tbuckley/cabot-search huggingface dataset:
District nebuliser compressor service: reliability and costs.
Authors: M E Dodd, S P Hanley, S C Johnson, A K Webb
Journal: Thorax (1995)

There is little information on the costs of maintaining a district nebuliser compressor service. This retrospective study examines the issue, reliability, and maintenance costs of electrical compressors to assist the prediction of future costs, taking into account recent safety legislation.Records of issue, repair, and replacement for the period 1982-91 were reviewed. The current policy of repairing and replacing as necessary, and three other theoretical costings, were considered.The number of compressors being issued is increasing. Repaired compressors are less reliable and frequency of repair is a function of compressor age. The current policy is the most cost effective.To repair and replace nebuliser compressors as necessary is the most economical policy under the present terms offered by the manufacturers, but changes in safety legislation will affect the provision of such services.
Clinical Outcomes in Non–Small Cell Lung Cancers Harboring Different Exon 19 Deletions in EGFR
Authors: Kuei-Pin Chung, Shang-Gin Wu, Jenn-Yu Wu, James Chih-Hsin Yang, Chong-Jen Yu, Pin-Fei Wei, Jin-Yuan Shih, Pan-Chyr Yang
Journal: Clinical Cancer Research (2012)

Several deletions in exon 19 of epidermal growth factor receptor (EGFR) gene have been reported in non-small cell lung cancer (NSCLC). It is unknown if deletions occurring at different amino acid positions or of different sizes are associated with different clinical outcome to EGFR tyrosine kinase inhibitors (TKI).This study enrolled NSCLC patients with deletions in EGFR exon 19. Patients who had received EGFR TKIs for advanced NSCLC were further evaluated for response rate (RR), progression-free survival (PFS), and overall survival (OS).In 308 patients with deletions in EGFR exon 19, 298 had deletions encompassing the entire amino acid string from L747 through E749 (LRE deletions). EGFR TKIs were used in 204 patients with advanced NSCLC. Patients with non-LRE deletions had the least RR, compared with those with deletions from E746 or L747 (42.9%, 68.2%, and 79.6%, respectively; P = 0.022). Patients with non-LRE deletions had relatively short median PFS, though not significantly different from those with deletions from E746 or L747 (5.9, 9.8, and 10.5 months, respectively; P = 0.665). The OS was not different among patients with deletions occurring at different amino acid positions (P = 0.776). Deletions in exon 19 of different sizes were not associated with different RR, PFS, or OS.Non-LRE deletions in exon 19 were associated with worse response to EGFR TKIs, compared with LRE deletions. Therefore, the expected clinical outcome under EGFR TKIs depends on not only the existence but also the types of deletions in exon 19.
Neutrophil-Derived Cathelicidin Promotes Adhesion of Classical Monocytes
Authors: Sarawuth Wantha, Jean-Eric Alard, Remco T.A. Megens, Anne M. van der Does, Yvonne Döring, Maik Drechsler, Christine T.N. Pham, Ming-Wei Wang, Ji-Min Wang, Richard L. Gallo, Philipp von Hundelshausen, Lennart Lindbom, Tilman Hackeng, Christian Weber, Oliver Soehnlein
Journal: Circulation Research (2013)

The leukocyte response in acute inflammation is characterized by an initial recruitment of neutrophils preceding a second wave of monocytes. Neutrophil-derived granule proteins were suggested to hold an important role in this cellular switch. The exact mechanisms by which neutrophils mediate these processes are only partially understood.To investigate the role of neutrophils and their granule contents in the adhesion of monocyte subpopulations in acute inflammation.Here, we show that neutrophil-derived cathelicidins (human: LL37, mouse: CRAMP) induce adhesion of classical monocytes but not of nonclassical monocytes in the mouse cremaster muscle and in in vitro flow chamber assays. CRAMP is released from emigrated neutrophils and then transported across the endothelium, where it is presented to rolling leukocytes. Endothelial-bound cathelicidin activates formyl-peptide receptor 2 on classical monocytes, resulting in monocytic β1- and β2-integrin conformational change toward an extended, active conformation that allows for adhesion to their respective ligands, vascular cell adhesion molecule 1 and intercellular adhesion molecule 1.These data elucidate a novel mechanism of neutrophil-mediated monocyte recruitment, which could be targeted in conditions where recruitment of classical monocytes plays an unfavorable role.
The Importance of Implementation Strategy in Scaling Up Xpert MTB/RIF for Diagnosis of Tuberculosis in the Indian Health-Care System: A Transmission Model
Authors: Henrik Salje, Jason R. Andrews, Sarang Deo, Srinath Satyanarayana, Amanda Y. Sun, Madhukar Pai, David W. Dowdy
Journal: PLoS Medicine (2014)

Using a modelling approach, David Dowdy and colleagues investigate how different implementation strategies for Xpert MTB/RIF within the complex, fragmented healthcare system of India may affect tuberculosis control. Please see later in the article for the Editors' Summary
Kidney Disease Caused by Dysregulation of the Complement Alternative Pathway
Authors: An S. De Vriese, Sanjeev Sethi, Jens Van Praet, Karl A. Nath, Fernando C. Fervenza
Journal: Journal of the American Society of Nephrology (2015)

Kidney diseases caused by genetic or acquired dysregulation of the complement alternative pathway (AP) are traditionally classified on the basis of clinical presentation (atypical hemolytic uremic syndrome as thrombotic microangiopathy), biopsy appearance (dense deposit disease and C3 GN), or clinical course (atypical postinfectious GN). Each is characterized by an inappropriate activation of the AP, eventuating in renal damage. The clinical diversity of these disorders highlights important differences in the triggers, the sites and intensity of involvement, and the outcome of the AP dysregulation. Nevertheless, we contend that these diseases should be grouped as disorders of the AP and classified on an etiologic basis. In this review, we define different pathophysiologic categories of AP dysfunction. The precise identification of the underlying abnormality is the key to predict the response to immune suppression, plasma infusion, and complement-inhibitory drugs and the outcome after transplantation. In a patient with presumed dysregulation of the AP, the collaboration of the clinician, the renal pathologist, and the biochemical and genetic laboratory is very much encouraged, because this enables the elucidation of both the underlying pathogenesis and the optimal therapeutic approach.
Experimental and Clinical Regenerative Capability of Human Bone Marrow Cells After Myocardial Infarction
Authors: Francisco Fernández-Avilés, José Alberto San Román, Javier García-Frade, María Eugenia Fernández, María Jesús Peñarrubia, Luis de la Fuente, Manuel Gómez-Bueno, Alberto Cantalapiedra, Jesús Fernández, Oliver Gutierrez, Pedro L. Sánchez, Carolina Hernández, Ricardo Sanz, Javier García-Sancho, Ana Sánchez
Journal: Circulation Research (2004)

Bone marrow mononuclear cells (BMCs) from 20 patients with extensive reperfused myocardial infarction (MI) were used to assess their myocardial regenerative capability “in vitro” and their effect on postinfarction left ventricular (LV) remodeling. Human BMCs were labeled, seeded on top of cryoinjured mice heart slices, and cultured. BMCs showed tropism for and ability to graft into the damaged mouse cardiac tissue and, after 1 week, acquired a cardiomyocyte phenotype and expressed cardiac proteins, including connexin43. In the clinical trial, autologous BMCs (78±41×10 6 per patient) were intracoronarily transplanted 13.5±5.5 days after MI. There were no adverse effects on microvascular function or myocardial injury. No major cardiac events occurred up to 11±5 months. At 6 months, magnetic resonance showed a decrease in the end-systolic volume, improvement of regional and global LV function, and increased thickness of the infarcted wall, whereas coronary restenosis was only 15%. No changes were found in a nonrandomized contemporary control group. Thus, BMCs are capable of nesting into the damaged myocardium and acquire a cardiac cell phenotype in vitro as well as safely benefiting ventricular remodeling in vivo. Large-scale randomized trials are needed now to assess the clinical efficacy of this treatment.
Single words, multiple words, and the functions of language
Authors: A. Charles Catania
Journal: Behavioral and Brain Sciences (1995)

Abstract Wilkins &amp; Wakefield assign importance to motor systems but skip from anatomy to cognitive structure with little attention to behavior. Organisms, no matter how sophisticated, that do not behave in accord with what they know will fall by the evolutionary wayside. Facts about behavior can supplement the authors' theory, whose hierarchical structures can accommodate an evolutionary scenario in which a million years or more of functionally varied utterances mainly limited to single words is followed by an explosion of linguistic diversity with the development in the last 50,000 years or so of syntactically organized multiple word utterances.
Regulation of the Natural Killer Cell Receptor Repertoire
Authors: David H. Raulet, Russell E. Vance, Christopher W. McMahon
Journal: Annual Review of Immunology (2001)

Natural killer cells express inhibitory receptors specific for MHC class I proteins and stimulatory receptors with diverse specificities. The MHC-specific receptors discriminate among different MHC class I alleles and are expressed in a variegated, overlapping fashion, such that each NK cell expresses several inhibitory and stimulatory receptors. Evidence suggests that individual developing NK cells initiate expression of inhibitory receptor genes in a sequential, cumulative, and stochastic fashion. Superimposed on the receptor acquisition process are multiple education mechanisms, which act to coordinate the stimulatory and inhibitory specificities of developing NK cells. One process influences the complement of receptors expressed by individual NK cells. Other mechanisms may prevent NK cell autoaggression even when the developing NK cell fails to express self-MHC-specific inhibitory receptors. Together, these mechanisms ensure a self-tolerant and maximally discriminating NK cell population. Like NK cells, a fraction of memory phenotype CD8(+) T cells, as well as other T cell subsets, express inhibitory class I--specific receptors in a variegated, overlapping fashion. The characteristics of these cells suggest that inhibitory receptor expression may be a response to prior antigenic stimulation as well as to poorly defined additional signals. A unifying hypothesis is that both NK cells and certain T cell subsets initiate expression of inhibitory receptors in response to stimulation.
Hydrogen Peroxide Promotes Aging-Related Platelet Hyperactivation and Thrombosis
Authors: Sanjana Dayal, Katina M. Wilson, David G. Motto, Francis J. Miller, Anil K. Chauhan, Steven R. Lentz
Journal: Circulation (2013)

Background— The incidence of thrombotic events increases during aging, but the mechanisms are not well understood. To investigate the prothrombotic role of oxidative stress during aging, we tested the hypothesis that aged mice overexpressing the antioxidant enzyme glutathione peroxidase-1 (Gpx1) are protected from experimental thrombosis. Methods and Results— Susceptibility to carotid artery thrombosis was first examined in wild-type C57BL/6J mice. After photochemical injury of the carotid artery, the time to stable occlusion was significantly shorter in 12- and 18-month-old mice compared with 4-month-old mice ( P &lt;0.01). Unlike wild-type mice, transgenic mice overexpressing Gpx1 (Gpx1 Tg) did not exhibit shortened times to occlusion of the carotid artery at 12 or 18 months of age. Wild-type mice also exhibited increased susceptibility to venous thrombosis after inferior vena cava ligation at 12 or 18 months of age ( P &lt;0.05 versus 4 months of age). Gpx1 Tg mice were protected from this aging-related enhanced susceptibility to venous thrombosis. Age-dependent platelet hyperactivation, evidenced by increased hydrogen peroxide, fibrinogen binding, and activation of fibrinogen receptor αIIbβ3, was observed in thrombin-activated platelets from wild-type but not Gpx1 Tg mice ( P &lt;0.05). Enhanced platelet activation responses in aged mice were also prevented by polyethylene glycol–catalase or apocynin, an inhibitor of NADPH oxidase. Aged mice displayed increased intraplatelet expression of p47 phox and superoxide dismutase-1, suggesting a mechanistic pathway for increased hydrogen peroxide generation. Conclusions— Our findings demonstrate that hydrogen peroxide is a key mediator of platelet hyperactivity and enhanced thrombotic susceptibility in aged mice.
Influence of the sex-linked defect in CBA/N mice on autoimmune responses to isologous erythrocytes. Ability to overcome the defect with age.
Authors: Y J Rosenberg
Journal: The Journal of Experimental Medicine (1979)

Normal mice spontaneously develop plaque-forming cells (PFC) specific for antigens on modified self erythrocytes (bromelain-treated mouse erythrocytes [BrMRBC] antigens). Our study demonstrates that the sex-linked defect that results in the inability of CBA/N mice to respond to several T-independent antigens (TI-2 antigens) also regulates the autoantibody response to BrMRBC antigens. Thus, in CBA/N homozygous mice and male F1 offspring of CBA/N-mothered crosses, e.g., (CBA/N X NZB)F1 males, such PFC are absent. To examine whether specific autoreactive B cells are present in defective mice, the latter were stimulated either nonspecifically with the mitogen LPS or by infection with lethal malaria (17XL Plasmodium yoelii) known to induce anti-BrMRBC PFC specifically. The results indicate that modest antibody responses to self antigens could be induced in young (5- to 7-wk old) defective mice and that these responses increased as a function of age. The data is consistent with the view that the defect in CBA/N mice does not result from an absence of functional anti-BrMRBC B cells but rather from low frequencies of the specific precursors, which can be triggered and expanded with age probably by environmental stimulations.
Genetic Architecture of Type 2 Diabetes: Recent Progress and Clinical Implications
Authors: Richard W. Grant, Allan F. Moore, Jose C. Florez
Journal: Diabetes Care (2009)

With the exception of rare monogenic disorders, most type 2 diabetes results from the interaction of genetic variation at multiple different chromosomal sites with environmentalexposures experienced throughout thelifespan (1). This complex genetic architecture has important consequences for understanding the pathophysiology of type 2 diabetes, both for researchers seeking mechanistic insight into disease progression and for clinicians hoping to translate this new genetic information into more effective patient management.

With nearly two dozen genes associated with type 2 diabetes, including some genetic variants that appear to modify responses to commonly prescribed diabetes medications and lifestyle interventions, we may be on the verge of a new era in which a patient's individual genetic profile can add useful information to clinical care. Indeed, commercial companies are already offering genome-wide genetic profiling that includes information related to diabetes risk (2). Further advances in type 2 diabetes genetic discovery hold the promise, as yet unrealized, of enabling clinicians to individualize care for their patients by basing their clinical decisions on patient risk for disease progression, propensity to develop specific complications, and likely response to different medication classes. At present it is unknown whether individual genetic information may also serve to effectively motivate patient behavior change, a cornerstone of diabetes and pre-diabetes management. In this review of polygenic type 2 diabetes, we focus on recent discoveries made via linkage analyses, candidate gene association studies, and genome-wide association (GWA) scans and highlight potential clinical applications of new genetic knowledge to risk prediction, pharmacologic management, and patient behavior. Monogenic diabetes has recently been reviewed elsewhere (3).

### Progress in gene discovery

#### Linkage studies and candidate genes.

In contrast to monogenic disorders, where results from single mutations lead to predictable phenotypes, the complex genetic architecture of susceptible and protective alleles in polygenic type 2 diabetes is more difficult to discern. Indeed, accumulating data suggest that type 2 diabetes …
Effect of a somatostatin infusion on circulating levels of adipokines in obese women
Authors: Antonello E. Rigamonti, Alessandro Sartorio, Sara M. Bonomo, Marialuisa Giunta, Guido Grassi, Mario Perotti, Silvano G. Cella, Eugenio E. Müller, Angela I. Pincelli
Journal: Metabolism (2012)
Predicting the risk of venous thromboembolism recurrence
Authors: John A. Heit
Journal: American Journal of Hematology (2012)

Venous thromboembolism (VTE) is a chronic disease with a 30% ten-year recurrence rate. The highest incidence of recurrence is in the first 6 months. Active cancer significantly increases the hazard of early recurrence, and the proportions of time on standard heparin with an APTT ≥ 0.2 anti-X(a) U/mL, and on warfarin with an INR ≥ 2.0, significantly reduce the hazard. The acute treatment duration does not affect recurrence risk after treatment is stopped. Independent predictors of late recurrence include increasing patient age and body mass index, leg paresis, active cancer and other persistent VTE risk factors, idiopathic VTE, antiphospholipid antibody syndrome, antithrombin, protein C or protein S deficiency, hyperhomocysteinemia and a persistently increased plasma fibrin D-dimer. A recommendation for secondary prophylaxis should be individualized based on the risk for recurrent VTE (especially fatal pulmonary embolism) and bleeding. The appropriateness of secondary prophylaxis should be continuously reevaluated, and the prophylaxis stopped if the benefit no longer exceeds the risk.
Chlamydia antibody testing and diagnosing tubal pathology in subfertile women: an individual patient data meta-analysis
Authors: K.A. Broeze, B.C. Opmeer, S.F.P.J. Coppus, N. Van Geloven, M.F.C. Alves, G. Ånestad, S. Bhattacharya, J. Allan, M.F. Guerra-Infante, J.E. Den Hartog, J.A. Land, A. Idahl, P.J.Q. Van der Linden, J.W. Mouton, E.H.Y. Ng, J.W. Van der Steeg, P. Steures, H.F. Svenstrup, A. Tiitinen, B. Toye, F. Van der Veen, B.W. Mol
Journal: Human Reproduction Update (2011)

The Chlamydia IgG antibody test (CAT) shows considerable variations in reported estimates of test accuracy, partly because of the use of different assays and cut-off values. The aim of this study was to reassess the accuracy of CAT in diagnosing tubal pathology by individual patient data (IPD) meta-analysis for three different CAT assays.We approached authors of primary studies that used micro-immunofluorescence tests (MIF), immunofluorescence tests (IF) or enzyme-linked immunosorbent assay tests (ELISA). Using the obtained IPD, we performed pooled receiver operator characteristics analysis and logistic regression analysis with a random effects model to compare the three assays. Tubal pathology was defined as either any tubal obstruction or bilateral tubal obstruction.We acquired data of 14 primary studies containing data of 6191 women, of which data of 3453 women were available for analysis. The areas under the curve for ELISA, IF and MIF were 0.64, 0.65 and 0.75, respectively (P-value < 0.001) for any tubal pathology and 0.66, 0.66 and 0.77, respectively (P-value = 0.01) for bilateral tubal pathology.In Chlamydia antibody testing, MIF is superior in the assessment of tubal pathology. In the initial screen for tubal pathology MIF should therefore be the test of first choice.
Reciprocal Binding of CTCF and BORIS to the NY-ESO-1 Promoter Coincides with Derepression of this Cancer-Testis Gene in Lung Cancer Cells
Authors: Julie A. Hong, Yang Kang, Ziedulla Abdullaev, Patrick T. Flanagan, Svetlana D. Pack, Maria R. Fischette, Mina T. Adnani, Dmitri I. Loukinov, Sergei Vatolin, John I. Risinger, Mary Custer, G. Aaron Chen, Ming Zhao, Dao M. Nguyen, J. Carl Barrett, Victor V. Lobanenkov, David S. Schrump
Journal: Cancer Research (2005)

Regulatory sequences recognized by the unique pair of paralogous factors, CTCF and BORIS, have been implicated in epigenetic regulation of imprinting and X chromosome inactivation. Lung cancers exhibit genome-wide demethylation associated with derepression of a specific class of genes encoding cancer-testis (CT) antigens such as NY-ESO-1. CT genes are normally expressed in BORIS-positive male germ cells deficient in CTCF and meCpG contents, but are strictly silenced in somatic cells. The present study was undertaken to ascertain if aberrant activation of BORIS contributes to derepression of NY-ESO-1 during pulmonary carcinogenesis. Preliminary experiments indicated that NY-ESO-1 expression coincided with derepression of BORIS in cultured lung cancer cells. Quantitative reverse transcription-PCR analysis revealed robust, coincident induction of BORIS and NY-ESO-1 expression in lung cancer cells, but not normal human bronchial epithelial cells following 5-aza-2'-deoxycytidine (5-azadC), Depsipeptide FK228 (DP), or sequential 5-azadC/DP exposure under clinically relevant conditions. Bisulfite sequencing, methylation-specific PCR, and chromatin immunoprecipitation (ChIP) experiments showed that induction of BORIS coincided with direct modulation of chromatin structure within a CpG island in the 5'-flanking noncoding region of this gene. Cotransfection experiments using promoter-reporter constructs confirmed that BORIS modulates NY-ESO-1 expression in lung cancer cells. Gel shift and ChIP experiments revealed a novel CTCF/BORIS-binding site in the NY-ESO-1 promoter, which unlike such sites in the H19-imprinting control region and X chromosome, is insensitive to CpG methylation in vitro. In vivo occupancy of this site by CTCF was associated with silencing of the NY-ESO-1 promoter, whereas switching from CTCF to BORIS occupancy coincided with derepression of NY-ESO-1. Collectively, these data indicate that reciprocal binding of CTCF and BORIS to the NY-ESO-1 promoter mediates epigenetic regulation of this CT gene in lung cancer cells, and suggest that induction of BORIS may be a novel strategy to augment immunogenicity of pulmonary carcinomas.
Increase of PD-L1 expressing B-precursor ALL cells in a patient resistant to the CD19/CD3-bispecific T cell engager antibody blinatumomab
Authors: Thomas Köhnke, Christina Krupka, Johanna Tischer, Thomas Knösel, Marion Subklewe
Journal: Journal of Hematology & Oncology (2015)

The bispecific T cell engager blinatumomab has shown encouraging clinical activity in B-precursor acute lymphoblastic leukemia (ALL). However, about half of relapsed/refractory patients do not respond to therapy. Here, we present the case of a 32-year-old male patient with refractory B-precursor ALL who was resistant to treatment with blinatumomab. Bone marrow immunohistochemistry revealed T cell infiltrates and an increase in programmed death-ligand 1 (PD-L1)-positive ALL cells as a potential immune escape mechanism. We were able to recapitulate the clinical observation in vitro by showing that blinatumomab was not able to mediate cytotoxicity of CD19-positive ALL cells using autologous T cells. In contrast, the addition of healthy donor T cells led to lysis of ALL cells. These results strongly encourage further systematic evaluation of checkpoint molecules in cases of blinatumomab treatment failure and might highlight a possible mechanism to overcome resistance to this otherwise highly effective treatment.