tbuckley/cabot-search huggingface dataset:
An active role for neurons in glioma progression: making sense of Scherer’s structures
Authors: Shawn Gillespie, Michelle Monje
Journal: Neuro-Oncology (2018)

Perineuronal satellitosis, the microanatomical clustering of glioma cells around neurons in the tumor microenvironment, has been recognized as a histopathological hallmark of high-grade gliomas since the seminal observations of Scherer in the 1930s. In this review, we explore the emerging understanding that neuron‒glioma cell interactions regulate malignancy and that neuronal activity is a critical determinant of glioma growth and progression. Elucidation of the interplay between normal and malignant neural circuitry is critical to realizing the promise of effective therapies for these seemingly intractable diseases. Here, we review current knowledge regarding the role of neuronal activity in the glioma microenvironment and highlight critical knowledge gaps in this burgeoning research space.
Tissue-resident macrophages in the intestine are long lived and defined by Tim-4 and CD4 expression
Authors: Tovah N. Shaw, Stephanie A. Houston, Kelly Wemyss, Hayley M. Bridgeman, Thomas A. Barbera, Tamsin Zangerle-Murray, Patrick Strangward, Amanda J.L. Ridley, Ping Wang, Samira Tamoutounour, Judith E. Allen, Joanne E. Konkel, John R. Grainger
Journal: The Journal of Experimental Medicine (2018)

A defining feature of resident gut macrophages is their high replenishment rate from blood monocytes attributed to tonic commensal stimulation of this site. In contrast, almost all other tissues contain locally maintained macrophage populations, which coexist with monocyte-replenished cells at homeostasis. In this study, we identified three transcriptionally distinct mouse gut macrophage subsets that segregate based on expression of Tim-4 and CD4. Challenging current understanding, Tim-4+CD4+ gut macrophages were found to be locally maintained, while Tim-4–CD4+ macrophages had a slow turnover from blood monocytes; indeed, Tim-4–CD4– macrophages were the only subset with the high monocyte-replenishment rate currently attributed to gut macrophages. Moreover, all macrophage subpopulations required live microbiota to sustain their numbers, not only those derived from blood monocytes. These findings oppose the prevailing paradigm that all macrophages in the adult mouse gut rapidly turn over from monocytes in a microbiome-dependent manner; instead, these findings supplant it with a model of ontogenetic diversity where locally maintained subsets coexist with rapidly replaced monocyte-derived populations.
Nerve ablation reduced blood pressure in two thirds of patients, trial finds
Authors: Jacqui Wise
Journal: BMJ (2018)

Renal denervation using ultrasound could prove to be an alternative to lifelong drug treatment for hypertension. Research published in the Lancet shows that the technique significantly reduced systolic blood pressure at two months in patients with hypertension that was resistant to drug treatment.1

The one hour operation uses ultrasound energy to disrupt the nerves between the kidneys and the brain that carry the signals controlling blood pressure.

Radiofrequency ablation of the renal nerves has been investigated previously, with mixed results. A 2017 Cochrane Collaboration meta-analysis found moderate quality …
New NCCN Guidelines: Cancer Management in People Living With HIV
Authors: Gita Suneja
Journal: Journal of the National Comprehensive Cancer Network (2018)

Since the emergence of HIV in the United States in the 1980s, cancer has been a part of the story. The good news is that antiretroviral therapy has improved survival for those living with HIV infection, with life expectancy now approaching that of uninfected people. Consequently, this patient population is living long enough to develop different types of cancer. At the 23rd NCCN Annual Conference, Gita Suneja, MD, MSHP, presented the debut of the new NCCN Guidelines for Cancer in People Living With HIV, discussing the intersection between cancer and HIV infection, the cancers most likely to develop in this group of patients, and the importance of oncologists working in conjunction with HIV specialists to render the most appropriate and individualized care.
Abstract 19355: Assessment of Myocardial Capillary Rarefaction Using Intracoronary Wave Intensity Analysis: A Validation in Cardiac Allograft Patients With Resultant Prognostic Insights
Authors: Chris J Broyd, Francisco Hernández-Pérez, Mauro Echavarria-Pinto, Alicia Quirós-Carretero, Pablo García-Pavía, Clara Salas, Pilar Jiménez-Quevedo, Nieves Gonzalo, Ivan Nuñez-Gil, Borja Ibañez, Luis Alonso-Pulpón, Antonio Fernández-Ortiz, Justin Davies, Javier Segovia, Javier Escaned
Journal: Circulation (2015)

Introduction: A decrease in capillary density (capillary rarefaction) is the predominant mechanism of microcirculatory dysfunction in certain heart conditions. Measuring capillary rarefaction with coronary flow reserve (CFR) or resistance measurements is hampered by the frequent presence of arteriolar remodelling. We investigated the potential of wave intensity analysis (WIA) to ascertain the presence of capillary rarefaction using transplant vasculopathy as a clinical model of microcirculatory disease. The prognostic implications of WIA-assessed capillary density in predicting cardiac allograft vasculopathy (CAV) was then also investigated. Methods: 52 patients with unobstructed coronary arteries underwent combined LAD pressure and flow measurements at rest and with intracoronary adenosine. CFR, hyperaemic microvascular resistance, coronary resistance index, coronary conductance (IHDVPS) and WIA were calculated. Simultaneous right ventricular biopsies were obtained and analysed for capillary density in 17 patients. All patients were then followed up with 1-3 yearly screening angiography and IVUS. Results: All patients were in sinus rhythm with normal LV function. A statistically significant relationship with capillary density was noted with CFR (r=0.52, p=0.048) and the backward decompression wave (BDW) (r=-0.65, p&lt;0.01) the latter of which was maintained with multiple regression analysis (p=0.02). Over a mean follow-up of 9.3 ± 5.2 years, the BDW was able to predict outcome in terms of CAV-events (-7.1 vs -4.5 x10 3 Wm -2 s -1 , p=0.04) as well as the development (7.9 vs 4.8 x10 3 Wm -2 s -1 , p=0.01) and severity (p=0.04) of angiographic CAV. There was a strong trend towards prediction of angiographic CAV disease with IHDVPS (1.7 vs 1.1 cm/s/mmHg, p=0.08) but no other relationships were noted with prognosis and microvascular indices. Conclusions: WIA is an excellent tool for assessing capillary rarefaction and provides a more focused insight into this domain of the microcirculation than other contemporary measures of microcirculatory function. In cardiac transplant patients, it is able to document the early histological changes of CAV and can predict CAV-related outcome as well as its angiographic presence and severity.
Nintedanib in Severe Pulmonary Arterial Hypertension
Authors: Manuel J. Richter, Jan Ewert, Friedrich Grimminger, Hossein Ardeschir Ghofrani, Baktybek Kojonazarov, Aleksandar Petrovic, Werner Seeger, Ralph T. Schermuly, Khodr Tello, Henning Gall
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
Clinical and Pathology Findings Associate Consistently with Larger Glomerular Volume
Authors: Aleksandar Denic, Jerry Mathew, Venkata V. Nagineni, R. Houston Thompson, Bradley C. Leibovich, Lilach O. Lerman, John C. Lieske, Mariam P. Alexander, Joshua J. Augustine, Walter K. Kremers, Andrew D. Rule
Journal: Journal of the American Society of Nephrology (2018)

Background Glomerular volume increases when demand exceeds nephron supply, which may lead to glomerulosclerosis. It is unclear if determinants of glomerular volume are consistent between populations that differ by severity of comorbidities. Methods We studied kidney biopsy specimens from living kidney donors ( n =2453) and patients who underwent radical nephrectomy for a renal tumor ( n =780). We scanned specimen sections into high-resolution digital images, manually traced glomerular profiles, and calculated mean glomerular volumes using the Weibel–Gomez stereologic formula (separately for nonsclerosed glomeruli and globally sclerosed glomeruli). We then assessed the relationship of glomerular volume with age, clinical characteristics, and nephrosclerosis on biopsy specimen. Results Compared with kidney donors, patients with tumors were older and more frequently men, obese, diabetic, or hypertensive, had more glomerulosclerosis and interstitial fibrosis on biopsy specimen, and had 12% larger nonsclerosed glomeruli ( P &lt;0.001). In both populations, male sex, taller height, obesity, hypertension, and proteinuria associated with larger nonsclerosed glomeruli to a similar extent. In patients with tumors, diabetes, glomerulosclerosis &gt;25%, and interstitial fibrosis &gt;25% also associated with larger nonsclerosed glomeruli. Independent clinical predictors of larger nonsclerotic glomeruli were family history of ESRD, male sex, taller height, obesity, diabetes, and proteinuria. After adjustment for these characteristics, nonsclerotic glomerular volume did not differ between populations and was stable up to age 75 years, after which it decreased with age. Many of these findings were also evident with globally sclerotic glomerular volume. Conclusions Characteristics associated with glomerular volume are consistent between patient populations with low and high levels of comorbidity.
Genome-wide distribution of linker histone H1.0 is independent of MeCP2
Authors: Aya Ito-Ishida, Hari Krishna Yamalanchili, Yingyao Shao, Steven A. Baker, Laura D. Heckman, Laura A. Lavery, Ji-yoen Kim, Laura M. Lombardi, Yaling Sun, Zhandong Liu, Huda Y. Zoghbi
Journal: Nature Neuroscience (2018)
Regulatory T cells induce activation rather than suppression of human basophils
Authors: Meenu Sharma, Mrinmoy Das, Emmanuel Stephen-Victor, Caroline Galeotti, Anupama Karnam, Mohan S. Maddur, Patrick Bruneval, Srini V. Kaveri, Jagadeesh Bayry
Journal: Science Immunology (2018)

Basophils are a rare granulocyte population that has been associated with allergic and inflammatory responses. It is essential to understand the regulatory mechanisms by which basophils are kept in check, considering the impact of dysregulated basophil function on immune responses under different pathological conditions. Among immunoregulatory cells, CD4+CD25+FoxP3+ regulatory T cells (Tregs) are the key players that maintain immune tolerance. The mechanisms by which Tregs regulate and suppress diverse immune cell subsets have been studied extensively, but the impact of Tregs on basophil functions is not well understood. We report that human basophils are refractory to Treg-mediated suppression and found that Tregs stimulate resting basophils to induce the expression of activation markers including CD69, CD203c, and CD13 and the release of basophil cytokines including IL-13, IL-8, and IL-4. Mechanistically, Tregs could induce human basophil activation via IL-3 and STAT5 activation, whereas cellular contact was dispensable. Inhibition of either IL-3-IL-3 receptor interactions or STAT5 phosphorylation abrogated Treg-mediated activation of basophils. These results provide evidence of direct positive effects that human Tregs have on basophil activation and reveal a previously unrecognized feature of this cell subset well known for immunosuppressive functions.
THE CASE OF ESD IN THE STOMACH USING THE “SRING-TO-RING” METHOD
Authors: V Kriazhov, A Mitrakov
Journal: Endoscopy (2018)

In this video, a case of performing ESD using “string-to-ring” method is presented to facilitate and increase the quality of dissection in stomach. The lesion is 1 cm in size, located in the middle third of the body of the stomach on the back wall. The “string-to-ring” method is to create traction using a threadixed to the edge of the tumor that is moved through a ring located on the clip on the opposite wall. Advantage of the method is its simplicity, the ability to change the force of tension, as well as the angle of traction of the tumor being removed in any desired direction. This technique simplifies ESD in submucosal fibrosis, and provides he most convenient access to the submucosa is achieved. The “string-to-ring” method allowed to shorten the operation time, reduce the number of intraoperative bleeding and perforations.
Comment on Bress et al. Effect of Intensive Versus Standard Blood Pressure Treatment According to Baseline Prediabetes Status: A Post Hoc Analysis of a Randomized Trial. Diabetes Care 2017;40:1401–1408
Authors: João Sérgio Neves, Miguel Bigotte Vieira, Lia Leitão, Catarina Viegas Dias, Rita Magriço, Ana Isabel Oliveira, Davide Carvalho
Journal: Diabetes Care (2018)

We read with interest the article by Bress et al. (1) reporting on the effect of intensive versus standard blood pressure treatment according to baseline prediabetes status in a post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT). The authors concluded that the beneficial effects of intensive blood pressure treatment were similar among patients with prediabetes and patients with normoglycemia. We have participated in the SPRINT Data Analysis Challenge (2), and we also analyzed the effects of glycemia status in this population. Whereas we agree with the conclusions presented by the authors, we believe it is also important to assess the effect …
The P2X4 purinergic receptor regulates hepatic myofibroblast activation during liver fibrogenesis
Authors: Camille Le Guilcher, Isabelle Garcin, Olivier Dellis, Florent Cauchois, Ali Tebbi, Isabelle Doignon, Catherine Guettier, Boris Julien, Thierry Tordjmann
Journal: Journal of Hepatology (2018)
Abstract 12783: Postoperative Cardioversions for New-onset Atrial Fibrillation in Cardiac Surgery
Authors: Tuomas Kiviniemi, Markus Malmberg, Fausto Biancari, Juha Hartikainen, Leo Ihlberg, Fredrik Yannopoulos, Teemu Riekkinen, Otto von Hellens, Joonas Lehto, Maunu Nissinen, Juhani K Airaksinen, Tuomo Nieminen
Journal: Circulation (2016)

Introduction: New-onset postoperative atrial fibrillation (AF) is a frequent complication after open-heart surgery and cardioversions (CV) are often performed to restore sinus rhythm in this setting. Thromboembolic risk related to early postoperative CV and the recurrence of AF in the long-term follow-up, however, remain largely unknown. Hypothesis: The FIN-bioAVR study sought to assess the rate of strokes and transient ischemic attacks (TIA) shortly after CV for AF in patients who underwent isolated aortic valve replacement with bioprosthesis. Methods: Between 2002 and 2014, 784 patients underwent isolated aortic valve replacement with a bioprosthesis in four Finnish University Hospitals. Results: During postoperative hospitalization when patients with prior chronic AF were excluded, 368/685 (53.7%) of patients had at least one new-onset paroxysm of AF (median time to diagnosis 3 [3] days), and early CV was performed in 122/368 (33.2%) of them. Baseline characteristics were comparable except that patients with CV had more often prior diagnosis of heart failure and less often chronic lung disease compared to those without CV. Hospital stay was significantly shorter, but at two-weeks follow-up, the rate of stroke/TIAs was 3.3% vs. 0.4% (p=0.05) in those with vs. without CV, respectively. Strikingly, early CV was associated with a trend of increased risk of two-week stroke/TIA rate compared to patients without CV (OR 7.66 (95%-CI 0.85-69.3, p=0.07)). In the median follow-up of 1682 [1514] days patients with early CV had more often recurrences of clinical AF (57% vs. 39%, p&lt;0.01). Conclusions: In this large real-world population of patients undergoing aortic valve bioprosthesis operation, the rate of new-onset in-hospital AF was over 50%. Nearly third of them had a CV and these patients had over 7-fold risk for thromboembolisms related to CV.
Abstract #163: Induce apoptosis of differentiated endothelial progenitor cell by vascular endothelial growth inhibitor
Authors: Fang Tian, Paulina Liang, Luyuan Li
Journal: Cancer Research (2009)

A growing body of evidence suggests that bone marrow-derived endothelial progenitor cells (EPC) play a critical role to the formation of new blood vessels in post-natal vasculogenesis. In our previous study we showed that vascular endothelial growth inhibitor (VEGI; TNFSF15), a member of the tumor necrosis factor superfamily, inhibited differentiation of endothelial progenitor cells (EPC) from mouse bone marrow isolated Sca-1+ stem cells. Here we further report that VEGI is able to induce apoptosis of differentiated EPC but not early stage EPC. The expression of death receptor 3 (DR3), a known receptor of VEGI, is readily detectable in differentiated EPC at protein level only after one week in culture, but not in early stage EPC. When treated with VEGI, an increase of phospho-Erk and a decrease of phospho-Akt are detected in early stage EPC, while activation of NF-\#954;B and JNK are seen in differentiated EPC. Moreover, neutralizing antibodies against DR3 or recombinant extracellular domain of DR3 substantially inhibits VEGI-induced NF-\#954;B and JNK activation. Results from TUNEL assays show that VEGI treatment specifically eliminates differentiated EPC by inducing apoptosis. Furthremore, VEGI induces caspase-3 activation in differentiated EPC, and treatment with DR3 neutralizing antibodies prior to the addition of VEGI effectively inhibits VEGI-induced caspase-3 activation. These findings indicate that VEGI not only negatively modulate the differentiation of EPC toward endothelial cells but also be able to induce apoptosis of differentiated EPC, which is, at least partly, mediated by death receptor-3 (DR3).   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 163.
Abstract 12834: Increased Plasma Serotonin and Circulating microRNA-1914 Reflect Oxidative Stress and Play Crucial Roles in Atherosclerosis
Authors: Tomonori Sugiura, Yasuaki Dohi, Yuji Hirowatari, Satoshi Fujii, Nobuyuki Ohte
Journal: Circulation (2016)

Introduction: Serotonin, synthesized from enterochromaffin cells, modulates vascular tonus and thrombus formation, and mediates development of atherosclerotic plaque. Oxidative stress is involved in vascular inflammation and progression of atherosclerosis. Hypothesis: We hypothesized that plasma serotonin plays a crucial role in increasing oxidative stress and aimed to identify the circulating microRNA(s) associated with serotonin ratio for coronary artery disease (CAD). Methods: Blood was sampled from 120 outpatients with cardiovascular risk factors but without a history of previous cardiovascular events. Serotonin levels both in platelet poor plasma (PPP) and whole blood (WB) were measured with HPLC, and the ratio of serotonin in PPP to that in WB (PPP/WB) was used as an index of platelet activation. For assessment of oxidative stress, serum levels of derivative reactive oxygen metabolites (d-ROM) were measured. Total RNA was isolated from subjects who were scheduled for coronary angiography with suspicion of CAD and a microRNA array analysis was performed. The expression levels of microRNAs were scaled by global normalization. Results: Serotonin levels in both PPP and PPP/WB ratio were significantly correlated with the d-ROM levels. Among enrolled patients, 25 subjects were diagnosed as having CAD. The levels of the PPP/WB ratio of serotonin, d-ROM, and CRP were significantly higher in subjects with CAD than in those without CAD. Logistic regression analysis performed with endpoint of having CAD revealed that the PPP/WB ratio of serotonin was independently associated with CAD. In subjects with CAD, 5 increased microRNAs and 30 decreased microRNAs were identified among more than 2000 microRNAs as compared to those without CAD. Among candidate microRNAs, expression of microRNA-1914 showed significant inverse correlation with PPP/WB ratio (r=-0.61, P&lt;0.05) and d-ROM levels (r=-0.63, P&lt;0.05). Conclusions: A significant association among platelet activation assessed by PPP and PPP/WB ratio and oxidative stress assessed by d-ROM, was detected in individuals with cardiovascular risk factors. Targeting serotonin-oxidative stress axis, and circulating microRNA-1914 may serve as novel strategy for diagnosis of atherosclerotic CAD.
Calcium and Vitamin D Supplements and Fractures in Community-Dwelling Adults
Authors: Panagiotis Anagnostis, Stavroula A. Paschou, Dimitrios G. Goulis
Journal: JAMA (2018)

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A rationally designed NRP1-independent superagonist SEMA3A mutant is an effective anticancer agent
Authors: Noemi Gioelli, Federica Maione, Chiara Camillo, Michela Ghitti, Donatella Valdembri, Noemi Morello, Marie Darche, Lorena Zentilin, Gabriella Cagnoni, Yaqi Qiu, Mauro Giacca, Maurizio Giustetto, Michel Paques, Ilaria Cascone, Giovanna Musco, Luca Tamagnone, Enrico Giraudo, Guido Serini
Journal: Science Translational Medicine (2018)

An NRP1-independent, non-natural SEMA3A mutant isoform is a parenterally deliverable anticancer drug that normalizes the vasculature.