tbuckley/cabot-search huggingface dataset:
Where next for cell-based therapy in ARDS
Authors: Andrew James Boyle, Cecilia M O’Kane, Daniel Francis McAuley
Journal: Thorax (2018)

Acute respiratory distress syndrome (ARDS) is a form of acute hypoxaemic respiratory failure that is characterised by non-cardiogenic pulmonary oedema which occurs as a consequence of the breakdown of the alveolar–capillary unit.1 ARDS impacts more than 10% of all intensive care unit admissions, and pneumonia is the most common risk factor for ARDS.2 Current standard of care aims to minimise iatrogenic lung injury from mechanical ventilation,3 4 while clinical trials of pharmacological therapies that have targeted the underlying mechanisms driving the development of ARDS have failed to show benefit.5 

Beyond pharmacological therapies, much interest in this field has focused on mesenchymal stromal cells (MSCs) as a potential therapeutic option for ARDS.6 In the latest development towards a cell-based therapy for ARDS, Park et al  report the use of an human ex vivo lung perfusion model of ARDS to investigate MSC-derived microvesicles (MVs) as a therapy for ARDS.7 MSCs are pluripotent cells that can be extracted from various sources including bone marrow, adipose tissue and umbilical cord. In ARDS they may represent an attractive therapy because of a broad range of potentially beneficial effects, including anti-inflammatory, pro-reparative and antimicrobial effects.8–10 Excessive host inflammation contributes to alveolar epithelial and capillary endothelial damage, and in this setting MSCs have immunomodulatory effects via the secretion of several anti-inflammatory compounds including Interleukin (IL) 10 and IL1 receptor antagonist. Loss of alveolar fluid clearance (AFC) in patients with ARDS contributes to alveolar flooding and is associated with increased hospital mortality.11 The delivery of MSCs to injured lungs restored AFC in a human ex vivo model of lung injury. This effect was in-part mediated by the secretion of keratinocyte growth factor (KGF), one of several soluble growth factors produced by MSCs.12 Approximately …
Abstract 11106: The Incidence of Sudden Cardiac Arrest Continues to Rise, but Outcome is at a Standstill in South Korea: Analyzed From National Health Insurance Database Cohort From 2003 to 2013
Authors: Pil-sung Yang, Hancheol Lee, Tae-Hoon Kim, Jae-Sun Uhm, Hui-Nam Pak, Moon-Hyoung Lee, Boyoung Joung
Journal: Circulation (2015)

Introduction: Sudden cardiac arrest (SCA) is a major clinical and public health problem. South Korea is aging faster than any other country, and the disease spectrum has changed profoundly in the last few decades. The purpose of this study was to investigate the change of the incidence and outcome of SCA over the past ten years. Methods: With the use of the National Health Insurance Database Cohort (NHID-Cohort) consisting of one million patients from 2003 through 2013, we identified the patient with sudden cardiac arrest using Korean Standard Classification of Diseases, 6th Revision, code I46. Results: In all, 5,307 (0.52%) patients with SCA were identified between 2003 and 2013. SCA occurred more frequent in men (59.3%) than women (40.7%) (p&lt;0.001). The annual incidence of SCA increased by 116.3% from 28.9 in 2003 to 62.5 in 2013 (per 100,000 person-year, p&lt;0.001). The increase of SCA was particularly predominant in patients with ≥60 years of age (from 153.8 to 259.1 per 100,000 person-year, p&lt;0.001) and those with low economic status (from 27.5 to 85.2 per 100,000 person-year, p&lt;0.001). Health care cost per 100,000 person-year also increased from $65,866 in 2003 to $241,534 in 2013 (p&lt;0.001). However, there was no significant improvement in one-month survival rate during the same period (11.9% in 2003, 13.4% in 2013, p=0.526). Conclusions: The incidence of SCA in South Korea continues to rise over the past ten years, especially in elderly people. Despite the tremendous advances in the field of cardiovascular medicine, outcome of SCA is at a standstill.
The Osteogenic Niche Is a Calcium Reservoir of Bone Micrometastases and Confers Unexpected Therapeutic Vulnerability
Authors: Hai Wang, Lin Tian, Jun Liu, Amit Goldstein, Igor Bado, Weijie Zhang, Benjamin R. Arenkiel, Zonghai Li, Meng Yang, Shiyu Du, Hong Zhao, David R. Rowley, Stephen T.C. Wong, Zbigniew Gugala, Xiang H.-F. Zhang
Journal: Cancer Cell (2018)
Competing Risks for a Diagnosis of Invasive Breast Cancer
Authors: Nicholas L. Syn
Journal: JAMA Oncology (2018)

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 Oncology 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 Oncology journal
Patient-Reported Outcomes and Factors Associated With Patient Satisfaction After Surgical Treatment of Facial Nonmelanoma Skin Cancer
Authors: Sarah E. Sasor, Julia A. Cook, Scott N. Loewenstein, William A. Wooden, Adam C. Cohen, Michael W. Chu, Sunil S. Tholpady
Journal: JAMA Surgery (2018)

and began covering outpatient knee replacements.It is unknown how these changes will affect hospital performance under the CJR program.Evidence suggests that bundled payments effectively reduce health expenditures. 5However, our findings suggest heterogeneous effects of the CJR program across different hospital types.Particularly, the SNHs were less likely to receive high reconciliation payments, indicating that the CJR program might disproportionately benefit hospitals that serve patients with higher socioeconomic status.In the interest of promoting equity in health care, future modifications of the CJR program might consider ways to counteract these potential imbalances.
Senescent phenotype of tumor-associated endothelial cells
Authors: Christiana Charalambous, Adel Kardosh, Lubna Qazi-Abdullah, Raphael Zidovetzki, Axel H. Schonthal, Thomas C. Chen, Florence M. Hofman
Journal: Cancer Research (2006)

1047  Blood vessels in solid tumors are structurally and functionally aberrant compared to vessels in normal tissue. To elucidate the nature of these abnormal features, we examined endothelial cells derived from human glioblastoma tumors. Our results provide the first demonstration that tumor-derived brain endothelial cells (TuBEC) have properties of senescent cells. Primary cultures of TuBEC exhibit senescence-associated β-galactosidase staining, cell cycle arrest at G0/G1, and increased levels of the cell cycle inhibitors p21 and p27, compared to normal brain endothelial cells (BEC). In addition, glioblastoma tissue sections expressed senescence-associated β-galactosidase, in contrast to normal brain tissue which was negative. TuBEC also demonstrate decreased expression of cyclin A and increased expression of cyclin D1 and the tumor suppressor protein p53. In addition, TuBEC demonstrate resistance to cytotoxic and cytostatic drugs currently used for glioblastoma treatment, and increased production of growth factors, such as PDGF. Furthermore, long-term culture of BEC in glioma cell conditioned media induced the appearance of β-galactosidase positive cells in the BEC population. These findings propose a novel aspect of tumor-endothelial cell interaction, whereby tumors not only stimulate angiogenesis, but also induce endothelial cells to become senescent. Thus, these results suggest that anti-angiogenic therapies need to target the unique tumor-associated endothelial cells population as well as the actively proliferating vasculature.
Inhibition of IL-6 and IL-8 enhances chemosensitization in multidrug resistant human breast cancer cells
Authors: Weimin Yang, Li-Pai Chen, Ruochun Huang, Ruo-Pan Huang
Journal: Cancer Research (2005)

5079  Drug resistance remains as a major hurdle to successful cancer treatment. Many mechanisms such as overexpression of multidrug resistant protein, increased turnover of drug metastasis, decreased apoptosis and impairment of signal transduction pathway can contribute multidrug resistance. Recent studies strongly suggest a close link between cytokines and drug resistance. To identify new targets involved in drug resistance, we established a multidrug resistant human breast cancer cell line MCF-7/R and examined the cytokine profile using cytokine antibody array technology. Among 120 cytokines/chemokines screened, IL-6, IL-8 and other 13 proteins were found to be markedly increased in drug resistant MCF-7/R cell line as compared to sensitive MCF-7/S cell line, while 7 proteins were specifically reduced in drug resistant MCF-7/R cells. Neutralizing antibody against IL-6 and IL-8 partially reversed the drug-resistance of MCF-7/R to taxol and doxorubicin, but neutralizing antibody of MCP-1 had no significant effect. Inhibition of endogenous IL-6 or IL-8 by siRNA technology significantly enhanced drug sensitivity of MCF-7/R cells. The drug sensitivity was not related to multidrug resistant protein since the expression of multidrug resistant protein remained unchanged in both IL-6 and IL-8 siRNA transfected cells. Our data suggest that increased expression levels of IL-6 and IL-8 may contribute to multidrug resistance in human breast cancer cells.
Genetic models reveal origin, persistence and non-redundant functions of IL-17–producing γδ T cells
Authors: Inga Sandrock, Annika Reinhardt, Sarina Ravens, Christoph Binz, Anneke Wilharm, Joana Martins, Linda Oberdörfer, Likai Tan, Stefan Lienenklaus, Baojun Zhang, Ronald Naumann, Yuan Zhuang, Andreas Krueger, Reinhold Förster, Immo Prinz
Journal: The Journal of Experimental Medicine (2018)

γδ T cells are highly conserved in jawed vertebrates, suggesting an essential role in the immune system. However, γδ T cell-deficient Tcrd-/- mice display surprisingly mild phenotypes. We hypothesized that the lack of γδ T cells in constitutive Tcrd-/- mice is functionally compensated by other lymphocytes taking over genuine γδ T cell functions. To test this, we generated a knock-in model for diphtheria toxin-mediated conditional γδ T cell depletion. In contrast to IFN-γ-producing γδ T cells, IL-17-producing γδ T cells (Tγδ17 cells) recovered inefficiently after depletion, and their niches were filled by expanding Th17 cells and ILC3s. Complementary genetic fate mapping further demonstrated that Tγδ17 cells are long-lived and persisting lymphocytes. Investigating the function of γδ T cells, conditional depletion but not constitutive deficiency protected from imiquimod-induced psoriasis. Together, we clarify that fetal thymus-derived Tγδ17 cells are nonredundant local effector cells in IL-17-driven skin pathology.
Abstract P161: Effect of Yoga Program on Cardiovascular Function in Elderly with Stage-I Hypertension
Authors: Satish G Patil
Journal: Circulation (2016)

Introduction: Hypertension is a major cause of cardiovascular (CV) morbidity and mortality in elderly population. Hypertension along with aging leads to left ventricular hypertrophy, systolic and diastolic dysfunction and congestive heart failure. We aimed to determine the effect of yoga program on cardiovascular indices in elderly with stage-I hypertension. Hypothesis: We hypothesize that yoga lifestyle modality may induce significant beneficial changes in cardiovascular function in elderly individuals with hypertension. Yoga program may be more beneficial than walking for cardiovascular health in elderly. Methods: A parallel arm, open label, single blind, randomized controlled study was conducted on elderly people with stage-I hypertension aged above 60 years (n=44). Yoga group (n=24) was assigned for yoga practice (includes asanas, pranayama and meditation) and control group (n=20) for brisk-walk for one hour in the morning for 6 days in a week for three months. The outcome measures were cardiovascular indices derived from pulse wave analysis such as left ventricular ejection time (ET), diastolic time (DT) pulse duration (PD), percentage of mean arterial pressure (%MAP), upstroke time (UT), ejection slope (ES), ejection duration index (ED%), pre-ejection period (PEP), and heart rate. Results: The mean within-yoga group change in PD(ms) was -50.29 (CI=-98.5, -2.07; p=0.042), DT(ms): -49.04 (CI=-88.47, -9.61; p=0.017), ED%: 2.107 (CI=0.92, 3.28; p=0.001), HR(bpm): 4.41 (CI=0.43, 8.4; p=0.031), %MAP: 2.08 (CI=0.71, 3.44; p=0.04), ES (mmHg/ms): 14.62 (CI=-3.99, 33.24; p=0.118), ET (ms): -0.66 (CI=11.89, 10.55; p=0.903), UT(ms): -2.54 (CI=14.95, 9.87; p=0.676), PEP (ms): -1.25 (CI=-4.17, 1.67; p=0.11). The mean within-control group change in PD(ms) was 11.15 (CI=-52.26, 74.56; p=0.717), DT(ms): 11.3 (CI=-50.56, 73.16; p=0.706), ED%: -0.101 (CI=-2.7, 2.5; p=0.936), HR (bpm): 0.35 (CI=-4.71, 5.41; p=0.887), %MAP: 0.65 (CI=-1.11, 2.41; p=0.451), ES(mmHg/ms): 0.75 (CI=-15.8, 17.38; p=0.926), ET(ms): 2.2 (CI=-10.5, 14.9; p=0.721), UT(ms): 4.7 (CI=-8.19, 17.59; p=455), PEP (ms): 2.1 (CI=-0.52, 4.72; p=0.11). Analysis of Covariance showed a significant change between-groups in PD (p=0.021), DT (p=0.02), UT (p=0.048), ED% (p=0.049), HR (p=0.036) while no significant difference was observed in ES (p=0.248), ET (p=0.245), PEP (p=0.102) and %MAP (p=0.262). Conclusions: These findings indicate that the yoga practice can induce beneficial changes in cardiovascular function in elderly hypertensive subjects. Further, yoga may be better than walking in improving cardiac health in older individuals.
A Novel Exercise Intervention and Functional Status in Very Elderly Patients During Acute Hospitalization
Authors: William J. Hall
Journal: JAMA Internal Medicine (2018)

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
A modified clinicopathological tumor staging system for survival prediction of patients with penile cancer
Authors: Zai‐Shang Li, Antonio Augusto Ornellas, Christian Schwentner, Xiang Li, Alcides Chaux, Georges Netto, Arthur L. Burnett, Yong Tang, JiunHung Geng, Kai Yao, Xiao‐Feng Chen, Bin Wang, Hong Liao, Nan Liu, Peng Chen, Yong‐Hong Lei, Qi‐Wu Mi, Hui‐Lan Rao, Ying‐Ming Xiao, Qi‐Lin Wang, Zi‐Ke Qin, Zhuo‐Wei Liu, Yong‐Hong Li, Zi‐Jun Zou, Jun‐Hang Luo, Hui Li, Hui Han, Fang‐Jian Zhou
Journal: Cancer Communications (2018)

Abstract Background The 8th American Joint Committee on Cancer tumor–node–metastasis (AJCC‐TNM) staging system is based on a few retrospective single‐center studies. We aimed to test the prognostic validity of the staging system and to determine whether a modified clinicopathological tumor staging system that includes lymphovascular embolization could increase the accuracy of prognostic prediction for patients with stage T2–3 penile cancer. Methods A training cohort of 411 patients who were treated at 2 centers in China and Brazil between 2000 and 2015 were staged according to the 8th AJCC‐TNM staging system. The internal validation was analyzed by bootstrap‐corrected C‐indexes (resampled 1000 times). Data from 436 patients who were treated at 15 centers over four continents were used for external validation. Results A survivorship overlap was observed between T2 and T3 patients ( P = 0.587) classified according to the 8th AJCC‐TNM staging system. Lymphovascular embolization was a significant prognostic factor for metastasis and survival (all P &lt; 0.001). Based on the multivariate analysis, only lymphovascular embolization showed a significant influence on cancer‐specific survival (CSS) (hazard ratio = 1.587, 95% confidence interval = 1.253–2.011; P = 0.001). T2 and T3 patients with lymphovascular embolization showed significantly shorter CSS than did those without lymphovascular embolization ( P &lt; 0.001). Therefore, a modified clinicopathological staging system was proposed, with the T2 and T3 categories of the 8th AJCC‐TNM staging system being subdivided into two new categories as follows: t2 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra without lymphovascular invasion, and t3 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra with lymphovascular invasion. The modified staging system involving lymphovascular embolization showed improved prognostic stratification with significant differences in CSS among all categories (all P &lt; 0.005) and exhibited higher accuracy in predicting patient prognoses than did the 8th AJCC‐TNM staging system (C‐index, 0.739 vs. 0.696). These results were confirmed in the external validation cohort. Conclusions T2–3 penile cancers are heterogeneous, and a modified clinicopathological staging system that incorporates lymphovascular embolization may better predict the prognosis of patients with penile cancer than does the 8th AJCC‐TNM staging system. Trial registration This study was retrospectively registered on Chinese Clinical Trail Registry: ChiCTR16008041 (2016‐03‐02). http://www.chictr.org.cn
Diagnostic accuracy of leptospirosis whole-cell lateral flow assays: a systematic review and meta-analysis
Authors: M.J. Maze, K.J. Sharples, K.J. Allan, M.P. Rubach, J.A. Crump
Journal: Clinical Microbiology and Infection (2018)

BackgroundLeptospirosis is under-diagnosed by clinicians in many high-incidence countries, because reference diagnostic tests are largely unavailable. Lateral flow assays (LFA) that use antigen derived from heat-treated whole cell Leptospira biflexa serovar Patoc have the potential to improve leptospirosis diagnosis in resource-limited settings.ObjectivesWe sought to summarize estimates of sensitivity and specificity of LFA by conducting a systematic review and meta-analysis of evaluations of the accuracy of LFA to diagnose human leptospirosis.Data sourcesOn 4 July 2017 we searched three medical databases.Study eligibility criteriaArticles were included if they were a study of LFA sensitivity and specificity.ParticipantsPatients with suspected leptospirosis.InterventionsNil.MethodsFor included articles, we assessed study quality, characteristics of participants and diagnostic testing methods. We estimated sensitivity and specificity for each study against the study-defined case definition as the reference standard, and performed a meta-analysis using a random-effects bivariate model.ResultsOur search identified 225 unique reports, of which we included nine (4%) published reports containing 11 studies. We classified one (9%) study as high quality. Nine (82%) studies used reference tests with considerable risk of misclassification. Our pooled estimates of sensitivity and specificity were 79% (95% CI 70%–86%) and 92% (95% CI 85%–96%), respectively.ConclusionsAs the evidence base for determining the accuracy of LFA is small and at risk of bias, pooled estimates of sensitivity and specificity should be interpreted with caution. Further studies should use either reference tests with high sensitivity and specificity or statistical techniques that account for an imperfect reference standard.
Neuroendocrine Liver Metastasis—a Specific Set of Markers to Detect Primary Tumor Sites
Authors: Andreas Selberherr, Oskar Koperek, Philipp Riss, Christian Scheuba, Reto Kaderli, Aurel Perren, Bruno Niederle
Journal: Endocrine Pathology (2018)

The diagnosis of neuroendocrine neoplasia (NEN) is often made at an advanced stage of disease, including hepatic metastasis. At this point, the primary may still be unknown and sometimes cannot even be detected by functional imaging, especially in very small tumors of the pancreas (pan) and small intestinal (si) entities. The site of the primary may be based on biopsy specimens of the liver applying a specific set of markers. Specimens of liver metastases from 87 patients with NENs were studied. In retrospect, 50 patients had si and 37 pan NENs. Tissue samples were evaluated by immunohistochemistry. The markers applied were insulin gene enhancer protein Islet-1 (ISL-1), homeobox protein CDX-2 (CDX2), thyroid transcription factor 1 (TTF-1), and serotonin. Positive stains for CDX2 were documented in 43 (86%) and for serotonin in 45 (90%) of 50 siNENs. Three panNENs were positive for CDX2 and one for serotonin, respectively. ISL-1 was negative throughout in siNENs and also negative in 8 of 50 panNENs (21.6%). TTF-1 was negative in more than 90% of the specimens of either entity. Immunohistochemical markers in liver metastasis can lead the way to the site of the primary NEN. They should always be used in combined clusters.