tbuckley/cabot-search huggingface dataset:
Phenotypic Mapping of Pathologic Cross-Talk between Glioblastoma and Innate Immune Cells by Synthetic Genetic Tracing
Authors: Matthias Jürgen Schmitt, Carlos Company, Yuliia Dramaretska, Iros Barozzi, Andreas Göhrig, Sonia Kertalli, Melanie Großmann, Heike Naumann, Maria Pilar Sanchez-Bailon, Danielle Hulsman, Rainer Glass, Massimo Squatrito, Michela Serresi, Gaetano Gargiulo
Journal: Cancer Discovery (2020)

Glioblastoma is a lethal brain tumor that exhibits heterogeneity and resistance to therapy. Our understanding of tumor homeostasis is limited by a lack of genetic tools to selectively identify tumor states and fate transitions. Here, we use glioblastoma subtype signatures to construct synthetic genetic tracing cassettes and investigate tumor heterogeneity at cellular and molecular levels, in vitro and in vivo. Through synthetic locus control regions, we demonstrate that proneural glioblastoma is a hardwired identity, whereas mesenchymal glioblastoma is an adaptive and metastable cell state driven by proinflammatory and differentiation cues and DNA damage, but not hypoxia. Importantly, we discovered that innate immune cells divert glioblastoma cells to a proneural-to-mesenchymal transition that confers therapeutic resistance. Our synthetic genetic tracing methodology is simple, scalable, and widely applicable to study homeostasis in development and diseases. In glioblastoma, the method causally links distinct (micro)environmental, genetic, and pharmacologic perturbations and mesenchymal commitment. SIGNIFICANCE: Glioblastoma is heterogeneous and incurable. Here, we designed synthetic reporters to reflect the transcriptional output of tumor cell states and signaling pathways' activity. This method is generally applicable to study homeostasis in normal tissues and diseases. In glioblastoma, synthetic genetic tracing causally connects cellular and molecular heterogeneity to therapeutic responses.This article is highlighted in the In This Issue feature, p. 521.
Methodological standards for qualitative and mixed methods patient centered outcomes research
Authors: Bridget Gaglio, Michelle Henton, Amanda Barbeau, Emily Evans, David Hickam, Robin Newhouse, Susan Zickmund
Journal: BMJ (2020)

Many publications provide guidance on how to use qualitative and mixed methods in health researchThe methodological standards reported here and adopted by Patient-Centered Outcomes Research Institute (PCORI) synthesize and refine various recommendations to improve the design, conduct, and reporting of patient centered, comparative, clinical effectiveness research PCORI has developed and adopted standards that provide guidance on key areas where research applications and research reports
Clipping a gastric lesion before resection: not a contraindication for endoscopic submucosal dissection
Authors: Marta Rodríguez-Carrasco, Madalena Souto Moura, Ana Luísa Cunha, Mário Dinis-Ribeiro
Journal: Endoscopy (2020)

A 53-year-old woman underwent an upper gastrointestinal endoscopy because of dyspepsia. A 15-mm, type 0-IIa lesion was identified in the lesser curvature of the distal corpus. After a biopsy was taken, a moderate hemorrhage occurred and two metal clips were applied ([Fig. 1 a]). The histopathological result showed high grade dysplasia so the patient was referred to our department to undergo endoscopic resection.
Human Brain Surrogates Research: The Onrushing Ethical Dilemma
Authors: Henry T. Greely
Journal: The American Journal of Bioethics (2020)

Human brain research is moving into a dilemma. The best way to understand how the human brain works is to study living human brains in living human beings, but ethical and legal standards make it difficult to do powerful research with actual human beings. So neuroscientists have developed four types of surrogates for living human brains in human bodies: genetically edited non-human animals, human/non-human brain chimeras, human neural organoids, and living ex vivo human brain tissues. These new and rapidly improving models offer the hope of understanding human brain function better. If we make our models "too good," they may themselves deserve some of the kinds of ethical and legal respect that have limited brain research in human beings. This article is an initial effort to outline that dilemma.
Oral decontamination with colistin plus neomycin in solid organ transplant recipients colonized by multidrug-resistant Enterobacterales: a multicentre, randomized, controlled, open-label, parallel-group clinical trial
Authors: Maria Carmen Fariñas, Claudia González-Rico, Marta Fernández-Martínez, Jesús Fortún, Rosa Escudero-Sanchez, Asunción Moreno, Marta Bodro, Patricia Muñoz, Maricela Valerio, Miguel Montejo, Javier Nieto, Juan Carlos Ruiz-San Millan, Fernando Casafont-Morencos, Luis Martinez-Martínez, Concepción Fariñas-Álvarez, Carlos Armiñanzas, Francisco Arnaiz de las Revillas, Jorge Calvo, Antonio Cuadrado, Virginia Flor, Emilio Fábrega, Mónica Gozalo, Aitziber Illaro, Emilio Rodrigo, Ana Fernández, Javier Graus, Pilar Martin Dávil, Adolfo Martínez, Patricia Ruiz Garbajosa, Ana M. Sánchez-Díaz, Laura Linares, Frederic Cofan, Francesc Marco, Miquel Navasa, Maitane Aranzamendi, María José Blanco, Caroline Agnelli Bento, Marina Machado, María Olmedo, Cristina Rincón Sanz, María Luisa Rodríguez Ferrero, Luis Alberto Sánchez Cámara, Teresa Vicente-Rangel, Irene Gracia-Ahufinger, Fernando Rodríguez, Julián Torre-Cisneros, Aurora Páez Vega, José María Aguadov, Fernando Chaves, Elena Resino
Journal: Clinical Microbiology and Infection (2020)
Advances in biomaterials and regenerative medicine for primary ovarian insufficiency therapy
Authors: Sichen Zhang, Dashuai Zhu, Xuan Mei, Zhenhua Li, Junlang Li, Mengjie Xie, Halle Jiang Williams Lutz, Shaowei Wang, Ke Cheng
Journal: Bioactive Materials (2020)

Primary ovarian insufficiency (POI) is an ovarian dysfunction that affects more than 1 % of women and is characterized by hormone imbalances that afflict women before the age of 40. The typical perimenopausal symptoms result from abnormal levels of sex hormones, especially estrogen. The most prevalent treatment is hormone replacement therapy (HRT), which can relieve symptoms and improve quality of life. However, HRT cannot restore ovarian functions, including secretion, ovulation, and fertility. Recently, as part of a developing field of regenerative medicine, stem cell therapy has been proposed for the treatment of POI. Thus, we recapitulate the literature focusing on the use of stem cells and biomaterials for POI treatment, and sum up the underlying mechanisms of action. A thorough understanding of the work already done can aid in the development of guidelines for future translational applications and clinical trials that aim to cure POI by using regenerative medicine and biomedical engineering strategies.
Abciximab During Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: Intracoronary, Intravenous, or Not at All?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: John A. Bittl
Journal: Journal of the American College of Cardiology (2013)
Lipid metabolism and cancer
Authors: Xueli Bian, Rui Liu, Ying Meng, Dongming Xing, Daqian Xu, Zhimin Lu
Journal: The Journal of Experimental Medicine (2020)

Dysregulation in lipid metabolism is among the most prominent metabolic alterations in cancer. Cancer cells harness lipid metabolism to obtain energy, components for biological membranes, and signaling molecules needed for proliferation, survival, invasion, metastasis, and response to the tumor microenvironment impact and cancer therapy. Here, we summarize and discuss current knowledge about the advances made in understanding the regulation of lipid metabolism in cancer cells and introduce different approaches that have been clinically used to disrupt lipid metabolism in cancer therapy.
Effects of empagliflozin on estimated extracellular volume, estimated plasma volume, and measured glomerular filtration rate in patients with heart failure (Empire HF Renal): a prespecified substudy of a double-blind, randomised, placebo-controlled trial
Authors: Jesper Jensen, Massar Omar, Caroline Kistorp, Christian Tuxen, Ida Gustafsson, Lars Køber, Finn Gustafsson, Jens Faber, Mariam Elmegaard Malik, Emil Loldrup Fosbøl, Niels Eske Bruun, Julie Lyng Forman, Lars Thorbjørn Jensen, Jacob Eifer Møller, Morten Schou
Journal: The Lancet Diabetes & Endocrinology (2020)
Abstract 12381: Ca2+/Calmodulin-dependent Protein Kinase II (CaMKII) Initiates Expression of Inflammatory Genes and Inflammatory Cell Infiltration in Response to Pressure Overload Through Signaling in Cardiomyocytes
Authors: Takeshi Suetomi, Andrew Willeford, Shigeki Miyamoto, Joan Heller Brown
Journal: Circulation (2017)

Introduction and Hypothesis: Inflammation is associated with pressure overload induced cardiac remodeling and heart failure. CaMKII is also known mediate cardiac remodeling and heart failure develo...
Novel rare genetic variants in idiopathic pulmonary fibrosis
Authors: Arnold S. Kristof
Journal: European Respiratory Journal (2020)

<b>The study by Nathan and co-workers on rare surfactant protein A genetic variants in patients with familial IPF illustrates the power of rare disease research consortia, and highlights the challenges in developing individualised approaches for IPF patients</b>https://bit.ly/35uC5lw
Targeting <scp>BCL</scp>‐2 with venetoclax and dexamethasone in patients with relapsed/refractory t(11;14) multiple myeloma
Authors: Jonathan L. Kaufman, Cristina Gasparetto, Fredrik H. Schjesvold, Philippe Moreau, Cyrille Touzeau, Thierry Facon, Lawrence H. Boise, Yanwen Jiang, Xiaoqing Yang, Fengjiao Dunbar, Deeksha Vishwamitra, Stefanie Unger, Tammy Macartney, John Pesko, Yao Yu, Ahmed Hamed Salem, Jeremy A. Ross, Wan‐Jen Hong, Paulo C. Maciag, James M. Pauff, Shaji Kumar
Journal: American Journal of Hematology (2020)

Abstract Venetoclax (Ven) is a selective small‐molecule inhibitor of BCL‐2 that exhibits antitumoral activity against MM cells with t(11;14) translocation. We evaluated the safety and efficacy of Ven and dexamethasone (VenDex) combination in patients with t(11;14) positive relapsed/refractory (R/R) multiple myeloma (MM). This open‐label, multicenter study had two distinct phases (phase one [P1], phase two [P2]). Patients in both phases received VenDex (oral Ven 800 mg/day + oral Dex 40 mg [20 mg for patients ≥75 years] on days 1, 8, and 15, per 21–day cycle). The primary objective of the P1 VenDex cohort was to assess safety and pharmacokinetics. Phase two further evaluated efficacy with objective response rate (ORR) and very good partial response or better. Correlative studies explored baseline BCL2 (BCL‐2) and BCL2L1 (BCL‐X L ) gene expression, cytogenetics, and recurrent somatic mutations in MM. Twenty and 31 patients in P1 and P2 with t(11;14) positive translocation received VenDex. P1/P2 patients had received a median of 3/5 lines of prior therapy, and 20%/87% were refractory to daratumumab. Predominant grade 3/4 hematological adverse events (AEs) with ≥10% occurrence included lymphopenia (20%/19%), neutropenia (15%/7%), thrombocytopenia (10%/10%), and anemia (5%/16%). At a median follow‐up of 12.3/9.2 months, ORR was 60%/48%. The duration of response estimate at 12 months was 50%/61%, and the median time to progression was 12.4/10.8 months. In biomarker evaluable patients, response to VenDex was independent of concurrent del(17p) or gain(1q) and mutations in key oncogenic signaling pathways, including MAPK and NF‐kB. VenDex demonstrated efficacy and manageable safety in heavily‐pre‐treated patients with t(11;14) R/R MM.
A mechanistic rationale for the investigation of sodium–glucose co‐transporter 2 inhibitors in heart failure with preserved ejection fraction. Letter regarding the article ‘Baseline characteristics of patients with heart failure with preserved ejection fraction in the <scp>EMPEROR‐Preserved</scp> trial’
Authors: Steffen Pabel, Nazha Hamdani, Samuel Sossalla
Journal: European Journal of Heart Failure (2020)

Recently in this Journal Anker et al. published the trial design and baseline characteristics of the EMPEROR-Preserved trial.1, 2 Compared to previous heart failure with preserved ejection fraction (HFpEF) trials investigating established drugs for the treatment of heart failure with reduced ejection fraction (HFrEF), the mechanistic evidence of empagliflozin as a rationale for treating patients with HFpEF seems to be more promising. Accordingly, we believe that the first experimental findings in human HFrEF and HFpEF myocardium have to be taken into consideration in this elegant clinical trial as they pave the way for a deeper mechanistic understanding of the potential effects of empagliflozin in the EMPEROR-Preserved trial. In this Journal,3 we firstly demonstrated that empagliflozin has direct diabetes-independent cardiac effects in human explanted hearts and biopsies. In human myocardium from patients with HFrEF, empagliflozin reduced diastolic dysfunction without altering systolic force. Importantly, this could be expanded to human myocardium from patients with HFpEF by demonstrating that empagliflozin lowers the typical pathological diastolic stiffness due to improved phosphorylation of titin and other small myofilamentary proteins.3 In a further study, we showed that these direct cardiac effects are mediated by a reduction of myocardial inflammation and oxidative stress in human HFpEF myocardium leading to a reduced myofilament stiffness.4 The heterogeneity among HFpEF patients is high and previous trials failed to provide prognostic relevant treatment options for HFpEF patients. However, we noted that in the EMPEROR-Preserved trial the number of patients with comorbidities associated with inflammation and oxidative stress (i.e. diabetes mellitus, chronic kidney disease) is higher compared to previous HFpEF trials.2 Our translational human in-vitro data indicate that empagliflozin might be useful to specifically target these mechanisms in the myocardium of HFpEF patients and may therefore improve diastolic function. Utilizing human hearts with the disease of question is necessary to overcome the limitations of animal models. These translational aspects should be considered for the rationale of the EMPEROR-Preserved trial. We wish the trialists every success and hope that this study will reveal a new therapeutic option for a mechanistic treatment of HFpEF patients. Open access funding enabled and organized by ProjektDEAL.
Travel-related infections presenting in Europe: A 20-year analysis of EuroTravNet surveillance data
Authors: Martin P. Grobusch, Leisa Weld, Abraham Goorhuis, Davidson H. Hamer, Mirjam Schunk, Sabine Jordan, Frank P. Mockenhaupt, François Chappuis, Hilmir Asgeirsson, Eric Caumes, Mogens Jensenius, Perry J.J. van Genderen, Francesco Castelli, Rogelio López-Velez, Vanessa Field, Emmanuel Bottieau, Israel Molina, Christophe Rapp, Marta Díaz Ménendez, Effrossyni Gkrania-Klotsas, Carsten S. Larsen, Denis Malvy, David Lalloo, Federico Gobbi, Simin A. Florescu, Philippe Gautret, Patricia Schlagenhauf
Journal: The Lancet Regional Health - Europe (2021)

Disease epidemiology of (re-)emerging infectious diseases is changing rapidly, rendering surveillance of travel-associated illness important.We evaluated travel-related illness encountered at EuroTravNet clinics, the European surveillance sub-network of GeoSentinel, between March 1, 1998 and March 31, 2018.103,739 ill travellers were evaluated, including 11,239 (10.8%) migrants, 89,620 (86.4%) patients seen post-travel, and 2,880 (2.8%) during and after travel. Despite increasing numbers of patient encounters over 20 years, the regions of exposure by year of clinic visits have remained stable. In 5-year increments, greater proportions of patients were migrants or visiting friends and relatives (VFR); business travel-associated illness remained stable; tourism-related illness decreased. Falciparum malaria was amongst the most-frequently diagnosed illnesses with 5,254 cases (5.1% of all patients) and the most-frequent cause of death (risk ratio versus all other illnesses 2.5:1). Animal exposures requiring rabies post-exposure prophylaxis increased from 0.7% (1998-2002) to 3.6% (2013-2018). The proportion of patients with seasonal influenza increased from zero in 1998-2002 to 0.9% in 2013-2018. There were 44 cases of viral haemorrhagic fever, most during the past five years. Arboviral infection numbers increased significantly as did the range of presenting arboviral diseases, dengue and chikungunya diagnoses increased by 2.6% and 1%, respectively.Travel medicine must adapt to serve the changing profile of travellers, with an increase in migrants and persons visiting relatives and friends and the strong emergence of vector-borne diseases, with potential for further local transmission in Europe.This project was supported by a cooperative agreement (U50CK00189) between the Centers for Disease Control and Prevention to the International Society of Travel Medicine (ISTM) and funding from the ISTM and the Public Health Agency of Canada.
AKI Perspectives and Practices in Latin America (LA) During COVID-19: Analysis from GlomCon Latin America Working Group
Authors: Javier Soto-Vargas, Desiree Garcia Anton, Diana Aguirre, Denisse Arellano-Mendez, Franco H. Cabeza Rivera, Julio A. Gutierrez-Prieto, Blanca Martinez-Chagolla, Sonia Rodriguez Ramirez, Carmen Avila-Casado
Journal: Journal of the American Society of Nephrology (2020)

Background: The epidemiology, clinical presentation, management and outcomes of COVID-19 comes from early reports from China and Europe with AKI prevalence ranging widely from 0 5% to 29%  However, knowledge about this pandemic is still emerging  With the epicenter now in the western hemisphere, we aim to determine the behavior and possible differences in presentation of AKI in COVID-19 patients in Latin America  To our knowledge, this is the first of such study  Methods: Descriptive analysis extracted from an online survey carried out among nephrologists, renal pathologists and other health workers treating kidney diseases between May 20-27, 2020 from sixteen Spanish speaking Latin American countries divided into 6 categories  We present the results for the AKI category  Results: 430 responses were obtained of which 360 (84%) were considered for analysis  86% of the participants were nephrologists  35% of the respondents reported the prevalence of AKI to be <5%, while 32% estimated it at 6-10%  The majority of AKI in these patients was stage 3 according to 31% of the respondents  Roughly half of the nephrologists witnessed new onset proteinuria which was almost exclusively (96%) subnephrotic  The majority (64%) reported no hematuria  Half of the participants (50 2%) reported that renal replacement therapy (RRT) was never or rarely required  Intermittent hemodialysis was the main RRT used reported by 88% of those surveyed followed by continuous renal replacement therapy (33%), peritoneal dialysis (24%) and prolonged intermittent RRT (19%)  The most common complications during RRT were hypotension (60 3%) and circuit clotting (36 6%)  Over one third of the participants (35%) estimated the mortality of patients with AKI and COVID to be <20%  Conclusions: Our survey highlights potential differences in the presentation, management and outcomes of AKI in patients with COVID-19 in LA;among those, a lower prevalence, higher need for RRT and lower mortality  More studies are warranted to better understand AKI in hispanic COVID-19 patients as well as its distinct characteristics compared to the rest of the world
Abstract 13943: Safety of High Intensity Statin in Asian Patients With Acute Myocardial Infarction
Authors: Po-Sheng Chen, Yi-Heng Li, Hui-Wen Lin, Sheng-Hsiang Lin
Journal: Circulation (2019)

Background: Although 2018 ACC/AHA lipid guideline recommended high-intensity statin (HIS) for secondary prevention in younger patients (<75 years) with atherosclerotic cardiovascular disease (ASCVD...
Covid-19: UK regulator approves lateral flow test for home use despite accuracy concerns
Authors: Elisabeth Mahase
Journal: BMJ (2020)

The UK’s regulator has approved the Innova lateral flow covid-19 test for people to self-administer despite warnings from some testing experts that it is inaccurate and may give people a false sense of security.

The Medicines and Healthcare Products Regulatory Agency (MHRA) announced that it had issued authorisation to the Department of Health and Social Care on 23 December to allow the use of the antigen lateral flow test for home testing to “detect infection in asymptomatic individuals.”

“A negative test result means that the test has not detected the presence of the covid-19 virus, at the time the test was taken,” it said. “Anyone receiving a negative …
Risks of and risk factors for COVID-19 disease in people with diabetes: a cohort study of the total population of Scotland
Authors: Stuart J McGurnaghan, Amanda Weir, Jen Bishop, Sharon Kennedy, Luke A K Blackbourn, David A McAllister, Sharon Hutchinson, Thomas M Caparrotta, Joseph Mellor, Anita Jeyam, Joseph E O'Reilly, Sarah H Wild, Sara Hatam, Andreas Höhn, Marco Colombo, Chris Robertson, Nazir Lone, Janet Murray, Elaine Butterly, John Petrie, Brian Kennon, Rory McCrimmon, Robert Lindsay, Ewan Pearson, Naveed Sattar, John McKnight, Sam Philip, Andrew Collier, Jim McMenamin, Alison Smith-Palmer, David Goldberg, Paul M McKeigue, Helen M Colhoun, Alice Whettlock, Allan McLeod, Andrew Gasiorowski, Andrew Merrick, Andy McAuley, April Went, Calum Purdie, Colin Fischbacher, Colin Ramsey, David Bailey, David Henderson, Eisin McDonald, Genna Drennan, Graeme Gowans, Graeme Reid, Heather Murdoch, Jade Carruthers, Josie Murray, Karen Heatlie, Lorraine Donaldson, Martin Paton, Martin Reid, Melissa Llano, Michelle Murphy-Hall, Ross Hall, Ross Cameron, Susan Brownlie, Adam Gaffney, Aynsley Milne, Christopher Sullivan, Edward McArdle, Elaine Glass, Johanna Young, William Malcolm, Jodie McCoubrey
Journal: The Lancet Diabetes & Endocrinology (2020)
Bilateral Renal Artery Thrombosis in a COVID-19 Patient with Anuric AKI
Authors: Nitzy N. Munoz Casablanca, Osama El Shamy, Steven G. Coca, Jaime Uribarri, Shuchita Sharma
Journal: Journal of the American Society of Nephrology (2020)

Munoz Casablanca, Nitzy N.; El Shamy, Osama; Coca, Steven G.; Uribarri, Jaime; Sharma, Shuchita Author Information
Hospital Readmission Is Common Among COVID-19 Survivors
Authors: Bridget M. Kuehn
Journal: JAMA (2020)

Hospital Readmission Is Common Among COVID-19 SurvivorsNearly 1 in 10 patients who were discharged after receiving inpatient care for coronavirus disease 2019 (COVID-19) earlier this year were readmitted within 2 months, according to a recent study.To help fill the knowledge gap about posthospitalization COVID-19 outcomes, CDC investigators analyzed hospital records and administrative data for 126 137 patients with COVID-19 who were admitted between March and July.They found that 15% of the patients died during their initial hospitalization.Among survivors, 9% were readmitted to the same hospital within 2 months of discharge and 1.6% were readmitted more than once.Fifteen percent of patients discharged to nursing home care were readmitted to a hospital, as were 12% who were discharged to home health care and 7% who didn't need professional care at home.Fewer than 0.1% of readmitted patients died.Diseases of the circulatory, respiratory, or digestive systems were readmitted patients' most common discharge diagnoses.Having preexisting pulmonary disease, heart failure, diabetes, or chronic kidney disease increased patients' odds of readmission.Patients discharged to homebased or self-care were less likely to be readmitted, but two-thirds of those who were had 1 or more of those chronic condi-