tbuckley/cabot-search huggingface dataset:
Making Every Word Count for Nonresponsive Patients
Authors: Lorina Naci, Adrian M. Owen
Journal: JAMA Neurology (2013)

<h3>Importance</h3> Despite the apparent absence of external signs of consciousness, a significant small proportion of patients with disorders of consciousness can respond to commands by willfully modulating their brain activity, even respond to yes or no questions, by performing mental imagery tasks. However, little is known about the mental life of such responsive patients, for example, with regard to whether they can have coherent thoughts or selectively maintain attention to specific events in their environment. The ability to selectively pay attention would provide evidence of a patient's preserved cognition and a method for brain-based communication, thus far untested with functional magnetic resonance imaging in this patient group. <h3>Objective</h3> To test whether selective auditory attention can be used to detect conscious awareness and communicate with behaviorally nonresponsive patients. <h3>Design, Setting, and Participants</h3> Case study performed in 3 patients with severe brain injury, 2 diagnosed as being in a minimally conscious state and 1 as being in a vegetative state. The patients constituted a convenience sample. <h3>Main Outcomes and Measures</h3> Functional magnetic resonance imaging data were acquired as the patients were asked to selectively attend to auditory stimuli, thereby conveying their ability to follow commands and communicate. <h3>Results</h3> All patients demonstrated command following according to instructions. Two patients (1 in a minimally conscious state and 1 in a vegetative state) were also able to guide their attention to repeatedly communicate correct answers to binary (yes or no) questions. <h3>Conclusions and Relevance</h3> To our knowledge, we show for the first time with functional magnetic resonance imaging that behaviorally nonresponsive patients can use selective auditory attention to convey their ability to follow commands and communicate. One patient in a minimally conscious state was able to use attention to establish functional communication in the scanner, despite his inability to produce any communication responses in repeated bedside examinations. More important, 1 patient, who had been in a vegetative state for 12 years before the scanning and subsequent to it, was able to use attention to correctly communicate answers to several binary questions. The technique may be useful in establishing basic communication with patients who appear unresponsive to bedside examinations and cannot respond with existing neuroimaging methods.
Inherited IL-17RC deficiency in patients with chronic mucocutaneous candidiasis
Authors: Yun Ling, Sophie Cypowyj, Caner Aytekin, Miguel Galicchio, Yildiz Camcioglu, Serdar Nepesov, Aydan Ikinciogullari, Figen Dogu, Aziz Belkadi, Romain Levy, Mélanie Migaud, Bertrand Boisson, Alexandre Bolze, Yuval Itan, Nicolas Goudin, Julien Cottineau, Capucine Picard, Laurent Abel, Jacinta Bustamante, Jean-Laurent Casanova, Anne Puel
Journal: The Journal of Experimental Medicine (2015)

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections of the skin, nail, oral, and genital mucosae with Candida species, mainly C. albicans. Autosomal-recessive (AR) IL-17RA and ACT1 deficiencies and autosomal-dominant IL-17F deficiency, each reported in a single kindred, underlie CMC in otherwise healthy patients. We report three patients from unrelated kindreds, aged 8, 12, and 37 yr with isolated CMC, who display AR IL-17RC deficiency. The patients are homozygous for different nonsense alleles that prevent the expression of IL-17RC on the cell surface. The defect is complete, abolishing cellular responses to IL-17A and IL-17F homo- and heterodimers. However, in contrast to what is observed for the IL-17RA– and ACT1-deficient patients tested, the response to IL-17E (IL-25) is maintained in these IL-17RC–deficient patients. These experiments of nature indicate that human IL-17RC is essential for mucocutaneous immunity to C. albicans but is otherwise largely redundant.
Proteome-Wide Measurement of Protein Half-Lives and Translation Rates in Vasopressin-Sensitive Collecting Duct Cells
Authors: Pablo C. Sandoval, Dane H. Slentz, Trairak Pisitkun, Fahad Saeed, Jason D. Hoffert, Mark A. Knepper
Journal: Journal of the American Society of Nephrology (2013)

Vasopressin regulates water excretion, in part, by controlling the abundances of the water channel aquaporin-2 (AQP2) protein and regulatory proteins in the renal collecting duct. To determine whether vasopressin-induced alterations in protein abundance result from modulation of protein production, protein degradation, or both, we used protein mass spectrometry with dynamic stable isotope labeling in cell culture to achieve a proteome-wide determination of protein half-lives and relative translation rates in mpkCCD cells. Measurements were made at steady state in the absence or presence of the vasopressin analog, desmopressin (dDAVP). Desmopressin altered the translation rate rather than the stability of most responding proteins, but it significantly increased both the translation rate and the half-life of AQP2. In addition, proteins associated with vasopressin action, including Mal2, Akap12, gelsolin, myosin light chain kinase, annexin-2, and Hsp70, manifested altered translation rates. Interestingly, desmopressin increased the translation of seven glutathione S-transferase proteins and enhanced protein S-glutathionylation, uncovering a previously unexplored vasopressin-induced post-translational modification. Additional bioinformatic analysis of the mpkCCD proteome indicated a correlation between protein function and protein half-life. In particular, processes that are rapidly regulated, such as transcription, endocytosis, cell cycle regulation, and ubiquitylation are associated with proteins with especially short half-lives. These data extend our understanding of the mechanisms underlying vasopressin signaling and provide a broad resource for additional investigation of collecting duct function (http://helixweb.nih.gov/ESBL/Database/ProteinHalfLives/index.html).
Biology of Epithelial Ovarian Cancer: Implications for Screening Women at High Genetic Risk
Authors: Russell Hogg, Michael Friedlander
Journal: Journal of Clinical Oncology (2004)

Our aim was to analyze the clinicopathologic features of screen-detected ovarian cancers identified in women, either at general population risk or high genetic risk of ovarian cancer, who have participated in screening studies.Studies published between 1988 and April 2003 were categorized by the population screened and the primary screening modalities used. Each report was examined with reference to the histologic type, stage, and grade of screen-detected cancers. Reports of studies of prophylactically removed ovaries from women at high risk of ovarian cancer were also reviewed.Of the stage I tumors detected by screening women at population risk, almost half were borderline ovarian tumors, granulosa-cell tumors, or germ-cell tumors, which is disproportionate to their frequency. Furthermore, of the stage I invasive epithelial cancers diagnosed in women at population risk, the majority were endometrioid, clear-cell, and mucinous histologic subtypes. Most ovarian cancers that occur in women at high genetic risk are high-grade serous cancers, and these are infrequently screen detected at an early stage.The clinicopathologic features of screen-detected ovarian cancers suggest that screening may not reduce mortality in women at increased genetic risk. Prospective screening studies are required in genetically high-risk populations to answer this important question. Women electing surveillance should be aware of the lack of proven benefit and the low likelihood of detecting early stage serous cancers. Bilateral salpingo-oophorectomy appears to be the most effective approach to decrease the risk of ovarian cancer and thereby reduce mortality in high-risk women.
Isotonic smooth muscle response in human bronchi exposed in vitro to nitrogen dioxide
Authors: P Chitano, RE Lucchini, F Calabro, M Saetta, P Maestrelli, LM Fabbri, CE Mapp
Journal: European Respiratory Journal (1996)

Exposure to nitrogen dioxide (NO2), a common oxidant airborne pollutant, has been shown to cause reversible effects on lung function and airway responsiveness, in addition to airways inflammation. However, there have been conflicting reports concerning NO2-induced airway hyperresponsiveness. In the present study, we investigated the isotonic smooth muscle response in isolated human bronchi previously exposed in vitro to NO2. Bronchial segments were obtained from 12 patients who had undergone thoracotomy for lung cancer. Bronchial segments from each patient were exposed to air and to 2.5 parts per million (ppm) NO2 for 4 h. The contractile response of bronchial rings to acetylcholine, neurokinin A (NKA), and substance P was then studied under isotonic conditions. The response to NKA was also studied in rings, with or without epithelium, exposed either to air or 7 ppm NO2. No NO2-induced alteration of the bronchial smooth muscle isotonic response was found under any of the experimental conditions. We conclude that in vitro exposure to up to 7 ppm nitrogen dioxide does not cause alterations of the human bronchial smooth muscle shortening capacity.
Acute Myeloid Leukemia Following Hodgkin Lymphoma: A Population-Based Study of 35 511 Patients
Authors: Sara J. Schonfeld, Ethel S. Gilbert, Graça M. Dores, Charles F. Lynch, David C. Hodgson, Per Hall, Hans Storm, Aage Andersen, Eero Pukkala, Eric Holowaty, Magnus Kaijser, Michael Andersson, Heikki Joensuu, Sophie D. Fosså, James M. Allan, Lois B. Travis
Journal: JNCI Journal of the National Cancer Institute (2006)

Treatments for Hodgkin lymphoma are associated with large relative risks of acute myeloid leukemia (AML), but there are few estimates of the excess absolute risk (EAR), a useful measure of disease burden. One-year Hodgkin lymphoma survivors (N = 35,511) were identified within 14 population-based cancer registries in Nordic countries and North America from January 1, 1970, through December 31, 2001. We used Poisson regression analysis to model the EAR of AML, per 10,000 person-years. A total of 217 Hodgkin lymphoma survivors were diagnosed with AML (10.8 expected; unadjusted EAR = 6.2; 95% confidence interval = 5.4 to 7.1). Excess absolute risk for AML was highest during the first 10 years after Hodgkin lymphoma diagnosis but remained elevated thereafter. In subsequent analyses, adjusted for time since Hodgkin lymphoma diagnosis and presented for the 5-9 year interval, the EAR was statistically significantly (P < .001) larger in patients diagnosed with Hodgkin lymphoma at age 35 years and older than in those diagnosed before 35 years of age. The EAR of AML declined statistically significantly after 1984 (7.0 to 4.2 and 16.4 to 9.9 in the < 35 and > or = 35 age groups, respectively), which may be associated with modifications in chemotherapy.
High Mutation Rates in the Mitochondrial Genomes of Daphnia pulex
Authors: S. Xu, S. Schaack, A. Seyfert, E. Choi, M. Lynch, M. E. Cristescu
Journal: Molecular Biology and Evolution (2011)

Despite the great utility of mitochondrial DNA (mtDNA) sequence data in population genetics and phylogenetics, key parameters describing the process of mitochondrial mutation (e.g., the rate and spectrum of mutational change) are based on few direct estimates. Furthermore, the variation in the mtDNA mutation process within species or between lineages with contrasting reproductive strategies remains poorly understood. In this study, we directly estimate the mtDNA mutation rate and spectrum using Daphnia pulex mutation-accumulation (MA) lines derived from sexual (cyclically parthenogenetic) and asexual (obligately parthenogenetic) lineages. The nearly complete mitochondrial genome sequences of 82 sexual and 47 asexual MA lines reveal high mtDNA mutation rate of 1.37 × 10−7 and 1.73 × 10−7 per nucleotide per generation, respectively. The Daphnia mtDNA mutation rate is among the highest in eukaryotes, and its spectrum is dominated by insertions and deletions (70%), largely due to the presence of mutational hotspots at homopolymeric nucleotide stretches. Maximum likelihood estimates of the Daphnia mitochondrial effective population size reveal that between five and ten copies of mitochondrial genomes are transmitted per female per generation. Comparison between sexual and asexual lineages reveals no statistically different mutation rates and highly similar mutation spectra.
Extracorporeal Life Support in Critically Ill Adults
Authors: Corey E. Ventetuolo, Christopher S. Muratore
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Extracorporeal life support (ECLS) has become increasingly popular as a salvage strategy for critically ill adults. Major advances in technology and the severe acute respiratory distress syndrome that characterized the 2009 influenza A(H1N1) pandemic have stimulated renewed interest in the use of venovenous extracorporeal membrane oxygenation (ECMO) and extracorporeal carbon dioxide removal to support the respiratory system. Theoretical advantages of ECLS for respiratory failure include the ability to rest the lungs by avoiding injurious mechanical ventilator settings and the potential to facilitate early mobilization, which may be advantageous for bridging to recovery or to lung transplantation. The use of venoarterial ECMO has been expanded and applied to critically ill adults with hemodynamic compromise from a variety of etiologies, beyond postcardiotomy failure. Although technology and general care of the ECLS patient have evolved, ECLS is not without potentially serious complications and remains unproven as a treatment modality. The therapy is now being tested in clinical trials, although numerous questions remain about the application of ECLS and its impact on outcomes in critically ill adults.
Acquired Melanocytic Nevi in Childhood and Familial Melanoma
Authors: Astrid Vredenborg, Stefan Böhringer, Stephanie E. Boonk, Nelleke A. Gruis, Coby Out-Luijting, Ncole A. Kukutsch, Wilma Bergman
Journal: JAMA Dermatology (2013)

In the surveillance of familial melanoma, the identification of children at greater risk of developing melanoma later in life would serve as a helpful tool.To determine whether acquired melanocytic nevi in childhood are an indicator of risk of melanoma in children from families with familial melanoma.A 20-year follow-up study of a cohort of children from families with familial melanoma. Phenotypical data on melanocytic nevi were collected from a random sample of 133 members of families with familial melanoma 2 to 18 years of age with variable risks of being a mutation carrier. More than 20 years of follow-up data (gene-carrier status, diagnosis of melanoma, and excisions of nevi) were collected. In a subgroup of 40 people, childhood phenotypical data were compared with data on nevus numbers in adulthood. Survival analyses, correlation analyses, and t tests were calculated to examine associations.Nevus count and distribution in childhood were correlated with the occurrence of melanoma and mutation carrier status.Significant risk factors for melanoma were found, specifically in the group with the highest risk of being a mutation carrier: total number of atypical nevi in childhood (hazard ratio [HR], 1.21; 95% CI, 1.02-1.44; P = .03), the nevus count of atypical nevi on the buttocks (HR, 14.00; 95% CI, 2.94-66.55; P = .001), and the number of excisions during follow-up (HR, 1.27; 95% CI, 1.23-1.31; P < .001). The analysis also found a correlation between the distribution of nevi in childhood and adulthood and the distribution of melanomas (correlation, 0.89; 95% CI, 0.67-0.96; and correlation, 0.99; 95% CI, 0.98-1.00; P < .001, respectively for both).Numbers and distribution of melanocytic nevi in childhood are major indicators of the risk of melanoma in patients from families with familial melanoma.
Hypoxic induction of interleukin-8 gene expression in human endothelial cells.
Authors: M Karakurum, R Shreeniwas, J Chen, D Pinsky, S D Yan, M Anderson, K Sunouchi, J Major, T Hamilton, K Kuwabara
Journal: Journal of Clinical Investigation (1994)

Because leukocyte-mediated tissue damage is an important component of the pathologic picture in ischemia/reperfusion, we have sought mechanisms by which PMNs are directed into hypoxic tissue. Incubation of human endothelial cells (ECs) in hypoxia, PO2 approximately 14-18 Torr, led to time-dependent release of IL-8 antigen into the conditioned medium; this was accompanied by increased chemotactic activity for PMNs, blocked by antibody to IL-8. Production of IL-8 by hypoxic ECs occurred concomitantly with both increased levels of IL-8 mRNA, based on polymerase chain reaction analysis, and increased IL-8 transcription, based on nuclear run-on assays. Northern analysis of mRNA from hypoxic ECs also demonstrated increased levels of mRNA for macrophage chemotactic protein-1, another member of the chemokine superfamily of proinflammatory cytokines. IL-8 gene induction was associated with the presence of increased binding activity in nuclear extracts from hypoxic ECs for the NF-kB site. Studies with human umbilical vein segments exposed to hypoxia also demonstrated increased elaboration of IL-8 antigen compared with normoxic controls. In mice exposed to hypoxia (PO2 approximately 30-40 Torr), there was increased pulmonary leukostasis, as evidenced by increased myeloperoxidase activity in tissue homogenates. In parallel, increased levels of transcripts for IP-10, a murine homologue in the chemokine family related to IL-8, were observed in hypoxic lung tissue. Taken together, these data suggest that hypoxia constitutes a stimulus for leukocyte chemotaxis and tissue leukostasis.
Does smoking protect against osteoarthritis? Meta-analysis of observational studies
Authors: M. Hui, M. Doherty, W. Zhang
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> To determine whether smoking is protective against the development of osteoarthritis (OA). <h3>Methods</h3> Observational studies for the association between smoking and OA were systematically searched through Medline (1950–), Embase (1980–), Web of Science (1960–), PubMed, Google and relevant references. ORs and 95% CIs were directly retrieved or calculated. Current standards for reporting using MOOSE were followed. Quality-related aspects such as study design, setting, sample selection and confounding bias were recorded. Stratified and meta-regression analyses were undertaken to examine the covariates. <h3>Results</h3> Of 48 studies (537 730 participants) identified from the systematic literature search, 8 were cohort, 21 cross-sectional and 19 case–control. There was an overall negative association between smoking and OA (OR=0.87; 95% CI 0.80 to 0.94) and subgroup analysis confirmed this in case–control studies (OR=0.82; 95% CI 0.70 to 0.95), but not in cohort (OR=0.92; 95% CI 0.81 to 1.06) or cross-sectional studies (OR=0.89; 95% CI 0.78 to 1.01). Within case–control studies a negative association occurred only in hospital settings (OR=0.65; 95% CI 0.52 to 0.81), not in community settings (OR=0.90; 95% CI 0.75 to 1.08). The association was also seen in knee OA, radiographic OA and smoking as a secondary exposure (covariate or confounding factor). Meta-regression analysis demonstrated that a hospital setting and smoking as a secondary exposure were the major source of the negative association. <h3>Conclusions</h3> The protective effect of smoking in OA observed in some epidemiological studies is likely to be false. It may be caused by selection bias, often in a hospital setting where control subjects have smoking-related conditions and studies that are not primarily designed to investigate smoking. Critical appraisal of such studies is needed.
Lung delivery of salbutamol by dry powder inhaler (Turbuhaler) and small volume antistatic metal spacer (Airomir CFC-free MDI plus NebuChamber)
Authors: BJ Lipworth, DJ Clark
Journal: European Respiratory Journal (1997)

As a worldwide ban on the use of chlorofluorocarbons (CFCs) in inhaler devices approaches, considerable attention has been focused on the production of CFC-free delivery devices. The aim of our study was to compare the delivery of salbutamol by dry powder inhaler (DPI), Turbuhaler and a CFC-free metered-dose inhaler (MDI), Airomir, used with a novel small volume metal spacer (NebuChamber). Ten healthy volunteers, mean (SEM) age 21 (0.7) yrs were studied in a randomized, single (investigator)-blind cross-over design. Single doses of 1,200 microg salbutamol, from Turbuhaler DPI and Airomir CFC-free MDI via a NebuChamber, were given as 12 sequential 100 microg inhalations over 6 min. The lung delivery of salbutamol was assessed by measuring the plasma salbutamol profile over the first 20 min after inhalation. Plasma salbutamol concentration was expressed as maximal (Cmax) and average (Cav) value. Significant differences (p&lt;0.001) were found between the NebuChamber (N) and the Turbuhaler (T) for salbutamol Cmax and Cav. This amounted to a 1.89 fold difference (95% CI 1.56-2.22) between these devices for Cmax, and a 1.78 fold difference (95% CI 1.42-2.15) for Cav. We have demonstrated that, in vivo, salbutamol from a chlorofluorocarbon-free metered-dose inhaler given via a small volume metal spacer (NebuChamber) produces significantly greater delivery than from an efficient dry powder inhaler (Turbuhaler).
Obstructive sleep apnea (OSA) in elderly patients. Role of continuos positive airway pressure (CPAP) treatment. A multicenter randomized controlled clinical trial
Authors: Lucía Zamora Molina, Miguel Angel Martinez Garcia, Eusebi Chiner, Luis Hernández Blasco, Jose Cortes, Pablo Catalan, Silvia Ponce, J.M. Diaz, Esther Pastor, L. Vigil, C. Carmona, J.M. Monserrat, F. Aizpuru, P. Lloberes, M. Mayos, M.J. Selma Ferrer, Berta Román Bernal, J.F. Cifuentes, A. Muñoz
Journal: European Respiratory Journal (2014)

OBJECTIVE:  To analyze the effect of CPAP treatment on various clinical variables, Quebec sleep questionnaire(QSQ),and neurocognitive tests in elderly patients who have a severe OSA (AHI≥30) .   METHODS:  A multicenter, randomized, controlled, clinical trial in a consecutive cohort of patients ≥ 70 years old with severe OSA to receive or not receive CPAP. Anthropometric data , clinical records, OSA related clinical symptoms, QSQ, neurocognitive, anxiety and depression ( HADS) tests were collected. Patients were monitored 3 times during the study, including variable measurements at the beginning and at 3 months. It was felt that there was good adherence to. The intragroup and intergroup comparison was performed jointly using an ANCOVA test on an intention to treat analysis (ITT).   RESULTS:  We randomized 214/285 elderly patients (105 CPAP and 109 not CPAP). There were no significant differences between baseline variables of the randomized groups. Mean age was 76 (4) years, 69% were men. The mean AHI was 50 (15) and 38% presented daytime sleepiness. The average use of CPAP was 4.9 (2.5) hours, with 69% patients with good adherence (CPAP ≥ 4h/night). CPAP group achieves a greater improvement in all quality of life domains (p   CONCLUSIONS:  In elderly patients with severe OSA, CPAP treatment resulted in an improvement in quality of life, sleep-related symptoms, anxiety and depression indexes and some neurocognitive aspects.