ilan Ber, Asi Cohen, Einav Simon, Olga Boico, Liran Shani, Tanya M. Gottlieb, Roy Navon, Eran Barash, Kfir Oved, Eran Eden, Arne Simon, Johannes G. Liese, Markus Knuf, Michal Stein, Renata Yacobov, Ellen Bamberger, Sven Schneider, Susanna Esposito, Tobias Tenenbaum
Journal: Clinical Microbiology and Infection (2021)

Identifying infection aetiology is essential for appropriate antibiotic use. Previous studies have shown that a host-protein signature consisting of TNF-related apoptosis-induced ligand (TRAIL), interferon-γ-induced protein-10 (IP-10), and C-reactive protein (CRP) can accurately differentiate bacterial from viral infections.This prospective, multicentre cohort study, entitled AutoPilot-Dx, aimed to validate signature performance and to estimate its potential impact on antibiotic use across a broad paediatric population (>90 days to 18 years) with respiratory tract infections, or fever without source, at emergency departments and wards in Italy and Germany. Infection aetiology was adjudicated by experts based on clinical and laboratory investigations, including multiplex PCR and follow-up data.In total, 1140 patients were recruited (February 2017-December 2018), of which 1008 met the eligibility criteria (mean age 3.5 years, 41.9% female). Viral and bacterial infections were adjudicated for 628 (85.8%) and 104 (14.2%) children, respectively; 276 patients were assigned an indeterminate reference standard outcome. For the 732 children with reference standard aetiology, the signature discriminated bacterial from viral infections with a sensitivity of 93.7% (95%CI 88.7-98.7), a specificity of 94.2% (92.2-96.1), positive predictive value of 73.0% (65.0-81.0), and negative predictive value of 98.9% (98.0-99.8); in 9.8% the test results were equivocal. The signature performed consistently across different patient subgroups and detected bacterial immune responses in viral PCR-positive patients.The findings validate the high diagnostic performance of the TRAIL/IP-10/CRP signature in a broad paediatric cohort, and support its potential to reduce antibiotic overuse in children with viral infections.
Targeting <i>JAK2</i> Gene Rearrangements with a Novel Kinase Inhibitor in a Preclinical Model of Pediatric Acute Lymphoblastic Leukemia
Authors: Manuel Quadri, Claudia Saitta, Sonia Palamini, Chiara Palmi, Andrea Biondi, Giovanni Cazzaniga, Grazia Fazio
Journal: Blood (2021)
Abstract 9552: RNA Sequencing of Cardiac and Renal Tissue in a Rat Model of Chronic Kidney Disease Reveals Chronodisruption as Common Pathway
Authors: Jef Van Den Eynde, Xander Jacquemin, Hilde Gillijns, Willy Gsell, Uwe Himmelreich, Aernout Luttun, Keir McCutcheon, Stefan P Janssens, Wouter Oosterlinck
Journal: Circulation (2021)

Introduction: Chronic kidney disease (CKD) is often accompanied by cardiovascular disease, which is referred to as type 4 cardiorenal syndrome. Management is challenging due to the multifactorial nature of the condition, and treatment of one organ may negatively impact the other. Hypothesis: More insights into the common molecular disease processes in the heart and kidney might provide a source for new therapies. We used RNA sequencing to identify pathways that were dysregulated in both organs. Methods: Cardiac and renal tissue samples from four 5/6 th partial nephrectomized (NX) and four sham-operated (SHAM) female Sprague-Dawley rats were analyzed using RNA sequencing. Strand-specific and rRNA depleted cDNA libraries were generated and were sequenced on NovaSeq (Ilumina) with 20 million reads per library. Results: In comparison to SHAM, the kidneys of NX animals had 290 differentially expressed genes (DEGs), showing increased expression of genes that map to Gene Ontology terms including collagen fibril organization , circadian regulation of gene expression , mitotic cell cycle , neutrophil chemotaxis , and inflammatory response . Within the hearts of NX animals, 8 DEGs were found, including those related to circadian regulation of gene expression (Per2, Per3, Arntl/Bmal1, BHLHE41) , as well as the Adra1d , C2cd4b , Ubtd1 , and Atp2b2 genes. Four genes were differentially expressed in both organs. Three of them were related to circadian rhythm, with Per2 and Per3 being downregulated and Arntl/Bmal1 being upregulated. Furthermore, Adra1d was downregulated in both organs. Conclusions: This comprehensive RNA sequencing in a rat model of type 4 cardiorenal syndrome identified chronodisruption as a common pathway, suggesting that circadian rhythms could be a novel target for intervention. Figure Legend. (A) Venn diagram with number of DEGs and vulcano plots for heart (left) and kidney (right). (B) GO terms for heart. (C) GO terms for kidney.
Abstract 14351: Low-Level Inflammation in the Prevalent Oral Disease Gingivitis Induces Surrogate Markers of Atherosclerosis in Young Healthy Individuals. A Single-Subject Interventional Study
Authors: Karsten Grote, Joerg Eberhard, Maren Luchtefeld, Harald Schuett, Meike Stiesch, Bernhard Schieffer
Journal: Circulation (2012)

Background: Gingivitis is a low-level oral infection induced by bacterial deposits on the teeth with a high prevalence within Western populations. A potential link between the more severe oral dise...
Classical and Non-Classical Phenotypes of Erdheim-Chester Disease: Correlating Clinical, Radiographic, and Genotypic Findings
Authors: Antonious Z. Hazim, Gordon Ruan, Aldo A. Acosta-Medina, Jithma P. Abeykoon, Aishwarya Ravindran, Robert Vassallo, Jay Ryu, W. Oliver Tobin, Matthew Koster, N Nora Bennani, Karen Rech, Mithun V. Shah, Jason R. Young, Gaurav Goyal, Ronald Go
Journal: Blood (2021)
Low Mutational Burden of Extra Nodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue in Patients with Primary Sjogren's Syndrome
Authors: Johanna A.A. Bult, Jessica R. Plaça, Erlin A. Haacke, Gwenny M. Verstappen, Frederik K.L. Spijkervet, Frans G.M. Kroese, Wouter J. Plattel, Joost S.P. Vermaat, Hendrika Bootsma, Bert Van der Vegt, Arjan Diepstra, Anke Van Den Berg, Klaas Kok, Marcel Nijland
Journal: Blood (2021)
Abstract 10022: Young Adults Hospitalized with Diabetes Remain at 25% Higher Risk of Acute Myocardial Infarction with Cannabis Use Disorder: A Nationwide Matched Analysis
Authors: Rupak Desai, Dr Dyutima, Confesora Valdez, Maria J Rueda, Lorannys Y Sanchez, Violeta Spasova, Zaymis D Castillo, Christiana A Igbenabor, Mirian D Galan, Zainab J Gandhi, Sandeep Singh
Journal: Circulation (2021)

Background: The impact of cannabis use on diabetes mellitus and associated cardiovascular events remains understudied. Rising trends in recreational cannabis use in the young prompted us to evaluate the risk and outcomes of acute myocardial infarction (AMI) in young diabetics with cannabis use disorder (CUD). Methods: We queried the National Inpatient Sample (2015 October-2017) to identify young adult admissions with diabetes. Demographically (age, sex, and race) matched (1:1) cohorts (CUD+ vs. CUD) were compared for comorbidities and risk of AMI and subsequent inpatient outcomes among young diabetics. Multivariable regression analysis was performed adjusting for confounders. Results: Of young adults admitted with diabetes (median 35 [29-40] years, 59.3% male, 42.3% white), demographically matched CUD+ (n=32170) and CUD- (n=32170) cohorts were obtained (Table 1). The CUD+ cohort often consisted of non-elective admissions (91.7% vs. 85.45%), Medicaid enrollees (51.6% vs. 38.7%), patients from lower household income quartile (47.9% vs. 43.1%) vs. CUD- cohort and had higher burden of smoking, alcohol abuse, chronic pulmonary disease, depression, psychosis and neurological disorders (p&lt;0.001). On adjusted multivariable analysis, the risk of AMI was 25% higher (OR:1.25, 95%CI:1.02-1.51, p=0.03) in CUD+ cohort, however, there was no significant difference in the subsequent inpatient mortality. Male sex (aOR1.35), non-elective admission (aOR2.46), Medicaid/self-pay enrollment (aOR 2.0/3.8), AIDS (aOR6.24), coagulopathy (aOR1.85), peripheral vascular disease (aOR 1.82), hypertension (aOR 2.12), hyperlipidemia (aOR2.53), smoking (aOR1.78), and obesity (aOR1.36) were independent predictors of AMI. Conclusion: Young diabetics with CUD may have 25% higher risk of AMI hospitalizations. Male sex, cardiovascular comorbidities, tobacco smoking, AIDS and coagulopathy independently predicted higher risk of AMI among young diabetics with CUD.
Characteristics, Management and Outcomes of Patients with Intravascular Lymphoma: A Mayo Clinic Experience
Authors: Karan Seegobin, Muhamad Alhaj Moustafa, Umair Majeed, Liuyan Jiang, David Menke, Ke Li, Mohamed A. Kharfan-Dabaja, Ernesto Ayala, Madiha Iqbal, Grzegorz S. Nowakowski, Thomas M. Habermann, Thomas E. Witzig, Patrick B. Johnston, Carrie A. Thompson, Stephen M. Ansell, Han W. Tun
Journal: Blood (2021)
Impact of Novel Agents on the Outcomes of Patients with Classic Hodgkin Lymphoma That Relapsed after Autologous Stem Cell Transplant
Authors: Aung M Tun, Yucai Wang, Aasiya Matin, David J. Inwards, Patrick B. Johnston, Ivana N. Micallef, Luis F. Porrata, Jose C. Villasboas, Jonas Paludo, Han W. Tun, Allison C. Rosenthal, James R. Cerhan, Thomas M. Habermann, Thomas E. Witzig, Grzegorz S. Nowakowski, Stephen M. Ansell
Journal: Blood (2021)
A novel role for endoplasmic reticulum protein 46 (ERp46) in platelet function and arterial thrombosis in mice
Authors: Junsong Zhou, Yi Wu, Lubica Rauova, Gavin Koma, Lu Wang, Mortimer Poncz, Hong Li, Tong Liu, Karen P. Fong, Joel S. Bennett, Satya P. Kunapuli, David W. Essex
Journal: Blood (2021)
Pharmacodynamic Analysis of CAR-T Cell Persistence in Patients with Hematologic Malignancies Treated with NKTR-255, an IL-15 Receptor Agonist That Enhances CD8 + T-Cells: Preliminary Results from a Phase 1 Study
Authors: Cameron J. Turtle, Elizabeth Budde, Krina K. Patel, Miguel-Angel Perales, Andrew J. Cowan, Hayder Saeed, Julio C. Chavez, Alexandre V. Hirayama, Delaney R. Kirchmeier, Murali Janakiram, Kai Wu, Lawrence Fong, Zachary Lee, Neha Dixit, Xiaoli Wang, Kazuharu Kai, Mario Q. Marcondes, Jonathan Zalevsky, Nina Shah
Journal: Blood (2021)
The Deglycosylated Form of 1E12, a Monoclonal Anti-PF4 IgG, Strongly Inhibits Antibody-Triggered Cellular Activation in Vaccine-Induced Thrombotic Thrombocytopenia, and Is a Potential New Treatment for Vιττ
Authors: Caroline Vayne, Raghavendra Palankar, Sandra Billy, Stefan Handtke, Thomas Thiele, Claire Pouplard, Andreas Greinacher, Yves Gruel, Jérôme Rollin
Journal: Blood (2021)
Peripheral Blood Single-Cell Genotyping and Phenotyping in Multiple Myeloma Reveals Shared Mutations across Multiple Hematopoietic Cell Lineages
Authors: David G. Coffey, Aditi Agrawal, Maurizio Morri, Edus H. Warren, Robert Durruthy-Durruthy, Marc Arribas-Layton, Yue Wang, Norma F. Neff
Journal: Blood (2021)
Ex Vivo Drug Sensitivity Assay Correlates with Clinical Response and Identifies Panobinostat and Bortezomib As a Potential Novel Drug Combination for Pediatric AML
Authors: Debbie C Strachan, Christine Gu, Ryosuke Kita, Michelle A Richardson, Erica K Anderson, Alan K Gonzalez, Noah J Keogh, Hailey H Oviedo, Michelle C Alozie, Raushan Rashid, Maci Terrell, Andrea N Marcogliese, Marianne T Santaguida, Alexandra McLean Stevens
Journal: Blood (2021)
Pre-Existing Anti-FVIII Immunity Alters Therapeutic Platelet-Targeted FVIII Engraftment in the System Preconditioned with Busulfan Alone through Cytotoxic CD8 T Cells
Authors: Weiqing Jing, Christina Baumgartner, Feng Xue, Jocelyn A. Schroeder, Qizhen Shi
Journal: Blood (2021)
The potential role of exosomal circRNAs in the tumor microenvironment: insights into cancer diagnosis and therapy
Authors: Juan Li, Guo Zhang, Chen-Guang Liu, Xiaoqiang Xiang, Minh T.N. Le, Gautam Sethi, Lingzhi Wang, Boon-Cher Goh, Zhaowu Ma
Journal: Theranostics (2021)

Exosomes are multifunctional regulators of intercellular communication by carrying various messages under both physiological and pathological status of cancer patients. Accumulating studies have identified the presence of circular RNAs (circRNAs) in exosomes with crucial regulatory roles in diverse pathophysiological processes. Exosomal circRNAs derived from donor cells can modulate crosstalk with recipient cells locally or remotely to enhance cancer development and propagation, and play crucial roles in the tumor microenvironment (TME), leading to significant enhancement of tumor immunity, metabolism, angiogenesis, drug resistance, epithelial mesenchymal transition (EMT), invasion and metastasis. In this review, we describe the advances of exosomal circRNAs and their roles in modulating cancer hallmarks, especially those in the TME. Moreover, clinical application potential of exosomal circRNAs in cancer diagnosis and therapy are highlighted, bridging the gap between basic knowledge and clinical practice.
Abstract 9081: Fatal Occlusive Pulmonary Vasculopathy in Rats Late After Perinatal Hypoxia: Hyperproliferative and Pro-Inflammatory Phenotypes and Related Differential Dna Methylation in Cultured Pulmonary Arterial Smooth Muscle Cells as the Potential Substrate
Authors: Hironori Oshita, Hirofumi Sawada, Yoshihide Mitani, NAOKI TSUBOYA, Jane Kabwe, Junko Maruyama, Ali Yusuf, Hiromasa Ito, Ryuji Okamoto, Noriko Yodoya, Shoichiro Otsuki, Hiroyuki Ohashi, Kazunobu Oya, Yuhko Kobayashi, Issei Kobayashi, Kaoru Dohi, Yuhei Nishimura, Shinji Saitoh, sawada hirofumi, Masahiro Hirayama
Journal: Circulation (2021)

Background: Perinatal insults increase the risk of developing various adult-onset vascular diseases. Although we recently established a fatal SU5416/hypoxia-induced model with worsening pulmonary vascular disease (PVD) in rats late after exposure to perinatal hypoxia, the mechanisms are elusive. Hypothesis: In rats with fatal occlusive PVD late after perinatal hypoxia, cultured pulmonary arterial smooth muscle cells (PASMCs) from rats before SU5416/hypoxia treatment exhibit phenotypic and epigenetic changes. Methods: PVD was induced in 7-week-old rats exposed to perinatal hypoxia or ambient air by injecting SU5416 followed by exposure to hypoxia for 3 weeks (SU5416/hypoxia). Rats were assessed at the baseline (7 weeks of age) and 8 weeks after SU5416 injection (15 weeks of age). Proliferation, cytokine production and genome-wide DNA methylation profile were evaluated in PASMC isolated from the baseline rats with/without perinatal hypoxia. Results: In SU5416/hypoxia rats, perinatal hypoxia reduced body weight gain and survival, and increased right ventricular systolic pressure, Fulton index and occlusive PVD (p&lt;.05), which were associated with an increase in perivascular macrophages, expression of prepro-endothelin-1 mRNA and eNOS protein in the lung (p&lt;.05) but not with impaired alveolarization or worsening right ventricular fibrosis. In PASMCs isolated from the baseline rats, perinatal hypoxia enhanced PDGF-BB-induced cell proliferation and phosphorylation of extracellular signal-regulated kinase as well as TNFα-induced expression of IL-6, monocyte chemotactic protein 1 and phosphorylation of p38 (p&lt;.05). DNA methylation profiling identified 35 differentially methylated regions (DMRs). Methylation in the region encoding phosducin like protein (Pdcl) was associated with decreased PDGF-BB-induced expression of Pdcl mRNA in PASMCs with perinatal hypoxia. Functional enrichment analysis of DMRs revealed the relation to cell proliferation and inflammatory process (ie, Wnt5A and ROR1). Conclusions: In SU5416/hypoxia rats late after perinatal hypoxia, hyperproliferative and pro-inflammatory phenotypes and functionally related differential DNA methylation in PASMCs may be the substrate for the fatal occlusive PVD.
Real World Prospective Observational Multicenter Trial of Venetoclax-Based Therapy for Patients with AML Reveals Unique Patterns of Patient Selection and Treatment Utilization - Revive Study
Authors: Ofir Wolach, Itai Levi, David Lavie, Jonathan Canaani, Sigal Tavor, Ilana Hellmann, Tamar Tadmor, Tsila Zuckerman, Galia Stemer, Jenia Berelovich, Keren Ofek, Neta Frankel, Moshe Grunspan, Yishai Ofran, Yakir Moshe
Journal: Blood (2021)
Ambient Air Pollution in Relation to SARS-CoV-2 Infection, Antibody Response, and COVID-19 Disease: A Cohort Study in Catalonia, Spain (COVICAT Study)
Authors: Manolis Kogevinas, Gemma Castaño-Vinyals, Marianna Karachaliou, Ana Espinosa, Rafael de Cid, Judith Garcia-Aymerich, Anna Carreras, Beatriz Cortés, Vanessa Pleguezuelos, Alfons Jiménez, Marta Vidal, Cristina O’Callaghan-Gordo, Marta Cirach, Rebeca Santano, Diana Barrios, Laura Puyol, Rocío Rubio, Luis Izquierdo, Mark Nieuwenhuijsen, Payam Dadvand, Ruth Aguilar, Gemma Moncunill, Carlota Dobaño, Cathryn Tonne
Journal: Environmental Health Perspectives (2021)

Background: Emerging evidence links ambient air pollution with coronavirus 2019 (COVID-19) disease, an association that is methodologically challenging to investigate. Objectives: We examined the association between long-term exposure to air pollution with SARS-CoV-2 infection measured through antibody response, level of antibody response among those infected, and COVID-19 disease. Methods: We contacted 9,605 adult participants from a population-based cohort study in Catalonia between June and November 2020; most participants were between 40 and 65 years of age. We drew blood samples from 4,103 participants and measured immunoglobulin M (IgM), IgA, and IgG antibodies against five viral target antigens to establish infection to the virus and levels of antibody response among those infected. We defined COVID-19 disease using self-reported hospital admission, prior positive diagnostic test, or more than three self-reported COVID-19 symptoms after contact with a COVID-19 case. We estimated prepandemic (2018–2019) exposure to fine particulate matter [PM with an aerodynamic diameter of ≤2.5μm (PM2.5)], nitrogen dioxide (NO2), black carbon (BC), and ozone (O3) at the residential address using hybrid land-use regression models. We calculated log-binomial risk ratios (RRs), adjusting for individual- and area-level covariates. Results: Among those tested for SARS-CoV-2 antibodies, 743 (18.1%) were seropositive. Air pollution levels were not statistically significantly associated with SARS-CoV-2 infection: Adjusted RRs per interquartile range were 1.07 (95% CI: 0.97, 1.18) for NO2, 1.04 (95% CI: 0.94, 1.14) for PM2.5, 1.00 (95% CI: 0.92, 1.09) for BC, and 0.97 (95% CI: 0.89, 1.06) for O3. Among infected participants, exposure to NO2 and PM2.5 were positively associated with IgG levels for all viral target antigens. Among all participants, 481 (5.0%) had COVID-19 disease. Air pollution levels were associated with COVID-19 disease: adjusted RRs=1.14 (95% CI: 1.00, 1.29) for NO2 and 1.17 (95% CI: 1.03, 1.32) for PM2.5. Exposure to O3 was associated with a slightly decreased risk (RR=0.92; 95% CI: 0.83, 1.03). Associations of air pollution with COVID-19 disease were more pronounced for severe COVID-19, with RRs=1.26 (95% CI: 0.89, 1.79) for NO2 and 1.51 (95% CI: 1.06, 2.16) for PM2.5. Discussion: Exposure to air pollution was associated with a higher risk of COVID-19 disease and level of antibody response among infected but not with SARS-CoV-2 infection. https://doi.org/10.1289/EHP9726
Importance of schizophrenic symptoms in the diagnosis of mania
Authors: R Abrams, M A Taylor
Journal: American Journal of Psychiatry (1981)

The authors examined a sample of 111 consecutively admitted patients who satisfied inclusion criteria for mania and further characterized them as exhibiting none, one, or two or more of five clinical features often believed to be associated with a diagnosis of schizophrenia: formal thought disorder, first-rank symptoms, auditory hallucinations, persecutory delusions, and catatonia. The presence and number of such symptoms were unrelated to any of the major demographic, clinical, historical, laboratory, or familial variables studied. The authors conclude that schizophrenic symptoms do not play an important role in patients who satisfy modern criteria for the diagnosis of mania.
Assessment of Excess Mortality and Household Income in Rural Bangladesh During the COVID-19 Pandemic in 2020
Authors: Prabhat Barnwal, Yuling Yao, Yiqian Wang, Nishat Akter Juy, Shabib Raihan, Mohammad Ashraful Haque, Alexander van Geen
Journal: JAMA Network Open (2021)

<h3>Importance</h3> A slow or incomplete civil registry makes it impossible to determine excess mortality due to COVID-19 and difficult to inform policy. <h3>Objective</h3> To quantify the association of the COVID-19 pandemic with excess mortality and household income in rural Bangladesh in 2020. <h3>Design, Setting, and Participants</h3> This repeated survey study is based on an in-person census followed by 2 rounds of telephone calls. Data were collected from a sample of 135 villages within a densely populated 350-km<sup>2</sup>rural area of Bangladesh. Household data were obtained first in person and subsequently over the telephone. For the analysis, mortality data were stratified by month, age, sex, and household education. Mortality rates were modeled by bayesian multilevel regression, and the strata were aggregated to the population by poststratification. Data analysis was performed from February to April 2021. <h3>Exposures</h3> Date and cause of any changes in household composition, as well as changes in income and food availability. <h3>Main Outcomes and Measures</h3> Mortality rates were compared for 2019 and 2020, both without adjustment and after adjustment for nonresponse and differences in demographic variables between surveys. Income and food availability reported for January, May, and November 2020 were also compared. <h3>Results</h3> Enumerators collected data from an initial 16 054 households in January 2020; 14 551 households (91%) responded when contacted again by telephone in May 2020, and 11 933 households (74%)responded when reached again over the telephone in November 2020, for a total of 58 806 individuals (29 726 female participants [50.5%]; mean [SD] age, 26.4 [19.8] years). A total of 276 deaths were reported between February and the end of October 2020 for the subset of the population that could be contacted twice over the telephone, slightly below the 289 deaths reported for the same population over the same period in 2019. After adjustment for survey nonresponse and poststratification, 2020 mortality changed by −8% (95% CI, −21% to 7%) compared with an annualized mortality of 6.1 deaths per 1000 individuals in 2019. However, in May 2020, salaried primary income earners reported a 40% decrease in monthly income (from 17 485 to 10 835 Bangladeshi Taka), and self-employed earners reported a 60% decrease in monthly income (23 083 to 8521 Bangladeshi Taka), with only a small recovery observed by November 2020. <h3>Conclusions and Relevance</h3> In this study of households in rural Bangladesh, all-cause mortality was lower in 2020 compared with 2019. Restrictions imposed by the government may have limited the scale of the COVID-19 pandemic in rural areas, although economic data suggest that these restrictions need to be accompanied by expanded welfare programs.