tbuckley/cabot-search huggingface dataset:
SMS: Smart Model Selection in PhyML
Authors: Vincent Lefort, Jean-Emmanuel Longueville, Olivier Gascuel
Journal: Molecular Biology and Evolution (2017)

Model selection using likelihood-based criteria (e.g., AIC) is one of the first steps in phylogenetic analysis. One must select both a substitution matrix and a model for rates across sites. A simple method is to test all combinations and select the best one. We describe heuristics to avoid these extensive calculations. Runtime is divided by ∼2 with results remaining nearly the same, and the method performs well compared with ProtTest and jModelTest2. Our software, "Smart Model Selection" (SMS), is implemented in the PhyML environment and available using two interfaces: command-line (to be integrated in pipelines) and a web server (http://www.atgc-montpellier.fr/phyml-sms/).
Dihydrotestosterone: Biochemistry, Physiology, and Clinical Implications of Elevated Blood Levels
Authors: Ronald S. Swerdloff, Robert E. Dudley, Stephanie T. Page, Christina Wang, Wael A. Salameh
Journal: Endocrine Reviews (2017)

Benefits associated with lowered serum DHT levels after 5α-reductase inhibitor (5AR-I) therapy in men have contributed to a misconception that circulating DHT levels are an important stimulus for androgenic action in target tissues (e.g., prostate). Yet evidence from clinical studies indicates that intracellular concentrations of androgens (particularly in androgen-sensitive tissues) are essentially independent of circulating levels. To assess the clinical significance of modest elevations in serum DHT and the DHT/testosterone (T) ratio observed in response to common T replacement therapy, a comprehensive review of the published literature was performed to identify relevant data. Although the primary focus of this review is about DHT in men, we also provide a brief overview of DHT in women. The available published data are limited by the lack of large, well-controlled studies of long duration that are sufficiently powered to expose subtle safety signals. Nonetheless, the preponderance of available clinical data indicates that modest elevations in circulating levels of DHT in response to androgen therapy should not be of concern in clinical practice. Elevated DHT has not been associated with increased risk of prostate disease (e.g., cancer or benign hyperplasia) nor does it appear to have any systemic effects on cardiovascular disease safety parameters (including increased risk of polycythemia) beyond those commonly observed with available T preparations. Well-controlled, long-term studies of transdermal DHT preparations have failed to identify safety signals unique to markedly elevated circulating DHT concentrations or signals materially different from T.
Inequity in organ allocation for patients awaiting liver transplantation: Rationale for uncapping the model for end-stage liver disease
Authors: Mitra K. Nadim, Joseph DiNorcia, Lingyun Ji, Susan Groshen, Josh Levitsky, Randall S. Sung, W. Ray Kim, Kenneth Andreoni, David Mulligan, Yuri S. Genyk
Journal: Journal of Hepatology (2017)
Expression Pattern of Immunosurveillance-Related Antigen Is a Critical Prognostic Factor of Adult T-Cell Leukemia/Lymphoma
Authors: Naoko Asano, Hiroaki Miyoshi, Takeharu Kato, Joji Shimono, Noriaki Yoshida, Daisuke Kurita, Yuya Sasaki, Keisuke Kawamoto, Koichi Ohshima, Masao Seto
Journal: Blood (2016)
Endoluminal appendectomy: the first description in humans for acute appendicitis
Authors: Everson Artifon, Ricardo Uemura, Carlos Furuya Júnior, Carolina Santos, Diego Coca, Hugo Guedes, José Otoch
Journal: Endoscopy (2017)

Appendix inversion into the cecal lumen can be demonstrated, and its endoluminal appendectomy is feasible [1]. We describe the first procedure to remove the appendix using colonoscopy during acute appendicitis presentation.
After the Medical Error
Authors: Miranda Worthen
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Dynamic real-time signaling profiles of live primary cells to characterize the response of PI3K and MAPK pathways in HER2+ breast cancer cells to attenuation with lapatinib: Tests of reproducibility of method.
Authors: Lance G. Laing, Ian A. MacNeil, Benjamin E. Rich, Edward Greeno
Journal: Journal of Clinical Oncology (2014)

e11597 Background: This report provides evidence that an assay using live primary cells can reliably measure the real-time dynamic signaling of different cells and the attenuated response to therapies targeting the signaling. Characterization of live cells has delivered impressive results in the discovery of new therapeutic compounds. As a first step to translating these discovery results to the administration of the correct drug to the right patient, an assay is presented that measures in real-time the complex changes of viable patient cells growing on a nanoelectrode in a standard 96-well microplate. Since cell health and function modulate adhesion and phenotypic properties leading to changes near the electrode-cell interface, an impedance biosensor is capable of detecting and quantifying changes in cell health and specific pathway perturbation. The electrode impedance measurement is referred to as a cell attachment signal (CAS) and is expressed in ohms. The attachment of the cells via a specific ECM provides a quality control signal as well as coupling the cell communication link to the nanoelectrode. Methods: To confirm the reproducibility of the assay, a HER2+ breast cancer cell line (SKBr3) was tested with NRG1b, EGF, and lapatinib, a dual tyrosine kinase inhibitor which disrupts PI3K and MAPK pathway signaling. Each test measures the live cells’ CAS under three different conditions: 1) cells in buffer; 2) cells exposed first to lapatinib and then to either NRG1b or EGF; and 3) cells exposed only to either NRG1b or EGF. Tests were run over 3 days with 2 runs of tests performed each day. A total of 576 measurements were recorded. This experiment was then repeated using live primary cells extracted from a fresh HER2+ breast cancer specimen. Results: The CV of the CAS measurements taken using SKBr3 cells and the CV of the CAS measurements derived from the primary cells were both less than 10%. Conclusions: These results provide evidence the assay is a suitably robust method to analyze cellular functional pathway signaling activity in primary cells extracted from fresh tumor specimens.
Study of the role played by natural antisens transcripts (NAT) in breast cancer through the regulation of the expression of their paired protein coding genes
Authors: S. El Guendi, S. Wenric, B. Charloteaux, L. Karim, B. Hennuy, W. Bezzaou, M. Boukerroucha, G. Jerusalem, C. Josse, V. Bours
Journal: Annals of Oncology (2017)
Acquired hemophilia <scp>A</scp>: Updated review of evidence and treatment guidance
Authors: Rebecca Kruse‐Jarres, Christine L. Kempton, Francesco Baudo, Peter W. Collins, Paul Knoebl, Cindy A. Leissinger, Andreas Tiede, Craig M. Kessler
Journal: American Journal of Hematology (2017)

Abstract Acquired hemophilia A (AHA) is a rare disease resulting from autoantibodies (inhibitors) against endogenous factor VIII (FVIII) that leads to bleeding, which is often spontaneous and severe. AHA tends to occur in elderly patients with comorbidities and is associated with high mortality risk from underlying comorbidities, bleeding, or treatment complications. Treatment, which consists of hemostatic management and eradication of the inhibitors, can be challenging to manage. Few data are available to guide the management of AHA‐related bleeding and eradication of the disease‐causing antibodies. Endorsed by the Hemostasis and Thrombosis Research Society of North America, an international panel of experts in AHA analyzed key questions, reviewed the literature, weighed the evidence and formed a consensus to update existing guidelines. AHA is likely underdiagnosed and misdiagnosed in real‐world clinical practice. Recommendations for the management of AHA are summarized here based on the available data, integrated with the clinical experience of panel participants.
Pirfenidone Reduces Respiratory-related Hospitalizations in Idiopathic Pulmonary Fibrosis
Authors: Brett Ley, Jeffrey Swigris, Bann-mo Day, John L. Stauffer, Karina Raimundo, Willis Chou, Harold R. Collard
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Respiratory-related hospitalizations of patients with idiopathic pulmonary fibrosis (IPF) are more frequent than those for acute IPF exacerbations and are associated with poor outcomes.To compare the risk of nonelective hospitalization by type (all-cause, respiratory related, and non-respiratory related) and death after hospitalization with use of pirfenidone versus placebo over 52 weeks using data derived from three phase III IPF clinical trials.Individual patient data was pooled from three phase III randomized, placebo-controlled studies of pirfenidone for IPF (the two CAPACITY [Clinical Studies Assessing Pirfenidone in IPF: Research of Efficacy and Safety Outcomes] trials and the ASCEND [Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis] trial), including all patients randomized to pirfenidone 2,403 mg/d (n = 623) or placebo (n = 624). The risk of hospitalization over 52 weeks was compared using standard time-to-event methods. Among those hospitalized, the risk of death after hospitalization was compared with adjustment for treatment group propensity.A total of 1,247 patients (692 from the CAPACITY trials and 555 from the ASCEND trial) were included in the pooled analysis. Pirfenidone was associated with lower risk of respiratory-related hospitalization than placebo (7% vs. 12%; hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.36-0.77; P = 0.001), but all-cause (HR, 0.91; 95% CI, 0.70-1.19; P = 0.528) or non-respiratory-related hospitalization (HR, 1.32; 95% CI, 0.92-1.88; P = 0.145) was not. Among those hospitalized for any reason, treatment with pirfenidone was associated with lower risk of death after hospitalization up to 52 weeks after randomization, but this association was no longer significant with longer follow-up.In a pooled analysis of three phase III IPF clinical trials, patients receiving pirfenidone had a lower risk of nonelective respiratory-related hospitalization over the course of 1 year. The effect of pirfenidone on death after hospitalization is uncertain.
Erratum to: Unraveling the clonal hierarchy of somatic genomic aberrations
Authors: Davide Prandi, Sylvan C. Baca, Alessandro Romanel, Christopher E. Barbieri, Juan-Miguel Mosquera, Jacqueline Fontugne, Himisha Beltran, Andrea Sboner, Levi A. Garraway, Mark A. Rubin, Francesca Demichelis
Journal: Genome biology (2017)
CFS-Cytology in Secondary CNS Malignancies
Authors: G. Th. A. M. Bots
Journal: Neuro-Oncology (1980)

For already 80 years cytological examinations of the Cerebro Spinal Fluid (C.S.F.) are performed to diagnose diseases of the Central Nervous System (CNS). But it is only in the last 15 years that marked improvements in the technique of the preparation of the sediment established it as a reliable diagnostic procedure. In Leyden, like in most of Europe, we use the sedimentation chamber technique introduced by Sayk about 20 years ago. This method is economical, gives excellent conservation of the cells and for one sediment only 1 ml fluid is necessary. May-Grünwald/ Giemsa is preferred by us as the staining of choice.
A Road Map for Precision Cancer Medicine Using Personalized Models
Authors: Gabriele Picco, Mathew J. Garnett
Journal: Cancer Discovery (2017)

Abstract Summary: A study by Pauli and colleagues in this issue of Cancer Discovery describes the creation of a precision cancer platform for patients with advanced disease, integrating DNA sequencing of patient tumors with the generation of patient-derived organoids and xenografts. They propose the use of this platform for drug testing to nominate therapeutic options for individual patients and for therapeutic biomarker discovery. Cancer Discov; 7(5); 456–8. ©2017 AACR. See related article by Pauli et al., p. 462.
Safety and Efficacy of Recombinant Factor XIII (FXIII) in Patients with Congenital FXIII A-Subunit Deficiency, Results from the Mentor™2 Trial
Authors: Manuel Carcao, Carmen Altisent, Giancarlo Castaman, Katsuyuki Fukutake, Aida Inbal, Bryce A. Kerlin, Craig M. Kessler, Riitta Lassila, Johannes Oldenburg, Anders Rosholm, May-Lill Garly, Diane J. Nugent
Journal: Blood (2016)
Correlation of mammographic breast density with Ki-67 expression in benign breast epithelial cells obtained by random periareolar fine needle aspiration of high risk women
Authors: Q. J. Khan, B. F. Kimler, E. J. Smith, A. P. O’Dea, P. Sharma, C. J. Fabian
Journal: Journal of Clinical Oncology (2006)

1011 &gt;Background: Known risk factors for breast cancer development include elements incorporated into the Gail risk model, mammographic breast density and cytologic atypia detected by Random Periareolar Fine Needle Aspiration (RPFNA). Ki-67 expression is a possible risk biomarker and is currently being used as a response biomarker in chemoprevention trials. We have previously shown that Ki-67 expression is higher in RPFNA specimens of benign breast cells exhibiting cytologic atypia. It is not known whether there is a correlation between mammographic density and Ki-67 expression in benign breast ductal cells obtained by RPFNA. Methods: 344 women at high risk of developing breast cancer (based on personal or family history) seen at The University of Kansas Medical Center high risk breast clinic, who underwent RPFNA with cytomorphology and Ki-67 assessment, plus a mammogram were included in the study. Mammographic breast density was assessed using the Cumulus program. Categorical variables were analyzed by Chi-square test and continuous variables were analyzed by non-parametric test and linear regression. Results: 40% of women were premenopausal, 7% perimenopausal and 53% were postmenopausal. Median age was 49 years, median 5 year Gail Risk was 2.2%, and median Ki-67 was 1.9%. Median mammographic breast density was 37%. Ki-67 expression increased with cytologic abnormality and number of cells collected, but was unrelated to Gail risk (as observed previously). Breast density was higher in pre-menopausal women (p=0.001), those with lower BMI (p&lt; 0.001), and lower 5-year Gail risk (p=0.012); Breast density showed no correlation with Ki-67 expression or cytomorphology. Conclusion: Given the lack of correlation of mammographic breast density with either cytomorphology or Ki-67 expression in RPFNA specimens, mammographic density and Ki-67 expression should be considered as potentially complementary response biomarkers for breast cancer chemoprevention trials. No significant financial relationships to disclose.
Role of Glypican-3 in the control of death and proliferation of murine mammary adenocarcinoma cells
Authors: Maria Giselle Peters, Bibiana Iglesias, Lydia I. Puricelli, Elisa D. Bal de Kier Joffé
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

3689 

Glypican-3 (GPC3) is a glycoprotein expressed in the embryo and down regulated in most adult tissues, with levels still present in mesothelium, mammary gland, ovary and macrophages. Recent reports indicate that GPC3 expression is down regulated in breast tumors, suggesting that GPC3 is involved in the regulation of growth and/or apoptosis. Previously a murine mammary tumor cell line LM3, not able to express GPC3, was stably transfected with the rat GPC3 gene to determine the role of this glycoprotein in tumor progression. We demonstrated that LM3-GPC3 cells were significantly less invasive and metastatic than control LM3-vector cells when inoculated into in syngeneic mice. The aim of this study was to elucidate some of the mechanisms involved in the metastatic/invasive capacity reduction, focusing in the in vitro analysis of cell growth and death. When LM3 cells were seeded at low density, GPC3 expression induced a significant reduction of the clonogenic capacity. In agreement with these observations, LM3-GPC3 cells presented a significantly lower mitotic index than control cells. Next it was studied whether GPC3 was able to regulate the sensitivity to cell death. LM3-GPC3 cells were significantly more susceptible to apoptosis induced by nutrient depletion (69.85±6.9% of apoptotic cells in LM3-GPC3 vs. 33.98±0.4% in LM3-vector, 96 h). Then, by means of WB and IHC, we analyzed the expression of the pro-apoptotic proteins Caspase-9 and Bax and of the anti-apoptotic Bcl-2 and Bcl-xL in cells growing in the presence or absence of FBS. Basal levels of pro-apoptotic molecules Caspase-9 and Bax were significantly higher in GPC3 expressing cells. Serum withdrawal increased Caspase-9 expression but did not modulate Bax. GPC3 also induced a significant reduction in the level of the anti-apoptotic proteins Bcl-2 and Bcl-xL and these levels seemed not to be regulated by FBS depletion. The influence of GPC3 on the expression of cell cycle regulators, either in the presence or absence of FBS, was also studied. GPC3 did not modulate the basal expression either cyclins D1 and B1 or CDKI p16, but it induced an increase of the CDKIs p21 and p27 expression. Interestingly serum withdrawal significantly increased the expression of all these proteins. Our results provide new evidence supporting the idea that GPC3 participates in the regulation of cell growth and apoptosis, probably through the modulation of pro-apoptotic, anti-apoptotic and cell cycle proteins. These results could explain the reduced invasive and metastatic ability of LM3-GPC3 cells.
Phase-2 Study of Sotatercept (ACE-011) in Myeloproliferative Neoplasm-Associated Myelofibrosis and Anemia
Authors: Prithviraj Bose, Naval Daver, Elias J. Jabbour, Allison Pike, Kate J Newberry, Lingsha Zhou, Sherry Pierce, Xuemei Wang, Hagop M. Kantarjian, Srdan Verstovsek
Journal: Blood (2016)
Genomics and proteomics-based discovery of novel cancer biomarkers and molecular targets for cell-permeable peptide/small molecule-based drugs.
Authors: Yataro Daigo, Atsushi Takano, Yusuke Nakamura
Journal: Journal of Clinical Oncology (2012)

e13552 Background: Identification of cancer-specific oncoproteins is an effective approach to develop new diagnostics and therapeutics. Methods: We have established a strategy as follows to identify new oncoproteins, which can be applied as biomarkers and drug development; i) To identify genes overexpressed in 120 clinical lung cancers using the cDNA microarray representing 27,648 genes, ii) To verify the genes for their low expression in 23 normal tissues by northern-blotting, iii) To validate the clinicopathological significance of their protein expression by tissue microarray covering 262 cases of non-small cell lung cancers (NSCLCs), iv) To verify whether they are essential for the growth of cancer cells by siRNAs, v) To do immunoprecipitation assays and mass-spectrometric analysis to identify their interacting proteins in cancer cells, and screening of cell-permeable peptides that could inhibit the protein-protein interaction that is essential for carcinogenesis. Results: We identified 35 oncoproteins to be upregulated in the majority of lung cancers, and further selected CDCA5 (cell division cycle associated 5) as a good candidate. Tumor tissue microarray analysis of 262 NSCLC patients revealed that CDCA5 positivity was an independent prognostic factor. Suppression of CDCA5 expression with siRNAs inhibited the growth of lung cancer cells; concordantly, induction of exogenous expression of CDCA5 conferred growth-promoting activity in mammalian cells. We also found that extracellular signal-regulated kinase (ERK) kinase interacted with and phosphorylated CDCA5 at Serine 209 in vivo. Functional inhibition of the interaction between CDCA5 and ERK kinase by a cell-permeable peptide corresponding to a 20-amino-acid sequence part of CDCA5, which included the Serine 209 phosphorylation site by ERK, significantly reduced phosphorylation of CDCA5 and resulted in growth suppression of lung cancer cells. Conclusions: CDCA5 positivity should be useful as a novel prognostic biomarker in the clinic. Selective suppression of the ERK-CDCA5 pathway by cell-permeable peptide or small molecule-based drugs could be a promising strategy for cancer therapy.
Nine compounds from the Root Bark of Lycium chinense and their anti-inflammatory activities
Authors: Yanan Yang, Yawen An, Wei Wang, Ning Du, Jinghua Zhang, Ziming Feng, Jianshuang Jiang, Peicheng Zhang
Journal: Acta Pharmaceutica Sinica B (2017)

Two new compounds, named lyciumlignan D (1) and lyciumphenyl propanoid A (2), along with seven known compounds, were isolated from the root bark of Lycium chinense. Their structures were elucidated using spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR, CD), as well as by comparison with those of the literature. Compounds 3-9 were isolated from this genus for the first time. In the in vitro assay, compounds 3, 6, and 7 exhibited stronger anti-inflammatory effects than the positive control curcumin at a concentration of 10 μmol/L.
Enhanced Education for Noninvasive Cardiac Testing
Authors: Avinainder Singh, Sanjay Divakaran, Ron Blankstein
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal