tbuckley/cabot-search huggingface dataset:
Ironing out mechanisms of iron homeostasis and disorders of iron deficiency
Authors: Navid Koleini, Jason S. Shapiro, Justin Geier, Hossein Ardehali
Journal: Journal of Clinical Investigation (2021)

Iron plays an important role in mammalian physiological processes. It is a critical component for the function of many proteins, including enzymes that require heme and iron-sulfur clusters. However, excess iron is also detrimental because of its ability to catalyze the formation of reactive oxygen species. As a result, cellular and systemic iron levels are tightly regulated to prevent oxidative damage. Iron deficiency can lead to a number of pathological conditions, the most prominent being anemia. Iron deficiency should be corrected to improve adult patients’ symptoms and to facilitate normal growth during fetal development and childhood. However, inappropriate use of intravenous iron in chronic conditions, such as cancer and heart failure, in the absence of clear iron deficiency can lead to unwanted side effects. Thus, this form of therapy should be reserved for certain patients who cannot tolerate oral iron and need rapid iron replenishment. Here, we will review cellular and systemic iron homeostasis and will discuss complications of iron deficiency.
Equity and the JAMA Network
Authors: Phil B. Fontanarosa, Annette Flanagin, John Z. Ayanian, Robert O. Bonow, Neil M. Bressler, Dimitri Christakis, Mary L. Disis, S. Andrew Josephson, Melina R. Kibbe, Dost Öngür, Jay F. Piccirillo, Rita F. Redberg, Frederick P. Rivara, Kanade Shinkai, Clyde W. Yancy
Journal: JAMA Neurology (2021)

The key objective of JAMA is "To promote the science and art of medicine and the betterment of the public health"; similar objectives and mission statements are supported by all 12 JAMA Network Journals.Together this family of journals is committed to publishing the best research, reviews, and opinion articles to advance medical science, promote public health, and improve patient care.The ultimate goal is to promulgate truth in science and medicine.On February 23, 2021, a podcast titled "Structural Racism for Doctors-What Is It?" was posted by the JAMA Network and on the following day, a tweet was posted to promote the podcast.Assertions in both that disavowed the presence of structural racism in medicine and among physicians were wrong, misguided, and uninformed.An extensive evidence base strongly supports the presence of structural racism in medicine and its adverse influence on health. 1 The process for reviewing and publishing the podcast and tweet was also flawed.On March 4, 2021, Howard Bauchner, MD, editor in chief of JAMA and the 12 JAMA Network Journals, took responsibility and issued an apology for the podcast and tweet.This editorial team also expresses a profound apology for the misinformation in the podcast and tweet and recognizes the hurt, anger, and outrage that resulted.These events and developments make it clear that JAMA and the JAMA Network Journals can and must do better and advance toward inclusion and antiracism in all journal-related activities.Even though these journals have made progress, additional commitment and work are needed to build on and intensify these efforts to achieve meaningful, sustainable change.For instance, previous efforts include the more than 650 research, review, and opinion articles on race, racism, and racial and ethnic disparities and inequities that have been published in JAMA and the JAMA Network Journals since 2015, 1 including editorials in JAMA on topics such as race and medic al research, 2 race and poverty and medicine, 3 enhancing diversity in medical schools, 4 and equity related to COVID-19 vaccines. 5n addition, within the past year, JAMA Network Open and JAMA Health Forum issued calls for manuscripts on prevention and effects of systemic racism in health 6,7 ; JAMA Psychiatry initiated an editorial fellowship prioritized to early-career academic psychiatrists from underrepresented backgrounds; and JAMA Surgery issued a "Call to Action" to all surgery journal editors for diversity in the editorial and peer review process.
Considering the possibilities and pitfalls of Generative Pre-trained Transformer 3 (GPT-3) in healthcare delivery
Authors: Diane M. Korngiebel, Sean D. Mooney
Journal: npj Digital Medicine (2021)

Natural language computer applications are becoming increasingly sophisticated and, with the recent release of Generative Pre-trained Transformer 3, they could be deployed in healthcare-related contexts that have historically comprised human-to-human interaction. However, for GPT-3 and similar applications to be considered for use in health-related contexts, possibilities and pitfalls need thoughtful exploration. In this article, we briefly introduce some opportunities and cautions that would accompany advanced Natural Language Processing applications deployed in eHealth.
Effect of Sodium Nitrite on Survival of Cardiac Arrest to Hospital Admission
Authors: Wentao Sang, Feng Xu
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
circPDE4B prevents articular cartilage degeneration and promotes repair by acting as a scaffold for RIC8A and MID1
Authors: Shuying Shen, Yute Yang, Panyang Shen, Jun Ma, Bin Fang, Qingxin Wang, Kefan Wang, Peihua Shi, Shunwu Fan, Xiangqian Fang
Journal: Annals of the Rheumatic Diseases (2021)

Circular RNAs (circRNAs) have emerged as significant biological regulators. Herein, we aimed to elucidate the role of an unidentified circRNA (circPDE4B) that is reportedly downregulated in osteoarthritis (OA) tissues.The effects of circPDE4B were explored in human and mouse chondrocytes in vitro. Specifically, RNA pull-down (RPD)-mass spectrometry analysis (MS), immunoprecipitation, glutathione-S-transferase (GST) pull-down, RNA immunoprecipitation and RPD assays were performed to verify the interactions between circPDE4B and the RIC8 guanine nucleotide exchange factor A (RIC8A)/midline 1 (MID1) complex. A mouse model of OA was also employed to confirm the role of circPDE4B in OA pathogenesis in vivo.circPDE4B regulates chondrocyte cell viability and extracellular matrix metabolism. Mechanistically, FUS RNA binding protein (FUS) was found to promote the splicing of circPDE4B, while downregulation of circPDE4B in OA is partially caused by upstream inhibition of FUS. Moreover, circPDE4B facilitates the association between RIC8A and MID1 by acting as a scaffold to promote RIC8A degradation through proteasomal degradation. Furthermore, ubiquitination of RIC8A at K415 abrogates RIC8A degradation. The circPDE4B-RIC8A axis was observed to play an important role in regulating downstream p38 mitogen-activated protein kinase (MAPK) signalling. Furthermore, delivery of a circPDE4B adeno-associated virus (AAV) abrogates the breakdown of cartilage matrix by medial meniscus destabilisation in mice, whereas a RIC8A AAV induces the opposite effect.This work highlights the function of the circPDE4B-RIC8A axis in OA joints, as well as its regulation of MAPK-p38, suggesting this axis as a potential therapeutic target for OA.
An external validation of the QCovid risk prediction algorithm for risk of mortality from COVID-19 in adults: a national validation cohort study in England
Authors: Vahé Nafilyan, Ben Humberstone, Nisha Mehta, Ian Diamond, Carol Coupland, Luke Lorenzi, Piotr Pawelek, Ryan Schofield, Jasper Morgan, Paul Brown, Ronan Lyons, Aziz Sheikh, Julia Hippisley-Cox
Journal: The Lancet Digital Health (2021)

Public policy measures and clinical risk assessments relevant to COVID-19 need to be aided by risk prediction models that are rigorously developed and validated. We aimed to externally validate a risk prediction algorithm (QCovid) to estimate mortality outcomes from COVID-19 in adults in England.We did a population-based cohort study using the UK Office for National Statistics Public Health Linked Data Asset, a cohort of individuals aged 19-100 years, based on the 2011 census and linked to Hospital Episode Statistics, the General Practice Extraction Service data for pandemic planning and research, and radiotherapy and systemic chemotherapy records. The primary outcome was time to COVID-19 death, defined as confirmed or suspected COVID-19 death as per death certification. Two periods were used: (1) Jan 24 to April 30, 2020, and (2) May 1 to July 28, 2020. We assessed the performance of the QCovid algorithms using measures of discrimination and calibration. Using predicted 90-day risk of COVID-19 death, we calculated r2 values, Brier scores, and measures of discrimination and calibration with corresponding 95% CIs over the two time periods.We included 34 897 648 adults aged 19-100 years resident in England. 26 985 (0·08%) COVID-19 deaths occurred during the first period and 13 177 (0·04%) during the second. The algorithms had good discrimination and calibration in both periods. In the first period, they explained 77·1% (95% CI 76·9-77·4) of the variation in time to death in men and 76·3% (76·0-76·6) in women. The D statistic was 3·761 (3·732-3·789) for men and 3·671 (3·640-3·702) for women and Harrell's C was 0·935 (0·933-0·937) for men and 0·945 (0·943-0·947) for women. Similar results were obtained for the second time period. In the top 5% of patients with the highest predicted risks of death, the sensitivity for identifying deaths in the first period was 65·94% for men and 71·67% for women.The QCovid population-based risk algorithm performed well, showing high levels of discrimination for COVID-19 deaths in men and women for both time periods. QCovid has the potential to be dynamically updated as the pandemic evolves and, therefore, has potential use in guiding national policy.UK National Institute for Health Research.
Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents
Authors: Robert W. Frenck, Nicola P. Klein, Nicholas Kitchin, Alejandra Gurtman, Judith Absalon, Stephen Lockhart, John L. Perez, Emmanuel B. Walter, Shelly Senders, Ruth Bailey, Kena A. Swanson, Hua Ma, Xia Xu, Kenneth Koury, Warren V. Kalina, David Cooper, Timothy Jennings, Donald M. Brandon, Stephen J. Thomas, Özlem Türeci, Dina B. Tresnan, Susan Mather, Philip R. Dormitzer, Uğur Şahin, Kathrin U. Jansen, William C. Gruber
Journal: New England Journal of Medicine (2021)

BackgroundUntil very recently, vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had not been authorized for emergency use in persons younger than 16 years of age. Safe, effective vaccines are needed to protect this population, facilitate in-person learning and socialization, and contribute to herd immunity.MethodsIn this ongoing multinational, placebo-controlled, observer-blinded trial, we randomly assigned participants in a 1:1 ratio to receive two injections, 21 days apart, of 30 μg of BNT162b2 or placebo. Noninferiority of the immune response to BNT162b2 in 12-to-15-year-old participants as compared with that in 16-to-25-year-old participants was an immunogenicity objective. Safety (reactogenicity and adverse events) and efficacy against confirmed coronavirus disease 2019 (Covid-19; onset, ≥7 days after dose 2) in the 12-to-15-year-old cohort were assessed.ResultsOverall, 2260 adolescents 12 to 15 years of age received injections; 1131 received BNT162b2, and 1129 received placebo. As has been found in other age groups, BNT162b2 had a favorable safety and side-effect profile, with mainly transient mild-to-moderate reactogenicity (predominantly injection-site pain [in 79 to 86% of participants], fatigue [in 60 to 66%], and headache [in 55 to 65%]); there were no vaccine-related serious adverse events and few overall severe adverse events. The geometric mean ratio of SARS-CoV-2 50% neutralizing titers after dose 2 in 12-to-15-year-old participants relative to 16-to-25-year-old participants was 1.76 (95% confidence interval [CI], 1.47 to 2.10), which met the noninferiority criterion of a lower boundary of the two-sided 95% confidence interval greater than 0.67 and indicated a greater response in the 12-to-15-year-old cohort. Among participants without evidence of previous SARS-CoV-2 infection, no Covid-19 cases with an onset of 7 or more days after dose 2 were noted among BNT162b2 recipients, and 16 cases occurred among placebo recipients. The observed vaccine efficacy was 100% (95% CI, 75.3 to 100).ConclusionsThe BNT162b2 vaccine in 12-to-15-year-old recipients had a favorable safety profile, produced a greater immune response than in young adults, and was highly effective against Covid-19. (Funded by BioNTech and Pfizer; C4591001 ClinicalTrials.gov number, NCT04368728.)
Equity and the JAMA Network
Authors: Phil B. Fontanarosa, Annette Flanagin, John Z. Ayanian, Robert O. Bonow, Neil M. Bressler, Dimitri Christakis, Mary L. Disis, S. Andrew Josephson, Melina R. Kibbe, Dost Öngür, Jay F. Piccirillo, Rita F. Redberg, Frederick P. Rivara, Kanade Shinkai, Clyde W. Yancy
Journal: JAMA Cardiology (2021)

Unfortunately, this issue of affordability and budget impact may have direct implications for the incorporation of SGLT2 inhibitors into routine clinical practice and the related viability of a 4-pillar strategy as a new standard of care.Approximately 67% of the estimated 3.1 million patients with heart failure and reduced ejection fraction in the US are expected to be candidates for SGLT2 inhibitors. 11At the current Medicare Part D drug pricing (approximately $16 per pill), full deployment of dapagliflozin in eligible candidates would increase the annual societal cost of heart failure management by $12 billion.Sacubitril-valsartan, which has had an unexpectedly slow incorporation into US clinical practice since receiving US Food and Drug Administration approval in 2015, is similarly priced, has comparable clinical effectiveness, and is cost-effective. 12 The reasons for its anemic uptake are incompletely defined, but even with full inclusion on formular-ies and elimination of preapproval requirements, use remains very low, and patient-borne out-of-pocket costs may be a key factor. 8Analyses of claims data suggest that rates of abandonment of new prescriptions at retail pharmacies are less than 5% when there are no out-of-pocket costs but increase to approximately 45% when out-of-pocket costs are $125 and 60% when out-of-pocket costs exceed $500. 13 Will the 4-pillar standard of care represent passage into a new era of heart failure treatment, or will the economics of the 4 pillars signal nothing further beyond current practice?With more emerging heart failure therapies on the horizon (eg, vericiguat, omecamtiv mecarbil), clinicians and patients are faced with the possibility of even more (expensive) pillars to come.Hercules, for all his strength of purpose, did not have to contend with the cost consequences of what he did.Modern medicine does.
Suppression of the fibrotic encapsulation of silicone implants by inhibiting the mechanical activation of pro-fibrotic TGF-β
Authors: Nina Noskovicova, Ronen Schuster, Sander van Putten, Maya Ezzo, Anne Koehler, Stellar Boo, Nuno M. Coelho, David Griggs, Peter Ruminski, Christopher A. McCulloch, Boris Hinz
Journal: Nature Biomedical Engineering (2021)
AB0601 COMPARISON OF THE EFFECT OF DIFFERENT PHYSICAL THERAPY PROGRAM IN THE REHABILITATION OF KNEE OSTEOARTHRITIS PATIENTS
Authors: A. Vizdoaga, V. Salaru, M. Cebanu, V. Sadovici-Bobeica, N. Loghin-Oprea, L. Mazur-Nicorici, T. Rotaru, M. Garabajiu, M. Mazur
Journal: Annals of the Rheumatic Diseases (2021)

Background: Knee osteoarthritis (OA) is an increasingly common and disabling problem in worldwide. Exercises are considered the cornerstone of non-surgical management of knee OA and is recommended in all current clinical guidelines. The diversity of exercise programs determines the need to compare their efficiency, in order to recommend the best option for the patient. Objectives: The aim of the present study was to compare the effect on knee functionality of conventional exercises program and combinate with manual therapy in patients with knee osteoarthritis. Methods: 164 patients that fulfilled the ACR classification criteria for knee osteoarthritis (127 females and 37 males) ranging in age from 42 to 84 years (mean 62,2 SD 8,76), participated in a 10 days two-arm randomized trial. One group (Gr.1) received an exercises program, the other group additionally manual therapy methods (Gr.2). Pain and function were measured with a Visual Analogue Scale (VAS, mm) and Knee Injury and Osteoarthritis Outcomes Score (KOOS) with 5 domains (Pain, Symptoms, Activity in Daily Living (ADL), Sport and recreation (Sport/rec.) and Quality of life (QoL)). Results: In the Gr.1 were 82 patients mean age 61,8±9,2 years and in Gr.2 – 82 patients 62,7±8,3 years (p&gt;0.05). The initial level of pain (63,4±14,2 vs 60,2±18,8mm) and knee functionality according to KOOS (Tab1.) were similar in both groups, p&gt;0.05. After 10 days rehabilitation program, VAS in Gr.1 was 39,6±14,8 mm, in Gr.2- 28,5±11,6 mm, (p&lt;0.01). The KOOS results at the end of the rehabilitation program were with improvement, statistically significative in the Gr.2 (p&lt;0,05). Table 1. The KOOS results at baseline and after 10 days of rehabilitation program. KOOS scales (M±SD), % Group 1 Group 2 Baseline After 10 days Baseline After 10 days Pain 55,5 ±13,8 63,4±13,6 53,0±22,3 64,3±19,1 Symptoms 59,0±18,7 65,6±18,1 56,6±19,0 69,0±15,9 ADL 46,3±15,5 54,5±16,0 43,0±19,9 55,1±18,2 Sport/rec 15,6±17,3 23,1±19,6 16,0±24,3 30,5±23,6 QoL 29,3±22,2 36,5± 22,9 34,8±23,9 50,6±18,9 Conclusion: The reduction of pain and recovery of function were found in both groups, with better results in patients who received manual therapy and exercises program. This study supports the routine manual therapy in rehabilitation program in patients with knee osteoarthritis. Disclosure of Interests: None declared.
AB0845 THE COMBINATION OF PLASMA FIBRINOGEN CONCENTRATION AND NEUTROPHIL-LYMPHOCYTE RATIO (F-NLR) AS A NOVEL INFLAMMATORY MARKER OF RHEUMATOID ARTHRITIS
Authors: M. Liu, Z. Huang, Y. Huang, Z. Huang, Q. Huang, T. W. LI
Journal: Annals of the Rheumatic Diseases (2021)

Background: The combined index of fibrinogen and neutrophil-lymphocyte ratio (F-NLR) has recently been reported as a new predictive factor in patients with cancer. However, the fibrinogen and NLR have not been simultaneously evaluated in rheumatoid arthritis (RA). Objectives: This study aimed to explore the clinical value of F-NLR in RA and its relationship with disease activity. Methods: This retrospective study collected 143 RA patients and 82 age- and gender-matched healthy controls. Neutrophil, lymphocyte, monocyte, platelet, fibrinogen, NLR, monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), Disease Activity Score of 28 joints-ESR (DAS28-ESR) and other laboratory parameters were recorded. Receiver operating characteristic (ROC) curves were used to defined the optimization cut-off values of fibrinogen and NLR, which were 3.9g/L and 2.42. The F-NLR score was 2 for patients with high fibrinogen (&gt; 3.9g/L) and elevated NLR (&gt; 2.42), while those with one or neither were indexed as 1 or 0. The correlations between F-NLR as well as other inflammatory indexes and DAS28-ESR were measured. Results: The F-NLR score was higher in RA patients than that in healthy individuals ( P &lt; 0.05). The proportion of higher F-NLR score increased significantly along with the disease activity ( P &lt; 0.05). According to the ROC curve which was conducted to discriminate RA patients from healthy subjects, the area under curve (AUC) of F-NLR (0.803, 95% CI: 0.744 - 0.861) was higher than that of fibrinogen (0.735, 95% CI: 0.670 - 0.801), NLR (0.724, 95% CI: 0.655 - 0.794), MLR (0.687, 95% CI: 0.615 - 0.759) and PLR (0.732, 95% CI: 0.664 - 0.800). Furthermore, F-NLR was more strongly associated with DAS28-ESR (r = 0.572, P &lt; 0.001) when compared with fibrinogen (r = 0.518, P &lt; 0.001), NLR (r = 0.365, P &lt; 0.001), MLR (r = 0.140, P = 0.096), PLR (r = 0.239, P = 0.004), CRP (r = 0.539, P &lt; 0.001) and ESR (r = 0.487, P &lt; 0.001). Conclusion: The results demonstrated that the F-NLR score was elevated in RA patients. The F-NLR score may be a potential marker to monitor the disease activity of RA patients. References: [1]Wang H, Zhao J, Zhang M, Han L, Wang M, Xingde L. The combination of plasma fibrinogen and neutrophil lymphocyte ratio (F-NLR) is a predictive factor in patients with resectable non small cell lung cancer. J Cell Physiol. 2018 May; 233(5):4216-4224. Disclosure of Interests: None declared