tbuckley/cabot-search huggingface dataset:
Ustekinumab for the treatment of patients with active ankylosing spondylitis: results of a 28-week, prospective, open-label, proof-of-concept study (TOPAS)
Authors: Denis Poddubnyy, Kay-Geert A Hermann, Johanna Callhoff, Joachim Listing, Joachim Sieper
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> To evaluate efficacy and safety of ustekinumab in patients with ankylosing spondylitis (AS). <h3>Methods</h3> In this prospective, open-label, single-arm, proof-of-concept clinical trial (ClinicalTrials.gov identifier NCT01330901), ustekinumab in a dose of 90 mg was administered subcutaneously at baseline, week 4 and week 16 in 20 patients with active AS. Eligible patients were required to have a diagnosis of AS according to the modified New York criteria and an active disease defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥4 despite previous non-steroidal anti-inflammatory drug (NSAID) treatment. The primary study endpoint was the proportion of patients reached the Assessment of SpondyloArthritis International Society 40 (ASAS40) response at week 24. <h3>Results</h3> At week 24, ASAS40 response was reached by 65% of the patients. ASAS20, ASAS5/6 and ASAS partial remission were observed in 75%, 50% and 30% of the patients, respectively. A ≥50% improvement of the BASDAI (BASDAI50) occurred in 55% of the patients. A total of 50% and 20% of the patients achieved the AS Disease Activity Score (ASDAS) clinically important improvement and major improvement, respectively. At week 24, 35% of the patients had an ASDAS inactive disease (ASDAS &lt;1.3). Significant improvement of other patient-reported outcome parameters and active inflammation as detected by MRI as well as significant reduction of NSAIDs intake occurred during the treatment. Clinical response correlated with reduction of active inflammation on MRI and of serum C reactive protein level. Overall, ustekinumab was well tolerated. <h3>Conclusions</h3> In this prospective, open-label, proof-of-concept clinical trial, ustekinumab treatment was associated with a reduction of signs and symptoms in active AS and was well tolerated.
Would you dope? A general population test of the Goldman dilemma
Authors: J M Connor, J Mazanov
Journal: British Journal of Sports Medicine (2009)

Objective: To test Goldman's dilemma on a general population sample by asking whether they would take the Faustian bargain of a drug that guaranteed sporting success but would result in their death in 5 years' time. Between 1982 and 1995 a bi-annual survey using this dilemma suggested half of all elite athletes would take the drug. Design: A random telephone survey of 250 members of the Australian general public, with counterbalanced presentation of success and death. Main outcome measures: Respondents gave age, gender, sports engagement and response to the dilemma (yes/no). Results: Only two of a sample of 250 reported they would take the bargain offered by the dilemma. Conclusions: Athletes differ markedly from the general population in response to the dilemma. This raises significant practical and ethical dilemmas for athlete support personnel. The psychometry of the dilemma needs to be established more comprehensively for general and athlete populations.
Splicing factor 3b subunit 1 (Sf3b1) haploinsufficient mice display features of low risk Myelodysplastic syndromes with ring sideroblasts
Authors: Valeria Visconte, Ali Tabarroki, Li Zhang, Yvonne Parker, Edy Hasrouni, Reda Mahfouz, Kyoichi Isono, Haruhiko Koseki, Mikkael A Sekeres, Yogen Saunthararajah, John Barnard, Daniel Lindner, Heesun J Rogers, Ramon V Tiu
Journal: Journal of Hematology & Oncology (2014)

The presence of somatic mutations in splicing factor 3b subunit 1 (SF3B1) in patients with Myelodysplastic syndromes with ring sideroblasts (MDS-RS) highlights the importance of the RNA-splicing machinery in MDS. We previously reported the presence of bone marrow (BM) RS in Sf3b1 heterozygous (Sf3b1 (+/-)) mice which are rarely found in mouse models of MDS. Sf3b1 (+/-) mice were originally engineered to study the interaction between polycomb genes and other proteins.We used routine blood tests and histopathologic analysis of BM, spleen, and liver to evaluate the hematologic and morphologic characteristics of Sf3b1 (+/-) mice in the context of MDS by comparing the long term follow-up (15 months) of Sf3b1 (+/-) and Sf3b1 (+/+) mice. We then performed a comprehensive RNA-sequencing analysis to evaluate the transcriptome of BM cells from Sf3b1 (+/-) and Sf3b1 (+/+) mice.Sf3b1 (+/-) exhibited macrocytic anemia (MCV: 49.5 ± 1.6 vs 47.2 ± 1.4; Hgb: 5.5 ± 1.7 vs 7.2 ± 1.0) and thrombocytosis (PLTs: 911.4 ± 212.1 vs 878.4 ± 240.9) compared to Sf3b1 (+/+) mice. BM analysis showed dyserythropoiesis and occasional RS in Sf3b1 (+/-) mice. The splenic architecture showed increased megakaryocytes with hyperchromatic nuclei, and evidence of extramedullary hematopoiesis. RNA-sequencing showed higher expression of a gene set containing Jak2 in Sf3b1 (+/-) compared to Sf3b1 (+/+).Our study indicates that Sf3b1 (+/-) mice manifest features of low risk MDS-RS and may be relevant for preclinical therapeutic studies.
The <i>miR-17-92</i> Cluster of MicroRNAs Confers Tumorigenicity by Inhibiting Oncogene-Induced Senescence
Authors: Lixin Hong, Maoyi Lai, Michelle Chen, Changchuan Xie, Rong Liao, Young Jun Kang, Changchun Xiao, Wen-Yuan Hu, Jiahuai Han, Peiqing Sun
Journal: Cancer Research (2010)

In mammalian cells, activation of oncogenes usually triggers innate tumor-suppressing defense mechanisms, including apoptosis and senescence, which are compromised by additional mutations before cancers are developed. The miR-17-92 gene cluster, a polycistron encoding six microRNAs (miRNA), is frequently overexpressed in human cancers and has been shown to promote several aspects of oncogenic transformation, including evasion of apoptosis. In the current study, we show a new role of miR-17-92 in inhibiting oncogenic ras-induced senescence. Further dissection of the miRNA components in this cluster reveals that the miR-17/20a seed family accounts for this antisenescence activity. miR-17 and miR-20a are both necessary and sufficient for conferring resistance to ras-induced senescence by directly targeting p21(WAF1), a key effector of senescence. By contrast, these components are not essential for the ability of miR-17-92 to evade Myc-induced apoptosis. Moreover, disruption of senescence by miR-17-92 or its miR-17/20a components leads to enhanced oncogenic transformation by activated ras in primary human cells. Taken together with previous reports that miR-17-92 inhibits apoptosis by suppressing Pten via the miR-19 components, our results indicate that this miRNA cluster promotes tumorigenesis by antagonizing both tumor-suppressing mechanisms, apoptosis, and senescence, through the activities of different miRNA components encoded in this cluster.
Ethnic Differences in Pancreatic Fat Accumulation and Its Relationship With Other Fat Depots and Inflammatory Markers
Authors: Kim-Anne Lê, Emily E. Ventura, Jessica Q. Fisher, Jaimie N. Davis, Marc J. Weigensberg, Mark Punyanitya, Houchun H. Hu, Krishna S. Nayak, Michael I. Goran
Journal: Diabetes Care (2011)

OBJECTIVE Visceral adipose tissue (VAT) and hepatic fat are associated with insulin resistance and vary by sex and ethnicity. Recently, pancreatic fat fraction (PFF) has also been linked with increasing obesity. Our aim was to assess ethnic and sex differences in PFF and its relationship to other fat depots, circulating free fatty acids (FFA), insulin secretion and sensitivity, and inflammation in obese adolescents and young adults. RESEARCH DESIGN AND METHODS We examined 138 (40 males, 98 females) obese Hispanics and African Americans (13–25 years). Subcutaneous adipose tissue and VAT volumes, hepatic fat fraction (HFF), and PFF were determined by magnetic resonance imaging. Insulin sensitivity and β-cell function were assessed during an intravenous glucose tolerance test. RESULTS Hispanics had higher PFF than African Americans (7.3 ± 3.8 vs. 6.2 ± 2.6%, P = 0.03); this ethnic difference was higher in young adults compared with children and adolescents (ethnicity × age: P = 0.01). Males had higher PFF than females (P &amp;lt; 0.0001). PFF was positively correlated with VAT (r = 0.45, P &amp;lt; 0.0001), HFF (r = 0.29, P &amp;lt; 0.0001), and FFA (r = 0.32, P = 0.001). PFF positively correlated with inflammatory markers but lost significance when adjusted for VAT. In multiple stepwise regression analysis, VAT and FFA were the best predictors of PFF (adjusted R2 = 0.40). There were no significant correlations between PFF and markers of insulin sensitivity or β-cell function. CONCLUSIONS PFF is higher in Hispanics than African Americans, and this difference increases with age. In young obese individuals, PFF is related to VAT, HFF, and circulating FFA, thus possibly contributing to their increased risk for type 2 diabetes and related metabolic disorders.
Robots for Use in Autism Research
Authors: Brian Scassellati, None Henny Admoni, Maja Matarić
Journal: Annual Review of Biomedical Engineering (2012)

Autism spectrum disorders are a group of lifelong disabilities that affect people's ability to communicate and to understand social cues. Research into applying robots as therapy tools has shown that robots seem to improve engagement and elicit novel social behaviors from people (particularly children and teenagers) with autism. Robot therapy for autism has been explored as one of the first application domains in the field of socially assistive robotics (SAR), which aims to develop robots that assist people with special needs through social interactions. In this review, we discuss the past decade's work in SAR systems designed for autism therapy by analyzing robot design decisions, human-robot interactions, and system evaluations. We conclude by discussing challenges and future trends for this young but rapidly developing research area.
Characterization of a reference material for BCR-ABL (M-BCR) mRNA quantitation by real-time amplification assays: towards new standards for gene expression measurements
Authors: J Saldanha, M Silvy, N Beaufils, R Arlinghaus, G Barbany, S Branford, J-M Cayuela, G Cazzaniga, M Gonzalez, D Grimwade, V Kairisto, K Miyamura, M Lawler, T Lion, E Macintyre, F-X Mahon, M C Muller, M Ostergaard, H Pfeifer, G Saglio, C Sawyers, O Spinelli, V H J van der Velden, J Q Wang, K Zoi, V Patel, P Phillips, P Matejtschuk, J Gabert
Journal: Leukemia (2007)
Combination Biomarkers to Diagnose Sepsis in the Critically Ill Patient
Authors: Sébastien Gibot, Marie C. Béné, Robin Noel, Frédéric Massin, Julien Guy, Aurélie Cravoisy, Damien Barraud, Marcelo De Carvalho Bittencourt, Jean-Pierre Quenot, Pierre-Edouard Bollaert, Gilbert Faure, Pierre-Emmanuel Charles
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Although the outcome of sepsis benefits from the prompt administration of appropriate antibiotics on correct diagnosis, the assessment of infection in critically ill patients is often a challenge for clinicians. In this setting, simple biomarkers, especially when used in combination, could prove useful.To determine the usefulness of combination biomarkers to diagnose sepsis.Three hundred consecutive patients were enrolled to construct a biologic score that was next validated in an independent prospective cohort of 79 critically ill patients from another center.Plasma concentrations of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and procalcitonin (PCT) were assayed, and the expression of the high-affinity immunoglobulin-Fc fragment receptor I (FcγRI) CD64 on neutrophils (polymorphonuclear [PMN] CD64 index) in flow cytometry was measured. A "bioscore" combining these biomarkers was constructed. Serum concentrations of PCT and sTREM-1 and the PMN CD64 index were higher in patients with sepsis compared with all others (P < 0.001 for the three markers). These biomarkers were all independent predictors of infection, the best receiver-operating characteristic curve being obtained for the PMN CD64 index. The performance of the bioscore, better than that of each individual biomarker, was externally confirmed in the validation cohort.This prospective study, including inceptive and validation cohorts of unselected intensive care unit patients, demonstrates the high performance of a bioscore combining the PMN CD64 index together with PCT and sTREM-1 serum levels in diagnosing sepsis in the critically ill patient.
Comparison of Balloon-Expandable vs Self-expandable Valves in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Mohamed Abdel-Wahab, Julinda Mehilli, Christian Frerker, Franz-Josef Neumann, Thomas Kurz, Ralph Tölg, Dirk Zachow, Elena Guerra, Steffen Massberg, Ulrich Schäfer, Mohamed El-Mawardy, Gert Richardt
Journal: JAMA (2014)

Transcatheter aortic valve replacement (TAVR) is an effective treatment option for high-risk patients with severe aortic stenosis. Different from surgery, transcatheter deployment of valves requires either a balloon-expandable or self-expandable system. A randomized comparison of these 2 systems has not been performed.To determine whether the balloon-expandable device is associated with a better success rate than the self-expandable device.The CHOICE study was an investigator-initiated trial in high-risk patients with severe aortic stenosis and an anatomy suitable for the transfemoral TAVR procedure. One hundred twenty-one patients were randomly assigned to receive a balloon-expandable valve (Edwards Sapien XT) and 120 were assigned to receive a self-expandable valve (Medtronic CoreValve). Patients were enrolled between March 2012 and December 2013 at 5 centers in Germany.Transfemoral TAVR with a balloon-expandable or self-expandable device.The primary end point was device success, which is a composite end point including successful vascular access and deployment of the device and retrieval of the delivery system, correct position of the device, intended performance of the heart valve without moderate or severe regurgitation, and only 1 valve implanted in the proper anatomical location. Secondary end points included cardiovascular mortality, bleeding and vascular complications, postprocedural pacemaker placement, and a combined safety end point at 30 days, including all-cause mortality, major stroke, and other serious complications.Device success occurred in 116 of 121 patients (95.9%) in the balloon-expandable valve group and 93 of 120 patients (77.5%) in the self-expandable valve group (relative risk [RR], 1.24, 95% CI, 1.12-1.37, P < .001). This was attributed to a significantly lower frequency of residual more-than-mild aortic regurgitation (4.1% vs 18.3%; RR, 0.23; 95% CI, 0.09-0.58; P < .001) and the less frequent need for implanting more than 1 valve (0.8% vs 5.8%, P = .03) in the balloon-expandable valve group. Cardiovascular mortality at 30 days was 4.1% in the balloon-expandable valve group and 4.3% in the self-expandable valve group (RR, 0.97; 95% CI, 0.29-3.25; P = .99). Bleeding and vascular complications were not significantly different, and the combined safety end point occurred in 18.2% of those in the balloon-expandable valve group and 23.1% of the self-expandable valve group (RR, 0.79; 95% CI, 0.48-1.30; P = .42). Placement of a new permanent pacemaker was less frequent in the balloon-expandable valve group (17.3% vs 37.6%, P = .001).Among patients with high-risk aortic stenosis undergoing TAVR, the use of a balloon-expandable valve resulted in a greater rate of device success than use of a self-expandable valve.clinicaltrials.gov Identifier: NCT01645202.
Increasing level of CD56+ T-cells in peripheral blood in sarcoidosis
Authors: J-M. Naccache, M. Kambouchner, P. O. Schischmanoff, F. Baran-Marszak, M. Raphaël, R. Fagard, D. Valeyre
Journal: European Respiratory Journal (2006)

Increasing level of CD56+ T-cells in peripheral blood in sarcoidosisTo the Editors:We read with interest the recent paper by KATCHAR et al. [1] reporting the characterisation of natural killer (NK) cells and CD56+ T-cells in sarcoidosis patients.The authors observed that, in the lung of patients with pulmonary sarcoidosis, NK cells have a distinct phenotype.They produce cytokines and participate actively in the T-helper (Th)-1-like inflammatory response.In addition, although they did not find any difference in the NK cell number between sarcoidosis patients and control subjects, the authors found an elevation of CD56+ T-cells in the peripheral blood (PB) of sarcoidosis patients.CD56+ T-cells are large granular lymphocytes with a significant proportion of CD4-CD8-cells or cd T-cells, and, to our knowledge, this is the first study in which such expansion of CD56+ T-cells in PB is described in sarcoidosis.In a recent prospective study, we analysed the NK cells and CD56+ T-cells content in PB from 32 patients with pulmonary sarcoidosis and from 18 healthy volunteers by flow cytometry.
Novel Genes Associated with Malignant Melanoma but not Benign Melanocytic Lesions
Authors: Dmitri Talantov, Abhijit Mazumder, Jack X. Yu, Thomas Briggs, Yuqiu Jiang, John Backus, David Atkins, Yixin Wang
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Cutaneous melanoma is a common, aggressive cancer with increasing incidence. The identification of melanoma-specific deregulated genes could provide molecular markers for lymph node staging assays and further insight into melanoma tumorigenesis. Experimental Design: Total RNA isolated from 45 primary melanoma, 18 benign skin nevi, and 7 normal skin tissue specimens were analyzed on an Affymetrix Hu133A microarray containing 22,000 probe sets. Results: Hierarchical clustering revealed a distinct separation of the melanoma samples from the benign and normal specimens. Novel genes associated with malignant melanoma were identified. Differential gene expression of two melanoma-specific genes, PLAB and L1CAM, were tested by a one-step quantitative reverse transcription-PCR assay on primary malignant melanoma, benign nevi, and normal skin samples, as well as on malignant melanoma lymph node metastasis and melanoma-free lymph nodes. The performance of the markers was compared with conventional melanoma markers such as tyrosinase, gp100, and MART1. Conclusion: Our study systematically identified novel melanoma-specific genes and showed the feasibility of using a combination of PLAB and L1CAM in a reverse transcription-PCR assay to differentiate clinically relevant samples containing benign or malignant melanocytes.
Renin Inhibition
Authors: Naomi D.L. Fisher, Norman K. Hollenberg
Journal: Journal of the American Society of Nephrology (2005)

Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers has become a crucial element in cardiovascular and renal medicine. This review evaluates the potential of renin inhibition as an adjunct to therapies that depend on renin system interruption.
A subset of natural killer cells in peripheral blood displays a mature T cell phenotype.
Authors: R E Schmidt, C Murray, J F Daley, S F Schlossman, J Ritz
Journal: The Journal of Experimental Medicine (1986)

Normal human PBMC were analyzed for the presence of cells expressing both T3 and NKH1 antigens, using direct two-color immunofluorescence. In six individuals, NKH1+T3+ cells were found to represent 2.5% of PBMC and 24% of the total number of NKH1+ cells. Purified NKH1+T3+ cells were shown to have the typical morphology of large granular lymphocytes (LGL). NKH1+T3+ cells also exhibited spontaneous cytotoxicity against K562 target cells and this lytic activity could be inhibited by anti-T3 mAb. Similar results were obtained with NKH1+T3+ cells cultured in vitro in lymphocyte-conditioned medium. Taken together, these results indicate that NKH1+T3+ cells represent a unique population of NK-active cells in normal peripheral blood. Although these cells exhibit LGL morphology and NK activity, this appears to be mediated through a functional T cell-like receptor for target antigen.
Variations in Resource Utilization Among Medical Specialties and Systems of Care
Authors: Richard L. Kravitz, Sheldon Greenfield
Journal: Annual Review of Public Health (1995)

As sweeping changes in the organization and delivery of health care are implemented, it is important to examine the relationship between various types of cost-containment efforts, health care costs, and quality of care. This article reviews the evidence that physician specialty training, the organization of physicians, and the method of physician payment are significant influences upon the utilization of health care services. Data from before the late 1980s raised the possibility that family practitioners employed fewer resources than general internists and that health maintenance organizations used fewer resources than solo practitioners. However, the studies from which these data were derived were marred by insufficient attention to patient mix, failure to account for interactions between specialty and system, and inadequate regard for the complexities of modern practice structures. More recent data from the Medical Outcomes Study (MOS) overcomes some but not all of these problems. In general, it can be safely concluded that primary care specialty training, group practice, and prepaid care are associated with less utilization. Nevertheless, much more research is needed to address remaining methodologic problems and to obtain data that are generalizable to the wide array of modern practice settings.
Differential Contribution of Monocytes to Heart Macrophages in Steady-State and After Myocardial Infarction
Authors: Timo Heidt, Gabriel Courties, Partha Dutta, Hendrik B. Sager, Matt Sebas, Yoshiko Iwamoto, Yuan Sun, Nicolas Da Silva, Peter Panizzi, Anja M. van der Laan, Filip K. Swirski, Ralph Weissleder, Matthias Nahrendorf
Journal: Circulation Research (2014)

Rationale : Macrophages populate the steady-state myocardium. Previously, all macrophages were thought to arise from monocytes; however, it emerged that, in several organs, tissue-resident macrophages may self-maintain through local proliferation. Objective : Our aim was to study the contribution of monocytes to cardiac-resident macrophages in steady state, after macrophage depletion in CD11b DTR/+ mice and in myocardial infarction. Methods and Results : Using in vivo fate mapping and flow cytometry, we estimated that during steady state the heart macrophage population turns over in ≈1 month. To explore the source of cardiac-resident macrophages, we joined the circulation of mice using parabiosis. After 6 weeks, we observed blood monocyte chimerism of 35.3±3.4%, whereas heart macrophages showed a much lower chimerism of 2.7±0.5% ( P &lt;0.01). Macrophages self-renewed locally through proliferation: 2.1±0.3% incorporated bromodeoxyuridine 2 hours after a single injection, and 13.7±1.4% heart macrophages stained positive for the cell cycle marker Ki-67. The cells likely participate in defense against infection, because we found them to ingest fluorescently labeled bacteria. In ischemic myocardium, we observed that tissue-resident macrophages died locally, whereas some also migrated to hematopoietic organs. If the steady state was perturbed by coronary ligation or diphtheria toxin–induced macrophage depletion in CD11b DTR/+ mice, blood monocytes replenished heart macrophages. However, in the chronic phase after myocardial infarction, macrophages residing in the infarct were again independent from the blood monocyte pool, returning to the steady-state situation. Conclusions : In this study, we show differential contribution of monocytes to heart macrophages during steady state, after macrophage depletion or in the acute and chronic phase after myocardial infarction. We found that macrophages participate in the immunosurveillance of myocardial tissue. These data correspond with previous studies on tissue-resident macrophages and raise important questions on the fate and function of macrophages during the development of heart failure.