tbuckley/cabot-search huggingface dataset:
Abstract 14994: Androgen Receptor Modulates Androgen-mediated Enhancement of Ischemia-induced Neovascularization via Genomic Action
Authors: Yuen Ting Lam, Laura Lecce, David J Handelsman, Martin K Ng
Journal: Circulation (2015)

Introduction: Increasing evidence indicates that androgens regulate ischemia-induced neovascularization. However, the role of androgen receptor (AR), a ligand-dependent nuclear transcription factor, remains poorly understood with genomic and non-genomic mechanisms proposed. Hypothesis: Using AR knockout mice (ARKO), which contain a transcriptionally inactive AR due to an in-frame deletion of the second zinc finger of the DNA-binding domain of AR, we hypothesized that AR genomic function plays a role in modulating androgen-mediated augmentation of ischemia-induced neovascularization. Methods and Results: Wild type (ARWT) and ARKO were implanted with dihydrotestosterone (DHT) or placebo (P) pellets following induction of hindlimb ischemia (HLI). Laser Doppler Perfusion Imaging revealed that DHT enhanced blood flow recovery in ARWT post-HLI. By contrast, DHT-mediated enhancement of blood flow recovery was abrogated in ARKO. Ischemia-induced vasculogenesis was examined by flow cytometry to assess the levels of Sca1+/CXCR4+ progenitor cells. DHT augmented the levels of Sca1+/CXCR4+ progenitor cells in bone marrow (DHT: 10.87 ± 0.817 vs. P: 5.057 ±0.503, p&lt;0.001) and circulating blood (DHT: 8.827 ± 1.122 vs. P: 5.150 ± 0.924) in ARWT at day 3 post-HLI. The augmentation of bone marrow and circulating Sca1+/CXCR4+ progenitor cell levels by DHT was absent in ARKO post-HLI. Transplantation of ARWT or ARKO bone marrow into irradiated recipients further revealed that ischemia-induced elevation of circulating progenitor cells was abolished in recipients with ARKO bone marrow. DHT augmented ischemia-induced HIF-1α expression (DHT: 2.39- vs. P: 1.4-fold increase at day 3 post HLI, p&lt;0.05) and promoted the production of stromal derived factor-1 (SDF-1) in ARWT. However, DHT augmentation of HIF-1α and SDF-1 were attenuated in ARKO post-HLI. In vitro, DHT-induced HIF-1α transcriptional activity and DHT-augmented tubule formation of endothelial cells via paracrine effect were attenuated in cells isolated from ARKO. Conclusions: Augmentation of ischemia-induced bone marrow-derived progenitor cell mobilization and HIF-1α-associated angiogenesis by androgens is dependent on the genomic action of AR.
Hepatitis C Virus
Authors: Arthur Kim
Journal: Annals of Internal Medicine (2016)

This issue provides a clinical overview of hepatitis C virus, focusing on transmission, prevention, screening, diagnosis, evaluation, and treatment. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.
Analysis of <i>NTRK1</i> gene fusion incidence in an unselected cohort of non-small cell lung cancer patients.
Authors: Robert Charles Doebele, Severine Kako, Anh T. Le, Marcos da Costa Silva, Aria Vaishnavi, Luca Toschi, Armando Santoro, Massimo Roncalli, Dara Aisner, Marileila Varella-Garcia
Journal: Journal of Clinical Oncology (2014)

8048 Background: The identification and therapeutic targeting of oncogenic drivers in lung adenocarcinoma has led to significant clinical improvements for patients with EGFR mutations or ALK fusions. We recently discovered a new oncogenic fusion involving NTRK1 that can be targeted by kinase inhibitors against the TRK family of receptor tyrosine kinases. We therefore investigated NTRK1cytogenetic patterns of tumor samples from NSCLC patients to determine the incidence and clinical characteristics of patients in this unselected cohort. Methods: A tumor microarray (TMA) previously analyzed by ALK (12/445=2.7%), ROS1 (5/429=1.2%) and RET (6/348=1.7%) FISH containing 447 tumor samples from patients with NSCLC was analyzed. Clinical characteristics of the TMA have been reported previously. Fluorescence in situ hybridization (FISH) screening using a novel dual color NTRK1 break-apart assay was performed. RT-PCR was performed on RNA extracted from corresponding tumor blocks to confirm the presence and identify of the NTRK1fusion partner. A novel proximity-ligation assay (PLA) to detect TRKA activation by detecting TRK-SHC1 protein complexes was developed as a complimentary, proteomic method for the detection of TRK activation, regardless of the mechanism of activation. Results: NTRK1 FISH analysis was successfully performed on 443 of 447 tumor samples (99.1%). Five of 443 (1.1%) tumor samples exhibited patterns indicating an NTRK1 rearrangement with split (n=1), single 3’ (n=1), or single 5’ (n=3) signals. Clinical characteristics of the 5 NTRK1+ patients are as follows: 3 female; 2 never-smokers; and 3 adenocarcinoma, 1 squamous cell carcinoma, and 1 large cell neuroendocrine carcinoma histology. An additional 5 samples had atypical cytogenetic patterns and 7 samples demonstrated focal NTRK1gene amplification warranting further exploration by alternate methodologies. Conclusions: NTRK1 gene rearrangements were detected in 1.1% of tumor samples from an unselected cohort of NSCLC patients. Additional NTRK1 cytogenetic patterns were observed and warrant further evaluation. Confirmatory testing by PCR to evaluate the specific NTRK1 fusion transcripts and a novel TRK PLA method will be presented.
A Closer Inspection of the Number Needed to Biopsy—Reply
Authors: Kathryn T. Shahwan, Alexa B. Kimball
Journal: JAMA Dermatology (2016)

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 Dermatology 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 Dermatology journal
Experiences and Expressions of Spirituality at the End of Life in the Intensive Care Unit
Authors: Marilyn Swinton, Mita Giacomini, Feli Toledo, Trudy Rose, Tracy Hand-Breckenridge, Anne Boyle, Anne Woods, France Clarke, Melissa Shears, Robert Sheppard, Deborah Cook
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: The austere setting of the intensive care unit (ICU) can suppress expressions of spirituality.Objectives: To describe how family members and clinicians experience and express spirituality during the dying process in a 21-bed medical–surgical ICU.Methods: Reflecting the care of 70 dying patients, we conducted 208 semistructured qualitative interviews with 76 family members and 150 clinicians participating in the Three Wishes Project. Interviews were recorded and transcribed verbatim. Data were analyzed by three investigators using qualitative interpretive description.Measurements and Main Results: Participants characterize dying as a spiritual event. Spirituality is an integral part of the life narrative of the patient before, during, and after death. Experiences and expressions of spirituality for patients, families, and clinicians during end-of-life care in the ICU are supported by eliciting and implementing wishes in several ways. Eliciting wishes stimulates conversations for people of diverse spiritual orientations to respond to death in personally meaningful ways that facilitate continuity and closure, and ease emotional trauma. Soliciting wishes identifies positive aspirations, which provide comfort in the face of death. The act of soliciting wishes brings clinician humanity to the fore. Wishing makes individual spiritual preferences and practices more accessible. Wishes may be grounded in spiritual goals, such as peace, comfort, connections, and tributes; they may seek a spiritually enhanced environment or represent specific spiritual interventions.Conclusions: Family members and clinicians consider spirituality an important dimension of end-of-life care. The Three Wishes Project invites and supports the expression of myriad forms of spirituality during the dying process in the ICU.
Whole Genome Sequencing of Azole-Resistant Aspergillus Fumigatus Strains from Hematopoietic Stem Cell Recipients Identifies Candidate Molecular Targets Potentially Implicated in Novel Resistance Mediating Mechanisms - First Results
Authors: Maximilian Mossner, Birgit Spiess, Johann-Christoph Jann, Verena Nowak, Julia Obländer, Oliver Bader, Wolf-Karsten Hofmann, Daniel Nowak, Dieter Buchheidt, Tobias Boch
Journal: Blood (2015)
Ascorbic Acid and Vitamin B12
Authors: Victor Herbert
Journal: JAMA (1979)

To the Editor.—  In their BRIEF REPORT, Ascorbic Acid and Vitamin B 12  in this issue ofThe Journal, Newmark et al (p 2319) allege that the vitamin B 12 levels we found in foods were inaccurate. The Table in their article shows that the allegation is not so, since it rests on comparison of foods we extracted in 1974, which happened to have low vitamin B 12 content, with foods we extracted in 1977, which had average vitamin B 12 content.  Their Table also shows that one half of the food vitamin B 12 extractable by the Veterans Administration methods appears to become unextractable (or destroyed) by that method of extraction (and assay) in the presence of 0.5 g of ascorbic acid. Because humans do not add the cyanide or metabisulfite of the Association of Official Analytical Chemists (AOAC) and British assay methods to their food to extract the
Proteasome subunit expression analysis and chemosensitivity in relapsed paediatric acute leukaemia patients receiving bortezomib-containing chemotherapy
Authors: Denise Niewerth, Gertjan J. L. Kaspers, Gerrit Jansen, Johan van Meerloo, Sonja Zweegman, Gaye Jenkins, James A. Whitlock, Stephen P. Hunger, Xiaomin Lu, Todd A. Alonzo, Peter M. van de Ven, Terzah M. Horton, Jacqueline Cloos
Journal: Journal of Hematology & Oncology (2016)

Drug combinations of the proteasome inhibitor bortezomib with cytotoxic chemotherapy are currently evaluated in phase 2 and 3 trials for the treatment of paediatric acute myeloid leukaemia (AML) and acute lymphocytic leukaemia (ALL). We investigated whether expression ratios of immunoproteasome to constitutive proteasome in leukaemic cells correlated with response to bortezomib-containing re-induction chemotherapy in patients with relapsed and refractory acute leukaemia, enrolled in two Children's Oncology Group phase 2 trials of bortezomib for ALL (COG-AALL07P1) and AML (COG-AAML07P1). Expression of proteasome subunits was examined in 72 patient samples (ALL n = 60, AML n = 12) obtained before start of therapy. Statistical significance between groups was determined by Mann-Whitney U test. Ratios of immunoproteasome to constitutive proteasome subunit expression were significantly higher in pre-B ALL cells than in AML cells for both β5i/β5 and β1i/β1 subunits (p = 0.004 and p < 0.001). These ratios correlated with therapy response in AML patients; β1i/β1 ratios were significantly higher (p = 0.028) between patients who did (n = 4) and did not reach complete remission (CR) (n = 8), although for β5i/β5 ratios, this did not reach significance. For ALL patients, the subunit ratios were also higher for patients who showed a good early response to therapy but this relation was not statistically significant. Overall, for this study, the patients were treated with combination therapy, so response was not only attributed to proteasome inhibition. Moreover, the leukaemic blast cells were not purified for these samples. These first ex vivo results encourage further studies into relative proteasome subunit expression to improve proteasome inhibition-containing therapy and as a potential indicator of bortezomib response in acute leukaemia.
Twenty-Five Years of Endocrine Disruption Science: Remembering Theo Colborn
Authors: Carol F. Kwiatkowski, Ashley L. Bolden, Richard A. Liroff, Johanna R. Rochester, John G. Vandenbergh
Journal: Environmental Health Perspectives (2016)

Summary:For nearly 30 years, Dr. Theo Colborn (1927–2014) dedicated herself to studying the harmful effects of endocrine-disrupting chemicals on wildlife, humans, and the environment. More recently, she extended this effort to address the health impacts of unconventional oil and gas development. Colborn was a visionary leader who excelled at synthesizing scientific findings across disciplines. Using her unique insights and strong moral convictions, she changed the face of toxicological research, influenced chemical regulatory policy, and educated the public. In 2003, Colborn started a nonprofit organization—The Endocrine Disruption Exchange (TEDX). As we celebrate the 25th anniversary of endocrine disruption science, TEDX continues her legacy of analyzing the extensive body of environmental health research and developing unique educational resources to support public policy and education. Among other tools, TEDX currently uses the systematic review framework developed by the National Toxicology Program at the National Institute of Environmental Health Sciences, to answer research questions of pressing concern. In this article, we pay homage to the tenacious woman and the exemplary contribution she made to the field of environmental health. Recommendations for the future of the field are drawn from her wisdom.
Modulation of long noncoding RNAs by risk SNPs underlying genetic predispositions to prostate cancer
Authors: Haiyang Guo, Musaddeque Ahmed, Fan Zhang, Cindy Q Yao, SiDe Li, Yi Liang, Junjie Hua, Fraser Soares, Yifei Sun, Jens Langstein, Yuchen Li, Christine Poon, Swneke D Bailey, Kinjal Desai, Teng Fei, Qiyuan Li, Dorota H Sendorek, Michael Fraser, John R Prensner, Trevor J Pugh, Mark Pomerantz, Robert G Bristow, Mathieu Lupien, Felix Y Feng, Paul C Boutros, Matthew L Freedman, Martin J Walsh, Housheng Hansen He
Journal: Nature Genetics (2016)
Study Provides Insights on ALS
Authors: Tracy Hampton
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
RNA Sequencing Identifies Transcriptionally Viable Gene Fusions in Esophageal Adenocarcinomas
Authors: Andrew E. Blum, Srividya Venkitachalam, Yan Guo, Ann Marie Kieber-Emmons, Lakshmeswari Ravi, Apoorva K. Chandar, Prasad G. Iyer, Marcia I. Canto, Jean S. Wang, Nicholas J. Shaheen, Jill S. Barnholtz-Sloan, Sanford D. Markowitz, Joseph E. Willis, Yu Shyr, Amitabh Chak, Vinay Varadan, Kishore Guda
Journal: Cancer Research (2016)

Abstract Esophageal adenocarcinoma is a deadly cancer with increasing incidence in the United States, but mechanisms underlying pathogenesis are still mostly elusive. In addressing this question, we assessed gene fusion landscapes by comprehensive RNA sequencing (RNAseq) of 55 pretreatment esophageal adenocarcinoma and 49 nonmalignant biopsy tissues from patients undergoing endoscopy for Barrett's esophagus. In this cohort, we identified 21 novel candidate esophageal adenocarcinoma–associated fusions occurring in 3.33% to 11.67% of esophageal adenocarcinomas. Two candidate fusions were selected for validation by PCR and Sanger sequencing in an independent set of pretreatment esophageal adenocarcinoma (N = 115) and nonmalignant (N = 183) biopsy tissues. In particular, we observed RPS6KB1–VMP1 gene fusion as a recurrent event occurring in approximately 10% of esophageal adenocarcinoma cases. Notably, esophageal adenocarcinoma cases harboring RPS6KB1–VMP1 fusions exhibited significantly poorer overall survival as compared with fusion-negative cases. Mechanistic investigations established that the RPS6KB1–VMP1 transcript coded for a fusion protein, which significantly enhanced the growth rate of nondysplastic Barrett's esophagus cells. Compared with the wild-type VMP1 protein, which mediates normal cellular autophagy, RPS6KB1–VMP1 fusion exhibited aberrant subcellular localization and was relatively ineffective in triggering autophagy. Overall, our findings identified RPS6KB1–VMP1 as a genetic fusion that promotes esophageal adenocarcinoma by modulating autophagy-related processes, offering new insights into the molecular pathogenesis of esophageal adenocarcinomas. Cancer Res; 76(19); 5628–33. ©2016 AACR.
Safety of Long-Acting Beta-Agonists in Children with Asthma
Authors: Andrew Bush, Urs Frey
Journal: New England Journal of Medicine (2016)

Has there ever been more of a Jekyll-and-Hyde protein than the airway β2 receptor? Short-acting beta-agonists give rapid relief from bronchospasm, but their overuse is a factor in asthma-related deaths, and the less-selective agents have been associated with epidemics of patients dying during acute asthma attacks. In children with uncontrolled asthma, the Best Add-on Therapy Giving Effective Responses (BADGER) study showed that the addition of long-acting beta-agonists (LABAs) was more effective than increasing the dose of inhaled glucocorticoids in controlling asthma,1 but the accompanying editorial2 highlighted the limited evidence regarding the safety of this approach and instead favored increasing . . .
Deux épidémies d’oreillons chez des enfants vaccinés avec la souche Rubini en Espagne indiquent une faible efficacité vaccinale
Authors: C Pons, T Pelayo, I Pachon, A Galmes, L González, C Sánchez, F Martinez
Journal: Eurosurveillance (2000)

Cet article presente une etude descriptive de deux epidemies d’oreillons survenues en 1998 dans deux villes espagnoles, ainsi qu’une evaluation de l’efficacite du vaccin utilise. Il apporte une preuve de la faible protection conferee par le vaccin contenant la souche Rubini, vis-a-vis du virus des oreillons. Cette faiblesse avait ete observee anterieurement chez des sujets vaccines avec ce vaccin.
Sharp rise in patients waiting more than 18 weeks for elective surgery
Authors: Gareth Iacobucci
Journal: BMJ (2016)

The number of patients in England who waited for more than 18 weeks for elective surgery rose by almost 80% last year, a new analysis has shown.

The report by the Patients Association1 found that 92 739 patients waited for over 18 weeks in 2015 compared with 51 388 patients in 2014, a year-on-year increase of 79.5%.

The data were based on 112 responses to Freedom of Information requests that were sent by the association to every NHS trust in England (a 78% response rate).

The report also found that 77% of these organisations were not notifying patients of their rights and options under the NHS Constitution when the 18 week target for elective care had been missed.

In addition, it found that the average waiting times for five elective procedures (hip replacement, knee replacement, hernia, adenoid, and tonsillectomy) were over …
Breast Implants and Connective-Tissue Disease
Authors: M. Elizabeth Karns
Journal: JAMA (1996)

<h3>To the Editor.</h3> —The Women's Health Study described by Dr Hennekens and colleagues<sup>1</sup>reported a 24% increase in the risk of connective-tissue disease in women with breast implants. However, the authors failed to consider an important point—the possibility of selection bias into the study of only the healthiest women. The consent form of the study requires that the participants had to agree to not take aspirin or other drugs with aspirinlike effects for 5 years. Any women with connective-tissue disease or chronic pain would have difficulty agreeing to this study condition. Aching joints and muscles are frequent complaints of women with breast implants and are usually self-medicated with these drugs. The effect of this condition would be a strong self-selection bias out of the study. A woman may not return the questionnaire once she had read the consent form—indeed, less than 25% responded. A large underestimate of the actual