tbuckley/cabot-search huggingface dataset:
Abstract 14665: Left Ventricular Shape Analysis Predicts Heart Failure and Coronary Heart Disease: the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Bharath Ambale Venkatesh, Kihei Yoneyama, Ravi K Sharma, Yoshiaki Ohyama, Colin Wu, Burke Gregory, Shea Steven, Antoinette Gomes, Bluemke David, Lima A Joao
Journal: Circulation (2014)

Introduction: Left ventricular shape is identified as an important component of remodeling. We investigate whether sphericity index (SI) predicts congestive heart failure (CHF) and coronary heart disease (CHD) over 10 years in the MESA population.

Methods: As part of the Multi Ethnic Study of Atherosclerosis, 5004 participants free of known cardiovascular disease had MRI in 2000-2002. Cine images were used to compute SI = volume/ (length3 * pi/6) of LV using QMass. The highest and lowest quintiles of SI corresponding to high eccentricity and high concentricity respectively were compared against the reference group comprised of the second, third and fourth quintiles combined. Cox regression assessed the predictive performance of groups of high and low SI (compared to reference) to predict CHF and CHD over a 10-year follow-up period adjusted to age, gender, race, BMI, smoking, systolic blood pressure, hypertension medication, HDL, heart rate, total cholesterol, diabetes, LV mass, ejection fraction, and calcium score.

Results: At baseline, participants were aged 61±10 yrs; 52% men; 39/13/26/22% Cauc/Chinese/Afr-Amer/Hispanic; 42% hypertensive; and 11.6% diabetic. SI at end-diastole was 0.29±0.08 and predicted neither CHD nor CHF after adjustment. SI at end-systole was 0.16±0.07 and showed independent prediction power for CHF at both lowest and highest groups compared to the reference. The lowest group of SI also predicted CHD compared to the middle group.

Conclusions: Both low and high sphericity indicative of increased concentricity and increased eccentricity of the LV chamber respectively were predictive of CHF; while increased concentricity alone was predictive of CHD.

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Parcellating cortical functional networks in individuals
Authors: Danhong Wang, Randy L Buckner, Michael D Fox, Daphne J Holt, Avram J Holmes, Sophia Stoecklein, Georg Langs, Ruiqi Pan, Tianyi Qian, Kuncheng Li, Justin T Baker, Steven M Stufflebeam, Kai Wang, Xiaomin Wang, Bo Hong, Hesheng Liu
Journal: Nature Neuroscience (2015)
Racial and Ethnic Variations in Lung Cancer Incidence and Mortality: Results From the Women’s Health Initiative
Authors: Manali I. Patel, Ange Wang, Kristopher Kapphahn, Manisha Desai, Rowan T. Chlebowski, Michael S. Simon, Chloe E. Bird, Giselle Corbie-Smith, Scarlett Lin Gomez, Lucile L. Adams-Campbell, Michele L. Cote, Marcia L. Stefanick, Heather A. Wakelee
Journal: Journal of Clinical Oncology (2015)

This study aimed to evaluate racial/ethnic differences in lung cancer incidence and mortality in the Women's Health Initiative Study, a longitudinal prospective cohort evaluation of postmenopausal women recruited from 40 clinical centers.Lung cancer diagnoses were centrally adjudicated by pathology review. Baseline survey questionnaires collected sociodemographic and health information. Logistic regression models estimated incidence and mortality odds by race/ethnicity adjusted for age, education, calcium/vitamin D, body mass index, smoking (status, age at start, duration, and pack-years), alcohol, family history, oral contraceptive, hormones, physical activity, and diet.The cohort included 129,951 women--108,487 (83%) non-Hispanic white (NHW); 10,892 (8%) non-Hispanic black (NHB); 4,882 (4%) Hispanic; 3,696 (3%) Asian/Pacific Islander (API); 534 (< 1%) American Indian/Alaskan Native; and 1,994 (1%) other. In unadjusted models, Hispanics had 66% lower odds of lung cancer compared with NHW (odds ratio [OR], 0.34; 95% CI, 0.2 to 0.5), followed by API (OR, 0.45; 95% CI, 0.27 to 0.75) and NHB (OR, 0.75; 95% CI, 0.59 to 0.95). In fully adjusted multivariable models, the decreased lung cancer risk for Hispanic compared with NHW women attenuated to the null (OR, 0.59; 95% CI, 0.35 to 0.99). In unadjusted models Hispanic and API women had decreased risk of death compared with NHW women (OR, 0.30 [95% CI, 0.15 to 0.62] and 0.34 [95% CI, 0.16 to 0.75, respectively); however, no racial/ethnic differences were found in risk of lung cancer death in fully adjusted models.Differences in lung cancer incidence and mortality are associated with sociodemographic, clinical, and behavioral factors. These findings suggest modifiable exposures and behaviors may contribute to differences in incidence of and mortality by race/ethnicity for postmenopausal women. Interventions focused on these factors may reduce racial/ethnic differences in lung cancer incidence and mortality.
Architecture, Function, and Assembly of the Mouse Visual System
Authors: Tania A. Seabrook, Timothy J. Burbridge, Michael C. Crair, Andrew D. Huberman
Journal: Annual Review of Neuroscience (2017)

Vision is the sense humans rely on most to navigate the world, make decisions, and perform complex tasks. Understanding how humans see thus represents one of the most fundamental and important goals of neuroscience. The use of the mouse as a model for parsing how vision works at a fundamental level started approximately a decade ago, ushered in by the mouse's convenient size, relatively low cost, and, above all, amenability to genetic perturbations. In the course of that effort, a large cadre of new and powerful tools for in vivo labeling, monitoring, and manipulation of neurons were applied to this species. As a consequence, a significant body of work now exists on the architecture, function, and development of mouse central visual pathways. Excitingly, much of that work includes causal testing of the role of specific cell types and circuits in visual perception and behavior-something rare to find in studies of the visual system of other species. Indeed, one could argue that more information is now available about the mouse visual system than any other sensory system, in any species, including humans. As such, the mouse visual system has become a platform for multilevel analysis of the mammalian central nervous system generally. Here we review the mouse visual system structure, function, and development literature and comment on the similarities and differences between the visual system of this and other model species. We also make it a point to highlight the aspects of mouse visual circuitry that remain opaque and that are in need of additional experimentation to enrich our understanding of how vision works on a broad scale.
Effect of erythrocyte mass on arterial blood pressure in dialysis patients receiving maintenance erythropoietin therapy.
Authors: C J Kaupke, S Kim, N D Vaziri
Journal: Journal of the American Society of Nephrology (1994)

Treatment of renal anemia with recombinant human erythropoietin (rEPO) frequently raises arterial blood pressure. The objective of this study was to determine whether this is a direct effect of rEPO or a consequence of the expansion of erythrocyte mass. Twenty-three chronic hemodialysis patients receiving maintenance rEPO therapy who had uncontrolled anemia due to iron deficiency were studied. It was anticipated that repletion of iron stores with iv iron dextran would restore rEPO responsiveness, leading to a gradual rise in hematocrit to the target values (0.30 to 0.33). The effect of the increase in hematocrit on arterial blood pressure could then be dissected from the direct effect of rEPO in patients receiving constant doses of rEPO throughout the study period. To this end, arterial blood pressure, iron indices, hematocrit, and measures of fluid balance were monitored at baseline and for a 10-wk period after iron repletion. In eight patients, the hematocrit transiently rose above 0.33, triggering a reduction in rEPO dosage. In the remaining 15 patients, rEPO dosage was held constant during the study period. In this subgroup, repletion of iron stores led to a rise in hematocrit from 0.25 +/- 0.04 to 0.32 +/- 0.04 (P < 0.001) within 4 wk. Despite the significant rise in hematocrit, both systolic and diastolic blood pressure values remained virtually unchanged. Likewise, body weight and interdialytic fluid gain were unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)
Ergocalciferol Supplementation in Hemodialysis Patients With Vitamin D Deficiency: A Randomized Clinical Trial
Authors: Dana C. Miskulin, Karen Majchrzak, Hocine Tighiouart, Richard S. Muther, Toros Kapoian, Doug S. Johnson, Daniel E. Weiner
Journal: Journal of the American Society of Nephrology (2015)

Locally produced 1,25-dihydroxyvitamin D3 may have pleiotropic effects outside of bone. Experimental and observational studies suggest that nutritional vitamin D may enhance erythropoiesis in settings of 25-hydroxy vitamin D (25(OH)D) deficiency. We conducted a double-blind, placebo-controlled, randomized clinical trial to assess the effects of supplementation with ergocalciferol on epoetin utilization and other secondary outcomes in patients on hemodialysis with serum 25(OH)D &lt;30 ng/ml. In all, 276 patients were randomized to 6 months of ergocalciferol or placebo. Mean±SD serum 25(OH)D increased from 16.0±5.9 ng/ml at baseline to 39.2±14.9 ng/ml in the ergocalciferol arm and did not change (16.9±6.4 ng/ml and 17.5±7.4 ng/ml, respectively) in the placebo arm. There was no significant change in epoetin dose over 6 months in the ergocalciferol or placebo arms (geometric mean rate 0.98 [95% confidence interval (95% CI), 0.94 to 1.02] versus 0.99 [95% CI, 0.95 to 1.03], respectively) and no difference across arms ( P =0.78). No change occurred in serum calcium, phosphorus, intact parathyroid hormone, or C-reactive protein levels, cinacalcet use, or phosphate binder or calcitriol dose in either study arm. Rates of all-cause, cardiovascular, and infection-related hospitalizations did not differ by study arm, although statistical power was limited for these outcomes. In conclusion, 6 months of supplementation with ergocalciferol increased serum 25(OH)D levels in patients on hemodialysis with vitamin D insufficiency or deficiency, but had no effect on epoetin utilization or secondary biochemical and clinical outcomes.
Ewing's tumors with primary lung metastases: survival analysis of 114 (European Intergroup) Cooperative Ewing's Sarcoma Studies patients.
Authors: M Paulussen, S Ahrens, A W Craft, J Dunst, B Fröhlich, S Jabar, C Rübe, W Winkelmann, S Wissing, A Zoubek, H Jürgens
Journal: Journal of Clinical Oncology (1998)

PURPOSE To analyze event-free survival (EFS) and prognostic factors in patients who present with Ewing's tumors (ET) of bone and synchronous pulmonary and/or pleural metastases (ppm). PATIENTS AND METHODS Of 1,270 patients (pts) registered at the continental office of the German/European Intergroup Cooperative Ewing's Sarcoma Studies (CESS81, CESS86, EICESS92), 114 were diagnosed ET with ppm. Patients underwent neoadjuvant therapy and local treatment of the primary tumor. Whole-lung irradiation 15 to 18 Gy was applied to 75 ppm-pts. EFS and 95% confidence intervals (CIs) were estimated according to the Kaplan-Meier method, and prognostic factors were analyzed by log-rank tests and Cox and logistic regression procedures. RESULTS On November 1, 1997, at a median time under study of 5.9 years, the 5-year EFS was 0.36 (95% CI, 0.26 to 0.46) and the 10-year EFS was 0.30 (95% CI, 0.19 to 0.41). Thirty-seven of 59 (63%) first relapses involved lung and/or pleura, and the lungs were the only site of relapse in 26 of 59 (44%) ppm-pts. Risk factors identified in univariate and multivariate tests were poor response of the primary tumor toward chemotherapy, metastatic lesions in both lungs, and treatment without additional lung irradiation. CONCLUSION Chemotherapy response of the primary tumor is a prognostic factor in patients with ET with ppm. Strategies of treatment intensification warrant further evaluation.
Transcriptome-wide high-throughput deep m6A-seq reveals unique differential m6A methylation patterns between three organs in Arabidopsis thaliana
Authors: Yizhen Wan, Kai Tang, Dayong Zhang, Shaojun Xie, Xiaohong Zhu, Zegang Wang, Zhaobo Lang
Journal: Genome biology (2015)

m6A is a ubiquitous RNA modification in eukaryotes. Transcriptome-wide m6A patterns in Arabidopsis have been assayed recently. However, differential m6A patterns between organs have not been well characterized. Over two-third of the transcripts in Arabidopsis are modified by m6A. In contrast to a recent observation of m6A enrichment in 5′ mRNA, we find that m6A is distributed predominantly near stop codons. Interestingly, 85 % of the modified transcripts show high m6A methylation extent compared to their transcript level. The 290 highly methylated transcripts are mainly associated with transporters, stress responses, redox, regulation factors, and some non-coding RNAs. On average, the proportion of transcripts showing differential methylation between two plant organs is higher than that showing differential transcript levels. The transcripts with extensively higher m6A methylation in an organ are associated with the unique biological processes of this organ, suggesting that m6A may be another important contributor to organ differentiation in Arabidopsis. Highly expressed genes are relatively less methylated and vice versa, and different RNAs have distinct m6A patterns, which hint at mRNA fate. Intriguingly, most of the transposable element transcripts maintained a fragmented form with a relatively low transcript level and high m6A methylation in the cells. This is the first study to comprehensively analyze m6A patterns in a variety of RNAs, the relationship between transcript level and m6A methylation extent, and differential m6A patterns across organs in Arabidopsis.
Unrelated cord blood transplantation for childhood acute myelogenous leukemia: The influence of cytogenetic risk group stratification
Authors: G Michel, R Cunha, A Ruggeri, T A O'Brien, H Bittencourt, J H Dalle, F Locatelli, A P Iori, M Mauad, C Oudin, F Giannotti, F Volt, E Gluckman, P Bader, V Rocha
Journal: Leukemia (2015)
Hormone Replacement Therapy After Breast Cancer: A Systematic Review and Quantitative Assessment of Risk
Authors: Nananda F. Col, Linda K. Hirota, Richard K. Orr, John K. Erban, John B. Wong, Joseph Lau
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Hormone replacement therapy (HRT) is typically withheld from women with breast cancer because of concern that it might increase the risk of recurrence. The purpose of this study was to quantify the risk of recurrent breast cancer associated with HRT among breast cancer survivors. METHODS: We performed a systematic literature review through May 1999, calculating the relative risk (RR) of breast cancer recurrence in each study by comparing the number of recurrences in the HRT group to those in the control group. In studies that did not contain a control group, we constructed one by estimating the expected number of recurrences based on data from the Early Breast Cancer Trialists’ Collaborative Group, adjusting for nodal status and disease-free interval. RRs across all studies were combined using random-effects models. RESULTS: Of the 11 eligible studies, four had control groups and included 214 breast cancer survivors who began HRT after a mean disease-free interval of 52 months. Over a mean follow-up of 30 months, 17 of 214 HRT users experienced recurrence (4.2% per year), compared with 66 of 623 controls (5.4% per year). HRT did not seem to affect breast cancer recurrence risk (RR = 0.64, 95% confidence interval [CI], 0.36 to 1.15). Including all 11 studies in the analyses (669 HRT users), using estimated control groups for the seven uncontrolled trials, the combined RR was 0.82 (95% CI, 0.58 to 1.15). CONCLUSION: Although our analyses suggest that HRT has no significant effect on breast cancer recurrence, these findings were based on observational data subject to a variety of biases.
Induction chemotherapy (CTX) followed by concurrent chemoradiotherapy (CRT) in patients (pts) with nasopharyngeal cancer (NPC)
Authors: J.-H. Choi, H. Y. Lim, J. S. Park, H. C. Kim, S. Kang, Y. T. Oh, M. Chun, C. H. Kim
Journal: Journal of Clinical Oncology (2004)

5598 Background: A randomized trial has demonstrated that concurrent CRT is superior to radiotherapy (RT) alone in advanced NPC (Intergroup 0099, J Clin Oncol 16:1310, 1998). Methods: Between October 1996 and October 2001, we treated 35 pts with NPC (stage I: 1, II: 12, III: 7, IV: 15) with 1 cycle of induction CTX (5-fluorouracil 1000 mg/m2 D1–4, cisplatin 20 mg/m2 D1–4) followed by concurrent CRT starting on day 22. CRT consisted of RT (7020 cGy at 180 cGy/day) with concurrent cisplatin 20 mg/m2 on D22–25, D43–46, and D64–67. Results: Based on post-treatment imaging, complete response (CR) was achieved in 33 pts (94%), partial response in 1 pt, and one pt demonstrated progressive disease. Among pts with CR, 11 pts recurred: 6 locoregional, 5 distant. Twelve pts died, 10 with recurrence or disease progression, 1 with radiation induced brain necrosis, and 1 from unknown cause. Four-year progression-free survival and overall survival of total pts were 59% and 64%, respectively, with 46 months median follow-up in survivors. Major toxicities were oral mucositis (grade 3 or 4: 20 pts), radiation dermatitis (grade 3: 11 pts), and leukopenia (grade 3: 6 pts). Furthermore, thirty-one patients (89%) experienced at least one type of otototoxicity: otitis media (27 pts), sensorineural and/or conductive hearing loss (21 pts), external otitis (7 pts), tinnitus (5 pts). Conclusions: The outcome of pts treated with this combined modality therapy appears to be comparable with that of Intergroup 0099 trial with high CR rate. In addition, ototoxicity seems to be a very frequent and clinically significant complication of CRT for NPC. No significant financial relationships to disclose.
Serial Activation of the Inducible Caspase 9 Safety Switch After Human Stem Cell Transplantation
Authors: Xiaoou Zhou, Swati Naik, Olga Dakhova, Gianpietro Dotti, Helen E. Heslop, Malcolm K. Brenner
Journal: Molecular Therapy (2015)

Activation of the inducible caspase 9 (iC9) safety gene by a dimerizing drug (chemical inducer of dimerization (CID) AP1903) effectively resolves the symptoms and signs of graft-versus-host disease (GvHD) in haploidentical stem cell transplant (HSCT) recipients. However, after CID treatment, 1% of iC9-T cells remain and can regrow over time; although these resurgent T cells do not cause recurrent GvHD, it remains unclear whether repeat CID treatments are a safe and feasible way to further deplete residual gene-modified T cells should any other adverse effects associated with them occur. Here, we report a patient who received an infusion of haploidentical iC9-T cells after HSCT and subsequently received three treatments with AP1903. There was a mild (grade 2) and transient pancytopenia following each AP1903 administration but no non-hematological toxicity. Ninety five percent of circulating iC9-T cells (CD3(+)CD19(+)) were eliminated after the first AP1903 treatment. Three months later, the residual cells had expanded more than eightfold and had a lower level of iC9 expression. Each repeated AP1903 administration eliminated a diminishing percentage of the residual repopulating cells, but elimination could be enhanced by T-cell activation. These data support the safety and efficiency of repeated CID treatments for persistent or recurring toxicity from T-cell therapies.
Histone methyltransferases and demethylases: regulators in balancing osteogenic and adipogenic differentiation of mesenchymal stem cells
Authors: Peng Deng, Qian-Ming Chen, Christine Hong, Cun-Yu Wang
Journal: International Journal of Oral Science (2015)

Mesenchymal stem cells (MSCs) are characterized by their self-renewing capacity and differentiation potential into multiple tissues. Thus, management of the differentiation capacities of MSCs is important for MSC-based regenerative medicine, such as craniofacial bone regeneration, and in new treatments for metabolic bone diseases, such as osteoporosis. In recent years, histone modification has been a growing topic in the field of MSC lineage specification, in which the Su(var)3–9, enhancer-of-zeste, trithorax (SET) domain-containing family and the Jumonji C (JmjC) domain-containing family represent the major histone lysine methyltransferases (KMTs) and histone lysine demethylases (KDMs), respectively. In this review, we summarize the current understanding of the epigenetic mechanisms by which SET domain-containing KMTs and JmjC domain-containing KDMs balance the osteogenic and adipogenic differentiation of MSCs. Two enzyme families with opposite actions regulate the differentiation of stem cells, and could be exploited to enhance bone repair. The enzymes catalyse modifications of proteins called histones, around which DNA molecules are wrapped; one enzyme family adds methyl groups, the other removes them. These modifications affect gene expression and regulate the development of mesenchymal stem cells (MSCs). Christine Hong and Cun-Yu Wang from the University of California, USA, and colleagues have reviewed the roles of these enzymes. Both enzyme families are essential in determining whether MSCs develop into bone or fat cells, so manipulating them could enable directed differentiation to aid bone repair. The authors conclude that in order to realize the full clinical potential, future work must determine exactly how the opposing functions of the enzymes are balanced during differentiation.