tbuckley/cabot-search huggingface dataset:
Abstract 12159: Impact of Varying Onset Timing of Diastolic Tricuspid Annular Movement and Tricuspid Inflow on Predictive Values of Doppler-derived Indices for Clinical Outcomes in Pulmonary Arterial Hypertension
Authors: Hiroko Takahama, Garvan C Kane
Journal: Circulation (2015)

Background: In right heart failure, Doppler-derived indices such as RV performance index (RIMP) and tricuspid regurgitant duration (TRD) have been linked to clinical outcomes, but variably. We tested the hypothesis that this variability is based on varying timing and predictive value of the onset of diastolic phase, according to right atrial pressure (RAP) and to whether tissue or flow Doppler is used. Methods: We reviewed echocardiograms and catheter examinations for 151 consecutive patients with pulmonary arterial hypertension. Te’ and TE were defined as the time from QRS onset to the onset of early diastolic velocity on tissue Doppler imaging at the tricuspid valve annulus and to TRD terminal indicating the onset of tricuspid inflow. All measurements were corrected for heart rate. The patients were grouped into low (RAP &lt; 10mmHg, n = 84) and high RAP groups (RAP ≧ 10mmHg, n = 67). Results: Over 3 years, there were 62 total deaths and 8 lung transplantations. In low RAP group, Te’ was prolonged in association with an increase in Tau (R = 0.51, p = 0.0001) and prolonged Te’ predicted higher mortality (HR = 1.20 / 10ms, p = 0.02). In high RAP group, Te’ was still prolonged as Tau increased (R = 0.43, p = 0.008) independently of RAP, while TE was reversely shortened as RAP rose (R = 0.41, p = 0.0006) and shortened TE predicted higher mortality (HR = 0.86 / 10ms, p = 0.008). An increase in RIMP using tissue Doppler only in low RAP group and shortened TRD only in high RAP group predicted higher mortality (HR = 2.09 / 0.1, p = 0.002 and HR = 0.89 / 10ms, p = 0.02, respectively), keeping in line with Te’ and TE, respectively. Conclusions: Both the onset of diastolic tricuspid annular movement and the onset of tricuspid inflow relate to relaxation disorder. As RAP elevates, only the tricuspid inflow onsets early. These observations should be considered when interpreting Doppler-derived indices: they predict clinical outcomes in a limited group of patients according to RAP and to whether tissue or flow is focused on.
Antiproliferative effect of anti PAR antibody on breast and prostate cancer cells
Authors: Alin Ionescu, Elena Ivan, Slavisa Gasic, James F. Holland, Micsumica Platica, Ovidiu Platica
Journal: Cancer Research (2005)

550   Previously, we reported the isolation of a novel gene located on chromosome 1 in Epidermal Differentiation Complex (EDC) which encodes a 146 amino acids transmembrane protein that we called Prostate Androgen Regulated (PAR) gene. The PAR gene is expressed as a single mRNA species in all normal tissues studied and is over expressed in majority of tumors, including breast and prostate. The modulation of PAR expression induced by transfection with gene encoding sequence in sense and antisense orientation suggests that PAR is a protooncogene. Here we report the effect of anti P1 (PAR) antibodies on proliferation of MCF 7 and DU 145 cancer cells. Anti P1 antibody is a highly specific, affinity purified rabbit polyclonal antibody raised against a 20 amino acid antigenic peptide (P1) selected from the amino terminal deduced PAR sequence. On Western blots this antibody reacted with P1 peptide, with recombinant PAR protein prepared in E coli, and with lysates from LNCaP and MCF 7 cells, but not with BSA or protein standards. Antibody activity was completely abolished by antibody pre treatment with P1 peptide indicating its specificity. In tissue culture this antibody induced inhibition of cell proliferation of DU 145 and MCF 7 cells in a dose and time dependent manner. At a concentration of 9 μg/ml about 90% of MCF 7 cells were dead within 4-5 days compared with the control cells treated with IgG from normal rabbits. MCF 10F normal breast cells were not affected by the same treatment. When given ip twice a week in dose of 50 μg/mouse the anti P1 antibody significantly inhibited the growth of DU 145 cells tumors in CB17 SCID mice. Anti PAR antibody induced apoptosis in DU145 cells as evidenced by flow cytometric detection of sub-G1 DNA content. This apoptotic process was associated with down-regulation of Bcl-2 and an increase of caspase-3 activity. Further work is carried out in our laboratory to determine the mechanism of antiproliferative effect of these antibodies.
Serial circulating omega 3 polyunsaturated fatty acids and healthy ageing among older adults in the Cardiovascular Health Study: prospective cohort study
Authors: Heidi TM Lai, Marcia C de Oliveira Otto, Rozenn N Lemaitre, Barbara McKnight, Xiaoling Song, Irena B King, Paulo HM Chaves, Michelle C Odden, Anne B Newman, David S Siscovick, Dariush Mozaffarian
Journal: BMJ (2018)

Abstract Objective To determine the longitudinal association between serial biomarker measures of circulating omega 3 polyunsaturated fatty acid (n3-PUFA) levels and healthy ageing. Design Prospective cohort study. Setting Four communities in the United States (Cardiovascular Health Study) from 1992 to 2015. Participants 2622 adults with a mean (SD) age of 74.4 (4.8) and with successful healthy ageing at baseline in 1992-93. Exposure Cumulative levels of plasma phospholipid n3-PUFAs were measured using gas chromatography in 1992-93, 1998-99, and 2005-06, expressed as percentage of total fatty acids, including α-linolenic acid from plants and eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid from seafoood. Main outcome measure Healthy ageing defined as survival without chronic diseases (ie, cardiovascular disease, cancer, lung disease, and severe chronic kidney disease), the absence of cognitive and physical dysfunction, or death from other causes not part of the healthy ageing outcome after age 65. Events were centrally adjudicated or determined from medical records and diagnostic tests. Results Higher levels of long chain n3-PUFAs were associated with an 18% lower risk (95% confidence interval 7% to 28%) of unhealthy ageing per interquintile range after multivariable adjustments with time-varying exposure and covariates. Individually, higher eicosapentaenoic acid and docosapentaenoic acid (but not docosahexaenoic acid) levels were associated with a lower risk: 15% (6% to 23%) and 16% (6% to 25%), respectively. α-linolenic acid from plants was not noticeably associated with unhealthy ageing (hazard ratio 0.92, 95% confidence interval 0.83 to 1.02). Conclusions In older adults, a higher cumulative level of serially measured circulating n3-PUFAs from seafood (eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid), eicosapentaenoic acid, and docosapentaenoic acid (but not docosahexaenoic acid from seafood or α-linolenic acid from plants) was associated with a higher likelihood of healthy ageing. These findings support guidelines for increased dietary consumption of n3-PUFAs in older adults.
A comparison of matched interim analysis publications and final analysis publications in oncology clinical trials
Authors: C. Wayant, M. Vassar
Journal: Annals of Oncology (2018)

BackgroundProgression-free survival is an increasingly popular surrogate end point for overall survival. The strength of correlation between the two end points varies, raising questions about the correlation between results of interim analyses that report mature progression-free survival data with the subsequent final publication that report overall survival.MethodsWe searched PubMed from 2005 to 2015 for randomized controlled trials that measured both progression-free survival and overall survival. We matched interim publications that reported mature progression-free survival data with their final analyses that reported overall survival. We included 25 matched pairs and 8 unmatched interim analyses whose final analyses are not published. Our primary objectives are to compare interim publications with matched final publications in terms of journal prominence and Altmetric score and to compare progression-free survival and overall survival effect sizes.ResultsAll interim analyses (n = 33) were prespecified and there was a statistically significant progression-free survival benefit in 31 (93.9%). Only eight matched final analyses had statistically significant overall survival data. Interim analyses were more often published in top-5 general medicine journals (P < 0.01) but not in top-5 oncology journals (P = 0.26). Altmetric scores were higher in interim analyses (P < 0.01). Progression-free survival effect sizes from interim analyses were a median of 31% larger than overall survival effect sizes from final analyses.ConclusionInterim analyses with progression-free survival data may generate hype in oncology, as evidenced by journal impact factors and Altmetric scores. The cause of this hype may be due, in part, to large progression-free survival effect sizes. Regardless, in trials that investigate progression-free and overall survival, publishing interim analyses with mature progression-free survival data apart from the final analyses with mature overall survival should be cautioned.
Abstract 20688: A Phenome-Wide Association Study to Assess Pleiotropic Effects of LPA
Authors: Maya S Safarova, Xiao Fan, Gail P Jarvik, Kathleen A Leppig, Laura J Rasmussen-Torvik, Sarah Pendergrass, Amy Sturm, Bahram Namjou, Amy Shah, Robert Carroll, Wendy K Chung, Wei-Qi Wei, Michael Stein, Marc S Williams, Dan M Roden, Josh C Denny, Iftikhar J Kullo
Journal: Circulation (2017)

Introduction: Lipoprotein(a) (Lp(a)) is a risk factor for atherosclerosis but its physiological function remains obscure. Furthermore, the potential introduction of LPA targeting therapies into cli...
The Krüppel-Like Factors and Control of Energy Homeostasis
Authors: Paishiun N Hsieh, Liyan Fan, David R Sweet, Mukesh K Jain
Journal: Endocrine Reviews (2018)

Nutrient handling by higher organisms is a complex process that is regulated at the transcriptional level. Studies over the past 15 years have highlighted the critical importance of a family of transcriptional regulators termed the Krüppel-like factors (KLFs) in metabolism. Within an organ, distinct KLFs direct networks of metabolic gene targets to achieve specialized functions. This regulation is often orchestrated in concert with recruitment of tissue-specific transcriptional regulators, particularly members of the nuclear receptor family. Upon nutrient entry into the intestine, gut, and liver, KLFs control a range of functions from bile synthesis to intestinal stem cell maintenance to effect nutrient acquisition. Subsequently, coordinated KLF activity across multiple organs distributes nutrients to sites of storage or liberates them for use in response to changes in nutrient status. Finally, in energy-consuming organs like cardiac and skeletal muscle, KLFs tune local metabolic programs to precisely match substrate uptake, flux, and use, particularly via mitochondrial function, with energetic demand; this is achieved in part via circulating mediators, including glucocorticoids and insulin. Here, we summarize current understanding of KLFs in regulation of nutrient absorption, interorgan circulation, and tissue-specific use.
Mosaic loss of chromosome Y in leukocytes matters
Authors: Lars A. Forsberg, Jonatan Halvardson, Edyta Rychlicka-Buniowska, Marcus Danielsson, Behrooz Torabi Moghadam, Jonas Mattisson, Chiara Rasi, Hanna Davies, Lars Lind, Vilmantas Giedraitis, Lars Lannfelt, Lena Kilander, Martin Ingelsson, Jan P. Dumanski
Journal: Nature Genetics (2018)
Bendamustine Is Highly Active in Heavily Pre-Treated Relapsed and Refractory Hodgkin Lymphoma and Serves as a Bridge to Allogeneic Stem Cell Transplant.
Authors: Alison J. Moskowitz, Paul A. Hamlin, John Gerecitano, Steven M. Horwitz, Matthew Matasar, Jessica Meikle, Ariela Noy, Maria Lia Palomba, Carol S. Portlock, David J. Straus, Jill M Vanak, Andrew D. Zelenetz, Craig H Moskowitz
Journal: Blood (2009)
Pre-eclampsia and risk of dementia later in life: nationwide cohort study
Authors: Saima Basit, Jan Wohlfahrt, Heather A Boyd
Journal: BMJ (2018)

Abstract Objective To explore associations between pre-eclampsia and later dementia, overall and by dementia subtype and timing of onset. Design Nationwide register based cohort study. Setting Denmark. Population All women with at least one live birth or stillbirth between 1978 and 2015. Main outcome measure Hazard ratios comparing dementia rates among women with and without a history of pre-eclampsia, estimated using Cox regression. Results The cohort consisted of 1 178 005 women with 20 352 695 person years of follow-up. Women with a history of pre-eclampsia had more than three times the risk of vascular dementia (hazard ratio 3.46, 95% confidence interval 1.97 to 6.10) later in life, compared with women with no history of pre-eclampsia. The association with vascular dementia seemed to be stronger for late onset disease (hazard ratio 6.53, 2.82 to 15.1) than for early onset disease (2.32, 1.06 to 5.06) (P=0.08). Adjustment for diabetes, hypertension, and cardiovascular disease attenuated the hazard ratios only moderately; sensitivity analyses suggested that body mass index was unlikely to explain the association with vascular dementia. In contrast, only modest associations were observed for Alzheimer’s disease (hazard ratio 1.45, 1.05 to 1.99) and other/unspecified dementia (1.40, 1.08 to 1.83). Conclusions Pre-eclampsia was associated with an increased risk of dementia, particularly vascular dementia. Cardiovascular disease, hypertension, and diabetes were unlikely to mediate the associations substantially, suggesting that pre-eclampsia and vascular dementia may share underlying mechanisms or susceptibility pathways. Asking about a history of pre-eclampsia could help physicians to identify women who might benefit from screening for early signs of disease, allowing for early clinical intervention.
Stepped Up e-Cigarette Enforcement
Authors: Rebecca Voelker
Journal: JAMA (2018)

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
LPA4-Mediated Vascular Network Formation Increases the Efficacy of Anti–PD-1 Therapy against Brain Tumors
Authors: Daisuke Eino, Yohei Tsukada, Hisamichi Naito, Yonehiro Kanemura, Tomohiro Iba, Taku Wakabayashi, Fumitaka Muramatsu, Hiroyasu Kidoya, Hideyuki Arita, Naoki Kagawa, Yasunori Fujimoto, Kazuhiro Takara, Haruhiko Kishima, Nobuyuki Takakura
Journal: Cancer Research (2018)

Abstract The structure and function of tumor blood vessels profoundly affects the tumor microenvironment. Signals mediated through the lysophosphatidic acid receptor 4 (LPA4) promote vascular network formation to restore normal vascular barrier function in subcutaneous tumors and thus improve drug delivery. However, the characteristics of the vasculature vary by organ and tumor types, and how drug delivery and leukocyte trafficking are affected by modification of vascular function by LPA in different cancers is unclear. Here, we show that LPA4 activation promotes the formation of fine vascular structures in brain tumors. RhoA/ROCK signaling contributed to LPA-induced endothelial cell–cell adhesion, and RhoA/ROCK activity following LPA4 stimulation regulated expression of VCAM-1. This resulted in increased lymphocyte infiltration into the tumor. LPA improved delivery of exogenous IgG into brain tumors and enhanced the anticancer effect of anti–programmed cell death-1 antibody therapy. These results indicate the effects of LPA on vascular structure and function apply not only to chemotherapy but also to immunotherapy. Significance: These findings demonstrate that lysophosphatidic acid, a lipid mediator, promotes development of a fine capillary network in brain tumors by inducing tightening of endothelial cell-to-cell adhesion, facilitating improved drug delivery, and lymphocyte penetration.
Innate Lymphoid Cells and T Cells Contribute to the Interleukin‐17A Signature Detected in the Synovial Fluid of Patients With Juvenile Idiopathic Arthritis
Authors: Elizabeth C. Rosser, Hannah Lom, David Bending, Chantal L. Duurland, Mona Bajaj‐Elliott, Lucy R. Wedderburn
Journal: Arthritis & Rheumatology (2018)

Evidence suggests that aberrant function of innate lymphoid cells (ILCs), whose functional and transcriptional profiles overlap with those of Th cell subsets, contributes to immune-mediated pathologies. To date, analysis of juvenile idiopathic arthritis (JIA) immune pathology has concentrated on the contribution of CD4+ T cells; we have previously identified an expansion of Th17 cells within the synovial fluid (SF) of JIA patients. We undertook this study to extend this analysis to further investigate the role of ILCs and other interleukin-17 (IL-17)-producing T cell subsets in JIA.ILCs and CD3+ T cell subsets were defined in peripheral blood mononuclear cells (PBMCs) from healthy adults, healthy children, and JIA patients and in SF mononuclear cells (SFMCs) from JIA patients using flow cytometry. Defined subsets in SFMCs were correlated with clinical measures including physician's global assessment of disease activity on a visual analog scale, number of joints with active disease, and erythrocyte sedimentation rate. Transcription factor and cytokine profiles of sorted ILCs were assessed by quantitative reverse transcriptase-polymerase chain reaction.Group 1 ILCs (ILC1s), NKp44- group 3 ILCs (natural cytotoxicity receptor-negative [NCR-] ILC3s), and NKp44+ ILC3s (NCR+ ILC3s) were enriched in JIA SFMCs compared to PBMCs, which corresponded to an increase in transcripts for TBX21, IFNG, and IL17A. Of the ILC subsets, the frequency of NCR- ILC3s in JIA SFMCs displayed the strongest positive association with clinical measures, which was mirrored by an expansion in IL-17A+CD4+, IL-17A+CD8+, and IL-17A+ γδ T cells.We demonstrate that the strength of the IL-17A signature in JIA SFMCs is determined by multiple lymphoid cell types, including NCR- ILC3s and IL-17A+CD4+, IL-17A+CD8+, and IL-17A+ γδ T cells. These observations may have important implications for the development of stratified therapeutics.
Abstract 19648: Post-exercise Blood Pressure Following Different Resistance Training Methods in Treated Older Hypertensive Women
Authors: Ana Luiza M Correia, Rafael Gauche, André B Gadelha, Flávio M Paiva, Sílvia G Neri, Ricardo M Lima
Journal: Circulation (2015)

Introduction: The purpose of this study was to examine post-exercise blood pressure following different resistance training methods in treated older hypertensive women. Methods: The sample consisted of 14 female volunteers with controlled hypertension (age 69.86 ± 5.67 years, weight 59.31 ± 9.77 kg, height 1.52 ± 0.06 m, BMI 25.76 ± 4.44 kg/m2) who attended six Laboratory visits. The first four visits aimed at collecting anthropometric data, familiarization and determining the training load. In the fifth and sixth visits, volunteers performed a traditional resistance exercise method (TRE) and a circuit resistance exercise method (CRE), in a randomized order. The sessions were separated by at least 48 hours, involved the following exercises: leg press, seated row, knee extension, bench press, knee flexion, lateral raise with dumbbells and seated calf raises. In TRE, the exercises were performed in three sets of 12 repetitions with an interval of 60 seconds between sets and exercises. In the CRE, the exercises were performed in circuit, with 3 rounds of 12 repetitions with 30 seconds rest between exercises and 60 seconds between rounds. The intensity was adjusted corresponding to the level 4 of the scale of perceived exertion to resistance exercise. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at rest, 15, 30, 45 and 60 minutes after the exercise sessions. Mean blood pressure (MBP) was calculated. Data normality was verified with the Shapiro-Wilk test. ANOVA for repeated measures (time X method) was used for data analysis. Significance was set at p &lt;0.05. Results: Although mean SBP values were reduced following exercise, no significant effects of time, methods or time X method interaction were noted in SBP, DBP and MBP. Conclusions: Both resistance training methods, on intensity corresponding to the level 4 of perceived exertion scale, were not able to significantly alter the blood pressure of treated older hypertensive women
The European Sleep Apnoea Database (ESADA) ERS Clinical Research Collaboration: past, present and future
Authors: Maria R. Bonsignore, Jan Hedner
Journal: European Respiratory Journal (2018)

<b>The European Sleep Apnoea Database (ESADA) ERS Clinical Research Collaboration records data in over 25 000 patients with OSA from 33 European countries, to conduct clinical research and improve OSA patient care and outcomes</b>http://ow.ly/DuDf30lZRP6
Pediatric Esophageal Squamous Cell Carcinoma Staged With 18F-FDG PET/CT
Authors: Melissa Cindy Kong, Helen Ruth Nadel
Journal: Clinical Nuclear Medicine (2018)

A 15-year-old boy with autism and swallowing dysfunction presented with a 6-month history of fatigue, intermittent abdominal pain, and weight loss. He later became febrile and had multiple episodes of coffee ground emesis and melena stools. An upper endoscopy showed an esophageal mass, and a subsequent F-FDG PET/CT scan confirmed this finding. PET/CT also revealed metastatic disease in local lymph nodes, thus upstaging the patient and indicating poor prognosis. Consideration of these severe results and the patient's quality of life helped guide decision making in patient management, with the ultimate decision to pursue palliative care.