tbuckley/cabot-search huggingface dataset:
Genetics of Atrial Fibrillation in 2020
Authors: Carolina Roselli, Michiel Rienstra, Patrick T. Ellinor
Journal: Circulation Research (2020)

Atrial fibrillation is a common heart rhythm disorder that leads to an increased risk for stroke and heart failure. Atrial fibrillation is a complex disease with both environmental and genetic risk factors that contribute to the arrhythmia. Over the last decade, rapid progress has been made in identifying the genetic basis for this common condition. In this review, we provide an overview of the primary types of genetic analyses performed for atrial fibrillation, including linkage studies, genome-wide association studies, and studies of rare coding variation. With these results in mind, we aim to highlighting the existing knowledge gaps and future directions for atrial fibrillation genetics research.
Dual Thyroid Ectopia and Heterotopic Thyroid Autotransplantation
Authors: Shanmuga Sundaram Palaniswamy, Padma Subramanyam
Journal: Clinical Nuclear Medicine (2020)

Abstract Ectopic thyroid gland can be detected at any age. It is a developmental defect that results from abnormal migration of the primitive thyroid bud. Dual ectopia is very rare, and only a few cases have been reported in literature. Patients with thyroid ectopia may be either euthyroid or hypothyroid. Concept of thyroid autotransplantation is based on restoring euthyroidism and is an attempt to preserve the autoregulatory mechanism of hormone production. This is a case of dual ectopia who underwent heterotopic thyroid autotranplantation. Images demonstrate hypertrophy of the transplanted thyroid tissue with gradual restoration of thyroid trapping function.
Large-scale implementation of pooled RNA extraction and RT-PCR for SARS-CoV-2 detection
Authors: R. Ben-Ami, A. Klochendler, M. Seidel, T. Sido, O. Gurel-Gurevich, M. Yassour, E. Meshorer, G. Benedek, I. Fogel, E. Oiknine-Djian, A. Gertler, Z. Rotstein, B. Lavi, Y. Dor, D.G. Wolf, M. Salton, Y. Drier, A. Klochendler, A. Eden, A. Klar, A. Geldman, A. Arbel, A. Peretz, B. Shalom, B.L. Ochana, D. Avrahami-Tzfati, D. Neiman, D. Steinberg, D. Ben Zvi, E. Shpigel, G. Atlan, H. Klein, H. Chekroun, H. Shani, I. Hazan, I. Ansari, I. Magenheim, J. Moss, J. Magenheim, L. Peretz, L. Feigin, M. Saraby, M. Sherman, M. Bentata, M. Avital, M. Kott, M. Peyser, M. Weitz, M. Shacham, M. Grunewald, N. Sasson, N. Wallis, N. Azazmeh, N. Tzarum, O. Fridlich, R. Sher, R. Condiotti, R. Refaeli, R. Ben Ami, R. Zaken-Gallili, R. Helman, S. Ofek, S. Tzaban, S. Piyanzin, S. Anzi, S. Dagan, S. Lilenthal, T. Sido, T. Licht, T. Friehmann, Y. Kaufman, A. Pery, A. Saada, A. Dekel, A. Yeffet, A. Shaag, A. Michael-Gayego, E. Shay, E. Arbib, H. Onallah, K. Ben-Meir, L. Levinzon, L. Cohen-Daniel, L. Natan, M. Hamdan, M. Rivkin, M. Shwieki, O. Vorontsov, R. Barsuk, R. Abramovitch, R. Gutorov, S. Sirhan, S. Abdeen, Y. Yachnin, Y. Daitch
Journal: Clinical Microbiology and Infection (2020)
Usefulness of Liver Magnetic Resonance Elastography for Estimating Right-Atrial Pressure in Heart Failure Patients
Authors: Yoshiya Kato, Toshiyuki Nagai, Noriko Oyama-Manabe, Satonori Tsuneta, Michikazu Nakai, Yuta Kobayashi, Hirokazu Komoriyama, Kazunori Omote, Shingo Tsujinaga, Takuma Sato, Takao Konishi, Kiwamu Kamiya, Hiroyuki Iwano, Toshihisa Anzai
Journal: JACC. Cardiovascular imaging (2020)
Clinical presentation of Covid-19 in health care workers from a French University Hospital
Authors: Aude Jary, Philippe Flandre, Agnès Chabouis, Séverine Nguyen, Stéphane Marot, Sonia Burrel, David Boutolleau, Vincent Calvez, Anne-Geneviève Marcelin, Martine Louet
Journal: Journal of Infection (2020)
Frequent STAT3 Mutations in CD8+ T Cells from Patients with Pure Red Cell Aplasia
Authors: Toru Kawakami, Nodoka Sekiguchi, Jun Kobayashi, Tatsuya Imi, Kazuyuki Matsuda, Taku Yamane, Sayaka Nishina, Yasushi Senoo, Hitoshi Sakai, Toshiro Ito, Tomonobu Koizumi, Makoto Hirokawa, Shinji Nakao, Hideyuki Nakazawa, Fumihiro Ishida
Journal: Blood (2018)
Fetal exposure to oncoantigen elicited antigen-specific adaptive immunity against tumorigenesis
Authors: Jeng-Chang Chen, Liang-Shiou Ou, Ming-Ling Kuo, Li-Yun Tseng, Hsueh-Ling Chang
Journal: Journal for ImmunoTherapy of Cancer (2020)

Envisioned as a similar process to tumorigenesis in terms of biological behaviors and molecular basis, embryogenesis necessitates an immune surveillance system to eliminate erratically transformed cells. Our previous study demonstrated that fetal macrophage-like phagocytes triggered Th2-skewed immunity following endocytosing prenatally administered ovalbumin to facilitate postnatal allergic airway responses, highlighting the critical role fetal phagocytes played in dealing with antigens present in developing fetuses and shaping subsequent immune responses. It prompted us to examine whether fetuses could mount Th1 tumoricidal immunity against tumorigenesis following in utero exposure to tumor antigens.Gestational day 14 murine fetuses underwent in utero injection of Th1-promoting human papilloma virus (HPV) E7 peptides. Postnatally, recipients were examined for immunological consequences and the resistance to TC-1 tumorigenesis.Fetal exposure to HPV E7 did not cause tolerance but rather immunization in the recipients, characterized by proinflammatory Th1 polarization of their lymphocytes. Fetal macrophage-like phagocytes were responsible for taking up HPV E7 and triggering HPV E7-specific T-cell cytotoxicity and humoral immunity that rendered recipients resistant to TC-1 tumorigenesis in postnatal life. Adoptive transfer of HPV E7-loaded fetal phagocytes also elicited Th1 immunity with rapid expansion of HPV E7-specific cytotoxic CD8+ T-cell clones in response to TC-1 cell challenge so as to protect the recipients from TC-1 tumorigenesis, but failed to completely eliminate pre-existing TC-1 cells despite perceptible attenuation of local TC-1 tumor growth.Our study revealed that Th2-biasing fetus was not immune-privileged to foreign peptides, but competent to mount Th1 cytotoxic immunity and generate immunoglobulins against tumorigenesis following in utero exposure to Th1-promoting oncoantigen. It shed light on the role of fetal macrophage-like phagocytes in bridging toward tumor antigen-specific cellular and humoral immunity potentially as an immune surveillance system to eliminate transformed cells that might be egressing during embryogenesis and leftover until postnatal life.
First-in-human phase I study of immunomodulatory E7046, an antagonist of PGE<sub>2</sub>-receptor E-type 4 (EP4), in patients with advanced cancers
Authors: David S Hong, Aparna Parikh, Geoffrey I Shapiro, Andrea Varga, Aung Naing, Funda Meric-Bernstam, Özlem Ataman, Larisa Reyderman, Terri A Binder, Min Ren, Mingjie Liu, Satish Dayal, Amy Y Siu, Pallavi Sachdev, Lucy Xu, Vijay Bhagawati-Prasad, Ilian Tchakov, Chean Eng Ooi, Xingfeng Bao, Aurelien Marabelle
Journal: Journal for ImmunoTherapy of Cancer (2020)

E7046 is a highly selective, small-molecule antagonist of the E-type prostanoid receptor 4 (EP4) for prostaglandin E2, an immunosuppressive mediator of the tumor immune microenvironment. This first-in-human phase 1 study assessed the safety, tolerability, pharmacokinetics, pharmacodynamics, maximum tolerated dose (MTD) and recommended phase 2 dose of E7046.This first-in-human study enrolled 30 patients with advanced tumors of cancer types associated with high levels of myeloid infiltrates. E7046 was administered orally once-daily in sequential escalating dose cohorts (125, 250, 500, and 750 mg) with ≥6 patients per cohort. Tumor assessments were performed every 6 weeks. Paired tumor biopsies and blood samples, before and on treatment, were collected for pharmacokinetic and pharmacodynamic characterization of the treatment.No dose-limiting toxicities were observed, and the MTD was not reached. E7046 had an elimination half-life (t1/2) of 12 hours, and drug exposure increased dose-dependently from 125 to 500 mg. Target modulation by E7046 was supported by changes in genes downstream of EP4 with concurrent enhanced antitumoral immune responses. A best response of stable disease (per irRECIST) was reported in 23% of patients treated with E7046 (n=30) (125 mg: n=2; 250 mg: n=2; 750 mg: n=3). Over half (4/7) of the patients with stable disease had treatment duration of 18 weeks or more, and three patients (3/15; 20%) achieved metabolic responses.In this first-in-human study, E7046 administered orally once daily demonstrated manageable tolerability, immunomodulatory effects, and a best response of stable disease (≥18 weeks) in several heavily pretreated patients with advanced malignancies. The 250 and 500 mg doses are proposed for further development in the combination setting.NCT02540291.
Assessment of Extreme Risk Protection Order Use in California From 2016 to 2019
Authors: Rocco Pallin, Julia P. Schleimer, Veronica A. Pear, Garen J. Wintemute
Journal: JAMA Network Open (2020)

<h3>Importance</h3> A total of 19 states and the District of Columbia now have extreme risk protection order (ERPO) or similar policies, and others are considering them; however, little research exists describing their use. <h3>Objective</h3> To characterize early use of California's ERPO policy by providing the first aggregate, statewide description of ERPOs, individuals subject to them, and petitioners. <h3>Design, Setting, and Participants</h3> This cross-sectional study analyzed 1094 respondents to ERPOs recorded in the California Department of Justice California Restraining and Protective Order System from 2016 to 2019. Descriptive analyses of orders issued between January 1, 2016, and December 31, 2019 in California were performed, and univariate Moran I was calculated to examine county-level spatial autocorrelation of the policy's use. <h3>Main Outcomes and Measures</h3> The primary study outcomes included the characteristics of ERPO respondents (demographic characteristics), petitioners (law enforcement vs family or household members), and orders (type and service) as well as temporal and spatial variation in policy use during the first 4 years of implementation. <h3>Results</h3> Of 1094 respondents during the study period, most were men (999 [91.3%]) and white individuals (654 [59.8%]), with a mean age of 41.8 years (range, 14 to 98 years). A law enforcement officer was the petitioner in 1053 cases (96.3%). The number of respondents increased during the study period from 71 in 2016 to 717 in 2019, and there was substantial county-level variation in ERPO use (ranging from 0 to 355 respondents), with significant spatial clustering in counts of ERPO respondents among neighboring counties (observed Moran I, 0.18, mean [SD] Moran I from reference distribution, −0.02 (0.05);<i>z</i>value, 3.90;<i>P</i> = .005). <h3>Conclusions and Relevance</h3> This study, among the first to describe the early utilization of an ERPO or similar policy, found a substantial increase in the use of ERPOs in California from 2016 to 2019. These results could inform policy makers and other stakeholders involved in policy implementation and outreach in California and elsewhere. Similar studies in other states would be useful to understand variation.
Successful treatment of superior mesenteric artery syndrome by endoscopic ultrasound-guided gastrojejunostomy
Authors: Michiel Bronswijk, Lennert Fransen, Giuseppe Vanella, Martin Hiele, Schalk van der Merwe
Journal: Endoscopy (2020)

An 88-year-old man with a history of extensive cardiovascular co-morbidities was admitted to our tertiary center following prolonged vomiting, anorexia, and upper abdominal pain. He had lost 10 kilograms over the course of 4 months as a result. An abdominal computed tomography (CT) scan was performed to rule out neoplasia. Surprisingly, the scan revealed extensive gastroduodenal distention and a high-grade stenosis of the third part of the duodenum (D3) caused by extrinsic compression by the superior mesenteric artery ([Fig. 1], arrow). Furthermore, a significantly reduced aortomesenteric angle was identified (9.1°, normal: 25 – 60°) ([Fig. 2]); these findings are compatible with superior mesenteric artery syndrome [1]. Nasogastric tube decompression and parenteral feeding were commenced, resulting in only temporary relief of symptoms. Unfortunately, endoscopic placement of a nasojejunal feeding tube also failed.
Genome-Wide Association Study of Over One Million Participants Identifies 49 Novel Loci Associated With Coronary Artery Disease
Authors: K G Aragam, T Jiang, S Kanoni, G Anuj, B Wolford, I Surakka, C Grace, G Thorleifsson, C Nelson, C Roselli, G Hindy, W Wang, Venegas Mlm., J C Hopewell, C Ruff, M S Sabatine, H C Watkins, J Danesh, P T Ellinor, H Holm, R J Clarke, H Schunkert, M Farrall, J Erdmann, K Stefansson, U Thorsteinsdottir, C Willer, N J Samani, P Deloukas, S Kathiresan, A Butterworth
Journal: Circulation (2019)
Review of influenza-associated pulmonary aspergillosis in ICU patients and proposal for a case definition: an expert opinion
Authors: Paul E. Verweij, Bart J. A. Rijnders, Roger J. M. Brüggemann, Elie Azoulay, Matteo Bassetti, Stijn Blot, Thierry Calandra, Cornelius J. Clancy, Oliver A. Cornely, Tom Chiller, Pieter Depuydt, Daniele Roberto Giacobbe, Nico A. F. Janssen, Bart-Jan Kullberg, Katrien Lagrou, Cornelia Lass-Flörl, Russell E. Lewis, Peter Wei-Lun Liu, Olivier Lortholary, Johan Maertens, Ignacio Martin-Loeches, M. Hong Nguyen, Thomas F. Patterson, Thomas R. Rogers, Jeroen A. Schouten, Isabel Spriet, Lore Vanderbeke, Joost Wauters, Frank L. van de Veerdonk
Journal: Intensive Care Medicine (2020)

Invasive pulmonary aspergillosis is increasingly reported in patients with influenza admitted to the intensive care unit (ICU). Classification of patients with influenza-associated pulmonary aspergillosis (IAPA) using the current definitions for invasive fungal diseases has proven difficult, and our aim was to develop case definitions for IAPA that can facilitate clinical studies. A group of 29 international experts reviewed current insights into the epidemiology, diagnosis and management of IAPA and proposed a case definition of IAPA through a process of informal consensus. Since IAPA may develop in a wide range of hosts, an entry criterion was proposed and not host factors. The entry criterion was defined as a patient requiring ICU admission for respiratory distress with a positive influenza test temporally related to ICU admission. In addition, proven IAPA required histological evidence of invasive septate hyphae and mycological evidence for Aspergillus. Probable IAPA required the detection of galactomannan or positive Aspergillus culture in bronchoalveolar lavage (BAL) or serum with pulmonary infiltrates or a positive culture in upper respiratory samples with bronchoscopic evidence for tracheobronchitis or cavitating pulmonary infiltrates of recent onset. The IAPA case definitions may be useful to classify patients with COVID-19-associated pulmonary aspergillosis (CAPA), while awaiting further studies that provide more insight into the interaction between Aspergillus and the SARS-CoV-2-infected lung. A consensus case definition of IAPA is proposed, which will facilitate research into the epidemiology, diagnosis and management of this emerging acute and severe Aspergillus disease, and may be of use to study CAPA.
Abstract 9664: Importance of Early Initiation of Anti-Tumor Necrosis Factor-a With Etanercept for Slowing the Progression of Heart Failure: Insights into the Underlying Cellular and Molecular Mechanisms
Authors: Xiaowei Zhang, Che Ping Cheng, Tiankai Li, Zhe Chen, Yixi Liu, Peng Zhou, Heng-Jie Cheng
Journal: Circulation (2019)

Background: Elevated levels of tumor necrosis factor-α (TNFα) contribute to heart failure (HF) progression, which may suggest therapeutic value of antagonizing TNFα for HF patients. However, clinic...
GM-CSF-based treatments in COVID-19: reconciling opposing therapeutic approaches
Authors: Frederick M. Lang, Kevin M.-C. Lee, John R. Teijaro, Burkhard Becher, John A. Hamilton
Journal: Nature reviews. Immunology (2020)

Therapeutics against coronavirus disease 2019 (COVID-19) are urgently needed. Granulocyte–macrophage colony-stimulating factor (GM-CSF), a myelopoietic growth factor and pro-inflammatory cytokine, plays a critical role in alveolar macrophage homeostasis, lung inflammation and immunological disease. Both administration and inhibition of GM-CSF are currently being therapeutically tested in COVID-19 clinical trials. This Perspective discusses the pleiotropic biology of GM-CSF and the scientific merits behind these contrasting approaches. Recombinant granulocyte–macrophage colony-stimulating factor (GM-CSF) as well as antibodies targeted at GM-CSF or its receptor are being tested in clinical trials for coronavirus disease 2019 (COVID-19). This Perspective introduces the pleiotropic functions of GM-CSF and explores the rationale behind these different approaches.
Abstract 15459: Effects of Change in Glucose Intolerance Status on Risk of Incident Cardiovascular Disease: Tehran Lipid and Glucose Study
Authors: Maryam Kabootari, Farzad Hadaegh, Mitra Hasheminia, Fereidoun Azizi
Journal: Circulation (2019)

Objective: We aimed to assess whether risk of cardiovascular disease (CVD) in prediabetes is dependent on development of diabetes during follow-up. Methods: In a prospective population-based cohort...
Correcting β-thalassemia by combined therapies that restrict iron and modulate erythropoietin activity
Authors: Carla Casu, Mariateresa Pettinato, Alison Liu, Mariam Aghajan, Vania Lo Presti, Maria Rosa Lidonnici, Kevin A. Munoz, Emir O’Hara, Violante Olivari, Simona Maria Di Modica, Sheri Booten, Shuling Guo, Garry Neil, Reem Miari, Nir Shapir, Inbal Zafir-Lavie, Hagit Domev, Giuliana Ferrari, Despina Sitara, Antonella Nai, Stefano Rivella
Journal: Blood (2020)

β-Thalassemia intermedia is a disorder characterized by ineffective erythropoiesis (IE), anemia, splenomegaly, and systemic iron overload. Novel approaches are being explored based on the modulation of pathways that reduce iron absorption (ie, using hepcidin activators like Tmprss6-antisense oligonucleotides [ASOs]) or increase erythropoiesis (by erythropoietin [EPO] administration or modulating the ability of transferrin receptor 2 [Tfr2] to control red blood cell [RBC] synthesis). Targeting Tmprss6 messenger RNA by Tmprss6-ASO was proven to be effective in improving IE and splenomegaly by inducing iron restriction. However, we postulated that combinatorial strategies might be superior to single therapies. Here, we combined Tmprss6-ASO with EPO administration or removal of a single Tfr2 allele in the bone marrow of animals affected by β-thalassemia intermedia (Hbbth3/+). EPO administration alone or removal of a single Tfr2 allele increased hemoglobin levels and RBCs. However, EPO or Tfr2 single-allele deletion alone, respectively, exacerbated or did not improve splenomegaly in β-thalassemic mice. To overcome this issue, we postulated that some level of iron restriction (by targeting Tmprss6) would improve splenomegaly while preserving the beneficial effects on RBC production mediated by EPO or Tfr2 deletion. While administration of Tmprss6-ASO alone improved the anemia, the combination of Tmprss6-ASO + EPO or Tmprss6-ASO + Tfr2 single-allele deletion produced significantly higher hemoglobin levels and reduced splenomegaly. In conclusion, our results clearly indicate that these combinatorial approaches are superior to single treatments in ameliorating IE and anemia in β-thalassemia and could provide guidance to translate some of these approaches into viable therapies.
Lenograstim-Induced Nodal Extramedullary Hematopoiesis
Authors: Benjamin Leroy-Freschini, Alina Nicolae, Aurore Iltis-Roux
Journal: Clinical Nuclear Medicine (2020)

Abstract We report the case of a 23-year-old man with nodal EMH (extramedullary hematopoiesis) occurring during treatment for a stage IIA “gray-zone” lymphoma. Although it is often related to myeloproliferative bone marrow disease, benign etiologies such as lenograstim treatment after chemotherapy can also induce EMH and be responsible for false-positive 18 F-FDG PET/CT examinations. In this respect, GLUT overexpression in hematopoietic lineages and macrophages of the inflammatory environment are responsible for increased 18 F-FDG uptake. Histopathologic confirmation of new hypermetabolic lesions on follow-up PET/CT may be required when the new lesions do not conform with the treatment responses in the preexisting lesions.
OP0102 Infection in systemic lupus erythematosus (sle), a 21 years study
Authors: M Akbarian, S Shahnia, S Ehsani, F Gharibdoost, F Shahram, A Nadji, AR Jamshidi, F Davatchi
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Infection is a major source of morbidity and mortality in patients with SLE. The prevalence of infection in SLE is different in various countries and is due to many factors. <h3>Objectives</h3> The aim of our study was to evaluate the incidence of various infections in Iranian SLE patients and its contribution to mortality during a 21 years period (1974–97). <h3>Methods</h3> We evaluated retrospectively 1165 patients for 21 years. For each patient 266 parameters were systemically checked. Each episode of infection was evaluated according to the organic involvement, type of infection and the infective agent, presence of steroid therapy. <h3>Results</h3> During this 21 years period 393 infection episodes were noted in 224 patients. The total follow-up time was 820 years (mean: 3.66). The mean interval between the beginning of the illness and the occurrence of the infectious episode was 3.4 years. Urinary tract infection (UTI) was the most frequent (24.9%). The UTI was seen in 9.3% of patients. The most frequent bacteria was Escherichia coli (68.4% of UTI). Pulmonary infections were seen in 11.9% of infection cases. In infectious pneumonia, 72.2% was due to Pneumococci. Septic arthritis was seen in 17 cases (4.3% of all infections) and Osteomyelitis in 5 cases (1.3%). The most frequent bacteria for musculoskeletal infections were Salmonella. Soft tissue infections (abscesses, cellulitis, infectious ulcer and infectious lymphadenitis) were seen in 67 cases (17%). The most frequent bacteria were Staphylococcus aureus. Septicemia was seen in 64 cases (16.3%) of patients. The most frequent bacteria were salmonella. The mean steroid dose in patients who died of infection was 48.6 mg/day versus 25.3 mg in others (P &lt; 0.0001). To determine the effectivity of simple laboratory tests in early diagnosis of severe infections, patients were divided into three groups according to the severity of their illness. Severe infections were accompanied with higher levels of ESR (P = 0.0005), CRP (P = 0.00001) and serum creatinine (P = 0.00001) and lower levels of serum complement (P = 0.006) while Anti-DNA and active urinary sediment were not among differentiating factors. There was a significant increase in WBC count in severe infections when steroid dose was below 40 mg/day (P &lt; 0.0001 versus P &lt; 0.4 when the steroid dose was more than 40 mg). <h3>Conclusion</h3> UTI was the most common infection and E. coli was the most frequent infective organism. Apart lower UTI, soft tissue infections, sepsis, and pulmonary infections were the commonest infections while S. aureus and salmonella were the most common agents. Moreover, high dose of steroids is a significant predisposing factor for infections as mentioned in other published studies. A high WBC count, raised CRP and ESR can be helpful for the diagnosis of an infection with organisms such as Salmonella, Staphylococcus, Pseudomonas or Candida albicans.