tbuckley/cabot-search huggingface dataset:
Establishing a novel colorectal cancer predictive model based on unique gut microbial single nucleotide variant markers
Authors: Chenchen Ma, Kaining Chen, Yuanyuan Wang, Chaoping Cen, Qixiao Zhai, Jiachao Zhang
Journal: Gut Microbes (2021)

Current metagenomic species-based colorectal cancer (CRC) microbial biomarkers may confuse diagnosis because the genetic content of different microbial strains, even those belonging to the same species, may differ from 5% to 30%. Here, a total of 7549 non-redundant single nucleotide variants (SNVs) were annotated in 25 species from 3 CRC cohorts (n = 249). Then, 22 microbial SNV markers that contributed to distinguishing subjects with CRC from healthy subjects were identified by the random forest algorithm to construct a novel CRC predictive model. Excitingly, the predictive model showed high accuracy both in the training (AUC = 75.35%) and validation cohorts (AUC = 73.08%-88.02%). We further explored the specificity of these SNV markers in a broader background by performing a meta-analysis across 4 metabolic disease cohorts. Among these SNV markers, 3 SNVs that were enriched in CRC patients and located in the genomes of Eubacterium rectale and Faecalibacterium prausnitzii were CRC specific (AUC = 72.51%-94.07%).
Right Heart Score for Predicting Outcome in Idiopathic, Familial, or Drug- and Toxin-Associated Pulmonary Arterial Hypertension
Authors: François Haddad, Onno A. Spruijt, Andre Y. Denault, Olaf Mercier, Nathan Brunner, David Furman, Elie Fadel, Harm J. Bogaard, Ingela Schnittger, Bojan Vrtovec, Joseph C. Wu, Vinicio de Jesus Perez, Anton Vonk-Noordegraaf, Roham T. Zamanian
Journal: JACC. Cardiovascular imaging (2015)
Abstract 16969: Burden of Cardiovascular Disease, ECG Patterns and Echocardiographic Data Among COVID-19 Survivors and Non-Survivors at a Large Health System in New York
Authors: Arvind Devanabanda, Eitezaz Mahmood, Avneet SINGH, Perwaiz Meraj, Haisam Ismail, rajiv jauhar
Journal: Circulation (2020)

Introduction: The prognostic importance of cardiac and metabolic risk factors among COVID-19 patients is unknown. The aim of our investigation is to report clinical significance of risk factors, ECG patterns, inflammatory markers and LVEF for survival with COVID-19. Methods: 10,018 patients and ECGs, from 13 hospitals in New York City area were included in this retrospective analysis between March 1 and April 30, 2020. Survivors and non-survivors were studied for presence of comorbidities and clinical outcomes of length of stay (LOS), ICU stay, ventilator use, inotrope use and pressor use. Differences between the groups were compared with the Student t test. Results: There were 7,837 survivors and 2,181 non-survivors. Table shows more patients with age &gt; 65 died. Hypertension, diabetes, obesity, coronary artery disease, heart failure and peripheral vascular disease, COPD, chronic kidney disease were significantly elevated in non-survivors. Admission Inflammatory markers were significantly elevated in non-survivors. Significantly increased ECG intervals of QRS, QTc, atrial fibrillation, atrial flutter, and bundle branch block were noted in non-survivors. LVEF &lt; 40% was significantly higher in non-survivors. ICU stay, LOS, pressor use and ventilator use were significantly elevated in non-survivors. Conclusions: More patients with age &gt; 65 were survivors. Among non-survivors, cardiac, metabolic comorbidities, burden of atrial arrhythmias, admission inflammatory markers, LVEF&lt; 40%, and clinical outcomes were significantly worse.
Idiopathic pulmonary fibrosis: prime time for a precision-based approach to treatment with <i>N</i>-acetylcysteine
Authors: Anna J. Podolanczuk, Imre Noth, Ganesh Raghu
Journal: European Respiratory Journal (2021)

Oxidative stress, the total sum of molecular and cellular processes that result from excess oxidant production and antioxidant depletion, has long been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF) [1, 2]. Bronchoalveolar lavage fluid from patients with IPF exhibits enhanced oxidative activity, and high levels of the oxidants hydrogen peroxide, superoxide and hydroxyl radicals induce injury to alveolar epithelial cells [3]. At the same time, glutathione levels are depleted in the lower respiratory tract of IPF patients compared to healthy subjects and correlate with disease severity [4, 5]. Excess production of reactive oxygen species in IPF occurs in activated inflammatory and alveolar epithelial cells through induction of NADPH oxidase, endoplasmic reticulum stress and uncoupling of the mitochondrial electron transport chain [2]. Exogenous oxidants from cigarette smoke, occupational exposure, air pollution and others further augment the oxidant burden in the lungs of people genetically predisposed to IPF [1]. Increased oxidative stress leads to DNA damage, alveolar epithelial cell apoptosis, release of pro-fibrotic cytokines and activation of matrix metalloproteinases, promoting myofibroblast proliferation and extracellular matrix remodelling (figure 1). Transforming growth factor β inhibits glutathione synthesis in a positive feedback loop, leading to ongoing cellular damage. Prime time for a precision-based approach for treatment of idiopathic pulmonary fibrosis with an antioxidant, N -acetylcysteine <https://bit.ly/30gl9vG> The authors would like to thank Fernando J. Martinez, Gregory Cosgrove and Kevin Flaherty for their input.
Effect of Machine Learning on Dispatcher Recognition of Out-of-Hospital Cardiac Arrest During Calls to Emergency Medical Services
Authors: Stig Nikolaj Blomberg, Helle Collatz Christensen, Freddy Lippert, Annette Kjær Ersbøll, Christian Torp-Petersen, Michael R. Sayre, Peter J. Kudenchuk, Fredrik Folke
Journal: JAMA Network Open (2021)

Emergency medical dispatchers fail to identify approximately 25% of cases of out-of-hospital cardiac arrest (OHCA), resulting in lost opportunities to save lives by initiating cardiopulmonary resuscitation.To examine how a machine learning model trained to identify OHCA and alert dispatchers during emergency calls affected OHCA recognition and response.This double-masked, 2-group, randomized clinical trial analyzed all calls to emergency number 112 (equivalent to 911) in Denmark. Calls were processed by a machine learning model using speech recognition software. The machine learning model assessed ongoing calls, and calls in which the model identified OHCA were randomized. The trial was performed at Copenhagen Emergency Medical Services, Denmark, between September 1, 2018, and December 31, 2019.Dispatchers in the intervention group were alerted when the machine learning model identified out-of-hospital cardiac arrest, and those in the control group followed normal protocols without alert.The primary end point was the rate of dispatcher recognition of subsequently confirmed OHCA.A total of 169 049 emergency calls were examined, of which the machine learning model identified 5242 as suspected OHCA. Calls were randomized to control (2661 [50.8%]) or intervention (2581 [49.2%]) groups. Of these, 336 (12.6%) and 318 (12.3%), respectively, had confirmed OHCA. The mean (SD) age among of these 654 patients was 70 (16.1) years, and 419 of 627 patients (67.8%) with known gender were men. Dispatchers in the intervention group recognized 296 confirmed OHCA cases (93.1%) with machine learning assistance compared with 304 confirmed OHCA cases (90.5%) using standard protocols without machine learning assistance (P = .15). Machine learning alerts alone had a significantly higher sensitivity than dispatchers without alerts for confirmed OHCA (85.0% vs 77.5%; P < .001) but lower specificity (97.4% vs 99.6%; P < .001) and positive predictive value (17.8% vs 55.8%; P < .001).This randomized clinical trial did not find any significant improvement in dispatchers' ability to recognize cardiac arrest when supported by machine learning even though artificial intelligence did surpass human recognition.ClinicalTrials.gov Identifier: NCT04219306.
Genetic screening for single-cell variability modulators driving therapy resistance
Authors: Eduardo A. Torre, Eri Arai, Sareh Bayatpour, Connie L. Jiang, Lauren E. Beck, Benjamin L. Emert, Sydney M. Shaffer, Ian A. Mellis, Mitchell E. Fane, Gretchen M. Alicea, Krista A. Budinich, Ashani T. Weeraratna, Junwei Shi, Arjun Raj
Journal: Nature Genetics (2021)
When Two Tests Are Better Than One: Adding Late Gadolinium Enhancement to First-Pass Perfusion Cardiovascular Magnetic Resonance⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Christopher M. Kramer
Journal: Journal of the American College of Cardiology (2006)
Assessment of Prescription Opioid Medical Use and Misuse Among Parents and Their Adolescent Offspring in the US
Authors: Pamela C. Griesler, Mei-Chen Hu, Melanie M. Wall, Denise B. Kandel
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Limited information is available regarding the association between parental and adolescent medical prescription opioid use and misuse in the US. <h3>Objective</h3> To examine the associations between parental and adolescent prescription opioid medical use and misuse. <h3>Design, Setting, and Participants</h3> This cross-sectional, nationally representative study included 15 200 parent-adolescent dyads from the annual 2015-2017 National Survey on Drug Use and Health. Data were collected from January 6, 2015, to December 20, 2017, and analyzed from October 4, 2019, to October 15, 2020. <h3>Exposures</h3> Parental past 12-month exclusive medical prescription opioid use and any misuse (ie, using without a prescription or in any way not directed by a physician). <h3>Main Outcomes and Measures</h3> Adolescent past 12-month medical prescription opioid use or misuse. Multivariable regressions estimated associations between parental and offspring medical prescription opioid use or misuse, controlling for sociodemographic and psychosocial variables. <h3>Results</h3> Respondents included 9400 mother-child and 5800 father-child dyads in the same household; children were aged 12 to 17 years (52.8% male; mean [SD] age, 14.5 [1.7] years). Controlling for other factors, parental medical prescription opioid use was associated with adolescent prescription opioid medical use (adjusted odds ratio [aOR], 1.28; 95% CI, 1.06-1.53) and misuse (aOR, 1.53; 95% CI, 1.07-2.25), whereas parental misuse was not. Parental medical prescription stimulant use was associated with adolescent medical prescription opioid use (aOR, 1.40; 95% CI, 1.02-1.91). Parental marijuana use (aOR, 1.84; 95% CI, 1.13-2.99), parent-adolescent conflict (aOR, 1.26; 95% CI, 1.05-1.52), and adolescent depression (aOR, 1.75; 95% CI, 1.26-2.44) were associated with adolescent prescription opioid misuse. Adolescent delinquency (aOR, 1.55; 95% CI, 1.38-1.74) and perceived schoolmates' drug use (aOR, 2.87; 95% CI, 1.95-4.23) were also associated with adolescent misuse and more weakly with medical use (aORs, 1.13 [95% CI, 1.05-1.22] and 1.61 [95% CI, 1.32-1.96], respectively). <h3>Conclusions and Relevance</h3> Youth use of prescription opioids is in part a structural/environmental issue. The findings of this study suggest that parental medical prescription opioid use is associated with offspring prescription opioid use, whereas parental misuse is not. Restricting physicians' opioid prescribing to parents is a crucial public health goal. In addition, parents could be educated on the risks of their prescription opioid use for offspring and on practices to mitigate risk, including safe medication storage and disposal. Screening for parental prescription opioid use could be part of pediatric practice. Addressing adolescent mental health could also reduce adolescent prescription opioid misuse.
Functional lower airways genomic profiling of the microbiome to capture active microbial metabolism
Authors: Imran Sulaiman, Benjamin G. Wu, Yonghua Li, Jun-Chieh Tsay, Maya Sauthoff, Adrienne S. Scott, Kun Ji, Sergei B. Koralov, Michael Weiden, Jose C. Clemente, Drew Jones, Yvonne J. Huang, Kathleen A. Stringer, Lingdi Zhang, Adam Geber, Stephanie Banakis, Laura Tipton, Elodie Ghedin, Leopoldo N. Segal
Journal: European Respiratory Journal (2021)

Background Microbiome studies of the lower airways based on bacterial 16S rRNA gene sequencing assess microbial community structure but can only infer functional characteristics. Microbial products, such as short-chain fatty acids (SCFAs), in the lower airways have significant impact on the host's immune tone. Thus, functional approaches to the analyses of the microbiome are necessary. Methods Here we used upper and lower airway samples from a research bronchoscopy smoker cohort. In addition, we validated our results in an experimental mouse model. We extended our microbiota characterisation beyond 16S rRNA gene sequencing with the use of whole-genome shotgun (WGS) and RNA metatranscriptome sequencing. SCFAs were also measured in lower airway samples and correlated with each of the sequencing datasets. In the mouse model, 16S rRNA gene and RNA metatranscriptome sequencing were performed. Results Functional evaluations of the lower airway microbiota using inferred metagenome, WGS and metatranscriptome data were dissimilar. Comparison with measured levels of SCFAs shows that the inferred metagenome from the 16S rRNA gene sequencing data was poorly correlated, while better correlations were noted when SCFA levels were compared with WGS and metatranscriptome data. Modelling lower airway aspiration with oral commensals in a mouse model showed that the metatranscriptome most efficiently captures transient active microbial metabolism, which was overestimated by 16S rRNA gene sequencing. Conclusions Functional characterisation of the lower airway microbiota through metatranscriptome data identifies metabolically active organisms capable of producing metabolites with immunomodulatory capacity, such as SCFAs.
Advances in pathogenesis and precision medicine for nasopharyngeal carcinoma
Authors: Qian‐Ying Zhu, Ge‐Xin Zhao, Yan Li, Girish Talakatta, Hai‐Qiang Mai, Quynh‐Thu Le, Lawrence S. Young, Mu‐Sheng Zeng
Journal: MedComm (2021)

Nasopharyngeal carcinoma (NPC) is a squamous carcinoma with apparent geographical and racial distribution, mostly prevalent in East and Southeast Asia, particularly concentrated in southern China. The epidemiological trend over the past decades has suggested a substantial reduction in the incidence rate and mortality rate due to NPC. These results may reflect changes in lifestyle and environment, and more importantly, a deeper comprehension of the pathogenic mechanism of NPC, leading to much progress in the preventing, screening, and treating for this cancer. Herein, we present the recent advances on the key signal pathways involved in pathogenesis of NPC, the mechanism of Epstein-Barr virus (EBV) entry into the cell, and the progress of EBV vaccine and screening biomarkers. We will also discuss in depth the development of various therapeutic approaches including radiotherapy, chemotherapy, surgery, targeted therapy, and immunotherapy. These research advancements have led to a new era of precision medicine in NPC.
Latent tuberculosis infection prevalence in second generation immigrants from high to low TB burden countries
Authors: D. Shlomi, I. Galor, A. More, B. Oberman, L. Fireman
Journal: Pulmonology (2021)

Latent tuberculosis infection (LTBI) diagnosis in a country with a low tuberculosis burden is complicated. Since the prevalence of LTBI in second generation immigrants has not been well recognized, we conducted a cross-sectional study which aimed to explore the differences in LTBI prevalence between offspring of immigrants from high tuberculosis (TB) burden countries and those whose parents were born in countries with a low TB burden.Between May 2014 and April 2018 young native Israelis who were required to perform pre-occupational tuberculin skin tests (TST) (medical and paramedical personnel or teaching assistants of immigrants from high TB burden countries) and who had a TST result of 10mm and above were tested for QuantiFERON-TB In Tube (QFT-GIT). Statistical comparisons were made between second generation immigrants and those with both parents from a low TB burden country.Of 102 patients, 71 were born to parents both of whom were from low-risk countries, 14 to one parent from a high-risk country and 17 to parents both of whom were from a high-risk country. The odds ratio for LTBI was 4.5 (95% CI, 1.2...17.2; p=0.03) if both parents were born in a high-risk country compared to both parents being from a low-risk country and 4.01 (95% CI, 1.12...14.3; p=0.03) higher compared to persons for whom at least one parent was born in a low-risk country.The risk for latent TB is significantly higher in second generation immigrants if both parents were born in a high-risk country. IGRA should be considered before treatment to patients with a positive TST if at least one parent was born in a low-risk country in order to confirm LTBI.
Th1 cytokine interferon gamma improves response in HER2 breast cancer by modulating the ubiquitin proteasomal pathway
Authors: Yongsheng Jia, Krithika N. Kodumudi, Ganesan Ramamoorthi, Amrita Basu, Colin Snyder, Doris Wiener, Shari Pilon-Thomas, Payal Grover, Hongtao Zhang, Mark I. Greene, Qianxing Mo, Zhongsheng Tong, Yong-Zi Chen, Ricardo L.B. Costa, Hyo Han, Catherine Lee, Hatem Soliman, Jose R. Conejo-Garcia, Gary Koski, Brian J. Czerniecki
Journal: Molecular Therapy (2021)

HER2 breast cancer (BC) remains a significant problem in patients with locally advanced or metastatic BC. We investigated the relationship between T helper 1 (Th1) immune response and the proteasomal degradation pathway (PDP), in HER2-sensitive and -resistant cells. HER2 overexpression is partially maintained because E3 ubiquitin ligase Cullin5 (CUL5), which degrades HER2, is frequently mutated or underexpressed, while the client-protective co-chaperones cell division cycle 37 (Cdc37) and heat shock protein 90 (Hsp90) are increased translating to diminished survival. The Th1 cytokine interferon (IFN)-γ caused increased CUL5 expression and marked dissociation of both Cdc37 and Hsp90 from HER2, causing significant surface loss of HER2, diminished growth, and induction of tumor senescence. In HER2-resistant mammary carcinoma, either IFN-γ or Th1-polarizing anti-HER2 vaccination, when administered with anti-HER2 antibodies, demonstrated increased intratumor CUL5 expression, decreased surface HER2, and tumor senescence with significant therapeutic activity. IFN-γ synergized with multiple HER2-targeted agents to decrease surface HER2 expression, resulting in decreased tumor growth. These data suggest a novel function of IFN-γ that regulates HER2 through the PDP pathway and provides an opportunity to impact HER2 responses through anti-tumor immunity.
Analytical and clinical performance of the panbio COVID-19 antigen-detecting rapid diagnostic test
Authors: Andrea Alemany, Bàrbara Baró, Dan Ouchi, Pau Rodó, Maria Ubals, Marc Corbacho-Monné, Júlia Vergara-Alert, Jordi Rodon, Joaquim Segalés, Cristina Esteban, Gema Fernández, Lidia Ruiz, Quique Bassat, Bonaventura Clotet, Jordi Ara, Martí Vall-Mayans, Camila G-Beiras, Ignacio Blanco, Oriol Mitjà
Journal: Journal of Infection (2021)
Acute coronary syndromes: summary of updated NICE guidance
Authors: Simon J Corbett, Saoussen Ftouh, Sedina Lewis, Kate Lovibond
Journal: BMJ (2021)

### What you need to know

Acute coronary syndromes (ACS), comprising ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina, are an important cause of morbidity and mortality in the UK and worldwide.1 The National Institute for Health and Care Excellence (NICE) previously published four guidelines to improve care for people in the UK who have had an ACS.2345 In 2018, NICE identified eight key areas of clinical practice across all aspects of existing ACS guidelines that should be reviewed for update on the basis of new evidence and stakeholder feedback (box 1).

Box 1 
### Clinical areas updated in the NICE guideline on acute coronary syndromes (NG185)RETURN TO TEXT

Rather than individually updating the four existing ACS guidelines, all four guidelines have been incorporated into one overarching updated guideline covering all aspects …
Association of Higher Hydroxychloroquine Blood Levels With Reduced Thrombosis Risk in Systemic Lupus Erythematosus
Authors: Michelle Petri, Maximilian F. Konig, Jessica Li, Daniel W. Goldman
Journal: Arthritis & Rheumatology (2021)

Objective Hydroxychloroquine (HCQ) has a primary role in the prophylaxis and treatment of systemic lupus erythematosus (SLE) and may be protective against thrombosis in SLE. Optimal weight‐based dosing of HCQ is unknown. This study was undertaken to examine the usefulness of HCQ blood monitoring in predicting thrombosis risk in a longitudinal SLE cohort. Methods HCQ levels were serially quantified from EDTA whole blood by liquid chromatography–tandem mass spectrometry. The mean HCQ blood levels calculated prior to thrombosis or until the last visit were compared using t ‐tests between patients with and those without thrombosis. Pooled logistic regression was used to analyze the association between rates of thrombosis and HCQ blood level. Rate ratios (RRs) and 95% confidence intervals (95% CIs) were calculated. Results In 739 patients with SLE, thrombosis occurred in 38 patients (5.1%). The mean ± SD HCQ blood level was lower in patients who developed thrombosis versus those who did not develop thrombosis (720 ± 489 ng/ml versus 935 ± 580 ng/ml; P = 0.025). Thrombosis rates were reduced by 13% for every 200‐ng/ml increase in the most recent HCQ blood level (RR 0.87 [95% CI 0.78–0.98], P = 0.025) and by 13% for mean HCQ blood level (RR 0.87 [95% CI 0.76–1.00], P = 0.056). Thrombotic events were reduced by 69% in patients with mean HCQ blood levels ≥1,068 ng/ml versus those with levels &lt;648 ng/ml (RR 0.31 [95% CI 0.11–0.86], P = 0.024). This remained significant after adjustment for confounders (RR 0.34 [95% CI 0.12–0.94], P = 0.037). Conclusion Low HCQ blood levels are associated with thrombotic events in SLE. Longitudinal measurement of HCQ levels may allow for personalized HCQ dosing strategies. Recommendations for empirical dose reduction may reduce or eliminate the benefits of HCQ in this high‐risk population.
Novel MSX1 variants identified in families with nonsyndromic oligodontia
Authors: Jinglei Zheng, Miao Yu, Haochen Liu, Tao Cai, Hailan Feng, Yang Liu, Dong Han
Journal: International Journal of Oral Science (2021)

Abstract The goal of this study was to identify MSX1 gene variants in multiple Chinese families with nonsyndromic oligodontia and analyse the functional influence of these variants. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify the causal gene variants in five families with nonsyndromic oligodontia, and a series of bioinformatics databases were used for variant confirmation and functional prediction. Phenotypic characterization of the members of these families was described, and an in vitro analysis was performed for functional evaluation. Five novel MSX1 heterozygous variants were identified: three missense variants [c.662A&gt;C (p.Q221P), c.670C&gt;T (p.R224C), and c.809C&gt;T (p.S270L)], one nonsense variant [c.364G&gt;T (p.G122*)], and one frameshift variant [c.277delG (p.A93Rfs*67)]. Preliminary in vitro studies demonstrated that the subcellular localization of MSX1 was abnormal with the p.Q221P, p.R224C, p.G122*, and p.A93Rfs*67 variants compared to the wild type. Three variants (p.Q221P, p.G122*, and p.A93Rfs*67) were classified as pathogenic or likely pathogenic, while p.S270L and p.R224C were of uncertain significance in the current data. Moreover, we summarized and analysed the MSX1 -related tooth agenesis positions and found that the type and variant locus were not related to the severity of tooth loss. Our results expand the variant spectrum of nonsyndromic oligodontia and provide valuable information for genetic counselling.