tbuckley/cabot-search huggingface dataset:
Abstract 32: Racial Differences in Cardiorespiratory Fitness Between African and Caucasian Americans: A Meta-analysis
Authors: Damon L Swift, Tyara R Nevels, Hope Landrine, Carl J Lavie, Robert L Newton, Bhibha M Das, Paul Vos, Joseph A Houmard
Journal: Circulation (2017)

Introduction: Cardiorespiratory fitness (CRF) is an independent risk factor for cardiovascular disease (CVD). Recent data suggests that African Americans (AA) have reduced levels of CRF compared to Caucasian Americans (CA). However, this viewpoint has not been widely accepted and it is unclear whether racial differences in CRF may be of a large enough magnitude to increase the risk of CVD. Methods: A literature review was conducted for studies comparing CRF levels between AA and CA adults. Studies were eligible for inclusion if CRF was assessed by an exercise test (submaximal or maximal), CRF was compared between AA and CA adults, examined an adult study population, and was published in a peer-reviewed journal. Potential studies were excluded if the sample included children or adolescents, the sample size was less than 15 participants in each racial group, or the study evaluated participants who had significant health conditions. Meta-analyses were performed comparing CRF between AAs and CAs in two analyses: 1) all studies compared using metabolic equivalents (METs) and 2) restricted only to studies that quantified CRF by directing measuring maximal oxygen consumption (considered the gold standard). Both fixed effects and random effects models were fit to these data. Because of the heterogeneity only results from the random effects models are reported. Analyses were performed using R (version 3.1, R Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-project.org/) and the rmeta package (version 2.6). Results: There were 27 studies (n=131,084) that that met the criteria for the meta-analysis (23 studies excluded). In both the analyses for METs (27 studies, Summary effect: 0.91, CI: 0.8 to 1.0) and directly measured VO 2 max (16 studies, Summary effect: 3.2, CI: 2.1 to 4.3) as the criteria for CRF, AA had lower fitness compared to CA adults. Conclusions: The present study suggests that AAs have lower CRF compared to CAs based on epidemiological studies and clinical trials whether directly measured using indirect calorimetry or maximal METs estimated from exercise testing. A difference of 0.91 METs is associated with ~13.7% higher risk of CVD based on previous epidemiological data. Thus, lower CRF in AA adults may represent a health disparity risk factor and interventions to improve CRF in sedentary AAs may be warranted.
Romidepsin (Depsipeptide, FK228) Induces Clinically Significant Responses in Treatment-Refractory CTCL: Interim Report of a Phase II Multicenter Study.
Authors: Adam Lerner, M.F. Demierre, S. Whittaker, T. Robak, E. Baran, W. McCulloch, A.G. Prentice
Journal: Blood (2006)
Clinical Relevance of Vascular Endothelial Growth Factor (VEGFA) and VEGF Receptor (VEGFR2) Gene Single Nucleotide Polymorphism on the Treatment Outcomes Following Imatinib Mesylate Therapy.
Authors: Dong Hwan Kim, Hee Kyung Ahn, Wei Xu, Suzanne Kamel-Reid, Xiangdong Liu, Katherine Siminovitch, Jeffrey H. Lipton
Journal: Blood (2008)
Interference with Bone Marrow Stroma Derived Factors CXCL12 and TGFBI Increases Apoptosis in ALL Cells and Enhances Antileukemia Effects of Dexamethasone, Methotrexate, Vincristine and 6-Mercaptopurine
Authors: Sana Usmani, Olena Tkachencko, Leti Nunez, Craig A. Mullen
Journal: Blood (2015)
Preventing Severe Asthma Exacerbations in Children. A Randomized Trial of Mite-Impermeable Bedcovers
Authors: Clare S. Murray, Philip Foden, Helen Sumner, Elizabeth Shepley, Adnan Custovic, Angela Simpson
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Allergen exposure in sensitized individuals with asthma interacts with viruses to increase the risk of asthma exacerbation.Objectives: To evaluate the use of house dust mite–impermeable bedding and its impact on severe asthma exacerbations in children.Methods: We randomized mite-sensitized children with asthma (ages 3–17 yr) after an emergency hospital attendance with an asthma exacerbation to receive mite-impermeable (active group) or control (placebo group) bed encasings.Measurements and Main Results: Over a 12-month intervention period, the occurrence of severe asthma exacerbations was investigated. Of 434 children with asthma who consented, 286 (mean age, 7.7 yr; male sex, 65.8%) were mite sensitized, and 284 were randomized (146 to the active group and 138 to the placebo group). At 12 months, significantly fewer children in the active group than in the placebo group had attended the hospital with an exacerbation (36 [29.3%] of 123 vs. 49 [41.5%] of 118; P = 0.047). In the multivariable analysis, the risk of emergency hospital attendance was 45% lower in the active group (hazard ratio, 0.55; 95% confidence interval [CI], 0.36–0.85; P = 0.006) than in the placebo group. The annual rate of emergency hospital attendance with exacerbations was 27% lower in the active group than in the placebo group, but this did not reach significance (estimated marginal mean [95% CI], active, 0.38 [0.26–0.56] vs. placebo, 0.52 [0.35–0.76]; P = 0.18). No difference between the groups in the risk of prednisolone use for exacerbation was found (hazard ratio, 0.82; 95% CI, 0.58–1.17; P = 0.28).Conclusions: Mite-impermeable encasings are effective in reducing the number of mite-sensitized children with asthma attending the hospital with asthma exacerbations but not the number requiring oral prednisolone. This simple measure may reduce the health care burden of asthma exacerbations in children.Clinical trial registered with www.isrctn.com (ISRCTN 69543196).
Frequency and prognosis of Clonal Chromosomal Abnormalities Following Stem Cell Transplantation (SCT) in Acute Myeloid Leukemia (AML)
Authors: Javi er Grau, Adela Cisneros, Lurdes Zamora, Juan Manuel Sancho, Isabel Granada, Neus Ruiz-Xivillé, Marisol Xandri, Ramon Guardia, Cristalina Fernandez, Encarnación Santafé, Carmen Villena, Marta Cabezón, Esther Sancho, Blanca Xicoy, Laia López, Inés Rodriguez, Miriam Moreno, Elisa Orna, Christelle Ferra, Montserrat Batlle, Francisco Javier Roncalés, Alonso Flores, Jordi Juncà, José Tomás Navarro, Josep Maria Ribera, Evarist Feliu, Fuensanta Millá
Journal: Blood (2008)
Abstract P6-11-15: Pre-clinical investigation of estrogen receptor β agonists for the treatment of breast cancer
Authors: C Samayoa, NK Krishnegowda, RK Vadlamudi, RR Tekmal
Journal: Cancer Research (2017)

Abstract Breast Cancer is the primary cause of cancer-associated mortality worldwide, and in United States alone, more than 250,000 women are diagnosed every year. Current breast cancer treatment strategies focus on Estrogen Receptor α signaling, given that the majority of cases diagnosed are ERα positive. These treatment strategies include endocrine therapies; such as anti-estrogens or aromatase inhibitors. Although, endocrine therapy has been demonstrated to be successful and effective, therapy resistance commonly arises and results in relapse. While current endocrine therapies focus on ERα signaling, emerging studies highlight the importance of Estrogen Receptor β.Unlike ERα, ERβ has been shown to have tumor-suppressive function in various cancers, including breast cancer. Recent studies have identified, synthesized, and tested the clinical safety of ERβ-selective agonists. The objective of this study was to investigate the utility of using ERβ agonists in the treatment of breast cancer. To investigate the utility of ERβ agonists in the treatment of breast cancer, we used in-vitro and in-vivo pre-clinical models systems. Our results demonstrated that treatment with ERβ agonists, S-Equol and LY500307, was able to inhibit the short-term and long-term growth of both endocrine therapy sensitive and resistant breast cancer cells. Progression through the cell cycle, cell migration and cell invasion was also abrogated upon treatment. In-vivo, our syngeneic tumor mouse model demonstrates a decline in tumor growth rate after treating with a combination of letrozole and ERβ agonist. Gene expression array analysis reveal that treatment with ERβ agonist elicits changes in key signaling molecules involved in cell death and cell cycle pathways. In Letrozole resistant cells, Letrozole treatment had not effect on gene expression, while LY500307 treatment resulted in the modulation of 780 genes. Interestingly, combining Letrozole with LY500307 resulted in the modulation of 966 genes, of which 417 were unique to the combination treatment. Our studies suggest that activation of ERβ signaling is a valuable strategy in the treatment of breast cancer, even in cases which have developed resistance to current endocrine therapies. Citation Format: Samayoa C, Krishnegowda NK, Vadlamudi RK, Tekmal RR. Pre-clinical investigation of estrogen receptor β agonists for the treatment of breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-11-15.
Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) in Patients with Haematological Lymphoid Malignancies: Long Term Follow-up in a Single Centre Series.
Authors: Malek Benakli, Redhouane Ahmed nacer, Amina Talbi, Rachida Belhadj, Farih Mehdid, Nadia Rahmoune, Farida Harieche, Soumeya Abderahmani, Keltoum Saidani, Sabrina Akhrouf, Faiza Boumansour, Fatiha Zerhouni, Rose-Marie Hamladji
Journal: Blood (2009)
Abstract P2-07-12: The association between patient comorbidity and breast cancer survival
Authors: J Han, H-B Lee, E-S Lee, YJ Kang, Y Kim, J Choi, J Rhu, W Han, D-Y Noh, H-G Moon
Journal: Cancer Research (2017)

Abstract Background There are studies suggesting significant association between the patient's comorbidity and perioperative outcomes. In breast cancer, patient comorbidity can also influence the oncologic outcome by affecting the decisions regarding adjuvant treatments. In this study, we examined the long-term oncologic outcome in breast cancer patients who underwent curative surgery according to their pre-existing comorbid conditions. Methods The medical records of 2,501 patients who underwent surgery for primary breast cancer from June 2006 to June 2010 were reviewed retrospectively. The patients were classified into three groups (ASA 1, 2, 3) according to preoperative ASA status determined by the anesthesiologists. Clinico-pathologic characteristics and survival outcomes of the patients were compared among the different co-morbidity groups. Result There were 1,792 (71.6%), 665 (26.6%), and 44 (1.8%) patients in ASA 1, 2, and 3, respectively. Total 95 (3.8%) deaths and 269 (10.8%) recurrences (loco-regional and distant) occurred during the median follow-up period of 71 months. Patients with high comorbidity showed significantly higher rate of death (51 (2.8%), 38 (5.7%) and 6 (13.6%) deaths in ASA 1, 2 and 3 group, respectively, p&amp;lt;0.001). The ASA 3 patients also showed significantly higher rate of breast cancer recurrence when compared to other groups (180 (10.0%), 80 (12.0%) and 9 (20.5%) in ASA 1, 2 and 3, respectively, p=0.041). Cox multivariate analysis demonstrated that high ASA score (ASA 3) was an independent prognostic factor in DFS, OS and BCSS (95% confidence interval [CI], 1.661-6.780; p=0.001, 1.753-11.321; p=0.002 and 2.222-18.429; p=0.001). Fewer patients in the high co-morbidity group received adjuvant therapies (77 (4.3%), 44 (6.6%) and 8 (18.2%) in ASA 1, 2 and 3, p&amp;lt;0.001). The increased recurrence of breast cancer in the high morbidity group was most seen in patients who did not receive adjuvant therapies. The incidence of serious adverse effect during the adjuvant therapy did not differ according to the co-morbidity conditions. Conclusion In this study, high comorbidity was related to increased risk of death and recurrence in breast cancer. The increased risk of recurrence in high co-morbidity group was mostly seen in patients who did not receive adjuvant therapies. In patients who underwent the adjuvant therapies, the incidence of serious adverse effects did not differ according to the co-morbidity status. Citation Format: Han J, Lee H-B, Lee E-S, Kang YJ, Kim Y, Choi J, Rhu J, Han W, Noh D-Y, Moon H-G. The association between patient comorbidity and breast cancer survival [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-07-12.
Structure-Guided Identification of a Family of Dual Receptor-Binding PfEMP1 that Is Associated with Cerebral Malaria
Authors: Frank Lennartz, Yvonne Adams, Anja Bengtsson, Rebecca W. Olsen, Louise Turner, Nicaise T. Ndam, Gertrude Ecklu-Mensah, Azizath Moussiliou, Michael F. Ofori, Benoit Gamain, John P. Lusingu, Jens E.V. Petersen, Christian W. Wang, Sofia Nunes-Silva, Jakob S. Jespersen, Clinton K.Y. Lau, Thor G. Theander, Thomas Lavstsen, Lars Hviid, Matthew K. Higgins, Anja T.R. Jensen
Journal: Cell Host & Microbe (2017)

Cerebral malaria is a deadly outcome of infection by Plasmodium falciparum, occurring when parasite-infected erythrocytes accumulate in the brain. These erythrocytes display parasite proteins of the PfEMP1 family that bind various endothelial receptors. Despite the importance of cerebral malaria, a binding phenotype linked to its symptoms has not been identified. Here, we used structural biology to determine how a group of PfEMP1 proteins interacts with intercellular adhesion molecule 1 (ICAM-1), allowing us to predict binders from a specific sequence motif alone. Analysis of multiple Plasmodium falciparum genomes showed that ICAM-1-binding PfEMP1s also interact with endothelial protein C receptor (EPCR), allowing infected erythrocytes to synergistically bind both receptors. Expression of these PfEMP1s, predicted to bind both ICAM-1 and EPCR, is associated with increased risk of developing cerebral malaria. This study therefore reveals an important PfEMP1-binding phenotype that could be targeted as part of a strategy to prevent cerebral malaria.
Final results from the phase I study expansion cohort of Debio0932, an oral HSP90 inhibitor, in patients with solid tumors.
Authors: Pierre Fumoleau, Jean-Charles Soria, Jean-Pierre Delord, Riccardo Belli, Silvano Brienza, Claudio Zanna, Alice Destaillats, Elisabeth Rouits, Antoine Hollebecque, Anas Gazzah, Nicolas Isambert
Journal: Journal of Clinical Oncology (2014)

2550^ Background: Debio 0932 is an oral second-generation heat shock protein 90 (HSP90) inhibitor that has shown promising anti-tumor activity against a broad range of tumors in pre-clinical models. Here we report the results of the expansion part of a phase I study in patients with advanced solid tumor or lymphoma. Methods: 30 patients with solid tumor comprising 15 NSCLC patients were enrolled. Patients received the treatment schedule derived from results of the dose-escalation phase, i.e. 1000 mg Debio 0932 QD. PK samples were taken on day 1 and 29. CYP 450 and transporter polymorphism was explored through Affymetrix DMET chip. Results: The safety population analysis considered 39 patients of which 30 enrolled into the expansion phase and additional 9 patients treated at 1000 mg QD during the dose-escalation phase of the study. Adverse events (AEs) and the frequencies are reported in the Table. The main reason for treatment withdrawal was progressive disease. Although no objective tumor responses were seen, 25% of patients evaluable for response achieved disease stabilization including long lasting episode. Moreover, one partial metabolic response (PMR) and 5 (41.7%) stable metabolic response (SMR), were observed in the 12 NSCLC evaluable patients. Debio 0932 was rapidly absorbed and subjected to first-pass metabolism. Large inter-individual variability in PK was observed but without evidence of food effect. No obvious relationship between PGx and PK was evidenced. Conclusions: Debio 0932 mono-therapy at recommended dose of 1000mg was generally well tolerated and showed signs of activity in patients with advanced NSCLC and can be administered in fed state. A phase I-II study of Debio 0932 in combination with standard of care in NSCLC is ongoing. Clinical trial information: NCT01168752. ALL N=39 NSCLC N=15 Mean age (range) (yrs) 56 (22-74) 57 (35-70) Gender M/F [N(%)] 23 (59%) / 16 (41%) 8 (53%) / 7 (47%) Predominant cancer types (%) Lung-NSCLC 38.5% Colorectal 15.4% Kidney 12.8% ≥ 3 Previous treatment regimes (%) 79% 80% Days on treatment (range) 63 (10-264) 66 (20-264) Most frequent AEs (%) Diarrhoea Nausea Decreased appetite Vomiting Asthenia . 72 % 64 % 62 % 59 % 54 % . 80 % 53 % 60 % 67 % 47 % Best overall tumor response (%) SD PD . 25 % 75 % . 14 % 86 %
A suspected viral rash in pregnancy
Authors: Jack Carruthers, Alison Holmes, Azeem Majeed
Journal: BMJ (2017)

A pregnant woman at 12 weeks' gestation seeks help for a red rash covering her back and chest.She is worried that the rash might be caused by a virus.She is originally from Bangladesh and is unsure about her vaccination history.Viral exanthema can cause rash in a pregnant woman and should be considered even in countries that have comprehensive vaccination programmes.In the UK, for example, three cases of congenital rubella syndrome have been notified in recent years in women born outside the UK. 1 This article focuses on viral rashes.For a more general overview of rash in pregnancy, see the review by Vaughan-Jones et al. 2 Vaccination coverage for viral infections varies globally.The World Health Organization estimates that adult varicella immunity is greater than 95% in the US but only 75% in India. 3imilarly, global measles and rubella immunisation coverage is only 85% and 44%, respectively.
Telomere Gene Complex Mutations Are Frequently Found with Shortened Telomeres in Bone Marrow Failure Syndromes and Idiopathic Pulmonary Fibrosis; Correlation with Haematological and Clinical Features
Authors: Shreyans A Gandhi, Jie Jiang, Nana benson-Quarm, Syed A Mian, Steve Best, Austin Kulasekararaj, Judith C Marsh, Ghulam Mufti
Journal: Blood (2014)
Imiquimod has strain-dependent effects in mice and does not uniquely model human psoriasis
Authors: William R. Swindell, Kellie A. Michaels, Andrew J. Sutter, Doina Diaconu, Yi Fritz, Xianying Xing, Mrinal K. Sarkar, Yun Liang, Alex Tsoi, Johann E. Gudjonsson, Nicole L. Ward
Journal: Genome Medicine (2017)

Imiquimod (IMQ) produces a cutaneous phenotype in mice frequently studied as an acute model of human psoriasis. Whether this phenotype depends on strain or sex has never been systematically investigated on a large scale. Such effects, however, could lead to conflicts among studies, while further impacting study outcomes and efforts to translate research findings. RNA-seq was used to evaluate the psoriasiform phenotype elicited by 6 days of Aldara (5% IMQ) treatment in both sexes of seven mouse strains (C57BL/6 J (B6), BALB/cJ, CD1, DBA/1 J, FVB/NJ, 129X1/SvJ, and MOLF/EiJ). In most strains, IMQ altered gene expression in a manner consistent with human psoriasis, partly due to innate immune activation and decreased homeostatic gene expression. The response of MOLF males was aberrant, however, with decreased expression of differentiation-associated genes (elevated in other strains). Key aspects of the IMQ response differed between the two most commonly studied strains (BALB/c and B6). Compared with BALB/c, the B6 phenotype showed increased expression of genes associated with DNA replication, IL-17A stimulation, and activated CD8+ T cells, but decreased expression of genes associated with interferon signaling and CD4+ T cells. Although IMQ-induced expression shifts mirrored psoriasis, responses in BALB/c, 129/SvJ, DBA, and MOLF mice were more consistent with other human skin conditions (e.g., wounds or infections). IMQ responses in B6 mice were most consistent with human psoriasis and best replicated expression patterns specific to psoriasis lesions. These findings demonstrate strain-dependent aspects of IMQ dermatitis in mice. We have shown that IMQ does not uniquely model psoriasis but in fact triggers a core set of pathways active in diverse skin diseases. Nonetheless, our findings suggest that B6 mice provide a better background than other strains for modeling psoriasis disease mechanisms.
Adjustment of creatinine (Cr) to avoid severe thrombocytopenia of carboplatin (C) plus gemcitabine (G) in non-small cell lung cancer (NSCLC)
Authors: A. Horiike, E. Miyauchi, I. Motokawa, K. Kudo, F. Ohyanagi, M. Mun, Y. Sakao, S. Okumura, K. Nakagawa, T. Horai, M. Nishio
Journal: Journal of Clinical Oncology (2009)

2525 Background: Carboplatin plus gemcitabine (CG) is a standard regimen for advanced NSCLC. Although the dose of C is calculated from Cr clearance (CCr) by Calvert‘s formula, severe thrombocytopenia sometimes occurs in the CG regimen. Severe thrombocytopenia might arise from differences in the methods of measuring Cr values. We have used two different techniques, the Jaffé method and the enzymatic method. When the enzymatic method was used, CCr overestimated the glomerular filtration rate and the dose of C calculated by Calvert‘s formula leads to overdosing. The aim of this study was to clarify whether severe thrombocytopenia could be avoided by adjusting the CCr in the CG regimen when Cr is measured by the enzymatic method. Methods: All patients (pts) were treated with CG (C, AUC = 5 on day 1; G, 1,000 mg/m 2 on days 1 and 8) every 3 weeks for 4 cycles. Serum Cr values were measured by the enzymatic method and CCr was estimated by the Cockcroft-Gault formula in all patients. In the non-adjusted group, the dose of C was calculated by Calvert‘s formula with no adjustment of CCr. In the adjusted group, the dose of C was calculated by Calvert‘s formula, adjusting Cr as follows: (serum Cr +0.2). We compared the correlations between Cr values and the nadir of thrombocytes, and the frequencies of severe thrombocytopenia in both groups. Results: 32 pts and 28 pts were enrolled in the non-adjusted and the adjusted groups, respectively. Grade 3/4 thrombocytopenia was observed in 19 pts (60%) and these pts had low levels of serum Cr values. On the other hand, significantly fewer cases of grade 3/4 thrombocytopenia were observed in the adjusted group (8 pts; 29%, p &lt; 0.0001). In addition, there was a significant correlation between Cr values and the nadir of thrombocytes in the non-adjusted group (R= 0.442, p= 0.0105), but no significant correlation was observed in the adjusted group (R= -0.196, p= 0.3212). These results suggest that adjustment of CCr can reduce the variable nadir of thrombocytes in the CG regimen when Cr is measured by the enzymatic method. Conclusions: If Cr is measured by the enzymatic method, adjustment of Cr is needed to avoid severe thrombocytopenia in the CG regimen. No significant financial relationships to disclose.