tbuckley/cabot-search huggingface dataset:
Congestive Heart Failure Cardiopoietic Regenerative Therapy (<scp>CHART</scp>‐1) trial design
Authors: Jozef Bartunek, Beth Davison, Warren Sherman, Thomas Povsic, Timothy D. Henry, Bernard Gersh, Marco Metra, Gerasimos Filippatos, Roger Hajjar, Atta Behfar, Christian Homsy, Gad Cotter, William Wijns, Michal Tendera, Andre Terzic
Journal: European Journal of Heart Failure (2015)

Abstract Aims Cardiopoiesis is a conditioning programme that aims to upgrade the cardioregenerative aptitude of patient‐derived stem cells through lineage specification. Cardiopoietic stem cells tested initially for feasibility and safety exhibited signs of clinical benefit in patients with ischaemic heart failure ( HF ) warranting definitive evaluation. Accordingly, CHART ‐1 is designed as a large randomized, sham‐controlled multicentre study aimed to validate cardiopoietic stem cell therapy. Methods Patients ( n = 240) with chronic HF secondary to ischaemic heart disease, reduced LVEF (&lt;35%), and at high risk for recurrent HF ‐related events, despite optimal medical therapy, will be randomized 1:1 to receive 600 × 10 6 bone marrow‐derived and lineage‐directed autologous cardiopoietic stem cells administered via a retention‐enhanced intramyocardial injection catheter or a sham procedure. The primary efficacy endpoint is a hierarchical composite of mortality, worsening HF , Minnesota Living with Heart Failure Questionnaire score, 6 min walk test, LV end‐systolic volume, and LVEF at 9 months. The secondary efficacy endpoint is the time to cardiovascular death or worsening HF at 12 months. Safety endpoints include mortality, readmissions, aborted sudden deaths, and serious adverse events at 12 and 24 months. Conclusion The CHART ‐1 clinical trial is powered to examine the therapeutic impact of lineage‐directed stem cells as a strategy to achieve cardiac regeneration in HF populations. On completion, CHART ‐1 will offer a definitive evaluation of the efficacy and safety of cardiopoietic stem cells in the treatment of chronic ischaemic HF . Trial registration: NCT01768702
Priscilla Kincaid-Smith
Authors: Ned Stafford
Journal: BMJ (2015)

At concentrations found in human after ingestion of 1-2 cups of green tea, Epicatechin-3-gallate (ECG) modulates Na/K-ATPase conformation and activity. Akin to ouabain, an archetypal Na/K-ATPase ligand of the cardiotonic steroids (CTS) family, ECG also activates PKCɛ translocation and increases the force of contraction of the rat heart. This study evaluated whether, like ouabain, ECG also modulates Na/K-ATPase/Src receptor function and triggers pre- and post-conditioning against ischemia/reperfusion (I/R) injury. In vitro, ECG activated the purified Na/K-ATPase/Src complex. In Langendorff-perfused rat hearts, sub-micromolar concentrations of ECG administered either before or after ischemia reduced infarct size by more than 40%, decreased lactate dehydrogenase release, and improved the recovery of cardiac function. ECG protection was blocked by PKCɛ inhibition and attenuated by mitochondrial KATP channel inhibition. In a unique mammalian cell system with depleted Na/K-ATPase α1 expression, ECG-induced PKCɛ activation persisted but protection against I/R was blunted. Taken together, these results reveal a Na/K-ATPase- and PKCɛ-dependent mechanism of protection by ECG that is also distinct from the mechanism of action of ouabain. These ECG properties likely contribute to the positive impact of green tea consumption on cardiovascular health and warrant further investigation into the role of cardiac Na/K-ATPase signaling in the cardioprotective effect of green tea consumption. <h3>SIGNIFICANCE STATEMENT</h3> Consumption of green tea, the richest dietary source of ECG, is associated with a reduced risk of cardiac mortality. Anti-oxidant effects of ECG and other tea polyphenols are well known, but reported for concentrations well above dietary levels. Therefore, the mechanism underlying the cardioprotective effect of green tea remains incompletely understood. This study provides experimental evidence that ECG concentrations commonly detected in human after consumption of a cup of tea trigger Na/K-ATPase/Src receptor in a cell-free system, activate a CTS-like signaling pathway, and provide PKCε-dependent protection against ischemia/reperfusion injury in rat hearts. Mechanistic studies in mammalian cells with targeted Na/K-ATPase depletion revealed that although Na/K-ATPase does not mediate ECG-induced PKCɛ activation, it is required for ECG-induced protection against ischemia/reperfusion injury.
Efficacy and safety of fluticasone propionate/formoterol in paediatric patients with asthma
Authors: Anna Ploszczuk, Miroslava Bosheva, Kay Spooner, Tammy McIver, Sanjeeva Dissanayake
Journal: European Respiratory Journal (2014)

Background: 

Fluticasone propionate (FP) and formoterol (FORM) have been combined in a single inhaler (FP/FORM; flutiform ® ) for the treatment of adolescents and adults with asthma. This study assessed the efficacy and safety of FP/FORM in paediatric asthma patients.

Methods: 

A total of 512 patients aged 5 to <12yrs were randomised 1:1:1 to 12 weeks of treatment with either FP/FORM (100/10µg BID), FP 100µg BID) or fluticasone propionate/salmeterol (FP/SAL) (100/50µg BID) in a double-blind, parallel group, multicentre study. The objectives were to demonstrate superiority of FP/FORM to FP and non-inferiority to FP/SAL. The primary endpoint was the change from predose FEV1 at baseline to 2-hour postdose FEV1 over the 12 weeks. The two key secondary endpoints were FEV1 AUC0-4h at Week 12 and change from pre-dose FEV1 over the 12 weeks.

Results: 

FP/FORM was superior to FP for change from predose FEV1 at baseline to 2-hour postdose FEV1 (treatment difference = 0.07L; 95%CI: 0.03, 0.11; P<0.001) and FEV1 AUC0-4h at Week 12 (treatment difference = 0.09L; 95%CI: 0.04, 0.13; P<0.001). FP/FORM was non-inferior to FP/SAL for change from predose FEV1 at baseline to 2-hour postdose FEV1 (treatment difference = -0.00L; 95%CI: -0.04, 0.04; P<0.001), AUC0-4h at Week 12 (treatment difference = 0.01; 95%CI: -0.03, 0.06; P<0.001) and change from predose FEV1 (treatment difference = -0.02L; 95%CI: -0.06, 0.02; P<0.001). The safety and tolerability profiles of all treatments were similar.

Conclusions: 

In children 5 to <12yrs with asthma, FP/FORM was superior to FP, and non-inferior to FP/SAL for improvements in lung function, with a similar tolerability profile to both FP and FP/SAL.

Sponsor: Mundipharma Research Ltd.
Quality control, modeling, and visualization of CRISPR screens with MAGeCK-VISPR
Authors: Wei Li, Johannes Köster, Han Xu, Chen-Hao Chen, Tengfei Xiao, Jun S. Liu, Myles Brown, X. Shirley Liu
Journal: Genome biology (2015)

High-throughput CRISPR screens have shown great promise in functional genomics. We present MAGeCK-VISPR, a comprehensive quality control (QC), analysis, and visualization workflow for CRISPR screens. MAGeCK-VISPR defines a set of QC measures to assess the quality of an experiment, and includes a maximum-likelihood algorithm to call essential genes simultaneously under multiple conditions. The algorithm uses a generalized linear model to deconvolute different effects, and employs expectation-maximization to iteratively estimate sgRNA knockout efficiency and gene essentiality. MAGeCK-VISPR also includes VISPR, a framework for the interactive visualization and exploration of QC and analysis results. MAGeCK-VISPR is freely available at http://bitbucket.org/liulab/mageck-vispr .
Development of the Manchester sleep symptoms index in COPD
Authors: Janelle Yorke, Adam Garrow, Matt Khan, Sarah Tyson, Dave Singh, Jorgen Vestbo
Journal: European Respiratory Journal (2014)

Aim: In COPD disturbed sleep is related to exacerbation frequency, quality of life and mortality. We developed the Manchester Sleep Symptoms Index-COPD (MSSI-C) to assess night-time symptoms and disturbed sleep. Methods: Identification of potential items was guided by qualitative work with COPD patients and age-matched controls. COPD specific and general symptoms items were retained. A cross-sectional study then identified items for final inclusion. Hierarchical methods and Rasch analysis were used to inform item deletion and the development of a unidimensional scale. Internal consistency and test-retest reliability were assessed. Concurrent validity was examined using Pearson9s correlation with the St George9s Respiratory Questionnaire (SGRQ). Results: Qualitative data from 45 patients with COPD and 12 age-matched controls informed the initial 22 item-list. The cross-sectional study included 204 patients (GOLD: 1: 17% 2:48% 3:26% 4: 9%; male 62%, mean age 65 sd 7 years) and 54 age-matched controls (mean age 68 sd 5 years, male 50%). 11 items were removed during hierarchical methods and a further 4 due to similar responses between COPD and non-COPD groups. The final MSSI-C contains items relating to falling asleep and night-time awakening: breathlessness, chest tightness, cough and sputum. The MSSI-C demonstrated good internal consistency (Cronbach9s alpha 0.9) and test-retest repeatability (>0.7). MSSI-C scores significantly correlated with the SGRQ (Symptoms: r=0.59; Impacts: r=0.60; Activity: r=0.38). Conclusion: The MSSI-C shows good preliminary reliability and validity, and should lead to a better understanding of the impact that symptoms specific to COPD have on sleep outcomes.
An autoimmune “attack” on melanocytes triggers psoriasis and cellular hyperplasia
Authors: James G. Krueger
Journal: The Journal of Experimental Medicine (2015)

![Figure][1] 

Insight from James Krueger



A new study by [Jorg Prinz’s group][2] has identified a melanocyte-derived autoantigen that triggers T cell activation in psoriasis vulgaris.

For two decades, psoriasis has been classified as a probable autoimmune disease based on a strong
In or out? initiating a clinic NIV service
Authors: Michael Newnham, Helen Stone, Maryam Ahmed, Gail Knowles, Marie Mountford, Naveed Mustfa
Journal: European Respiratory Journal (2014)

Introduction  Non-invasive ventilation (NIV) has become a well-established treatment for patients with a wide variety of diagnoses and evidence of ventilatory failure. It is increasingly used for older and more functionally impaired patients. Initiating patients onto NIV as an inpatient is associated with an average length of stay of 5 days (cost £1250). Our tertiary NIV unit has recently introduced a clinic NIV initiation service for carefully selected patients who were unwilling or unable to be admitted to hospital.  Methods  A retrospective study of patients undergoing clinic NIV initiation in 2012-2013. Data was collected on demography, spirometry, sniff nasal inspiratory pressure (SNIP), initial and subsequent blood gases, ventilator settings and overnight oximetry. Clinic NIV is initiated by nurse specialists with capillary blood gases and patient/carer training.  Results  22 patients were included. There was a range of indications: 8 severe obstructive sleep apnoea, 4 neuromuscular weakness, 3 overlap, 2 obesity hypoventilation and 5 other diagnoses. Average age was 65, with 50% male. Average FEV1 1.52 (58%), FVC 2.04 (60%), ratio 75 and SNIP -39cmH20. Average initial blood gases were pH 7.42, pO 2  7.8, pCO 2  6.1, HCO 3  29.9 with a subsequent pCO 2,  of 5.6 and HCO 3  of 28.3. The mean initial IPAP/EPAP settings were 15/7. There were 15 calls to the NIV help hotline with potential problems. 11 patients (50%) had documented symptomatic improvement. 20 patients remain on NIV (mean duration is 275 days). 4.5% of patients died during follow up.  Conclusions  In selected patients, clinic NIV initiation is a viable alternative to inpatient initiation, saving the equivalent of 110 bed days and £27,500. This may relieve pressure on acute NIV services.
Clinical and Genetic Evaluation of Familial Steroid-Responsive Nephrotic Syndrome in Childhood
Authors: ARNO FUCHSHUBER, OLIVIER GRIBOUVAL, VERA RONNER, SABINE KROISS, STEPHANIE KARLE, MATTHIAS BRANDIS, FRIEDHELM HILDEBRANDT
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Steroid-responsive idiopathic nephrotic syndrome (SSINS) is the most common form of nephrotic syndrome in childhood. This article reports a cohort of familial SSINS with disease onset in childhood. The clinical course in terms of age at onset, symptoms during the initial phase, renal morphology, and outcome was evaluated. Furthermore, linkage to NPHS2 , the gene for autosomal-recessive steroid-resistant INS on chromosome 1, was examined. Two families with haplotypes consistent with linkage to NPHS2 were evaluated for mutations in the NPHS2 gene. Familial SSINS (32 patients from 15 families, minimal change NS in 12 of 12 biopsies) was found to be a clinically homogeneous entity. Interfamilial and intrafamilial variability with respect to the age at disease onset was low, indicating a strong genetic influence on disease onset. By linkage studies and mutational analysis, familial SSINS was found to be genetically distinct from NPHS2 . This is the first report of a large cohort of familial SSINS. Exclusion of linkage to NPHS2 makes likely the existence of a distinct gene locus for SSINS.
Carcinosarcoma of the Stomach
Journal: JAMA (1963)

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
Antitumor effector B cells directly kill tumor cells involving the CXCL12/CXCR4 pathway and their therapeutic efficacy is enhanced by IL-2
Authors: Qiao Li, Yang Xia
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts In cancer immunotherapy, effector B cells can inhibit spontaneous tumor metastases as well as local tumor growth in animal models. We have previously reported that anti-tumor effector B cells generated from tumor-draining lymph node (TDLN) could directly kill tumor cells via the
Are oncologists effective in modifying patient-perceived breast cancer risk and associated anxiety?
Authors: W. C. Mertens, D. Katz, M. Quinlan, D. Hoffman, C. Carr, G. Makari-Judson
Journal: Journal of Clinical Oncology (2005)

8159 Background: While studies have evaluated genetic/nurse counseling and risk perception, few have assessed oncologist counselors. Methods: High-risk clinic patients consented prior to consultation and completed the Brief Symptom Inventory-18 (BSI) and 5-year/lifetime risk perceptions immediately before (PRE) and after (POST) counseling. Gail model estimates were shared during counseling. Results: 61 patients were enrolled. Mean PRE perceptions were much greater than Gail estimates (5-year: 32.2% vs. 3.0%, p<.0001; lifetime: 46.2% vs. 24.1%, p<.0001). POST perceptions decreased significantly (5-year mean: 10.9%, p<.0005; lifetime 13.6%, p<.0003) but still exceeded Gail estimates (5-year: p<.0001; lifetime: p=.02). No correlations were found between PRE/POST perceptions and Gail estimates. Perception change differed between physicians (range of means: 5-year -1.1 to -29.4%, p=.002; lifetime -9.4 to -32.6%, p=.05) as did POST perception and Gail estimate differences. PRE BSI T-scores were greater for anxiety (ANX; p=.03) than standardized norms; all POST indices demonstrated declines (p<.0001). Increasing PRE 5-year perception was associated in a stepwise multivariate model with increasing PRE ANX (p=.006), number of 1o relatives with breast cancer (p=.01) and body-mass index (BMI; p=.02), while POST 5-year perception was associated with PRE perception (p<.0001) and counseling physician (p=.002); lifetime models were similar. Greater ratio of POST 5-year risk perception to Gail estimates was associated with higher PRE perception (p<.0001) and BMI (p=.05), younger age (p=.0006), and physician (p=.007). Increased PRE ANX was associated with increased PRE 5-year risk perception (p=.001) and younger age (p=.002); POST ANX was associated with PRE ANX (p<.0001), genetic counseling recommendation (p=.04), and physician (p=.06). Conclusions: PRE 5-year risk perceptions are associated with PRE ANX and predict POST perceptions which remain several-fold greater than Gail estimates. Even in a prospective trial of perception modification, oncologists were only partially successful. Individual counselor effectiveness varied considerably; this factor requires attention in future studies. No significant financial relationships to disclose.
Developmental hierarchy during early human B-cell ontogeny after autologous bone marrow transplantation using autografts depleted of CD19+ B-cell precursors by an anti-CD19 pan-B-cell immunotoxin containing pokeweed antiviral protein
Authors: FM Uckun, S Haissig, JA Ledbetter, P Fidler, DE Myers, V Kuebelbeck, D Weisdorf, K Gajl-Peczalska, JH Kersey, NK Ramsay
Journal: Blood (1992)
Molecular Characterization of an Endometrial Endometrioid Adenocarcinoma Metastatic to a Thyroid Hürthle Cell Adenoma Showing Cancerization of Follicles
Authors: Amir H. Afrogheh, Emily Meserve, Peter M. Sadow, Antonia E. Stephen, Vânia Nosé, Suzanne Berlin, William C. Faquin
Journal: Endocrine Pathology (2015)
Isolation, preparation, and assessment of the immunogenicity effectiveness of a novel inactivated rotavirus vaccine strain: ZTR-68, rotavirus A genotype G1P[8]
Authors: Jinyuan Wu, Shan Yi, Guangming Zhang, Guofa Mu, Na Yin, Kai Mi, Yan Zhou, Yuping Xie, Nan Xiao, Hongjun Li, Maosheng Sun
Journal: The Lancet (2015)
Dual Role of Mesenchymal Stem Cells Allows for Microvascularized Bone Tissue‐Like Environments in PEG Hydrogels
Authors: Ulrich Blache, Stéphanie Metzger, Queralt Vallmajo‐Martin, Ivan Martin, Valentin Djonov, Martin Ehrbar
Journal: Advanced Healthcare Materials (2015)

In vitro engineered tissues which recapitulate functional and morphological properties of bone marrow and bone tissue will be desirable to study bone regeneration under fully controlled conditions. Among the key players in the initial phase of bone regeneration are mesenchymal stem cells (MSCs) and endothelial cells (ECs) that are in close contact in many tissues. Additionally, the generation of tissue constructs for in vivo transplantations has included the use of ECs since insufficient vascularization is one of the bottlenecks in (bone) tissue engineering. Here, 3D cocultures of human bone marrow derived MSCs (hBM‐MSCs) and human umbilical vein endothelial cells (HUVECs) in synthetic biomimetic poly(ethylene glycol) (PEG)‐based matrices are directed toward vascularized bone mimicking tissue constructs. In this environment, bone morphogenetic protein‐2 (BMP‐2) or fibroblast growth factor‐2 (FGF‐2) promotes the formation of vascular networks. However, while osteogenic differentiation is achieved with BMP‐2, the treatment with FGF‐2 suppressed osteogenic differentiation. Thus, this study shows that cocultures of hBM‐MSCs and HUVECs in biological inert PEG matrices can be directed toward bone and bone marrow‐like 3D tissue constructs.
Whole Exome Sequencing Identifies Rare Protein‐Coding Variants in Behçet's Disease
Authors: Mikhail Ognenovski, Paul Renauer, Elizabeth Gensterblum, Ina Kötter, Theodoros Xenitidis, Jörg C. Henes, Bruno Casali, Carlo Salvarani, Haner Direskeneli, Kenneth M. Kaufman, Amr H. Sawalha
Journal: Arthritis & Rheumatology (2015)

Objective Behçet's disease (BD) is a systemic inflammatory disease with an incompletely understood etiology. Despite the identification of multiple common genetic variants associated with BD, rare genetic variants have been less explored. We undertook this study to investigate the role of rare variants in BD by performing whole exome sequencing in BD patients of European descent. Methods Whole exome sequencing was performed in a discovery set comprising 14 German BD patients of European descent. For replication and validation, Sanger sequencing and Sequenom genotyping were performed in the discovery set and in 2 additional independent sets of 49 German BD patients and 129 Italian BD patients of European descent. Genetic association analysis was then performed in BD patients and 503 controls of European descent. Functional effects of associated genetic variants were assessed using bioinformatic approaches. Results Using whole exome sequencing, we identified 77 rare variants (in 74 genes) with predicted protein‐damaging effects in BD. These variants were genotyped in 2 additional patient sets and then analyzed to reveal significant associations with BD at 2 genetic variants detected in all 3 patient sets that remained significant after Bonferroni correction. We detected genetic association between BD and LIMK2 (rs149034313), involved in regulating cytoskeletal reorganization, and between BD and NEIL1 (rs5745908), involved in base excision DNA repair ( P = 3.22 × 10 −4 and P = 5.16 × 10 −4 , respectively). The LIMK2 association is a missense variant with predicted protein damage that may influence functional interactions with proteins involved in cytoskeletal regulation by Rho GTPase, inflammation mediated by chemokine and cytokine signaling pathways, T cell activation, and angiogenesis (Bonferroni‐corrected P = 5.63 × 10 −14 , P = 7.29 × 10 −6 , P = 1.15 × 10 −5 , and P = 6.40 × 10 −3 , respectively). The genetic association in NEIL1 is a predicted splice donor variant that may introduce a deleterious intron retention and result in a noncoding transcript variant. Conclusion We used whole exome sequencing in BD for the first time and identified 2 rare putative protein‐damaging genetic variants associated with this disease. These genetic variants might influence cytoskeletal regulation and DNA repair mechanisms in BD and might provide further insight into increased leukocyte tissue infiltration and the role of oxidative stress in BD.