tbuckley/cabot-search huggingface dataset:
Risk of hospital admission with coronavirus disease 2019 in healthcare workers and their households: nationwide linkage cohort study
Authors: Anoop S V Shah, Rachael Wood, Ciara Gribben, David Caldwell, Jennifer Bishop, Amanda Weir, Sharon Kennedy, Martin Reid, Alison Smith-Palmer, David Goldberg, Jim McMenamin, Colin Fischbacher, Chris Robertson, Sharon Hutchinson, Paul McKeigue, Helen Colhoun, David A McAllister
Journal: BMJ (2020)

Abstract Objective To assess the risk of hospital admission for coronavirus disease 2019 (covid-19) among patient facing and non-patient facing healthcare workers and their household members. Design Nationwide linkage cohort study. Setting Scotland, UK, 1 March to 6 June 2020. Participants Healthcare workers aged 18-65 years, their households, and other members of the general population. Main outcome measure Admission to hospital with covid-19. Results The cohort comprised 158 445 healthcare workers, most of them (90 733; 57.3%) being patient facing, and 229 905 household members. Of all hospital admissions for covid-19 in the working age population (18-65 year olds), 17.2% (360/2097) were in healthcare workers or their households. After adjustment for age, sex, ethnicity, socioeconomic deprivation, and comorbidity, the risk of admission due to covid-19 in non-patient facing healthcare workers and their households was similar to the risk in the general population (hazard ratio 0.81 (95% confidence interval 0.52 to 1.26) and 0.86 (0.49 to 1.51), respectively). In models adjusting for the same covariates, however, patient facing healthcare workers, compared with non-patient facing healthcare workers, were at higher risk (hazard ratio 3.30, 2.13 to 5.13), as were household members of patient facing healthcare workers (1.79, 1.10 to 2.91). After sub-division of patient facing healthcare workers into those who worked in “front door,” intensive care, and non-intensive care aerosol generating settings and other, those in front door roles were at higher risk (hazard ratio 2.09, 1.49 to 2.94). For most patient facing healthcare workers and their households, the estimated absolute risk of hospital admission with covid-19 was less than 0.5%, but it was 1% and above in older men with comorbidity. Conclusions Healthcare workers and their households contributed a sixth of covid-19 cases admitted to hospital. Although the absolute risk of admission was low overall, patient facing healthcare workers and their household members had threefold and twofold increased risks of admission with covid-19.
Abstract MP110: Inhibition of the Unfolded Protein Response Reduces Arrhythmic Risk After Myocardial Infarction
Authors: Man Liu, Hong Liu, Preethy Parthiban, guangbin shi, Gyeoung-Jin Kang, Feng Feng, Anyu Zhou, Lianzhi Gu, Alena Talkachova, Samuel C Dudley
Journal: Circulation Research (2020)

Background: Ischemic cardiomyopathy is associated with an increased risk of sudden death, activation of the unfolded protein response (UPR), and reductions in multiple cardiac ion channels and transporters. When activated, the protein kinase-like ER kinase (PERK) arm of the unfolded protein response (UPR) reduces protein translation and abundance. We hypothesize that inhibition of PERK could prevent cardiac ion channel downregulation and reduce arrhythmic risk after myocardial infarct (MI). Methods: The MI mouse model was induced by a left anterior descending coronary artery ligation. Pharmacological inhibition of PERK was achieved with a specific inhibitor, GSK2606414. Genetic inhibition of PERK was achieved by cardiac-specific PERK knockout in C57BL/6J mice (PERKKO). Echocardiography, telemetry, and electrophysiological measurements were performed to monitor cardiac function and arrhythmias. Results: Three weeks after surgery, the wild type MI mice exhibited decreased ejection fraction (EF%), ventricular tachycardia (VT) and prolonged QTc intervals. The UPR effectors (phospho-PERK, phospho-IRE1, and ATF6N) were elevated significantly (1.7- to 5.9-fold) at protein levels, and all major cardiac ion channels showed decreased protein expression in MI hearts. MI cardiomyocytes showed decreased currents for all major channels (I Na , I CaL , I to , I K1 , and I Kur : 60±6%, 53±9%, 27±6%, 55±7%, and 40±7% of sham, respectively, P&lt;0.05 vs. sham) with significantly prolonged action potential duration (APD 90 : 291±43 ms of MI vs. 100±12 ms of sham, P&lt;0.05) and decreased maximum upstroke velocity (dV/dt max : 95±4 V/s of MI vs. 132±6 ms of sham, P&lt;0.05) of the action potential phase 0. GSK treatment restored I Na and I to , shortened APD, and increased dV/dt max . PERKKO mice exhibited reduced electrical remodeling in response to MI with shortened QTc intervals, less VT episodes, and higher survival rates. Conclusion: PERK is activated during MI and contributes to arrhythmic risk by downregulation of select cardiac ion channels. PERK inhibition prevented these changes and reduced arrhythmic risk. These results suggest that ion channel downregulation during MI is a fundamental arrhythmic mechanism and maintaining ion channel levels is antiarrhythmic.
Final Report of Reduced Anthracycline Dose Intensity with the Addition of Dose Dense Rituximab in Children, Adolescents and Young Adults with De Novo Good Risk Mature B-Cell Non Hodgkin Lymphoma (B-NHL)
Authors: Jessica C. Hochberg, Stanton Goldman, Matthew J. Barth, Qiuhu Shi, Liana Klejmont, Lauren Harrison, Jackie Basso, Yaya Chu, Humayun Islam, Perry Gerard, Javier Oesterheld, Kenneth Matthew Heym, Ivan I. Kirov, Richard A. Drachtman, Paul Harker-Murray, Sherrie L. Perkins, Rodney R. Miles, Bruce Shiramizu, Mitchell S Cairo
Journal: Blood (2020)
PIM Kinase Inhibition Decreases the Proangiogenic Properties of Multiple Myeloma Cells and Affects the Metabolic State of the Vascular Endothelium
Authors: Filip Garbicz, Anna Szumera-Ciećkiewicz, Joanna Barankiewicz, Dorota Komar, Michał Pawlak, Sonia Dębek, Aleksandra Matrejek, Thorsten Stuehmer, Aleksander Salomon-Perzynski, Agata Malenda, Krzysztof Brzózka, Tomasz Rzymski, Andrea Massimiliano Tomirotti, Ewa Lech-Marańda, Monika Prochorec-Sobieszek, Maciej Szydlowski, Przemyslaw Juszczynski
Journal: Blood (2020)
Phase II Study of Pembrolizumab Plus GVD As Second-Line Therapy for Relapsed or Refractory Classical Hodgkin Lymphoma
Authors: Alison J. Moskowitz, Gunjan Shah, Heiko Schöder, Nivetha Ganesan, Helen Hancock, Theresa Davey, Samia Sohail, Alayna Santarosa, Lauren Pomerantz, Christine Jarjies, Natasha Galasso, Rachel Neuman, Anita Kumar, Oscar B Lahoud, Connie Lee Batlevi, Paul A. Hamlin, David J. Straus, Ildefonso Rodriguez-Rivera, Colette Owens, Philip Caron, Andrew M. Intlekofer, Audrey Hamilton, Steven M. Horwitz, Lorenzo Falchi, Erel Joffe, Maria Lia Palomba, Ariela Noy, Matthew J Matasar, Georgios Pongas, Santosha Vardhana, Gottfried R. von Keudell, Joachim Yahalom, Andrew D Zelenetz, Craig H. Moskowitz
Journal: Blood (2020)
Nicholas Wilson-Holt
Authors: Will Westlake, Andrew Wilson
Journal: BMJ (2020)

Nicholas Wilson-Holt (“Nick”) decided from an early age that his future career lay in medicine. He was educated at Aldenham School in Hertfordshire, and as a young boy he supplemented his academic studies with chemistry experiments and biological dissections conducted in the garden shed.

He studied preclinical medicine at the Royal London Hospital, switching to the Middlesex for a BSc in immunology, during which time he published a book on the subject, and stayed there to complete his medical degree.

After qualifying he developed an interest in ophthalmology …
Comparison of a Combination of Vosaroxin (VOS) and Intermediate-Dose Cytarabine (IDAC) with Idac for the Consolidation Therapy of Younger Patients with Favorable- and Intermediate-Risk Acute Myeloid Leukemia (AML) in First Complete Remission (CR): Preliminary Results of a Randomized Phase 2 R4-VOS Study of the French ALFA-Filo AML Intergroup
Authors: Norbert Vey, Corentin Orvain, Christian Recher, Arnaud Pigneux, Marc Bernard, Anne Banos, Pierre Peterlin, Sylvain Chantepie, Xavier Thomas, Cecile Pautas, Claude Gardin, Emilie Lemasle, Emmanuel Raffoux, Romain Guieze, Chantal Himberlin, Clémence Loiseau, Amine Belhabri, Isabelle Luquet, Christine Terré, Martin Carre, Claude Preudhomme, Eric Delabesse, Karine Celli-Lebras, Ariane C Mineur, Jean-Francois Brasme, Jean Francois Hamel, Hervé Dombret, Mathilde Hunault
Journal: Blood (2020)
Emergence of<i>NPM1</i>Wild-Type Myeloid Neoplasms after Chemotherapy for Acute Leukemia with<i>NPM1</i>Mutation: Proposed Mechanisms of Clonal Evolution
Authors: Sandra Castaño-Díez, Monica Lopez-Guerra, Francesca Guijarro, Alex Bataller Torralba, Daniel Esteban, Carlos Castillo, Carlos Jiménez-Vicente, Paola Charry, Colomer Dolors, María Rozman, Jordi Esteve, Marina Diaz-Beyá
Journal: Blood (2020)
Thrombin Generation and D-Dimer Significantly Predict for Early Disease Progression and Mortality in Patients with Gastrointestinal Cancer
Authors: Marina Pesenti, Marina Marchetti, Cinzia Giaccherini, Cristina Verzeroli, Laura Russo, Giampietro Gasparini, Roberta Sarmiento, Luigi Celio, Giovanna Masci, Sara Gamba, Patricia Gomez-Rosas, Nadia FJ Schillaci, Silvia Bolognini, Carmen J Tartari, Erika Diani, Alfonso Vignoli, Carlo Tondini, Sandro Barni, Francesco Giuliani, Fausto Petrelli, Andrea D'Alessio, Filippo De Braud, Armando Santoro, Roberto Labianca, Anna Falanga
Journal: Blood (2020)
Winter pressure has hit GPs and hospitals in tier 3 areas six weeks earlier than normal
Authors: Ingrid Torjesen
Journal: BMJ (2020)

Winter pressure has hit GPs and hospitals in tier 3 areas six weeks earlier than normal Ingrid TorjesenGPs in areas of England under the tier 3 covid-19 restrictions have said their workloads reached levels in early October that they would not normally see before the end of November, and they are worried how the NHS will cope this winter.
Favorable Outcomes in Pediatric Patients in the Phase 3 Hgb-207 (Northstar-2) and Hgb-212 (Northstar-3) Studies of Betibeglogene Autotemcel Gene Therapy for the Treatment of Transfusion-Dependent β-Thalassemia
Authors: Alexis A. Thompson, Janet L. Kwiatkowski, John B. Porter, Suradej Hongeng, Evangelia Yannaki, Andreas E. Kulozik, Martin G. Sauer, Adrian J. Thrasher, Isabelle Thuret, Ashutosh Lal, Ruiting Guo, Weijian Liu, Richard A. Colvin, Mark C. Walters, Franco Locatelli
Journal: Blood (2020)
Three-dimensional facial-image analysis to predict heterogeneity of the human ageing rate and the impact of lifestyle
Authors: Xian Xia, Xingwei Chen, Gang Wu, Fang Li, Yiyang Wang, Yang Chen, Mingxu Chen, Xinyu Wang, Weiyang Chen, Bo Xian, Weizhong Chen, Yaqiang Cao, Chi Xu, Wenxuan Gong, Guoyu Chen, Donghong Cai, Wenxin Wei, Yizhen Yan, Kangping Liu, Nan Qiao, Xiaohui Zhao, Jin Jia, Wei Wang, Brian K. Kennedy, Kang Zhang, Carlo V. Cannistraci, Yong Zhou, Jing-Dong J. Han
Journal: Nature Metabolism (2020)
The PVT1 lncRNA is a novel epigenetic enhancer of MYC, and a promising risk-stratification biomarker in colorectal cancer
Authors: Kunitoshi Shigeyasu, Shusuke Toden, Tsuyoshi Ozawa, Takatoshi Matsuyama, Takeshi Nagasaka, Toshiaki Ishikawa, Debashis Sahoo, Pradipta Ghosh, Hiroyuki Uetake, Toshiyoshi Fujiwara, Ajay Goel
Journal: Molecular Cancer (2020)

Abstract Accumulating evidence suggests that dysregulation of transcriptional enhancers plays a significant role in cancer pathogenesis. Herein, we performed a genome-wide discovery of enhancer elements in colorectal cancer (CRC). We identified PVT1 locus as a previously unrecognized transcriptional regulator in CRC with a significantly high enhancer activity, which ultimately was responsible for regulating the expression of MYC oncogene. High expression of the PVT1 long-non-coding RNA (lncRNA) transcribed from the PVT1 locus was associated with poor survival among patients with stage II and III CRCs ( p &lt; 0.05). Aberrant methylation of the PVT1 locus inversely correlated with the reduced expression of the corresponding the PVT1 lncRNA, as well as MYC gene expression. Bioinformatic analyses of CRC-transcriptomes revealed that the PVT1 locus may also broadly impact the expression and function of other key genes within two key CRC-associated signaling pathways – the TGFβ/SMAD and Wnt/β-Catenin pathways. We conclude that the PVT1 is a novel oncogenic enhancer of MYC and its activity is controlled through epigenetic regulation mediated through aberrant methylation in CRC. Our findings also suggest that the PVT1 lncRNA expression is a promising prognostic biomarker and a potential therapeutic target in CRC.
Inhibition of Wnt/Beta-Catenin Pathway Impairs Natural Killer (NK) Cells Induced Apoptosis of Myeloid Leukemia Cells
Authors: Tarcila Santos Datoguia, Vanessa Araújo Varela, Elayne Bragança Jardim, Mariane Tami Amano, Natalia Mazini, Bruna Bizarro, Danilo Candido de Almeida, Nelson Hamerschlak, Fabio Pires de Souza Santos, Welbert Oliveira Pereira
Journal: Blood (2020)
Abstract 391: Mir-A-3p Targets Atf3 to Reduce Calcium Deposition in Vascular Smooth Muscle Cells
Authors: Nakwon CHOE, Duk-hwa Kwon, Juhee Ryu, SERA SHIN, Hosouk Joung, Youngkeun Ahn, Young-Kook Kim, Hyun Kook
Journal: Circulation Research (2020)

Vascular calcification, the ectopic deposition of calcium in blood vessels, develops in association with various metabolic diseases and atherosclerosis and is an independent predictor for morbidity and mortality of these diseases. Here we report that reduction of microRNA-A-3p (miR-A-3p) causes an increase in ATF3, activating transcription factor 3, a novel osteogenic transcription factor, in vascular smooth muscle cells. Both miRNA and mRNA microarrays were performed with rat vascular smooth muscle cells and reciprocally regulated pairs of miRNA and mRNA were selected after bioinformatic analysis. Inorganic phosphate significantly reduced the expression of miR-A-3p in A10 cells. The transcript level was also reduced in vitamin D3-administered mouse aortas. miR-A-3p mimic reduced calcium deposition, whereas miR-A-3p inhibitor increased it. The Atf3 mRNA level was upregulated in cellular vascular calcification model, and miR-A-3p reduced the Atf3 mRNA and protein levels. Transfection with Atf3 could recover the miR-A-3p-induced reduction of calcium deposition. Our results suggest that reduction of miR-A-3p may contribute to the development of vascular calcification by de-repression of ATF3
FBXO11-mediated proteolysis of BAHD1 relieves PRC2-dependent transcriptional repression in erythropoiesis
Authors: Peng Xu, Daniel C. Scott, Beisi Xu, Yu Yao, Ruopeng Feng, Li Cheng, Kalin Mayberry, Yong-Dong Wang, Wenjian Bi, Lance E. Palmer, Moeko T. King, Hong Wang, Yuxin Li, Yiping Fan, Arno F. Alpi, Chunliang Li, Junmin Peng, James Papizan, Shondra M. Pruett-Miller, Ria Spallek, Florian Bassermann, Yong Cheng, Brenda A. Schulman, Mitchell J. Weiss
Journal: Blood (2020)
Abstract MP153: TET2 Regulates Type I Interferon Signaling in the Hematopoietic Response to Myocardial Infarction
Authors: Claire Zhang, David M Calcagno, Avinash Toomu, Kenneth M Huang, Zhenxing Fu, Kevin R King
Journal: Circulation Research (2020)

Myocardial infarction (MI) elicits a rapid and vigorous reaction from the bone marrow hematopoietic compartment, inducing a massive efflux of myeloid first responders into the bloodstream. These cells traffic to the infarct, where they mediate cardiac remodeling and repair through inflammatory signaling and recruitment of additional immune cells to the injured myocardium. A hyperinflammatory myeloid compartment, as is produced by mutations in epigenetic regulator TET2 associated with clonal hematopoiesis, can thus drive adverse cardiac remodeling after MI and accelerate progression to heart failure. Whether loss of TET2 alters the transcriptional landscape of MI-induced myelopoiesis remains to be investigated in an unbiased fashion. Here, we performed single-cell RNA sequencing of &gt;16,000 bone marrow myeloid cells isolated from wild-type and Tet2 -/- mice after MI to characterize the emergency hematopoietic response in the presence and absence of TET2. Our data capture distinct transitional states of myeloid lineage commitment and maturation, originating from myeloid progenitors and progressing along divergent granulocytic and monocytic differentiation trajectories. Additionally, we delineate a subpopulation of interferon (IFN)-activated myeloid progenitors, monocytes, and neutrophils characterized by the concerted upregulation of various Type I IFN-stimulated genes, and find the fraction of IFN-activated cells, as well as the degree of activation, to be markedly higher in Tet2 -/- mice. We have previously described activation of this pathway after MI in mice, and demonstrated cardioprotective effects of its genetic or pharmacological inhibition. Our findings reveal heightened activation of the antiviral Type I interferon response among bone marrow myeloid cells of Tet2 -/- mice during MI-induced emergency hematopoiesis. This highlights IFN signaling as a potential candidate driver of cardiovascular pathologies (including atherosclerosis, myocardial infarction, and heart failure) associated with TET2-mediated clonal hematopoiesis. Further studies are necessary to investigate whether Tet2 -/- mice exhibit enhanced response to blockade of Type I IFN signaling after MI, and to determine whether myeloid cells of TET2 -mutant humans are similarly activated.
Gram negative organisms and viral infections in neonatal sepsis
Authors: Li En Tan
Journal: BMJ (2020)

This is a well written article on neonatal sepsis.1 It’s worth noting, however, that in developing countries group B streptococcus is a relatively uncommon microbial cause of neonatal sepsis, responsible for only 2-8% of cases. Klebsiella species, Escherichia coli , …
Abstract 11932: Eosinophil Improves Cardiac Functions After Myocardial Infarction
Authors: Jing Liu, Chongzhe Yang, Peter Libby, Junli Guo, Guo-Ping Shi
Journal: Circulation (2018)

Introduction: Clinical studies demonstrated that blood and cardiac eosinophil counts and eosinophil cationic protein (ECP) level predicted human coronary heart diseases (CHD). Yet, eosinophil funct...
Prognostic Value of PET/CT Metrics in Patients with Relapsed and Refractory (r/r) Diffuse Large B-Cell Lymphoma (DLBCL) Treated with Platinum-Based Chemotherapy: An Intent-to-Treat Analysis
Authors: Juan Pablo Alderuccio, Russ A Kuker, Priscila Barreto-Coelho, Bianca Marie Martinez, Feng Miao, Amer Beitinjaneh, Trent Peng Wang, Isildinha M Reis, Izidore S. Lossos, Craig H. Moskowitz
Journal: Blood (2020)
M2 Macrophages, but Not M1 Macrophages, Support Megakaryopoiesis Via up-Regulating PI3K-AKT Pathway
Authors: Hong-Yan Zhao, Qi Wen, Zhong-Shi Lyu, Shu-Qian Tang, Yuan-Yuan Zhang, Meng Lyu, Yu Wang, Lan-Ping Xu, Xiao-Hui Zhang, Yuan Kong, Xiao-Jun Huang
Journal: Blood (2020)
Efficacy and Safety Profile of Proteasome Inhibitor Based Drug Regimens for Treatment of Newly Diagnosed AL Amyloidosis: A Systematic Review
Authors: Saad Javed, Tariq Iqtidar Sadiq Syed, Hejab Fatima, Syed Hashim Ali Inam, Tayyab Rehan, Syed Maaz Abdullah, Mohammed Musa Najmuddin, Mobeen Zaka Haider, Karun Neupane, Muhammad Khawar Sana, Abdul Jabbar Dar, Ali Jaan, Muhammad Ali Mirza, Faiz Anwer
Journal: Blood (2020)
Abstract 402: Human CD271-positive Adipose Derived Stem Cells are the Angiogenic Subset Decreased by Donor Insulin Resistance
Authors: Oto Inoue, Soichiro Usui, Kosei Yamaguchi, Yusuke Takeda, Chiaki Goten, Ayano Nomura, Shinichiro Takashima, Kenji Sakata, Masa-aki Kawashiri, Masayuki Takamura
Journal: Circulation Research (2020)

Introduction: Type 2 diabetes mellitus (T2DM) is an important risk factor for cardiovascular diseases (CVDs). Recently, cell therapy using adipose-derived stem cells (ADSCs) has emerged as an attractive therapy for severe CVDs because of their angiogenic potentials. However, whether and how T2DM would impair human ADSC angiogenic capacity is still uncertain. We previously reported that CD31 - CD34 + CD271 + ADSCs (CD271 + ADSCs) were specifically decreased in adipose tissue of T2DM patients. Therefore, we aimed to investigate the angiogenic capacity of CD271 + ADSCs. Furthermore, we evaluate which patients’ parameters regard as T2DM would decrease the amount of CD271 + ADSCs. Methods and Results: Human CD45 - CD34 + CD31 - ADSCs were obtained from subcutaneous adipose tissue of healthy donors, separated into CD271 + and CD271 - subsets by FACS, and cultured. Both subsets of ADSCs were assessed gene expression profile by microarray. Microarray analysis and validation PCR elucidated that PI3K/Akt/mTOR pathway was significantly up-regulated in CD271 + ADSCs compared to in CD271 - ADSCs. ( p &lt; 0.05). Then, we compared in vivo angiogenic capacity in xenograft experiments of nude mice subjected to hindlimb ischemia. Angiogenesis was evaluated histologically using perfused lectin (capillary density) at day 14. Cell therapy using CD271 + ADSCs demonstrated about 3-fold more lectin + capillaries compared to CD271 - ADSCs or PBS injection ( p &lt; 0.005, n = 5 / group). Next, we established cultured ADSCs obtained from CD271 knock-out mice (KO-ADSCs) and compared their angiogenic capacity with those from WT mice. Consistently, KO-ADSCs demonstrated impaired in vivo angiogenic capacity ( p &lt; 0.005, n = 5 / group). Finally, we collected 23 samples of adipose tissue obtained from CVD patients and evaluated the frequency of CD271 + ADSCs in CD45 - CD34 + CD31 - ADSCs. Among studied parameters, HOMA-IR, an index of insulin resistance, was negatively correlated with the frequency of CD271+ ADSCs ( r = -0.64, p &lt; 0.005). Conclusions: Human CD271 + ADSCs demonstrated enhanced in vivo angiogenic capacity with higher mTOR expression. Donor insulin resistance might decrease this regenerative subset of ADSCs. These findings would be critical for development and improvement of ADSC therapy.
Proteomics in Pediatric Acute Myeloid and T-Cell Lymphoblastic Leukemia: Shared Individual Protein Expression Patterns Co-Cluster into Overall Distinct Combinations
Authors: Fieke W Hoff, Anneke D. van Dijk, Yihua Qiu, Eveline S. de Bont, Steven M. Kornblau, Terzah M Horton
Journal: Blood (2020)