tbuckley/cabot-search huggingface dataset:
PB2414 AWARENESS AND KNOWLEDGE OF CARDIOVASCULAR DISEASE RISK AMONG THALASSEMIA PATIENTS
Authors: A. Meloni, S. Maffei, L. Pistoia, I. Traghella, A. Spiga, F. Massei, M. Serra, G. Guerrini, P. Giovangrossi, I. Fotzi, P. Marcheschi, A. Pepe
Journal: HemaSphere (2019)

Background: Cardiovascular diseases (CVDs) are the main cause of morbidity and mortality for thalassemia major (TM) patients but also for the general population in industrialized countries. Different studies revealed broad misconceptions with regard to the leading cause of death and impact of heart disease among the general population. Aims: We evaluated for the first time knowledge and awareness of CVD among TM patients in Italy. Methods: An anonymous questionnaire was completed by 44 TM patients (25 females, 39.95 ± 6.89 years) consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network. Results: Table 1 shows the answers to the first part of the questionnaire. The first two questions were multiple‐choice questions. The 74.4% of TM patients defined cancer (in general, breast/prostate or hepatic) as the greatest health problem for people of the same age. Out of the 13 patients with a CVD, only two defined CVD as the greatest health problem. The 44,1% of patients indicated cancer as the greatest danger to their future health. The other questions were yes/no questions. The 80.5% of TM patients thought that CVD was the leading cause of death in Italy. The percentage of patients who answered positively to this question was no significantly different among those with CVD than those without CVD. The 41.7% of patients who considered CVD to be the main cause of death named CVD as the greatest health problem. Summary/Conclusion: Although TM patients are aware that CVD is the leading cause of death, they seem to have a misperception of the impact of CVD on their personal current and future health status. Our data highlight the need to empower knowledge and perception of CVD in TM as a real health problem and not just as a potentially lethal threat. image
Abstract 16490: Comparing O2 Pulse at Cardiopulmonary Exercise Testing With 2D and 3D Evaluation at Stress Echocardiography
Authors: Martina Evangelista, Eleonora Alfonzetti, Francesco Bandera, Marco Guazzi
Journal: Circulation (2017)

Introduction: O2 pulse (i.e. the ratio of VO2/HR) is a reference variable, obtained during cardiopulmonary exercise testing (CPET), which reflects the non-invasive measure of stroke volume (SV). No...
Paraventricular Thalamus Projection Neurons Integrate Cortical and Hypothalamic Signals for Cue-Reward Processing
Authors: James M. Otis, ManHua Zhu, Vijay M.K. Namboodiri, Cory A. Cook, Oksana Kosyk, Ana M. Matan, Rose Ying, Yoshiko Hashikawa, Koichi Hashikawa, Ivan Trujillo-Pisanty, Jiami Guo, Randall L. Ung, Jose Rodriguez-Romaguera, E.S. Anton, Garret D. Stuber
Journal: Neuron (2019)
Efficacy and safety of brentuximab vedotin plus bendamustine in advanced‐stage primary cutaneous T‐cell lymphomas
Authors: M. Dumont, C. Ram‐Wolff, M. Roelens, P. Brice, R. Peffault de Latour, M. Battistella, I. Madelaine, J. Delyon, F. Herms, J.‐D. Bouaziz, H. Moins‐Teisserenc, C. Lebbé, M. Bagot, A. Masson
Journal: British Journal of Dermatology (2019)
Abstract 028: Infant Growth Trajectories and Lipid Levels in Adolescence: Evidence From a Chilean Infancy Cohort
Authors: Ann Von Holle, Kari E North, Sheila Gahagan, Estela Blanco, Misa Graff, Anne Justice, Betsy Lozoff, Raquel Burrows, Annie Green Howard, Saroja Voruganti
Journal: Circulation (2018)

Introduction: Growth in early infancy is hypothesized to affect chronic disease risk factors later in life. To date, most reports draw on European ancestry cohorts with few observations of early growth. To determine if previous findings generalize to diverse study populations and to accommodate more detailed growth estimates, we investigated the association between monthly infant growth from birth to 5 months and dyslipidemia in adolescents in a Hispanic/Latino cohort. Methods: We characterized infant growth in males (n=345) and females (n=308) from the Santiago Longitudinal Study (SLS) using three metrics: weight (kg), length (cm) and weight-for-length (g/cm). Nonlinear mixed effects (SITAR) and latent growth mixture models (LGMM) were two approaches to estimate infant growth characteristics. Growth functioned as an exposure and lipid levels at 17 years were the outcome, including HDL-C, LDL-C, and TG. We used a false discovery rate of 0.05 to report findings. Results: Height trajectories presented the strongest evidence for an effect on dyslipidemia in adolescence in both the SITAR and LGMM models. SITAR analyses demonstrated an inverse relationship between height velocity before six months of age and HDL-C levels in adolescence. LGMM models offered more nuanced findings. A two-class height trajectory model offered the best fit: one group (n~268) had shorter length at birth accompanied by lower velocity/higher acceleration; the other group (n~406) had higher length at birth and higher velocity/lower acceleration. The lower velocity/higher acceleration group had lower mean HDL-C (mg/dL) (35.4, se=0.9) than the higher velocity/lower acceleration group (43.8, se=0.7), χ2(1)=36.4, p-value=&lt;0.001. Similarly, the best-fitting 3-class weight trajectory model indicated the lower velocity/medium acceleration group had a higher mean LDL-C (mg/dL) (97.7, se=1.6, n~441) than the highest velocity/lowest acceleration group (88.8, se=2.0, n~202), χ2(1)=15.2, p-value=&lt;0.001. A similar pattern for LDL-C emerged for the weight-for-length trajectories, χ2(1)=8.6, p-value=0.003. Summary: This study provides evidence of associations between infant growth from 0 and 5 months and blood lipid profiles during adolescence. Based on two different analytic approaches, characteristics of infant length trajectories were associated with HDL-C at mean age 17 years. These findings align with the well-established relationship between height and CVD in adulthood. Furthermore, groups with higher acceleration in all three trajectory types were more likely to have adverse lipid outcomes. Future research can inform the role of infant body size change in the context of downstream effects and CVD risk.
Reply to Aubry and Veziris: Smear Microscopy Complements Xpert MTB/RIF When Considering Nontuberculous Mycobacterial Infections
Authors: Hyun-Woo Choi, Ju-Hyeon Shin, Seung-Jung Kee, Yong-Soo Kwon, Taeo Ma, Hyun-Seung Lee, Sejong Chun, Eun Jeong Won, Jong-Hee Shin
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

MTB/RIF.In epidemiological settings in which NTM diseases are more frequent than tuberculosis, the balance would be even more against replacing microscopy with Xpert MTB/RIF (2).Moreover, although the lack of specificity of microscopy is well known (not all acid-fast bacilli are tuberculous bacilli; some are NTM), it must be underlined that Xpert MTB/RIF also lacks specificity.In the authors' study, Xpert's positive predictive value was 75%.In other words, a quarter of tuberculosis treatments started on the basis of Xpert MTB/RIF would have been done erroneously.Overall, we believe that the Xpert MTB/RIF assay should be used as an identification test in patients who have undergone an initial screening: either positive-smear microscopy or, in case of a high clinical suspicion of tuberculosis, in case of negative-smear microscopy.
How the Central American Seaway and an Ancient Northern Passage Affected Flatfish Diversification
Authors: Lisa Byrne, François Chapleau, Stéphane Aris-Brosou
Journal: Molecular Biology and Evolution (2018)

While the natural history of flatfish has been debated for decades, the mode of diversification of this biologically and economically important group has never been elucidated. To address this question, we assembled the largest molecular data set to date, covering > 300 species (out of ca. 800 extant), from 13 of the 14 known families over nine genes, and employed relaxed molecular clocks to uncover their patterns of diversification. As the fossil record of flatfish is contentious, we used sister species distributed on both sides of the American continent to calibrate clock models based on the closure of the Central American Seaway (CAS), and on their current species range. We show that flatfish diversified in two bouts, as species that are today distributed around the equator diverged during the closure of CAS, whereas those with a northern range diverged after this, hereby suggesting the existence of a postCAS closure dispersal for these northern species, most likely along a trans-Arctic northern route, a hypothesis fully compatible with paleogeographic reconstructions.
Long‐Term Risk of Hepatocellular Carcinoma in HCV Patients Treated With Direct Acting Antiviral Agents
Authors: Fasiha Kanwal, Jennifer R. Kramer, Steven M. Asch, Yumei Cao, Liang Li, Hashem B. El‐Serag
Journal: Hepatology (2019)

Sustained virologic response (SVR) after direct acting antiviral agents (DAAs) holds promise for reducing hepatocellular cancer (HCC). DAAs have recently been available long enough to estimate the long‐term risk. We conducted a retrospective cohort study of hepatitis C virus (HCV) patients who achieved SVR with DAAs from 129 Veterans Health Administration hospitals between January 1, 2015, and December 31, 2015, with follow‐up through September 30, 2018. We calculated the overall and quarterly HCC incidence rates. We examined the effect of demographic, clinical, and behavioral factors and the decline or increase of FIB‐4 and aspartate aminotransferase to platelet ratio index (APRI) on HCC risk. Among the 18,076 patients with SVR, 544 incident cases of HCC were diagnosed during the mean 2.9 years of follow‐up. The cumulative 1, 2, and 3‐year risks of HCC were 1.1%, 1.9% and 2.8%, respectively. Cirrhosis was strongly associated with HCC risk (adjusted hazard ratio = 4.13, 95% confidence interval = 3.34‐5.11). The quarterly incidence rate of HCC remained stable between 1.00 and 1.23/100 person‐years (PY) and 1.5 to 2.3/100 PY in patients with cirrhosis. The risk of HCC was the highest in patients who had persistently high FIB‐4/APRI and both with and without cirrhosis. HCC risk fell in patients with cirrhosis who experienced a decrease of FIB‐4/APRI scores yet remained higher than the accepted threshold for HCC surveillance. HCC risk was also higher in patients with alcohol use, older age, and infection with HCV genotype 3. Most patients treated at an early stage of liver fibrosis had a stable low risk. Conclusion : Patients successfully treated with DAAs and at risk of HCC did not regress after 3.6 years of follow‐up. HCC risk remained above the accepted thresholds for surveillance in patients with cirrhosis. These data have important implications for HCC surveillance in cured HCV patients.
Diffuse Poikilodermatous Patches in a Middle-aged Man
Authors: Paola C. Aldana, Gibran Shaikh, Marcia S. Driscoll
Journal: JAMA Dermatology (2019)

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Abstract 15813: Loss-of-Function Mutation in Toll-Like Receptor 4 Partially Protects Against Peripheral and Cardiac Insulin Resistance During a Long-Term High-Fat Diet
Authors: Ellen Jackson, Elizabeth Rendina-Ruedy, Matt Priest, Brenda Smith, Veronique Lacombe
Journal: Circulation (2014)

Diabetes mellitus is an epidemic disease characterized by alterations in glucose transport, which is tightly regulated by a family of specialized proteins called the glucose transporters (GLUTs). Although diabetic cardiomyopathy is a common complication in diabetic patients, its pathogenesis is still not well understood. Toll-like receptor (TLR) 4, which plays a central role in pathogen recognition by the innate immune system, may also play a critical role in linking inflammation and metabolic disease. We hypothesized that TLR4 activation triggers cardiac insulin resistance. We used mice with a loss-of function mutation in TLR4 (C3H/HeJ) and age-matched wild-type (WT, C57BL/6N) mice (n=8/group) to investigate how feeding a high-fat diet (HFD, 60% kcal from fat) for 16 weeks affected whole-body and cardiac glucose metabolism. After 16 weeks, WT mice fed a HFD were obese and developed hyperglycemia and insulin resistance compared to WT mice on a control diet (10% kcal from fat). The C3H/HeJ mice were partially protected against HFD-induced obesity and insulin resistance. In the heart, WT mice fed a HFD had a 30% decrease (P&lt;0.05) in GLUT4 protein content as measured by Western Blot of cardiac crude membrane protein extracts. In contrast, the loss-of-function point mutation in TLR4 partially rescued cardiac GLUT4 content in the face of a HFD. Interestingly, there was a 40% increase (P&lt;0.05) in the novel GLUT isoform, GLUT8, in the heart when mice of either genotype were fed a HFD. Additionally, GLUT4 protein content was negatively (P&lt;0.05) correlated with GLUT8 content in the myocardium, suggesting that GLUT8 may act as a compensatory mechanism in the face of HFD-induced GLUT4 downregulation. Phosphorylated Akt, a key protein of the insulin signaling pathway, was positively (P&lt;0.05) correlated with GLUT4 content, while the basal/inactive form was negatively correlated. In conclusion, these data suggest that activation of TLR4 activation during diabetes and obesity alters glucose transport by an Akt mechanism, and as such is a pathogenic factor during peripheral and cardiac insulin resistance. Overall, TLR4 appears to be a key modulator in the cross-talk between inflammatory and metabolic pathways, as well as a potential therapeutic target for diabetes.
PB2175 LONG TERM FOLLOW‐UP OF MAINTENANCE THERAPY WITH INTEREFRON ALPHA AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANT IN MULTIPLE MYELOMA PATIENTS–SINGLE CENTER EXPERIENCE
Authors: J. Batinic, S. Bašić‐Kinda, D. Pulanić, A. Ostojić, B. Dreta, I. Hude, D. Sertić, R. Serventi Seiwerth, N. Duraković, P. Rončević, I. Bojanić, K. Gjadrov‐Kuveždić, K. Dubravčić, D. Batinić, I. Ilić, I. Aurer, D. Nemet
Journal: HemaSphere (2019)

Background: Maintenance therapy after autologous hematopoietic stem cell transplantation (AHSCT) in multiple myeloma (MM) patients was a matter of debate until recently, when lenalidomide in this setting proved to increase overall survival (OS). Before lenalidomide interferon alpha (IFN) was standard maintenance therapy. Aims: The aim of this analysis was to determine the impact of maintenance therapy after AHSCT on progression free survival (PFS) and OS in MM patients treated at our institution between 1993 and 2014. Methods We performed a retrospective analysis of outcomes of MM patients autografted at our institution between 1993 and 2014. We identified 274 pts. who had PFS at least 6 months posttransplant; median age was 57, range 28‐71, 48% were male. 124 of them received tandem and 150 single AHSCT. Median follow‐up was 62 mo. Posttransplant 200 patients received IFN, 44 thalidomide and 30 no maintenance according to physicians’ choice. Results: Patients receiving IFN had longer 5‐year PFS compared to patients receiving thalidomide or no maintenance (52% vs. 34% vs. 31%, respectively, p &lt; 0.001). OS was best in the IFN group, intermediate in the thalidomide and worst in the no maintenance group (67% vs. 59% vs. 32%, respectively, p &lt; 0.001). The difference was limited to patients receiving tandem transplants. In this group 5‐year PFS was 61% vs. 35% vs 0% (p &lt; 0.001) and OS 85% vs. 67% vs. 65% (p = 0.003) in the IFN, thalidomide and no maintenance group respectively. In patients that received a single transplant 5‐year PFS was 43% vs. 33% vs 36% (p = 0.157) and 5‐year OS 70% vs. 75% vs. 54% (p = 0.06) in the IFN, thalidomide and no maintenance group respectively. Summary/Conclusion: Our results indicate that maintenance therapy has beneficial effects on OS and PFS in MM patients treated with tandem, but not single AHSCT. IFN is superior in this setting to thalidomide and could be considered as a treatment option when lenalidomide is not available.
EVALUATION OF SERINE BIOSYNTHESIS PATHWAY AS A POTENTIAL THERAPEUTIC TARGET IN BURKITT LYMPHOMA
Authors: M. Noyszewska-Kania, E. Bialopiotrowicz, M. Cybulska, A. Grochowska, M. Kopczynski, M. Mikula, N. Kachamakova-Trojanowska, A. Loboda, M. Prochorec-Sobieszek, A. Szumera-Ciećkiewicz, M. Firczuk, A. Graczyk-Jarzynka, R. Zagozdzon, A. Zabek, P. Mlynarz, P. Gorniak, M. Szydlowski, E. Jablonska, A. Polak, P. Kowalczyk, K. Piechna, T. Rzymski, K. Brzozka, P. Juszczynski
Journal: HemaSphere (2019)
PS1233 HES1 AND HES4 HAVE SIMILAR AND DIVERSE CAPACITIES TO MEDIATE HUMAN NOTCH‐DEPENDENT HEMATOPOIETIC LINEAGE DECISIONS
Authors: M. De Decker, M. Lavaert, J. Roels, L. Tilleman, F. Van Nieuwerburgh, T. Taghon
Journal: HemaSphere (2019)

Background: Multipotent hematopoietic stem cells (HSCs) originate in the bone marrow and give rise to all the different cell types in the blood. This process is orchestrated by interactions between cell‐intrinsic mechanisms and the environmental niche that results in the activation of particular molecular networks that drive specific hematopoietic lineage differentiation. One important example is the development of T cells in the thymus. Following colonization by thymus seeding progenitors, Delta‐like‐ligand‐4 (DLL4) that is expressed by thymic epithelial cells triggers the Notch1 receptor that is expressed on these multipotent hematopoietic progenitor cells (HPCs). Activation of the Notch signaling pathway results in the induction of T‐lineage differentiation through the upregulation of T cell‐specific genes that also prevent differentiation towards other hematopoietic lineages. Aims: In both mouse and human, Notch1 activation is the main initial driver to induce T cell development in hematopoietic stem cells. However, although well described in mice, the role of Notch1 target genes during human hematopoietic developmental choices is still rather unclear. Previous studies in human have shown that TCF1, GATA3 and BCL11B are necessary for the initial stages of T cell differentiation by repressing other hematopoietic lineages, but other transcription factors may also function during these developmental choices. Here, we focused on the function of the Notch1 target genes HES1 and HES4 . Methods: We cocultured CB CD34 + Lin − hematopoietic precursor cells with enforced HES1 and HES4 expression on OP9‐DLL4 and MS‐5 stromal cells in conditions that support T‐, B‐, NK‐ and myeloid‐lineage differentiation. In addition, we performed RNA sequencing to identify HES1‐ and HES4‐induced molecular changes during human early hematopoiesis. Results: Our data illustrate that HES1 mainly acts as a repressor of differentiation by maintaining a quiescent stem cell signature in CD34 + HPCs. In contrast, while HES4 can inhibit the NK and myeloid potential of HPCs, it does not affect B cell development. Furthermore, even though HES4 does not alter the Notch ligand requirements to induce T cell development, it promotes early T cell differentiation when Notch1 signaling is present. Summary/Conclusion: Overall, we show that even though HES1 and HES4 are both induced through Notch1 activation during normal human T cell development, they display both unique and similar features during human hematopoiesis.
Acylglycerol Kinase Maintains Metabolic State and Immune Responses of CD8+ T Cells
Authors: Zhilin Hu, Guojun Qu, Xiaoyan Yu, Haojie Jiang, Xiao-Lu Teng, Lei Ding, Qianwen Hu, Xinwei Guo, Yan Zhou, Feng Wang, Hua-Bing Li, Lei Chen, Jin Jiang, Bing Su, Junling Liu, Qiang Zou
Journal: Cell Metabolism (2019)
Abstract 14911: Induction Of Regression Of Atherosclerosis By The LXR-agonist R211945-a Multimodality Non-invasive Assessment And Comparison With Atorvastatin
Authors: Esad Vucic, Claudia Calcagno, Steve Dickson, James Rudd, Katsumi Hayashi, Jan Bucerius, Erin Moshier, Jessica Mounessa, Michelle Roytman, Matthew Moon, James Lin, Tatsuo Tanimoto, Karen Brown, Masakatsu Kotsuma, Sotirios Tsimikas, Edward Fisher, Klaas Nicolay, Valentin Fuster, Zahi Fayad
Journal: Circulation (2011)

Background: Liver-x-receptor (LXR)-agonists induce reversal cholesterol transport and modulate inflammation. Objective: R211945, an LXR-agonist, promotes reverse cholesterol transport while mitigat...
Epidermal Wnt signalling regulates transcriptome heterogeneity and proliferative fate in neighbouring cells
Authors: Arsham Ghahramani, Giacomo Donati, Nicholas M. Luscombe, Fiona M. Watt
Journal: Genome biology (2018)

Canonical Wnt/beta-catenin signalling regulates self-renewal and lineage selection within the mammalian epidermis. Although the transcriptional response of keratinocytes that receive a Wnt signal is well characterized, little is known about the mechanism by which keratinocytes in proximity to the Wnt-receiving cell are co-opted to undergo a change in cell fate. To address this, we perform single-cell RNA-sequencing on mouse keratinocytes co-cultured with and without beta-catenin-activated neighbouring cells. We identify five distinct cell states in cultures that had not been exposed to the beta-catenin stimulus and show that the stimulus redistributes wild-type subpopulation proportions. Using temporal single-cell analysis, we reconstruct the cell fate change induced by Wnt activation from neighbouring cells. Gene expression heterogeneity is reduced in neighbouring cells and this effect is most dramatic for protein synthesis-associated genes. Changes in gene expression are accompanied by a shift to a more proliferative stem cell state. By integrating imaging and reconstructed sequential gene expression changes during the state transition we identify transcription factors, including Smad4 and Bcl3, that are responsible for effecting the transition in a contact-dependent manner. Our data indicate that non-cell autonomous Wnt/beta-catenin signalling decreases transcriptional heterogeneity. This furthers our understanding of how epidermal Wnt signalling orchestrates regeneration and self-renewal.