tbuckley/cabot-search huggingface dataset:
255O Genetic mutations of Tim-3 ligand, and exhausted Tim-3+CD8+ T cells and survival in diffuse large B cell lymphoma
Authors: X. Wang, T. Zhang, Y. Hong, X. Liu, L. Qiu, L. Li, Z. Qian, S. Zhou, B. Meng, Q. Zhai, H. Zhang
Journal: Annals of Oncology (2020)
Abstract PO-025: Mitochondrial elongation through Drp1 deletion increases CD8 T cell oxidative phosphorylation and memory formation
Authors: Marissa A. Gonzales, Timothy NJ Bullock
Journal: Cancer Research (2020)

Abstract Despite the positive effects of tumor infiltrating lymphocytes (TIL) seen in patients with melanoma and other tumor types, TIL often fail to completely control disease progression even with immune responses enhanced by checkpoint blockade or other immunotherapy. These TIL exhibit characteristics of exhaustion such as poor proliferation, poor effector function, and an increase in inhibitory receptor expression. By flow cytometry, we find that TIL have lower mitochondrial mass as well as lower mitochondrial membrane potential when compared to functional effector T-cells. During the activation and differentiation of T cells, the metabolic demands fluctuate between the necessity for glycolysis or oxidative phosphorylation (OXPHOS), which is supported by shifting of the mitochondrial network state. Using mice lacking Drp1, a mitochondrial fission protein, in T cells as a model of elongated mitochondria, we see increased spare respiratory capacity and OXPHOS as compared to WT T cells with fission capability. We find that these mice are more likely to generate memory precursor CD8 T cells as represented by KLRG1 lo and CD127 hi during a primary response to anti-CD40, PolyI:C, and ovalbumin protein. As indicated by the increase in memory precursors, we find that Drp1 −/− T cells form more memory than WT animals after a 28-day rest period. At this time, mice were challenged with an adenovirus expressing ovalbumin to elicit a recall response. This recall response of CD8 T cells is greater in animals lacking Drp1 in the T cells. In addition to the increase in T cell numbers, we anticipate an increase in the metabolic and possibly cytokine function of these cells, which is still under investigation. We aim to exploit mitochondrial dynamics to enforce elongation of the mitochondrial network of TIL in order to improve TIL functions and have begun investigations into mitochondrial elongation in T cells in mice bearing B16OVA melanoma tumors. Citation Format: Marissa A. Gonzales, Timothy NJ Bullock. Mitochondrial elongation through Drp1 deletion increases CD8 T cell oxidative phosphorylation and memory formation [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-025.
Real‐life study in non‐atopic severe asthma patients achieving disease control by omalizumab treatment
Authors: Paloma Campo, Gregorio Soto Campos, Ana Moreira, Santiago Quirce, Alicia Padilla‐Galo, Eva Martínez‐Moragón, Aizea Mardones, Ignacio Dávila
Journal: Allergy (2020)
18459 Dietary factors in patients with hidradenitis suppurativa
Authors: Catherine M. Ludwig, Kendra D. Marr, Elizabeth Mata, Omar Rivzi, Alyssa Thompson, Aleksi J. Hendricks, Melody Maarouf, Jennifer M. Fernandez, Kyla N. Price, Jennifer Hsiao, Vivian Shi
Journal: Journal of the American Academy of Dermatology (2020)
Preclinical Applications of Multi-Platform Imaging in Animal Models of Cancer
Authors: Natalie J. Serkova, Kristine Glunde, Chad R. Haney, Mohammed Farhoud, Alexandra De Lille, Elizabeth F. Redente, Dmitri Simberg, David C. Westerly, Lynn Griffin, Ralph P. Mason
Journal: Cancer Research (2020)

Abstract In animal models of cancer, oncologic imaging has evolved from a simple assessment of tumor location and size to sophisticated multimodality exploration of molecular, physiologic, genetic, immunologic, and biochemical events at microscopic to macroscopic levels, performed noninvasively and sometimes in real time. Here, we briefly review animal imaging technology and molecular imaging probes together with selected applications from recent literature. Fast and sensitive optical imaging is primarily used to track luciferase-expressing tumor cells, image molecular targets with fluorescence probes, and to report on metabolic and physiologic phenotypes using smart switchable luminescent probes. MicroPET/single-photon emission CT have proven to be two of the most translational modalities for molecular and metabolic imaging of cancers: immuno-PET is a promising and rapidly evolving area of imaging research. Sophisticated MRI techniques provide high-resolution images of small metastases, tumor inflammation, perfusion, oxygenation, and acidity. Disseminated tumors to the bone and lung are easily detected by microCT, while ultrasound provides real-time visualization of tumor vasculature and perfusion. Recently available photoacoustic imaging provides real-time evaluation of vascular patency, oxygenation, and nanoparticle distributions. New hybrid instruments, such as PET-MRI, promise more convenient combination of the capabilities of each modality, enabling enhanced research efficacy and throughput.
Abstract 15321: Emergent Valve Surgery Improves Clinical Results in Infective Endocarditis Patients Complicated With Acute Cerebral Infarction: Analysis Using Propensity Matching Score
Authors: Takaaki Samura, Daisuke Yoshioka, Koichi Toda, Shigeru Miyagawa, Yasushi Yoshikawa, Hiroki Hata, Satoshi Kainuma, Ryohei Matsuura, Shohei Yoshida, Takayoshi Ueno, Toru Kuratani, Yoshiki Sawa
Journal: Circulation (2018)

Introduction: Acute cerebral infarction (CI) is a severe complication seen in 20% to 40% of patients with infective endocarditis (IE). Conventionally, the presence of acute CI has been indication f...
Beta-Blockade for Mitral Regurgitation: Could the Management of Valvular Heart Disease Actually Be Moving Into the 21st Century?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Blase A. Carabello
Journal: Journal of the American College of Cardiology (2012)
Patient-derived orthotopic xenograft models of medulloblastoma lack a functional blood-brain barrier
Authors: Laura A Genovesi, Simon Puttick, Amanda Millar, Marija Kojic, Pengxiang Ji, Anne K Lagendijk, Caterina Brighi, Claudine S Bonder, Christelle Adolphe, Brandon J Wainwright
Journal: Neuro-Oncology (2020)

Novel targeted therapies for children diagnosed with medulloblastoma (MB), the most common malignant pediatric brain tumor, are urgently required. A major hurdle in the development of effective therapies is the impaired delivery of systemic therapies to tumor cells due to a specialized endothelial blood-brain barrier (BBB). Accordingly, the integrity of the BBB is an essential consideration in any preclinical model used for assessing novel therapeutics. This study sought to assess the functional integrity of the BBB in several preclinical mouse models of MB.Dynamic contrast enhancement magnetic resonance imaging (MRI) was used to evaluate blood-brain-tumor barrier (BBTB) permeability in a murine genetically engineered mouse model (GEMM) of Sonic Hedgehog (SHH) MB, patient-derived orthotopic xenograft models of MB (SHH and Gp3), and orthotopic transplantation of GEMM tumor cells, enabling a comparison of the direct effects of transplantation on the integrity of the BBTB. Immunofluorescence analysis was performed to compare the structural and subcellular features of tumor-associated vasculature in all models.Contrast enhancement was observed in all transplantation models of MB. No contrast enhancement was observed in the GEMM despite significant tumor burden. Cellular analysis of BBTB integrity revealed aberrancies in all transplantation models, correlating to the varying levels of BBTB permeability observed by MRI in these models.These results highlight functional differences in the integrity of the BBTB and tumor vessel phenotype between commonly utilized preclinical models of MB, with important implications for the preclinical evaluation of novel therapeutic agents for MB.
THU0114 A77 1726 decreases cd69 upregulation induced by il-15 on human peripheral blood lymphocytes
Authors: AM Ortiz, A Laffon, FI Romero, I Gonzalez-Alvaro
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> We have previously described that cyclosporin A inhibits CD69 expression induced by IL-15 on human peripheral blood lymphocytes (PBL).<sup>1</sup> The expression of CD69 has a putative role in the intercellular contact-mediated TNF-alpha production by macrophages and could be a potential target in the treatment of Rheumatoid Arthritis. In addition, Janus Kinase 3 (JAK3) has been involved in the signal transmission of the IL-2 and IL-15 receptors. Furthermore, it has been described that A77 1726 (the active metabolite of leflunomide) may inhibit the effect of some tyrosine kinases, including the JAK3. <h3>Objectives</h3> To analyse the effect of A77 1726 upon the CD69 expression induced by different cytokines on PBL. <h3>Methods</h3> Purified PBL from healthy donors were incubated with IL-2 (50 IU/ml), IL-6 (5 ng/ml), IL-15 (5 ng/ml), TNF-alpha (20 ng/ml), or medium, separately and in the presence of cyclosporin A (0.1 ? 10 μg/ml) and/or A77 1726 (0.1 ? 100 μM). After 24 h of culture, cells were washed and CD69 expression assessed through indirect immunofluorescence and flow cytometry. Data are shown as mean ± SD. Paired Student t test was used for statistical analysis. <h3>Results</h3> Cells incubated with IL-15 in the presence of A77 1726 showed a significant lower CD69 expression than those incubated with IL-15 alone in a dose dependent manner (p &lt; 0.05 for all concentrations). The highest inhibitory effect, without evidence of toxicity, was observed at 100 μM with a reduction in CD69 expression of 47.3 ± 20.3% (n = 6). A similar effect was achieved with a specific JAK3 inhibitor, 4-(4?-Hydroxyphenyl) amino-6,7-dimethoxyquinazoline. A77 1726 also significantly inhibited the effect of IL-2 and IL-6, but not the CD69 up-regulation mediated by TNF-alpha. Treatment of PBL with a combination of CsA (0.1 μg/ml) and A77 1726 (0.1–1 μM) induced a similar inhibition of the CD69 expression achieved with each of the drugs at the maximal dose assayed (10 μg/ml and 100μM, respectively). <h3>Conclusion</h3> The inhibition of IL-15 induced CD69 expression on PBL by A77 1726 might be also responsible for the therapeutic effect of leflunomide in RA. Furthermore, the combination of cyclosporin A and leflunomide might be an interesting approach to the treatment of this disease, as demonstrated in an antigen induced arthritis model in rats.<sup>2</sup> <h3>References</h3> Ortiz AM, García-Vicuña R, Sancho D, Laffon A, Sánchez-Madrid F, González-Álvaro I. Cyclosporin A inhibits CD69 expression induced on synovial fluid and peripheral blood lymphocytes by IL-15. J Rheumatol. 2000;21:2329–38 Thoss K, Henzgen S, Petrow PK, Katenkamp D, Brauer R. Immunomodulation of rat antigen-induced arthritis by leflunomide alone and in combination with cyclosporin A. Inflamm Res. 1996;45:103–7
Remnant Cholesterol: “Non-(HDL-C + LDL-C)” as a Coronary Artery Disease Risk Factor⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Ruth McPherson
Journal: Journal of the American College of Cardiology (2013)
17955 Comparison of SPF50+ and SPF100+ sunscreens on the induction of cutaneous pigmentation over multiple days: A real-world, single-center, randomized, double-blinded evaluation
Authors: Indermeet Kohli, Cynthia Nicholson, Joshua D. Williams, InSeok Seo, Xiaoyan Tian, Evren Atillasoy, Henry W. Lim, Iltefat H. Hamzavi
Journal: Journal of the American Academy of Dermatology (2020)
Covid-19: England will return to regional restrictions amid rapid testing push
Authors: Shaun Griffin
Journal: BMJ (2020)

England will move to a revised system of regional, tiered restrictions when the current national lockdown ends on 2 December, the prime minister has announced.

In a statement to the House of Commons on 23 November Boris Johnson set out a covid-19 winter plan,1 confirming that current national restrictions would revert to a modified version of the previous three tier system.

In tier 1 of the new regional system Johnson said that people should work from home wherever possible. In tier 2 alcohol may be served in hospitality settings only as part of a substantial meal. And in tier 3 indoor entertainment, hotels, and other accommodation will have to close, along with all forms of hospitality except for delivery …
399P Real-world insights into patients (pts) with advanced NSCLC and MET alterations
Authors: M. Bittoni, J.C-H. Yang, J-Y. Shih, N. Peled, E. Smit, R. Camidge, D. Carbone, D. Oksen, E. Boutmy, A. Johne, P. Paik
Journal: Annals of Oncology (2020)
Making the case for ‘physical activity security’: the 2020 WHO guidelines on physical activity and sedentary behaviour from a Global South perspective
Authors: Estelle Victoria Lambert, Tracy Kolbe-Alexander, Deepti Adlakha, Adewale Oyeyemi, Nana Kwame Anokye, Shifalika Goenka, Patricia Mogrovejo, Deborah Salvo
Journal: British Journal of Sports Medicine (2020)

With relatively few exceptions, the majority of evidence concerning the health benefits of physical activity (PA) has been gleaned from high-income countries (HICs).1 In the opening editorial to this special issue,2 the editors suggest that under-representation of lower and middle-income countries (LMICs, often referred to as ‘Global South’) in the PA literature is more than ‘just another research gap’. Arguably, this gap reflects very real differences in context, competing health and developmental priorities, available resources and undoubtedly, political will.

Juxtaposed against the clear benefits of PA, most LMICs are characterised by the coexistence of both non-communicable and infectious chronic diseases, such as tuberculosis and HIV/AIDS.3 Obesity often coexists with maternal and childhood undernutrition and household food insecurity and health disparities have been exacerabated by the COVID-19 crisis. Political circumstances are often adverse, with many LMICs experiencing conflict, humanitarian crises, and/or social unrest and embedded inequalities (eg, the legacy of apartheid in South Africa). Lack of safety from crime and traffic, poorly designed and often overcrowded urban environments, low prioritisation of physical education in schools, and inequitable distribution of green space, are endemic to most LMICs.4 5 Thus, PA, even for transport, is difficult at best, and largely undertaken by necessity rather than by choice. Meanwhile, recreational PA is inaccessible for most in these settings.6 As such, and with rapid urbanisation in LMICs, often into poverty,7 we are required to view PA through the ‘lens’ of equity. This demands us to elevate the discussion for PA above health, and frame it as a …
SP0161 Why rheumatic diseases are underestimated in poland?
Authors: B Moskalewicz
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> Poland has a population of 38 millions people, what means an eighth rank among 43 European countries. When 5 million (13% of total population) suffer from chronic rheumatic problems and rheumatic diseases constitute the first cause of disability, arthritis should be defined as public health problem at the national and prehaps European level too. Unfortunately, public opinion is under the pressure of clinical, individual approach to health care. Individualisation of health issues produces invisible social dramas, id est: social isolation of disabled, enormous bureaucratic disfunctions of care system and also shifting out cost of treatment to patients' family. Rheumatic patients have serious troubles to maintain satisfying personal relations and to participate in religious or social/political life. Those results of chronic rheumatic diseases are usually neglected in public dispute on health priorities. Three "curtains" exist in public health theatre making difficult to perceive rheumatic problems: social attitudes towards disability self marginalisation of arthritis patients family support instead of systemic resolutions. Governmental agencies, using a traditional model of public activity are highly bureaucratic: centralised, impersonal, hierarchical and specialised. Self-help groups are quite opposite: locally centred, personal, non-hierarchical and non-specialised. The two actors of public health performance act in different ways and their political influence changes. As governmental agencies failed so far to remove all three courtains, it is time for NGOs to play a crucial role.
Gated SPECT Myocardial Perfusion Imaging for the Prediction of Incident Heart Failure: An Old Dog Learns a New Trick⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: Prem Soman, James E. Udelson
Journal: JACC. Cardiovascular imaging (2009)
Is It the Same or a Different Ventricular Tachycardia?: An Additional Use for Defibrillator Electrograms⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Jesus Almendral, Francis Marchlinski
Journal: Journal of the American College of Cardiology (2010)
Concurrent Dexamethasone Limits the Clinical Benefit of Immune Checkpoint Blockade in Glioblastoma
Authors: J. Bryan Iorgulescu, Prafulla C. Gokhale, Maria C. Speranza, Benjamin K. Eschle, Michael J. Poitras, Margaret K. Wilkens, Kara M. Soroko, Chhayheng Chhoeu, Aine Knott, Yan Gao, Mary Jane Lim-Fat, Gregory J. Baker, Dennis M. Bonal, Quang-Dé Nguyen, Gareth R. L. Grant, Keith L. Ligon, Peter K. Sorger, E. Antonio Chiocca, Ana C. Anderson, Paul T. Kirschmeier, Arlene H. Sharpe, Gordon J. Freeman, David A. Reardon
Journal: Clinical Cancer Research (2020)

Dexamethasone, a uniquely potent corticosteroid, is frequently administered to patients with brain tumors to decrease tumor-associated edema, but limited data exist describing how dexamethasone affects the immune system systemically and intratumorally in patients with glioblastoma (GBM), particularly in the context of immunotherapy.We evaluated the dose-dependent effects of dexamethasone when administered with programmed cell death 1 (PD-1) blockade and/or radiotherapy in immunocompetent C57BL/6 mice with syngeneic GL261 and CT-2A GBM tumors. Clinically, the effect of dexamethasone on survival was evaluated in 181 patients with isocitrate dehydrogenase (IDH) wild-type GBM treated with PD-(L)1 blockade, with adjustment for relevant prognostic factors.Despite the inherent responsiveness of GL261 to immune checkpoint blockade, concurrent dexamethasone administration with anti-PD-1 therapy reduced survival in a dose-dependent manner. Concurrent dexamethasone also abrogated survival following anti-PD-1 therapy with or without radiotherapy in immune-resistant CT-2A models. Dexamethasone decreased T-lymphocyte numbers by increasing apoptosis, in addition to decreasing lymphocyte functional capacity. Myeloid and natural killer cell populations were also generally reduced by dexamethasone. Thus, dexamethasone appears to negatively affect both adaptive and innate immune responses. As a clinical correlate, a retrospective analysis of 181 consecutive patients with IDH wild-type GBM treated with PD-(L)1 blockade revealed poorer survival among those on baseline dexamethasone. Upon multivariable adjustment with relevant prognostic factors, baseline dexamethasone administration was the strongest predictor of poor survival [reference, no dexamethasone; <2 mg HR, 2.16; 95% confidence interval (CI), 1.30-3.68; P = 0.003 and ≥2 mg HR, 1.97; 95% CI, 1.23-3.16; P = 0.005].Our preclinical and clinical data indicate that concurrent dexamethasone therapy may be detrimental to immunotherapeutic approaches for patients with GBM.
Are All End Points Created Equal?: The Case for Weighting⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. The authors have reported that they have no relationships to disclose.
Authors: Robert F. Wilson, Alan K. Berger
Journal: Journal of the American College of Cardiology (2011)
Declarations of pharma funding are still not transparent enough, say critics
Authors: Lynn Eaton
Journal: BMJ (2020)

Exact details of the £542.9m (€605.8m; $725m) that drug companies spent on healthcare organisations and healthcare professionals in 2019 have been disclosed—five months later than planned, as a direct result of the covid-19 pandemic.

The Association of British Pharmaceutical Industries (ABPI) has been publishing its annual summary of pharmaceutical companies’ spending since 2016, following criticism about the industry’s lack of transparency.

Although some of the figures were published in June,1 the detailed breakdown was delayed for the NHS to check the accuracy of the data before they are published.

The figures show that the bulk of funding from companies went towards research and development by organisations or individuals—£381.9m or 70% of the total …
2007 Charles T. Dotter Memorial Lecture—Renal Artery Stenosis and Cardiovascular Risks—The New Paradigms in Diagnosis and Treatment
Authors: Thomas Sos
Journal: Circulation (2007)

Renal artery stenosis (RAS), hypertension, and renal insufficiency are each frequently present especially in the elderly population. RAS is often present without any clinical signs or symptoms, and even when hypertension or renal insufficiency is also present, these conditions may be coincidental rather than causally related. However, when RAS is physiologically significant (10% peak systolic trans-stenotic pressure gradient), it is one of the few potentially reversible causes of renal insufficiency and hypertension. RVH is mediated by angiotensin II, a powerful vaso-constrictor producing systemic hypertension, cellular hypertrophy, proliferation of vascular smooth muscle cells, vascular and left ventricular hypertrophy, accelerated atherosclerosis, and progressive glomerular sclerosis, independent of the level of hypertension. Physiologically significant RAS also has direct effects on sympathetic nerve activity, nitric oxide production, and intrarenal prostaglandin concentration. Patients with atheromatous RAS (ARAS) and end-stage renal disease have a significantly higher mortality rate than the general dialysis population. Some advocate prophylactic intervention for asymptomatic and hemodynamically insignificant ARAS; however, ARAS is a marker for but not an independent risk factor for major adverse cardiac events. Aggressive statin therapy arrests progression and produces regression of coronary and carotid atheroma. Patients with asymptomatic and hemodynamically nonsignificant ARAS should be treated with aggressive statin and glucose control therapy, aspirin, and lifestyle modifications. This would likely produce all the potential benefits of prophylactic stenting, the very long-term durability and fate of which are unknown, and without any of its known major risks such as cholesterol embolisation and the 15% to 20% restenosis that can occur even in “low-risk” patients. In summary, appropriately selected patients with ARAS and renal insufficiency benefit from interventional therapy, whereas those with clinically and hemodynamically nonsignificant stenoses should be treated by aggressive medical therapy, including statins and life style modifications.
Technology of deep brain stimulation: current status and future directions
Authors: Joachim K. Krauss, Nir Lipsman, Tipu Aziz, Alexandre Boutet, Peter Brown, Jin Woo Chang, Benjamin Davidson, Warren M. Grill, Marwan I. Hariz, Andreas Horn, Michael Schulder, Antonios Mammis, Peter A. Tass, Jens Volkmann, Andres M. Lozano
Journal: Nature Reviews Neurology (2020)