tbuckley/cabot-search huggingface dataset:
Effect of corrected Global Lung Function Initiative reference equations on carbon monoxide transfer factor interpretation
Authors: Warren R. Ruehland, Celia J. Lanteri, Pam Matsas, Danny J. Brazzale
Journal: European Respiratory Journal (2021)

<b>Updating to corrected GLI <i>T</i><sub>LCO</sub> reference equations from the original GLI equations in a clinical population results in small changes in the lower limit of normal that are more pronounced in females, but there is minimal effect on test interpretation</b>https://bit.ly/2MTdErd
Comparison of Solid Tumor Treatment Response Observed in Clinical Practice With Response Reported in Clinical Trials
Authors: Bruce A. Feinberg, Marjorie E. Zettler, Andrew J. Klink, Choo H. Lee, Ajeet Gajra, Jonathan K. Kish
Journal: JAMA Network Open (2021)

In clinical trials supporting the regulatory approval of oncology drugs, solid tumor response is assessed using Response Evaluation Criteria in Solid Tumors (RECIST). Calculation of RECIST-based responses requires sequential, timed imaging data, which presents challenges to the method's application in real-world evidence research.To evaluate the feasibility and validity of a novel real-world RECIST method in assessing tumor burden associated with therapy for a large heterogeneous patient population undergoing treatment in routine clinical practice.This cohort study used physician-abstracted data pooled from retrospective, multisite electronic health record (EHR) review studies of patients treated with anticancer drugs at US oncology practices from 2014 through 2017. Included patients were receiving first-line treatment for thyroid cancer, breast cancer, or metastatic melanoma. Data were analyzed from March through August 2020.Undergoing treatment with immunotherapy or targeted therapy.Tumor response was classified according to RECIST guidelines (ie, change in sum diameter of target lesions) post hoc with measurements derived from imaging scans and reports.Among 1308 completed electronic case report forms, 956 forms (73.1%) had adequate data to classify real-world RECIST response. The greatest difference between physician-recorded responses and real-world RECIST-based responses was found in the proportion of complete responses: 118 responses (12.3%) vs 46 responses (4.8%) (P < .001). Among 609 patients in the metastatic melanoma population, complete responses were reported in 112 physician-recorded responses (18.4%) vs 44 real-world RECIST-based responses (7.2%) (P < .001), compared with 11 of 247 responses (4.5%) to 31 of 192 responses (16.1%) across pivotal trials of the same melanoma therapies.These findings suggest that comparing tumor lesion sizes and categorizing treatment response according to RECIST guidelines may be feasible using real-world data. This study found that physician-recorded assessments were associated with overestimation of treatment response, with the largest overestimation among complete responses. Real-world RECIST-based assessments were associated with better approximations of tumor response reported in clinical trials compared with those reported in EHRs.
Remodeling Alzheimer-amyloidosis models by seeding
Authors: Brittany S. Ulm, David R. Borchelt, Brenda D. Moore
Journal: Molecular Neurodegeneration (2021)

Abstract Alzheimer’s disease (AD) is among the most prevalent neurodegenerative diseases, with brain pathology defined by extracellular amyloid beta deposits and intracellular tau aggregates. To aid in research efforts to improve understanding of this disease, transgenic murine models have been developed that replicate aspects of AD pathology. Familial AD is associated with mutations in the amyloid precursor protein and in the presenilins (associated with amyloidosis); transgenic amyloid models feature one or more of these mutant genes. Recent advances in seeding methods provide a means to alter the morphology of resultant amyloid deposits and the age that pathology develops. In this review, we discuss the variety of factors that influence the seeding of amyloid beta pathology, including the source of seed, the time interval after seeding, the nature of the transgenic host, and the preparation of the seeding inoculum.
Benralizumab for adolescent patients with severe, eosinophilic asthma: Safety and efficacy after 3 years of treatment
Authors: William W. Busse, Eugene R. Bleecker, J. Mark FitzGerald, Gary T. Ferguson, Peter Barker, Laura Brooks, Richard F. Olsson, Ubaldo J. Martin, Mitchell Goldman
Journal: Journal of Allergy and Clinical Immunology (2021)
Outcome of BCR-ABL/Philadelphia Positive Acute Lymphoblastic Leukemia: A Single Centre Experience from Developing Country
Authors: Narendra Agrawal, Priyanka Verma, Neha Yadav, Rayaz Ahmed, Mukul Aggarwal, Pragya Bhandari, Niharika Bhatia, Jyotsna Kapoor, Dinesh Bhurani
Journal: Blood (2017)
SUBCLINICAL ATRIAL TACHYARRHYTHMIAS ARE NOT ASSOCIATED WITH WORSE OUTCOME IN CARDIAC RESYNCHRONIZATION THERAPY PATIENTS
Authors: Frederik Hendrik Verbrugge, Petra Nijst, Philip De Vusser, Hugo van Herendael, David Verhaert, Pieter Vandervoort, Matthias Dupont, Wilfried Mullens, Maximo Rivero-Ayerza
Journal: Journal of the American College of Cardiology (2013)
Community Transmission of SARS-CoV-2 at Three Fitness Facilities — Hawaii, June–July 2020
Authors: Laura M. Groves, Lauren Usagawa, Joe Elm, Eleanor Low, Augustina Manuzak, Joshua Quint, Katherine E. Center, Ann M. Buff, Sarah K. Kemble
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

the Hawaii Department of Health was notified that a fitness instructor (instructor A) had experienced signs and symptoms compatible with coronavirus disease 2019 (COVID-19)* and received a positive reverse transcription-polymerase chain reaction (RT-PCR) test result for SARS-CoV-2, the virus that causes COVID-19.At the time, Honolulu County reported community transmission of a 7-day average of 2-3 cases per 100,000 persons per day (1).Before the onset of symptoms, instructor A taught classes at two fitness facilities in Honolulu, facilities X and Y. Twenty-one COVID-19 cases were linked to instructor A, including a case in another fitness instructor (instructor B).The aggregate attack rates in classes taught by both instructors <1 day, 1 to <2 days, and ≥2 days before symptom onset were 95% (20 of 21), 13% (one of eight), and 0% (zero of 33), respectively.Among the 21 secondary cases, 20 (95%) persons had symptomatic illness, two (10%) of whom were hospitalized.At the time of this outbreak, use of masks was not required in fitness facilities.To reduce SARS-CoV-2 transmission in fitness facilities, staff members and patrons should wear a mask (including during high-intensity exercise), and facilities should implement engineering and administrative controls including 1) improving ventilation; 2) enforcing consistent and correct mask use and physical distancing (maintaining ≥6 ft of distance between all persons, limiting physical contact and class size, and preventing crowded spaces); 3) reminding all patrons and staff members to stay home when ill; and 4) increasing opportunities for hand hygiene.Conducting exercise activities entirely outdoors or virtually could further reduce SARS-CoV-2 transmission risk.* Signs and symptoms included fever,
Genomic evolution and diverse models of systemic metastases in colorectal cancer
Authors: Hai-Ning Chen, Yang Shu, Fei Liao, Xue Liao, Hongying Zhang, Yun Qin, Zhu Wang, Maochao Luo, Qiuluo Liu, Zhinan Xue, Minyuan Cao, Shouyue Zhang, Wei-Han Zhang, Qianqian Hou, Xuyang Xia, Han Luo, Yan Zhang, Lie Yang, Jian-Kun Hu, Xianghui Fu, Bo Liu, Hongbo Hu, Canhua Huang, Yong Peng, Wei Cheng, Lunzhi Dai, Li Yang, Wei Zhang, Biao Dong, Yuan Li, Yuquan Wei, Heng Xu, Zong-Guang Zhou
Journal: Gut (2021)

Objective The systemic spread of colorectal cancer (CRC) is dominated by the portal system and exhibits diverse patterns of metastasis without systematical genomic investigation. Here, we evaluated the genomic evolution of CRC with multiorgan metastases using multiregion sequencing. Design Whole-exome sequencing was performed on multiple regions (n=74) of matched primary tumour, adjacent non-cancerous mucosa, liver metastasis and lung metastasis from six patients with CRC. Phylogenetic reconstruction and evolutionary analyses were used to investigate the metastatic seeding pattern and clonal origin. Recurrent driver gene mutations were analysed across patients and validated in two independent cohorts. Metastatic assays were performed to examine the effect of the novel driver gene on the malignant behaviour of CRC cells. Results Based on the migration patterns and clonal origins, three models were revealed (sequential, branch-off and diaspora), which not only supported the anatomic assumption that CRC cells spread to lung after clonally expanding in the liver, but also illustrated the direct seeding of extrahepatic metastases from primary tumours independently. Unlike other cancer types, polyphyletic seeding occurs in CRC, which may result in late metastases with intermetastatic driver gene heterogeneity. In cases with rapid dissemination, we found recurrent trunk loss-of-function mutations in ZFP36L2 , which is enriched in metastatic CRC and associated with poor overall survival. CRISPR/Cas9-mediated knockout of ZFP36L2 enhances the metastatic potential of CRC cells. Conclusion Our results provide genomic evidence for metastatic evolution and indicate that biopsy/sequencing of metastases may be considered for patients with CRC with multiorgan or late postoperative metastasis.
Exosomes in atherosclerosis: performers, bystanders, biomarkers, and therapeutic targets
Authors: Chen Wang, Zhelong Li, Yunnan Liu, Lijun Yuan
Journal: Theranostics (2021)

Exosomes are nanosized lipid vesicles originating from the endosomal system that carry many macromolecules from their parental cells and play important roles in intercellular communication. The functions and underlying mechanisms of exosomes in atherosclerosis have recently been intensively studied. In this review, we briefly introduce exosome biology and then focus on advances in the roles of exosomes in atherosclerosis, specifically exosomal changes associated with atherosclerosis, their cellular origins and potential functional cargos, and their detailed impacts on recipient cells. We also discuss the potential of exosomes as biomarkers and drug carriers for managing atherosclerosis.
New Insights Into Plaque Erosion as a Mechanism of Acute Coronary Syndromes
Authors: Dhaval Kolte, Peter Libby, Ik-Kyung Jang
Journal: JAMA (2021)

This Viewpoint summarizes the pathophysiology and clinical features of atherosclerotic plaque erosion as an underlying mechanism of acute coronary syndromes (ACS) distinct from plaque rupture and reviews evidence that antithrombotic therapy without PCI and stenting may be optimal treatment.
Fine particulate matter and out-of-hospital cardiac arrest of respiratory origin
Authors: Sunao Kojima, Takehiro Michikawa, Kunihiko Matsui, Hisao Ogawa, Shin Yamazaki, Hiroshi Nitta, Akinori Takami, Kayo Ueda, Yoshio Tahara, Naohiro Yonemoto, Hiroshi Nonogi, Ken Nagao, Takanori Ikeda, Yoshio Kobayashi
Journal: European Respiratory Journal (2021)

<b>Particulate matter is a potential risk factor for out-of-hospital cardiac arrests (OHCAs) of respiratory origin. The percent increase in incidence of OHCA of respiratory origin is equivalent to that of PM<sub>2.5</sub> exposure-related OHCAs of cardiac origin.</b>http://bit.ly/3tDXym0
Abstract 16226: Single-cell RNA Sequencing Coupled With Optical Imaging for Targeted Real-time Visualization of the Cardiac Conduction System
Authors: William R Goodyer, Benjamin Beyersdorf, Nynke Van Den Berg, Nazan Puluca, Jan Buikema, Soah Lee, Darren Salmi, Elise Robinson, Stephan Rogalla, Henry Chubb, Kara Motonaga, Scott R Ceresnak, Anne M Dubin, Eben Rosenthal, Sean M Wu
Journal: Circulation (2020)

Introduction: Optical imaging has the potential to revolutionize cardiothoracic surgery by allowing for the real-time visualization of structures often inadvertently damaged due to inadequate visibility. The cardiac conduction system (CCS) consists of specialized cells embedded within the heart that are essential for cardiac function yet indistinguishable from heart muscle tissue. Intraoperative CCS injury is a major complication in cardiac surgery, representing a significant source of morbidity and mortality. To date, there exists no intraoperative method to visualize the CCS. Hypothesis: We hypothesized that unique, CCS-specific cell surface markers could be used for the in vivo labelling of the CCS. Objectives: Use single-cell RNA sequencing (scRNAseq) to discover cell surface markers that may serve as the basis for generating optical imaging agents for real-time CCS visualization. Methods/Results: Gene expression analysis of a comprehensive scRNAseq dataset of the entire murine CCS revealed significant enrichment of a host of CCS-specific cell surface genes. A subset of genes were subsequently validated in the CCS of mice and/or human tissue. In total, 7 novel cell surface markers were confirmed to have unique expression patterns throughout or within distinct components of the CCS. Next, optical imaging agents were created consisting of a near-infrared (NIR) dye conjugated to antibodies directed against two distinct CCS-specific cell surface markers. Each optical imaging agent demonstrated high sensitivity and specificity in labeling the entire CCS in vivo following a single intravenous injection in mice. Specificity was confirmed within intact, whole hearts using both closed-field NIR imaging and whole mount immunolabeling with volume imaging (iDISCO+). Dosage, timecourse and biodistribution analyses were performed as well as safety validation by surface ECG. Conclusions: In summary, we coupled scRNAseq with optical imaging to create novel tools for the real-time visualization of a complex tissue substructure. We provide a proof-of-principle for broadening the scope of optical imaging but also address a significant unmet clinical need, laying the foundation for translational opportunities in cardiac intervention and imaging.
Cardiac Complications of SARS CoV-2 Associated Multi-System Inflammatory Syndrome in Children (mis-c)
Authors: A. S. Harahsheh, C. A. Sable, Y. H. Loke, R. L. DeBiasi, L. Olivieri, M. T. Donofrio, K. Parikh, C. I. Berul, A. Austin, M. Bell, A. Christopher, R. R. Cross, N. Dham, L. Frank, J. N. Kline, T. Ronis, K. L. Smith, C. Spurney, H. Srinivasalu, D. L. Wessel, J. Zhang, A. Krishnan
Journal: Circulation (2020)
Real-time clinician text feeds from electronic health records
Authors: James T. H. Teo, Vlad Dinu, William Bernal, Phil Davidson, Vitaliy Oliynyk, Cormac Breen, Richard D. Barker, Richard J. B. Dobson
Journal: npj Digital Medicine (2021)

Abstract Analyses of search engine and social media feeds have been attempted for infectious disease outbreaks, but have been found to be susceptible to artefactual distortions from health scares or keyword spamming in social media or the public internet. We describe an approach using real-time aggregation of keywords and phrases of freetext from real-time clinician-generated documentation in electronic health records to produce a customisable real-time viral pneumonia signal providing up to 4 days warning for secondary care capacity planning. This low-cost approach is open-source, is locally customisable, is not dependent on any specific electronic health record system and can provide an ensemble of signals if deployed at multiple organisational scales.
Development and validation of a disease risk stratification system for patients with haematological malignancies: a retrospective cohort study of the European Society for Blood and Marrow Transplantation registry
Authors: Roni Shouval, Joshua A Fein, Myriam Labopin, Christina Cho, Ali Bazarbachi, Frédéric Baron, Gesine Bug, Fabio Ciceri, Selim Corbacioglu, Jacques-Emmanuel Galimard, Sebastian Giebel, Maria H Gilleece, Sergio Giralt, Ann Jakubowski, Silvia Montoto, Richard J O'Reilly, Esperanza B Papadopoulos, Zinaida Peric, Annalisa Ruggeri, Jaime Sanz, Craig S Sauter, Bipin N Savani, Christoph Schmid, Alexandros Spyridonidis, Roni Tamari, Jurjen Versluis, Ibrahim Yakoub-Agha, Miguel Angel Perales, Mohamad Mohty, Arnon Nagler
Journal: The Lancet Haematology (2021)
Avacopan — Time to Replace Glucocorticoids?
Authors: Kenneth J. Warrington
Journal: New England Journal of Medicine (2021)

In recent decades, substantial advances in the treatment of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis have led to a decrease in disease-related morbidity and mortality. The regimen for inducing remission in patients with severe ANCA-associated vasculitis has evolved on the basis of data from randomized clinical trials and typically consists of a tapering course of glucocorticoids in combination with cyclophosphamide or rituximab.1 Despite these advances, glucocorticoids have remained an anchoring medication in updated regimens, and they contribute to treatment-related toxic effects. Along with evaluation of the efficacy and safety of newer agents such as rituximab, there has been a drive to . . .
Environmental Spread of Extended Spectrum Beta-Lactamase (ESBL) Producing <i>Escherichia coli</i> and ESBL Genes among Children and Domestic Animals in Ecuador
Authors: Liseth Salinas, Fernanda Loayza, Paúl Cárdenas, Carlos Saraiva, Timothy J. Johnson, Heather Amato, Jay P. Graham, Gabriel Trueba
Journal: Environmental Health Perspectives (2021)

There is a significant gap in our understanding of the sources of multidrug-resistant bacteria and resistance genes in community settings where human-animal interfaces exist.This study characterized the relationship of third-generation cephalosporin-resistant Escherichia coli (3GCR-EC) isolated from animal feces in the environment and child feces based on phenotypic antimicrobial resistance (AMR) and whole genome sequencing (WGS).We examined 3GCR-EC isolated from environmental fecal samples of domestic animals and child fecal samples in Ecuador. We analyzed phenotypic and genotypic AMR, as well as clonal relationships (CRs) based on pairwise single-nucleotide polymorphisms (SNPs) analysis of 3GCR-EC core genomes. CRs were defined as isolates with fewer than 100 different SNPs.A total of 264 3GCR-EC isolates from children (n=21), dogs (n=20), and chickens (n=18) living in the same region of Quito, Ecuador, were identified. We detected 16 CRs total, which were found between 7 children and 5 domestic animals (5 CRs) and between 19 domestic animals (11 CRs). We observed that several clonally related 3GCR-EC isolates had acquired different plasmids and AMR genes. Most CRs were observed in different homes (n=14) at relatively large distances. Isolates from children and domestic animals shared the same blaCTX-M allelic variants, and the most prevalent were blaCTX-M-55 and blaCTX-M-65, which were found in isolates from children, dogs, and chickens.This study provides evidence of highly dynamic horizontal transfer of AMR genes and mobile genetic elements (MGEs) in the E. coli community and shows that some 3GCR-EC and (extended-spectrum β-lactamase) ESBL genes may have moved relatively large distances among domestic animals and children in semirural communities near Quito, Ecuador. Child-animal contact and the presence of domestic animal feces in the environment potentially serve as important sources of drug-resistant bacteria and ESBL genes. https://doi.org/10.1289/EHP7729.
Suboptimal Intermediates Underlie Evolution of the Bicoid Homeodomain
Authors: Pinar Onal, Himari Imaya Gunasinghe, Kristaley Yui Umezawa, Michael Zheng, Jia Ling, Leen Azeez, Anecine Dalmeus, Tasmima Tazin, Stephen Small
Journal: Molecular Biology and Evolution (2021)

Changes in regulatory networks generate materials for evolution to create phenotypic diversity. For transcription networks, multiple studies have shown that alterations in binding sites of cis-regulatory elements correlate well with the gain or loss of specific features of the body plan. Less is known about alterations in the amino acid sequences of the transcription factors (TFs) that bind these elements. Here we study the evolution of Bicoid (Bcd), a homeodomain (HD) protein that is critical for anterior embryo patterning in Drosophila. The ancestor of Bcd (AncBcd) emerged after a duplication of a Zerknullt (Zen)-like ancestral protein (AncZB) in a suborder of flies. AncBcd diverged from AncZB, gaining novel transcriptional and translational activities. We focus on the evolution of the HD of AncBcd, which binds to DNA and RNA, and is comprised of four subdomains: an N-terminal arm (NT) and three helices; H1, H2, and Recognition Helix (RH). Using chimeras of subdomains and gene rescue assays in Drosophila, we show that robust patterning activity of the Bcd HD (high frequency rescue to adulthood) is achieved only when amino acid substitutions in three separate subdomains (NT, H1, and RH) are combined. Other combinations of subdomains also yield full rescue, but with lower penetrance, suggesting alternative suboptimal activities. Our results suggest a multistep pathway for the evolution of the Bcd HD that involved intermediate HD sequences with suboptimal activities, which constrained and enabled further evolutionary changes. They also demonstrate critical epistatic forces that contribute to the robust function of a DNA-binding domain.
A cold-stress-inducible PERK/OGT axis controls TOM70-assisted mitochondrial protein import and cristae formation
Authors: Pedro Latorre-Muro, Katherine E. O’Malley, Christopher F. Bennett, Elizabeth A. Perry, Eduardo Balsa, Clint D.J. Tavares, Mark Jedrychowski, Steven P. Gygi, Pere Puigserver
Journal: Cell Metabolism (2021)