tbuckley/cabot-search huggingface dataset:
Management of non-alcoholic fatty liver disease
Authors: Maria Letizia Petroni, Lucia Brodosi, Elisabetta Bugianesi, Giulio Marchesini
Journal: BMJ (2021)

ABSTRACT Non-alcoholic fatty liver disease is a very common medical condition, driven by a combination of genetic and lifestyle factors, ultimately producing a severe chronic liver disease and increased cardiovascular risk. Most people are asymptomatic for a long time, and their daily life is unaffected, leading to difficulty in identifying and managing people who slowly progress to non-alcoholic steatohepatitis (NASH), NASH-cirrhosis, and eventually hepatocellular carcinoma. Despite advances in the understanding of pathogenic mechanisms and the identification of liver fibrosis as the strongest factor in predicting disease progression, no specific treatments have been approved by regulatory agencies. Outside controlled trials, treatment is generally limited to lifestyle intervention aimed at weight loss. Pioglitazone remains the drug of choice to reduce progression of fibrosis in people with diabetes, although it is often used off-label in the absence of diabetes. Vitamin E is mainly used in children and may be considered in adults without diabetes. Several drugs are under investigation according to the agreed targets of reduced NASH activity without worsening of fibrosis or improving fibrosis without worsening of NASH. Anti-inflammatory, anti-fibrotic agents and metabolism modulators have been tested in either phase III or phase IIb randomized controlled trials; a few failed, and others have produced marginally positive results, but only a few are being tested in extension studies. The development of non-invasive, easily repeatable surrogate biomarkers and/or imaging tools is crucial to facilitate clinical studies and limit liver biopsy.
YTHDF1 Regulates Pulmonary Hypertension through Translational Control of MAGED1
Authors: Li Hu, Jie Wang, Huijie Huang, Yanfang Yu, Jingjing Ding, Youjia Yu, Kai Li, Dong Wei, Qing Ye, Fangzhu Wang, Bin Shen, Jingyu Chen, David J. R. Fulton, Feng Chen
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Posttranscriptional modifications are implicated in vascular remodeling of pulmonary hypertension (PH). m6A (N6-methyladenosine) is an abundant RNA modification that is involved in various biological processes. Whether m6A RNA modification and m6A effector proteins play a role in pulmonary vascular remodeling and PH has not been demonstrated.Objectives: To determine whether m6A modification and m6A effectors contribute to the pathogenesis of PH.Methods: m6A modification and YTHDF1 expression were measured in human and experimental PH samples. RNA immunoprecipitation analysis and m6A sequencing were employed to screen m6A-marked transcripts. Genetic approaches were employed to assess the respective roles of YTHDF1 and MAGED1 in PH. Primary cell isolation and cultivation were used for function analysis of pulmonary artery smooth muscle cells (PASMCs).Measurements and Main Results: Elevated m6A levels and increased YTHDF1 protein expression were found in human and rodent PH samples as well as in hypoxic PASMCs. The deletion of YTHDF1 ameliorated PASMC proliferation, phenotype switch, and PH development both in vivo and in vitro. m6A RNA immunoprecipitation analysis identified MAGED1 as an m6A-regulated gene in PH, and genetic ablation of MAGED1 improved vascular remodeling and hemodynamic parameters in SU5416/hypoxia mice. YTHDF1 recognized and promoted translation of MAGED1 in an m6A-dependent manner that was absent in METTL3-deficient PASMCs. In addition, MAGED1 silencing inhibited hypoxia-induced proliferation of PASMCs through downregulating PCNA.Conclusions: YTHDF1 promotes PASMC proliferation and PH by enhancing MAGED1 translation. This study identifies the m6A RNA modification as a novel mediator of pathological changes in PASMCs and PH.
Urgent needs of low-income and middle-income countries for COVID-19 vaccines and therapeutics
Authors: J Peter Figueroa, Maria Elena Bottazzi, Peter Hotez, Carolina Batista, Onder Ergonul, Sarah Gilbert, Mayda Gursel, Mazen Hassanain, Jerome H Kim, Bhavna Lall, Heidi Larson, Denise Naniche, Timothy Sheahan, Shmuel Shoham, Annelies Wilder-Smith, Natalie Strub-Wourgaft, Prashant Yadav, Gagandeep Kang
Journal: The Lancet (2021)

WHO and partners have learnt from the mis-steps in the response to the 2009 H1N1 influenza pandemic1 and established the Access to COVID-19 Tools (ACT) Accelerator to promote equitable access to vaccines, therapeutics, and diagnostics.2 However, many high-income countries already have bilateral agreements with manufacturers of COVID-19 vaccines.3 The COVAX Facility of the ACT Accelerator has agreements to access 2 billion doses of WHO pre-qualified vaccines during 2021, but this represents only 20% of the vaccine needs of participating countries.
Noninvasive Detection of Vulnerable Coronary Plaques: Locking the Barn Door Before the Horse Is Stolen⁎⁎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: Eugene Braunwald
Journal: Journal of the American College of Cardiology (2009)
High-Density, Targeted Monitoring of Tyrosine Phosphorylation Reveals Activated Signaling Networks in Human Tumors
Authors: Lauren E. Stopfer, Cameron T. Flower, Aaron S. Gajadhar, Bhavin Patel, Sebastien Gallien, Daniel Lopez-Ferrer, Forest M. White
Journal: Cancer Research (2021)

Tyrosine phosphorylation (pTyr) plays a pivotal role in signal transduction and is commonly dysregulated in cancer. As a result, profiling tumor pTyr levels may reveal therapeutic insights critical to combating disease. Existing discovery and targeted mass spectrometry-based methods used to monitor pTyr networks involve a tradeoff between broad coverage of the pTyr network, reproducibility in target identification across analyses, and accurate quantification. To address these limitations, we developed a targeted approach, termed "SureQuant pTyr," coupling low input pTyr enrichment with a panel of isotopically labeled internal standard peptides to guide data acquisition of low-abundance tyrosine phosphopeptides. SureQuant pTyr allowed for reliable quantification of several hundred commonly dysregulated pTyr targets with high quantitative accuracy, improving the robustness and usability of targeted mass spectrometry assays. We established the clinical applicability of SureQuant pTyr by profiling pTyr signaling levels in human colorectal tumors using minimal sample input, characterizing patient-specific oncogenic-driving mechanisms. While in some cases pTyr profiles aligned with previously reported proteomic, genomic, and transcriptomic molecular characterizations, we highlighted instances of new insights gained using pTyr characterization and emphasized the complementary nature of pTyr measurements with traditional biomarkers for improving patient stratification and identifying therapeutic targets. The turn-key nature of this approach opens the door to rapid and reproducible pTyr profiling in research and clinical settings alike and enables pTyr-based measurements for applications in precision medicine. SIGNIFICANCE: SureQuant pTyr is a mass spectrometry-based targeted method that enables sensitive and selective targeted quantitation of several hundred low-abundance tyrosine phosphorylated peptides commonly dysregulated in cancer, including oncogenic signaling networks.
Optimization of skin testing
Authors: N. R. Niemeijer, A. F. Fluks, J. G. R. de Monchy
Journal: Allergy (1993)

In this multicenter study we evaluated the results of a previous study (part I) in a relatively large Dutch patient population, using the two previously tested allergens (house-dust mite and grass pollen) and two other standardized allergens (tree pollen and cat dander). The obtained skin test results were expressed as a histamine ratio and compared with RAST and clinical history (CH). The sensitivity and specificity were calculated at different cutoff values of the skin tests. The optimum cutoff values of 0.7 intracutaneous tests (ICT) and 0.4 skin prick tests (SPT) resulted in a predictive value for the detection of allergic sensitization of 83% (RAST) and 77% (CH), and 91% (RAST) and 86% (CH), for the ICT and SPT, respectively. As the ICT and SPT were performed in different centers, the results of these methods cannot be compared. No systemic side-effects of the skin tests were recorded. These results generally correspond well with the predictions regarding safety and predictive value of part I of this study, in which a limited number of patients was studied. In conclusion, through the use of a limited number of standardized allergens in a small group of patients, it may be possible to predict a safe and efficacious concentration for routine skin testing and to extrapolate from these results to other standardized allergens.
The immune checkpoint CD73 (NT5E) in gastric adenocarcinoma (GAC): Biological characterization and clinical implications.
Authors: Massimiliano Salati, Andrea Spallanzani, Fabio Gelsomino, Andrea Botticelli, Bruna Cerbelli, Laura Riggi, Alessandro Bocconi, Raffaella D'Onofrio, Stefania Benatti, Gabriele Luppi, Massimo Dominici
Journal: Journal of Clinical Oncology (2021)

235 Background: CD73, an ecto-5’-nucleotidase (NT5E), serves as an immune checkpoint by generating adenosine, which in turn leads to immune-suppression and immune-escape. Elevated tissue levels of CD73 have been linked to poor patient survival across several cancer types and CD73 blockade is currently being tested in clinical trials. The biological role of CD73 and its translational relevance is largely unexplored in gastric adenocarcinoma (GAC). Methods: Data mining from transcriptomics big data sources including GEPIA2, HPA and Coexpedia platforms was performed to extract relevant information regarding CD73 expression profile, co-expressed network, association with clinico-pathologic features and survival of GAC. Difference between groups were evaluated by Student's t-test, while correlation analysis was performed through Pearson’s coefficient. Kaplan-Meier methods was used to estimate survival and log-rank test to make comparison between curves. Results: RNA sequencing expression data of 9,736 tumors and 8,587 normal tissue samples from the TCGA and the GTEx projects were analyzed. CD73 mRNA was significantly more expressed in tumour (n = 408) compared to paired normal samples (n = 211) (16.19 vs 3.5 transcripts/million; p &lt; 0.001) and its expression level increased with pathologic stage (from stage I to III). CD73 gene was listed among the top-ten survival-associated genes (p = 4.74e-5) in GAC and together with FGF1 it displayed the greatest survival contribution in this disease among clinically validated genes. Regarding its impact on survival, GAC patients with high CD73 expression (n = 192) experienced a poorer overall survival (OS) compared to the low CD73 group (n = 192) (HR 1.9; log-rank p &lt; 0.001), while regarding relapse-free survival (RFS), the unfavourable value of CD73 expression emerged after 20 months (HR 1.3; log-rank p = 0.23). The prognostic role on OS was validated in a cohort of 354 GAC, where high CD73 expression resulted in 5-year OS of 19% vs 46% (p = 0.00010). When inquiring for context-associated co-expression networks, Caveolin 1 (score = 10.939), FOS-like antigen 1 (score = 7.525) and plasminogen activator urokinase receptor (score = 7.422) were top-ranked co-expressed genes. Conclusions: In this hypothesis-generating analysis, we provided insights into CD73 expression pattern, co-expression networking and prognostic significance in GAC. Future studies in clinically annotated populations are warranted to confirm the value of CD73 in GAC.
Screening for Rheumatic Heart Disease—Quo Vadis?
Authors: Kumar Narayanan, Xavier Jouven, Eloi Marijon
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Aspirin in the Prevention of Cardiovascular Disease and Cancer
Authors: Emanuela Ricciotti, Garret A. FitzGerald
Journal: Annual Review of Medicine (2021)

More than a century after its synthesis, daily aspirin, given at a low dose, is a milestone treatment for the secondary prevention of cardiovascular disease (CVD). Its role in primary prevention of CVD is still debated. Older randomized controlled trials showed that aspirin reduced the low incidence of myocardial infarction but correspondingly increased the low incidence of serious gastrointestinal bleeds without altering mortality. More recent trials see the benefit attenuated, perhaps obscured by other cardioprotective practices, while the bleeding risk remains, especially in older patients. Indirect evidence, both preclinical and clinical, suggests that aspirin may protect against sporadic colorectal cancer and perhaps other cancers. However, further studies are still necessary to warrant the consumption of aspirin for primary prevention of CVD and cancer by apparently healthy individuals.
Evaluation of Ruxolitinib for Steroid-Refractory Chronic Graft-vs-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Hengwei Wu, Jimin Shi, Yi Luo, Yamin Tan, Mingming Zhang, Xiaoyu Lai, Jian Yu, Lizhen Liu, Huarui Fu, He Huang, Yanmin Zhao
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Ruxolitinib, a selective inhibitor of the Janus kinases 1/2 signaling pathway, has shown a significant response in steroid-refractory chronic graft-vs-host disease (SR-cGVHD), a major cause of morbidity and mortality in individuals who have undergone allogeneic hematopoietic stem cell transplantation (HSCT). <h3>Objectives</h3> To investigate the clinical response to ruxolitinib in patients with SR-cGVHD after allogeneic HSCT and to evaluate its safety profile during the treatment course. <h3>Design, Setting, and Participants</h3> This single-center case series included 41 consecutive patients who were treated with ruxolitinib for SR-cGVHD after allogeneic HSCT between August 2017 and December 2019. Data were collected from each patient's medical record at the First Affiliated Hospital of Zhejiang University School of Medicine. Data analysis was conducted from March to May 2020. <h3>Exposure</h3> Ruxolitinib. <h3>Main Outcomes and Measures</h3> Treatment responses, factors associated with response, and adverse effects during ruxolitinib administration. <h3>Findings</h3> Overall, 41 patients (median [range] age, 31 [17-56] years; 14 [34.1%] women) were treated with ruxolitinib and included in this study. A total of 15 patients (36.6%) had a complete remission, and 14 (34.1%) had a partial remission, with an overall response rate of 70.7% (29 patients; 95% CI, 56.2%-85.3%). Lung involvement (odds ratio, 0.112; 95% CI, 0.020-0.639;<i>P</i> = .01) and matched related donors (odds ratio, 0.149; 95% CI, 0.022-0.981;<i>P</i> = .048) were associated with less favorable treatment response. Major adverse events associated with ruxolitinib were cytopenias and infectious complications. The median (range) follow-up for this cohort was 14.9 (1.4-32.5) months. Prolonged survival was observed in patients with a male donor (<i>P</i> = .006), complete remission before transplantation (<i>P</i> = .02), baseline moderate cGVHD (<i>P</i> = .02), and skin cGVHD (<i>P</i> = .001). <h3>Conclusions and Relevance</h3> In this small, single-site case series, ruxolitinib demonstrated a significant response in heavily pretreated patients with SR-cGVHD and a reasonably well-tolerated safety profile. The results add to the body of literature suggesting ruxolitinib as a promising treatment option in SR-cGVHD.
Covid-19: NHS will prioritise four most at-risk groups for second doses, says Stevens
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The NHS will prioritise giving second doses of covid-19 vaccine to over 70s, clinically extremely vulnerable people, and frontline health workers before it starts vaccinating other at-risk groups, the chief executive of NHS England has said.The government's target is to vaccinate all care home residents and staff, all over 70s, all clinically extremely vulnerable people, and all healthcare staff with a first dose by mid-February and to offer all UK adults a vaccine by autumn.
Prenatal Opioid Exposure and Motor Cortex Volume
Authors: Gideon Koren
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Annals Graphic Medicine - Dr. Mom: The Emotions of Getting the COVID-19 Vaccine
Authors: Grace E. Farris
Journal: Annals of Internal Medicine (2021)

Web Exclusives26 January 2021Annals Graphic Medicine - Dr. Mom: The Emotions of Getting the COVID-19 VaccineFREEGrace E. Farris, MDGrace E. Farris, MDUniversity of Texas, Austin, Texas (G.E.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G20-0119 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Author, Article, and Disclosure InformationAuthors: Grace E. Farris, MDAffiliations: University of Texas, Austin, Texas (G.E.F.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G18-0042.Author/Illustrator Information: Grace E. Farris, MD, is an assistant professor of medicine at Dell Medical School at the University of Texas in Austin, Texas. You can view her work at her website: www.farrisgrace.com.About Dr. Mom: In Dr. Mom, physician and cartoonist Grace Farris examines work–life balance while mothering and doctoring. Dr. Mom appears monthly in Annals Graphic Medicine at Annals.org.This article was published at Annals.org on 26 January 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics February 2021Volume 174, Issue 2 Page: W20-W21 ePublished: 26 January 2021 Issue Published: February 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Ceramide and sphingosine-1 phosphate in COPD lungs
Authors: Evgeny V Berdyshev, Karina A Serban, Kelly S Schweitzer, Irina A Bronova, Andrew Mikosz, Irina Petrache
Journal: Thorax (2021)

Studies of chronic obstructive pulmonary disease (COPD) using animal models and patient plasma indicate dysregulation of sphingolipid metabolism, but data in COPD lungs are sparse. Mass spectrometric and immunostaining measurements of lungs from 69 COPD, 16 smokers without COPD and 13 subjects with interstitial lung disease identified decoupling of lung ceramide and sphingosine-1 phosphate (S1P) levels and decreased sphingosine kinase-1 (SphK1) activity in COPD. The correlation of ceramide abundance in distal COPD lungs with apoptosis and the inverse correlation between SphK1 activity and presence of emphysema suggest that disruption of ceramide-to-S1P metabolism is an important determinant of emphysema phenotype in COPD.
Socioeconomic status (SES) and survival outcomes in patients with gastrointestinal (GI) cancers: An analysis of 1.4 million patients in the National Cancer Database (NCDB).
Authors: Mohamed E. Salem, Sally Jeanne Trufan, James Thomas Symanowski, Kunal C. Kadakia, Marion L. Hartley, Kristi D Graves, Laura W. Musselwhite, Edward S. Kim, Derek Raghavan, Jimmy J. Hwang
Journal: Journal of Clinical Oncology (2021)

458 Background: SES and access to care are factors that may impact patient outcomes. We examined the impact of SES on survival in patients (pts) with GI cancers. Methods: Data obtained from the NCDB were used to examine the association between SES and outcomes of GI cancer pts. Pts were categorized by income and education levels. Logistic regression, Cox proportional hazards models, and chi-square tests were used to examine the differences between the groups. Results: A total of 1,409,177 pts diagnosed with GI cancers between 2004 and 2016 were retrospectively studied (table). The majority of pts were male (54.3%), and 83.7% were white, 11.5% black, and 4.7% of other races. Of the entire cohort, 31% of pts lived in the highest income areas, whereas 18.3% were in the lowest and 50.6% in middle-income areas; 23% lived in the highest high school graduation rate (&gt;93%) areas, whereas 17.4% lived in the lowest graduation rate (&lt; 79%) areas; and 82.4% resided in metropolitan areas. Pts in the lowest compared to highest income areas were more likely to be black (OR: 6.5, 6.4-6.6), uninsured (2.9, 2.8-3.0), or have Medicaid (4.13, 4.04-4.22), and have a Charlson-Deyo score ≥ 1 (1.35, 1.33-1.36). In the multivariate analysis, cancer type, stage, tumor differentiation, income, education, insurance status, gender, race, Charlson-Deyo score, and type of treatment center were independent predictors for survival. After controlling for other factors, black pts had a 3% increased risk of death (HR adj = 1.03; 1.02-1.03; p &lt; 0.001). Pts from lowest vs highest education areas had a 2% increased risk of death (HR adj = 1.02; 1.01-1.03; p &lt; 0.001). Pts from the lowest income vs highest income areas had a 13% increased risk of death (HR adj = 1.13; 1.12-1.14; p &lt; 0.001). Pts with Medicaid insurance had a 33% (HR adj : 1.33, CI 1.32-1.34, p &lt; 0.001) and uninsured pts had 22% (HR adj : 1.22 (1.20-1.23, p &lt; 0.001) increased risk of death compared to pts with private insurance. Pts from urban or rural areas vs metropolitan areas had a 1% increased risk of death (HR adj = 1.01; 1.00-1.02; p &lt; 0.001). Conclusions: Low SES is associated with worse survival in pts with any GI cancer. Pts with low-income status and Medicaid or no health insurance had the highest risk of mortality. These stark inequities must be addressed with renewed efforts to identify, treat, and better support pts at highest risk for poor outcomes. [Table: see text]