tbuckley/cabot-search huggingface dataset:
Exhaled volatile organic compounds as markers for medication use in asthma
Authors: Paul Brinkman, Waqar M. Ahmed, Cristina Gómez, Hugo H. Knobel, Hans Weda, Teunis J. Vink, Tamara M. Nijsen, Craig E. Wheelock, Sven-Erik Dahlen, Paolo Montuschi, Richard G. Knowles, Susanne J. Vijverberg, Anke H. Maitland-van der Zee, Peter J. Sterk, Stephen J. Fowler
Journal: European Respiratory Journal (2019)

Introduction Asthma is a heterogeneous condition, characterised by chronic inflammation of the airways, typically managed with inhaled bronchodilators and corticosteroids. In the case of uncontrolled asthma, oral corticosteroids (OCSs) are often prescribed. Good adherence and inhalation technique are associated with improved outcomes; however, it is difficult to monitor appropriate drug intake and effectiveness in individual patients. Exhaled breath contains thousands of volatile organic compounds (VOCs) that reflect changes in the body's chemistry and may be useful for monitoring drug pharmacokinetics/pharmacodynamics. We aimed to investigate the association of exhaled VOCs in severe asthma patients from the U-BIOPRED cohort (by gas chromatography coupled with time-of-flight mass spectrometry) with urinary levels of salbutamol and OCSs (by liquid chromatography coupled with high-resolution mass spectrometry). Methods Samples were collected at baseline and after 12–18 months of follow-up. Statistical analysis was based on univariate and multivariate modelling, followed by area under the receiver operating characteristic curve (AUC) calculation. Results were verified through longitudinal replication and independent validation. Results Data were available for 78 patients (baseline n=48, replication n=30 and validation n=30). Baseline AUC values were 82.1% (95% CI 70.4–93.9%) for salbutamol and 78.8% (95% CI 65.8–91.8%) for OCS. These outcomes could be adequately replicated and validated. Additional regression analysis between qualified exhaled VOCs and urinary concentrations of salbutamol and prednisone showed statistically significant correlations (p&lt;0.01). Conclusion We have linked exhaled VOCs to urinary detection of salbutamol and OCSs. This merits further development of breathomics into a point-of-care tool for therapeutic drug monitoring.
Scrotal Fibroepithelial Polyp With Acute and Chronic Inflammation Mimics Malignancy on 18F-FDG PET/CT Imaging
Authors: Tzyy-Ling Chuang, Chih-En Tseng, Shih-Wen Huang, Yuh-Feng Wang
Journal: Clinical Nuclear Medicine (2019)

Abstract Computed tomography (CT) of a 68-year-old man showed multiple small nodules in the bilateral lungs (maximum 14 mm in the left upper lobe). CT-guided biopsy of left upper lobe lesion showed no tumor or granuloma. Fluorodeoxyglucose (FDG) PET/CT showed multiple nodules with background-to-mild FDG-avid activity, and an incidental left scrotal skin lesion with intensely increased accumulation of 18 F-FDG (SUVmax, 11.7), suspected malignant. After urologist consultation, local dermatological findings suggested a huge wart. Excision was done, and pathology concluded nodular papillary fibroepithelial polyp with acute and chronic inflammation.
современные Методы определения фиброза печени
Authors: V.I. Didenko
Journal: GASTROENTEROLOGY (2013)

Фиброз печени — ключевое звено в развитии патологического процесса в ткани печени, и степень фиброза является достаточно чувствительным неспецифическим маркером патологических изменений в печени под воздействием различных этиологических факторов. Различают инвазивные, малоинвазивные и неинвазивные методы определения фиброза печени. К инвазивным методам относится пункционная трепанобиопсия — золотой стандарт. К малоинвазивным методам — прямые и непрямые маркеры фиброза. К неинвазивным методам — эластография и эластометрия. В современной гепатологии используются все перечисленные методы.
Flourishing as a Definition of Health
Authors: Alan J. Card
Journal: JAMA (2019)

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
Aetiology of invasive bacterial infection and antimicrobial resistance in neonates in sub-Saharan Africa: a systematic review and meta-analysis in line with the STROBE-NI reporting guidelines
Authors: Uduak Okomo, Edem N K Akpalu, Kirsty Le Doare, Anna Roca, Simon Cousens, Alexander Jarde, Mike Sharland, Beate Kampmann, Joy E Lawn
Journal: The Lancet Infectious Diseases (2019)
Abstract #1852: Valproic acid causes growth inhibition in oral cancer by inducing terminal differentiation
Authors: Sok Ching Cheong, Chai Phei Gan, Sharifah Hamid, Siti Mazlipah Ismail, Soo-Hwang Teo, Nicholas Saunders, Rosnah Zain
Journal: Cancer Research (2009)

Introduction: Oral cancer is a major medical problem in many countries in Asia. These cases are often presented at late stages of the disease where treatment options are limited. Histone deacetylase inhibitors (HDACIs) are a class of drugs shown to be able to regulate the acetylation of histones and histone proteins to inhibit the growth of cancer in vitro and in vivo. Valproic acid (VPA), classically used in the treatment of epilepsy have been shown to be a HDACI, and is currently undergoing Phase II clinical trials for the treatment of cancer. VPA has been shown to be effective in inhibiting cell proliferation and inducing differentiation. In addition, it has been shown to enhance the efficacy of other drugs including all-trans-retinoic acid (ATRA). In this study, we evaluated the effects of VPA in oral cancer cell lines and determined if a combination of VPA and ATRA could be used to control oral cancer. Materials and Methods: Five oral cancer cell lines were used in this study: ORL-48, 166, 215, 156 and SCC-15. Cytotoxicity and growth inhibition was evaluated with MTT and clonogenic assays respectively. The mechanism of cellular growth inhibition was investigated by looking at the expression of cell cycle genes and markers of terminal differentiation and senescence. Results: We demonstrate that VPA is cytotoxic to ORL-215, and SCC-15 with IC50 of 1.38 and 1.28 mM respectively. In addition, via clonogenic assays, we show that VPA also has cytostatic effects on ORL-215, 166 and SCC-15 where IC50 values were 1.79, 0.46 and 1.06 mM respectively. By comparing cell lines that were responsive and resistant to VPA, we demonstrate that the cytostatic response to VPA was associated with an increase in p21 expression and up-regulation of terminal differentiation markers involucrin and SPRR1b. These data suggest that the growth inhibition was at least partly due to the induction of terminal differentiation. We also investigated if a combination of VPA and ATRA could induce cytotoxicity in oral cancer cells particularly those that were resistant to VPA treatment alone. Although VPA could restore the expression of retinoic acid receptor-\#946; we did not see an increase in cell killing when both VPA and ATRA were used consecutively. Conclusion: We demonstrate that VPA has cytotoxic and cytostatic effects on oral cancer cell lines. We further demonstrate that this is due to an increase in p21 expression and the induction of terminal differentiation. We suggest that VPA could be a relevant drug for the treatment of oral cancer in patients who have minimal residual disease after curative attempt by surgery, chemotherapy and/or radiotherapy particularly in oral cancer where secondary or recurrent tumours are frequent.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1852.
A Theranostic Cathepsin Activity-Based Probe for Noninvasive Intervention in Cardiovascular Diseases
Authors: Tommy Weiss-Sadan, Yael Ben-Nun, David Maimoun, Emmanuelle Merquiol, Ihab Abd-Elrahman, Israel Gotsman, Galia Blum
Journal: Theranostics (2019)

Despite the common use of lipid-lowering medications, cardiovascular diseases continue to be a significant health concern.Atherosclerosis, one of the most frequent causes of cardiovascular morbidity, involves extensive inflammatory activity and remodeling of the vascular endothelium.This relentless inflammatory condition can ultimately give rise to clinical manifestations, such as ischemic heart disease or stroke.Accumulating evidence over the past decades implicates cysteine protease cathepsins in cardiovascular disorders.In particular, Cathepsins B, L, and S are over-expressed during vascular inflammation, and their activity is associated with impaired clinical outcomes.Here we took advantage of these molecular events to introduce a non-invasive detection and treatment approach to modulate vascular inflammation using a Photosensitizing quenched Activity-Based Probed (PS-qABP) that targets these proteases.Methods: We tested the application of this approach in LDL receptor-deficient mice and used non-invasive imaging and heart cross-section staining to assess the theranostic efficacy of this probe.Moreover, we used fresh human endarterectomy tissues to analyze cathepsin signals on gel, and verified cathepsin identity by mass spectrometry.Results: We showed that our PS-qABP can rapidly accumulate in areas of inflammatory atheromas in vivo, and application of light therapy profoundly reduced lesional immune cell content without affecting smooth muscle cell and collagen contents.Lastly, using human tissue samples we provided proof-of-concept for future clinical applications of this technology.Conclusions: Photodynamic therapy guided by cysteine cathepsin activity is an effective approach to reduce vascular inflammation and attenuate atherosclerosis progression.This approach could potentially be applied in clinical settings.
Positron Emission Tomography–Guided Treatment in Early-Stage Favorable Hodgkin Lymphoma: Final Results of the International, Randomized Phase III HD16 Trial by the German Hodgkin Study Group
Authors: Michael Fuchs, Helen Goergen, Carsten Kobe, Georg Kuhnert, Andreas Lohri, Richard Greil, Stephanie Sasse, Max S. Topp, Erhardt Schäfer, Bernd Hertenstein, Martin Soekler, Martin Vogelhuber, Josée M. Zijlstra, Ulrich Bernd Keller, Stefan W. Krause, Martin Wilhelm, Georg Maschmeyer, Julia Thiemer, Ulrich Dührsen, Julia Meissner, Andreas Viardot, Hans Eich, Christian Baues, Volker Diehl, Andreas Rosenwald, Bastian von Tresckow, Markus Dietlein, Peter Borchmann, Andreas Engert
Journal: Journal of Clinical Oncology (2019)

PURPOSE Combined-modality treatment (CMT) with 2× ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and small-field radiotherapy is standard of care for patients with early-stage favorable Hodgkin lymphoma (HL). However, the role of radiotherapy has been challenged. Positron emission tomography (PET) after 2× ABVD (PET-2) might help to predict individual outcomes and guide treatment. METHODS Between November 2009 and December 2015, we recruited patients age 18 to 75 years with newly diagnosed, early-stage favorable HL for this international randomized phase III trial. Patients were assigned to standard CMT of 2× ABVD and 20-Gy involved-field radiotherapy or PET-guided treatment, omitting involved-field radiotherapy after negative PET-2 (Deauville score &lt; 3). Primary objectives were to exclude inferiority of 10% or more in 5-year progression-free survival (PFS) of ABVD alone compared with CMT in a per-protocol analysis among PET-2–negative patients (noninferiority margin for hazard ratio, 3.01) and to confirm PET-2 positivity (Deauville score ≥ 3) as a risk factor for PFS among CMT-treated patients. RESULTS We enrolled 1,150 patients. Median follow-up was 45 months. Among 628 PET-2–negative, per-protocol–treated patients, 5-year PFS was 93.4% (95% CI, 90.4% to 96.5%) with CMT and 86.1% (95% CI, 81.4% to 90.9%) with ABVD (difference 7.3% [95% CI, 1.6% to 13.0%]; hazard ratio, 1.78 [95% CI, 1.02 to 3.12]). Five-year overall survival was 98.1% (95% CI, 96.5% to 99.8%) with CMT and 98.4% (95% CI, 96.5% to 100.0%) with ABVD. Among 693 patients who were assigned to CMT, 5-year PFS was 93.2% (95% CI, 90.2% to 96.2%) among PET-2–negative patients and 88.4% (95% CI, 84.2% to 92.6%) in PET-2–positive patients ( P = .047). When using the more common liver cutoff (Deauville score, 4) for PET-2 positivity, the difference was more pronounced (5-year PFS, 93.1% [95% CI, 90.7% to 95.5%] v 80.9% [95% CI, 72.2% to 89.7%]; P = .0011). CONCLUSION In early-stage favorable HL, a positive PET after two cycles ABVD indicates a high risk for treatment failure, particularly when a Deauville score of 4 is used as a cutoff for positivity. In PET-2–negative patients, radiotherapy cannot be omitted from CMT without clinically relevant loss of tumor control.
Influence of health insurance status on breast cancer diagnosis and treatment delay: A safety net hospital's experience
Authors: B. K. Vakkalanka, K. Ruda, T. O'Brien
Journal: Journal of Clinical Oncology (2007)

6592 Background: Given barriers to access, uninsured women with breast cancer might experience delays in diagnosis and treatment when compared to insured women. The influence of insurance status on breast cancer outcome was addressed at a single institution whose mission statement requires that all pts be treated the same, regardless of their ability to pay Methods: Records of all pts with breast cancer seen from 1/00- 12/04 at a safety net hospital were reviewed. Insurance status was defined at the time of the first abnormal mammogram. Cases were divided into Group A (private insurance), B (medicaid or medicare) or C (uninsured). Time to diagnosis (TDx) was defined as the interval from abnormal mammogram to pathologic diagnosis of breast cancer. Time to treatment (TRx) was defined as time from pathologic diagnosis to definitive surgical therapy. Results: 560 cases were reviewed. Group A: 48%, B: 33%, C: 19%. Median age= 57 (GrpA=53, B= 67, C= 55). Race Caucasian 59%; AA 34%; other 7%. Stage (0, I, II, III and IV, in %, respectively): Grp A= 14.6, 42.9, 31.5, 7.1 and 3.9; Grp B= 13.1, 46, 22.7, 12.5 and 5.7; Grp C = 13.9, 33.7, 32.7, 11.9 and 7.9. No significant diff between groups, although there was a trend towards later (III/IV) pts in grps B and C than A (18.2% and 19.8% vs 10.9%, respectively). Mean TDx: Grp A= 50.6 days, B= 68.1d and C=52.8d; p= 0.006 when Group B was compared to the other two groups but there was no difference between uninsured and private groups. Mean TRx: 43.8d, 48.6d and 47.8 days, respectively, for groups A, B and C, without any statistical difference between any of the groups. Conclusions: A 5-year review of breast cancer cases at a large safety net hospital did not reveal any difference in the time to diagnosis or initiation of treatment for insured vs. uninsured pts. Uninsured and medicaid/medicare pts tended to present with later stage disease, perhaps due to access problems. A statistically significant delay in diagnosis was noted in the medicaid/medicare group but it is unlikely that this difference (18 days) was clinically important. Because uninsured pts are provided care at greatly discounted rates at our institution, these results may differ from those at other institutions. Further studies addressing this issue are warranted. No significant financial relationships to disclose.
Solving the Riddle of the Evolution of Shine-Dalgarno Based Translation in Chloroplasts
Authors: Iddo Weiner, Noam Shahar, Pini Marco, Iftach Yacoby, Tamir Tuller
Journal: Molecular Biology and Evolution (2019)

Chloroplasts originated from an ancient cyanobacterium and still harbor a bacterial-like genome. However, the centrality of Shine-Dalgarno ribosome binding, which predominantly regulates proteobacterial translation initiation, is significantly decreased in chloroplasts. As plastid ribosomal RNA anti-Shine-Dalgarno elements are similar to their bacterial counterparts, these sites alone cannot explain this decline. By computational simulation we show that upstream point mutations modulate the local structure of ribosomal RNA in chloroplasts, creating significantly tighter structures around the anti-Shine-Dalgarno locus, which in-turn reduce the probability of ribosome binding. To validate our model, we expressed two reporter genes (mCherry, hydrogenase) harboring a Shine-Dalgarno motif in the Chlamydomonas reinhardtii chloroplast. Coexpressing them with a 16S ribosomal RNA, modified according to our model, significantly enhances mCherry and hydrogenase expression compared with coexpression with an endogenous 16S gene.
<i>Cutibacterium acnes</i> in acne pathophysiology – the chicken or the egg?
Authors: F.R. Ochsendorf
Journal: British Journal of Dermatology (2019)

Linked Article: Ramasamy et al. Br J Dermatol 2019; 181:691–699. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Anti-TNF therapy in IBD exerts its therapeutic effect through macrophage IL-10 signalling
Authors: Pim J Koelink, Felicia M Bloemendaal, Bofeng Li, Liset Westera, Esther W M Vogels, Manon van Roest, Anouk K Gloudemans, Angelique B van 't Wout, Hannelie Korf, Séverine Vermeire, Anje A te Velde, Cyriel Y Ponsioen, Geert RAM D'Haens, J Sjef Verbeek, Terrence L Geiger, Manon E Wildenberg, Gijs R van den Brink
Journal: Gut (2019)

Objective Macrophage interleukin (IL)-10 signalling plays a critical role in the maintenance of a regulatory phenotype that prevents the development of IBD. We have previously found that anti-tumour necrosis factor (TNF) monoclonal antibodies act through Fcγ-receptor (FcγR) signalling to promote repolarisation of proinflammatory intestinal macrophages to a CD206+ regulatory phenotype. The role of IL-10 in anti-TNF-induced macrophage repolarisation has not been examined. Design We used human peripheral blood monocytes and mouse bone marrow-derived macrophages to study IL-10 production and CD206+ regulatory macrophage differentiation. To determine whether the efficacy of anti-TNF was dependent on IL-10 signalling in vivo and in which cell type, we used the CD4+CD45Rb high T-cell transfer model in combination with several genetic mouse models. Results Anti-TNF therapy increased macrophage IL-10 production in an FcγR-dependent manner, which caused differentiation of macrophages to a more regulatory CD206+ phenotype in vitro. Pharmacological blockade of IL-10 signalling prevented the induction of these CD206+ regulatory macrophages and diminished the therapeutic efficacy of anti-TNF therapy in the CD4+CD45Rb high T-cell transfer model of IBD. Using cell type-specific IL-10 receptor mutant mice, we found that IL-10 signalling in macrophages but not T cells was critical for the induction of CD206+ regulatory macrophages and therapeutic response to anti-TNF. Conclusion The therapeutic efficacy of anti-TNF in resolving intestinal inflammation is critically dependent on IL-10 signalling in macrophages.
BCAP31 drives TNBC development by modulating ligand-independent EGFR trafficking and spontaneous EGFR phosphorylation
Authors: Wenyan Fu, Hefen Sun, Yang Zhao, Mengting Chen, Xueli Yang, Yang Liu, Wei Jin
Journal: Theranostics (2019)

Identification of novel targets for triple-negative breast cancer (TNBC) is an urgent task as targeted therapies have increased the lifespans of Oestrogen Receptor
A novel patient‐reported outcome for paediatric localized scleroderma: a qualitative assessment of content validity
Authors: C.K. Zigler, K. Ardalan, S. Lane, K.L. Schollaert, K.S. Torok
Journal: British Journal of Dermatology (2019)

According to current standards, no existing patient-reported outcome (PRO) measures have high-quality validity evidence for use with individuals diagnosed with paediatric localized scleroderma (LS). This severely hinders patient-centred LS-focused research, including much needed clinical trials.
Effect of high flow oxygen on exertional dyspnea in cancer patients: A double-blind randomized clinical trial.
Authors: David Hui, Liliana Larsson, Sajan Thomas, Carol Harrison, Jimin Wu, Donald Mahler, Kenneth R. Hess, Juan Lopez-Mattei, Kara Thompson, Daniel Richard Gomez, Melenda Jeter, Steven H. Lin, Anne S. Tsao, George Eapen, Karen Basen-Engquist, Eduardo Bruera
Journal: Journal of Clinical Oncology (2019)

11600 Background: High flow oxygen therapy is effective for hypoxemic respiratory failure. However, its effect on dyspnea in non-hypoxemic patients is unknown. In this 2x2 factorial, double-blind randomized clinical trial, we assessed the effect of flow rate (high vs. low) and gas (oxygen vs. air) on exertional dyspnea in cancer patients. Methods: Non-hypoxemic patients with cancer completed two structured cycle ergometer exercise tests with Low Flow Air [LFAir] at 2 L/min. They were then randomized to receive High Flow Oxygen [HFOx] with up to 60 L/min, High Flow Air [HFAir], Low Flow Oxygen [LFOx] or LFAir during a constant work rate exercise test at 80% maximum. Dyspnea intensity was assessed with the modified 0-10 Borg scale. The primary outcome was difference in the slope of dyspnea intensity vs. time during the third test. Secondary outcomes included difference in exercise time, vital signs, and adverse events. We estimated that 10 patients per arm will provide 86% power to detect a 1-standard deviation main effect and 86% power to detect a 2-SD interaction effect with an alpha of 5%. A linear mixed effects model was used to assess the impact of flow rate and gas on study outcomes. Results: 45 patients were randomized and 44 completed the study (10, 11, 12, 11 patients on HFOx, HFAir, LFOx, LFAir, respectively). The mean age was 63 (range 47-77); 18 (41%) were female; 34 (44%) had lung cancer; and 20 (46%) had metastatic disease. In mixed effects model, the association between the change in dyspnea intensity over time with flow rate differed significantly between oxygen and air (P = 0.04). Specifically, HFOx (slope difference -0.20, P &lt; 0.001) and LFOx (-0.14, P = 0.01) were significantly better than LFAir, but not HFAir (+0.09, P = 0.09). Exercise time also significantly increased with HFOx (difference +2.5 min, P = 0.009) compared to LFAir, but not HFAir (+0.63 min, P = 0.48) or LFOx (+0.39 min, P = 0.65). HFOx was well tolerated without significant adverse effects. Conclusions: The combination of high flow rate and oxygen improved dyspnea and exercise duration during constant work exercise test in non-hypoxemic cancer patients. Larger trials are needed to confirm the benefits of HFOx during exercises. Clinical trial information: NCT02357134.