tbuckley/cabot-search huggingface dataset:
Underdiagnosis and Overdiagnosis of Chronic Obstructive Pulmonary Disease
Authors: Nermin Diab, Andrea S. Gershon, Don D. Sin, Wan C. Tan, Jean Bourbeau, Louis-Philippe Boulet, Shawn D. Aaron
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Section:ChooseTop of pageAbstract <<Epidemiology and Prevalen...Defining Under- and Overd...Prevalence of Undiagnosed...Prevalence of Underdiagno...Factors Associated with U...Burden of Underdiagnosis ...Prevalence of Overdiagnos...Factors Associated with O...Burden of Overdiagnosis o...Potential Solutions to Re...Potential Solutions to Re...Conclusions and Future Di...ReferencesCITING ARTICLES
The Rise in Atopic Dermatitis in Young Children
Authors: Tamar Hajar, Eric L. Simpson
Journal: JAMA Network Open (2018)

Cathrine H. Mohn, MD; Hege Salvesen Blix, MSc, Pharm, PhD; Jon Anders Halvorsen, MD, PhD; Per Nafstad, MD, PhD; Morten Valberg, MSc, PhD; Per Lagerløv, MD, PhD
Pulmonary Artery Rupture after Ultrasound-assisted Catheter-directed Thrombolysis
Authors: Gustavo Fernandez Romero, Bashir Riyaz, Rohit Gupta, Brian O’Murchu, Vladimir Lakhter, Claudia Nieves Prado, Talal Akhter, Gary Cohen, Parth Rali
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
Changes in the Synaptic Proteome in Tauopathy and Rescue of Tau-Induced Synapse Loss by C1q Antibodies
Authors: Borislav Dejanovic, Melanie A. Huntley, Ann De Mazière, William J. Meilandt, Tiffany Wu, Karpagam Srinivasan, Zhiyu Jiang, Vineela Gandham, Brad A. Friedman, Hai Ngu, Oded Foreman, Richard A.D. Carano, Ben Chih, Judith Klumperman, Corey Bakalarski, Jesse E. Hanson, Morgan Sheng
Journal: Neuron (2018)
‘Test n Treat’ (TnT): a cluster randomized feasibility trial of on-site rapid Chlamydia trachomatis tests and treatment in ethnically diverse, sexually active teenagers attending technical colleges
Authors: P. Oakeshott, S. Kerry-Barnard, C. Fleming, R. Phillips, V.M. Drennan, E.J. Adams, W. Majewska, E.M. Harding-Esch, E.C. Cousins, T. Planche, A. Green, R.I. Bartholomew, S.T. Sadiq, F. Reid
Journal: Clinical Microbiology and Infection (2018)

We conducted a cluster-randomized feasibility trial of 90-minute Chlamydia trachomatis tests and same day on-site treatment ('Test n Treat/TnT') in six technical colleges in London, England, to assess TnT uptake rates; follow-up rates; prevalence of C. trachomatis at baseline and 7 months; time to treatment; acceptability of TnT.Participants completed questionnaires and provided genitourinary samples at baseline and 7 months. Participants were informed that baseline samples would not be tested for 7 months and were advised to get screened independently. Colleges were randomly allocated 1:1 to intervention (TnT) or control (no TnT). One month and 4 months post recruitment, participants at intervention colleges were texted invitations for on-site free C. trachomatis tests. A purposive sample of students who did/did not attend for screening were interviewed (n = 26).Five hundred and nine sexually active students were recruited: median age 17.9 years, 47% male, 50% black ethnicity, 55% reporting two or more sexual partners in the previous year. TnT uptake was 13% (33/259; 95% CI 8.9-17.4%) at 1 month and 10% (26/259; 6.7-14.4%) at 4 months with overall C. trachomatis positivity 5.1% (3/59; 1.1-14.2%). Follow-up at 7 months was 62% (317/509) for questionnaires and 52% (264/509) for samples. C. trachomatis prevalence was 6.2% (31/503) at baseline and 6.1% (16/264) at 7 months. Median time from test to treatment was 15 h. Interviews suggested low test uptake was associated with not feeling at risk, perceptions of stigma, and little knowledge of sexually transmitted infections (STIs).Despite high C. trachomatis rates at baseline and follow-up, uptake of testing was low. Like many countries, England urgently needs better sex education, including making STI testing routine/normal. Trial registration ISRCTN58038795.
Efficacy and saftey of capecitabine, oxaliplatin, and irinotecan (xeloxiri) as salvage therapy for patients with treatment-refractory metastatic colorectal cancer: A prospective, open-label, phase II study.
Authors: Thomas Cheung Yau, Vikki YF Tang, Joanne Chiu, Hilda Wong, Roland Ching-Yu Leung
Journal: Journal of Clinical Oncology (2014)

e14511 Background: Treatment options for metastatic colorectal cancer (mCRC) patients that progress after standard approved therapies are limited. This study aimed to explore the efficacy and safety of combining capecitabine, oxaliplatin, and irinotecan (xeloxiri) in treating treatment-refractory mCRC patients. Methods: Patients with documented mCRC and progression during or within two month after the last standard therapy were enrolled. All the recruited patients received the xeloxiri regimen: oral capecitabine 1250 mg/m2 bid from D1-7 of a two-week cycle, oxaliplatin 85 mg/m2 on D1, and irinotecan 165 mg/m2on D1. The primary endpoint was objective response rate (RR). Secondary endpoints were progression-free survival (PFS) overall survival (OS) and adverse events (AEs). Exploratory biomarkers: NRAS and BRAFwere examined. Results: There were 28 patients who were enrolled and the median age was 55 years. Fifteen (60%) patients had KRAS wild type disease. Median number of prior systemic regimes for metastatic disease was three. All the enrolled patients had documented disease progression with prior 5-FU, irinotecan or oxaliplatin administration. All the KRAS wild type patients had disease progression with prior cetuximab-based therapies and 67% patients failed bevacizumab as well. All KRAS mutant patients except one had disease progression with prior bevacizumab based regimes. Overall, six (21%) patients achieved partial response, and 12 (43%) patients had stable disease. Thus, 64% of the enrolled patients derived clinical benefit from xeloxiri regimen. The median PFS was 6.2 months (95% C.I. 2.8-7.4) and median OS was 10.3 months (95% C.I. 6.8-12.9). The most common non-hematological AEs included neuropathy (41%), diarrhea (41%) and malaise (30%). The most common grade 3-4 AEs were neutropenia (37%), thrombocytopenia (15%) and anemia (15%). Exploratory correlative biomarkers results (NRAS and BRAF) will be presented. Conclusions: The xeloxiri regimen has promising efficacy and survival benefits in mCRC patients who had failed all the standard treatment options. Clinical trial information: HKU064.
Ixazomib Plus Lenalidomide-Dexamethasone (IRd) in Relapsed/Refractory Multiple Myeloma (MM) Patients (Pts) - Effectiveness in Routine Clinical Practice Is Similar to the Efficacy in the Phase 3 Tourmaline-MM1 Trial: A Pooled Analysis from the Insight MM Observational Study and the Czech Registry of Monoclonal Gammopathies (RMG)
Authors: Roman Hajek, Evangelos Terpos, Hans C. Lee, Ajai Chari, Caitlin L. Costello, Noemi Puig, Xavier Leleu, Jesus G. Berdeja, Faith E. Davies, Katja Weisel, Saad Z. Usmani, Vania T. M. Hungria, Mario Boccadoro, Robert M Rifkin, Jeffrey A Zonder, Gordon Cook, Lucie Brožová, Magda Bařinová, Kaili Ren, Roxanne Cacioppo, Tomas Skacel, Dawn Marie Stull, Vladimir Maisnar
Journal: Blood (2018)
Bcl11b sets pro-T cell fate by site-specific cofactor recruitment and by repressing Id2 and Zbtb16
Authors: Hiroyuki Hosokawa, Maile Romero-Wolf, Mary A. Yui, Jonas Ungerbäck, Maria L. G. Quiloan, Masaki Matsumoto, Keiichi I. Nakayama, Tomoaki Tanaka, Ellen V. Rothenberg
Journal: Nature Immunology (2018)
Preliminary Safety, Pharmacokinetic, and Pharmacodynamic Results from a Phase 1b/2 Dose-Escalation and Cohort-Expansion Study of the Noncovalent, Reversible Bruton's Tyrosine Kinase Inhibitor (BTKi), Vecabrutinib, in B-Lymphoid Malignancies
Authors: John N. Allan, William G. Wierda, Krish Patel, Susan M. O'Brien, Anthony R Mato, Matthew S Davids, Richard R. Furman, John M. Pagel, Judith A. Fox, Renee Ward, Pietro Taverna, Jennifer R. Brown
Journal: Blood (2018)
Metabolic features of cancer cells
Authors: Yugang Wang, Yan Xia, Zhimin Lu
Journal: Cancer Communications (2018)

Abstract Cancer cells uniquely reprogram their cellular activities to support their rapid proliferation and migration and to counteract metabolic and genotoxic stress during cancer progression. In this reprograming, cancer cells’ metabolism and other cellular activities are integrated and mutually regulated, and cancer cells modulate metabolic enzymes spatially and temporally so that these enzymes not only have altered metabolic activities but also have modulated subcellular localization and gain non‐canonical functions. This review and several others in this issue of Cancer Communications discuss these enzymes’ newly acquired functions and the non‐canonical functions of some metabolites as features of cancer cell metabolism, which play critical roles in various cellular activities, including gene expression, anabolism, catabolism, redox homeostasis, and DNA repair.
Variability in Partial Nephrectomy Outcomes: Does Your Surgeon Matter?
Authors: Julien Dagenais, Riccardo Bertolo, Juan Garisto, Matthew J. Maurice, Pascal Mouracade, Onder Kara, Jaya Chavali, Jianbo Li, Ryan Nelson, Amr Fergany, Robert Abouassaly, Jihad H. Kaouk
Journal: European Urology (2018)
Self-assembly of porphyrin-grafted lipid into nanoparticles encapsulating doxorubicin for synergistic chemo-photodynamic therapy and fluorescence imaging
Authors: Sadaf Hameed, Pravin Bhattarai, Xiaolong Liang, Nisi Zhang, Yunxue Xu, Min Chen, Zhifei Dai
Journal: Theranostics (2018)

The limited clinical efficacy of monotherapies in the clinic has urged the development of novel combination platforms.Taking advantage of light-triggered photodynamic treatment combined together with the controlled release of nanomedicine, it has been possible to treat cancer without eliciting any adverse effects.However, the challenges imposed by limited drug loading capacity and complex synthesis process of organic nanoparticles (NPs) have seriously impeded advances in chemo-photodynamic combination therapy.In this experiment, we utilize our previously synthesized porphyrin-grafted lipid (PGL) NPs to load highly effective chemotherapeutic drug, doxorubicin (DOX) for synergistic chemo-photodynamic therapy.Methods: A relatively simple and inexpensive rapid injection method was used to prepare porphyrin-grafted lipid (PGL) NPs.The self-assembled PGL NPs were used further to encapsulate DOX via a pH-gradient loading protocol.The self-assembled liposome-like PGL NPs having a hydrophilic core were optimized to load DOX at an encapsulation efficiency (EE) of ~99%.The resultant PGL-DOX NPs were intact, highly stable and importantly these NPs successfully escaped from the endo-lysosomal compartment after laser irradiation to release DOX in the cytosol.The therapeutic efficacy of the aforementioned formulation was validated both in vitro and in vivo.Results: PGL-DOX NPs demonstrated excellent cellular uptake, chemo-photodynamic response, and fluorescence imaging ability in different cell lines.Under laser irradiation, cells treated with a low molar concentration of PGL-DOX NPs reduced cell viability significantly.Moreover, in vivo experiments conducted in a xenograft mouse model further demonstrated the excellent tumor accumulation capability of PGL-DOX NPs driven by the enhanced permeability and retention (EPR) effect.Through fluorescence imaging, the biodistribution of PGL-DOX NPs in tumor and major organs was also easily monitored in real time in vivo.The inherent ability of porphyrin to generate ROS under laser irradiation combined with the cytotoxic effect of the anticancer drug DOX significantly suppressed tumor growth in vivo.Conclusion: In summary, the PGL-DOX NPs combined chemo-photodynamic nanoplatform may serve as a potential candidate for cancer theranostics.
Novel Agents and Drug Development Needs in Advanced Clear Cell Renal Cancer
Authors: Thomas Powles, Brian Rini
Journal: Journal of Clinical Oncology (2018)

The treatment of metastatic clear cell renal cancer is changing rapidly, with the focus switching from vascular endothelial growth factor-targeted therapies to immune checkpoint inhibitors and novel combinations. Specifically, recent data with programmed death ligand inhibitors is revolutionizing the standard approach to metastatic renal cell carcinoma. However, there is speculation around a number of newer potentially therapeutic targets, such as indoleamine 2,3-dioxygenase, transforming growth factor-β, interleukin-10, and adenosine. In this article, we review novel treatments, promising combinations, and consideration in both trial design and clinical application of therapeutics that will influence practice in the future.
Abstract 15546: Echo Z-Scores Adjusted for Body Surface Area Are Not Affected by Age, Sex, or Race: The Pediatric Heart Network Normal Echo Database
Authors: Leo Lopez, Steven D Colan, Mario Stylianou, Suzanne Granger, Felicia L Trachtenberg, Peter C Frommelt, Gail D Pearson, Joseph A Camarda, James F Cnota, Meryl S Cohen, Andreea Dragulescu, Michele A Frommelt, Olukayode David Garuba, Tiffanie R Johnson, Wyman W Lai, Joseph Mahgerefteh, Ricardo Pignatelli, Ashwin Prakash, Ritu Sachdeva, Brian D Soriano, Jonathan H Soslow, Christopher Spurney, Shubhika Srivastava, Carolyn L Taylor, Poonam P Thankavel, Mary E van der Velde, L. LuAnn Minich
Journal: Circulation (2017)

Background: Published databases of normal pediatric echo measurements are limited by insufficient sample sizes to assess the effects of age, sex, and race. Variable indexing methods have resulted i...
Normal mortality of the COBRA early rheumatoid arthritis trial cohort after 23 years of follow-up
Authors: Pomme BM Poppelaars, Lilian H D van Tuyl, Maarten Boers
Journal: Annals of the Rheumatic Diseases (2019)

Mortality in patients with rheumatoid arthritis (RA) is higher than in the general population. We investigated mortality in the COBRA-trial cohort after 23 years follow-up, compared with a reference sample of the Dutch population.The COBRA-trial randomised patients with early RA to sulfasalazine monotherapy (SSZ, n=79) or a combination of SSZ, low-dose methotrexate and initially high, step-down prednisolone (COBRA, n=76). We compared the mortality in the COBRA-trial up to 2017 to a reference sample of the general population in the Netherlands (standardised mortality ratio, SMR), and its relation to early prognostic factors through stepwise Cox regression.Duration of follow-up in patients alive was mean 23 (range 22-24) years. In total, 44 patients died (28%, SMR=0.80 [95% CI 0.59 to 1.06]); 20 of 75 COBRA patients (27%, SMR 0.75 [0.47 to 1.14]) and 24 of 79 SSZ patients (30%, SMR 0.85 [0.56 to 1.25]); p=0.61). In the reference sample of the general population, 55 people (36%) died. 5 factors were significantly associated with increased mortality hazard: damage progression at 28 weeks; high Health Assessment Questionnaire (HAQ) score and absence of HLA-DR 2 or 3; disease duration from start of complaints was also significant, but showed an uninterpretable pattern.This prospective trial cohort study of early RA is one of the first to show similar mortality compared with the general population after 23 years of follow-up. It confirms that early, intensive treatment of RA has long-term benefits and suggests that treating to target is especially important for patients with poor prognosis.
Engaging Diverse English- and Spanish-Speaking Older Adults in Advance Care Planning
Authors: Rebecca L. Sudore, Dean Schillinger, Mary T. Katen, Ying Shi, W. John Boscardin, Stacy Osua, Deborah E. Barnes
Journal: JAMA Internal Medicine (2018)

IMPORTANCE Advance care planning improves the receipt of medical care aligned with patients' values; however, it remains suboptimal among diverse patient populations.To mitigate literacy, cultural, and language barriers to advance care planning, easy-to-read advance directives and a patient-directed, online advance care planning program called PREPARE For Your Care (PREPARE) were created in English and Spanish.OBJECTIVE To compare the efficacy of PREPARE plus an easy-to-read advance directive with an advance directive alone to increase advance care planning documentation and patient-reported engagement. DESIGN, SETTING, AND PARTICIPANTSA comparative efficacy randomized clinical trial was conducted from February 1, 2014, to November 30, 2017, at 4 safety-net, primary-care clinics in San Francisco among 986 English-speaking or Spanish-speaking primary care patients 55 years or older with 2 or more chronic or serious illnesses.INTERVENTIONS Participants were randomized to PREPARE plus an easy-to-read advance directive (PREPARE arm) or the advance directive alone.There were no clinician-level or system-level interventions.Staff were blinded for all follow-up measurements. MAIN OUTCOMES AND MEASURESThe primary outcome was documentation of new advance care planning (ie, legal forms and/or documented discussions) at 15 months.Patient-reported outcomes included advance care planning engagement at baseline, 1 week, 3 months, 6 months, and 12 months using validated surveys.Intention-to-treat analyses were performed using mixed-effects logistic and linear regression, controlling for time, health literacy, and baseline advance care planning, clustering by physician, and stratifying by language.RESULTS Among the 986 participants (603 women and 383 men), the mean (SD) age was 63.3 (6.4) years, 387 of 975 (39.7%) had limited health literacy, and 445 (45.1%) were Spanish speaking.No participant characteristic differed between the 2 groups, and retention was 85.9% (832 of 969) among survivors.Compared with the advance directive alone, PREPARE resulted in a higher rate of advance care planning documentation (unadjusted, 43.0% [207 of 481] vs 33.1% [167 of 505]; P < .001;adjusted, 43.0% vs 32.0%; P < .001)and higher self-reported increased advance care planning engagement scores (98.1% vs 89.5%; P < .001).Results remained significant among English speakers and Spanish speakers. CONCLUSIONS AND RELEVANCEThe patient-facing PREPARE program and an easy-to-read advance directive, without clinician-level or system-level interventions, increased documentation of advance care planning and patient-reported engagement, with statistically higher gains for PREPARE vs advance directive alone.These tools may mitigate literacy and language barriers to advance care planning, allow patients to begin planning on their own, and could substantially improve the process for diverse English-speaking and Spanish-speaking populations.
THU0015 Oestrogen dependent regulation of micro-rna in rheumatoid arthritis
Authors: K. Andersson, R. Pullerits, H. Forsblad-d’Elia, M. Erlandsson, S.T. Silfverswärd, M. Bokarewa
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Oestrogen has ameliorating effects on rheumatoid arthritis (RA). Oestrogen receptor (ER) signalling affects micro-RNA (miR) expression and processing in breast cancer, while its effect on miR profile in RA have never been studied. <h3>Objectives</h3> To study the effect of the oestrogen replacement therapy and oestrogen receptor signalling on the miR transcription and bioprocessing in RA patients. <h3>Methods</h3> The expression of the key miR processing enzymes Dicer, Drosha and DGCR8 was measured in the leukocytes of the peripheral blood of 145 female RA patients (age 53 years, disease duration 9.8 years) by RT-PCR and analysed with respect to the levels of ERα, used as surrogate marker of active ERα signalling. Total RNA was prepared from the serum samples of 46 postmenopausal female RA patients who received treatment with oestradiol (E2), noretisterone acetate, vitamin D<sub>3</sub> and calcium (n=22, mean E2 levels 229.4±143.2 pg/ml) or vitamin D<sub>3</sub> and calcium supplementation only (n=24, mean E2 levels 30.8±8.7 pg/ml). Serum was obtained after 12 and 24 months of treatment and was stored at −70 °C until the time of analysis. MicroRNA transcription was performed by 3D-Gene microarray measuring &gt;2560 miRs (TATAA Biocenter, Gothenburg). <h3>Results</h3> A higher ERα expression in RA female patients was associated with increased transcription of the major miR processing proteins Dicer (p=0.0057), Drosha (p=0.019) and DGRC8 (p=0.0095). This activated transcription of miR biomachinery could indicate a higher demand and a facilitated miR maturation. The E2-treatment significantly changed the profile, but not the levels, of miRs in serum, where only 50% of the miR transcripts were present both in E2-treated and control samples. Also the profile of miRs related to RA and of those regulating translation of ERα and Dicer, Drosha, and DGCR8 proteins was affected. Extensive bioinformatic analysis of the miR-targeting genes affected during E2-treatment, revealed a reduction of gene clusters aiding autoimmune pathology and the RA-associated molecular processes including DNA replication (p=2.6x10–4), peptidyl-serine phosphorylation (p=2x10–4), protein localization to nucleus and nuclear import (p=5x10–4). <h3>Conclusions</h3> Activation of ERα significantly enhances the miR processing, and affects the profile of miR transcription in female RA patients. The change in miR profile during E2-treatment could contribute to a significantly change in the miR landscape and disposition of intracellular processes in RA. <h3>Disclosure of Interest</h3> None declared
Antihypertensive drug use and cSCC risk
Authors: K.A. Su, L.A. Habel, N.S. Achacoso, G.D. Friedman, M.M. Asgari
Journal: British Journal of Dermatology (2018)

Over one billion people worldwide have high blood pressure. Many of the medications used to treat high blood pressure are photosensitizing, meaning they make the skin more sensitive to sunlight. As a result, these medications might increase the risk of skin cancer, the most common type of cancer worldwide. This study, from the U.S.A., aimed to find out if people who take blood pressure medications with photosensitizing properties have an increased risk of a certain type of skin cancer called cutaneous squamous cell carcinoma, the second most common type of skin cancer. The researchers identified a group of patients with high blood pressure and looked at what blood pressure medications they took and whether they were ever diagnosed with cutaneous squamous cell carcinoma. The researchers found that patients who take blood pressure medications with photosensitizing properties, including loop diuretics, potassium‐sparing diuretics, and thiazide diuretics, have an increased risk of cutaneous squamous cell carcinoma. The researchers found that the more prescriptions for these medications the patients received, the higher their risk of cutaneous squamous cell carcinoma was. This study suggests that patients taking blood pressure medications with photosensitizing properties may benefit from education on safe sun practices and closer screening for cutaneous squamous cell carcinoma.
Results from Part A of the Hemoglobin Oxygen Affinity Modulation to Inhibit HbS Polymerization (HOPE) Trial (GBT440-031), a Placebo-Controlled Randomized Study Evaluating Voxelotor (GBT440) in Adults and Adolescents with Sickle Cell Disease
Authors: Elliott Vichinsky, Carolyn Hoppe, Jo Howard, Kenneth I. Ataga, Videlis Nduba, Amal El-Beshlawy, David L. Diuguid, Salam Al-Kindi, Clark Brown, Hoda Hassab, Paul Telfer, Dimitris A. Tsitsikas, Selma Unal, Julie Kanter, Miguel R. Abboud, Victor R. Gordeuk, Joshua Lehrer-Graiwer, Claire Sherman, Margaret Tonda, Allison Intondi, Yifah Yaron, Russell E. Ware
Journal: Blood (2018)