tbuckley/cabot-search huggingface dataset:
Cochlear Implants in Adults and Children
Authors: George A. Gates
Journal: JAMA (1995)

<h3>Objective.</h3> —To provide clinicians and other health care providers with a current consensus on the benefits, limitations, and technical and safety issues that need to be considered in the use of cochlear implants. <h3>Participants.</h3> —A nonfederal, nonadvocate, 14-member consensus panel representing the fields of otolaryngology, audiology, speech-language pathology, pediatrics, psychology, and education, and including a public representative. In addition, 24 experts in auditory anatomy and physiology, otolaryngology, audiology, aural rehabilitation, education, speech-language pathology, and bioengineering presented data to the consensus panel and a conference audience of 650. <h3>Evidence.</h3> —The literature was searched through MEDLINE and an extensive bibliography of references was provided to the panel and the conference audience. Experts prepared abstracts with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. <h3>Consensus.</h3> —The panel, answering predefined consensus questions, developed its conclusions based on the scientific evidence presented in open forum and the scientific literature. <h3>Consensus Statement.</h3> —The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. <h3>Conclusions.</h3> —Cochlear implantation improves communication ability in most adults with severe-to-profound deafness and frequently leads to positive psychological and social benefits as well. Currently, children at least 2 years old and adults with profound deafness are candidates for implantation. Cochlear implant candidacy should be extended to adults with severe hearing impairment and open-set sentence discrimination that is less than or equal to 30% in the best-aided condition. Access to optimal education and (re)habilitation services is important for adults and is critical for children to maximize the benefits available from cochlear implantation. (<i>JAMA</i>. 1995;274:1955-1961)
Evaluation of a Congenital Infantile Fibrosarcoma by Comprehensive Genomic Profiling Reveals an LMNA-NTRK1 Gene Fusion Responsive to Crizotinib
Authors: Victor Wong, Dean Pavlick, Tim Brennan, Roman Yelensky, John Crawford, Jeffrey S. Ross, Vincent A. Miller, Denise Malicki, Philip J. Stephens, Siraj M. Ali, Hyunah Ahn
Journal: JNCI Journal of the National Cancer Institute (2015)
The cellular receptor (CD4) of the human immunodeficiency virus is expressed on neurons and glial cells in human brain.
Authors: I Funke, A Hahn, E P Rieber, E Weiss, G Riethmüller
Journal: The Journal of Experimental Medicine (1987)

The expression of the CD4 antigen in normal human brain was investigated in parallel by immunohistochemical and Northern blot analyses. With anti-CD4 antibodies detecting different epitopes of the molecule, CD4+ neurons were defined in the cerebellum, thalamus, and pons. CD4+ glial cells were identified in the thalamus and pons. CD4-specific mRNA was detected in all three subareas and in the hippocampus, while other subareas were negative. The CD4+ cells were negative with anti-T cell antibodies (anti-CD2 and anti-CD8), as well as with antimonocyte antibodies (M-M 522 and M-M 42).
Functional comparison of DCs generated in vivo with Flt3 ligand or in vitro from blood monocytes: differential regulation of function by specific classes of physiologic stimuli
Authors: Michael Jefford, Max Schnurr, Tracey Toy, Kelly-Anne Masterman, Amanda Shin, Tina Beecroft, Tsin Yee Tai, Ken Shortman, Mark Shackleton, Ian D. Davis, Phil Parente, Thomas Luft, Weisan Chen, Jonathan Cebon, Eugene Maraskovsky
Journal: Blood (2003)
selection pressure on the decision-making process in conflict
Authors: toshiya matsushima
Journal: Behavioral and Brain Sciences (2005)

it is argued in the target article that hemispheric lateralization is advantageous when faced with conflicting choices. as decision-making processes must have been subject to a strong selection pressure, the sensitivity of response latencies could suggest a modular and hierarchical organization of behavioral execution, as was formulated by tinbergen (1951).
Human Enterovirus RNA in Monthly Fecal Samples and Islet Autoimmunity in Norwegian Children With High Genetic Risk for Type 1 Diabetes
Authors: German Tapia, Ondrej Cinek, Trond Rasmussen, Elisabet Witsø, Bjørn Grinde, Lars Christian Stene, Kjersti Skjold Rønningen
Journal: Diabetes Care (2010)

OBJECTIVE To test whether the frequency of human enterovirus RNA in fecal samples collected monthly from early infancy was associated with development of multiple islet autoantibodies in children with the highest risk HLA genotype. RESEARCH DESIGN AND METHODS Individuals carrying the HLA DRB1*0401-DQA1*03-DQB1*0302/DRB1*03-DQA1*05-DQB1*02 genotype were identified at birth and followed with monthly stool samples from age 3 to 35 months. Blood samples taken at age 3, 6, 9, and 12 months and then annually were tested for autoantibodies to insulin, GAD 65 and IA-2. Among 911 children, 27 developed positivity for two or more islet autoantibodies in two or more consecutive samples (case subjects). Two control subjects per case subject were matched by follow-up time, date of birth, and county of residence. Stool samples were analyzed for enterovirus with a semiquantitative real-time RT-PCR. RESULTS The frequency of human enterovirus RNA in stool samples from case subjects before seroconversion (43 of 339, 12.7%) did not differ from the frequency in control subjects (94 of 692, 13.6%) (P = 0.97). Results remained essentially unchanged after adjustment for potential confounders, restriction to various time windows before seroconversion, or infections in the 1st year of life or after inclusion of samples collected after seroconversion. There was no difference in the average quantity of enterovirus RNA or in the frequency of repeatedly positive samples. The estimated relative risk for islet autoimmunity per enterovirus RNA–positive sample during follow-up (nested case-control analysis) was 1.12 (95% CI 0.66–1.91). CONCLUSIONS There was no support for the hypothesis that fecal shedding of enteroviral RNA is a major predictor of advanced islet autoimmunity.
Are the antimicrobial properties of macrolides required for their therapeutic efficacy in chronic neutrophilic airway diseases?
Authors: Guy G Brusselle
Journal: Thorax (2015)

Macrolide antibiotics have been demonstrated to be efficacious in diverse chronic airway diseases characterised by neutrophilic airway inflammation, encompassing cystic fibrosis (CF), non-CF bronchiectasis, diffuse panbronchiolitis, exacerbation-prone COPD and neutrophilic severe asthma.1–8 Many exogenous and endogenous factors can elicit airway neutrophilia: infections (bacterial, viral, virus-like …), pollution (smoking, indoor and outdoor air pollution) and other factors (eg, auto-immunity, gastro-oesophageal reflux with aspiration). Macrolides such as erythromycin, clarithromycin and azithromycin not only have antimicrobial properties, but also broad anti-inflammatory and immunomodulatory effects.9 The antimicrobial effects of macrolides include direct bacterial killing, the prevention of biofilm formation by interfering with microbial quorum sensing, and the stimulation of phagocytosis of bacteria by macrophages. However, chronic use of macrolides has been associated with the occurrence of macrolide-resistant bacteria in the commensal flora of the pharynx of individual patients, and also induces the risk of an increase in antibiotic resistance at the population level.10 Therefore, it is crucial to address the research question whether the antimicrobial properties of macrolides are necessary for their therapeutic efficacy in chronic neutrophilic airway diseases. If not, then the development and use of non-antibiotic macrolides is warranted, since these novel drugs would retain the therapeutic efficacy without the risk of inducing microbial resistance.

In the current issue of Thorax , two complimentary papers address thoroughly the therapeutic potential of macrolides in two different chronic airway diseases which represent a high unmet medical need: bronchiolitis obliterans syndrome (BOS) after lung transplantation and steroid-resistant severe asthma. In the first paper, Corris et al 11 performed the first randomised controlled trial of azithromycin in the treatment of BOS post lung transplantation. In the second paper, Essilfie et al 12 investigated the effects of clarithromycin in two mouse models of steroid-resistant asthma, and investigated in depth the mechanisms of action.

BOS …
Decisive Data Sets in Phylogenomics: Lessons from Studies on the Phylogenetic Relationships of Primarily Wingless Insects
Authors: Emiliano Dell’Ampio, Karen Meusemann, Nikolaus U. Szucsich, Ralph S. Peters, Benjamin Meyer, Janus Borner, Malte Petersen, Andre J. Aberer, Alexandros Stamatakis, Manfred G. Walzl, Bui Quang Minh, Arndt von Haeseler, Ingo Ebersberger, Günther Pass, Bernhard Misof
Journal: Molecular Biology and Evolution (2013)

Phylogenetic relationships of the primarily wingless insects are still considered unresolved. Even the most comprehensive phylogenomic studies that addressed this question did not yield congruent results. To get a grip on these problems, we here analyzed the sources of incongruence in these phylogenomic studies by using an extended transcriptome data set. Our analyses showed that unevenly distributed missing data can be severely misleading by inflating node support despite the absence of phylogenetic signal. In consequence, only decisive data sets should be used which exclusively comprise data blocks containing all taxa whose relationships are addressed. Additionally, we used Four-cluster Likelihood Mapping (FcLM) to measure the degree of congruence among genes of a data set, as a measure of support alternative to bootstrap. FcLM showed incongruent signal among genes, which in our case is correlated neither with functional class assignment of these genes nor with model misspecification due to unpartitioned analyses. The herein analyzed data set is the currently largest data set covering primarily wingless insects, but failed to elucidate their interordinal phylogenetic relationships. Although this is unsatisfying from a phylogenetic perspective, we try to show that the analyses of structure and signal within phylogenomic data can protect us from biased phylogenetic inferences due to analytical artifacts.
Interleukin-17 Promotes Formation and Growth of Prostate Adenocarcinoma in Mouse Models
Authors: Qiuyang Zhang, Sen Liu, Dongxia Ge, Qingsong Zhang, Yun Xue, Zhenggang Xiong, Asim B. Abdel-Mageed, Leann Myers, Steven M. Hill, Brian G. Rowan, Oliver Sartor, Jonathan Melamed, Zhenbang Chen, Zongbing You
Journal: Cancer Research (2012)

Abstract The contributions of interleukin (IL)-17 to cancer remain unclear and somewhat controversial. We took a genetic approach to explore its role in prostate cancers by interbreeding IL-17 receptor C (IL-17RC)–deficient mice with mice that are conditionally mutant for PTEN, one established preclinical model for prostate cancer. Mice that were IL-17RC–deficient (IL-17RC−) displayed prostates that were smaller than mice that maintained IL-17RC expression (IL-17RC+). In addition, IL-17RC− mice developed a reduced number of invasive prostate adenocarcinomas with lower rates of cellular proliferation and higher apoptosis than IL-17RC+ mice. Moreover, the fibromuscular stroma surrounding prostatic glands was relatively thicker in IL-17RC− mice and was associated with decreased matrix metalloproteinase (Mmp)7 expression and increased Timp1, 2, and 4 expression, whereas administration of recombinant mouse IL-17 induced prostatic expression of Mmp7. Taken together, our results suggested that IL-17 promotes the formation and growth of prostate adenocarcinoma, and that an IL-17–MMP7 signaling axis is required for the transition of prostatic intraepithelial neoplasia to frank adenocarcinoma. Cancer Res; 72(10); 2589–99. ©2012 AACR.
Perturbation of Iron Homeostasis Promotes the Evolution of Antibiotic Resistance
Authors: Orsolya Méhi, Balázs Bogos, Bálint Csörgő, Ferenc Pál, Ákos Nyerges, Balázs Papp, Csaba Pál
Journal: Molecular Biology and Evolution (2014)

Evolution of antibiotic resistance in microbes is frequently achieved by acquisition of spontaneous mutations during antimicrobial therapy. Here, we demonstrate that inactivation of a central transcriptional regulator of iron homeostasis (Fur) facilitates laboratory evolution of ciprofloxacin resistance in Escherichia coli. To decipher the underlying molecular mechanisms, we first performed a global transcriptome analysis and demonstrated that the set of genes regulated by Fur changes substantially in response to antibiotic treatment. We hypothesized that the impact of Fur on evolvability under antibiotic pressure is due to the elevated intracellular concentration of free iron and the consequent enhancement of oxidative damage-induced mutagenesis. In agreement with expectations, overexpression of iron storage proteins, inhibition of iron transport, or anaerobic conditions drastically suppressed the evolution of resistance, whereas inhibition of the SOS response-mediated mutagenesis had only a minor effect. Finally, we provide evidence that a cell permeable iron chelator inhibits the evolution of resistance. In sum, our work revealed the central role of iron metabolism in the de novo evolution of antibiotic resistance, a pattern that could influence the development of novel antimicrobial strategies.
Survival Benefit of Lung Transplant for Cystic Fibrosis since Lung Allocation Score Implementation
Authors: Gabriel Thabut, Jason D. Christie, Hervé Mal, Michel Fournier, Olivier Brugière, Guy Leseche, Yves Castier, Dimitris Rizopoulos
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

The survival benefit of lung transplantation (LT) in adult patients with cystic fibrosis (CF) is debated.We sought to assess the survival benefit of LT in adult patients with CF.We used data from the United Network for Organ Sharing Registry to identify adult patients with CF on a wait list for LT in the United States between 2005 and 2009. Survival times while on the wait list and after LT were modeled by use of a Cox model that incorporated transplantation status as a time-dependent covariate. Evolution in lung allocation score (LAS) while on the wait list was used as a surrogate for disease severity. We fitted a model for the joint distribution of survival and longitudinal disease process (LAS over time).A total of 704 adult patients with CF were registered on a wait list during the study period. The cumulative incidence of LT was 39.3% (95% confidence interval, 35.6-42.9%) at 3 months and 64.7% (61.0-68.4%) at 12 months, whereas the incidence of death while on the wait list at the same times was 8.5% (6.4-10.6%) and 12.9% (10.3-15.5%), respectively. Survival after LT was 96.5% (94.7-98.2%) at 3 months; 88.4% (85.1-91.8%) at 12 months; and 67.8% (59.9-76.8%) at 3 years. LT conferred a 69% reduction in the instantaneous risk of death (51-80%). The interaction between LAS and LT was significant: the higher the LAS, the greater the survival benefit of LT (P < 0.001).LT confers a survival benefit for adult patients with CF.
Vasodilatation in the Canine Leg caused by Intra-arterial Infusion of Thrombin and Tissue Thromboplastin
Authors: A. Delin, P. Olsson, A.-C. Teger-Nilsson
Journal: Cardiovascular Research (1967)

Thrombin was infused into a canine femoral artery. At low concentrations vasodilatation occurred. At high concentrations the vasodilatation was followed by intravascular coagulation. Heparinization of the animal or diisopropylfluorophosphate treatment of the thrombin inhibited both the vasodilating and procoagulant activity. Tissue thromboplastin had similar effects on femoral vascular resistance. Heparinization of the animal inhibited the procoagulant but not the vasodilating activity. In thrombin, but not in tissue thromboplastin, the vasodilating and procoagulant activities are correlated.
The role of methotrexate co-medication in TNF-inhibitor treatment in patients with psoriatic arthritis: results from 440 patients included in the NOR-DMARD study
Authors: Karen Minde Fagerli, Elisabeth Lie, Désirée van der Heijde, Marte Schrumpf Heiberg, Åse Stavland Lexberg, Eric Rødevand, Synøve Kalstad, Knut Mikkelsen, Tore K Kvien
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The role of co-medication with tumour necrosis factor inhibitors (TNFi) is well established in rheumatoid arthritis and ankylosing spondylitis. In psoriatic arthritis (PsA) there is little evidence available on this issue. <h3>Material and methods</h3> The analyses were based on data from the Norwegian longitudinal observational study on disease-modifying antirheumatic drugs (NOR-DMARD). Patients with PsA starting their first TNFi, either as monotherapy or with concomitant methotrexate (MTX), were selected. Baseline characteristics, responses after 3, 6 and 12 months, and drug survival were compared between those with and without MTX co-medication. A secondary analysis was performed on patients who had confirmed swollen joints at baseline. Cox regression was used to identify predictors of discontinuation. <h3>Results</h3> We included 440 patients, 170 receiving TNFi as monotherapy and 270 receiving concomitant MTX. The groups had similar baseline characteristics, except for number of swollen joints, which was higher in the concomitant MTX group. Responses were similar in the two groups in both analyses. Drug survival analyses revealed a borderline significant difference in favour of patients receiving co-medication (p=0.07), and this was most prominent for patients receiving infliximab (IFX) (p=0.01). In the Cox regression analysis lack of concomitant MTX and current smoking were independent predictors of discontinuation of TNFi. <h3>Conclusions</h3> We found similar responses to TNFi in patients with and without concomitant MTX, but drug survival was superior in patients receiving co-medication. The effect of MTX on drug survival was most prominent in patients receiving IFX. Smoking at baseline and use of TNFi as monotherapy were identified as independent predictors of drug discontinuation.
DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity
Authors: Qian Zhang, Christopher G. Dove, Jyh Liang Hor, Heardley M. Murdock, Dara M. Strauss-Albee, Jordan A. Garcia, Judith N. Mandl, Rachael A. Grodick, Huie Jing, Devon B. Chandler-Brown, Timothy E. Lenardo, Greg Crawford, Helen F. Matthews, Alexandra F. Freeman, Richard J. Cornall, Ronald N. Germain, Scott N. Mueller, Helen C. Su
Journal: The Journal of Experimental Medicine (2014)

DOCK8 mutations result in an inherited combined immunodeficiency characterized by increased susceptibility to skin and other infections. We show that when DOCK8-deficient T and NK cells migrate through confined spaces, they develop cell shape and nuclear deformation abnormalities that do not impair chemotaxis but contribute to a distinct form of catastrophic cell death we term cytothripsis. Such defects arise during lymphocyte migration in collagen-dense tissues when DOCK8, through CDC42 and p21-activated kinase (PAK), is unavailable to coordinate cytoskeletal structures. Cytothripsis of DOCK8-deficient cells prevents the generation of long-lived skin-resident memory CD8 T cells, which in turn impairs control of herpesvirus skin infections. Our results establish that DOCK8-regulated shape integrity of lymphocytes prevents cytothripsis and promotes antiviral immunity in the skin.
Bedside prediction of mortality from bacteremic sepsis. A dynamic analysis of ICU patients.
Authors: D Pittet, B Thiévent, R P Wenzel, N Li, R Auckenthaler, P M Suter
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The prognosis in patients with sepsis depends on severity of acute illness, underlying chronic diseases, and complications associated with infection. Adjusting for these factors is essential for evaluation of new therapies. The purpose of the present study was to determine variables readily identifiable at the bedside that predict mortality in intensive care unit (ICU) patients with sepsis and positive blood cultures. For a 5-yr period, all patients of a surgical ICU presenting with positive blood cultures and sepsis were systematically analyzed for clinical variables and organ dysfunctions at the day of onset of sepsis and bacteremia and during the subsequent clinical course. The prognostic value of these variables was determined using logistic regression procedures. Of the 5,457 admissions to the ICU, 176 patients developed sepsis with positive blood cultures (3.2 per 100 admissions). The fatality rate was 35% at 28 days after the onset of sepsis; in-hospital mortality was 43%. Independent predictors of mortality at onset of sepsis were previous antibiotic therapy (odds ratio [OR], 2.40; 95% confidence interval [CI95], 1.59 to 3.62; p = 0.034), hypothermia (OR, 1.43; CI95, 1.04 to 2.44; p = 0.030), requirement for mechanical ventilation (OR, 2.97; CI95, 1.96 to 4.51; p = 0.009), and onset-of-sepsis APACHE II score (OR, 1.21; CI95, 1.13 to 1.29; p < 0.001). Vital organ dysfunctions developing after the onset of sepsis influenced outcome markedly. The best two independent prognostic factors were the APACHE II score at the onset of sepsis (OR, 1.13 per unit; CI95, 1.08 to 1.17; p = 0.0016) and the number of organ dysfunctions developing thereafter (OR, 2.39; CI95, 2.02 to 2.82; p < 0.001). In ICU patients with sepsis and positive blood cultures, outcome can be predicted by the severity of illness at onset of sepsis and the number of vital organ dysfunctions developing subsequently. These variables are easily assessed at the bedside and should be included in the evaluation of new therapeutic strategies.
A Lysinated Thiophene‐Based Semiconductor as a Multifunctional Neural Bioorganic Interface
Authors: Simone Bonetti, Assunta Pistone, Marco Brucale, Saskia Karges, Laura Favaretto, Massimo Zambianchi, Tamara Posati, Anna Sagnella, Marco Caprini, Stefano Toffanin, Roberto Zamboni, Nadia Camaioni, Michele Muccini, Manuela Melucci, Valentina Benfenati
Journal: Advanced Healthcare Materials (2015)

Lysinated molecular organic semiconductors are introduced as valuable multifunctional platforms for neural cells growth and interfacing. Cast films of quaterthiophene (T4) semiconductor covalently modified with lysine‐end moieties (T4Lys) are fabricated and their stability, morphology, optical/electrical, and biocompatibility properties are characterized. T4Lys films exhibit fluorescence and electronic transport as generally observed for unsubstituted oligothiophenes combined to humidity‐activated ionic conduction promoted by the charged lysine‐end moieties. The Lys insertion in T4 enables adhesion of primary culture of rat dorsal root ganglion (DRG), which is not achievable by plating cells on T4. Notably, on T4Lys, the number on adhering neurons/area is higher and displays a twofold longer neurite length than neurons plated on glass coated with poly‐ l ‐lysine. Finally, by whole‐cell patch‐clamp, it is shown that the biofunctionality of neurons cultured on T4Lys is preserved. The present study introduces an innovative concept for organic material neural interface that combines optical and iono‐electronic functionalities with improved biocompatibility and neuron affinity promoted by Lys linkage and the softness of organic semiconductors. Lysinated organic semiconductors could set the scene for the fabrication of simplified bioorganic devices geometry for cells bidirectional communication or optoelectronic control of neural cells biofunctionality.