tbuckley/cabot-search huggingface dataset:
The Price of Freedom from Tricuspid Regurgitation
Authors: Joanna Chikwe, Mario Gaudino
Journal: New England Journal of Medicine (2021)

Progressive tricuspid regurgitation is common, particularly in patients undergoing mitral-valve surgery. Severe tricuspid regurgitation decreases survival and quality of life due to right ventricular dysfunction, congestive hepatopathy, and renal failure. The tricuspid valve can easily be repaired during mitral-valve surgery, and consensus guidelines recommend concomitant repair of mild or moderate tricuspid regurgitation with annular dilatation of 4.0 cm or more.1 However, these recommendations are based on mostly observational data, and controversy surrounds the most effective strategy, which contributes to wide variation in practice: concomitant tricuspid repair rates at cardiac surgery programs in the United States range from under 5% to . . .
A Multicenter, Real World Analysis of Primary Central Nervous System Lymphoma in Those with and without Human Immunodeficiency Virus
Authors: Christopher Dittus, Natalie S Grover, Tarsheen Sethi, Jonathon B. Cohen, Alfredo Voloschin, Janhvi Rabadey, Xianming Tan, Anne W. Beaven, Steven I. Park
Journal: Blood (2021)
Cortical VIP neurons locally control the gain but globally control the coherence of gamma band rhythms
Authors: Julia Veit, Gregory Handy, Daniel P. Mossing, Brent Doiron, Hillel Adesnik
Journal: Neuron (2022)

Gamma band synchronization can facilitate local and long-range neural communication. In the primary visual cortex, visual stimulus properties within a specific location determine local synchronization strength, while the match of stimulus properties between distant locations controls long-range synchronization. The neural basis for the differential control of local and global gamma band synchronization is unknown. Combining electrophysiology, optogenetics, and computational modeling, we found that VIP disinhibitory interneurons in mouse cortex linearly scale gamma power locally without changing its stimulus tuning. Conversely, they suppress long-range synchronization when two regions process non-matched stimuli, tuning gamma coherence globally. Modeling shows that like-to-like connectivity across space and specific VIP→SST inhibition capture these opposing effects. VIP neurons thus differentially impact local and global properties of gamma rhythms depending on visual stimulus statistics. They may thereby construct gamma-band filters for spatially extended but continuous image features, such as contours, facilitating the downstream generation of coherent visual percepts.
Global recovery requires degrowth, not ever increasing GDP
Authors: Mark Dick
Journal: BMJ (2021)

I was surprised by this paragraph in Stern and Ward’s essay1: “Greater understanding of the urgency required to cut emissions has been accompanied by mounting evidence that it does not mean sacrificing economic development and growth. Annual emissions by the United Kingdom, for example, fell by 43.8% between 1990 and 2019, whereas its gross domestic product [GDP] rose by 78% …
DDRE-18. THERAPEUTIC EFFECTS OF TASQUINIMOD ON GLIOBLASTOMA
Authors: Junfeng Liu, Raziye Piranlioglu, Naoyuki Shono, Alexander Lee Ling, Himanshu Soni, Hiroshi Nakashima, E Antonio Chiocca
Journal: Neuro-Oncology (2021)

Abstract Glioblastoma is the most aggressive and most common primary malignant brain tumor in adults. This disease is still incurable despite multimodal therapies. We evaluated Tasquinimod, an oral HDAC4 inhibitor, in use with oncolytic HSV therapy. Tasquinimod is known to bind to HDAC4 and S100A9 to modulate myeloid population and angiogenesis in the tumors. This drug is being clinically evaluated in prostate and other solid tumors and multiple myeloma. However, the therapeutic effect of Tasquinimod in glioblastoma is not known. We found that Tasquinimod could change the immune-suppressive phenotype of MDSCs and polarize M2 macrophages towards M1 phenotype in ex vivo assay using mouse bone marrow cells treated with glioma conditioned media. We also tested Tasquinimod and oncolytic HSV in murine CT2A in C57/B6 mice and primary human GBM xenograft model in athymic mice. While the therapeutic effect of Tasquinimod or oHSV alone was not significant or marginal, the combo group show significantly longer survival. The study of underlying mechanisms is still ongoing. In conclusion, Tasquinimod combined with oncolytic HSV could have a better therapeutic effect on glioblastoma.
A Resident-Led Quality Improvement Initiative to Optimize Care for Children and Young Adults with Sickle Cell Disease Vaso-Occlusive Pain with Intranasal Fentanyl in the Emergency Department
Authors: Wilson Andres Vasconez Samaniego, Cristina Matheus, Claudia Aguilar-Velez, Prasanth Narahari, Priyanka Nair, Shanique Sterling, Roxana Middleton, Hector Chavez
Journal: Blood (2021)
Impact of Gender on Molecular AML Subclasses - a Harmony Alliance Study
Authors: Tommaso Matteuzzi, Daniele Dall'Olio, Eric Sträng, Alessandra Merlotti, Javier Martinez Elicegui, Axel Benner, Maral Saadati, Julia Krzykalla, Caroline A. Heckman, Ana Heredia Casanoves, Jurjen Versluis, María Abáigar, Alberto Hernandez-Sanchez, Laura Jamilis, Peter JM Valk, Klaus H. Metzeler, Rosa Ayala, Joaquin Martinez Lopez, Herve Dombret, Pau Montesinos, Jorge Sierra, Claude Preudomme, Frederick Damm, Ken I Mills, Raúl Azibeiro Melchor, Jiří Mayer, Christian Thiede, Maria Teresa Voso, Sergio Amadori, Guillermo Sanz, Frederico Calado, Konstanze Döhner, Verena I Gaidzik, Michael Heuser, Torsten Haferlach, Marta Sobas, Amin T. Turki, Dirk Reinhardt, Rubén Villoria Medina, Michel van Speybroeck, Renate Schulze-Rath, Jesús M Hernández Rivas, Brian J.P Huntly, Hartmut Döhner, Gert J. Ossenkoppele, Castellani Gastone, Lars Bullinger
Journal: Blood (2021)
Pre-Clinical Characterization of a Novel Fusion Protein (AT-03), with Pan-Amyloid Binding and Removal
Authors: Christophe Sirac, Arnaud Jaccard, Roussine Codo, Sebastien Bender, Gemma Martinez-Rivas, Frank Bridoux, Gregory D Bell, Spencer Guthrie, Suganya Selvarajah, Stephen J. Kennel, Angela Williams, James S. Foster, Jonathan S. Wall
Journal: Blood (2021)
Publisher Correction: Bortezomib-based induction, high-dose melphalan and lenalidomide maintenance in myeloma up to 70 years of age
Authors: Elias K. Mai, Kaya Miah, Uta Bertsch, Jan Dürig, Christof Scheid, Katja C. Weisel, Christina Kunz, Markus Munder, Hans-Walter Lindemann, Maximilian Merz, Dirk Hose, Anna Jauch, Anja Seckinger, Steffen Luntz, Sandra Sauer, Stephan Fuhrmann, Peter Brossart, Ahmet Elmaagacli, Martin Goerner, Helga Bernhard, Martin Hoffmann, Marc S. Raab, Igor W. Blau, Mathias Hänel, Axel Benner, Hans J. Salwender, Hartmut Goldschmidt
Journal: Leukemia (2021)
Effects of BCL11A Shmir-Induced Post-Transcriptional Silencing on Hemoglobin Polymer Inhibition in Single Red Blood Cells at Physiologic Oxygen Tension
Authors: Daniel C. De Souza, Erica B. Esrick, Nicolas Hebert, Giuseppe Di Caprio, Marioara Ciuculescu, Emily Morris, Myriam Armant, Bronner P. Gonçalves, Ethan Schonbrun, Christian Brendel, David K. Wood, Pablo Bartolucci, David A. Williams, John M. Higgins
Journal: Blood (2021)
Second Treatment Free Remission after Combination Therapy with Ruxolitinib Plus Tyrosine Kinase Inhibitors in Chronic Phase Chronic Myeloid Leukemia (CML)
Authors: Kendra Sweet, Ehab L. Atallah, Jerry P. Radich, Mei-Jie Zhang, Eva Sahakian, Melanie Mediavilla-Varela, Alexis Vistocky, Michael C. Heinrich, James E. Thompson, Michael J. Mauro, Kathryn E Flynn, Arielle Baim, Javier Pinilla Ibarz
Journal: Blood (2021)
Integrating Touchscreen-Based Geriatric Assessment and Frailty Screening for Adults with Acute Myelogenous Leukemia to Drive Personalized Treatment Decisions
Authors: Omer Hassan Jamy, Stacey Ingram, D'Ambra Dent, William Dudley, Matthew Dudley, Julie M Scott, Debra M Wujcik
Journal: Blood (2021)
Safety and Efficacy of Lower Intensity Induction Therapy with Intravenous Prexigebersen (BP1001) in Patients with High-Risk and Relapsed/Refractory Acute Myeloid Leukemia (AML)
Authors: Maro Ohanian, Tara L. Lin, Ellen Ritchie, Michael Craig, Apurv Agrawal, Kathleen G. Halka, Naveen Pemmaraju, Gautam Borthakur, Miranda Lim, Sherry A. Pierce, Ana Tari Ashizawa, Hagop Kantarjian, Jorge E. Cortes, Gail J. Roboz
Journal: Blood (2021)
Busulfan (Bu) and Cyclophosphamide (Cy) Based Conditioning Regimen Still Holds the Promise of Being a Safe and Efficacious Regimen for Allogeneic Transplantation in Patients with Transfusion Dependent Thalassemia (TDT) Even in High Risk
Authors: Pallavi Mehta, Aakanksha A Singh, Neha Yadav, Narendra Agrawal, Rayaz Ahmed, Vishvdeep Khushoo, Dinesh Bhurani
Journal: Blood (2021)
Fibroblast membrane-camouflaged nanoparticles for inflammation treatment in the early stage
Authors: Lizhong Sun, Libang He, Wei Wu, Li Luo, Mingyue Han, Yifang Liu, Shijie Shi, Kaijing Zhong, Jiaojiao Yang, Jiyao Li
Journal: International Journal of Oral Science (2021)

Abstract Unrestrained inflammation is harmful to tissue repair and regeneration. Immune cell membrane-camouflaged nanoparticles have been proven to show promise as inflammation targets and multitargeted inflammation controls in the treatment of severe inflammation. Prevention and early intervention of inflammation can reduce the risk of irreversible tissue damage and loss of function, but no cell membrane-camouflaged nanotechnology has been reported to achieve stage-specific treatment in these conditions. In this study, we investigated the prophylactic and therapeutic efficacy of fibroblast membrane-camouflaged nanoparticles for topical treatment of early inflammation (early pulpitis as the model) with the help of in-depth bioinformatics and molecular biology investigations in vitro and in vivo. Nanoparticles have been proven to act as sentinels to detect and competitively neutralize invasive Escherichia coli lipopolysaccharide ( E. coli LPS) with resident fibroblasts to effectively inhibit the activation of intricate signaling pathways. Moreover, nanoparticles can alleviate the secretion of multiple inflammatory cytokines to achieve multitargeted anti-inflammatory effects, attenuating inflammatory conditions in the early stage. Our work verified the feasibility of fibroblast membrane-camouflaged nanoparticles for inflammation treatment in the early stage, which widens the potential cell types for inflammation regulation.
Outcomes of Large B-Cell Lymphoma Patients By Post CAR-T Salvage Regimen at a Single Institution
Authors: Audrey M. Sigmund, Nathan Denlinger, Amneet Bajwa, Patrick Elder, David A. Bond, Jonathan E Brammer, Ayman Saad, Sam Penza, Marcos J.G. de Lima, Samantha Jaglowski, Adam S Kittai
Journal: Blood (2021)
Clinical Outcome of t-AML with Respect to Genetic Abnormalities and Treatment Intensity - Single Center Analysis over the Past Two Decades
Authors: Monika Adamska, Ewelina Kowal-Wisniewska, Marta Baranska, Anna Przybylowicz-Chalecka, Anna Lojko-Dankowska, Monika Joks, Zuzanna Kandula, Malgorzata Jarmuz-Szymczak, Lidia Gil
Journal: Blood (2021)
Abstract 9330: Machine Learning Can Enable the Automation of Clinical Endpoint Adjudication
Authors: Halsey Lea, Sreenath Nampally, Emmette R Hutchison, Christoffer Stedt, Andreas. Järemo, Anders Persson, James Weatherall, Faisal M Khan, Tomas Andersson, Shameer Khader, Glynn Dennis, Deepak L Bhatt, Philippe G Steg
Journal: Circulation (2021)

Introduction: Clinical Endpoint Adjudication is a critical component of Cardiovascular (CV) clinical outcome trials and relies on manual decision making to adjudicate clinical events, including CV death. This process is resource intensive and subject to human-driven variance. As part of a broader initiative to automate data collection and analysis of clinical endpoints, we evaluated whether machine learning (ML) algorithms could replicate the outcomes of expert adjudication for CV death. Algorithms were trained on data from THEMIS (NCT01991795), a large, randomized trial comparing ticagrelor to placebo in patients with Type 2 Diabetes Mellitus. Methods: We deployed a deep learning, biomedical named entity (NE) extraction model called BERN to extract relevant NE’s from clinical text of THEMIS events. NE’s were transformed into a sparse, numerical matrix and concatenated with event-level structured features to form a data set of 962 events. Expert adjudicator consensus for CV death was used as ground truth. We trained models using grid search and cross validation, experimenting with XGBoost, Random Forest, Logistic Regression, and Naïve Bayes. Performance was assessed on a 25% (240 of 962) validation subset of the data excluded from training. Metrics used to evaluate performance were Precision, Recall, Accuracy and Area Under the Receiver Operating Characteristic Curve (AUC). Results: Best performance was observed on models trained using Naïve Bayes (&gt;97% ROC AUC on validation data), see Table. Top ranked features for classifying CV death included site investigator decision, sex, and NE’s associated with diagnoses or symptoms, such as “edema” and “chest pain.” Conclusion: With high consistency between automated and expert adjudication, our models demonstrate that machine learning may augment or even replace clinician adjudication in CV outcome trials. Subsequent research will focus on pursuing ML approaches to adjudicate other outcome events.
Effects of anti-aging interventions on intestinal microbiota
Authors: Yanjiao Du, Yue Gao, Bo Zeng, Xiaolan Fan, Deying Yang, Mingyao Yang
Journal: Gut Microbes (2021)

Identifying ways to deal with the challenges presented by aging is an urgent task, as we are facing an aging society. External factors such as diet, exercise and drug therapy have proven to be major elements in controlling healthy aging and prolonging life expectancy. More recently, the intestinal microbiota has also become a key factor in the anti-aging process. As the intestinal microbiota changes with aging, an imbalance in intestinal microorganisms can lead to many age-related degenerative diseases and unhealthy aging. This paper reviews recent research progress on the relationship between intestinal microorganisms and anti-aging effects, focusing on the changes and beneficial effects of intestinal microorganisms under dietary intervention, exercise and drug intervention. In addition, bacteriotherapy has been used to prevent frailty and unhealthy aging. Most of these anti-aging approaches improve the aging process and age-related diseases by regulating the homeostasis of intestinal flora and promoting a healthy intestinal environment. Intervention practices based on intestinal microorganisms show great potential in the field of anti-aging medicine.
Outcomes Following Acute Pulmonary Embolism in an Irish Population of over 1 Million Individuals: Opportunities for Quality Improvement and More Effective Resource Utilisation
Authors: Alexandra Tierney, Fionnuala Ni Ainle, Declan Lyons, Osasere Edebiri, Khalid Saeed, Sarah Kelliher, Kiran Saif, Rehman Faryal, Su Wai Maung, Howard Johnson, Michael Fitzpatrick, Roseann O' Doherty, Jillian Coll, Sara Mohamed, Mohamed Ali, Noirin Bannon, Annemarie O'Neill, Tomas Breslin, Karen Murphy, Barry Kevane
Journal: Blood (2021)
Outcomes of Patients with Budd-Chiari Syndrome and Factors Predicting the Need for TIPS &amp; Liver Transplantation - a Single-Center Long-Term Experience
Authors: Anusha Gopalam, Valerie K Shostrom, Vijaya R. Bhatt, Alex Nester, Laxmi Narayana Buddharaju, Marco Olivera, Krishna Gundabolu
Journal: Blood (2021)
CTNI-27. SINGLE AGENT ACTIVITY OF ONC201 IN NON-MIDLINE H3 K27M-MUTANT DIFFUSE GLIOMAS
Authors: Yazmin Odia, Ashley Sumrall, Timothy Cloughesy, Phioanh Nghiemphu, Matthew Hall, Doured Daghistani, Minesh Mehta, Andrew Lassman, Isabel Arrillaga-Romany, Sharon Gardner, Rohinton Tarapore, Guangrong Lu, Joshua Allen, Patrick Wen
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND H3 K27M-mutant diffuse midline glioma is an invariably lethal form of brain cancer that disproportionately affects children and young adults and has no effective treatment following front-line radiation. The initial disease definition in the 2016 WHO Classification of Tumors of the Central Nervous System regarded the H3 K27M mutation as pathognomonic, though the definition was updated in 2018 restricting the diagnosis to histologically diffuse gliomas that involve midline CNS structures (cIMPACT-NOW update 2). ONC201 is an investigational anti- cancer small molecule, DRD2 antagonist and ClpP agonist that has induced durable tumor regressions by RANO-HGG criteria in a registration cohort of recurrent diffuse midline glioma, H3 K27M-mutant patients treated with single agent ONC201. METHODS We present 7 patients with H3 K27M-mutant diffuse gliomas were enrolled in ONC201 clinical studies, excluded from the registration cohort due to involvement of non-midline CNS structures, all within the cerebral hemispheres (3 frontal, 1 temporal, 1 frontotemporal, 1 parietal, and 1 corona radiata). RESULTS Two of the 7 patients underwent objective responses by RANO-HGG criteria as assessed by investigator, which was associated with clinical benefit that included increased mobility and level of alertness. CONCLUSIONS These results demonstrate that H3 K27M-mutant diffuse gliomas occur outside of midline CNS structures, and suggest that ONC201 has single agent activity in H3 K27M-mutant gliomas irrespective of CNS location.
Deaths in children and young people in England after SARS-CoV-2 infection during the first pandemic year
Authors: Clare Smith, David Odd, Rachel Harwood, Joseph Ward, Mike Linney, Matthew Clark, Dougal Hargreaves, Shamez N. Ladhani, Elizabeth Draper, Peter J. Davis, Simon E. Kenny, Elizabeth Whittaker, Karen Luyt, Russell Viner, Lorna K. Fraser
Journal: Nature Medicine (2021)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is rarely fatal in children and young people (CYP, <18 years old), but quantifying the risk of death is challenging because CYP are often infected with SARS-CoV-2 exhibiting no or minimal symptoms. To distinguish between CYP who died as a result of SARS-CoV-2 infection and those who died of another cause but were coincidentally infected with the virus, we undertook a clinical review of all CYP deaths with a positive SARS-CoV-2 test from March 2020 to February 2021. The predominant SARS-CoV-2 variants were wild-type and Alpha. Here we show that, of 12,023,568 CYP living in England, 3,105 died, including 61 who were positive for SARS-CoV-2. Of these deaths, 25 were due to SARS-CoV-2 infection (mortality rate, two per million), including 22 due to coronavirus disease 2019—the clinical disease associated with SARS-CoV-2 infection—and 3 were due to pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. In total, 99.995% of CYP with a positive SARS-CoV-2 test survived. CYP older than 10 years, Asian and Black ethnic backgrounds and comorbidities were over-represented in SARS-CoV-2-related deaths compared with other CYP deaths. These results are important for guiding decisions on shielding and vaccinating children. New variants might have different mortality risks and should be evaluated in a similar way. A clinical review of all pediatric deaths in England from March 2020 to February 2021 attributes 25 deaths to SARS-CoV-2 infection and identifies risk factors to guide interventions.
Tandem Substitutions in Somatic Hypermutation
Authors: Marvyn T. Koning, Julieta Haydee Sepulveda Yanez, Diego Alvarez-Saravia, Bas Pilzecker, Pauline Van Schouwenburg, Mirjam van den Burg, Marcelo A. Navarrete, Heinz Jacobs, Hendrik Veelken
Journal: Blood (2021)
Covid-19: Austria enters lockdown as cases surge across Europe
Authors: Tony Sheldon
Journal: BMJ (2021)

<h3>Background</h3> Improvement interventions would be easier to treat if they were stable and uninfluenced by their environment, but in practice, contextual factors may create difficulties in implementing and sustaining changes. Managers of healthcare organisations play an important role in quality and safety improvement. We need more research in the nursing home and homecare settings to support managers in their quality and safety improvement work. The aim of this study was to explore managers’ response to a leadership intervention on quality and safety improvement. <h3>Methods</h3> This study reports findings from the SAFE-LEAD intervention undertaken from April 2018 to March 2019. The research design was a multiple case study of two nursing homes and two homecare services in four municipalities in Norway. We used a combination of qualitative methods including interviews, workshops, observations, site visits and document analysis in our data collection that took place over a 1-year period. <h3>Results</h3> Management continuity was key for the implementation process of the quality and safety leadership intervention. In the units where stable management teams were in place, the intervention was more rooted in the units, and changes in quality and safety practice occurred. The intervention served as an arena for managers to work with quality and safety improvement. We found that the workshops and use of the leadership guide contributed to a common understanding and commitment to quality and safety improvement among the managers. <h3>Conclusions</h3> This is a longitudinal study of managers’ response to a leadership intervention targeted to improve quality and safety work in nursing home and homecare settings. Our research demonstrates how the mechanisms of stable management and established structures are crucial for quality and safety improvement activities. Management continuity is key for participating in interventions and for using the leadership guide in quality and safety work.
Overdiagnosis and overtreatment during the covid-19 pandemic
Authors: Mahesh Devnani
Journal: BMJ (2021)

Although the overall use of healthcare services fell by about a third during the covid-19 pandemic, with greater reductions among people with less severe diseases, the issue of overdiagnosis and overtreatment adding to increased healthcare associated carbon emissions persisted.123

Repeated and unnecessary testing of patients with covid-19 using RT-PCR, blood tests, and radiological investigations was pervasive. Rampant …
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Authors: Marc G. Ghany, Wendy C. King, Mauricio Lisker‐Melman, Anna S. F. Lok, Norah Terrault, Harry L. A. Janssen, Mandana Khalili, Raymond T. Chung, William M. Lee, Daryl T. Y. Lau, Gavin A. Cloherty, Richard K. Sterling
Journal: Hepatology (2021)

could be differentiated between these two chronological phases and provide more clinical information.In summary, HBcrAg and HBV RNA were shown to add limited value in defining different clinical stages given that they are highly correlated with HBV-DNA levels.However, existing data from longitudinal cohorts have suggested that HBcrAg levels serve as complementary predictors in predicting long-term outcomes of CHB patients.More studies are needed to explore how to combine these novel biomarkers with HBV-DNA levels to guide physicians to implement precision medicine.
The Effect of Platelets on Thrombin Generation in Cord Blood and Peripheral Neonatal Blood in the Premature Infant; The Event Study
Authors: Claire Anne Murphy, Elaine Neary, Barry Kevane, Daniel O'Reilly, John O'Loughlin, Afif EL-Khuffash, Patricia Maguire, Fionnuala Ni Ainle, Naomi McCallion
Journal: Blood (2021)
From the Cochrane Library: Probiotics for treating eczema
Authors: Mindy D. Szeto, Shahzeb Hassan, Austin Hamp, Jarett Anderson, Torunn E. Sivesind, Jaclyn B. Anderson, Melissa R. Laughter, Areti Makrygeorgou, Robert J. Boyle, Robert P. Dellavalle
Journal: Journal of the American Academy of Dermatology (2021)
Whole Genome Sequencing Identifies Non-<i>KIT</i> Mutations and Cytogenetic Aberrations in Systemic Mastocytosis but Has Limited Sensitivity for Detection of <i>KIT</i> D816V
Authors: Gregor Hoermann, Manja Meggendorfer, Constance Baer, Heiko Müller, Wencke Walter, Stephan Hutter, Christian Pohlkamp, Niroshan Nadarajah, Wolfgang Kern, Torsten Haferlach, Claudia Haferlach
Journal: Blood (2021)