tbuckley/cabot-search huggingface dataset:
Patient-reported outcomes as predictors of COPD exacerbations - a prospective study
Authors: Alexandra Strassmann, Anja Frei, Lara Siebeling, Patrick Muggensturm, Marco Zoller, Gerben ter Riet, Milo Puhan
Journal: European Respiratory Journal (2014)

Although patients with Chronic Obstructive Pulmonary Disease (COPD), especially those with frequent exacerbations, show a compromised quality of life in cross-sectional studies, it remains unclear if patient-reported outcomes (PROs) can be used to predict COPD exacerbations. The aim of this study was to identify PROs that are predictors of COPD exacerbations during 2 years of follow-up.

We based the analysis on the prospective ICE COLD ERIC cohort study from Switzerland and the Netherlands (N = 409) that includes COPD patients (aged ≥ 40) with GOLD stages II to IV from general practitioners. PROs included the Chronic Respiratory Questionnaire (CRQ), the Hospital Anxiety and Depression Scale, the Feeling Thermometer, the Physical Activity Questionnaire (LAPAQ) and self-efficacy questions. COPD exacerbations during 2 years after baseline assessment were ascertained through patient self-reports and patient charts and centrally adjudicated by an expert committee (Puhan, M. et al. Eur Respir J 2013;42:956-963). We used negative binomial regression to assess the association of PROs and exacerbations.

After adjusting for age, sex, FEV1, previous exacerbations and smoking status only the CRQ total score (incidence rate ratio per one unit increase in CRQ score [1-7 scale] 0.89, 95% CI 0.79-1.00 p=0.049) and the CRQ dyspnea score (incidence rate ratio 0.90, 95% CI 0.82-0.98, p=0.014) predicted exacerbations statistically significantly. The CRQ fatigue, CRQ mastery and LAPAQ scores showed statistically significant associations in unadjusted analyses only.

The CRQ total and dyspnea scores were significant predictors of exacerbations and may be used in multivariate prediction models to predict COPD exacerbations.
Men and women back male pill
Authors: Bryan Christie
Journal: BMJ (2000)

A study carried out in four cities around the world has found high levels of support among both men and women for a male contraceptive pill. The results are expected to increase the interest of pharmaceutical companies in developing such a pill, which could be available within 5-10 years. Two thirds of the men questioned said that they would use a male pill and nearly all of the women said that they would trust their partners to take it.

The survey, reported in Human Reproduction …
BCR-ABL mRNA levels at and after the time of a complete cytogenetic response (CCR) predict the duration of CCR in imatinib mesylate–treated patients with CML
Authors: Richard D. Press, Zac Love, Ashlie A. Tronnes, Rui Yang, Thuan Tran, Solange Mongoue-Tchokote, Motomi Mori, Michael J. Mauro, Michael W. Deininger, Brian J. Druker
Journal: Blood (2006)
<i>In Utero</i>Exposure to Arsenic Alters Lung Development and Genes Related to Immune and Mucociliary Function in Mice
Authors: Kathryn A. Ramsey, Anthony Bosco, Katherine L. McKenna, Kim W. Carter, John G. Elliot, Luke J. Berry, Peter D. Sly, Alexander N. Larcombe, Graeme R. Zosky
Journal: Environmental Health Perspectives (2012)

Background: Exposure to arsenic via drinking water is a global environmental health problem. In utero exposure to arsenic via drinking water increases the risk of lower respiratory tract infections during infancy and mortality from bronchiectasis in early adulthood.Objectives: We aimed to investigate how arsenic exposure in early life alters lung development and pathways involved in innate immunity.Methods: Pregnant BALB/c, C57BL/6, and C3H/HeARC mice were exposed to 0 (control) or 100 μg/L arsenic via drinking water from gestation day 8 until the birth of their offspring. We measured somatic growth, lung volume, and lung mechanics of mice at 2 weeks of age. We used fixed lungs for structural analysis and collected lung tissue for gene expression analysis by microarray.Results: The response to arsenic was genetically determined, and C57BL/6 mice were the most susceptible. Arsenic-exposed C57BL/6 mice were smaller in size, had smaller lungs, and had impaired lung mechanics compared with controls. Exposure to arsenic in utero up-regulated the expression of genes in the lung involved in mucus production (Clca3, Muc5b, Scgb3a1), innate immunity (Reg3γ, Tff2, Dynlrb2, Lplunc1), and lung morphogenesis (Sox2). Arsenic exposure also induced mucous cell metaplasia and increased expression of CLCA3 protein in the large airways.Conclusions: Alterations in somatic growth, lung development, and the expression of genes involved in mucociliary clearance and innate immunity in the lung are potential mechanisms through which early life arsenic exposure impacts respiratory health.
Senescence bypass screen identifies TBX2, which represses Cdkn2a (p19ARF) and is amplified in a subset of human breast cancers
Authors: Jacqueline J.L. Jacobs, Petra Keblusek, Els Robanus-Maandag, Petra Kristel, Merel Lingbeek, Petra M. Nederlof, Tibor van Welsem, Marc J. van de Vijver, Eugene Y. Koh, George Q. Daley, Maarten van Lohuizen
Journal: Nature Genetics (2000)
Midday in the Harbor
Authors: M. Therese Southgate
Journal: JAMA (1998)

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
Bacteraemia due to OXA-48-carbapenemase-producing Enterobacteriaceae: a major clinical challenge
Authors: C. Navarro-San Francisco, M. Mora-Rillo, M.P. Romero-Gómez, F. Moreno-Ramos, A. Rico-Nieto, G. Ruiz-Carrascoso, R. Gómez-Gil, J.R. Arribas-López, J. Mingorance, J.R. Paño-Pardo
Journal: Clinical Microbiology and Infection (2012)
Abstract 3865: ATOH8 depletion can reprogram noncancer stem cells into cancer stem cells
Authors: Yangyang Song, Xin-Yuan Guan
Journal: Cancer Research (2014)

Abstract Introduction: The development of hepatocellular carcinoma (HCC), one of the most lethal of human malignancies, is caused by the accumulation of multiple genetic and epigenetic alterations. Recent advances in cancer stem cell (CSC) study have associated the poor prognosis of cancer with CSC. ATOH8 is a nucleus factor with an obvious structural similarity to the Drosophila proneural gene atonal. The aim of this study is to investigated the role of ATOH8 in CSC and its therapeutic potentials for HCC treatment. Experimental procedures: The clinical significance of ATOH8 in a cohort of 242 HCC cases was assessed by clinical correlation and Kaplan-Meier survival analyses. ATOH8-overexpressing and scliencing cell model was generated by Lentivirus system to detect its functional roles in HCC both in vivo and in vitro. iPS technology is used to analyze effects of ATOH8 on CSCs. Result: Downregulation of ATOH8 was detected in over 40% of 242 pairs primary HCC cases, which was significantly associated with disease free survival (P=0.031), high level of AFP (P=0.03) and diferentiation (P=0.01). Functional studies demonstrate the tumor suppressive role of ATOH8 in HCC, including the inhibition of cell growth, cell proliferation, tumor formation in SCID mice and cell motility when ATOH8 was introduced into HCC cells. Further study finds that ATOH8 depletion can enhance the stemness of HCC including the tumorigenicity and abilities for self-renewal, differentiation and chemo-resistance by repressing the transcription of stemness-related genes such as OCT4, NANOG, SOX2, AFP, and HCC cancer stem cell (CSC) surface markers such as CD24 and CD133. One interesting finding in this study is that knockdown of ATOH8 could increase CD133+ cell population in QSG7701 and BEL7402 cells. CD133+ cells induced by ATOH8 depletion were flow-sorted and their CSC property was characterized. The results found that flow-sorted CD133+ cells induced by ATOH8 depletion possessed most characteristics of CSC including the capacity to self-renew, differentiation, sustained proliferation and chemoresistance. In addition, ATOH8 depletion could enhance the frequency of pluripotent stem cells (iPSC) generation induced by 4 factors (OCT4, Sox2, Klf4 and cMyc). All these data strongly suggest that a non-CSC could be reprogrammed into a CSC under some circumstance such as downregulation of ATOH8. Conclusion: This study demonstrates that ATOH8 plays an important role in HCC development, and provides a potential new HCC therapeutic approach that ATOH8 could increase the chemosensitivity of HCC cells to chemotherapeutics as demonstrated in this study. Citation Format: Yangyang Song, Xin-Yuan Guan. ATOH8 depletion can reprogram noncancer stem cells into cancer stem cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3865. doi:10.1158/1538-7445.AM2014-3865
Perceptions of Safety Are Shaped by the Hospital Environment—Reply
Authors: Henry J. Michtalik, Peter J. Pronovost, Daniel J. Brotman
Journal: JAMA Internal Medicine (2013)

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
Geographic Variation in Hospitalization for Lower Respiratory Tract Infections Across One County
Authors: Andrew F. Beck, Todd A. Florin, Suzanne Campanella, Samir S. Shah
Journal: JAMA Pediatrics (2015)

Bronchiolitis and pneumonia are leading causes of pediatric hospitalizations. Identifying geographic patterns in hospitalization rates across small geographic areas could be particularly relevant to targeted patient-level and population-level health care.
Abstract 18458: A Novel Flow-chamber System for Quantitative Assessment of Whole Blood Thrombogenicity in Patients Undergoing Elective Percutaneous Coronary Intervention
Authors: Yuichiro Arima, Koichi Kaikita, Takamichi Ono, Satomi Iwashita, Miwa Ito, Masanobu Ishii, Kenichi Tsujita, Kenji Sakamoto, Eiichiro Yamamoto, Tomoko Tanaka, Sunao Kojima, Seiji Hokimoto, Hisao Ogawa
Journal: Circulation (2014)

Accurate evaluation of the clotting ability is important for patients undergoing percutaneous coronary intervention (PCI) to prevent thrombotic or bleeding complications. Recently, the Total Thrombus-formation Analysis System (T-TAS) was developed for quantitative analysis of platelet thrombus formation (PTF) using microchips with thrombogenic surfaces (collagen, PL chip; collagen plus tissue factor, AR chip) under shear stress conditions. In the present study, we evaluated the usefulness of the T-TAS for the assessment of whole blood thrombogenicity in patients undergoing PCI treated with antiplatelet therapy (APT). Consecutive 160 patients were divided into 3 groups; patients without any antiplatelet therapy (Control, n=30), with single antiplatelet therapy treated with aspirin (SAPT, n=31), and with dual antiplatelet therapy treated with aspirin and clopidogrel (DAPT, n=99). Blood samples obtained on admission were applied to the T-TAS to measure PTF area under the curve (PL-AUC, area under curve until 10 min for PL chip; AR-AUC, 30 min for AR chip) under various shear rates (1500, 2000 s–1 for PL chip; 300 s–1 for AR chip). Platelet functions were also tested using VerifyNow system. PL-AUC levels decreased significantly in SAPT and DAPT compared with Control group, while the levels were significantly lower in DAPT compared with SAPT (SAPT: 280.9±83.2, DAPT: 118.3±87.8, and Control: 355.2±90.8, p
Abstract 1705: Combinatorial therapeutics with targeting head and neck cancer initiating cells using active components from antrodia cinnamomea and conventional chemotherapy
Authors: Ching-Wen Chang, Jeng-Fan Lo
Journal: Cancer Research (2014)

Abstract Background: Cancer initiating cells (CICs), also termed as Cancer stem cells (CSCs), represent a rare subpopulation of cells, which are responsible for tumor growth. CICs such as head and neck cancer initiating cells (HN-CICs), are often resistant to either radio- or chemotherapy. Therefore, development for drug candidates that target HN-CICs specifically will be effective for future oral cancer therapy. Methods: In this study, we used the in vitro cell-based aldehyde dehydrogenase (ALDH) activity assay system, which has been demonstrated as a CICs marker, to screen for the active purified components from Antrodia Camphorata Mycelia extract (ACME), which can target HN-CICs. Next, the antitumorigenicity of combinatorial treatment with active components from ACME and conventional chemotherapy on HNSCC will be examined in vitro and in vivo. Results: Herein, we first screened for the active components from natural products of ACM significantly down regulate the ALDH activity and CD44 positivity of Head and neck squamous cell carcinoma (HNSCC). Consequently, treatment of YMGKI-2 (analogue of ergosterol), a single and active compound purified from ACME, not only inhibited the ALDH activity but also reduced self-renewal property and expression of stemness genes (Oct-4 and Nanog) in enriched HN-CICs. Moreover, the repressive HN-CICs properties by YMGKI-2 treatment were caused by promoting cell differentiation. Additionally, treatment of YMGKI-2 results in down-regulation of Cox-2 and Src molecular mechanisms which both play important role in CICs. Further, the tumorigenic properties of HNSCC cells were attenuated by YMGKI-2 treatment in vivo. Lastly, combinatorial treatments with YMGKI-2 and standard chemotherapeutic drugs reveal synergistic effects on killing both HN-CICs and non-HN-CICs in vitro and in vivo. Conclusion: Together, our results indicate that YMGKI-2 treatment significantly and selectively abolished the stemness properties and tumorigenicity of HN-CICs. These findings provide a new drug candidate from purified components of ACM as an alternative therapy in combination with conventional chemotherapy treatment modalities for head and neck cancer in the future. Citation Format: Ching-Wen Chang, Jeng-Fan Lo. Combinatorial therapeutics with targeting head and neck cancer initiating cells using active components from antrodia cinnamomea and conventional chemotherapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1705. doi:10.1158/1538-7445.AM2014-1705
Psychiatric training in the UK: the next steps
Authors: DINESH BHUGRA
Journal: World Psychiatry (2008)

Postgraduate education and training in the UK is undergoing tremendous change. In this paper the changes affecting psychiatry are described, with an account of the drivers. Patients, their carers and politicians all expect psychiatric service providers to have certain characteristics. Psychiatric training is becoming more competency focused and it is right that assessments of competencies also occur at the place that trainees work. There are key competencies that trainees need to take into account while learning and working. These are described along with the way forward.
Validation of bovine hoof slices as a model for infected human toenails: in vitro ciclopirox transungual permeation
Authors: D. Monti, L. Saccomani, P. Chetoni, S. Burgalassi, S. Tampucci, F. Mailland
Journal: British Journal of Dermatology (2011)

Topical therapy has recently been proposed for treating onychomycosis and other nail disturbances. However, the clinical outcome may be limited by the difficulty of active ingredients effectively penetrating the nail plate. Bovine hoof membranes have been widely used to predict in vitro efficacy of drug products in nail diseases. Many studies have compared bovine hooves with human healthy nails, considering the difference between healthy and unhealthy nails to be negligible.To validate bovine hoof slices as a model for human unhealthy nails by investigating the transungual permeation/retention of ciclopirox (CPX) through bovine hoof slices and excised infected human toenails after application of a new film-forming formulation (P-3051). To investigate the ability of CPX to achieve fungicidal concentrations in and through infected toenails.A new experimental technique based on a permeation unit allowed analysis by high-performance liquid chromatography of the amounts of CPX permeating through and retained in the membranes. The efficacy index was evaluated as follows: amount of permeated CPX/Trichophyton rubrum minimum inhibiting concentration.Extrapolated CPX flux through bovine hoof slices was about 14-fold higher than through infected human toenails, the difference being mainly due to the fourfold higher thickness of the toenails. In toenails, the CPX efficacy index for T. rubrum was positive (>1·0) soon after P-3051 application.This study confirms the validity of bovine hoof slices as a model for infected human nails, and suggests a substantial equivalence between the two models. Following P-3051 application, CPX reaches fungicidal concentrations in and through human infected toenails.
Abstract IA12: Preclinical models for targeting oncogenic Ras signaling in cancer
Authors: Kevin Shannon
Journal: Cancer Research (2015)

Abstract Somatic RAS mutations occur in 30% of human cancers, and are common in both melanoma and hematopoietic cancers. Importantly, whereas KRAS mutations predominate in epithelial cancers, NRAS is mutated much more often in melanoma and hematopoietic cancers. The most obvious therapeutic strategy for cancers with RAS mutations – developing specific inhibitors of the mutant protein – is extremely challenging due to the very high affinity of Ras for GTP, structural considerations of the Ras/GTPase activating protein (Ras/GAP) molecular switch, and the loss of normal enzymatic activity as a consequence of oncogenic RAS mutations. Given these issues, most recent drug discovery efforts have focused on inhibiting downstream biochemical targets of mutant Ras such as Raf, MEK, and Akt with many compounds undergoing clinical evaluation. We have exploited strains of mice that recapitulate endogenous expression of cancer-associated RAS alleles or NF1 inactivation to model human hematologic cancers and to conduct biologic and preclinical studies. In particular, we have deployed the MOL4070LTR retrovirus as an insertional mutagen to generate genetically heterogeneous transplantable myeloid and lymphoid leukemias characterized by hyperactive Ras signaling. We utilize cohorts of mice that are engrafted with the same primary leukemias for preclinical testing. In this presentation, I will focus on three biologic and therapeutic questions related to NRAS in tumorigenesis: (1) loss of the normal NRAS allele in cancers with oncogenic NRAS mutations; (2) responses of primary Nras mutant leukemias to MEK and PI3 kinase inhibitors; and, (3) potential strategies for selectively targeting oncogenic N-Ras in cancer. Note: This abstract was presented as part of the Joint Session: Clinical Science Interactions between Melanoma and Hematologic Malignancies with the AACR Special Conference: Hematologic Malignancies: Translating Discoveries to Novel Therapies held September 20-23, 2014 in Philadelphia, PA. Citation Format: Kevin Shannon. Preclinical models for targeting oncogenic Ras signaling in cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr IA12.
Prognostic implications of determining 180 kDa bullous pemphigoid antigen (BPAG2) gene/protein pathology in neonatal junctional epidermolysis bullosa
Authors: None Mellerio, None Denyer, None Atherton, None Eady, None Mcgrath
Journal: British Journal of Dermatology (1998)

Epidermolysis bullosa (EB) in neonates is often difficult to characterize, both in terms of making a precise diagnosis and in being able to comment accurately on the prognosis for the affected child. We present a case of a neonate with inherited mucocutaneous fragility and failure to thrive and detail our laboratory approach for classifying the subtype of EB in this child. Mutational analysis revealed a homozygous non-sense mutation in the gene encoding the 180 kDa bullous pemphigoid antigen, also known as type XVII collagen, predicting a non-lethal form of junctional EB. Identification of the underlying molecular pathology in this case was of use in improving diagnosis, classification, management and counselling.