tbuckley/cabot-search huggingface dataset:
Nutritional Physiology.
Journal: JAMA (1923)

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 Journals 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 2024 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
Bioprosthetic Valves for Transcatheter Aortic Valve Replacement
Authors: Michael J. Reardon
Journal: JAMA (2014)

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
The Human Connectome Project's neuroimaging approach
Authors: Matthew F Glasser, Stephen M Smith, Daniel S Marcus, Jesper L R Andersson, Edward J Auerbach, Timothy E J Behrens, Timothy S Coalson, Michael P Harms, Mark Jenkinson, Steen Moeller, Emma C Robinson, Stamatios N Sotiropoulos, Junqian Xu, Essa Yacoub, Kamil Ugurbil, David C Van Essen
Journal: Nature Neuroscience (2016)
Granulocyte macrophage colony-stimulating factor induces CCL17 production via IRF4 to mediate inflammation
Authors: Adrian Achuthan, Andrew D. Cook, Ming-Chin Lee, Reem Saleh, Hsu-Wei Khiew, Melody W.N. Chang, Cynthia Louis, Andrew J. Fleetwood, Derek C. Lacey, Anne D. Christensen, Ashlee T. Frye, Pui Yeng Lam, Hitoshi Kusano, Koji Nomura, Nancy Steiner, Irmgard Förster, Stephen L. Nutt, Moshe Olshansky, Stephen J. Turner, John A. Hamilton
Journal: Journal of Clinical Investigation (2016)

Data from preclinical and clinical studies have demonstrated that granulocyte macrophage colony-stimulating factor (GM-CSF) can function as a key proinflammatory cytokine. However, therapies that directly target GM-CSF function could lead to undesirable side effects, creating a need to delineate downstream pathways and mediators. In this work, we provide evidence that GM-CSF drives CCL17 production by acting through an IFN regulatory factor 4-dependent (IRF4-dependent) pathway in human monocytes, murine macrophages, and mice in vivo. In murine models of arthritis and pain, IRF4 regulated the formation of CCL17, which mediated the proinflammatory and algesic actions of GM-CSF. Mechanistically, GM-CSF upregulated IRF4 expression by enhancing JMJD3 demethylase activity. We also determined that CCL17 has chemokine-independent functions in inflammatory arthritis and pain. These findings indicate that GM-CSF can mediate inflammation and pain by regulating IRF4-induced CCL17 production, providing insights into a pathway with potential therapeutic avenues for the treatment of inflammatory diseases and their associated pain.
Venom Insulins of Cone Snails Diversify Rapidly and Track Prey Taxa
Authors: Helena Safavi-Hemami, Aiping Lu, Qing Li, Alexander E. Fedosov, Jason Biggs, Patrice Showers Corneli, Jon Seger, Mark Yandell, Baldomero M. Olivera
Journal: Molecular Biology and Evolution (2016)

A specialized insulin was recently found in the venom of a fish-hunting cone snail, Conus geographus Here we show that many worm-hunting and snail-hunting cones also express venom insulins, and that this novel gene family has diversified explosively. Cone snails express a highly conserved insulin in their nerve ring; presumably this conventional signaling insulin is finely tuned to the Conus insulin receptor, which also evolves very slowly. By contrast, the venom insulins diverge rapidly, apparently in response to biotic interactions with prey and also possibly the cones' own predators and competitors. Thus, the inwardly directed signaling insulins appear to experience predominantly purifying sele\ction to target an internal receptor that seldom changes, while the outwardly directed venom insulins frequently experience directional selection to target heterospecific insulin receptors in a changing mix of prey, predators and competitors. Prey insulin receptors may often be constrained in ways that prevent their evolutionary escape from targeted venom insulins, if amino-acid substitutions that result in escape also degrade the receptor's signaling functions.
Ex vivo propagation and characterization of circulating tumor cell clusters from late stage prostate cancer patients.
Authors: James Lim, Charles J. Ryan, Bruce Adams, Jeff Hough, Tianna Chow
Journal: Journal of Clinical Oncology (2016)

314 Background: Cells shed by a tumor into the bloodstream upon metastasis present an opportunity to study the properties of these cells for biomarker discovery, drug development, and personalized therapy. Enrichment and expansion of circulating tumor cells (CTCs) in culture enables molecular characterization not readily available for rare cells. Here, we demonstrate the successful identification and culture of rare circulating tumor cell clusters from peripheral blood of metastatic castration resistant prostate cancer patients (mCRPC). Methods: The approach to isolate CTC clusters relies on nucleated cell enrichment via Ficoll-based centrifugation from 15 mL of peripheral blood. A collagen-based cell-binding substrate was used to capture cell clusters with preferential affinity for collagen (i.e. epithelial-like cells). Hypoxic and pressurized culturing conditions were used to maintain and propagate adhered CTC clusters. After 7 days in culture, immunofluorescence imaging, qPCR and/or mRNAseq were performed on CTC clusters that had formed colonies. Results: Blood samples processed within 3 hours from time of draw yielded a 25% success rate (4/16) for identifying PSMA+/EpCAM+/CD45- CTC colonies. Morphologically distinct CTC colonies cultivated at 1% oxygen and increased hydrostatic pressure (2 PSI) were positive for PSMA and EpCAM staining as observed via confocal microscopy, with individual colonies ranging from approximately 50 to 1000 in cell number. Colonies consistently revealed white blood cell contaminants (T-cells and dendritic cells, 10 to 30% of colony) that did not appear to perturb colony growth. CTC colonies were collected for qPCR analysis and mRNAseq via laser-capture microdissection and/or micropipetting. Genomic analysis revealed differential gene expression patterns between CTC colonies cultured from the same patient sample, with a subset expressing neuroendocrine like signatures (AURKA), stem cell markers (SOX2, OCT4), and immuno-oncology relevant markers (PD-L1, CTLA4). Conclusions: In conclusion, we show that viable CTCs are amenable to ex vivo culture, providing both functional and molecular insights into a sub-population of CTCs with propagating potential. The presence of T-cells and dendritic cells on CTC colonies warrants further investigation, and may provide unique insights into immune-tumor interactions. The culturing platform is currently being evaluated as a research tool for biomarker discovery and as a clinical tool for disease monitoring and treatment decision-making.
<scp>I</scp>nvestigation of chromosome X inactivation and clinical phenotypes in female carriers of DKC1 mutations
Authors: Jialin Xu, Payal P. Khincha, Neelam Giri, Blanche P. Alter, Sharon A. Savage, Judy M.Y. Wong
Journal: American Journal of Hematology (2016)

Dyskeratosis congenita (DC) is an inherited bone marrow failure and cancer susceptibility syndrome caused by germline mutations in telomere biology genes. Germline mutations in DKC1 , which encodes the protein dyskerin, cause X‐linked recessive DC. Because of skewed X‐chromosome inactivation, female DKC1 mutation carriers do not typically develop clinical features of DC. This study evaluated female DKC1 mutation carriers with DC‐associated phenotypes to elucidate the molecular features of their mutations, in comparison with unaffected carriers and mutation‐negative female controls. All female DKC1 mutation carriers had normal leukocyte subset telomere lengths and similarly skewed X‐inactivation in multiple tissue types, regardless of phenotype. We observed dyskerin expression, telomerase RNA accumulation, and pseudouridylation present in all mutation carriers at levels comparable to healthy wild‐type controls. Our study suggests that mechanisms in addition to X chromosome inactivation, such as germline mosaicism or epigenetics, may contribute to DC‐like phenotypes present in female DKC1 mutation carriers. Future studies are warranted to understand the molecular mechanisms associated with the phenotypic variability in female DKC1 mutation carriers, and to identify those at risk of disease. Am. J. Hematol. 91:1215–1220, 2016. © 2016 Wiley Periodicals, Inc.
Margaret McCartney: Racism, immigration, and the NHS
Authors: Margaret McCartney
Journal: BMJ (2016)

Watching recent videos posted on social media has been a wake-up call: some racists have found legitimacy in the United Kingdom's vote to leave the European Union and are expressing their vile views more freely, sometimes at healthcare professionals.Certainly, most people who voted to leave the EU are not racist.But some are.I've overheard, "I voted Leave to get rid of the Muslims" and, "I wanted out of Europe so there would be fewer foreigners taking up beds in the NHS"-statements so ridiculous that responding seems pointless.But we're going to have to.
First Line Treatment of Advanced Stage Hodgkin Lymphoma with Six Cycles of BEACOPPescalated Results in Superior Overall Survival Compared to ABVD: Results of a Network Meta-Analysis Including 10,011 Patients
Authors: Peter Borchmann, Sven Trelle, Michaela Rancea, Heinz Haverkamp, Volker Diehl, Nicole Skoetz, Andreas Engert
Journal: Blood (2012)
IGF-1R and mTOR Blockade: Novel Resistance Mechanisms and Synergistic Drug Combinations for Ewing Sarcoma
Authors: Salah-Eddine Lamhamedi-Cherradi, Brian A Menegaz, Vandhana Ramamoorthy, Deeksha Vishwamitra, Ying Wang, Rebecca L Maywald, Adriana S Buford, Izabela Fokt, Stanislaw Skora, Jing Wang, Aung Naing, Alexander J Lazar, Eric M Rohren, Najat C Daw, Vivek Subbiah, Robert S Benjamin, Ravin Ratan, Waldemar Priebe, Antonios G Mikos, Hesham M Amin, Joseph A Ludwig
Journal: JNCI Journal of the National Cancer Institute (2016)

Therapies cotargeting insulin-like growth factor receptor 1 (IGF-1R) and mammalian target of rapamycin (mTOR) have demonstrated remarkable, albeit short-lived, clinical responses in a subset of Ewing sarcoma (ES) patients. However, the mechanisms of resistance and applicable strategies for overcoming drug resistance to the IGF-1R/mTOR blockade are still undefined.To elucidate predominant mechanism(s) of acquired drug resistance while identifying synergistic drug combinations that improve clinical efficacy, we generated more than 18 ES cell lines resistant to IGF-1R- or mTOR-targeted therapy. Two small-molecule inhibitors of IGF-1R were chosen, NVP-ADW-742 (IGF-1R-selective) and OSI-906 (a dual IGF-1R/insulin receptor alpha [IR-α] inhibitor). Reverse-phase protein lysate arrays (RPPAs) revealed proteomic changes linked to IGF-1R/mTOR resistance, and selected proteins were validated in cell-based assays, xenografts, and within human clinical samples. All statistical tests were two-sided.Novel mechanisms of resistance (MOR) emerged after dalotuzumab-, NVP-ADW-742-, and OSI-906-based targeting of IGF-1R. MOR to dalotuzumab included upregulation of IRS1, PI3K, and STAT3, as well as p38 MAPK, which was also induced by OSI-906. pEIF4E(Ser209), a key regulator of Cap-dependent translation, was induced in ridaforolimus-resistant ES cell lines. Unique drug combinations targeting IGF-1R and PI3K-alpha or Mnk and mTOR were synergistic in vivo and vitro (P < .001) as assessed respectively by Mantel-Cox and isobologram testing.We discovered new druggable targets expressed by chemoresistant ES cells, xenografts, and relapsed human tumors. Joint suppression of these newfound targets, in concert with IGF-1R or mTOR blockade, should improve clinical outcomes.
Computers in Medicine
Authors: William A. Yasnoff
Journal: JAMA (1982)

<h3>To the Editor.—</h3> As active practitioners in medical computer science, we were delighted to see the "Computer Year" section in the CONTEMPO issue (1981;245:2242). However, we are concerned that it may have created some misconceptions in its effort to extend its focus beyond the clinical laboratory. The use of computers in medicine encompasses topics such as artificial intelligence, image processing, pattern recognition, and the manmachine interface problem as well as topics related to information systems. Dr Krieg correctly points out that no specialty certification in this field exists. However, there is a small but growing number of physicians with advanced training in computer science. Since the early 1970s, the National Library of Medicine (NLM) has supported a number of training programs in computers and medicine. A 1979 survey revealed the existence of 28 such programs (ten supported by NLM), with 251 students currently enrolled.<sup>1</sup>A total of 126 degrees
First human case of tick-borne encephalitis virus infection acquired in the Netherlands, July 2016
Authors: Joris A de Graaf, Johan H J Reimerink, G Paul Voorn, Elisabeth A bij de Vaate, Ankje de Vries, Barry Rockx, Alie Schuitemaker, Vishal Hira
Journal: Eurosurveillance (2016)

In July 2016, the first autochthonous case of tick-borne encephalitis was diagnosed in the Netherlands, five days after a report that tick-borne encephalitis virus (TBEV) had been found in Dutch ticks. A person in their 60s without recent travel history suffered from neurological symptoms after a tick bite. TBEV serology was positive and the tick was positive in TBEV qRT-PCR. TBEV infection should be considered in patients with compatible symptoms in the Netherlands.
Anxiety in teenage girls rises sharply in past decade, finds study
Authors: Jacqui Wise
Journal: BMJ (2016)

The mental wellbeing of teenage girls in England seems to have worsened over the past 10 years, a survey by the Department for Education has found.1

The study included a representative sample of 13 100 people aged 14 who were surveyed in 2014 about their attitudes, health, and wellbeing, and it compared the findings with a previous cohort interviewed in 2005.

Young people’s general wellbeing was slightly worse in 2014 than in 2005 in terms of self reported health and psychological distress. This was observed particularly in girls, young people living in single parent or step families, and respondents with a longstanding illness or disability that affected their schooling. These groups also displayed less confidence in their ability to control the events …
Une méta-analyse comparant les aiguilles ProCore et standard pour l’obtention de prélèvements guidés par échoendoscopie
Authors: M Palazzo
Journal: Endoscopy (2016)

L'aspiration à l'aiguille fine guidée par échoendoscopie est souvent indispensable à la prise en charge des tumeurs digestives. Néanmoins, cette technique à de multiples limites dont la plus significative est la difficulté d'obtention de biopsies à visée histologique (c'est à dire comprenant un véritable fragment tissulaire) communément appelée "core biopsy". Seule la "core biopsy" permet une analyse de l'architecture tissulaire, qui peut s'avérer nécessaire lorsque la cytologie est insuffisante pour affirmer la malignité (adénocarcinome très bien différencié), pour caractériser certaines tumeurs (lymphomes et GIST) ou pour réaliser de l'immunohistochimie complexe (tumeurs rares, diagnostic différentiel difficile).
Improving The Analysis Of Gene Expression Profiles By Comparing AML Blasts With Their Nearest Normal Counterparts
Authors: Nicolas Rapin, Frederik Otzen Bagger, Johan Jendholm, Helena Isabel Mora-Jensen, Anders Krogh, Alexander Kohlmann, Christian Thiede, Niels Borregaard, Lars Bullinger, Ole Winther, Kim Theilgaard-Mönch, Bo Porse
Journal: Blood (2013)
Quantification of PD-L1 mRNA Expression in Lung Adenocarcinoma with <i>EGFR</i> mutation.
Authors: Kazutoshi Isobe, Atsushi Kakimoto, Naobumi Tochigi, Kyohei Kaburaki, Takashi Makino, Hahjime Otsuka, Go Sano, Keishi Sugino, Susumu Sakamoto, Yujiro Takai, Tetsuo Mikami, Kazutoshi Shibuya, Akira Iyoda, Sakae Homma
Journal: Journal of Clinical Oncology (2016)

e23261 Background: Programmed death-ligand 1 (PD-L1) expression on immunohistochemistry is associated with response to PD-1 blockade.However, the molecular mechanism and clinical significance of PD-L1 mRNA expression and the roles of cell apoptosis and other biomarkers have not been adequately studied in patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma. Methods: We studied 31 patients with recurrent postoperative EGFR-mutant lung adenocarcinoma (exon 19 deletion in 16, L858R in 14, G719C in 1) treated with gefitinib between January 2008 and January 2016. Using KCL22 cell line for calibration, we utilized relative quantification of PD-L1 mRNA expression on PCR analysis of formalin-fixed paraffin-embedded slides of surgical specimens to determine PD-L1 mRNA expression in and around the tumor. In addition, we assessed correlations of PD-L1 mRNA expression with expressions of BIM, PUMA, HER2, MET, EGFR, and VEGFA. Results: PD-L1 mRNA expression was noted in the tumor in 11 of 31 patients (35.4%) and around the tumor in 13 of 31 patients (41.9%). Patients with positive PD-L1 mRNA expression had significantly higher MET expression and significantly lower VEGFA expression as compared with patients without PD-L1 mRNA expression (p = 0.03 and p = 0.04, respectively). HER2 and EGFR expressions were not related toPD-L1 mRNA expression status. PD-L1 mRNA expression was positively correlated with total relative expressions of BIM and PUMA (r = 0.91, p < 0.001). Patients with PD-L1mRNA expression on the tumor had significantly shorter progression-free survival (PFS) after gefitinib therapy than did those without such expression (median PFS: 283 days vs. 584 days, respectively; p = 0.05). Conclusions: PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma was associated with MET, VEGFA, BIM, and PUMA mRNA expressions and with shorter PFS after gefitinib therapy.
Effects Of Thrombopoietin Receptor Agonists On APRIL Plasma Levels In Patients With Immune Thrombocytopenia
Authors: Nora V. Butta, Mayte Álvarez Román, Ihosvany Fernández Bello, Elena G. Arias Salgado, Isabel Rivas Pollmar, Monica Martin Salces, Miguel Canales, Victor Jimenez Yuste
Journal: Blood (2013)
Bone turnover markers at 3 months of aromatase inhibitor therapy for prediction of 1-year bone mineral density loss: The B-ABLE cohort.
Authors: Ignacio Tusquets, Sonia Servitja, Dani Prieto-Alhambra, Elisabet Torres, Laia Garrigos, Tamara Martos, Maria Rodriguez-Sanz, Adolf Diez-Perez, Joan Albanell, Xavi Nogues
Journal: Journal of Clinical Oncology (2014)

581 Background: Most guidelines recommend bone mineral density (BMD) monitoring at 1-2 years of aromatase inhibitor (AI) therapy for women who do not need bisphosphonate therapy according to baseline assessment. Bone turnover markers (BTM) are sensitive to change in bone remodeling, and can be easily measured in clinic, offering an opportunity to anticipate BMD loss. We aimed to establish the association between changes in levels of BTMs at 3 months and 1-year BMD loss. Methods: The B-ABLE prospective cohort includes a consecutive sample of women with early breast cancer eligible for AI therapy. BMD is measured per protocol by DEXA at baseline and yearly, and BTMs (NTX and CTX in a subsample, Bone Alkaline Phosphatase (BALP) and Osteocalcin in all) at baseline, 3-months, and at yearly visits thereafter. Change in BTM levels (3-month minus baseline) was the main exposure and relative 1-year Lumbar Spine BMD loss (baseline minus 1-year over baseline) the main outcome of this study. Linear regression was used to establish the association between exposure and outcome. Multivariate models were adjusted for age, weight, and height. Adjusted standardized beta (ASB) coefficients are reported and must be interpreted as the mean increase in % BMD loss per each standard deviation of 3-month BTM change. Results: Data was available on 350 women starting on AI not on bisphosphonates according to ASCO guidelines. 138 and 149 had NTX and CTX data respectively. Changes in NTX (ASB 0.19, p=0.002), CTX (ASB 0.41, p<0.001), BALP (ASB 0.13, p=0.004) and Osteocalcin (ASB 0.21, p<0.001) at 3 months were associated with 1-year BMD loss. Conclusions: Changes in BTM (particularly CTX, with a strongest association) concentrations at 3 months of AI therapy can be used to target women with high BMD loss at 1 year. This strategy would identify high-risk women for closer monitoring/treatment.