tbuckley/cabot-search huggingface dataset:
Topical Steroids in Chinese Cosmetics
Authors: Hongfu Xie, Xiao Xiao, Ji Li
Journal: JAMA Dermatology (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 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
Toward an Understanding of Structural Insights of Xanthine and Aldehyde Oxidases: An Overview of their Inhibitors and Role in Various Diseases
Authors: Raj Kumar, Gaurav Joshi, Harveen Kler, Sourav Kalra, Manpreet Kaur, Ramandeep Arya
Journal: Medicinal Research Reviews (2017)

Abstract Almost all drug molecules become the substrates for oxidoreductase enzymes, get metabolized into more hydrophilic products and eliminated from the body. These metabolites sometime may be more potent, active, inactive, or toxic in nature compared to parent molecule. Xanthine oxidoreductase and aldehyde oxidase belong to molybdenum containing family and are well characterized for their structures and functions, in particular to their ability to oxidize/hydroxylate the xenobiotics. Their upregulated clinical levels causing oxidative stress are associated with pathways either directly involved in the progression of diseases, gout, or indirectly with the succession of other diseases such as diabetes, cancer, etc. Herein, we have put forth a comprehensive review on the xanthine and aldehyde oxidases pertaining to their structures, functions, pathophysiological role, and a comparative analysis of structural insights of xanthine and aldehyde oxidases’ binding domains with endogenous ligands or inhibitors. Though both the enzymes are molybdenum containing and are likely to share some common pathways and interact with inhibitors in a similar manner but we have focused on structural prerequisites for inhibitor specificity to both the enzymes keeping in view of the existing X‐ray structures. This review also provides futuristic implications in the design of inhibitors derived from inorganic complexes or small organic molecules considering the spatial features and structural insights of both the enzymes.
The Joint Commission and the Opioid Epidemic
Authors: Neeraj Chhabra, Jerrold B. Leikin
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 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
Prognostic and predictive value of circulating ESR1 mutations in metastatic breast cancer patients (mBC) progressing under aromatase inhibitor (AI) treatment.
Authors: Laetitia Augusto, Nasrin Sarafan-Vasseur, Anne Perdrix, Ludivine Beaussire, Julien Delacour, David Sefrioui, Céline Calbrix, Jean-Michel Picquenot, Thierry Frébourg, Fabrice Jardin, Frédéric Di Fiore, Florian Clatot
Journal: Journal of Clinical Oncology (2016)

511 Background: We recently reported that the detection of somatic and circulating activating ESR1 mutations is related to AI resistance in hormone receptor positive (HR+) mBC (Sefrioui et al., 2015). We aimed to evaluate the predictive and prognostic values of circulating ESR1 mutations detection at time of progression in mBC patients under AI. Methods: This study is a monocentric retrospective analysis of all consecutive patients treated with first-line AI for HR+mBC from 2008/01 to 2010/12. ESR1 circulating mutations rates (D538G, Y537S/N/C) were assessed by droplet digital PCR on plasma samples at progression. The impact of the mutational status on OS, PFS and clinical response to subsequent treatments was determined by univariate and multivariate analysis. Results: A total of 144 HR+mBC patients was analyzed. Median follow-up from initiation of AI was 40 months (range 4-94). At progression, 44 patients (30.6 %) presented at least one ESR1 circulating mutation (D538G 54%, Y537S 45%, Y537N 34%, Y537C 4%). Median OS after progression was 15 months (2-44) for mutated patients vs 24 months (2-70) for non-mutated patients (HR=1.9; p=0.006). For the whole population, performance status>1 (HR=3.0; p<0.0001), circulating ESR1 mutation (HR=1.9; p=0.002), and high level of cfDNA (H=1.8; p=0.006) were independent prognostic factors for OS. The mutational status was also independently related to a worse PFS (HR=1.7; p=0.008). After progression, 56 patients were treated by chemotherapy, 55 by fulvestrant/tamoxifen, 14 by AI + everolimus and 19 by no or other modalities. The detection of circulating ESR1 mutation was independently related to a worse OS and PFS in the chemotherapy group (HR=2.0 for both; p=0.04 and p=0.03, respectively). A trend for a worse OS was also observed for mutated patients treated by fulvestrant/tamoxifen (p=0.09). Among mutated patients, no difference was observed in PFS and OS between the different treatment groups. Conclusions: Circulating ESR1 mutation detection at progression under AI is a strong and independent prognostic factor of OS in HR+mBC patients. This detection seems predictive of a worse outcome in any subsequent treatment.
Persistence of the AML1/ETO fusion transcript in patients treated with allogeneic bone marrow transplantation for t(8;21) leukemia
Authors: J Jurlander, MA Caligiuri, T Ruutu, MR Baer, MP Strout, AR Oberkircher, L Hoffmann, ED Ball, DA Frei-Lahr, NP Christiansen, AM Block, S Knuutila, GP Herzig, CD Bloomfield
Journal: Blood (1996)
Is incomplete estradiol suppression during aromatase inhibitor treatment in post-menopausal patients with breast cancer due to insufficient systemic drug concentrations?
Authors: Daniel Louis Hertz, Kelley M. Kidwell, Kelly A Speth, Christina L Gersch, Zeruesenay Desta, Anna Maria Storniolo, Vered Stearns, Todd C Skaar, Daniel F. Hayes, Norah Lynn Henry, James M. Rae
Journal: Journal of Clinical Oncology (2017)

1063 Background: Aromatase inhibitors (AI) suppress estrogen biosynthesis and are effective treatments for estrogen receptor (ER)-positive breast cancer. In a prospectively enrolled cohort we observed a subset of post-menopausal women who exhibit high plasma estradiol (E2) concentrations during AI treatment, which could potentially contribute to treatment failure. We tested the hypothesis that incomplete E2 suppression is due to insufficient systemic AI concentrations. Methods: Five hundred post-menopausal women with ER-positive breast cancer were randomized to daily exemestane (Exe) 25 mg or letrozole (Let) 2.5 mg. Plasma E2 was measured using GC/MS/MS (lower limit of quantification (LLOQ) = 1.25 pg/mL) at baseline and after 3 months. Let and Exe plasma concentrations measured after 1 or 3 months were compared with the magnitude of E2 depletion using four complementary statistical procedures to assess associations of drug concentrations with: 1) a binary outcome of E2 suppression below LLOQ (logistic regression), 2) 3-month E2 concentrations (linear regression), 3) absolute change from baseline in E2 concentrations (Spearman correlation), and 4) an ordinal outcome defined by E2: decreased to below LLOQ, decreased but not to LLOQ, stayed the same, or increased from baseline (cumulative logistic regression). Results: 397 patients with E2 and AI concentration measurements were evaluable (Exe n = 199, Let n = 198). Thirty (7.6%) patients (Exe n = 13, Let n = 17) had E2 concentrations above the LLOQ at 3 months (range: 1.42-63.8 pg/mL). Exe and Let concentrations were not associated with achievement of unmeasurable E2 concentrations, on-treatment E2 concentrations, E2 change from baseline, or ordinal groupings of E2 change (all p &gt; 0.05). In a parallel analysis there was no association of estrone-sulfate and drug concentrations (data not shown). Conclusions: Our results suggest that circulating drug concentrations do not explain incomplete E2 suppression in women receiving AI therapy. Additional studies are underway to determine whether age, body mass and genetic variation in the aromatase enzyme influence AI treatment response.
Exposure to Traffic-Related Air Pollution and Serum Inflammatory Cytokines in Children
Authors: Olena Gruzieva, Simon Kebede Merid, Anna Gref, Ashwini Gajulapuri, Nathanaël Lemonnier, Stéphane Ballereau, Bruna Gigante, Juha Kere, Charles Auffray, Erik Melén, Göran Pershagen
Journal: Environmental Health Perspectives (2017)

Background: Long-term exposure to ambient air pollution can lead to adverse health effects in children; however, underlying biological mechanisms are not fully understood. Objectives: We evaluated the effect of air pollution exposure during different time periods on mRNA expression as well as circulating levels of inflammatory cytokines in children. Methods: We measured a panel of 10 inflammatory markers in peripheral blood samples from 670 8-y-old children in the Barn/Child, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) birth cohort. Outdoor concentrations of nitrogen dioxide (NO2) and particulate matter (PM) with aerodynamic diameter <10μm (PM10) from road traffic were estimated for residential, daycare, and school addresses using dispersion modeling. Time-weighted average exposures during infancy and at biosampling were linked to serum cytokine levels using linear regression analysis. Furthermore, gene expression data from 16-year-olds in BAMSE (n=238) were used to evaluate links between air pollution exposure and expression of genes coding for the studied inflammatory markers. Results: A 10 μg/m3 increase of NO2 exposure during infancy was associated with a 13.6% (95% confidence interval (CI): 0.8; 28.1%) increase in interleukin-6 (IL-6) levels, as well as with a 27.8% (95% CI: 4.6, 56.2%) increase in IL-10 levels, the latter limited to children with asthma. However, no clear associations were observed for current exposure. Results were similar using PM10, which showed a high correlation with NO2. The functional analysis identified several differentially expressed genes in response to air pollution exposure during infancy, including IL10, IL13, and TNF. Conclusion: Our results indicate alterations in systemic inflammatory markers in 8-y-old children in relation to early-life exposure to traffic-related air pollution. https://doi.org/10.1289/EHP460
BRCA1/2 reversion mutations revealed in breast and gynecologic cancers sequenced during routine clinical care using tissue or liquid biopsy.
Authors: Paul Mayor, Laurie M. Gay, Erica Gornstein, Samantha Morley, Garrett Michael Frampton, Andreas Heilmann, James Sun, Jon Chung, Sugganth Daniel, Shakti Ramkissoon, Eric Allan Severson, James Suh, Jo-Anne Vergilio, Philip J. Stephens, Shashikant B. Lele, Jeffrey S. Ross, Julia Andrea Elvin
Journal: Journal of Clinical Oncology (2017)

5551 Background: Tumors with genomic alteration (GA) of BRCA1 or BRCA2 ( BRCA) may be more sensitive to platinum (Pt) therapies and PARP inhibitors (PARPi). However, secondary reversion mutations (revGA) can arise that may restore BRCA function and underlie reduced sensitivity to Pt compounds or PARPi. Methods: DNA extracted from FFPE tumor tissue or blood samples obtained during routine clinical care for patients with predominantly relapsed, refractory or metastatic breast cancer (10967) or ovarian/peritoneal cancer (8352) was analyzed by hybrid-capture, next-generation sequencing for all classes of GA: base substitutions, indels, rearrangements, and copy number changes. RevGA were any GA that could restore the reading frame if in cis with a nonsense or frameshift (fs) GA. Results: 1900/19329 (9.8% ± 0.4%) tumors had ≥1 deleterious BRCA GA. 38 samples harbored potential revGA in BRCA1 (16) or BRCA2 (22): breast carcinoma (Ca) (21), ovarian or peritoneal serous Ca (10), ovarian or peritoneal adenocarcinoma (3), and ovarian epithelial Ca NOS (4). 35/38 sequenced samples were metastases. All potential revGA were somatic and fell into 3 classes: overlapping indel (21), compensatory fs (6), and missense mutation (11). One case harbored both an overlapping indel and a missense mutation with potential to revert a nonsense alteration. For 6 patients, testing of multiple tissue samples reveals the acquisition of revGA over time. RevGA are generally observed at allele frequencies lower than the deleterious GA they may revert. Clinical histories for patients with reversion mutations will be presented. Conclusions: Genomic profiling of breast and gynecological carcinomas, using either tissue or liquid biopsies, reveals potential revGA that may restore some level of BRCA function. RevGA, although rare, can be acquired during the course of treatment. We identified potentially compensatory missense, fs and indel mutations with CGP. Comparison of allele frequencies suggests that revGA often arise as subclones. The acquisition of a revGA over time can be observed through testing of multiple samples, either tissue or liquid biopsy.
The Host Immune Response to Clostridium Difficile and the Immunomodulatory Effects of Probiotic Bacteria in Vitro
Authors: JA Ryan, A Fanning, B Sheil, L O'Mahony, F Shanahan
Journal: Endoscopy (2006)

Aims: Clostridium difficile is an anaerobic organism that is a significant cause of morbidity. Probiotic microorganisms within the gut may alter the host response to pathogens. The aim of this study was to assess the pro-inflammatory effect of C. difficile on an epithelial cell line and whether two different commensal bacterial strains attenuate this effect in vitro.
Fall in new HIV diagnoses among men who have sex with men (MSM) at selected London sexual health clinics since early 2015: testing or treatment or pre-exposure prophylaxis (PrEP)?
Authors: Alison E Brown, Hamish Mohammed, Dana Ogaz, Peter D Kirwan, Mandy Yung, Sophie G Nash, Martina Furegato, Gwenda Hughes, Nicky Connor, Valerie C Delpech, O Noel Gill
Journal: Eurosurveillance (2017)

Since October 2015 up to September 2016, HIV diagnoses fell by 32% compared with October 2014-September 2015 among men who have sex with men (MSM) attending selected London sexual health clinics. This coincided with high HIV testing volumes and rapid initiation of treatment on diagnosis. The fall was most apparent in new HIV testers. Intensified testing of high-risk populations, combined with immediately received anti-retroviral therapy and a pre-exposure prophylaxis (PrEP) programme, may make elimination of HIV achievable.
A case of generalised papules
Authors: Valencia Long, Henry Foong
Journal: BMJ (2017)

A 75 year old man who lived in a nursing home complained of itching and a rash that had lasted for four months. The man had experienced a traumatic cervical cord injury six months earlier and had sensory impairment but no other substantial medical history. On examination, he had markedly thickened crusts and hyperkeratosis on his hands and feet bilaterally, with involvement of his finger and toe web spaces (fig 1⇓, fig 2⇓). There were excoriated erythematous papules over his trunk and axillae (fig 3⇓) and erythematous papules or nodules on his glans penis. A fungal scrape was performed and this was negative for fungal elements.



Fig 1  Thickened crusts in the digits and palm





Fig 2  Crusts in the toe …
Factors influencing colorectal cancer screening participation rates in 2016
Authors: Jérôme Viguier, Jean-François Morere, Xavier Pivot, Alexis B. Cortot, Jean-Yves Blay, Chantal Touboul, Christine Lhomel, Laurent Greillier, Sébastien Couraud, François Eisinger
Journal: Annals of Oncology (2017)
Asthma and corticosteroids: time for a more precise approach to treatment
Authors: Eleanor M. Dunican, John V. Fahy
Journal: European Respiratory Journal (2017)

It is well known that corticosteroids improve asthma in a subgroup of patients and that this responder subgroup is invariably large enough to drive statistically significant differences in asthma outcomes when steroids are compared to placebo in unselected patients. The consistency of clinical trial data showing benefit from corticosteroids, especially in less severe patients, is the reason why asthma treatment guidelines consistently advocate their daily use in all but the mildest forms of asthma. Guidelines also typically advocate an empiric approach to corticosteroid dosing in which the dose of corticosteroid is increased as disease severity worsens. Such empiric approaches to treatment are now considered flawed and the emphasis is switching to development of treatment approaches that are guided by mechanism-based molecular endotypes rather than trait-based clinical phenotypes. The reason is simple: asthma traits such as symptoms and airflow limitation result from heterogeneous molecular mechanisms, and a one-size-fits all treatment paradigm to treat these traits does not make sense. Prescribing corticosteroids for asthma based on mechanism-based endotypes rather than trait-based phenotypes <http://ow.ly/HiHq30cA6Da>
Integration of Advanced Practice Clinicians in Neurology Practices
Authors: Paula Hardeman, Rhonda Hough
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
Efficacy and toxicity profile of eribulin mesylate for metastatic breast cancer (MBC) patients (pts) in the routine clinic: A French observational study.
Authors: Anne Patsouris, Benjamin Linot, Marie Robert, Carole Gourmelon, Mario Campone, Angelique Brunot, Claudia Lefeuvre-Plesse, Jerome Martin, Adele Marquis, Hugues Pierre Bourgeois, Mickael Som, Herve Desclos, Olivier Tredan
Journal: Journal of Clinical Oncology (2014)

e11555 Background: In the EMBRACE Phase III trial of heavily pretreated patients (pts) with metastatic breast cancer (MBC), eribulin, a microtubule dynamics inhibitor, has demonstrated a statistically significant improvement in overall survival (OS) versus current treatments. To assess the efficacy and toxicity of eribulin treatment in a French population of MBC pts we conducted an observational study evaluating the outcome in the routine clinic. Methods: From July 2013 to January 2014, a database was completed containing patient and tumor characteristics, treatment histories, outcome, and side effect profiles. Pts with histologically confirmed MBC must have received eribulin using standard protocols from July 2011 to July 2013. Data from 193 MBC pts from 7 French cancer centers were analyzed. Results: The median age was 60.9 years; 21.6% of pts were metastatic at diagnosis, and 38.9% have triple negative phenotype. 29% of pts had received >5 lines of prior chemotherapy. In the metastatic setting, 93%, 87.5% and 52,6% of patients have received taxane, capecitabine and vinorelbine respectively. At 3 months, 13.9% of patients had partial response, while 23.8% had stable disease. With a median follow-up of 5.5 months, median progression-free survival was 3.5 months and median OS was 9.9 months. The most common adverse event was neutropenia (15.7% ≥grade 3), with 2 episodes of febrile neutropenia. Toxicities leading to treatment discontinuation included asthenia (5.7%), peripheral neuropathy (2.1%) and liver dysfunction (2.1%). Conclusions: Data from this French cohort of heavily pretreated MBC pts are consistent with results of the EMBRACE study, with respect to both treatment outcome and manageable toxicity profile.
Early Detection of Hepatocellular Carcinoma Requires a Combined Surveillance Protocol in High-Risk Individuals
Authors: A Qasim, T Tajjudin, B Zaman, D Maguire, J Geoghegan, O Traynor, J Hegarty, A McCormick
Journal: Endoscopy (2006)

Background: Surveillance protocol for HCC involves radiological scanning and AFP levels at regular intervals.