tbuckley/cabot-search huggingface dataset:
Ready-to-Use Glucagon Analogue Quickly Reverses Hypoglycemia
Authors: Anita Slomski
Journal: JAMA (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 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
Extracellular Matrix Stiffness Regulates DNA Methylation by PKC<i>α</i>‐Dependent Nuclear Transport of DNMT3L
Authors: Xin‐Bin Zhao, Yun‐Ping Chen, Min Tan, Lan Zhao, Yuan‐Yuan Zhai, Yan‐Ling Sun, Yan Gong, Xi‐Qiao Feng, Jing Du, Yu‐Bo Fan
Journal: Advanced Healthcare Materials (2021)

Abstract Extracellular matrix (ECM) stiffness has profound effects on the regulation of cell functions. DNA methylation is an important epigenetic modification governing gene expression. However, the effects of ECM stiffness on DNA methylation remain elusive. Here, it is reported that DNA methylation is sensitive to ECM stiffness, with a global hypermethylation under stiff ECM condition in mouse embryonic stem cells (mESCs) and embryonic fibroblasts compared with soft ECM. Stiff ECM enhances DNA methylation of both promoters and gene bodies, especially the 5’ promoter regions of pluripotent genes. The enhanced DNA methylation is functionally required for the loss of pluripotent gene expression in mESCs grown on stiff ECM. Further experiments reveal that the nuclear transport of DNA methyltransferase 3‐like (DNMT3L) is promoted by stiff ECM in a protein kinase C α (PKC α )‐dependent manner and DNMT3L can be binding to Nanog promoter regions during cell–ECM interactions. These findings unveil DNA methylation as a novel target for the mechanical sensing mechanism of ECM stiffness, which provides a conserved mechanism for gene expression regulation during cell–ECM interactions.
Abstract 16460: Dual Antiplatelet Therapy for Three Months Followed by Monotherapy is Non-inferior to One Year Dual Antiplatelet Therapy in Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention- A Systematic Review and Meta-Analysis
Authors: Muhammad Fazeel Anwar, Behram A Khan, Syeda Fatima Hassan, Sarwat Nasreen, Saad Ullah Malik, Hafiz Muhammad Fazeel, Asim Tameez Ud Din, Jacqueliene Chung, Mohsin Mirza
Journal: Circulation (2019)

Introduction: Dual antiplatelet therapy (DAPT) is recommended as a standard treatment for patients with the acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI)...
Clinical outcomes after 4.5 years of eliglustat therapy for <scp>Gaucher</scp> disease type 1: Phase 3 <scp>ENGAGE</scp> trial final results
Authors: Pramod K. Mistry, Elena Lukina, Hadhami Ben Turkia, Suma P. Shankar, Hagit Baris Feldman, Marwan Ghosn, Atul Mehta, Seymour Packman, Heather Lau, Milan Petakov, Sarit Assouline, Manisha Balwani, Sumita Danda, Evgueniy Hadjiev, Andres Ortega, Meredith C. Foster, Sebastiaan J. M. Gaemers, M. Judith Peterschmitt
Journal: American Journal of Hematology (2021)

Eliglustat, an oral substrate reduction therapy, is approved for eligible adults with Gaucher disease type 1. In the Phase 3 ENGAGE trial of previously untreated adults with Gaucher disease type 1, eliglustat-treated patients had statistically significant improvements in organ volumes and hematologic parameters compared with placebo in the 9-month primary analysis. We report final outcomes by time on eliglustat among all patients who participated in the ENGAGE trial and extension. No patient deteriorated clinically or withdrew due to adverse events; 39/40 patients entered the open-label extension period and 34/40 (85%) remained in the trial until completion or switching to commercial eliglustat after its approval (2.3-6 years). Clinically meaningful improvements in Gaucher disease manifestations were seen in all patients concomitant with reductions in pathological lipid substrate levels (glucosylceramide and glucosylsphingosine). Among patients with 4.5 years of eliglustat exposure, mean spleen volume decreased by 66% (from 17.1 to 5.8 multiples of normal [MN], n = 13), mean liver volume decreased by 23% (from 1.5 to 1.1 MN, n = 13), mean hemoglobin increased 1.4 g/dl (from 11.9 to 13.4 g/dl, n = 12), mean platelet count increased by 87% (from 67.6 to 122.6 × 109 /L, n = 12), median chitotriosidase decreased by 82% (from 13 394 to 2312 nmol/h/ml, n = 11), median glucosylceramide decreased by 79% (from 11.5 to 2.4 μg/ml, n = 11), median glucosylsphingosine decreased by 84% (from 518.5 to 72.1 ng/ml, n = 10), and mean spine T-score increased from -1.07 (osteopenia) to -0.53 (normal) (n = 9). The magnitude of improvement in Gaucher disease manifestations and biomarkers over time was similar among the full trial cohort. Eliglustat was well-tolerated and led to clinically significant improvements in previously untreated patients with Gaucher disease type 1 during 4.5 years of treatment.
Anti-TNF treatment corrects IFN-γ–dependent proinflammatory signatures in Blau syndrome patient–derived macrophages
Authors: Yohko Kitagawa, Yuri Kawasaki, Yuichi Yamasaki, Naotomo Kambe, Syuji Takei, Megumu K. Saito
Journal: Journal of Allergy and Clinical Immunology (2021)
Overcoming the obstacles of current photodynamic therapy in tumors using nanoparticles
Authors: Donghyun Lee, Soonmin Kwon, Seok-young Jang, Eunyoung Park, Yeeun Lee, Heebeom Koo
Journal: Bioactive Materials (2021)

Photodynamic therapy (PDT) has been applied in clinical treatment of tumors for a long time. However, insufficient supply of pivotal factors including photosensitizer (PS), light, and oxygen in tumor tissue dramatically reduces the therapeutic efficacy of PDT. Nanoparticles have received an influx of attention as drug carriers, and recent studies have demonstrated their promising potential to overcome the obstacles of PDT in tumor tissue. Physicochemical optimization for passive targeting, ligand modification for active targeting, and stimuli-responsive release achieved efficient delivery of PS to tumor tissue. Various trials using upconversion NPs, two-photon lasers, X-rays, and bioluminescence have provided clues for efficient methods of light delivery to deep tissue. Attempts have been made to overcome unfavorable tumor microenvironments via artificial oxygen generation, Fenton reaction, and combination with other chemical drugs. In this review, we introduce these creative approaches to addressing the hurdles facing PDT in tumors. In particular, the studies that have been validated in animal experiments are preferred in this review over proof-of-concept studies that were only performed in cells.
Neurodegenerative disorders and gut-brain interactions
Authors: Alpana Singh, Ted M. Dawson, Subhash Kulkarni
Journal: Journal of Clinical Investigation (2021)

Neurodegenerative disorders (NDs) affect essential functions not only in the CNS, but also cause persistent gut dysfunctions, suggesting that they have an impact on both CNS and gut-innervating neurons. Although the CNS biology of NDs continues to be well studied, how gut-innervating neurons, including those that connect the gut to the brain, are affected by or involved in the etiology of these debilitating and progressive disorders has been understudied. Studies in recent years have shown how CNS and gut biology, aided by the gut-brain connecting neurons, modulate each other's functions. These studies underscore the importance of exploring the gut-innervating and gut-brain connecting neurons of the CNS and gut function in health, as well as the etiology and progression of dysfunction in NDs. In this Review, we discuss our current understanding of how the various gut-innervating neurons and gut physiology are involved in the etiology of NDs, including Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis, to cause progressive CNS and persistent gut dysfunction.
Healthcare Cost Impact of Continued Anticoagulation Therapy with Rivaroxaban Versus Aspirin for Prevention of Recurrent Symptomatic Venous Thromboembolism in the Einstein Choice Trial Population
Authors: Bruce L. Davidson, Philip S. Wells, Martin H. Prins, Jan Beyer-Westendorf, Anthonie Wa. Lensing, Lloyd Haskell, Bennett Levitan, François Laliberté, Veronica Ashton, Yongling Xiao, Dominique Lejeune, Concetta Crivera, Patrick Lefebvre, Qi Zhao, Zhong Yuan, Jeff Schein, Paolo Prandoni
Journal: Blood (2017)
Incidence of Cutaneous Reactions After Messenger RNA COVID-19 Vaccines
Authors: Lacey B. Robinson, Xiaoqing Fu, Dean Hashimoto, Paige Wickner, Erica S. Shenoy, Adam B. Landman, Kimberly G. Blumenthal
Journal: JAMA Dermatology (2021)

matous inflammation that expressed CD163, consonant with an M2 macrophage phenotype.Although the dynamic spectrum of TAMs has not been clearly delineated, 3 this shifting macrophage profile across clinically distinct lesions in 2 patients underscores the fundamental role and plasticity of macrophages in the evolution of this eruption.We suspect that the critical role of macrophages and their associated cytokines in wound healing and scar formation 4 as well as the production of interleukin 34, one of 2 distinct ligands for colonystimulating factor 1 receptor, by keratinocytes and hair follicles may contribute to this pathogenesis. 5he striking near-complete normalization of lesions on cessation of therapy in 3 patients suggests a compensatory immunologic response that facilitated repair.Recapitulation of this phenomenon in other disease states (eg, connective tissue disease) has wide-reaching implications.Limitations of this study include its observational nature and small sample size.A previous report describes 2 patients receiving treatment with nivolumab and cabiralizumab who developed atrophic lesions characterized histologically by dermal elastolysis, 6 which likely represents the same phenomenon seen in the present cohort.We suspect that additional cases of punctate anetoderma will emerge with increasing use of these combination therapies.
Abstract SY31-01: Remodeling of the cell surface proteome in cancer
Authors: James A. Wells
Journal: Cancer Research (2021)

Abstract The cell surface proteome (surfaceome) is the primary hub for cells to communicate with the outside world, and are major targets for immunotherapy. Oncogenes are known to cause huge changes in cells (see Figure 1). Our group has applied state-of-the-art proteomics methods to quantitatively compare the surfaceomes of oncogene transformed (KRAS, HER2, EGFR, BRAF, MEK, AKT and MYC) versus isogenic controls (1-3). Oncogenes lead to large and bi-directional remodeling of the surfaceomes of isogenic cell lines that can be exploited for target ID. Each oncogene has a unique signature that depends on cell line, but broadly similar across cell lines. Differences among related oncogenes converge when viewed at functional level by Geneset analysis. Proliferative oncogenes (EGFR, HER2, KRAS, BRAF, MEK) remodel the surfaceome primarily through MAPK pathway. MYC is much more unique, especially in the large changes induced in solute carrier proteins. We have also recently developed a technology to identify proteolytic cut sites in membrane proteins (4) which also show bi-direction remodeling. We show proteolysis is an orthogonal remodeling event, and the union with expression data offers new neo-epitope markers for immunotherapy. References 1. Martinko A.J., Truillet C., Julien O., Diaz J.E., Horlbeck, M.A., Whiteley G., Blonder J., Weissman J.S., Bandyopadhyay S., Evans M.J., Wells J.A. (2018) "Targeting RAS Driven Human Cancer Cells with Antibodies to Upregulated and Essential Cell-Surface Proteins." eLife. 2018;7:e31098 2. Leung, K. K., Wilson, G. M., Kirkemo, L. L., Riley, N. M., Coon, J. J., &amp; Wells, J. A. (2020). Broad and thematic remodeling of the surfaceome and glycoproteome on isogenic cells transformed with driving proliferative oncogenes. PNAS 117 (14), 7764-7775. 3. Chen, W., Mou, K. Y., Solomon, P., Aggarwal, R., Leung, K. K., &amp; Wells, J. A. (2021). Large remodeling of the Myc-induced cell surface proteome in B cells and prostate cells creates new opportunities for immunotherapy. PNAS, 118(4), 1-11. 4. Weeks, A. M., Byrnes, J. R., Lui, I., &amp; Wells, J. A. (2021). Mapping proteolytic neo-N termini at the surface of living cells. PNAS, 2020.02.23.961904. Citation Format: James A. Wells. Remodeling of the cell surface proteome in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr SY31-01.
Benefits of quitting: “more quit, more grit”
Authors: Jacob N Asplin
Journal: BMJ (2021)

Morgan’s lesson of embracing quitting as a decisive action rather than defeatist failure should ring loudly in the ears of current trainees exhausted by the efforts of the past 18 months.1 I can advocate for the “less grit, more quit” ethos—having found the UK foundation programme a demoralising experience, I quit medicine to join the Royal Marines Commandos as …
Ten Years of Experience in the Non-Intensive Treatment of Acute Leukemias in Elderly Patients of the Hematology Service of the National Medical Center November 20, ISSSTE
Authors: Jose L Alvarez, Yayra Pichardo, Maricela Ortiz, Veronica Mena, Rosa Jimenez, Luara Arana, M. Augusta Pacheco, Martha Alvarado
Journal: Blood (2017)
Considerations for Reducing Bias While Addressing Racial/Ethnic Disparities in Academic Surgery—Reply
Authors: Ruth Lewit, Ankush Gosain
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Ambulatory management of secondary spontaneous pneumothorax: a mirage, or a solution on the horizon?
Authors: Srinivas R. Mummadi, José M. Porcel
Journal: European Respiratory Journal (2021)

<b>Ambulatory management of selected patients with secondary spontaneous pneumothorax using small-bore chest catheters (12F) with an attached one-way flutter valve device seems feasible and safe</b>https://bit.ly/3oycMpG
Abstract 322: Postnatal Islet-1 Cardioblasts Are of Neural Crest and Not Second Heart-Field Lineage
Authors: Konstantinos E Hatzistergos, Joshua M Hare
Journal: Circulation Research (2016)

Introduction: The transcription factor Islet-1 (Isl1) is expressed in cardiac mesodermal and neural crest (CNC) lineages during cardiogenesis. A pool of Isl1 + cells persist in the perinatal heart (Isl1 + CPCs), some of which are touted as residual second heart-field (SHF)- derived cardioblasts. However, direct lineage-tracing evidence, supporting a SHF over a CNC origin of Isl1 + CPCs, are lacking. Hypothesis: Isl1 + CPCs are of CNC and not SHF lineage. Methods: The Isl1-nLacZ, Wnt1-Cre;tdTomato and Wnt1::FlpE;RC::Fela mice, and iPSCs derived from Wnt1-Cre;tdTomato mice (iPSC Wnt1 ) were employed to lineage-trace Isl1 + CPCs. Results: Temporal analysis of Isl1-nLacZ embryos illustrated a transient, stage-specific reporter gene activity in mesendodermal and neuroectodermal cells. Particularly, at embryonic day (E)9.5, reporter gene activity (x-gal), was strong in the outflow tract (OFT), and exhibited a weak, spotty pattern in the heart. At E12.5, x-gal was strong in the neural tube (NT); reduced in the OFT; and undetectable in the heart. Isl1 immunohistochemistry (IHC) illustrated similar activity of x-gal with endogenous Isl1 expression. Importantly, x-gal remained permanently undetected in the heart. Isl1 IHC in E12.5 Wnt1-Cre;tdTomato and Wnt1::FlpE;RC::Fela embryos indicated that Isl1 + cells in the OFT and NT colocalized with Wnt1 reporter transgenes. At E18.5 and postnatal day 1 (PN1), Isl1 + cells were exclusively of Wnt1 lineage, indicating that Isl1 + CPCs are CNC- and not SHF-derived. Since CNCs minimally contribute cardiomyocytes in mammals, a presumptive full cardiomyogenic capacity of Isl1 + CPCs potentially contrasts with a CNC origin. To address this controversy, we differentiated iPSC Wnt1 toward the CNC lineage, using a previously established embryoid body (EB) differentiation protocol involving transient BMP antagonism. At ~EB-day 9, tdTomato + /Isl1 + CNCs emerged, which progressively differentiated into spontaneously beating, Nkx2.5 + cardiomyocytes. Conclusions: Our findings clarify that Isl1 + CPCs are of CNC and not SHF origin, and suggest a novel role of the mammalian CNC, as a contributor of long-lived myocardial progenitors that could be targeted for heart-related therapeutic purposes.
Hematopoietic potential of neural stem cells [1] (multiple letters)
Authors: Angelo L. Vescovi, Rod Rietze, Maria Cristina Magli, Christopher Bjornson, Chu Chih Shih, Adam Mamelak, Thomas LeBon, Stephen J. Forman, Cindi M. Morshead, Derek Van Der Kooy, Norman N. Iscove
Journal: Nature Medicine (2002)
Recent pharmacological advances in the repurposing of artemisinin drugs
Authors: Yuqing Meng, Nan Ma, Haining Lyu, Yin Kwan Wong, Xing Zhang, Yongping Zhu, Peng Gao, Peng Sun, Yali Song, Lizhu Lin, Jigang Wang
Journal: Medicinal Research Reviews (2021)

Abstract Artemisinins are a family of sesquiterpene lactones originally derived from the sweet wormwood ( Artemisia annua ). Beyond their well‐characterized role as frontline antimalarial drugs, artemisinins have also received increased attention for other potential pharmaceutical effects, which include antiviral, antiparsitic, antifungal, anti‐inflammatory, and anticancer activities. With concerted efforts in further preclinical and clinical studies, artemisinin‐based drugs have the potential to be viable treatments for a great variety of human diseases. Here, we provide a comprehensive update on recent reports of pharmacological actions and applications of artemisinins outside of their better‐known antimalarial role and highlight their potential therapeutic viability for various diseases.
Abstract 367: Combined Effect of Dinitrophenol Preconditioning and Jagged-1 Over-expression in Mesenchymal Stem Cells Improved Cardiomyogenesis and Angiogenesis in Rat Model of Myocardial Infarction
Authors: Asmat Salim, Anwar Ali, Muhammad A Akhter, Irfan Khan, Nadia Naeem
Journal: Circulation Research (2016)

Cardiac regeneration following myocardial infarction (MI) largely depends on angiogenesis; an important physiological response that allows the heart to recover. Mesenchymal stem cells (MSCs) can be utilized as a source for cardiac regeneration and angiogenesis using various preconditioning strategies. We investigated the role of cardiomyogenic and angiogenic growth factors combined with preconditioning of MSCs using 2, 4, dinitrophenol (DNP). MSCs were isolated from rat bone marrow and treated with DNP; an uncoupler of oxidative phosphorylation. Based on our earlier report in which we showed that DNP treatment affect the expression of cardiomyogenic and angiogenic factors after different re-oxygenation periods, we selected jagged 1 (Jag1), neuropilin1 (Nrp1), TATA box 20 (Tbx20), and myogenin (Myo) to transfect MSCs. Rat MI models were developed through ligation of left anterior descending coronary artery and confirmed through echocardiographic evaluation 4 weeks post MI. The study was divided into different groups which include control; MI model; and MI groups that received untreated, DNP-treated, transfected-MSCs using the above mentioned growth factors and transfected and DNP-treated MSCs. Functional performance of the hearts was analyzed through echocardiography while regeneration of cardiomyocytes and angiogenesis were observed through histological examination. Significant (p&lt;0.05) improvement in the heart function was observed in case of all treatment groups when compared with the normal MSCs. Histological examination of the heart sections 4 weeks post MI showed that MSCs home towards the site of injury. Most prominent result was observed in case of Jag1-transfected and DNP treated MSCs with heart function comparable to that of the control group. Cardiac regeneration and newly developed blood vessels were prominent in the tissue sections. Significant reduction (p&lt;0.05) in the infarct size was also observed as compared to that in case of Myo, Tbx20 and Nrp1 groups. It is, therefore, concluded that Jag1-transfected MSCs can be a suitable angiogenic factor to be used in combination with DNP for preconditioning of MSCs for future regenerative therapy for cardiomyogenesis.
Survey Regarding Academic vs Private Practice Surgeons—A Gold Mine of Information—Reply
Authors: Stephen T. Mahoney, Michelle R. Brownstein
Journal: JAMA Surgery (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 Surgery 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 Surgery journal