tbuckley/cabot-search huggingface dataset:
Chronos: a cell population dynamics model of CRISPR experiments that improves inference of gene fitness effects
Authors: Joshua M. Dempster, Isabella Boyle, Francisca Vazquez, David E. Root, Jesse S. Boehm, William C. Hahn, Aviad Tsherniak, James M. McFarland
Journal: Genome biology (2021)

CRISPR loss of function screens are powerful tools to interrogate biology but exhibit a number of biases and artifacts that can confound the results. Here, we introduce Chronos, an algorithm for inferring gene knockout fitness effects based on an explicit model of cell proliferation dynamics after CRISPR gene knockout. We test Chronos on two pan-cancer CRISPR datasets and one longitudinal CRISPR screen. Chronos generally outperforms competitors in separation of controls and strength of biomarker associations, particularly when longitudinal data is available. Additionally, Chronos exhibits the lowest copy number and screen quality bias of evaluated methods. Chronos is available at https://github.com/broadinstitute/chronos .
Personal Interventions to Reduce Exposure to Outdoor Air Pollution
Authors: Robert J. Laumbach, Kevin R. Cromar
Journal: Annual Review of Public Health (2021)

Unhealthy levels of air pollution are breathed by billions of people worldwide, and air pollution is the leading environmental cause of death and disability globally. Efforts to reduce air pollution at its many sources have had limited success, and in many areas of the world, poor air quality continues to worsen. Personal interventions to reduce exposure to air pollution include avoiding sources, staying indoors, filtering indoor air, using face masks, and limiting physical activity when and where air pollution levels are elevated. The effectiveness of these interventions varies widely with circumstances and conditions of use. Compared with upstream reduction or control of emissions, personal interventions place burdens and risk of adverse unintended consequences on individuals. We review evidence regarding the balance of benefits and potential harms of personal interventions for reducing exposure to outdoor air pollution, which merit careful consideration before making public health recommendations with regard to who should use personal interventions and where, when, and how they should be used.
Abstract 11399: Time to Anti-Arrhythmic for Out-of-Hospital Cardiac Arrest
Authors: Ryan Huebinger, Hei Kit Chan, Bentley Bobrow, Summer Chavez, Kevin Schulz, Jeffrey L Jarvis
Journal: Circulation (2021)

Introduction: Initial shockable rhythm is the strongest predictor of good outcomes for patients with out-of-hospital cardiac arrest (OHCA). While preclinical models have shown benefit of anti-arrhythmics, clinical trials have shown a very modest impact of anti-arrhythmic drugs, possibly related to real-life delays in drug administration. Little is known regarding the time to administration of anti-arrhythmic drugs or the association of time to drug and outcome. We utilized a national EMS registry to evaluate the time of drug administration and the association with outcomes. Methods: We evaluated the 2018 and 2019 NEMSIS dataset, including all non-traumatic, adult 911 EMS encounters for cardiac arrests with initial shockable rhythm. We then calculated the time from 911 call to administration of anti-arrhythmic. We excluded cases with time to administration less than 0 or greater than 120 minutes. Stratified by initial antiarrhythmic (amiodarone and lidocaine), we created a mixed-effect logistic regression model evaluating the association between every 5 minute increase in time to antiarrhythmic and ROSC. We modeled EMS agency as a random intercept and adjusted the analysis for age, sex, race, bystander witnessed arrest, location of arrest and EMS response time. We excluded EMS witnessed arrests and cases with missing ROSC data. Results: There were 449,630 adult, non-traumatic cardiac arrests identified with 55,142 patients (12.3%) having an initial shockable rhythm; 17,769 (32.2%) received amiodarone and 2,855 (5.2%) received lidocaine initially. The median time in minutes to initial dose of amiodarone was 20.4 with IQR (16-26.7). The median time in minutes to initial dose of lidocaine administration was 20.2 with IQR (15.7-27.0). Increasing time to initial antiarrhythmic was associated with decreased odds of ROSC for both amiodarone (aOR 0.9; 95% CI 0.9-0.94) and lidocaine (aOR 0.9; 95% CI 0.8-0.96). Conclusion: Time to administration of anti-arrhythmic medication varied, but most patients received the first does of anti-arrhythmic drug more than 20 minutes after the initial 911 call. Time to administration of antiarrhythmic was linked to ROSC.
Late-Onset Congenital Erythropoietic Porphyria
Authors: Ya-Wen Hsiao, Tzeon-Jye Chiou, Yu-Chen Huang
Journal: JAMA Dermatology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Eco-friendly bacteria-killing by nanorods through mechano-puncture with top selectivity
Authors: Jing Ye, Bo Li, Yufeng Zheng, Shuilin Wu, Dafu Chen, Yong Han
Journal: Bioactive Materials (2021)

Nanorods can induce mechano-puncture of Staphylococcus aureus (S. aureus) that often impairs osseointegration of orthopedic implants, while the critical nanorod top sharpness able to puncture S. aureus and the predominant contributor between top sharpness and length to mechano-puncture activity remains elusive. Herein, we fabricated three kinds of Al2O3-wrapped nanorods patterned arrays with different lengths and top sharpness. The top-sharp nanorods have lengths of 469 and 884 nm and the shorter show a length identical to the top-flat nanorods. Driven by the equivalent adhesive force of S. aureus, the top-flat nanorods deform cell envelops, showing a bacteriostatic rate of 29% owing to proliferation-inhibited manner. The top-sharp nanorods puncture S. aureus, showing a bactericidal rate of 96% for the longer, and 98% for the shorter that simultaneously exhibits fair osseointegration in bacteria-infected rat tibias, identifying top sharpness as a predominate contributor to mechano-puncture activity. Based on finite-element simulation, such top-flat nanorod derives the maximum stress (Smax) of 5.65 MPa on cell wall, lower than its ultimate-tensile-strength (13 MPa); while such top-sharp and shorter nanorod derives Smax of 20.15 MPa to puncture cell envelop. Moreover, a critical top conical angle of 138° is identified for nanorods able to puncture S. aureus.
Patterns of Fetal and Infant Growth and Brain Morphology at Age 10 Years
Authors: Carolina C. V. Silva, Hanan El Marroun, Sara Sammallahti, Meike W. Vernooij, Ryan L. Muetzel, Susana Santos, Vincent W. V. Jaddoe
Journal: JAMA Network Open (2021)

Preterm birth and low birth weight are associated with brain developmental and neurocognitive outcomes in childhood; however, not much is known about the specific critical periods in fetal life and infancy for these outcomes.To examine the associations of fetal and infant growth patterns with brain morphology in children at school age.This population-based, prospective cohort study was conducted from February 1 to April 16, 2021, as a part of the Generation R Study in Rotterdam, the Netherlands. The study included 3098 singleton children born between April 1, 2002, and January 31, 2006.Fetal weight was estimated in the second and third trimesters of pregnancy by ultrasonography. Infant weight was measured at birth and at 6, 12, and 24 months. Fetal and infant weight acceleration or deceleration were defined as a change in SD scores greater than 0.67 between time points. Infant measurements also included peak weight velocity, and age and body mass index reached at adiposity peak.Brain structure, including global and regional brain volumes, was quantified by magnetic resonance imaging at age 10 years.The study evaluated 3098 children (mean [SD] age at follow-up, 10.1 [0.6] years; 1557 girls [50.3%]; and 1753 Dutch [57.8%]). One SD score-higher weight gain until the second and third trimesters, birth, and 6, 12, and 24 months was associated with larger total brain volume independently of growth during any other age windows (second trimester: 5.7 cm3; 95% CI, 1.2-10.2 cm3; third trimester: 15.3 cm3; 95% CI, 11.0-19.6 cm3; birth: 20.8 cm3; 95% CI, 16.4-25.1 cm3; 6 months: 15.6 cm3; 95% CI, 11.2-19.9 cm3; 12 months: 11.3 cm3; 95% CI, 7.0-15.6 cm3; and 24 months: 11.1 cm3; 95% CI, 6.8-15.4 cm3). Compared with children with normal fetal and infant growth, those with fetal and infant growth deceleration had the smallest total brain volume (-32.5 cm3; 95% CI, -53.2 to -11.9 cm3). Children with fetal weight deceleration followed by infant catch-up growth had similar brain volumes as children with normal growth. Higher peak weight velocity and body mass index reached at adiposity peak were associated with larger brain volumes. Similar results were observed for cerebral and cerebellar gray and white matter volumes.This cohort study's findings suggest that both fetal and infant weight growth might be critical for cerebral and cerebellar brain volumes during childhood. Whether these associations link to neurocognitive outcomes should be further studied.
Ixazomib Versus Lenalidomide or Ixazomib and Lenalidomide Combination As Maintenance Regimens for Patients with Multiple Myeloma: Interim Analysis of a Multi-Center Prospective Study in China
Authors: Zhe Zhuang, Ying Tian, Wei-wei Tian, Hong Yu, Dongmei Zou, Qinhua Liu, Lei Shi, Fei Dong, Yanping Ma, Ru Feng, Shuangjiao Liu, Hui Liu, Hongmei Jing, Li Bao, Wanling Sun, Rong Fu, Liangming Ma, Chen Wenming, Yin Wu, Junling Zhuang
Journal: Blood (2021)
A nanoconcrete welding strategy for constructing high-performance wound dressing
Authors: Yingshuai Wang, Yanxia Zhu, Penghe Zhao, Bin Wei, Mingjian Fan, Danyang Chen, Zhaokui Jin, Qianjun He
Journal: Bioactive Materials (2021)

Engineering biomaterials to meet specific biomedical applications raises high requirements of mechanical performances, and simultaneous strengthening and toughening of polymer are frequently necessary but very challenging in many cases. In this work, we propose a new concept of nanoconcrete welding polymer chains, where mesoporous CaCO3 (mCaCO3) nanoconcretes which are composed of amorphous and nanocrystalline phases are developed to powerfully weld polymer chains through siphoning-induced occlusion, hydration-driven crystallization and dehydration-driven compression of nanoconcretes. The mCaCO3 nanoconcrete welding technology is verified to be able to remarkably augment strength, toughness and anti-fatigue performances of a model polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate)-based porous membrane. Mechanistically, we have revealed polymer-occluded nanocrystal structure and welding-derived microstress which is much stronger than interfacial Van der Waals force, thus efficiently preventing the generation of microcracks and repairing initial microcracks by microcracks-induced hydration, crystallization and polymer welding of mCaCO3 nanoconcretes. Constructed porous membrane is used as wound dressing, exhibiting a special nanoplates-constructed surface topography as well as a porous structure with plentiful oriented, aligned and opened pore channels, improved hydrophilicity, water vapor permeability, anti-bacterial and cell adherence, in support of wound healing and skin structural/functional repairing. The proposed nanoconcrete-welding-polymer strategy breaks a new pathway for improving the mechanical performances of polymers.
Comprehensive Genomic Profiling of Neuroendocrine Carcinomas of the Gastrointestinal System
Authors: Shinichi Yachida, Yasushi Totoki, Michaël Noë, Yoichiro Nakatani, Masafumi Horie, Kenta Kawasaki, Hiromi Nakamura, Mihoko Saito-Adachi, Masami Suzuki, Erina Takai, Natsuko Hama, Ryota Higuchi, Seiko Hirono, Satoshi Shiba, Mamoru Kato, Eisaku Furukawa, Yasuhito Arai, Hirofumi Rokutan, Taiki Hashimoto, Shuichi Mitsunaga, Mitsuro Kanda, Hidenori Tanaka, So Takata, Ayaka Shimomura, Minoru Oshima, Wenzel M. Hackeng, Tomoyuki Okumura, Keiichi Okano, Masakazu Yamamoto, Hiroki Yamaue, Chigusa Morizane, Koji Arihiro, Toru Furukawa, Toshiro Sato, Tohru Kiyono, Lodewijk A.A. Brosens, Laura D. Wood, Ralph H. Hruban, Tatsuhiro Shibata
Journal: Cancer Discovery (2021)

Abstract The neuroendocrine carcinoma of the gastrointestinal system (GIS-NEC) is a rare but highly malignant neoplasm. We analyzed 115 cases using whole-genome/exome sequencing, transcriptome sequencing, DNA methylation assays, and/or ATAC-seq and found GIS-NECs to be genetically distinct from neuroendocrine tumors (GIS-NET) in the same location. Clear genomic differences were also evident between pancreatic NECs (Panc-NEC) and nonpancreatic GIS-NECs (Nonpanc-NEC). Panc-NECs could be classified into two subgroups (i.e., “ductal-type” and “acinar-type”) based on genomic features. Alterations in TP53 and RB1 proved common in GIS-NECs, and most Nonpanc-NECs with intact RB1 demonstrated mutually exclusive amplification of CCNE1 or MYC. Alterations of the Notch gene family were characteristic of Nonpanc-NECs. Transcription factors for neuroendocrine differentiation, especially the SOX2 gene, appeared overexpressed in most GIS-NECs due to hypermethylation of the promoter region. This first comprehensive study of genomic alterations in GIS-NECs uncovered several key biological processes underlying genesis of this very lethal form of cancer. Significance: GIS-NECs are genetically distinct from GIS-NETs. GIS-NECs arising in different organs show similar histopathologic features and share some genomic features, but considerable differences exist between Panc-NECs and Nonpanc-NECs. In addition, Panc-NECs could be classified into two subgroups (i.e., “ductal-type” and “acinar-type”) based on genomic and epigenomic features. This article is highlighted in the In This Issue feature, p. 587
Digging Deeper for the Truth of a STEMI Mimic—Reply
Authors: Bao-Ze Qu, Ting-Ting Li
Journal: JAMA Internal Medicine (2021)

In Reply We appreciate the insightful comments by Chen and An on our article.1 They raised 4 concerns about our case report of a STEMI (ST-segment elevation myocardial infarction) mimic, which we have addressed in this response.
Association of Complement and MAPK Activation With SARS-CoV-2–Associated Myocardial Inflammation
Authors: Ludwig T. Weckbach, Lisa Schweizer, Angelina Kraechan, Stephanie Bieber, Hellen Ishikawa-Ankerhold, Jörg Hausleiter, Steffen Massberg, Tobias Straub, Karin Klingel, Ulrich Grabmaier, Maximilian Zwiebel, Matthias Mann, Christian Schulz, Peter Boekstegers, Thomas Gehrig, Claudius Jacobshagen, Werner Moshage, Nikos Werner
Journal: JAMA Cardiology (2021)

Myocardial injury is a common feature of patients with SARS-CoV-2 infection. However, the cardiac inflammatory processes associated with SARS-CoV-2 infection are not completely understood.To investigate the inflammatory cardiac phenotype associated with SARS-CoV-2 infection compared with viral myocarditis, immune-mediated myocarditis, and noninflammatory cardiomyopathy by integrating histologic, transcriptomic, and proteomic profiling.This case series was a cooperative study between the Ludwig Maximilian University Hospital Munich and the Cardiopathology Referral Center at the University of Tübingen in Germany. A cohort of 19 patients with suspected myocarditis was examined; of those, 5 patients were hospitalized with SARS-CoV-2 infection between March and May 2020. Cardiac tissue specimens from those 5 patients were compared with specimens from 5 patients with immune-mediated myocarditis, 4 patients with non-SARS-CoV-2 viral myocarditis, and 5 patients with noninflammatory cardiomyopathy, collected from January to August 2019.Endomyocardial biopsy.The inflammatory cardiac phenotypes were measured by immunohistologic analysis, RNA exome capture sequencing, and mass spectrometry-based proteomic analysis of endomyocardial biopsy specimens.Among 19 participants, the median age was 58 years (range, 37-76 years), and 15 individuals (79%) were male. Data on race and ethnicity were not collected. The abundance of CD163+ macrophages was generally higher in the cardiac tissue of patients with myocarditis, whereas lymphocyte counts were lower in the tissue of patients with SARS-CoV-2 infection vs patients with non-SARS-CoV-2 virus-associated and immune-mediated myocarditis. Among those with SARS-CoV-2 infection, components of the complement cascade, including C1q subunits (transcriptomic analysis: 2.5-fold to 3.6-fold increase; proteomic analysis: 2.0-fold to 3.4-fold increase) and serine/cysteine proteinase inhibitor clade G member 1 (transcriptomic analysis: 1.7-fold increase; proteomic analysis: 2.6-fold increase), belonged to the most commonly upregulated transcripts and differentially abundant proteins. In cardiac macrophages, the abundance of C1q was highest in SARS-CoV-2 infection. Assessment of important signaling cascades identified an upregulation of the serine/threonine mitogen-activated protein kinase pathways.This case series found that the cardiac immune signature varied in inflammatory conditions with different etiologic characteristics. Future studies are needed to examine the role of these immune pathways in myocardial inflammation.
An overview of real‐world data sources for oncology and considerations for research
Authors: Lynne T. Penberthy, Donna R. Rivera, Jennifer L. Lund, Melissa A. Bruno, Anne‐Marie Meyer
Journal: CA A Cancer Journal for Clinicians (2021)

Abstract Generating evidence on the use, effectiveness, and safety of new cancer therapies is a priority for researchers, health care providers, payers, and regulators given the rapid pace of change in cancer diagnosis and treatments. The use of real‐world data (RWD) is integral to understanding the utilization patterns and outcomes of these new treatments among patients with cancer who are treated in clinical practice and community settings. An initial step in the use of RWD is careful study design to assess the suitability of an RWD source. This pivotal process can be guided by using a conceptual model that encourages predesign conceptualization. The primary types of RWD included are electronic health records, administrative claims data, cancer registries, and specialty data providers and networks. Careful consideration of each data type is necessary because they are collected for a specific purpose, capturing a set of data elements within a certain population for that purpose, and they vary by population coverage and longitudinality. In this review, the authors provide a high‐level assessment of the strengths and limitations of each data category to inform data source selection appropriate to the study question. Overall, the development and accessibility of RWD sources for cancer research are rapidly increasing, and the use of these data requires careful consideration of composition and utility to assess important questions in understanding the use and effectiveness of new therapies.
Performance of QuantiFERON-<i>TB</i>Gold Plus assays in children and adolescents at risk of tuberculosis: a cross-sectional multicentre study
Authors: Aleix Soler-Garcia, Anna Gamell, Tomàs Pérez-Porcuna, Antonio Soriano-Arandes, Begoña Santiago, Teresa Tórtola, María Jesús Ruiz-Serrano, José Javier Korta Murua, Matilde Bustillo-Alonso, María Isabel Garrote-Llanos, Paula Rodríguez-Molino, Ana Isabel Piqueras, Alfredo Tagarro, Manuel Monsonís, Marc Tebruegge, Antoni Noguera-Julian
Journal: Thorax (2021)

Introduction The QuantiFERON- TB Gold Plus (QFT-Plus) assay, which features two antigen-stimulated tubes (TB1 and TB2) instead of a single tube used in previous-generation interferon-gamma release assays (IGRAs), was launched in 2016. Despite this, data regarding the assay’s performance in the paediatric setting remain scarce. This study aimed to determine the performance of QFT-Plus in a large cohort of children and adolescents at risk of tuberculosis (TB) in a low-burden setting. Methods Cross-sectional, multicentre study at healthcare institutions participating in the Spanish Paediatric TB Research Network, including patients &lt;18 years who had a QFT-Plus performed between September 2016 and June 2020. Results Of 1726 patients (52.8% male, median age: 8.4 years), 260 (15.1%) underwent testing during contact tracing, 288 (16.7%) on clinical/radiological suspicion of tuberculosis disease (TBD), 649 (37.6%) during new-entrant migrant screening and 529 (30.6%) prior to initiation of immunosuppressive treatment. Overall, the sensitivity of QFT-Plus for TBD (n=189) and for latent tuberculosis infection (LTBI, n=195) was 83.6% and 68.2%, respectively. The agreement between QFT-Plus TB1 and TB2 antigen tubes was excellent (98.9%, κ=0.961). Only five (2.5%) patients with TBD had discordance between TB1 and TB2 results (TB1+/TB2−, n=2; TB1−/TB2+, n=3). Indeterminate assay results (n=54, 3.1%) were associated with young age, lymphopenia and elevated C reactive protein concentrations. Conclusions Our non-comparative study indicates that QFT-Plus does not have greater sensitivity than previous-generation IGRAs in children in both TBD and LTBI. In TBD, the addition of the second antigen tube, TB2, does not enhance the assay’s performance substantially.
ICGC-ARGO precision medicine: familial matters in pancreatic cancer
Authors: Michele Milella, Claudio Luchini, Rita T Lawlor, Amber L Johns, Raffaella Casolino, Takayuki Yoshino, Andrew V Biankin, Andrew V Biankin, Lincoln D Stein, Keunchil Park, Rita T Lawlor, Amber L Johns, Jan O Korbel, Nik Zeps, Mark A Rubin, Marco A Marra, Olivier Elemento, Steven Gallinger, David Tuveson, Lorenz Trumper, Raphael Koch, Aldo Scarpa, Paul Brennan, Christian Pilarsky, Sergey Nikolaev, Sun-Soo Yoon, Eun Sook Lee, Tatsuhiro Shibata, Xiaojian Wu, Jianmin Wu, Qimin Zhan, Wai Poon, Takayuki Yoshino, Khawla S. Al-Kuraya, Rosalind Eeles, Rebecca Fitzgerald, Carlos Caldas, Jean Abraham, David K Chang
Journal: The Lancet Oncology (2021)
Fluorescence Imaging and Photodynamic Inactivation of Bacteria Based on Cationic Cyclometalated Iridium(III) Complexes with Aggregation‐Induced Emission Properties (Adv. Healthcare Mater. 24/2021)
Authors: Po‐Yu Ho, Sin‐Ying Lee, Chuen Kam, Junfei Zhu, Guo‐Gang Shan, Yuning Hong, Wai‐Yeung Wong, Sijie Chen
Journal: Advanced Healthcare Materials (2021)