tbuckley/cabot-search huggingface dataset:
Abstract 11233: A Trigger and Response System for Preventing Cardiac Arrest in the Intensive Care Unit
Authors: Ari Moskowitz, Katherine Berg, Michael N Cocchi, Anne V Grossestreuer, Lakshman Balaji, Maureen Chase, Jesse L Yang, Sharon O'Donoghue, Michael Donnino
Journal: Circulation (2021)

Background: Although patients in the ICU are closely monitored, some ICU cardiac arrest events may be preventable. In this study we sought to reduce the rate of ICU cardiac arrests. Methods: This was a prospective study of a novel clinical trigger and response tool deployed in the ICUs of a single, tertiary academic medical center. An interrupted time series approach was used to assess the impact of the tool on ICU cardiac arrests. Results: Forty-three patients experienced an ICU cardiac arrest in the pre-intervention epoch (6.79 arrests per 1000 discharges) and 59 patients experienced an ICU cardiac arrest in the intervention epoch (7.91 arrests per 1000 discharges). In the intervention epoch, the clinical trigger and response tool was activated 106 times over a 1-year period, most commonly due to unexpected new or worsening hypotension. There was no step change in arrest-rate (2.24 arrests/1000 patients, 95%CI -1.82, 6.28, p=0.28) or slope change (-0.02 slope of arrest rate, 95%CI -0.14, 0.11, p=0.79) comparing the pre-intervention and intervention time epochs (see Figure). Cardiac arrests occurring in the pre-intervention epoch were more likely to be deemed ‘potentially preventable’ than those in the intervention epoch (25.6% prior to the intervention vs. 12.3% during the intervention, OR 0.58, 95%CI 0.20, 0.88, p&lt;0.01). Conclusions: A trigger-and-response tool did not reduce the incidence of ICU cardiac arrest. Arrests occurring after introduction of the tool were less likely to be rated as ‘potentially preventable.’
PKM2 Is Essential for Bladder Cancer Growth and Maintenance
Authors: Yong Xia, Xing Wang, Yan Liu, Ellen Shapiro, Herbert Lepor, Moon-Shong Tang, Tung-Tien Sun, Xue-Ru Wu
Journal: Cancer Research (2021)

Abstract Pyruvate kinase M2 (PKM2) has been shown to promote tumorigenesis by facilitating the Warburg effect and enhancing the activities of oncoproteins. However, this paradigm has recently been challenged by studies in which the absence of PKM2 failed to inhibit and instead accelerated tumorigenesis in mouse models. These results seem inconsistent with the fact that most human tumors overexpress PKM2. To further elucidate the role of PKM2 in tumorigenesis, we investigated the effect of PKM2 knockout in oncogenic HRAS-driven urothelial carcinoma. While PKM2 ablation in mouse urothelial cells did not affect tumor initiation, it impaired the growth and maintenance of HRAS-driven tumors. Chemical inhibition of PKM2 recapitulated these effects. Both conditions substantially reduced complex formation of PKM2 with STAT3, their nuclear translocation, and HIF1α- and VEGF-related angiogenesis. The reduction in nuclear STAT3 in the absence of PKM2 also correlated with decreased autophagy and increased apoptosis. Time-controlled, inducible PKM2 overexpression in simple urothelial hyperplasia did not trigger tumorigenesis, while overexpression of PKM2, but not PKM1, in nodular urothelial hyperplasia with angiogenesis strongly accelerated tumorigenesis. Finally, in human patients, PKM2 was overexpressed in low-grade nonmuscle-invasive and high-grade muscle-invasive bladder cancer. Based on these data, PKM2 is not required for tumor initiation but is essential for tumor growth and maintenance by enhancing angiogenesis and metabolic addiction. The PKM2–STAT3–HIF1α/VEGF signaling axis may play a critical role in bladder cancer and may serve as an actionable therapeutic target. Significance: Genetic manipulation and pharmacologic inhibition of PKM2 in mouse urothelial lesions highlight its essential role in promoting angiogenesis and metabolic addiction, events indispensable for tumor growth and maintenance.
Errors in Figure 2, Figure 3, and the Supplement
Journal: JAMA Network Open (2021)

Gregory Y. H. Lip, MD; Allison V. Keshishian, MPH; Yan Zhang, PhD; Amiee Kang, MPH; Amol D. Dhamane, MS; Xuemei Luo, PhD; Christian Klem, PharmD; Mauricio Ferri, MD; Jenny Jiang, MS; Huseyin Yuce, PhD; Steven Deitelzweig, MD
Abemaciclib With Endocrine Therapy in the Treatment of High-Risk Early Breast Cancer: ASCO Optimal Adjuvant Chemotherapy and Targeted Therapy Guideline Rapid Recommendation Update
Authors: Sharon H. Giordano, Rachel A. Freedman, Mark R. Somerfield
Journal: Journal of Clinical Oncology (2021)

ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options.
Signatures of immune selection in intact and defective proviruses distinguish HIV-1 elite controllers
Authors: Xiaodong Lian, Ce Gao, Xiaoming Sun, Chenyang Jiang, Kevin B. Einkauf, Kyra W. Seiger, Joshua M. Chevalier, Yuko Yuki, Maureen Martin, Rebecca Hoh, Michael J. Peluso, Mary Carrington, Ezequiel Ruiz-Mateos, Steven G. Deeks, Eric S. Rosenberg, Bruce D. Walker, Mathias Lichterfeld, Xu G. Yu
Journal: Science Translational Medicine (2021)

Immune selection footprints in proviral sequences distinguish individuals with natural, drug-free control of HIV-1.
Evaluation of Test to Stay Strategy on Secondary and Tertiary Transmission of SARS-CoV-2 in K–12 Schools — Lake County, Illinois, August 9–October 29, 2021
Authors: Natsumi Nemoto, Soneet Dhillon, Steven Fink, Emily J. Holman, Amyanne Keswani Cope, Thu-Ha Dinh, Juliana Meadows, Dina Taryal, Funmilayo Akindileni, Megan Franck, Emily Gelber, Lea Bacci, Sana Ahmed, Ebony S. Thomas, John C. Neatherlin
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

The COVID-19 pandemic has resulted in school closures and reduction of in-person learning (1). In August 2021, the Lake County Health Department (LCHD) in Illinois introduced a Test to Stay (TTS) strategy, whereby unvaccinated students, teachers, and staff members with certain school-related COVID-19 exposures could remain in school and participate in school-related extracurricular activities. Eligibility to participate in TTS required the following conditions to be met: 1) the exposure occurred while both the person with COVID-19 (index patient) and the close contact were masked; 2) the close contact remained asymptomatic, practiced consistent mask wearing, and maintained physical distancing; and 3) the close contact underwent testing for SARS-CoV-2 (the virus that causes COVID-19) on days 1, 3, 5, and 7 after exposure to the index patient. LCHD permitted kindergarten through grade 12 (K-12) schools in Lake County to implement TTS; 90 schools, representing 31 school districts in Lake County, implemented TTS during August 9-October 29, 2021. During the implementation period, 258 COVID-19 cases were reported. Among 1,035 students and staff members enrolled in TTS, the secondary attack risk (number of close contacts who received a positive SARS-CoV-2 test result within 14 days after exposure to an index patient, divided by total number of close contacts) was 1.5% (16 of 1,035). Among the 16 secondary cases identified, all were in students, and none appeared to transmit SARS-CoV-2 to other school-based contacts. However, nine tertiary cases were identified among household contacts of the 16 secondary cases, and four of the nine were fully vaccinated. Assuming a maximum of 8 missed school days for every 10-day quarantine period, up to 8,152 in-person learning days were saved among TTS participants. Implementation of TTS with other concurrent prevention strategies, including masking and physical distancing, limited further spread of SARS-CoV-2 within K-12 schools and allowed students to safely sustain in-person learning. Although vaccination remains the leading public health recommendation to protect against COVID-19 for those aged ≥5 years, schools might consider TTS as an option for allowing close contacts who are not fully vaccinated to remain in the classroom as an alternative to home quarantine.
Boosting Photothermal Theranostics via TICT and Molecular Motions for Photohyperthermia Therapy of Muscle‐Invasive Bladder Cancer (Adv. Healthcare Mater. 24/2021)
Authors: Sheng Zeng, Heqi Gao, Chuang Li, Shaoqiang Xing, Zhaoliang Xu, Qian Liu, Guangxue Feng, Dan Ding
Journal: Advanced Healthcare Materials (2021)

Photothermal Therapies In article number 2101063 by Qian Liu, Guangxue Feng, Dan Ding, and co-workers, a small photothermal molecule with active intramolecular motions and a dark state twisted intramolecular charge transfer feature is designed to boost the photothermal conversion ability. Such a design strategy enables the effective low-temperature photo-hyperthermia treatment of muscle-invasive bladder cancers at low drug and laser dosages with minimal side effects.
Computational Assessment of the Expression-Modulating Potential for Non-Coding Variants
Authors: Fang-Yuan Shi, Yu Wang, Dong Huang, Yu Liang, Nan Liang, Xiao-Wei Chen, Ge Gao
Journal: Genomics Proteomics & Bioinformatics (2021)

Large-scale genome-wide association studies (GWAS) and expression quantitative trait locus (eQTL) studies have identified multiple non-coding variants associated with genetic diseases by affecting gene expression. However, pinpointing causal variants effectively and efficiently remains a serious challenge. Here, we developed CARMEN, a novel algorithm to identify functional non-coding expression-modulating variants. Multiple evaluations demonstrated CARMEN's superior performance over state-of-the-art tools. Applying CARMEN to GWAS and eQTL datasets further pinpointed several causal variants other than the reported lead single-nucleotide polymorphisms (SNPs). CARMEN scales well with the massive datasets, and is available online as a web server at http://carmen.gao-lab.org.
Correction to: Relationship between SARS-CoV-2 infection and the incidence of ventilator-associated lower respiratory tract infections: a European multicenter cohort study
Authors: Anahita Rouzé, Ignacio Martin-Loeches, Pedro Povoa, Demosthenes Makris, Antonio Artigas, Mathilde Bouchereau, Fabien Lambiotte, Matthieu Metzelard, Pierre Cuchet, Claire Boulle Geronimi, Marie Labruyere, Fabienne Tamion, Martine Nyunga, Charles-Edouard Luyt, Julien Labreuche, Olivier Pouly, Justine Bardin, Anastasia Saade, Pierre Asfar, Jean-Luc Baudel, Alexandra Beurton, Denis Garot, Iliana Ioannidou, Louis Kreitmann, Jean-François Llitjos, Eleni Magira, Bruno Mégarbane, David Meguerditchian, Edgar Moglia, Armand Mekontso-Dessap, Jean Reignier, Matthieu Turpin, Alexandre Pierre, Gaetan Plantefeve, Christophe Vinsonneau, Pierre-Edouard Floch, Nicolas Weiss, Adrian Ceccato, Antoni Torres, Alain Duhamel, Saad Nseir, Raphaël Favory, Sébastien Preau, Mercé Jourdain, Julien Poissy, Chaouki Bouras, Piehr Saint Leger, Hanane Fodil, François Aptel, Thierry Van Der Linden, Arnaud W. Thille, Elie Azoulay, Frédéric Pène, Keyvan Razazi, François Bagate, Damien Contou, Guillaume Voiriot, Didier Thevenin, Bertrand Guidet, Loïc Le Guennec, Achille Kouatchet, Stephan Ehrmann, Guillaume Brunin, Elise Morawiec, Alexandre Boyer, Laurent Argaud, Sebastian Voicu, Ania Nieszkowska, Benjamin Kowalski, Gemma Goma, Emilio Diaz, Luis Morales, Vassiliki Tsolaki, George Gtavriilidis, Spyros D. Mentzelopoulos, David Nora, Sean Boyd, Luis Coelho, Julien Maizel, Damien Du Cheyron, Mehdi Imouloudene, Jean-Pierre Quenot, Arnaud Guilbert, Catia Cilloniz
Journal: Intensive Care Medicine (2021)

61.8) in Influenza pneumonia group, and 353/524 (67.4) in no viral infection.The authors apologize.
Polar Gini Curve: A Technique to Discover Gene Expression Spatial Patterns from Single-Cell RNA-Seq Data
Authors: Thanh Minh Nguyen, Jacob John Jeevan, Nuo Xu, Jake Y. Chen
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract In this work, we describe the development of Polar Gini Curve, a method for characterizing cluster markers by analyzing single-cell RNA sequencing (scRNA-seq) data. Polar Gini Curve combines the gene expression and the 2D coordinates (“spatial”) information to detect patterns of uniformity in any clustered cells from scRNA-seq data. We demonstrate that Polar Gini Curve can help users characterize the shape and density distribution of cells in a particular cluster, which can be generated during routine scRNA-seq data analysis. To quantify the extent to which a gene is uniformly distributed in a cell cluster space, we combine two polar Gini curves (PGCs)—one drawn upon the cell-points expressing the gene (the “foreground curve”) and the other drawn upon all cell-points in the cluster (the “background curve”). We show that genes with highly dissimilar foreground and background curves tend not to uniformly distributed in the cell cluster—thus having spatially divergent gene expression patterns within the cluster. Genes with similar foreground and background curves tend to uniformly distributed in the cell cluster—thus having uniform gene expression patterns within the cluster. Such quantitative attributes of PGCs can be applied to sensitively discover biomarkers across clusters from scRNA-seq data. We demonstrate the performance of the Polar Gini Curve framework in several simulation case studies. Using this framework to analyze a real-world neonatal mouse heart cell dataset, the detected biomarkers may characterize novel subtypes of cardiac muscle cells. The source code and data for Polar Gini Curve could be found at http://discovery.informatics.uab.edu/PGC/ or https://figshare.com/projects/Polar_Gini_Curve/76749.
137P Phase I dose-finding study of a novel anti-CTLA-4 antibody ADG116 as monotherapy in patients with advanced solid tumors
Authors: G. Richardson, A. Tolcher, F. Parnis, J. Park, A. Hamid, K. She, L. Liu, S. Zheng, G. Liu, X. Li, B. Li, X. Wang, M. Chen, S. Fischkoff, H. Gong, P. Luo
Journal: Annals of Oncology (2021)
Association of Birth Asphyxia With Regional White Matter Abnormalities Among Patients With Schizophrenia and Bipolar Disorders
Authors: Laura A. Wortinger, Claudia Barth, Stener Nerland, Kjetil Nordbø Jørgensen, Alexey A. Shadrin, Attila Szabo, Unn Kristin Haukvik, Lars T. Westlye, Ole A. Andreassen, Marianne Thoresen, Ingrid Agartz
Journal: JAMA Network Open (2021)

<h3>Importance</h3> White matter (WM) abnormalities are commonly reported in psychiatric disorders. Whether peripartum insufficiencies in brain oxygenation, known as birth asphyxia, are associated with WM of patients with severe mental disorders is unclear. <h3>Objective</h3> To examine the association between birth asphyxia and WM in adult patients with schizophrenia and bipolar disorders (BDs) compared with healthy adults. <h3>Design, Setting, and Participants</h3> In this case-control study, all individuals participating in the ongoing Thematically Organized Psychosis project were linked to the Medical Birth Registry of Norway (MBRN), where a subset of 271 patients (case group) and 529 healthy individuals (control group) had undergone diffusion-weighted imaging (DWI). Statistical analyses were performed from June 16, 2020, to March 9, 2021. <h3>Exposures</h3> Birth asphyxia was defined based on measures from standardized reporting at birth in the MBRN. <h3>Main Outcomes and Measures</h3> Associations between birth asphyxia and WM regions of interest diffusion metrics, ie, fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), were compared between groups using analysis of covariance, adjusted for age, age squared, and sex. <h3>Results</h3> Of the 850 adults included in the study, 271 were in the case group (140 [52%] female individuals; mean [SD] age, 28.64 [7.43] years) and 579 were in the control group (245 [42%] female individuals; mean [SD] age, 33.54 [8.31] years). Birth asphyxia measures were identified in 15% to 16% of participants, independent of group. The posterior limb of the internal capsule (PLIC) showed a significant diagnostic group × birth asphyxia interaction (<i>F</i><sub>(1, 843)</sub> = 11.46;<i>P</i> = .001), reflecting a stronger association between birth asphyxia and FA in the case group than the control group. RD, but not AD, also displayed a significant diagnostic group × birth asphyxia interaction (<i>F</i><sub>(1, 843)</sub> = 9.28;<i>P</i> = .002) in the PLIC, with higher values in patients with birth asphyxia and similar effect sizes as observed for FA. <h3>Conclusions and Relevance</h3> In this case-control study, abnormalities in the PLIC of adult patients with birth asphyxia may suggest a greater susceptibility to hypoxia in patients with severe mental illness, which could lead to myelin damage or impeded brain development. Echoing recent early-stage schizophrenia studies, abnormalities of the PLIC are relevant to psychiatric disorders, as the PLIC contains important WM brain pathways associated with language, cognitive function, and sensory function, which are impaired in schizophrenia and BDs.
Abstract 9123: Plasma Biomarkers Associated With PICU Mortality in Children With Cardiac Arrest and Acute Respiratory Distress Syndrome
Authors: Monique M Gardner, Matthew Kirschen, Jill Thompson, Adam Himebauch, Nadir Yehya, Alexis A Topjian
Journal: Circulation (2021)

Introduction: The post-cardiac arrest state is comprised of an ischemic and reperfusion syndrome, with inflammation similar to sepsis and acute respiratory distress syndrome (ARDS). However, it is unknown whether cardiac arrest has a distinct inflammatory profile relative to these other critical illness syndromes. Using plasma biomarkers of systemic inflammation measured in children with ARDS, we aimed to evaluate identify unique biomarkers in a sub-cohort with cardiac arrest, and the association of these biomarkers with mortality. Methods: This was a retrospective single-center cohort study of 17 biomarkers prospectively collected from pediatric subjects with ARDS between 2014-2019. Biomarkers were drawn within 24 hours after both ARDS diagnosis and cardiac arrest. Clinical characteristics and biomarkers were compared between those with ARDS and those with ARDS and cardiac arrest (ARDS+CA) using nonparametric tests. In ARDS+CA subjects, associations of biomarkers with mortality were tested with univariate and bivariate logistic regression. Results: Biomarkers were measured in 333 subjects: 301 with ARDS (median age 5.3 years, 55.5% male) and 32 ARDS+CA (median age 8 years, 53.1% male). Majority of arrests (68.7%) were out-of-hospital with median 11 minutes of CPR. ARDS+CA subjects were more likely to be immunosuppressed and present after aspiration or drowning than the ARDS cohort. ARDS severity, PRISM III score, vasoactive-ionotropic score and extra-pulmonary organ failure were worse in the ARDS+CA group (p&lt;0.05). Eight biomarkers were elevated in ARDS+CA compared to the ARDS cohort: sRAGE, nucleosomes, SP-D, CCL22, IL-6, HSP70, IL-8, and MIP-1b (p&lt;0.05). In the ARDS+CA cohort, 3 biomarkers were associated with mortality when controlling for markers of disease and cardiac arrest severity: sRAGE (unadjusted odds ratio 3.48 [IQR 1.35, 8.99], p=0.010), IL-6 (OR 1.75 [1.13, 2.71], p=0.012) and granzyme B (OR 3.74 [1.46, 9.57], p=0.006). Conclusion: sRAGE, IL-6 and granzyme B were independently associated with mortality after pediatric cardiac arrest in ARDS. This exploratory work suggests that cardiac arrest may induce a distinct inflammatory state that differs from other critical illness syndromes and further investigation is needed.
8P Pre-treatment blood gene expression changes associated with durable clinical benefit in metastatic non-small cell lung cancer with high PD-L1 expression receiving first-line pembrolizumab
Authors: M. Elshiaty, F. Lusky, F. Bozorgmehr, L. Gaissmaier, H. Schindler, I. Poschke, A. Angeles, F. Janke, M. Kriegsmann, J.B. Kuon, R. Shah, M.A. Schneider, L. Daniello, M. Meister, T. Muley, F. Eichhorn, H. Sültmann, A. Stenzinger, M. Thomas, P. Christopoulos
Journal: Annals of Oncology (2021)
Sustainability of Tobacco Treatment Programs in the Cancer Center Cessation Initiative
Authors: _ _
Journal: Journal of the National Comprehensive Cancer Network (2021)

The NCI’s Cancer Center Cessation Initiative (C3I) has a specific objective of helping cancer centers develop and implement sustainable programs to routinely address tobacco cessation with patients. Sustaining tobacco treatment programs requires the maintenance of (1) core program components, (2) ongoing implementation strategies, and (3) program outcomes evaluation. NCI funding of C3I included a commitment of resources toward sustainability. This article presents case studies to illustrate key strategies in developing sustainability capacity across 4 C3I-funded sites. Case studies are organized according to the domains of sustainability capacity defined in the Clinical Sustainability Assessment Tool (CSAT). We also describe the C3I Sustainability Working Group agenda to make scientific and practical contributions in 3 areas: (1) demonstrating the value of tobacco use treatment in cancer care, (2) identifying implementation strategies to support sustainability, and (3) providing evidence to inform policy changes that support the prioritization and financing of tobacco use treatment. By advancing this agenda, the Sustainability Working Group can play an active role in advancing and disseminating knowledge for tobacco treatment program sustainability to assist cancer care organizations in addressing tobacco use by patients with cancer within and beyond C3I.
Dysregulation of interaction between LOX<sup>high</sup> fibroblast and smooth muscle cells contributes to the pathogenesis of aortic dissection
Authors: Yinan Chen, Tao Zhang, Fang Yao, Xiang Gao, Dandan Li, Shufang Fu, Lin Mao, Fei Liu, Xuelin Zhang, Yongle Xu, Jianqing Deng, Weihao Li, Guangpu Fan, Cangsong Xiao, Yu Chen, Li Wang, Wei Guo, Bingying Zhou
Journal: Theranostics (2021)

Rationale: While cell-cell interaction plays a critical role in physiology and disease, a comprehensive understanding of its dynamics in vascular homeostasis and diseases is yet absent. Methods: Here, by use of single-cell RNA-sequencing and multi-color staining, we delineate the cellular composition and spatial characterization of human aorta with or without aortic dissection (AD). Results: Scrutinization of cell subtype alterations revealed significantly changed fibroblast (FB)-smooth muscle cell (SMC) interactions in AD. Of these cellular interactions, LOXhigh fibroblast (fibroblast subtype 2, FB2) in diseased state exerted the most pronounced effects on pathological deterioration of SMCs in AD. In addition, pharmacologically targeting the BMP (bone morphogenetic protein) signaling pathway effectively suppressed FB2 state transition and reduced AD incidence in mice. Finally, COL5A1 (collagen type V alpha 1 chain), one of the secreted proteins released from FB2, was significantly higher in the plasma of AD patients than in control patients, suggesting its potential use as a biomarker for AD diagnosis. Conclusions: Our work not only identified a pivotal role of a specific FB subtype in AD progression, but also shed light on cell interaction dynamics in vascular diseases.
The AKI care bundle: all bundle components are created equal—are they?
Authors: Thilo C. von Groote, Marlies Ostermann, Lui G. Forni, Melanie Meersch-Dini, Alexander Zarbock, Christoph Schmidt, Andreas Hoffmeier, Hugo Aken, Carola Wempe, Mira Küllmar, Gianluca Lucchese, Kamran Baig, Armando Cennamo, Ronak Rajani, Stuart McCorkell, Christian Arndt, Hinnerk Wulf, Marc Irqsusi, Fabrizio Monaco, Ambra Licia Di Prima, Mercedes García Alvarez, Stefano Italiano, Jordi Miralles Bagan, Gudrun Kunst, Shrijit Nair, Camilla L’Acqua, Eric Hoste, Wim Vandenberghe, Patrick M Honore, John A Kellum, Philippe Grieshaber, Christina Massoth, Raphael Weis
Journal: Intensive Care Medicine (2021)