tbuckley/cabot-search huggingface dataset:
Immune checkpoint silencing using RNAi-incorporated nanoparticles enhances antitumor immunity and therapeutic efficacy compared with antibody-based approaches
Authors: Ji Eun Won, Youngseon Byeon, Tae In Wi, Chan Mi Lee, Ju Hyeong Lee, Tae Heung Kang, Jeong-Won Lee, YoungJoo Lee, Yeong-Min Park, Hee Dong Han
Journal: Journal for ImmunoTherapy of Cancer (2022)

Cytotoxic CD8+ T cell-based cancer immunotherapy has been extensively studied and applied, however, tumor cells are known to evade immune responses through the expression of immune checkpoints, such as programmed death ligand 1 (PD-L1). To overcome these issues, antibody-based immune checkpoint blockades (eg, antiprogrammed cell death 1 (anti-PD-1) and anti-PD-L1) have been revolutionized to improve immune responses. However, their therapeutic efficacy is limited to 15%-20% of the overall objective response rate. Moreover, PD-L1 is secreted from tumor cells, which can interrupt antibody-mediated immune reactions in the tumor microenvironment.We developed poly(lactic-co-glycolic acid) nanoparticles (PLGA-NPs) encapsulating PD-L1 small interfering RNA (siRNA) and PD-1 siRNA, as a delivery platform to silence immune checkpoints. This study used the TC-1 and EG7 tumor models to determine the potential therapeutic efficacy of the PLGA (PD-L1 siRNA+PD-1 siRNA)-NPs, on administration twice per week for 4 weeks. Moreover, we observed combination effect of PLGA (PD-L1 siRNA+PD-1 siRNA)-NPs and PLGA (antigen+adjuvant)-NPs using TC-1 and EG7 tumor-bearing mouse models.PLGA (PD-L1 siRNA+PD-1 siRNA)-NPs boosted the host immune reaction by restoring CD8+ T cell function and promoting cytotoxic CD8+ T cell responses. We demonstrated that the combination of NP-based therapeutic vaccine and PLGA (siRNA)-NPs resulted in significant inhibition of tumor growth compared with the control and antibody-based treatments (p<0.001). The proposed system significantly inhibited tumor growth compared with the antibody-based approaches.Our findings suggest a potential combination approach for cancer immunotherapy using PLGA (PD-L1 siRNA+PD-1 siRNA)-NPs and PLGA (antigen+adjuvant)-NPs as novel immune checkpoint silencing agents.
Glymphatic system clears extracellular tau and protects from tau aggregation and neurodegeneration
Authors: Kazuhisa Ishida, Kaoru Yamada, Risa Nishiyama, Tadafumi Hashimoto, Itaru Nishida, Yoichiro Abe, Masato Yasui, Takeshi Iwatsubo
Journal: The Journal of Experimental Medicine (2022)

Accumulation of tau has been implicated in various neurodegenerative diseases termed tauopathies. Tau is a microtubule-associated protein but is also actively released into the extracellular fluids including brain interstitial fluid and cerebrospinal fluid (CSF). However, it remains elusive whether clearance of extracellular tau impacts tau-associated neurodegeneration. Here, we show that aquaporin-4 (AQP4), a major driver of the glymphatic clearance system, facilitates the elimination of extracellular tau from the brain to CSF and subsequently to deep cervical lymph nodes. Strikingly, deletion of AQP4 not only elevated tau in CSF but also markedly exacerbated phosphorylated tau deposition and the associated neurodegeneration in the brains of transgenic mice expressing P301S mutant tau. The current study identified the clearance pathway of extracellular tau in the central nervous system, suggesting that glymphatic clearance of extracellular tau is a novel regulatory mechanism whose impairment contributes to tau aggregation and neurodegeneration.
THE PUBLIC PRESS AND THE PHYSICIANS.
Journal: JAMA (1993)

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
Contents
Authors: C Weiler-Normann, A Lohse, I Veldhuijzen, R Wolter, V Rijckborst, M Mostert, H Voeten, Y Cheung, C Boucher, J Reijnders, O De Zwart, H Janssen, P Mahale, D Kontoyiannis, R Chemaly, Y Jiang, J Hwang, M Davila, H Torres, N Furusyo, E Ogawa, M Sudoh, M Murata, T Ihara, T Hayashi, H Ikezaki, S Hiramine, H Mukae, K Toyoda, H Taniai, K Okada, M Kainuma, E Kajiwara, J Hayashi, S Kaur, D Tripathi, K Dongre, V Garg, S Rooge, A Mukopadhyay, P Sakhuja, S Sarin, E Sola, H Watson, I Graupera, F Turo ´n, R Barreto, E Rodrı ´guez, M Pavesi, V Arroyo, M Guevara, P Gine, P.-H Chen, W.-C Chen, M.-C Hou, T.-T Liu, C.-J Chang, W.-C Liao, C.-W Su, H.-M Wang, H.-C Lin, F.-Y Lee, S.-D Lee, J Hoekstra, S Seijo, P Rautou, G Ducarme, L Boudaoud, D Luton, J Alijotas-Reig, M Casellas-Caro, B Condat, E Bresser, D Thabut, B Larroque, J Ga ´rcia-Paga, D Valla, A Plessier, A Furlan, F Lamballe, V Stagni, A Hussain, S Richelme, A Prodosmo, A Moumen, C Brun, I Del Barco Barrantes, J Arthur, A Koleske, A Nebreda, D Barila, F Maina, S Sockalingam, D Blank, N Abdelhamid, S Abbey, G Hirschfield, E Koehler, J Schouten, B Hansen, F Van Rooij, A Hofman, B Stricker, N Alkhouri, R De Vito, A Alisi, L Yerian, R Lopez, A Feldstein, V Nobili, L Valenti, A Fracanzani, R Rametta, M Fraquelli, G Soverini, S Pelusi, P Dongiovanni, D Conte, S Fargion, R Jalan, P Gines, J Olson, R Mookerjee, R Moreau, G Garcia-Tsao, P Kamath, G Dore, G Mccaughan, A.-C Piguet, P Martins, S Kozma, N De Wit, L Afman, M Mensink, M Mu ¨ller, S Haı ¨m-Boukobza, M.-P Ferey, A.-L Ve, A Jeblaoui, E Pe ´lissier, G Pelletier, L Teillet, A.-M Roque-Afonso, M Schaefer, L Capuron, A Friebe, C Diez-Quevedo, G Robaeys, S Neri, G Foster, A Kautz, D Forton, C Pariante, E Tsochatzis, P Manousou, A Dhillon, A Burroughs, E Ellis, D Mann, R.-N Feng, G.-Q Li, Y Li, C.-H Sun, W Dunn, J Schwimmer
Journal: Journal of Hepatology (2012)
Aerobic exercise for eight weeks provides protective effects towards liver and cardiometabolic health and adipose tissue remodeling under metabolic stress for one week: A study in mice
Authors: Youn Ju Kim, Hye Jin Kim, Sang Gyu Lee, Do Hyun Kim, Su In Jang, Hye Sun Go, Won Jun Lee, Je Kyung Seong
Journal: Metabolism (2022)

The relationship between exercise training and health benefits is under thorough investigation. However, the effects of exercise training on the maintenance of metabolic health are unclear.Our experimental design involved initial exercise training followed by a high-fat diet (HFD) challenge. Eight-week-old male was trained under voluntary wheel running aerobic exercise for eight weeks to determine the systemic metabolic changes induced by exercise training and whether such changes persisted even after discontinuing exercise. The mice were given either a normal chow diet (NCD) or HFD ad libitum for one week after discontinuation of exercise (CON-NCD, n = 29; EX-NCD, n = 29; CON-HFD, n = 30; EX-HFD, n = 31).Our study revealed that metabolic stress following the transition to an HFD in mice that discontinued training failed to reverse the aerobic exercise training-induced improvement in metabolism. We report that the mice subjected to exercise training could better counteract weight gain, adipose tissue hypertrophy, insulin resistance, fatty liver, and mitochondrial dysfunction in response to an HFD compared with untrained mice. This observation could be attributed to the fact that exercise enhances the browning of white fat, whole-body oxygen uptake, and heat generation. Furthermore, we suggest that the effects of exercise persist due to PPARα-FGF21-FGFR1 mechanisms, although additional pathways cannot be excluded and require further research. Although our study suggests the preventive potential of exercise, appropriate human trials are needed to demonstrate the efficacy in subjects who cannot perform sustained exercise; this may provide an important basis regarding human health.
PREVALENCE OF PULMONARY HYPERTENSION IN HOSPITALIZED HEART FAILURE PATIENTS WITH AND WITHOUT SARCOIDOSIS
Authors: Mukunthan Murthi, Ramtej Atluri, Sujitha Velagapudi, Andrea Torres, Genaro Velazquez, Hafeez Shaka, Karol Quelal
Journal: Journal of the American College of Cardiology (2021)
Sensible regulation and clinical implementation of clinical decision support software as a medical device
Authors: Makoto Mori, Robert Jarrin, Yuan Lu, Kushal Kadakia, Chenxi Huang, Joseph S. Ross, Harlan M. Krumholz
Journal: BMJ (2022)

Recently published research determined that the Epic Systems Corporation Sepsis Model-a widely implemented electronic health record (EHR) based software to identify patients with sepsis-performed poorly at identifying patients at risk for sepsis compared with standard workflows, despite generating added burden for clinicians. 1 While the company had internally validated the model in 2015, limited information was made public about the algorithm's performance because it-like many other clinical decision support tools-did not require clearance from the United States Food and Drug Administration (FDA) before being used in patient care.
Withdrawal of Rotavirus Vaccine Recommendation
Journal: JAMA (1999)

In July 1999, CDC recommended that health-care providers and parents postpone use of the rhesus rotavirus vaccine-tetravalent (RRV-TV) (RotaShield, Wyeth Laboratories, Inc., Marietta, Pennsylvania), for infants, at least until November 1999. This action was based on reports to the Vaccine Adverse Event Reporting System of intussusception (a type of bowel obstruction that occurs when the bowel folds in on itself) among 15 infants who received rotavirus vaccine. Also at that time, the manufacturer, in consultation with the Food and Drug Administration, voluntarily ceased further distribution of the vaccine.
PHILADELPHIA LETTER.
Authors: None M. D.
Journal: JAMA (1883)

Washington, D. C., July 2, 1883. <h3>Dear Sir:</h3> Allow me to suggest to you that, with the inauguration of the medical journal, which is to be the organ of the American Medical Association, you open your columns for the discussion of a scheme which shall have for its object the establishment of a Medical Benefit Society. We have plenty of time between now and the next annual meeting of the Association at Washington, in May, 1884, to ascertain how far such a scheme would be supported, and in what shape it would be best to put it, in order to bring it properly before the Association. That there is a great need for such a society every medical practitioner, of any length of service, will readily acknowledge, and, while we see aid societies and insurance companies working successfully around us for special purposes and for the general public, we cannot
Functioning Pancreatic Islet Cell Adenoma
Journal: JAMA (1963)

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
Vitamins during pregnancy and neural tube defects
Authors: James L. Mills, George G. Rhoads, Joe Leigh Simpson, George C. Cunningham
Journal: JAMA (1990)

<h3>To the Editor.—</h3> In their article entitled "Multivitamin/Folic Acid Supplementation in Early Pregnancy Reduces the Prevalence of Neural Tube Defects," Milunsky and coauthors<sup>1</sup>suggest that recall bias or undercounting vitamin use in early pregnancy could have resulted in our study's<sup>2</sup>finding that vitamin and folate supplement use was not associated with a decreased risk for neural tube defects. We do not consider recall bias a problem in our study, however, becausemore than half the women who reported supplement use were able to locate the bottle and read us the ingredients, good evidence that the data are accurately reported. Milunsky et al state that most of their subjects did not know their pregnancy outcomes at the time of their interviews. However, it would be important to know how many women, especially those with neural tube defects, knew the results of their maternal serum α-fetoprotein screening tests before they were
Influence of Patients’ Requests for Direct-to-Consumer Advertised Antidepressants: A Randomized Controlled Trial—Correction
Authors: Steven Landers, Paul Gunn, Susan Flocke, Antonnette Graham, George Kikano, Shirley Moore, Frances Bolton, Kurt Stange
Journal: JAMA (2005)

beneficiaries were provided by primary care physicians.From 1998 to 2003 there was rapid growth in house calls by nurse practitioners and physician assistants and a decline in house calls by podiatrists, psychiatrists, and general surgeons.Comment.House calls to Medicare beneficiaries became more common from 1998 to 2004.Although still relatively infrequent, these results indicate a reversal in the downward trend in house calls that was reported in a 1997 analysis. 1Factors that may have contributed to this change include the 1998 increase in Medicare reimbursement for home visits, growth in hospital-based house call programs, early hospital discharge programs, and efforts to increase the role of house calls in medical education. 2The rapid growth in the volume of house calls provided by nurse practitioners is consistent with the reported success of multidisciplinary home-based models of care that rely on nurse practitioners. 2 Limitations in these data include that they are from deidentified aggregated billing files.Characteristics of the individuals receiving house calls, such as age, health, number of house calls received, and geographic location were not available.House calls to Medicare Advantage enrollees were not included, and house calls that were not billed or allowed were not accounted for, so the estimates likely underrepresent the actual number of house calls.Further studies are needed to better understand patient-and physicianlevel factors contributing to the changes, as well as the impact of house calls on patient care and public health.
Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
Authors: Nadilly Bonagas, Nina M. S. Gustafsson, Martin Henriksson, Petra Marttila, Robert Gustafsson, Elisée Wiita, Sanjay Borhade, Alanna C. Green, Karl S. A. Vallin, Antonio Sarno, Richard Svensson, Camilla Göktürk, Therese Pham, Ann-Sofie Jemth, Olga Loseva, Victoria Cookson, Nicole Kiweler, Lars Sandberg, Azita Rasti, Judith E. Unterlass, Martin Haraldsson, Yasmin Andersson, Emma R. Scaletti, Christoffer Bengtsson, Cynthia B. J. Paulin, Kumar Sanjiv, Eldar Abdurakhmanov, Linda Pudelko, Ben Kunz, Matthieu Desroses, Petar Iliev, Katarina Färnegårdh, Andreas Krämer, Neeraj Garg, Maurice Michel, Sara Häggblad, Malin Jarvius, Christina Kalderén, Amanda Bögedahl Jensen, Ingrid Almlöf, Stella Karsten, Si Min Zhang, Maria Häggblad, Anders Eriksson, Jianping Liu, Björn Glinghammar, Natalia Nekhotiaeva, Fredrik Klingegård, Tobias Koolmeister, Ulf Martens, Sabin Llona-Minguez, Ruth Moulson, Helena Nordström, Vendela Parrow, Leif Dahllund, Birger Sjöberg, Irene L. Vargas, Duy Duc Vo, Johan Wannberg, Stefan Knapp, Hans E. Krokan, Per I. Arvidsson, Martin Scobie, Johannes Meiser, Pål Stenmark, Ulrika Warpman Berglund, Evert J. Homan, Thomas Helleday
Journal: Nature Cancer (2022)

Abstract The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors.
Erratum: Genome-wide association analyses identifies a susceptibility locus for tuberculosis on chromosome 18q11.2
Authors: Thorsten Thye, Fredrik O Vannberg, Sunny H Wong, Ellis Owusu-Dabo, Ivy Osei, John Gyapong, Giorgio Sirugo, Fatou Sisay-Joof, Anthony Enimil, Margaret A Chinbuah, Sian Floyd, David K Warndorff, Lifted Sichali, Simon Malema, Amelia C Crampin, Bagrey Ngwira, Yik Y Teo, Kerrin Small, Kirk Rockett, Dominic Kwiatkowski, Paul E Fine, Philip C Hill, Melanie Newport, Christian Lienhardt, Richard A Adegbola, Tumani Corrah, Andreas Ziegler, Andrew P Morris, Christian G Meyer, Rolf D Horstmann, Adrian V S Hill
Journal: Nature Genetics (2011)
Kinetic analysis of lipoproteins
Authors: A. C. Asmal
Journal: JAMA (1985)

<h3>In Reply.—</h3> A postmarketing surveillance survey of over 70,000 injections performed by Smith Laboratories, reported an associated lower frequency of anaphylaxis under local anesthesia<i>v</i>under general anesthesia (0.4%<i>v</i>0.6%, respectively) (product information letter, Smith Laboratories, June 1, 1984, p 3). The postmarketing surveillance forms are filled out in the operating room by the physician and anesthesiologist. The error of this type of reporting lies in the fact that all cases of allergic reaction are not anaphylactic reactions, so, although the anesthesiologist may have termed them "anaphylactic reactions," in reality, they might have been allergic reactions. There is no doubt that there is more polypharmacy involved with general anesthesia than local anesthesia, and, with the use of a large number of drugs, the chance for an allergic reaction is higher than with the use of a smaller number of drugs. Because of the nature of the procedures, a larger
2-Year Outcomes After Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients
Authors: John K. Forrest, G. Michael Deeb, Steven J. Yakubov, Joshua D. Rovin, Mubashir Mumtaz, Hemal Gada, Daniel O’Hair, Tanvir Bajwa, Paul Sorajja, John C. Heiser, William Merhi, Abeel Mangi, Douglas J. Spriggs, Neal S. Kleiman, Stanley J. Chetcuti, Paul S. Teirstein, George L. Zorn, Peter Tadros, Didier Tchétché, Jon R. Resar, Antony Walton, Thomas G. Gleason, Basel Ramlawi, Ayman Iskander, Ronald Caputo, Jae K. Oh, Jian Huang, Michael J. Reardon
Journal: Journal of the American College of Cardiology (2022)
Leads from the MMWR. Update: pneumococcal polysaccharide vaccine usage--United States
Journal: JAMA (1984)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
ORIGIN OF PERCUSSION.
Journal: JAMA (1899)

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