tbuckley/cabot-search huggingface dataset:
Whole-genome sequencing reveals transmission of vancomycin-resistant Enterococcus faecium in a healthcare network
Authors: Hayley J. Brodrick, Kathy E. Raven, Ewan M. Harrison, Beth Blane, Sandra Reuter, M. Estée Török, Julian Parkhill, Sharon J. Peacock
Journal: Genome Medicine (2016)

Background: Bacterial whole-genome sequencing (WGS) has the potential to identify reservoirs of multidrugresistant organisms and transmission of these pathogens across healthcare networks.We used WGS to define transmission of vancomycin-resistant enterococci (VRE) within a long-term care facility (LTCF), and between this and an acute hospital in the United Kingdom (UK).Methods: A longitudinal prospective observational study of faecal VRE carriage was conducted in a LTCF in Cambridge, UK.Stool samples were collected at recruitment, and then repeatedly until the end of the study period, discharge or death.Selective culture media were used to isolate VRE, which were subsequently sequenced and analysed.We also analysed the genomes of 45 Enterococcus faecium bloodstream isolates collected at Cambridge University Hospitals NHS Foundation Trust (CUH).Results: Forty-five residents were recruited during a 6-month period in 2014, and 693 stools were collected at a frequency of at least 1 week apart.Fifty-one stool samples from 3/45 participants (7 %) were positive for vancomycin-resistant E. faecium.Two residents carried multiple VRE lineages, and one carried a single VRE lineage.Genome analyses based on single nucleotide polymorphisms (SNPs) in the core genome indicated that VRE carried by each of the three residents were unrelated.Participants had extensive contact with the local healthcare network.We found that VRE genomes from LTCF residents and hospital-associated bloodstream infection were interspersed throughout the phylogenetic tree, with several instances of closely related VRE strains from the two settings.Conclusions: A proportion of LTCF residents are long-term carriers of VRE.Evidence for genetic relatedness between these and VRE associated with bloodstream infection in a nearby acute NHS Trust indicate a shared bacterial population.
Germline mutations in pancreatic cancer become better defined
Authors: Mary Kay Barton
Journal: CA A Cancer Journal for Clinicians (2016)

Key Points Germline mutations occur in approximately 15% of patients with PAC. These 2 studies suggest that genetic counseling and testing are appropriate for patients with early‐onset PAC or a family history of PAC, those with one of several associated cancers, and those of Ashkenazi Jewish ancestry. Further study and guidelines are needed to integrate genetic testing for PAC into practice.
Spontaneous Haemopneumothorax
Authors: A. J. Clyne, F. H. D. Hutter
Journal: BMJ (1955)

MMIQUI JOURNALor pelvis; (b) that blood eosinophilia is often intermittent, and may be absent on any particular examination; and (c) that a pleocytosis in the cerebrospinal fluid may not only show eosinophils, if a suitable stain is used, but is often associated with a paretic Lange curve.Finally recourse must be made to ventriculography, using air or opaque contrast media, which may not only define the site of the obstruction but also outline the shape and size of the cysts responsible, and give valuable information about the possibility of surgical removal.Sunumary Attention is drawn to clinical manifestations other than epileptic convulsions which frequently occur in cerebral cysticercosis, and to the countries other than India where infestation is often acquired.Cases are described illustrating periods of disordered behaviour, transient pareses, intermittent obstructive hydrocephalus, dysequilibrium, meningo-encephalitis, in- voluntary movements, failing vision, and mental distur- bances.Stress is laid on the cerebrovascular lesions, and on the importance of the posterior fossa forms of the disease.I wish to thank the medical staff of the Polish General Hos- pital, Penley, for referring to me Cases 1, 2, and 5; to Professor P. C. Cloake for permitting me to investigate Case 3; to Profes- sor W. H. Wynn for allowing me to include Case 4; and to Sir Russell Brain for permission to use brief extracts from
STUDIES ON RABBIT LYMPHOCYTES IN VITRO
Authors: Stewart Sell, David S. Rowe, P. G. H. Gell
Journal: The Journal of Experimental Medicine (1965)

In vitro cultures of the peripheral blood lymphocytes of rabbits may be stimulated with phytohaemagglutinin, staphylococcal filtrate, antiallotype serum, or sheep anti-rabbit whole serum to synthesize protein, RNA and DNA as indicated by the incorporation of radiolabelled precursor substances into these products. A sequence of events found in all stimulated cultures characteristically shows protein synthesis followed by RNA synthesis, histologic blast transformation, DNA synthesis, and mitosis, with the complete sequence requiring 48 hours. All four stimulants induce essentially identical metabolic changes. Characterization of the proteins synthesized by lymphocytes in vitro has failed to demonstrate immunoglobulin synthesis by stimulated or non-stimulated cultures. It is concluded that the majority of proteins produced by peripheral lymphocytes stimulated in vitro are most likely cellular proteins related to the metabolic alterations necessary for mitosis. Absorption of sheep antisera to whole rabbit serum with rabbit IgG does not always remove the transforming capacity of the sheep antisera. Thus, it is likely that antibodies to proteins other than IgG present in the small lymphocyte may also be able to stimulate transformation. A possible common mechanism for the induction of lymphoblast transformation may be the ability of both specific and non-specific stimulants to react with protein constituents of the lymphocyte which may also be present in serum.
Pulmonary toxicity with combined modality therapy for limited stage small-cell lung cancer.
Authors: B J Brooks, E J Seifter, T E Walsh, A S Lichter, P A Bunn, A Zabell, A Johnston-Early, M Edison, R W Makuch, M H Cohen
Journal: Journal of Clinical Oncology (1986)

To assess the pulmonary toxicity of radiation therapy combined with chemotherapy v chemotherapy alone, we reviewed the clinical course of 80 patients with limited stage small-cell lung cancer treated in a randomized prospective trial. Life-threatening pulmonary toxicity, defined as bilateral pulmonary infiltrates extending beyond radiation ports with symptoms requiring hospital admission, developed in 11 patients (28%) receiving combined modality therapy and in two (5%) receiving chemotherapy alone. Eight of these 13 patients died from pulmonary complications with no clinical evidence of tumor in five. Pulmonary toxicity initially presented at a median of 63 days (range, 21 to 150 days) after the start of combined modality therapy and at a median of 217 days after chemotherapy alone. Biopsies obtained in 11 patients with severe toxicity revealed only interstitial fibrosis with no evidence of an infectious agent. Review of pretreatment parameters such as age, performance status, and radiation portal area failed to reveal any significant differences between patients with or without pulmonary complications. However, initial pulmonary function tests (PFTs) revealed a significantly lower vital capacity (P = .03) and forced expiratory volume (FEV/1.0 second) (P = .04) in patients with subsequent pulmonary complications. Pulmonary toxicity was significantly more common with combined modality therapy than with chemotherapy alone (P = .017) and worse than expected with radiotherapy alone. Six- or 12-month PFTs in completely responding patients revealed improvement within the chemotherapy alone group and no clear trend within the combined modality group. For the group treated with radiation therapy and chemotherapy, there was significantly less improvement after 6 or 12 months in the forced vital capacity (P less than .005) and FEV/1.0 second (P less than .005) than observed for the group treated with chemotherapy alone. Despite the increased incidence of pulmonary toxicity, overall survival favored the combined modality arm (P = .07). Enhanced local control and disease-free survival appeared to compensate for the initial increased pulmonary morbidity and mortality in the group with combined modality therapy.
Tau Biology and Tau-Directed Therapies for Alzheimer’s Disease
Authors: Lidia Bakota, Roland Brandt
Journal: Drugs (2016)

Alzheimer's disease (AD) is characterised by a progressive loss of cognitive functions. Histopathologically, AD is defined by the presence of extracellular amyloid plaques containing Aβ and intracellular neurofibrillary tangles composed of hyperphosphorylated tau proteins. According to the now well-accepted amyloid cascade hypothesis is the Aβ pathology the primary driving force of AD pathogenesis, which then induces changes in tau protein leading to a neurodegenerative cascade during the progression of disease. Since many earlier drug trials aiming at preventing Aβ pathology failed to demonstrate efficacy, tau and microtubules have come into focus as prominent downstream targets. The article aims to develop the current concept of the involvement of tau in the neurodegenerative triad of synaptic loss, cell death and dendritic simplification. The function of tau as a microtubule-associated protein and versatile interaction partner will then be introduced and the rationale and progress of current tau-directed therapy will be discussed in the biological context.
Endometrial Carcinomas with <i>POLE</i> Exonuclease Domain Mutations Have a Favorable Prognosis
Authors: Melissa K. McConechy, Aline Talhouk, Samuel Leung, Derek Chiu, Winnie Yang, Janine Senz, Linda J. Reha-Krantz, Cheng-Han Lee, David G. Huntsman, C. Blake Gilks, Jessica N. McAlpine
Journal: Clinical Cancer Research (2016)

The aim of this study was to confirm the prognostic significance of POLE exonuclease domain mutations (EDM) in endometrial carcinoma patients. In addition, the effect of treatment on POLE-mutated tumors was assessed.A retrospective patient cohort of 496 endometrial carcinoma patients was identified for targeted sequencing of the POLE exonuclease domain, yielding 406 evaluable tumors. Univariable and multivariable analyses were performed to determine the effect of POLE mutation status on progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). Combining results from eight studies in a meta-analysis, we computed pooled HR for PFS, DSS, and OS.POLE EDMs were identified in 39 of 406 (9.6%) endometrial carcinomas. Women with POLE-mutated endometrial carcinomas were younger, with stage I (92%) tumors, grade 3 (62%), endometrioid histology (82%), and frequent (49%) lymphovascular invasion. In univariable analysis, POLE-mutated endometrial carcinomas had significantly improved outcomes compared with patients with no EDMs for PFS, DSS, and OS. In multivariable analysis, POLE EDMs were only significantly associated with improved PFS. The effect of adjuvant treatment on POLE-mutated cases could not be determined conclusively; however, both treated and untreated patients with POLE EDMs had good outcomes. Meta-analysis revealed an association between POLE EDMs and improved PFS and DSS with pooled HRs 0.34 [95% confidence interval (CI), 0.15-0.73] and 0.35 (95% CI, 0.13-0.92), respectively.POLE EDMs are prognostic markers associated with excellent outcomes for endometrial carcinoma patients. Further investigation is needed to conclusively determine if treatment is necessary for this group of women. Clin Cancer Res; 22(12); 2865-73. ©2016 AACR.
Liza Plus for neuromuscular assessment and training: mobile app user guide
Authors: Ezequiel Rey, Roberto Barcala-Furelos, Alexis Padron-Cabo
Journal: British Journal of Sports Medicine (2016)

Liza Plus

Fitness or health

Apple (iOS V.4.0 or later)

€5.99

Liza Plus is an easy-to-use application designed to conduct four common1 ,2 neuromuscular fitness tests and exercises on athletic and non-athletic populations. By using an iPhone accelerometer, Liza calculates the power and speed during exercise by measuring the vertical acceleration of the mass lifted by the subject in opposition to gravity. Liza filters the acquired accelerometer information and processes it to obtain the speed (cm/s); then Liza calculates the power (W) and other output data based on the load lifted in the specific exercise performed, similar to a linear encoder (Power=Force×Velocity, where Force=m (load lifted)×a). Users can measure performance during a workout session using a barbell (half squat, bench press) or body-weight exercises (countermovement jump (CMJ) or squat jump (SJ)) (figure 1). The free version ( Liza Lite ) allows one to perform only jump tests (CMJ and SJ). At the end of each test, the user can read …
Adoptive Transfer Of Ex Vivo “Educated” CD4+CD25+FoxP3+ Regulatory T Cells Effectively Treats Acute Graft Versus Host Disease Preserving Graft Versus Tumor Effect
Authors: Antonio Pierini, Dominik Schneidawind, Mareike Florek, Maite Alvarez, Yuqiong Pan, Jeanette Baker, Everett Meyer, Robert Negrin
Journal: Blood (2013)
Abstract 17178: Adaptive Statistical Iterative Reconstruction V: Impact on Image Quality in Ultra-low-dose Coronary Computed Tomography Angiography
Authors: Dominik C Benz, Christoph Gräni, Beatrice Hirt-Moch, Fran Mikulicic, Jan Vontobel, Tobias A Fuchs, Oliver Gaemperli, Philipp A Kaufmann, Ronny R Buechel
Journal: Circulation (2015)

Introduction: To accomplish a further decrease in radiation dose for coronary CT angiography (CCTA), advances in iterative reconstruction (IR) algorithms are necessary. The purpose of the present study was to investigate the impact of a latest generation adaptive statistical IR algorithm (ASiR-V, GE Healthcare) on CCTA signal intensity, noise and image quality (IQ). Methods: Sixty-five consecutive patients underwent clinically indicated CCTA using a latest generation 256-slice CT scanner (Revolution CT, GE Healthcare) and an ultra-low-dose CCTA protocol (i.e. a BMI-adapted tube current of 180-310 mA and tube voltage of 80-120 kVp). Datasets from each patient were reconstructed at different levels of ASiR-V (i.e. ASiR-V 0% [= filtered back projection, FBP], 20%, 40%, 60%, 80% and 100%). The signal intensity and noise (i.e. attenuation and its standard deviation [in HU]) were measured in each reconstruction by placing a region of interest in the aortic root as well as the proximal RCA and LMA. Furthermore, IQ was assessed for each coronary segment on a 5-point Likert scale by two blinded readers. Results: The ultra-low-dose CCTA protocol resulted in a median radiation dose of 0.49 mSv (IQR 0.40-0.60). Signal intensity in the LMA and RCA slightly but significantly decreased with increasing levels of ASiR-V (Table). Nevertheless, the substantial decrease in image noise resulted in a significant increase in signal-to-noise ratio (SNR) in the RCA and LMA. Correspondingly, IQ significantly increased with higher levels of ASiR-V. Applying ASiR-V at a level of 100% led to a 141-143% increase in SNR and a substantial increase in IQ compared to FBP. Of note, for reconstructions with ASiR-V 100%, a significant increase in IQ was even observed when compared to ASiR-V 80%. Conclusions: Increasing ASiR-V levels offer substantial image noise reduction and improved IQ for CCTA datasets acquired at low tube voltage and current, enabling application of ultra-low-dose CCTA protocols.
Prognostic factors in patients with locally advanced salivary gland cancers treated with surgery and postoperative radiotherapy (RT)
Authors: S. Y. Lai, T. M. Feinstein, R. R. Seethala, D. E. Heron, R. L. Ferris, J. R. Grandis, E. N. Myers, J. T. Johnson, A. E. Argiris
Journal: Journal of Clinical Oncology (2008)

6045 Background: We sought to review the experience of our center with the treatment of patients with locally advanced salivary gland cancers and identify prognostic factors of outcome. Methods: We reviewed records of patients with malignant salivary gland tumors registered within University of Pittsburgh databases from 1980–2006. Selection criteria included newly diagnosed stage III or IV disease treated with surgery followed by postoperative RT. Patients with early stage or distant metastatic disease, history of skin or other head and neck cancer, non-salivary gland pathology, history of immunosuppresion, or previous treatment were excluded. Parameters of interest included age, gender, stage, primary site, histologic type and pathologic features (grade, perineural invasion, extracapsular spread and positive margins), and treatment type. Results: Of 492 patients initially identified, 78 met the inclusion criteria. Characteristics were as follows: Male 42/female 36; median age 59 years (21–90); stage III, 41%; stage IV, 59%; N2 stage, 33%; N0–1, 67%. Primary site: parotid, 69%; submandibular, 8%; minor 23%. Histology: adenoid cystic carcinoma, 21%; salivary duct carcinoma, 22%; adenocarcinoma, 19%; mucoepidermoid carcinoma, 15%; carcinoma ex pleomorphic adenoma, 8%; acinic cell carcinoma, 6%; and other, 6%. 49% had positive margins and 64% perineural invasion. The median RT dose was 60 Gy; 13 pts received concurrent chemotherapy (10 with carboplatin). With a median follow-up of 3.9 years, the 3- and 5-year disease-free survival (DFS) was 70% and 52%, respectively; the 3- and 5-year overall survival was 71% and 58%, respectively. Primary site (others vs. minor salivary glands), stage (IV vs. III) and N stage (N2 vs. N0–1), and presence of perineural invasion were predictive of worse DFS in univariate analysis. On Cox-regression analysis, stage and site were independent predictors of DFS. Conclusions: The long-term outcome of patients with high-risk, locally advanced salivary gland cancers is unsatisfactory. Stage and primary site are important determinants of DFS. The addition of novel agents to postoperative RT should be explored in prospective clinical trials. No significant financial relationships to disclose.
Effect of Hippocampal and Amygdala Connectivity on the Relationship Between Preschool Poverty and School-Age Depression
Authors: Deanna Barch, David Pagliaccio, Andy Belden, Michael P. Harms, Michael Gaffrey, Chad M. Sylvester, Rebecca Tillman, Joan Luby
Journal: American Journal of Psychiatry (2016)

In this study, the authors tested the hypothesis that poverty experienced in early childhood, as measured by income-to-needs ratio, has an impact on functional brain connectivity at school age, which in turn mediates influences on child negative mood/depression.Participants were from a prospective longitudinal study of emotion development. Preschoolers 3-5 years of age were originally ascertained from primary care and day care sites in the St. Louis area and then underwent annual behavioral assessments for up to 12 years. Healthy preschoolers and those with a history of depression symptoms underwent neuroimaging at school age. Using functional MRI, the authors examined whole brain resting-state functional connectivity with the left and right hippocampus and amygdala.Lower income-to-needs ratio at preschool age was associated with reduced connectivity between hippocampus and amygdala and a number of regions at school age, including the superior frontal cortex, lingual gyrus, posterior cingulate, and putamen. Lower income-to-needs ratio predicted greater negative mood/depression severity at school age, as did connectivity between the left hippocampus and the right superior frontal cortex and between the right amygdala and the right lingual gyrus. Connectivity mediated the relationship between income-to-needs ratio and negative mood/depression at the time of scanning.These findings suggest that poverty in early childhood, as assessed by at least one measure, may influence the development of hippocampal and amygdala connectivity in a manner leading to negative mood symptoms during later childhood.
Increased expression levels of human telomerase reverse transcriptase (hTERT) mRNA correlates with poor prognosis in resected non-small cell lung cancer (NSCLC) patients
Authors: S. Carrera, G. López-Vivanco, B. Calvo, U. Aresti, M. S. Jangi, J. Ferreiro, A. Martínez-Bueno, I. Rubio, A. Muñoz, N. Ancizar
Journal: Journal of Clinical Oncology (2007)

10594 Background: Telomerase adds hexameric TTAGGG nucleotide repeats onto the ends of chromosomal DNAs to compensate for losses of each cell replication. In several tumors, telomerase is expressed in a way that tumoral cell proliferates indefinitely. Correlation between telomerase level expression, clinico-pathological characteristics and survival of lung cancer is not well established in NSCLC. Methods: We studied 149 consecutive patients (140 men/9 women) with resected NSCLC: 37.6% adenocarcinoma, 59 % squamous cell, and 3.4% large cell carcinoma. Pathological stage: I (36.9%), II (32.3%) and III (30.8%). Reverse transcription-polymerase chain reaction (RT-PCR) analysis was used for the detection hTERT expression in lung cancer tissues immediately snap-frozen in liquid nitrogen at -80 °C. Results: Median and mean values of hTERT mRNA were 18.27 and 475.29 (SE 309.76). There were no significant differences on expression according to sex, histology, smoking history and pathological stage (ANOVA). Patients with highest values of hTERT mRNA expression (percentile 95, cut-off value &gt;353) had worse median progression free survival (PFS) (p=0.024) and overall survival (OS) (p=0.020), using Kaplan-Meier method. Multivariate analysis by Cox regression yielded that hTERT level &gt; 353 independently predicted a worse PFS (HR=0.39; 95% CI 0.17–0.93, p=0.034) and OS (HR=0.32; 95% CI 0.12–0.82, p=0.017). Conclusions: A high level of telomerase expression in tumoral tissue is strongly associated with increased risk of recurrence and mortality in resected NSCLC. The level of hTERT mRNA would predict the prognosis of lung cancer patients. No significant financial relationships to disclose.