tbuckley/cabot-search huggingface dataset:
Breathlessness in COPD: linking symptom clusters with brain activity
Authors: Sarah L. Finnegan, Olivia K. Harrison, Catherine J. Harmer, Mari Herigstad, Najib M. Rahman, Andrea Reinecke, Kyle T.S. Pattinson
Journal: European Respiratory Journal (2021)

Background Current models of breathlessness often fail to explain disparities between patients' experiences of breathlessness and objective measures of lung function. While a mechanistic understanding of this discordance has thus far remained elusive, factors such as mood, attention and expectation have all been implicated as important modulators of breathlessness. Therefore, we have developed a model to better understand the relationships between these factors using unsupervised machine learning techniques. Subsequently we examined how expectation-related brain activity differed between these symptom-defined clusters of participants. Methods A cohort of 91 participants with mild-to-moderate chronic obstructive pulmonary disease (COPD) underwent functional brain imaging, self-report questionnaires and clinical measures of respiratory function. Unsupervised machine learning techniques of exploratory factor analysis and hierarchical cluster modelling were used to model brain–behaviour–breathlessness links. Results We successfully stratified participants across four key factors corresponding to mood, symptom burden and two capability measures. Two key groups resulted from this stratification, corresponding to high and low symptom burden. Compared with the high symptom burden group, the low symptom burden group demonstrated significantly greater brain activity within the anterior insula, a key region thought to be involved in monitoring internal bodily sensations (interoception). Conclusions This is the largest functional neuroimaging study of COPD to date, and is the first to provide a clear model linking brain, behaviour and breathlessness expectation. Furthermore, it was possible to stratify participants into groups, which then revealed differences in brain activity patterns. Together, these findings highlight the value of multimodal models of breathlessness in identifying behavioural phenotypes and for advancing understanding of differences in breathlessness burden.
Temporal and regional incidence of carbapenemase-producing Enterobacterales, Switzerland, 2013 to 2018
Authors: Alban Ramette, Michael Gasser, Patrice Nordmann, Reinhard Zbinden, Jacques Schrenzel, Damir Perisa, Andreas Kronenberg
Journal: Eurosurveillance (2021)

IntroductionIn contrast to countries where carbapenemase-producing Enterobacterales (CPE) are endemic, only sporadic cases were reported in Switzerland until 2013. An aggravation of the epidemiological situation in neighbouring European countries indicated the need for a surveillance study in Switzerland.AimWe aimed to describe CPE distributions in Switzerland and identify epidemiological factors associated with changes in incidence.MethodsData on all human CPE isolates from 2013 to 2018 were collected by the Swiss Centre for Antibiotic Resistance (ANRESIS) and analysed for temporal and regional trends by Generalised Poisson regression. Isolates associated with infection or colonisation were included in a primary analysis; a secondary analysis included invasive isolates only. Statistical detection of regional clusters was performed with WHONET/SaTScan.ResultsWe analysed 731 CPE isolates, of which 325 (44.5%) were associated with screenings and 173 (23.7%) with infections. Yearly detection of CPE isolates increased considerably during the study period from 65 to 212. The most frequently isolated species were Klebsiella pneumoniae (54%) and Escherichia coli (28%). The most frequent genotypes were OXA-48 (43%), KPC (21%) and NDM (14%). In contrast to the French-speaking parts of Switzerland (West, Geneva) where OXA-48 were the predominant genotypes (around 60%), KPC was the most frequently detected genotype in the Italian-speaking region (63%). WHONET/SaTScan outbreak detection analysis identified seven clusters in five regions of Switzerland.ConclusionsIn a first continuous surveillance of CPE in Switzerland, we found that the epidemiological situation aggravated nationwide and that regional patterns of CPE genotypes mirrored the situation in neighbouring European countries.
Risk of drug-induced interstitial lung disease in hospitalised patients: a nested case–control study
Authors: Taisuke Jo, Nobuaki Michihata, Hayato Yamana, Kojiro Morita, Miho Ishimaru, Yasuhiro Yamauchi, Wakae Hasegawa, Hirokazu Urushiyama, Kazuaki Uda, Hiroki Matsui, Kiyohide Fushimi, Hideo Yasunaga, Takahide Nagase
Journal: Thorax (2021)

Introduction Information on drug-induced interstitial lung disease (DILD) is limited due to its low incidence. This study investigated the frequencies of drug categories with potential risk in patients developing DILD during hospitalisation and analysed the risk of developing DILD associated with each of these drugs. Methods Using a Japanese national inpatient database, we identified patients without interstitial pneumonia on admission who developed DILD and required corticosteroid therapy during hospitalisation from July 2010 to March 2016. We conducted a nested case–control study; four controls from the entire non-DILD patient cohort were matched to each DILD case on age, sex, main diagnosis, admission year and hospital. We defined 42 classified categories of drugs with 216 generic names as drugs with potential risk of DILD, and we identified the use of these drugs during hospitalisation for each patient. We analysed the association between each drug category and DILD development using conditional logistic regression analyses. Results We retrospectively identified 2342 patients who developed DILD. After one-to-four case–control matching, 1541 case patients were matched with 5677 control patients. Six drug categories were significantly associated with the increased occurrence of DILD. These included epidermal growth factor receptor inhibitors (OR: 16.84, 95% CI 9.32 to 30.41) and class III antiarrhythmic drugs (OR: 7.01, 95% CI 3.86 to 12.73). Statins were associated with reduced risk of DILD (OR: 0.68, 95% CI 0.50 to 0.92). Conclusions We demonstrated significant associations between various drug categories and DILD. Our findings provide useful information on drug categories with potential risk to help physicians prevent and treat DILD.
A new therapy for refractory gastric cancer bleeding: endoscopic ultrasound-guided lauromacrogol injection
Authors: Chaoqun Han, Xin Ling, Jun Liu, Zhen Ding, Xiaohua Hou
Journal: Endoscopy (2021)

A 71-year-old man was admitted for intractable gastrointestinal bleeding because of residual gastric cancer with liver metastasis ( [Fig.1]). He presented having had three episodes of hematemesis or melena in the previous 30 days. Conventional endoscopic management for bleeding of unresectable gastric cancer is challenging because of the low clinical success rate and high amount of rebleeding [1]. After careful discussion with the patient and his family, treatment using endoscopic ultrasound (EUS)-guided lauromacrogol injection was decided.
Abstract 15706: Loss of Wnt/Ror2 Signaling is Associated With Reduced Pericyte Recruitment and Impaired Pulmonary Angiogenesis in Idiopathic Pulmonary Arterial Hypertension
Authors: Ke Yuan, Mark Orcholski, Cristina Panaroni, Joy Wu, Vinicio de Jesus Perez
Journal: Circulation (2013)

Pericytes are vascular cells that interact with endothelial cells (ECs) to provide mural support and promote vessel maturation. While abnormalities in EC-pericyte interactions could contribute to s...
Is artificial intelligence ready to replace expert endoscopists?
Authors: Naohisa Yahagi
Journal: Endoscopy (2021)

Artificial intelligence (AI) is one of the most rapidly evolving new fields of technology over the past decade. We are now in the era of the fourth industrial revolution, which is characterized by the development of robotics, biotechnology, nanotechnology, the internet of things (IoT), big data, and AI, among others, and we have reached a turning point that includes medical services.
Ectopic expression of interleukin 1 receptor type II enhances cell migration through activation of pre-interleukin 1α pathway
Authors: Pei-Fen Su, Shih-Yu Chang, Te-Chang Lee
Journal: Cancer Research (2008)

5386  Interleukin-1 receptor type II (IL1R2), a decoy receptor of pro-inflammatory interleukin 1 (IL-1), is enhanced by chronic exposure of human uroepithelial cell line HUC-1 to inorganic arsenite. To explore the biological roles of IL1R2 in uroepithelial cells, we ectopically expressed IL1R2 in HUC-1 cells and demonstrated that overexpression of IL1R2 specifically blocked NF-κB activity stimulated by exogenous IL-1β but not tumor necrosis factor-α. Meanwhile, we observed that ectopic expression of IL1R2 resulted in changes of cell morphology, enhanced migration activity, increased expression of precursor form IL-1α (pIL-1α), and its down-stream genes, such as interleukin 6 (IL6), interleukin 8 (IL8), and collagen α1 type 1 (COL1A1). Depletion of IL-1α by RNA interference technique in IL1R2-overexpressed HUC-1 cells reduced the expression of IL6, IL8, and COL1A1, indicating the involvement of pIL-1α pathway in triggering the expression of these downstream genes. However, reduced expression of either IL-1α or COL1A1, but not IL6 or IL8, significantly attenuated the migration activity in IL1R2 overexpressed cells. Furthermore, IL1R2 overexpression associated with enhanced expression of Samd-interacting protein 1 (SIP-1) as well as reduced expression of E-cadherin (E-cad). Since SIP-1 is a repressor of COL1A1-induced E-cad expression, the present results suggest that IL1R2 overexpression, in addition to inhibit the exogenous IL-1 signaling, activates the expression of COL1A1 via pIL-1α pathway that subsequently activates SIP-1 to suppress E-cad and hence enhances migration activity.
The kynurenine derivative 3-HAA sensitizes hepatocellular carcinoma to sorafenib by upregulating phosphatases
Authors: Guifang Gan, Zhaopeng Shi, Chengfang Shangguan, Jieying Zhang, Yuan Yuan, Lei Chen, Weiren Liu, Biao Li, Songshu Meng, Wujun Xiong, Jun Mi
Journal: Theranostics (2021)

Objectives: Sorafenib is the only FDA-approved first-line target drug for HCC patients. However, sorafenib merely confers 3-5 months of survival benefit with less than 30% of HCC patients sensitive to sorafenib therapy. Thus, it's necessary to develop a sensitizer for hepatocellular carcinoma (HCC) to sorafenib. Methods: The principal component analysis, gene ontology, and KEGG analysis are utilized following RNA-sequencing. The mass spectrometry analysis following immunoprecipitation is performed to discover the phosphatase targets. Most importantly, both the cell line-derived xenograft (CDX) and the patient-derived xenograft (PDX) mouse model are used to determine the effect of 3-HAA on sorafenib-resistant HCC in vivo. Results: In nude mice carrying HCC xenograft, tumor growth is inhibited by sorafenib or 3-HAA alone. When used in combination, the treatment particularly prevents the xenograft from growing. Combined treatment also suppresses the growth of sorafenib-resistant (≥30mg/kg) PDXs. In a set of mechanistic experiments, we find enhanced AKT activation and decreased apoptotic cells in de novo and acquired sorafenib-resistant HCC cells and tissues. 3-HAA decreases AKT phosphorylation and increases the apoptosis of HCC in both cultured cells and mouse xenografts by upregulation of phosphatases PPP1R15A/DUSP6. PPP1R15A/PPP1α directly reduces Akt phosphorylation while DUSP6 decreases Akt activity through inhibiting PDK1. The AKT activator abolishes 3-HAA inhibition of HCC growth in vitro and in mice. Conclusion: This study demonstrates that 3-HAA sensitizes HCC cells to sorafenib by upregulation of phosphatases, suggesting it as a promising molecule for HCC therapy.
Reverse Plasticity Underlies Rapid Evolution by Clonal Selection within Populations of Fibroblasts Propagated on a Novel Soft Substrate
Authors: Purboja Purkayastha, Kavya Pendyala, Ayush S Saxena, Hesamedin Hakimjavadi, Srikar Chamala, Purushottam Dixit, Charles F Baer, Tanmay P Lele
Journal: Molecular Biology and Evolution (2021)

Abstract Mechanical properties such as substrate stiffness are a ubiquitous feature of a cell’s environment. Many types of animal cells exhibit canonical phenotypic plasticity when grown on substrates of differing stiffness, in vitro and in vivo. Whether such plasticity is a multivariate optimum due to hundreds of millions of years of animal evolution, or instead is a compromise between conflicting selective demands, is unknown. We addressed these questions by means of experimental evolution of populations of mouse fibroblasts propagated for approximately 90 cell generations on soft or stiff substrates. The ancestral cells grow twice as fast on stiff substrate as on soft substrate and exhibit the canonical phenotypic plasticity. Soft-selected lines derived from a genetically diverse ancestral population increased growth rate on soft substrate to the ancestral level on stiff substrate and evolved the same multivariate phenotype. The pattern of plasticity in the soft-selected lines was opposite of the ancestral pattern, suggesting that reverse plasticity underlies the observed rapid evolution. Conversely, growth rate and phenotypes did not change in selected lines derived from clonal cells. Overall, our results suggest that the changes were the result of genetic evolution and not phenotypic plasticity per se. Whole-transcriptome analysis revealed consistent differentiation between ancestral and soft-selected populations, and that both emergent phenotypes and gene expression tended to revert in the soft-selected lines. However, the selected populations appear to have achieved the same phenotypic outcome by means of at least two distinct transcriptional architectures related to mechanotransduction and proliferation.
The Sensitivity and Costs of Testing for SARS-CoV-2 Infection With Saliva Versus Nasopharyngeal Swabs
Authors: Catherine Hill, Jean-Yves Thuret
Journal: Annals of Internal Medicine (2021)

LettersApril 2021The Sensitivity and Costs of Testing for SARS-CoV-2 Infection With Saliva Versus Nasopharyngeal SwabsFREECatherine Hill, MSc, Jean-Yves Thuret, PhDCatherine Hill, MScService de Biostatistique et d’Epidémiologie, Gustave Roussy, Paris-Saclay University, Villejuif, FranceSearch for more papers by this author, Jean-Yves Thuret, PhDUniversité Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, FranceSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L21-0092 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR: We read Bastos' and colleagues' timely review (1) with interest. However, we have noted a few discrepancies between the data in their Figure and the original data in some of the articles that they cite (specifically, references 41 and 50 to 58 of their review). We suspect that the rows of this forest plot became misaligned, because some of the incorrect data seem to pertain to a different article that the authors cite.Although it seems unlikely that these errors will change the authors' conclusions, they warrant correction. Of note, we have verified data only from published articles, not those posted on preprint servers.Reference1. Bastos ML, Perlman-Arrow S, Menzies D, et al. The sensitivity and costs of testing for SARS-CoV-2 infection with saliva versus nasopharyngeal swabs. A systematic review and meta-analysis. Ann Intern Med. 2021;174:501-10. doi:10.7326/M20-6569 LinkGoogle Scholar Comments 0 Comments Sign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Catherine Hill, MSc; Jean-Yves Thuret, PhDAffiliations: Service de Biostatistique et d’Epidémiologie, Gustave Roussy, Paris-Saclay University, Villejuif, FranceUniversité Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, FranceDisclosures: Authors have reported no disclosures of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L21-0092. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Sensitivity and Costs of Testing for SARS-CoV-2 Infection With Saliva Versus Nasopharyngeal Swabs Mayara Lisboa Bastos , Sara Perlman-Arrow , Dick Menzies , and Jonathon R. Campbell Metrics Cited byElectrochemical biosensors for SARS-CoV-2 detection: Voltametric or impedimetric transduction?The Efficacy of Health Surveys and Polymerase Chain Reaction Tests Prior to Judo Tournaments During the COVID-19 PandemicEmerging Biosensors to Detect Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): A Review April 2021Volume 174, Issue 4 Page: 582 ePublished: 20 April 2021 Issue Published: April 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Hypoxia-sensing CAR T cells provide safety and efficacy in treating solid tumors
Authors: Paris Kosti, James W. Opzoomer, Karen I. Larios-Martinez, Rhonda Henley-Smith, Cheryl L. Scudamore, Mary Okesola, Mustafa Y.M. Taher, David M. Davies, Tamara Muliaditan, Daniel Larcombe-Young, Natalie Woodman, Cheryl E. Gillett, Selvam Thavaraj, John Maher, James N. Arnold
Journal: Cell Reports Medicine (2021)

Utilizing T cells expressing chimeric antigen receptors (CARs) to identify and attack solid tumors has proven challenging, in large part because of the lack of tumor-specific targets to direct CAR binding. Tumor selectivity is crucial because on-target, off-tumor activation of CAR T cells can result in potentially lethal toxicities. This study presents a stringent hypoxia-sensing CAR T cell system that achieves selective expression of a pan-ErbB-targeted CAR within a solid tumor, a microenvironment characterized by inadequate oxygen supply. Using murine xenograft models, we demonstrate that, despite widespread expression of ErbB receptors in healthy organs, the approach provides anti-tumor efficacy without off-tumor toxicity. This dynamic on/off oxygen-sensing safety switch has the potential to facilitate unlimited expansion of the CAR T cell target repertoire for treating solid malignancies.
State-Level Economic Costs of Opioid Use Disorder and Fatal Opioid Overdose — United States, 2017
Authors: Feijun Luo, Mengyao Li, Curtis Florence
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

NSDUH classified respondents as having opioid use disorder during the past year if they had a heroin use disorder (dependence or abuse), pain reliever use disorder (dependence or abuse), or both during the past year.
Abstract 16890: Coronary Artery Calcium for Personalizing Antihypertensive Therapy: A Pooled Cohort Analysis
Authors: Gargya Malla, Vibhu Parcha, Rajat Kalra, Ambarish Pandey, Nasir Khurram, Pankaj Arora, Garima Arora
Journal: Circulation (2020)

Background: The 2017 American College of Cardiology/American Heart Association high blood pressure (BP) guidelines recommend risk assessment of atherosclerotic cardiovascular disease (CVD) to inform hypertension (HTN) treatment in adults with elevated BP or low-risk stage 1 HTN. Use of coronary artery calcium (CAC) score, an excellent imaging risk-prediction tool, to guide HTN therapy has not been well studied. Methods: Participants free of CVD were pooled from three population cohort studies; 1) Multiethnic Study of Atherosclerosis, 2) Coronary Artery Risk Development in Young Adults and 3) Jackson Heart Study. Risk for incident CVD events (heart failure, stroke or cardiovascular mortality) by the CAC status and the BP treatment group was assessed. Multivariable Cox proportional hazards models were used to estimate the hazard ratios. The 10-year number needed to treat to prevent a single CVD event was also estimated. Results: This study included 11,499 participants (mean age 56 years; 55.2% women; 42.1% blacks). CAC score was non-zero in 38.2% of the participants. Over a median follow-up of 8.5 years, 910 incident CVD events occurred. Compared to those with zero CAC, participants with non-zero CAC score had a higher CVD incidence rate (per 1000 person-years) at all BP levels (elevated BP/low-risk stage 1 HTN: 14.5 vs 2.7; high-risk stage 1 or stage 2 HTN: 27.1 vs 8.8). Multivariable adjusted hazards of adverse CVD events displayed similar patterns ( Figure ). Among those with zero CAC, the 10-year number needed to treat to prevent 1 CVD event was 154 for those with elevated BP/low-risk stage 1 HTN and 47 for those with high-risk stage 1 or stage 2 HTN. Among those with non-zero CAC score, the number needed to treat was lower, 33 and 18 respectively. Conclusions: Utilization of CAC score may be an effective precision medicine approach to personalize HTN therapy in elevated BP or low-risk stage 1 HTN when treatment is not recommended by the current guidelines.
Transcriptome Analysis in Yeast Reveals the Externality of Position Effects
Authors: Qian Gui, Shuyun Deng, ZhenZhen Zhou, Waifang Cao, Xin Zhang, Wenjun Shi, Xiujuan Cai, Wenbing Jiang, Zifeng Cui, Zheng Hu, Xiaoshu Chen
Journal: Molecular Biology and Evolution (2021)

The activity of a gene newly integrated into a chromosome depends on the genomic context of the integration site. This "position effect" has been widely reported, although the other side of the coin, that is, how integration affects the local chromosomal environment, has remained largely unexplored, as have the mechanism and phenotypic consequences of this "externality" of the position effect. Here, we examined the transcriptome profiles of approximately 250 Saccharomyces cerevisiae strains, each with GFP integrated into a different locus of the wild-type strain. We found that in genomic regions enriched in essential genes, GFP expression tended to be lower, and the genes near the integration site tended to show greater expression reduction. Further joint analysis with public genome-wide histone modification profiles indicated that this effect was associated with H3K4me2. More importantly, we found that changes in the expression of neighboring genes, but not GFP expression, significantly altered the cellular growth rate. As a result, genomic loci that showed high GFP expression immediately after integration were associated with growth disadvantages caused by elevated expression of neighboring genes, ultimately leading to a low total yield of GFP in the long run. Our results were consistent with competition for transcriptional resources among neighboring genes and revealed a previously unappreciated facet of position effects. This study highlights the impact of position effects on the fate of exogenous gene integration and has significant implications for biological engineering and the pathology of viral integration into the host genome.
NHS waiting list hits 14 year record high of 4.7 million people
Authors: Adrian O’Dowd
Journal: BMJ (2021)

Pressure is growing on the government to take urgent steps to tackle waiting time figures for the almost five million people seeking hospital treatment in England—a number that has reached a record high.

The latest referral to treatment statistics1 from NHS England published on 15 April show that 4.7 million people were waiting to begin treatment at the end of February this year—the highest number since records began in 2007. Of those 4.7 million people, 387 885 patients were waiting more than 52 weeks for routine operations and procedures, which was an increase from 224 205 in December 2020. It is also the highest number since December 2007. …
Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial
Authors: Jesse Dawson, Charles Y Liu, Gerard E Francisco, Steven C Cramer, Steven L Wolf, Anand Dixit, Jen Alexander, Rushna Ali, Benjamin L Brown, Wuwei Feng, Louis DeMark, Leigh R Hochberg, Steven A Kautz, Arshad Majid, Michael W O'Dell, David Pierce, Cecília N Prudente, Jessica Redgrave, Duncan L Turner, Navzer D Engineer, Teresa J Kimberley
Journal: The Lancet (2021)