tbuckley/cabot-search huggingface dataset:
Abstract B13: Intrinsic microsomal PGE2 synthase-1 associates with poor patient survival and T-cell infiltration, and regulates immunosuppression in human and mouse melanoma models
Authors: Sun-Hee Kim, Jason Roszik, Sungnam Cho, Dai Ogata, Suhendan Ekmekcioglu, Elizabeth A Grimm
Journal: Cancer Research (2020)

Abstract Our research has identified microsomal prostaglandin E2 synthase 1 (mPGES1) as an important downstream effector of the cyclooxygenase 2 (COX2) pathway often expressed by melanoma cells, and largely responsible for tumor-mediated immunosuppression. We observed clear correlations in expression and co-localization of COX2 and mPGES1, for which both are associated with increased expression of immunosuppressive markers in human melanoma. In a syngeneic melanoma mouse model, mPGES1 knockout increased melanoma expression of PD-L1 showing about 25% positive cells, increased infiltration of CD8a+ T cells (around 8 fold) and CD8a+ dendritic cells (around 10 fold) into tumors and suppressed tumor growth (around 70%). Durable tumor regression was observed in mice bearing mPGES1 knockout tumors that were given anti-PD-1 therapy. Analysis of a stage III melanoma tissue microarray revealed significant associations between high mPGES1 expression and low CD8+ infiltration, which correlated with poor survival. Collectively, our results are the first to illustrate a potential role for mPGES1-inhibition and selective targeting in melanoma immune evasion and in supporting the durability of response to PD-1 checkpoint immunotherapy. Research in the development of mPGES1 inhibitors is needed to validate their use as safe treatment options, but they appear attractive and feasible based on data to date. Citation Format: Sun-Hee Kim, Jason Roszik, Sungnam Cho, Dai Ogata, Suhendan Ekmekcioglu, Elizabeth A Grimm. Intrinsic microsomal PGE2 synthase-1 associates with poor patient survival and T-cell infiltration, and regulates immunosuppression in human and mouse melanoma models [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr B13.
An ace model for SARS-CoV-2 infection
Authors: Jack Major, Andreas Wack
Journal: The Journal of Experimental Medicine (2020)

Developing effective in vivo models for SARS-CoV-2 infection is crucial for mechanistic studies of COVID-19 disease progression. In this issue ofJEM, Israelow et al. (https://doi.org/10.1084/jem.20201241) generate a model that supports SARS-CoV-2 infection in mice, which they use to characterize type I IFN–driven pulmonary inflammation.
Intratrial Exposure to Vitamin D and New-Onset Diabetes Among Adults With Prediabetes: A Secondary Analysis From the Vitamin D and Type 2 Diabetes (D2d) Study
Authors: Bess Dawson-Hughes, Myrlene A. Staten, William C. Knowler, Jason Nelson, Ellen M. Vickery, Erin S. LeBlanc, Lisa M. Neff, Jean Park, Anastassios G. Pittas
Journal: Diabetes Care (2020)

OBJECTIVE Postrandomization biases may influence the estimate of efficacy of supplemental vitamin D in diabetes prevention trials. In the Vitamin D and Type 2 Diabetes (D2d) study, repeated measures of serum 25-hydroxyvitamin D [25(OH)D] level provided an opportunity to test whether intratrial vitamin D exposure affected diabetes risk and whether the effect was modified by trial assignment (vitamin D vs. placebo). RESEARCH DESIGN AND METHODS The D2d study compared the effect of daily supplementation with 100 μg (4,000 units) of vitamin D3 versus placebo on new-onset diabetes in adults with prediabetes. Intratrial vitamin D exposure was calculated as the cumulative rolling mean of annual serum 25(OH)D measurements. Hazard ratios for diabetes among participants who had intratrial 25(OH)D levels of &amp;lt;50, 75–99, 100–124, and ≥125 nmol/L were compared with those with levels of 50–74 nmol/L (the range considered adequate by the National Academy of Medicine) in the entire cohort and by trial assignment. RESULTS There was an interaction of trial assignment with intratrial 25(OH)D level in predicting diabetes risk (interaction P = 0.018). The hazard ratio for diabetes for an increase of 25 nmol/L in intratrial 25(OH)D level was 0.75 (95% CI 0.68–0.82) among those assigned to vitamin D and 0.90 (0.80–1.02) among those assigned to placebo. The hazard ratios for diabetes among participants treated with vitamin D who maintained intratrial 25(OH)D levels of 100–124 and ≥125 nmol/L were 0.48 (0.29–0.80) and 0.29 (0.17–0.50), respectively, compared with those who maintained a level of 50–74 nmol/L. CONCLUSIONS Daily vitamin D supplementation to maintain a serum 25(OH)D level ≥100 nmol/L is a promising approach to reducing the risk of diabetes in adults with prediabetes.
Association of <i>Staphylococcus aureus</i> Colonization and Pneumonia in the Intensive Care Unit
Authors: Fleur P. Paling, Derek Hazard, Marc J. M. Bonten, Herman Goossens, Hasan S. Jafri, Surbhi Malhotra-Kumar, Frangiscos Sifakis, Susanne Weber, Jan A. J. W. Kluytmans
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Carriage of<i>Staphylococcus aureus</i>is associated with<i>S aureus</i>infection. However, associations between<i>S aureus</i>carriage and the development of<i>S aureus</i>intensive care unit (ICU) pneumonia (SAIP) have not been quantified accurately, and interpretation of available data is hampered because of variations in definitions. <h3>Objective</h3> To quantify associations of patient-related and contextual factors, including<i>S aureus</i>colonization status, with the occurrence of SAIP. <h3>Design, Setting, and Participants</h3> This cohort study was conducted in ICUs of 30 hospitals in 11 European countries, geographically spread across 4 regions. Among patients with an anticipated length of stay 48 hours or longer who were undergoing mechanical ventilation at ICU admission,<i>S aureus</i>colonization was ascertained in the nose and lower respiratory tract. From this group,<i>S aureus</i>–colonized and noncolonized patients were enrolled into the study cohort in a 1:1 ratio. Data analysis was performed from May to November 2019. <h3>Main Outcomes and Measures</h3> SAIP was defined as any pneumonia during the ICU stay developing 48 hours or more after ICU admission with<i>S aureus</i>isolated from lower respiratory tract specimens or blood samples. The incidence of SAIP was derived in the study cohort and estimated on the weighted incidence calculation for the originating overarching population, while taking competing events into account. Weighted risk factor analysis was performed using Cox multivariable regression. <h3>Results</h3> The study cohort consisted of 1933 patients (mean [SD] age, 62.0 [16.0] years); 1252 patients (64.8%) were men, and 950 patients (49.1%) were<i>S aureus</i>carriers at ICU admission. In all, 304 patients (15.7%) developed ICU-acquired pneumonia, of whom 131 patients (6.8%) had SAIP. Weighted SAIP incidences were 11.7 events per 1000 patient-days in the ICU for<i>S aureus–</i>colonized patients and 2.9 events per 1000 patient-days in the ICU for noncolonized patients (overall incidence, 4.9 events per 1000 patient-days in the ICU). The only factor independently associated with SAIP was<i>S aureus</i>colonization status at ICU admission (cause-specific hazard ratio, 3.6; 95% CI, 2.2-6.0;<i>P</i> &lt; .001). There were marked regional differences in SAIP incidence and cause-specific hazard ratios for colonization status. <h3>Conclusions and Relevance</h3> SAIP incidence was 4.9 events per 1000 ICU patient-days for patients undergoing mechanical ventilation at ICU admission (or shortly thereafter). The daily risk of SAIP was 3.6 times higher in patients colonized with<i>S aureus</i>at ICU admission compared with noncolonized patients.
Assessment of treatment tolerance and parental perspective of outpatient pulsed-dye laser treatment for port wine birthmark without general anesthesia in infants and toddlers
Authors: Hao Feng, Grace Materne, Sabrina Ghalili, Margo Lederhandler, Hyemin Pomerantz, Mitalee Christman, Leonard J. Bernstein, Roy G. Geronemus
Journal: Journal of the American Academy of Dermatology (2020)
THE FOOD OF THE ARMY
Authors: R J L CROSNIER
Journal: JAMA (1918)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Breaking a Sweat
Authors: Katherine W. DiNardo, Ramkumar V. Venkateswaran, Anand Vaidya, Anant Vasudevan, Bisola O. Ojikutu
Journal: New England Journal of Medicine (2020)

A 57-year-old-man presented to a Boston-area hospital in March 2019 with a 3-week history of progressively worsening chills and intermittent fevers up to 39.8ºC. He reported the recent onset of drenching night sweats that required him to change his sheets several times per night, generalized malaise, fatigue, anorexia, and dull headaches. . . .
Randomized, Controlled Trial Comparing Mitral Valve Repair With Leaflet Resection Versus Leaflet Preservation on Functional Mitral Stenosis
Authors: Vincent Chan, C. David Mazer, Faeez Mohamad Ali, Adrian Quan, Marc Ruel, Benoit E. de Varennes, Alexander J. Gregory, Denis Bouchard, Richard P. Whitlock, Michael W.A. Chu, Aleksander Dokollari, Thierry Mesana, Deepak L. Bhatt, David A. Latter, Fei Zuo, Wendy Tsang, Hwee Teoh, Peter Jüni, Howard Leong-Poi, Subodh Verma
Journal: Circulation (2020)

Equipoise exists between the use of leaflet resection and preservation for surgical repair of mitral regurgitation caused by prolapse. We therefore performed a randomized, controlled trial comparing these 2 techniques, particularly in regard to functional mitral stenosis.One hundred four patients with degenerative mitral regurgitation surgically amenable to either leaflet resection or preservation were randomized at 7 specialized cardiac surgical centers. Exclusion criteria included anterior leaflet or commissural prolapse, as well as a mixed cause for mitral valve disease. Using previous data, we determined that a sample size of 88 subjects would provide 90% power to detect a 5-mm Hg difference in mean mitral valve gradient at peak exercise, assuming an SD of 6.7 mm with a 2-sided test with α=5% and 10% patient attrition. The primary end point was the mean mitral gradient at peak exercise 12 months after repair.Patient age, proportion who were female, and Society of Thoracic Surgeons risk score were 63.9±10.4 years, 19%, and 1.4±2.8% for those who were assigned to leaflet resection (n=54), and 66.3±10.8 years, 16%, and 1.9±2.6% for those who underwent leaflet preservation (n=50). There were no perioperative deaths or conversions to replacement. At 12 months, moderate mitral regurgitation was observed in 3 subjects in the leaflet resection group and 2 in the leaflet preservation group. The mean transmitral gradient at 12 months during peak exercise was 9.1±5.2 mm Hg after leaflet resection and 8.3±3.3 mm Hg after leaflet preservation (P=0.43). The participants had similar resting peak (8.3±4.4 mm Hg versus 8.4±2.6 mm Hg; P=0.96) and mean resting (3.2±1.9 mm Hg versus 3.1±1.1 mm Hg; P=0.67) mitral gradients after leaflet resection and leaflet preservation, respectively. The 6-minute walking distance was 451±147 m for those in the leaflet resection versus 481±95 m for the leaflet preservation group (P=0.27).In this adequately powered randomized trial, repair of mitral prolapse with either leaflet resection or leaflet preservation was associated with similar transmitral gradients at peak exercise at 12 months postoperatively. These data do not support the hypothesis that a strategy of leaflet resection (versus preservation) is associated with a risk of functional mitral stenosis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier NCT02552771.
Oncolytic Virus Therapy with HSV-1 for Hematological Malignancies
Authors: Ryo Ishino, Yumi Kawase, Toshio Kitawaki, Naoshi Sugimoto, Maki Oku, Shumpei Uchida, Osamu Imataki, Akihito Matsuoka, Teruhisa Taoka, Kimihiro Kawakami, Toin H. van Kuppevelt, Tomoki Todo, Akifumi Takaori-Kondo, Norimitsu Kadowaki
Journal: Molecular Therapy (2020)

Oncolytic herpes simplex virus type 1 (HSV-1) has been investigated to expand its application to various malignancies. Because hematopoietic cells are resistant to HSV-1, its application to hematological malignancies has been rare. Here, we show that the third generation oncolytic HSV-1, T-01, infected and killed 18 of 26 human cell lines and 8 of 15 primary cells derived from various lineages of hematological malignancies. T-01 replicated at low levels in the cell lines. Viral entry and the oncolytic effect were positively correlated with the expression level of nectin-1 and to a lesser extent 3-O-sulfated heparan sulfate, receptors for glycoprotein D of HSV-1, on tumor cells. Transfection of nectin-1 into nectin-1-negative tumor cells made them susceptible to T-01. The oncolytic effects did not appear to correlate with the expression or phosphorylation of antiviral molecules in the cyclic GMP-AMP (cGAS)-stimulator of interferon genes (STING) and PKR-eIF2α pathways. In an immunocompetent mouse model, intratumoral injection of T-01 into lymphoma induced regression of injected, as well as non-injected, contralateral tumors accompanied by abundant infiltration of antigen-specific CD8+ T cells. These data suggest that intratumoral injection of oncolytic HSV-1 may be applicable to systemic hematological malignancies. Nectin-1 expression may be the most useful biomarker for optimal efficacy.
NHS aims to become world’s first “net zero” health service by 2040
Authors: Ingrid Torjesen
Journal: BMJ (2020)

The NHS in England has committed itself to becoming “net zero” for greenhouse gas emissions for the care it provides and has set a target of 2040 to achieve this.

The NHS has control over certain emissions, such as those produced by its services, buildings, and vehicles, and it will take until 2028 to 2032 to reduce these by 80% and until 2040 to eliminate them, says a report it commissioned.1

It will take a further five years, until 2045, to reach “net zero” for all the emissions over which the NHS has influence, such as those relating to its supply chain and travel of patients and staff.

The 2040 and 2045 targets are “feasible,” says the report. It sets out the conclusions of an expert panel chaired by Nick Watts from the Lancet Countdown, a collaboration of experts who work to ensure that health is at the centre of how governments understand …
Inflammation as a Predictor of Recurrent Ventricular Tachycardia After Ablation in Patients With Myocarditis
Authors: Giovanni Peretto, Simone Sala, Cristina Basso, Stefania Rizzo, Andrea Radinovic, Antonio Frontera, Luca Rosario Limite, Gabriele Paglino, Caterina Bisceglia, Giacomo De Luca, Corrado Campochiaro, Silvia Sartorelli, Anna Palmisano, Antonio Esposito, Elena Busnardo, Andrea Villatore, Francesca Baratto, Manuela Cireddu, Alessandra Marzi, Giuseppe D’Angelo, Simone Gulletta, Pasquale Vergara, Francesco De Cobelli, Lorenzo Dagna, Patrizio Mazzone, Paolo Della Bella
Journal: Journal of the American College of Cardiology (2020)
Recent developments in targeting genes and pathways by RNAi‐based approaches in colorectal cancer
Authors: Asiyeh Jebelli, Behzad Baradaran, Jafar Mosafer, Amir Baghbanzadeh, Ahad Mokhtarzadeh, Lobat Tayebi
Journal: Medicinal Research Reviews (2020)

Abstract A wide spectrum of genetic and epigenetic variations together with environmental factors has made colorectal cancer (CRC), which involves the colon and rectum, a challenging and heterogeneous cancer. CRC cannot be effectively overcomed by common conventional therapies including surgery, chemotherapy, targeted therapy, and hormone replacement which highlights the need for a rational design of novel anticancer therapy. Accumulating evidence indicates that RNA interference (RNAi) could be an important avenue to generate great therapeutic efficacy for CRC by targeting genes that are responsible for the viability, cell cycle, proliferation, apoptosis, differentiation, metastasis, and invasion of CRC cells. In this review, we underline the documented benefits of small interfering RNAs and short hairpin RNAs to target genes and signaling pathways related to CRC tumorigenesis. We address the synergistic effects of RNAi‐mediated gene knockdown and inhibitors/chemotherapy agents to increase the sensitivity of CRC cells to common therapies. Finally, this review points new delivery systems/materials for improving the cellular uptake efficiency and reducing off‐target effects of RNAi.
Comprehensive Ex Vivo Comparison of 5 Clinically Used Conduit Configurations for Valve-Sparing Aortic Root Replacement Using a 3-Dimensional–Printed Heart Simulator
Authors: Michael J. Paulsen, Annabel M. Imbrie-Moore, Michael Baiocchi, Hanjay Wang, Camille E. Hironaka, Haley J. Lucian, Justin M. Farry, Akshara D. Thakore, Yuanjia Zhu, Michael Ma, John W. MacArthur, Y. Joseph Woo
Journal: Circulation (2020)

Background: Many graft configurations are clinically used for valve-sparing aortic root replacement, some specifically focused on recapitulating neosinus geometry. However, the specific impact of such neosinuses on valvular and root biomechanics and the potential influence on long-term durability are unknown. Methods: Using a custom 3-dimenstional–printed heart simulator with porcine aortic roots (n=5), the anticommissural plication, Stanford modification, straight graft (SG), Uni-Graft, and Valsalva graft configurations were tested in series using an incomplete counterbalanced measures design, with the native root as a control, to mitigate ordering effects. Hemodynamic and videometric data were analyzed using linear models with conduit as the fixed effect of interest and valve as a fixed nuisance effect with post hoc pairwise testing using Tukey’s correction. Results: Hemodynamics were clinically similar between grafts and control aortic roots. Regurgitant fraction varied between grafts, with SG and Uni-Graft groups having the lowest regurgitant fractions and anticommissural plication having the highest. Root distensibility was significantly lower in SG versus both control roots and all other grafts aside from the Stanford modification ( P ≤0.01 for each). All grafts except SG had significantly higher cusp opening velocities versus native roots ( P &lt;0.01 for each). Relative cusp opening forces were similar between SG, Uni-Graft, and control groups, whereas anticommissural plication, Stanford modification, and Valsalva grafts had significantly higher opening forces versus controls ( P &lt;0.01). Cusp closing velocities were similar between native roots and the SG group, and were significantly lower than observed in the other conduits ( P ≤0.01 for each). Only SG and Uni-Graft groups experienced relative cusp closing forces approaching that of the native root, whereas relative forces were &gt;5-fold higher in the anticommissural plication, Stanford modification, and Valsalva graft groups. Conclusions: In this ex vivo modeling system, clinically used valve-sparing aortic root replacement conduit configurations have comparable hemodynamics but differ in biomechanical performance, with the straight graft most closely recapitulating native aortic root biomechanics.
Expected medium and long term impact of the COVID-19 outbreak in oncology
Authors: G. Jerusalem, C. E. Onesti, D. G. Generali, N. Harbeck, H. Wildiers, G. Curigliano, M. Campone, V. Tjan-Heijnen, M. Martin, M. Cristofanilli, L. Pusztai, R. Bartsch, M. Peeters, G. Berchem, M. Tagliamento, J. Cortés, T. Ruhstaller, E. M. Ciruelos, S. Rottey, H. S. Rugo
Journal: Annals of Oncology (2020)
Transcription tipping points for T follicular helper cell and T-helper 1 cell fate commitment
Authors: Amania A. Sheikh, Joanna R. Groom
Journal: Cellular and Molecular Immunology (2020)

During viral infection, immune cells coordinate the induction of inflammatory responses that clear infection and humoral responses that promote protection. CD4+ T-cell differentiation sits at the center of this axis. Differentiation toward T-helper 1 (Th1) cells mediates inflammation and pathogen clearance, while T follicular helper (Tfh) cells facilitate germinal center (GC) reactions for the generation of high-affinity antibodies and immune memory. While Th1 and Tfh differentiation occurs in parallel, these CD4+ T-cell identities are mutually exclusive, and progression toward these ends is determined via the upregulation of T-bet and Bcl6, respectively. These lineage-defining transcription factors act in concert with multiple networks of transcriptional regulators that tip the T-bet and Bcl6 axis in CD4+ T-cell progenitors to either a Th1 or Tfh fate. It is now clear that these transcriptional networks are guided by cytokine cues that are not only varied between distinct viral infections but also dynamically altered throughout the duration of infection. Thus, multiple intrinsic and extrinsic factors combine to specify the fate, plasticity, and function of Th1 and Tfh cells during infection. Here, we review the current information on the mode of action of the lineage-defining transcription factors Bcl6 and T-bet and how they act individually and in complex to govern CD4+ T-cell ontogeny. Furthermore, we outline the multifaceted transcriptional regulatory networks that act upstream and downstream of Bcl6 and T-bet to tip the differentiation equilibrium toward either a Tfh or Th1 fate and how these are impacted by dynamic inflammatory cues.
Coronavirus in human diseases: Mechanisms and advances in clinical treatment
Authors: Panpan Lin, Manni Wang, Yuquan Wei, Taewan Kim, Xiawei Wei
Journal: MedComm (2020)

Abstract Coronaviruses (CoVs), a subfamily of coronavirinae, are a panel of single‐stranded RNA virus. Human coronavirus (HCoV) strains (HCoV‐229E, HCoV‐OC43, HCoV‐HKU1, HCoV‐NL63) usually cause mild upper respiratory diseases and are believed to be harmless. However, other HCoVs, associated with severe acute respiratory syndrome, Middle East respiratory syndrome, and COVID‐19, have been identified as important pathogens due to their potent infectivity and lethality worldwide. Moreover, currently, no effective antiviral drugs treatments are available so far. In this review, we summarize the biological characters of HCoVs, their association with human diseases, and current therapeutic options for the three severe HCoVs. We also highlight the discussion about novel treatment strategies for HCoVs infections.