tbuckley/cabot-search huggingface dataset:
Out of Place
Authors: Carol Snyder Halberstadt
Journal: JAMA (2017)

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Global MicroRNA Profiling in Human Bone Marrow Skeletal—Stromal or Mesenchymal–Stem Cells Identified Candidates for Bone Regeneration
Authors: Chi-Chih Chang, Morten T. Venø, Li Chen, Nicholas Ditzel, Dang Q.S. Le, Philipp Dillschneider, Moustapha Kassem, Jørgen Kjems
Journal: Molecular Therapy (2017)

Bone remodeling and regeneration are highly regulated multistep processes involving posttranscriptional regulation by microRNAs (miRNAs). Here, we performed a global profiling of differentially expressed miRNAs in bone-marrow-derived skeletal cells (BMSCs; also known as stromal or mesenchymal stem cells) during in vitro osteoblast differentiation. We functionally validated the regulatory effects of several miRNAs on osteoblast differentiation and identified 15 miRNAs, most significantly miR-222 and miR-423, as regulators of osteoblastogenesis. In addition, we tested the possible targeting of miRNAs for enhancing bone tissue regeneration. Scaffolds functionalized with miRNA nano-carriers enhanced osteoblastogenesis in 3D culture and retained this ability at least 2 weeks after storage. Additionally, anti-miR-222 enhanced in vivo ectopic bone formation through targeting the cell-cycle inhibitor CDKN1B (cyclin-dependent kinase inhibitor 1B). A number of additional miRNAs exerted additive osteoinductive effects on BMSC differentiation, suggesting that pools of miRNAs delivered locally from an implanted scaffold can provide a promising approach for enhanced bone regeneration. Bone remodeling and regeneration are highly regulated multistep processes involving posttranscriptional regulation by microRNAs (miRNAs). Here, we performed a global profiling of differentially expressed miRNAs in bone-marrow-derived skeletal cells (BMSCs; also known as stromal or mesenchymal stem cells) during in vitro osteoblast differentiation. We functionally validated the regulatory effects of several miRNAs on osteoblast differentiation and identified 15 miRNAs, most significantly miR-222 and miR-423, as regulators of osteoblastogenesis. In addition, we tested the possible targeting of miRNAs for enhancing bone tissue regeneration. Scaffolds functionalized with miRNA nano-carriers enhanced osteoblastogenesis in 3D culture and retained this ability at least 2 weeks after storage. Additionally, anti-miR-222 enhanced in vivo ectopic bone formation through targeting the cell-cycle inhibitor CDKN1B (cyclin-dependent kinase inhibitor 1B). A number of additional miRNAs exerted additive osteoinductive effects on BMSC differentiation, suggesting that pools of miRNAs delivered locally from an implanted scaffold can provide a promising approach for enhanced bone regeneration.
Fc receptors (FcR) on the surface of human breast cancer cells may facilitate the cytotoxic effects of hTRA-8, a new humanized apoptosis-inducing antibody.
Authors: April J. Adams, Jason M. Warram, Tandra R. Chaudhuri, Kurt R. Zinn
Journal: Cancer Research (2006)

5491  Introduction: A death receptor 5 (DR5) specific, mouse monoclonal antibody known as mTRA-8 was a promising therapeutic agent in mouse models of human breast cancer (Buchsbaum, et. al, Clin Can Res 9: 3731-41, 2003), and the humanized version (hTRA-8) is under study. Death receptor antibodies selectively induce apoptosis in tumor cells, a process that appears to require death receptor aggregation. Immune cells and endothelial cells within tumors express FcR and facilitate aggregation in vivo. Hypothesis: Breast cancer cells endogenously express FcR, which enhances the cytotoxicity of hTRA-8. Methods: The metastatic breast cancer cell line MDA-MB-231 (2LMP variant) was treated for 24 hrs with hTRA-8 in vitro with or without cross-linking antibody, to induce aggregation and subsequent apoptosis. ATPLite assays (n=3) measured cell viability after exposure. FcRs were measured by flow cytometry and Scatchard analyses using fluorescently labeled and Tc-99m-labeled hTRA-8, respectively, with appropriate controls. Results: Apoptosis induced by hTRA-8 was dose-dependent (ATP levels were diminished between 40-80% of controls) and an exogenous cross-linking reagent was not required at any concentration. The MDA-MB-231 cells expressed surface FcR2; control fluorescence averaged 253+55 while hTRA-8 averaged 527+17. Conclusion: Breast cancer cells may act in a paracrine or autocrine manner, facilitating the aggregation of DR5 receptors through the interaction between the DR5-hTRA-8 (receptor-ligand) complex and tumor-expressed FcR2.
Biologic treatment sequences for plaque psoriasis: a cost-utility analysis based on 10 years of Dutch real-world evidence from BioCAPTURE
Authors: S.L. Klijn, J.M.P.A. van den Reek, G. van de Wetering, A. van der Kolk, E.M.G.J. de Jong, W. Kievit
Journal: British Journal of Dermatology (2017)

Treatment with biologics may be indicated for patients with moderate-to-severe plaque psoriasis, but comparative evidence on cost-effectiveness is limited. Switching of biologics is common, but it is unclear what the effect is of differences in sequences of biologics.To evaluate the cost-effectiveness of different biologic treatment sequences for psoriasis based on real-world evidence.A sequence model was developed to evaluate the costs and health effects of three consecutive lines of biologic treatments [for example adalimumab-etanercept-ustekinumab (Ada-Eta-Ust) vs. Eta-Ust-Ada] over a 10-year time horizon in the Netherlands. The model was populated with data from the Dutch BioCAPTURE registry and scientific literature. Analyses were conducted of cost per quality-adjusted life year (QALY) and uncertainty was addressed by probabilistic as well as scenario analyses.Treatment of psoriasis with biologics for a 10-year period was estimated to be associated with a cost of €141 962 to €148 442 per patient depending on the treatment sequence used. Cumulative health effects ranged from 7·79 to 8·03 QALYs. Starting with Ada or Ust seems favourable concerning cost and utilities compared with strategies starting with Eta, although credible intervals were partly overlapping.The order in which biologics are used influences treatment cost-effectiveness, both in terms of costs and health effects. Initiation of a biologic treatment sequence for psoriasis might best be done with Ada or Ust; Eta seems less optimal from a health-economic perspective.
Emergency Department Stroke Care—Reply
Authors: Louis R. Caplan
Journal: JAMA Neurology (2017)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Neurology journal
The primary health-care system in China
Authors: Xi Li, Jiapeng Lu, Shuang Hu, KK Cheng, Jan De Maeseneer, Qingyue Meng, Elias Mossialos, Dong Roman Xu, Winnie Yip, Hongzhao Zhang, Harlan M Krumholz, Lixin Jiang, Shengshou Hu
Journal: The Lancet (2017)
Coactivation of Estrogen Receptor and IKKβ Induces a Dormant Metastatic Phenotype in ER-Positive Breast Cancer
Authors: Lamiaa El-Shennawy, Oleksii Dubrovskyi, Irida Kastrati, Jeanne M. Danes, Yiqun Zhang, Herbert E. Whiteley, Chad J. Creighton, Jonna Frasor
Journal: Cancer Research (2017)

Abstract A growing body of evidence suggests that the inflammatory NFκB pathway is associated with the progression of ER+ tumors to more aggressive stages. However, it is unknown whether NFκB is a driver or a consequence of aggressive ER+ disease. To investigate this question, we developed breast cancer cell lines expressing an inducible, constitutively active form of IκB kinase β (CA-IKKβ), a key kinase in the canonical NFκB pathway. We found that CA-IKKβ blocked E2-dependent cell proliferation in vitro and tumor growth in vivo in a reversible manner, suggesting that IKKβ may contribute to tumor dormancy and recurrence of ER+ disease. Moreover, coactivation of ER and IKKβ promoted cell migration and invasion in vitro and drove experimental metastasis in vivo. Gene expression profiling revealed a strong association between ER and CA-IKKβ–driven gene expression and clinically relevant invasion and metastasis gene signatures. Mechanistically, the invasive phenotype appeared to be driven by an expansion of a basal/stem-like cell population rather than EMT. Taken together, our findings suggest that coactivation of ER and the canonical NFκB pathway promotes a dormant, metastatic phenotype in ER+ breast cancer and implicates IKKβ as a driver of certain features of aggressive ER+ breast cancer. Significance: The canonical NFκB pathway promotes expansion of stem/basal-like cells and a dormant, metastatic phenotype in ER+ breast cancer cells. Cancer Res; 78(4); 974–84. ©2017 AACR.
Effects of post-abortion family planning services on preventing unintended pregnancy and repeat abortion (INPAC): a cluster randomised controlled trial in 30 Chinese provinces
Authors: Wei-Hong Zhang, Jiong Li, Yan Che, Shangchun Wu, Xu Qian, Xiaojing Dong, Jialin Xu, Lina Hu, Rachel Tolhurst, Marleen Temmerman
Journal: The Lancet (2017)
What's Next in CML - a Prospective Study Evaluating Sanger Sequencing and Next Generation Sequencing (NGS) for BCR-ABL1 Kinase Domain (KD) Mutation Screening
Authors: Simona Soverini, Luana Bavaro, Caterina De Benedittis, Margherita Martelli, Stefania Stella, Paolo Vigneri, Alessandra Iurlo, Nicola Orofino, Simona Sica, Federica Sorà, Sara Galimberti, Claudia Baratè, Francesco Albano, Antonella Russo Rossi, Fabio Ciceri, Francesca Lunghi, Fausto Castagnetti, Gabriele Gugliotta, Gianantonio Rosti, Elena Tenti, Fabio Stagno, Elisabetta Novella, Eros Di Bona, Massimiliano Bonifacio, Elisabetta Abruzzese, Marzia Salvucci, Mariella D'Adda, Rosaria Sancetta, Elisabetta Calistri, Monica Bocchia, Isabella Capodanno, Giuseppina Spinosa, Maria Antonella Laginestra, Santa Errichiello, Anna Serra, Francesca Carnuccio, Sabrina Coluzzi, Mario Annunziata, Caterina Musolino, Fabrizio Pane, Giuseppe Saglio, Michele Baccarani, Michele Cavo, Giovanni Martinelli
Journal: Blood (2017)
Group-wise similarity registration of point sets using Student’s t-mixture model for statistical shape models
Authors: Nishant Ravikumar, Ali Gooya, Serkan Çimen, Alejandro F. Frangi, Zeike A. Taylor
Journal: Medical Image Analysis (2017)

A probabilistic group-wise similarity registration technique based on Student's t-mixture model (TMM) and a multi-resolution extension of the same (mr-TMM) are proposed in this study, to robustly align shapes and establish valid correspondences, for the purpose of training statistical shape models (SSMs). Shape analysis across large cohorts requires automatic generation of the requisite training sets. Automated segmentation and landmarking of medical images often result in shapes with varying proportions of outliers and consequently require a robust method of alignment and correspondence estimation. Both TMM and mrTMM are validated by comparison with state-of-the-art registration algorithms based on Gaussian mixture models (GMMs), using both synthetic and clinical data. Four clinical data sets are used for validation: (a) 2D femoral heads (K= 1000 samples generated from DXA images of healthy subjects); (b) control-hippocampi (K= 50 samples generated from T1-weighted magnetic resonance (MR) images of healthy subjects); (c) MCI-hippocampi (K= 28 samples generated from MR images of patients diagnosed with mild cognitive impairment); and (d) heart shapes comprising left and right ventricular endocardium and epicardium (K= 30 samples generated from short-axis MR images of: 10 healthy subjects, 10 patients diagnosed with pulmonary hypertension and 10 diagnosed with hypertrophic cardiomyopathy). The proposed methods significantly outperformed the state-of-the-art in terms of registration accuracy in the experiments involving synthetic data, with mrTMM offering significant improvement over TMM. With the clinical data, both methods performed comparably to the state-of-the-art for the hippocampi and heart data sets, which contained few outliers. They outperformed the state-of-the-art for the femur data set, containing large proportions of outliers, in terms of alignment accuracy, and the quality of SSMs trained, quantified in terms of generalization, compactness and specificity.
Monocyte alterations in rheumatoid arthritis are dominated by preterm release from bone marrow and prominent triggering in the joint
Authors: Biljana Smiljanovic, Anna Radzikowska, Ewa Kuca-Warnawin, Weronika Kurowska, Joachim R Grün, Bruno Stuhlmüller, Marc Bonin, Ursula Schulte-Wrede, Till Sörensen, Chieko Kyogoku, Anne Bruns, Sandra Hermann, Sarah Ohrndorf, Karlfried Aupperle, Marina Backhaus, Gerd R Burmester, Andreas Radbruch, Andreas Grützkau, Wlodzimierz Maslinski, Thomas Häupl
Journal: Annals of the Rheumatic Diseases (2017)

Objective Rheumatoid arthritis (RA) accompanies infiltration and activation of monocytes in inflamed joints. We investigated dominant alterations of RA monocytes in bone marrow (BM), blood and inflamed joints. Methods CD14 + cells from BM and peripheral blood (PB) of patients with RA and osteoarthritis (OA) were profiled with GeneChip microarrays. Detailed functional analysis was performed with reference transcriptomes of BM precursors, monocyte blood subsets, monocyte activation and mobilisation. Cytometric profiling determined monocyte subsets of CD14 ++ CD16 − , CD14 ++ CD16 + and CD14 + CD16 + cells in BM, PB and synovial fluid (SF) and ELISAs quantified the release of activation markers into SF and serum. Results Investigation of genes differentially expressed between RA and OA monocytes with reference transcriptomes revealed gene patterns of early myeloid precursors in RA-BM and late myeloid precursors along with reduced terminal differentiation to CD14 + CD16 + monocytes in RA-PB. Patterns associated with tumor necrosis factor/lipopolysaccharide (TNF/LPS) stimulation were weak and more pronounced in RA-PB than RA-BM. Cytometric phenotyping of cells in BM, blood and SF disclosed differences related to monocyte subsets and confirmed the reduced frequency of terminally differentiated CD14 + CD16 + monocytes in RA-PB. Monocyte activation in SF was characterised by the predominance of CD14 ++ CD16 ++ CD163 + HLA-DR + cells and elevated concentrations of sCD14, sCD163 and S100P. Conclusion Patterns of less mature and less differentiated RA-BM and RA-PB monocytes suggest increased turnover with accelerated monocytopoiesis, BM egress and migration into inflamed joints. Predominant activation in the joint indicates the action of local and primary stimuli, which may also promote adaptive immune triggering through monocytes, potentially leading to new diagnostic and therapeutic strategies.
Adjuvant Chemotherapy for ER+ Breast Cancer: A Sea Change is Underway
Authors: Philip D Poorvu, Eric P Winer
Journal: JNCI Journal of the National Cancer Institute (2017)

Adjuvant breast cancer treatments-chemotherapy, human epidermal growth factor receptor 2 (HER2)-targeted therapies, and endocrine therapy-prevent recurrence and extend survival.Unfortunately, because risk assessment is imprecise and treatments are not uniformly effective, many women are treated to benefit a small number.If these therapies were entirely harmless, we would have few qualms about overtreatment.Chemotherapy has the most onerous short-term side effects and is the treatment that patients most wish to avoid.Moreover, long-term toxicities include secondary leukemia, heart failure, neuropathy, premature menopause, and infertility.Some women who receive adjuvant chemotherapy do not return to work or face difficulty in role functioning (1,2).The recognition that benefits are limited and that toxicity can be formidable has led to gradual adjustments in most oncologists' approach.There has also been a steady improvement in prognosis over the past decades, partially attributed to better outcomes associated with screen-detected cancers (3,4).Over the past 15 years, multiple genomic assays have been developed that more precisely characterize the risk of developing recurrent breast cancer (5).The 70-gene assay (Mammaprint) was evaluated in a complex randomized trial, which demonstrated that women with clinically high-risk but genomically low-risk cancers derive little benefit from adjuvant chemotherapy (6).In the United States, the most widely used genomic assay for estrogen receptor-positive (ERþ) breast cancer is the 21-gene recurrence score (RS).In 2004, Paik et al. demonstrated that the RS was prognostic in a group of node-negative patients (7).Subsequently, these investigators found that the RS was predictive of chemotherapy benefit and that patients with low and intermediate scores do not appear to achieve substantial risk reduction (7,8).The results of randomized trials are pending, but US oncologists have embraced the RS in decision-making.Its use, initially in node-negative patients, has expanded to include many women with node-positive disease, particularly those with limited lymph node involvement (9).
Anti-apolipoprotein A-1 autoantibodies are associated with immunodeficiency and systemic inflammation in HIV patients
Authors: Nathalie Satta, Sabrina Pagano, Fabrizio Montecucco, Baris Gencer, François Mach, Laurent Kaiser, Alexandra Calmy, Nicolas Vuilleumier, V. Aubert, J. Barth, M. Battegay, E. Bernasconi, J. Böni, H.C. Bucher, C. Burton-Jeangros, A. Calmy, M. Cavassini, M. Egger, L. Elzi, J. Fehr, J. Fellay, P. Francioli, H. Furrer, C.A. Fux, M. Gorgievski, H. Günthard, D. Haerry, B. Hasse, H.H. Hirsch, B. Hirschel, I. Hösli, C. Kahlert, L. Kaiser, O. Keiser, C. Kind, T. Klimkait, H. Kovari, B. Ledergerber, G. Martinetti, B. Martinez de Tejada, K. Metzner, N. Müller, D. Nadal, G. Pantaleo, A. Rauch, S. Regenass, M. Rickenbach, C. Rudin, P. Schmid, D. Schultze, F. Schöni-Affolter, J. Schüpbach, R. Speck, P. Taffé, P. Tarr, A. Telenti, A. Trkola, P. Vernazza, R. Weber, S. Yerly
Journal: Journal of Infection (2017)
Abstract 10115: The Diagnostic Value of Global and Territorial Longitudinal Strain at Rest for the Detection of Coronary Artery Disease in Patients Without Type 2 Diabetes Mellitus
Authors: Houjuan Zuo, Xiuting Yang, Dao Wen Wang, Hong Wang
Journal: Circulation (2015)

Background: Global longitudinal strain (GLS) at rest aids the detection of coronary artery disease (CAD). However, myocardial strains are affected by both ischemia and diabetes mellitus (DM), and previous studies that evaluated the performance of GLS for detecting ischemia always included a certain DM patients in the study population. Thus, we sought to investigate in patients with no DM the power of GLS for detecting three-vessel CAD, and whether territorial longitudinal strain (TLS) could help identifying individual coronary artery stenosis Methods and results: We retrospectively studied 211 consecutive patients with suspected CAD and normal left ventricular (LV) ejection fraction. The patients with DM were excluded. All patients underwent echocardiography and subsequently coronary angiography. LV global and segmental peak systolic longitudinal strain (PSLS) parameters were quantified by two-dimensional speckle tracking echocardiography (2D STE). Territorial PSLSs were calculated based on the perfusion territories of the 3-epicardial coronary arteries in a 17-segment LV model. Critical CAD was defined as luminal diameter stenosis ≥ 70% in ≥ 1 epicardial coronary artery. Totally 145 patients had critical CAD on coronary angiography. Significant differences were observed in all strain parameters between patients with and without CAD. The AUC for GLS in the detection of three-vessel CAD was 0.875 at a cutoff value of -19.05% with sensitivity 78.1% and specificity 72.7%, which increased to 0.926 after excluding apical segments (cutoff value -18.66%; sensitivity 84.4% and specificity 81.8%). The TLS values were significantly lower in regions supplied by stenotic compared with non-stenotic coronary arteries. It has better power to identify LCX and LAD stenosis than RCA stenosis. An area under the curve (AUC) for the TLS to identify critical LCX, LAD and RCA stenosis, in order of diagnostic accuracy, is 0.818 for LCX, 0.764 for LAD and lastly 0.723 for RCA. Conclusions: In patients with no DM and suspected CAD, GLS is an excellent predictor of three-vessel CAD with high accuracy. A higher cut point than that reported before was obtained and should be used. TLS could identify which coronary artery is stenotic with fair sensitivity and specificity.
Surgical Versus Percutaneous Coronary Revascularization in Patients With Diabetes and Acute Coronary Syndromes
Authors: Krishnan Ramanathan, James G. Abel, Julie E. Park, Anthony Fung, Verghese Mathew, Carolyn M. Taylor, G.B. John Mancini, Min Gao, Lillian Ding, Subodh Verma, Karin H. Humphries, Michael E. Farkouh
Journal: Journal of the American College of Cardiology (2017)
Association of Vedolizumab Level, Anti-Drug Antibodies, and α4β7 Occupancy With Response in Patients With Inflammatory Bowel Diseases
Authors: Bella Ungar, Uri Kopylov, Miri Yavzori, Ella Fudim, Orit Picard, Adi Lahat, Daniel Coscas, Matti Waterman, Ola Haj-Natour, Noam Orbach-Zingboim, Ren Mao, Minhu Chen, Yehuda Chowers, Rami Eliakim, Shomron Ben-Horin
Journal: Clinical Gastroenterology and Hepatology (2017)
A randomized controlled safety/efficacy trial of therapeutic vaccination in HIV-infected individuals who initiated antiretroviral therapy early in infection
Authors: Michael C. Sneller, J. Shawn Justement, Kathleen R. Gittens, Mary E. Petrone, Katherine E. Clarridge, Michael A. Proschan, Richard Kwan, Victoria Shi, Jana Blazkova, Eric W. Refsland, Daryl E. Morris, Kristen W. Cohen, M. Juliana McElrath, Rong Xu, Michael A. Egan, John H. Eldridge, Erika Benko, Colin Kovacs, Susan Moir, Tae-Wook Chun, Anthony S. Fauci
Journal: Science Translational Medicine (2017)

Despite lack of vaccine efficacy, the kinetics and magnitude of HIV rebound in early-treated patients affect future clinical trial design.