tbuckley/cabot-search huggingface dataset:
An Oncolytic Virus Expressing IL15/IL15Rα Combined with Off-the-Shelf EGFR-CAR NK Cells Targets Glioblastoma
Authors: Rui Ma, Ting Lu, Zhenlong Li, Kun-Yu Teng, Anthony G. Mansour, Melissa Yu, Lei Tian, Bo Xu, Shoubao Ma, Jianying Zhang, Tasha Barr, Yong Peng, Michael A. Caligiuri, Jianhua Yu
Journal: Cancer Research (2021)

Abstract IL15 is a pleiotropic cytokine with multiple roles that improve immune responses to tumor cells. Oncolytic viruses (OV) specifically lyse tumors and activate immune responses. Systemic administration of IL15 or its complex with the IL15Rα and chimeric antigen receptor (CAR) natural killer (NK) cells are currently being tested in the clinic. Here, we generated a herpes simplex 1–based OV-expressing human IL15/IL15Rα sushi domain fusion protein (named OV-IL15C), as well as off-the-shelf EGFR-CAR NK cells, and studied their monotherapy and combination efficacy in vitro and in multiple glioblastoma (GBM) mouse models. In vitro, soluble IL15/IL15Rα complex was secreted from OV-IL15C–infected GBM cells, which promoted GBM cytotoxicity and improved survival of NK and CD8+ T cells. Frozen, readily available off-the-shelf EGFR-CAR NK cells showed enhanced killing of tumor cells compared with empty vector–transduced NK cells. In vivo, OV-IL15C significantly inhibited tumor growth and prolonged survival of GBM-bearing mice in the presence of CD8+ T cells compared with parental OV. OV-IL15C plus EGFR-CAR NK cells synergistically suppressed tumor growth and significantly improved survival compared with either monotherapy, correlating with increased intracranial infiltration and activation of NK and CD8+ T cells and elevated persistence of CAR NK cells in an immunocompetent model. Collectively, OV-IL15C and off-the-shelf EGFR-CAR NK cells represent promising therapeutic strategies for GBM treatment to improve the clinical management of this devastating disease. Significance: The combination of an oncolytic virus expressing the IL15/IL15Rα complex and frozen, ready-to-use EGFR-CAR NK cells elicits strong antitumor responses in glioblastoma.
Application of 2021 American Diabetes Association Glycemic Treatment Clinical Practice Recommendations in Primary Care
Authors: Caitlin Colling, Steven J. Atlas, Deborah J. Wexler
Journal: Diabetes Care (2021)

We aimed to identify the proportion of primary care patients meeting criteria for sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) for cardiorenal comorbidities per 2021 American Diabetes Association (ADA) Standards of Care recommendations using readily available electronic health record (EHR) characteristics.We applied 2021 ADA recommendations to a primary care cohort of 13,350 adults with type 2 diabetes (T2D).We found that 33% of patients with diabetes would be eligible for an SGLT2i or GLP-1 RA based on cardiorenal comorbidities, 13% of patients met criteria for an SGLT2i based on heart failure or albuminuric chronic kidney disease (CKD), and 18% of patients met criteria for either agent based on atherosclerotic cardiovascular disease or CKD with an albumin-to-creatinine ratio of ≤300 mg/g.This EHR algorithm identified one-third of primary care patients with T2D as meeting criteria for SGLT2i and GLP-1 RA based on strict comorbidity definitions according to 2021 ADA recommendations.
Interferon-γ in the Management of Infectious Diseases
Authors: John I. Gallin
Journal: Annals of Internal Medicine (1995)

Interferon-γ has pleiotropic adjuvant effects on host defenses. These effects have made interferon-γ particularly useful for enhancing host defenses in patients with chronic granulomatous disease of childhood and thus for reducing the incidence of life-threatening infections in these patients. Increasingly, data suggest that interferon-γ will be useful for treating infections characterized by intracellular persistence in macrophages, such as toxoplasmosis, leishmaniasis, and mycobacteriosis. Interferon-γ is emerging as an important cytokine for use in the treatment of infectious diseases.
Abstract 16910: High-Frequency In-Person Visits During Clinical Trial Enrollment is Associated With Relative Reduction in Event Rates in Heart Failure Patients Followed Longitudinally
Authors: Liana C Brooks, Rohan R Bhat, Robyn F Farrell, Mark W Schoenike, John A Sbarbaro, Thomas F Cunningham, Rajeev Malhotra, Matthew G Nayor, Jennifer E Ho, Nasrien E Ibrahim, Erin Coglianese, Diane Cocca-Spofford, Gregory D Lewis
Journal: Circulation (2020)

Introduction: The COVID-19 Pandemic has mandated limiting routine visit frequency for patients with chronic cardiovascular (CV) diseases. In patients with heart failure (HF) followed longitudinally, the period of clinical trial participation provides an opportunity to evaluate the influence of high-frequency per-protocol in-person visits compared to less frequent routine visits during longitudinal clinical care. Hypothesis: Patients enrolled in clinical trials will have a lower CV and HF event rates during periods of trial enrollment than during non-trial periods. Methods: We examined clinical characteristics, CV and HF hospitalization rates, and outcomes in patients with HF receiving longitudinal HF care at a single center. We evaluated hospitalization rates during the 1-year preceding trial enrollment and hospitalization and death rates during enrollment in clinical trials and for up to 1 year following trial completion. Results: Among the 121 patients enrolled in HF clinical trials, 72% were HFrEF (age 62±11, 19% females, BMI 30.4±6.0, LVEF 25±7, NYHA 2.7±0.6, NT-proBNP 2336±2671) and 28% were HFpEF (age 69±9, BMI 32.1±5.5, 29% females, LVEF 60±10, NYHA 2.4±0.5, NT-proBNP 957±997). Average clinical trial exposure was 8±6.6 months. Per-protocol visit frequency was 16±7 per year during clinical trial enrollment. In the one-year pre-trial period, compared to the within-trial period, CV hospitalizations were 0.88/patient-year vs. 0.32/patient-year (p&lt;0.001) and HF hospitalizations were 0.63/patient-year and 0.24/patient-year (p&lt;0.001), with a mortality rate of 0.04/patient-year during trial participation. In the period of up-to 1 year following the end of trial enrollment CV and HF hospitalizations were intermediate at 0.51/patient-year and 0.27/patient-year with an annualized incremental mortality rate of 0.03/patient-year. Conclusion: In HF patients followed longitudinally at a single center, periods of clinical trial enrollment were associated with high visit frequency and lower CV and HF hospitalization rates. These findings highlight the potential benefits of trial enrollment and high-frequency visits for HF patients at a time when routine visit frequency is being carefully considered during the COVID-19 Pandemic.
In vivo screen identifies a SIK inhibitor that induces β cell proliferation through a transient UPR
Authors: Jérémie Charbord, Lipeng Ren, Rohit B. Sharma, Anna Johansson, Rasmus Ågren, Lianhe Chu, Dominika Tworus, Nadja Schulz, Pierre Charbord, Andrew F. Stewart, Peng Wang, Laura C. Alonso, Olov Andersson
Journal: Nature Metabolism (2021)
Abstract 16605: The Effectiveness and Safety of the Esophageal Temperature Monitoring During Catheter Ablation of Atrial Fibrillation
Authors: Miwa Ito, Hisanori Kanazawa, Tadashi Hoshiyama, Yusei Kawahara, Kenichi Tsujita
Journal: Circulation (2020)

Introduction: Esophageal injury is known to be a serious complication occurs after catheter ablation (CA) of atrial fibrillation (AF). Hypothesis: We investigated the factors associated with the occurrence of EI after CA. Also esophageal temperature monitoring (ETM) can be useful, multiple factors such as patient characteristics and specific strategies for radiofrequency energy delivery also merit consideration. Methods: Among 508 patients who underwent CA of AF, endoscopy was performed the next day after CA to examine for EI. The incidence of EI was compared between 200 patients who done ETM (ETM group) and 308 patients who didn’t done ETM (Non-ETM group) during CA. The Shortest Distance between esophagus and posterior left atrium measured on contrast Computed Tomography (SD-CT) was also compared between both groups. Results: No differences were observed between both groups in total amount of radiofrequency energy applications. However, EI occurred more frequently in Non-ETM group (8/200 patients; 4.0 % vs 27/308 patients; 8.8 %, p=0.042). There was no significant difference in SD-CT between ETM and Non-ETM group. However, SD-CT in patients with EI was significantly shorter than SD-CT in patients without EI, both in ETM (2.4±0.7 vs 4.3±0.9 mm, p&lt;0.001) and in Non-ETM group (2.5±0.2 vs 4.2±0.9 mm, p=0.017), respectively. Multiple regression analysis revealed that only SD-CT significantly correlated with EI. The area under a receiver operating characteristic curve using ST-CT as a predictive marker in EI patients was 0.968 (p&lt;0.001). When the cut-off value of EI was set at 2.9mm, the sensitivity and specificity for EI diagnosis were 96.6% and 87.5%. Conclusions: The use of ETM is absolutely safe and necessary in order to prevent the occurrence of thermal EI.
A Silent Curriculum
Authors: Katherine C. Brooks
Journal: JAMA (2015)

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
Abstract 022: Plasma Metabolome Related To Plant-based Diets And The Association With Type 2 Diabetes: A Prospective Cohort Study
Authors: Fenglei Wang, Megu Y Baden, Jun Li, Marta Guasch-Ferré, Yanping Li, Yi Wan, Shilpa N Bhupathiraju, Deirdre K Tobias, Clary Clish, Lorelei A Mucci, A. H Eliassen, Karen Costenbader, Elizabeth W Karlson, Alberto Ascherio, Eric B Rimm, JoAnn E Manson, Liming Liang, Frank Hu
Journal: Circulation (2021)

Background: Plant-based diets have been associated with a lower risk of type 2 diabetes. However, the underlying mechanisms are not completely understood, and the evidence using objective approaches to assess the adherence of plant-based diets is limited. Methods: In the Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-Up Study, we characterized the plasma metabolome related to plant-based diets and examined its association with the incidence of type 2 diabetes among 10 699 participants. Plasma metabolomic profiling was conducted by liquid chromatography-tandem mass spectrometry. Adherence to plant-based diets was assessed by three plant-based diet indices derived from the food frequency questionnaire: an overall plant-based diet index (PDI), a healthful PDI (hPDI), and an unhealthful PDI (uPDI). Metabolomic signatures reflecting the adherence to plant-based diets were created using elastic net regression, and their associations with risk of type 2 diabetes were subsequently evaluated using multivariable Cox proportional hazards regression. Results: Among 263 metabolites measured, nearly half were significantly associated with PDI (41.4%, 109 of 263), hPDI (51.7%, 136 of 263), and uPDI (40.3%, 106 of 263) after Bonferroni correction. We developed a metabolomic signature comprising 53 metabolites for PDI, 76 metabolites for hPDI, and 88 metabolites for uPDI, each robustly correlated with the corresponding diet index (r=0.34-0.36 for PDI, 0.43-0.44 for hPDI, and 0.36-0.37 for uPDI). We observed an inverse association of PDI metabolomic signature (HR 0.86, 95% CI 0.79-0.93 per one standard deviation) and hPDI metabolomic signature (0.79, 0.72-0.86) with type 2 diabetes risk after adjustment for body mass index and other potential confounders. These two inverse associations remained significant even further adjusting for the corresponding diet index PDI and hPDI. The metabolomic signature for uPDI was not associated with type 2 diabetes risk (1.00, 0.93-1.09). Conclusion: Plasma metabolome can robustly reflect adherence and metabolic response to plant-based diets. Metabolomic signatures reflecting greater adherence to an overall plant-based diet, especially a healthful plant-based diet, were associated with a lower risk of type 2 diabetes. These findings support and provide mechanistic insights on the important role of healthful plant-based diets in diabetes prevention.
Abstract 16189: Cardiovascular Risk Prediction Using Fully Automated Artificial Intelligence Algorithms for the Assessment of Right Ventricular Function From Cardiac Magnetic Resonance Images
Authors: shuo wang, Hena Patel, Tamari Miller, Keith Ameyaw, Akhil Narang, Daksh Chauhan, Stephanie Besser, Keigo Kawaji, Qiang Tang, Victor Mor-Avi, Patel R Amit
Journal: Circulation (2020)

Background: It is unclear whether artificial intelligence (AI) can provide automatic solutions to measure right ventricular ejection fraction (RVEF), due to the complex RV geometry. Although several deep learning (DL) algorithms are available to quantify RVEF from cardiac magnetic resonance (CMR) images, there has been no systematic comparison of these algorithms, and the prognostic value of these automated measurements is unknown. We aimed to determine whether RVEF measurements made using DL algorithms could be used to risk stratify patients similarly to measurements made by an expert. Methods: We identified from a pre-existing registry 200 patients who underwent CMR. RVEF was determined using 3 fully automated commercial DL algorithms (DL-RVEF) and also by a clinical expert (CLIN-RVEF) using conventional methodology. Each of the DL-RVEF approaches was compared against CLIN-RVEF using linear regression and Bland-Altman analyses. In addition, RVEF values were classified according to clinically important cutoffs: &lt;35%, 35-50%, ≥50%, and rates of disagreement with the reference classification were determined. ROC analysis was performed to evaluate the ability of CLIN-RVEF and each of the DL-RVEF based classifications to predict major adverse cardiovascular events (MACE). Results: The CLIN-RVEF and the three DL-RVEFs were obtained in all patients. We found only modest correlations between DL-RVEF and CLIN-RVEF (figure). The DL-RVEF algorithms had accuracy ranging from 0.59 to 0.78 for categorizing RV function. Nevertheless, ROC analysis showed no significant differences between the 4 approaches in predicting MACE, as reflected by respective AUC values of 0.68, 0.69, 0.64 and 0.63. Conclusions: Although the automated algorithms predicted patient outcomes as well as the CLIN-RVEF, the agreement between DL-RVEF and the clinical expert’s measurements was not optimal. DL approaches need further refinements to improve automated assessment of RV function.
Primary cilia control endothelial permeability by regulating expression and location of junction proteins
Authors: Mannekomba R Diagbouga, Sandrine Morel, Anne F Cayron, Julien Haemmerli, Marc Georges, Beerend P Hierck, Eric Allémann, Sylvain Lemeille, Philippe Bijlenga, Brenda R Kwak
Journal: Cardiovascular Research (2021)

Abstract Aims Wall shear stress (WSS) determines intracranial aneurysm (IA) development. Polycystic kidney disease (PKD) patients have a high IA incidence and risk of rupture. Dysfunction/absence of primary cilia in PKD endothelial cells (ECs) may impair mechano-transduction of WSS and favour vascular disorders. The molecular links between primary cilia dysfunction and IAs are unknown. Methods and results Wild-type and primary cilia-deficient Tg737orpk/orpk arterial ECs were submitted to physiological (30 dynes/cm2) or aneurysmal (2 dynes/cm2) WSS, and unbiased transcriptomics were performed. Tg737orpk/orpk ECs displayed a fivefold increase in the number of WSS-responsive genes compared to wild-type cells. Moreover, we observed a lower trans-endothelial resistance and a higher endothelial permeability, which correlated with disorganized intercellular junctions in Tg737orpk/orpk cells. We identified ZO-1 as a central regulator of primary cilia-dependent endothelial junction integrity. Finally, clinical and histological characteristics of IAs from non-PKD and PKD patients were analysed. IAs in PKD patients were more frequently located in the middle cerebral artery (MCA) territory than in non-PKD patients. IA domes from the MCA of PKD patients appeared thinner with less collagen and reduced endothelial ZO-1 compared with IA domes from non-PKD patients. Conclusion Primary cilia dampen the endothelial response to aneurysmal low WSS. In absence of primary cilia, ZO-1 expression levels are reduced, which disorganizes intercellular junctions resulting in increased endothelial permeability. This altered endothelial function may not only contribute to the severity of IA disease observed in PKD patients, but may also serve as a potential diagnostic tool to determine the vulnerability of IAs.
Origins and Early Management of Medical Child Abuse in Routine Pediatric Care
Authors: James C. Hamilton, John M. Leventhal, Andrea G. Asnes
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
Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma Determine Response to SLC7A11 Inhibition
Authors: George Sharbeen, Joshua A. McCarroll, Anouschka Akerman, Chantal Kopecky, Janet Youkhana, John Kokkinos, Jeff Holst, Cyrille Boyer, Mert Erkan, David Goldstein, Paul Timpson, Thomas R. Cox, Brooke A. Pereira, Jessica L. Chitty, Sigrid K. Fey, Arafath K. Najumudeen, Andrew D. Campbell, Owen J. Sansom, Rosa Mistica C. Ignacio, Stephanie Naim, Jie Liu, Nelson Russia, Julia Lee, Angela Chou, Amber Johns, Anthony J. Gill, Estrella Gonzales-Aloy, Val Gebski, Yi Fang Guan, Marina Pajic, Nigel Turner, Minoti V. Apte, Thomas P. Davis, Jennifer P. Morton, Koroush S. Haghighi, Jorjina Kasparian, Benjamin J. McLean, Yordanos F. Setargew, Phoebe A. Phillips
Journal: Cancer Research (2021)

Abstract Cancer-associated fibroblasts (CAF) are major contributors to pancreatic ductal adenocarcinoma (PDAC) progression through protumor signaling and the generation of fibrosis, the latter of which creates a physical barrier to drugs. CAF inhibition is thus an ideal component of any therapeutic approach for PDAC. SLC7A11 is a cystine transporter that has been identified as a potential therapeutic target in PDAC cells. However, no prior study has evaluated the role of SLC7A11 in PDAC tumor stroma and its prognostic significance. Here we show that high expression of SLC7A11 in human PDAC tumor stroma, but not tumor cells, is independently prognostic of poorer overall survival. Orthogonal approaches showed that PDAC-derived CAFs are highly dependent on SLC7A11 for cystine uptake and glutathione synthesis and that SLC7A11 inhibition significantly decreases CAF proliferation, reduces their resistance to oxidative stress, and inhibits their ability to remodel collagen and support PDAC cell growth. Importantly, specific ablation of SLC7A11 from the tumor compartment of transgenic mouse PDAC tumors did not affect tumor growth, suggesting the stroma can substantially influence PDAC tumor response to SLC7A11 inhibition. In a mouse orthotopic PDAC model utilizing human PDAC cells and CAFs, stable knockdown of SLC7A11 was required in both cell types to reduce tumor growth, metastatic spread, and intratumoral fibrosis, demonstrating the importance of targeting SLC7A11 in both compartments. Finally, treatment with a nanoparticle gene-silencing drug against SLC7A11, developed by our laboratory, reduced PDAC tumor growth, incidence of metastases, CAF activation, and fibrosis in orthotopic PDAC tumors. Overall, these findings identify an important role of SLC7A11 in PDAC-derived CAFs in supporting tumor growth. Significance: This study demonstrates that SLC7A11 in PDAC stromal cells is important for the tumor-promoting activity of CAFs and validates a clinically translatable nanomedicine for therapeutic SLC7A11 inhibition in PDAC.
IL-6 effector function of group 2 innate lymphoid cells (ILC2) is NOD2 dependent
Authors: Clare S. Hardman, Yi-Ling Chen, Maryam Salimi, Janina Nahler, Daniele Corridoni, Marta Jagielowicz, Chathuranga L. Fonseka, David Johnson, Emmanouela Repapi, David J. Cousins, Jillian L. Barlow, Andrew N. J. McKenzie, Alison Simmons, Graham Ogg
Journal: Science Immunology (2021)

Cutaneous group 2 innate lymphoid cells (ILC2) are spatially and epigenetically poised to respond to barrier compromise and associated immunological threats. ILC2, lacking rearranged antigen-specific receptors, are primarily activated by damage-associated cytokines and respond with type 2 cytokine production. To investigate ILC2 potential for direct sensing of skin pathogens and allergens, we performed RNA sequencing of ILC2 derived from in vivo challenged human skin or blood. We detected expression of
An Inexpensive Intervention to Reduce e-Cigarette Use Among Young Adults
Authors: Anand R. Habib, Mitchell H. Katz
Journal: JAMA Internal Medicine (2021)

The US Surgeon General has declared e-cigarette use among young adults an epidemic.1 A 2021 meta-analysis found that e-cigarette users had nearly 5 times greater odds of subsequent initiation of cigarette smoking.2 Interventions to decrease e-cigarette use among young adults are desperately needed.
GPs should return to offering face-to-face appointments without prior triage, says NHS
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The NHS has told general practices to return to offering patients face-to-face appointments without needing prior telephone or online triage, reversing a policy that has been in place since the start of the pandemic.

A row has surfaced in recent days after the Telegraph reported1 that NHS guidance continued to advise practices to use the “total triage” model, introduced in 2020 to reduce the risk of infection spreading at GP surgeries. The model requires patients to undergo a remote assessment before they can be offered a face-to-face consultation if one is deemed necessary.

But doctors and patient groups have voiced concerns that the system may be preventing some patients from accessing the care they need, and the Royal College of General Practitioners said in a report this week that remote consulting should be …