bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overview of the Food and Drug Administration Procedures for Expediting the Development and Evaluation of Drugs for the Treatment of Acquired Immunodeficiency Syndrome and Other Life-Threatening Illnesses
Authors: Hunter James R. , Rosen David L. , DeChristoforo Robert 
Published: October 2007

The acquired immunodeficiency syndrome (AIDS) epidemic has focused increased attention on new drug development and the Food and Drug Administration (FDA) evaluation process for durgs to treat patients with AIDS and other severely debilitating or life-threatening illnesses. To expedite the review of these experimental drugs and to make them available to patients earlier in the development process, the FDA has implemented new procedures and mechanisms. In the new drug regulations, the subpart E procedures commit the FDA to extensive and intensive participation in the initial stages of development of these drugs. Early consultation by the FDA with drug sponsors, more frequent meetings between the FDA and drug sponsors, larger and more extensive phase 1 and phase 2 trials, and postmarketing surveillance are some of the key features of these FDA procedures. The subpart E procedures reflect the philosophy that early involvement by the FDA in drug study design enhances the likelihood that the results from these studies will provide enough information to allow the FDA to more quickly assess the safety and efficacy of these drugs. Treatment Investigational New Drug Applications (INDs) increase the early availability of experimental drugs in the final stages of the FDA evaluation process, but before final approval. Both the parallel track proposal and the accelerated drug approval concept are additional mechanisms intended to increase the early availability of drugs for patients with AIDS. This is a US government work. There are no restrictions on its use.
Peak and Nadir Experiences and Their Consequences Described by Pediatric Oncology Nurses
Authors: Olson Mary Sue , Hinds Pamela S. , Euell Kerri , Quargnenti Alice , Milligan Mary , Foppiano Pheraby , Powell Brent 
Published: October 2007

Pediatric oncology nurses experience role-related stressors, some of which are inherent to the speciality, and their consequences. Despite these difficulties, nurses continue in the specialty. One variable that helps to explain their continued commitment is "meaning," or what pediatric oncology nurses find to be most significant and satisfying in their roles. One technique for determining meaning in a role is to inquire about the peak (significant and positive) and nadir (significant and negative) role-related experiences and the consequences of both kinds of experiences. The purpose of this study was to identify the peak and nadir experiences of pediatric oncology nurses and the short- and long-term consequences of those experiences. Using an interview format that consisted of four open-ended questions and a convenience sampling plan, five nurses interviewed 26 nurses from one pediatric cancer center and 38 nurses from a national sample. The interviewers completed an initial training session on interviewing and repeated that training two more times during data collection. Written or taped oral consent was obtained at the time of each interview. Using a content analytical technique (Krippendorff, 1980), four nurses independently coded each interview. Agreement ratings ranged from 75% to 100% per coded theme for an overall agreement level of 92%. Training for the coding process occurred initially and periodically throughout the analysis period. Fifteen different themes for peak experiences were identified, the majority of which reflect the nurses' experience with patients dying, or with patients recovering and living normal lives, or with the close relationships that develop between nurses and patients. Multiple short- and long-term consequences were identified and included changes in (1) values (becoming less judgmental), (2) behaviors (giving more empathic care), and (3) perspective (accepting limitations of care). Twenty-three different nadir themes were identified. A shared characteristic of several of these themes is the nurses' regret over a perceived inadequacy in handling a situation. Another common element is witnessing patient suffering and feeling unable to adequately relieve the suffering or provide comfort to the patient. The short-term consequences of nadir experiences tend to be negative and include guilt, anger, or dread. The long-term consequences tend to be positive and similar to the long-term consequences of peak experiences. Study findings indicate that pediatric oncology nurses do find meaning in their roles and that those who continue in the speciality are able to experience positive long-term consequences. Study findings will be used to develop a new scale to measure role-related meaning and to develop interventions designed to assist nurses in finding meaning in their roles even during particularly stressful periods.
ACE mediates ventilator-induced lung injury in ratsviaangiotensin II but not bradykinin
Authors: Wösten-van Asperen R. M. , Lutter R. , Haitsma J. J. , Merkus M. P. , van Woensel J. B. , van der Loos C. M. , Florquin S. , Lachmann B. , Bos A. P. 
Published: October 2007

Ventilator-induced lung injury is characterised by inflammation and apoptosis, but the underlying mechanisms are poorly understood. The present study proposed a role for angiotensin-converting enzyme (ACE)viaangiotensin II (Ang II) and/or bradykinin in acute lung injury. The authors assessed whether ACE and, if so, Ang II and/or bradykinin are implicated in inflammation and apoptosis by mechanical ventilation.Rats were ventilated for 4 h with low- or high-pressure amplitudes in the absence or presence of the ACE inhibitor captopril. Nonventilated animals served as controls. ACE activity, Ang II and bradykinin levels, as well as inflammatory parameters (total protein, macrophage inflammatory protein-2 and interleukin-6) were determined. Apoptosis was assessed by the number of activated caspase-3 and TUNEL (terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labelling)-positive cells.Bronchoalveolar lavage fluid ACE activity, levels of total protein, inflammatory parameters and the number of apoptotic cells were increased in the high-pressure amplitude group as compared with the control group. Blocking ACE activity by captopril attenuated inflammation and apoptosis in the latter group. Similar results were obtained by blocking Ang II receptors, but blocking bradykinin receptors did not attenuate the anti-inflammatory and anti-apoptotic effects of captopril.The current authors conclude that inflammation and apoptosis in ventilator-induced lung injury is, at least in part, due to angiotensin-converting enzyme-mediated angiotensin II production.
Virological diagnosis in community-acquired pneumonia in immunocompromised patients
Authors: Camps Serra M. , Cervera C. , Pumarola T. , Moreno A. , Perelló R. , Torres A. , Jiménez de Anta M. T. , Marcos M. A. 
Published: October 2007

Community-acquired pneumonia (CAP) is a serious lower respiratory tract infection associated with significant morbidity and mortality in immunocompromised patients. The present study evaluated the clinical spectrum of CAP in immunocompromised hosts and the role of respiratory viruses, as well as the yield of viral diagnostic methods.Conventional microbiological tests were routinely performed in immunocompromised patients with CAP. Nasopharyngeal swabs were processed for respiratory viruses by indirect immunofluorescence assay, cell culture and PCR. Four groups were defined according to aetiology of CAP, as follows: group 1 (nonviral), group 2 (mixed, nonviral and viral), group 3 (only viral) and group 4 (unknown aetiology).Over a 1-yr period, 92 patients were included. An aetiological diagnosis was achieved in 61 (66%) patients: 38 (41%), group 1; 12 (13%), group 2; and 11 (12%), group 3. The most frequent pathogen detected wasStreptococcus pneumoniae(n = 29, 48%), followed by rhinovirus (n = 11, 18%). PCR identified 95% of respiratory viruses. Clinical characteristics could not reliably distinguish among the different aetiological groups.Respiratory viruses represent a substantial part of the aetiologies of community-acquired pneumonia in immunocompromised patients and its routine assessment through PCR in nasopharyngeal swabs should be considered in the clinical care of these patients.
External validation of a COPD diagnostic questionnaire
Authors: Kotz D. , Nelemans P. , van Schayck C. P. , Wesseling G. J. 
Published: October 2007

The aim of the present study was to determine the external validity of a recently developed questionnaire for the identification of patients at increased risk of airflow limitation in smokers from the general population in the provinces of Dutch and Belgian Limburg (regions surrounding Maastricht, the Netherlands).As part of a study on the early detection of airflow limitation and subsequent smoking cessation treatment (International Standard Randomised Controlled Trial Number: 64481813), the recently developed chronic obstructive pulmonary disease (COPD) diagnostic questionnaire was used in current smokers aged 40–70 yrs, with a smoking history of ≥10 pack-yrs, who reported one or more respiratory symptom (cough, sputum production or dyspnoea), but who had no diagnosis of a respiratory disease (COPD or asthma). Spirometry performed according to American Thoracic Society/European Respiratory Society criteria served as a reference test.Of the 676 subjects who entered the analyses, 398 showed normal lung function and 278 had a diagnosis of COPD (post-bronchodilator forced expiratory volume in one second/forced vital capacity of <0.70). The ability of the COPD diagnostic questionnaire to discriminate between subjects with and without COPD was poor (area under the receiver operating characteristic curve of 0.65).In a high-risk population consisting of middle-aged current smokers with a smoking history of ≥10 pack-yrs, the chronic obstructive pulmonary disease diagnostic questionnaire is probably not useful as a diagnostic tool for the identification of patients with an increased risk of airflow limitation.
Sequential measurements of procalcitonin levels in diagnosing ventilator-associated pneumonia
Authors: Ramirez P. , Garcia M. A. , Ferrer M. , Aznar J. , Valencia M. , Sahuquillo J. M. , Menéndez R. , Asenjo M. A. , Torres A. 
Published: October 2007

The utility of procalcitonin levels to improve the accuracy of clinical and microbiological parameters in diagnosing ventilator-associated pneumonia (VAP) was evaluated.Sequential measurement of procalcitonin and C-reactive protein levels and the calculation of the simplified Clinical Pulmonary Infection Scores (CPIS) were performed in 44 patients mechanically-ventilated for >48 h with neither active infection for the duration or suspicion of VAP. Patients who developed extrapulmonary infection were excluded.In total, 20 cases were suspected of having VAP and diagnosis was microbiologically confirmed in nine. In patients with confirmed VAP, procalcitonin levels were higher than in those without VAP. C-reactive protein levels and CPIS were lower in patients without suspected VAP, but could not discriminate confirmed and nonconfirmed suspicion of VAP. The best sensitivity and specificity (78 and 97%, respectively) corresponded to procalcitonin. The CPIS resulted in the same sensitivity, but had a lower specificity (80%). C-reactive protein had the worst sensitivity (56%), but a good specificity (91%). A CPIS ≥6 combined with serum levels of procalcitonin ≥2.99 ng·mL−1did not improve the sensitivity (67%), but resulted in 100% specificity.Procalcitonin might be useful in the diagnosis of ventilator-associated pneumonia. Combined values of Clinical Pulmonary Infection Scores and procalcitonin below the cut-off points excluded false-positive diagnoses of ventilator-associated pneumonia.
Polymorphisms in the epidermal growth factor receptor gene and the risk of primary lung cancer: a case-control study
Authors: Choi Jin Eun , Ha Park Sun , Kim Kyung Mee , Lee Won Kee , Kam Sin , Cha Sung Ick , Ho Kim Chang , Mo Kang Young , Kim Young-Chul , Han Sung Beom , Jung Tae Hoon , Park Jae Yong 
Published: October 2007

AbstractBackgroundPolymorphisms in Epidermal Growth Factor Receptor (EGFR) gene may influence EGFR production and/or activity, thereby modulating susceptibility to lung cancer. To test this hypothesis, we investigated the association between polymorphisms in theEGFRgene and the risk of lung cancer in a Korean population.MethodsWe first examined the frequencies of 39 candidate polymorphisms in theEGFRgene in 27 healthy Korean individuals. After then, we genotyped five polymorphisms (127378C>T, 142285G>A, 162093G>A, 181946C>T and 187114T>C) that have variant allele frequencies greater than 10%, in 582 lung cancer patients and in 582 healthy controls.ResultsOf the 5 polymorphisms, the 181946C>T genotype distribution was significantly different between the cases and controls (P= 0.04). Compared with the 181946 CC + CT genotype, the 181946 TT genotype was associated with a significantly decreased risk of lung cancer (adjusted OR = 0.63, 95% CI = 0.45–0.88,P= 0.007). When the analyses were stratified by smoking status, the protective effect of the TT genotype was statistically significant in ever-smokers (adjusted OR = 0.59, 95% CI = 0.41–0.86,P= 0.007), but not in never-smokers (adjusted OR = 0.89, 95% CI = 0.45–1.75,P= 0.73;P= 0.08, test for homogeneity). Consistent with the results of the genotyping analysis, the CGGCT haplotype with the 181946C allele was associated with a significantly increased risk of lung cancer compared to the CGGTT haplotype carrying the 181946T allele (adjusted OR = 1.50, 95% CI = 1.09–2.07,P= 0.012 and Bonferroni correctedP-value = 0.048).ConclusionThese results suggest that theEGFRpolymorphisms, particularly the 181945C>T polymorphism, could be used as markers for the genetic susceptibility to lung cancer.
An integrative expression vector for Actinosynnema pretiosum
Authors: Goh Shan , Camattari Andrea , Ng Daniel , Song Ruth , Madden Kevin , Westpheling Janet , Wong Victor VT 
Published: October 2007

Abstract

Background
The Actinomycete Actinosynnema pretiosum ssp. auranticum has commercial importance due to its production of ansamitocin P-3 (AP-3), a potent antitumor agent. One way to increase AP-3 production would be to constitutively express selected genes so as to relieve bottlenecks in the biosynthetic pathway; however, an integrative expression vector for A. pretiosum is lacking. The aim of this study was to construct a vector for heterologous gene expression in A. pretiosum.

Results
A series of integrative expression vectors have been made with the following features: the IS117 transposase from Streptomyces coelicolor, the constitutive ermE* promoter from Saccharopolyspora erythraea, different ribosome-binding site (RBS) sequences and xylE as a translational reporter. Positive E. coli clones and A. pretiosum transconjugants were assayed by catechol. pAP42, containing an E. coli consensus RBS, and pAP43, containing an asm19 RBS, gave strong and moderate gene expression, respectively. In addition, an operon construct capable of multi-gene expression was created. Plasmid integration sites in transconjugants were investigated and four different sites were observed. Although the most common integration site was within a putative ORF with sequence similarity to NADH-flavin reductase, AP-3 levels and cell growth of transconjugants were unaffected.

Conclusion
A set of integrative vectors for constitutive gene expression in A. pretiosum has been constructed. Gene translation is easily determined by colorimetric assay on an agar plate. The vectors are suitable for studies relating to AP-3 biosynthesis as they do not affect AP-3 production.
Susceptibility of Anopheles gambiae and Anopheles stephensi to tropical isolates of Plasmodium falciparum
Authors: Hume Jennifer CC , Tunnicliff Mark , Ranford-Cartwright Lisa C , Day Karen P 
Published: October 2007

Abstract

Background
The susceptibility of anopheline mosquito species to Plasmodium infection is known to be variable with some mosquitoes more permissive to infection than others. Little work, however, has been carried out investigating the susceptibility of major malaria vectors to geographically diverse tropical isolates of Plasmodium falciparum aside from examining the possibility of infection extending its range from tropical regions into more temperate zones.

Methods
This study investigates the susceptibility of two major tropical mosquito hosts (Anopheles gambiae and Anopheles stephensi) to P. falciparum isolates of different tropical geographical origins. Cultured parasite isolates were fed via membrane feeders simultaneously to both mosquito species and the resulting mosquito infections were compared.

Results
Infection prevalence was variable with African parasites equally successful in both mosquito species, Thai parasites significantly more successful in An. stephensi, and PNG parasites largely unsuccessful in both species.

Conclusion
Infection success of P. falciparum was variable according to geographical origin of both the parasite and the mosquito. Data presented raise the possibility that local adaptation of tropical parasites and mosquitoes has a role to play in limiting gene flow between allopatric parasite populations.
Single-walled carbon nanotube interactions with HeLa cells
Authors: Yehia Hadi N , Draper Rockford K , Mikoryak Carole , Walker Erin Kate , Bajaj Pooja , Musselman Inga H , Daigrepont Meredith C , Dieckmann Gregg R , Pantano Paul 
Published: October 2007

Abstract
This work concerns exposing cultured human epithelial-like HeLa cells to single-walled carbon nanotubes (SWNTs) dispersed in cell culture media supplemented with serum. First, the as-received CoMoCAT SWNT-containing powder was characterized using scanning electron microscopy and thermal gravimetric analyses. Characterizations of the purified dispersions, termed DM-SWNTs, involved atomic force microscopy, inductively coupled plasma – mass spectrometry, and absorption and Raman spectroscopies. Confocal microRaman spectroscopy was used to demonstrate that DM-SWNTs were taken up by HeLa cells in a time- and temperature-dependent fashion. Transmission electron microscopy revealed SWNT-like material in intracellular vacuoles. The morphologies and growth rates of HeLa cells exposed to DM-SWNTs were statistically similar to control cells over the course of 4 d. Finally, flow cytometry was used to show that the fluorescence from MitoSOX™ Red, a selective indicator of superoxide in mitochondria, was statistically similar in both control cells and cells incubated in DM-SWNTs. The combined results indicate that under our sample preparation protocols and assay conditions, CoMoCAT DM-SWNT dispersions are not inherently cytotoxic to HeLa cells. We conclude with recommendations for improving the accuracy and comparability of carbon nanotube (CNT) cytotoxicity reports.
Isolated HIV-1 core is active for reverse transcription
Authors: Warrilow David , Stenzel Deborah , Harrich David 
Published: October 2007

Abstract
Whether purified HIV-1 virion cores are capable of reverse transcription or require uncoating to be activated is currently controversial. To address this question we purified cores from a virus culture and tested for the ability to generate authentic reverse transcription products. A dense fraction (approximately 1.28 g/ml) prepared without detergent, possibly derived from disrupted virions, was found to naturally occur as a minor sub-fraction in our preparations. Core-like particles were identified in this active fraction by electron microscopy. We are the first to report the detection of authentic strong-stop, first-strand transfer and full-length minus strand products in this core fraction without requirement for an uncoating activity.
Metamorphosis of an identified serotonergic neuron in the Drosophila olfactory system
Authors: Roy Bidisha , Singh Ajeet P , Shetty Chetak , Chaudhary Varun , North Annemarie , Landgraf Matthias , VijayRaghavan K , Rodrigues Veronica 
Published: October 2007

Abstract
Background
Odors are detected by sensory neurons that carry information to the olfactory lobe where they connect to projection neurons and local interneurons in glomeruli: anatomically well-characterized structures that collect, integrate and relay information to higher centers. Recent studies have revealed that the sensitivity of such networks can be modulated by wide-field feedback neurons. The connectivity and function of such feedback neurons are themselves subject to alteration by external cues, such as hormones, stress, or experience. Very little is known about how this class of central neurons changes its anatomical properties to perform functions in altered developmental contexts. A mechanistic understanding of how central neurons change their anatomy to meet new functional requirements will benefit greatly from the establishment of a model preparation where cellular and molecular changes can be examined in an identified central neuron.

Results
In this study, we examine a wide-field serotonergic neuron in the Drosophila olfactory pathway and map the dramatic changes that it undergoes from larva to adult. We show that expression of a dominant-negative form of the ecdysterone receptor prevents remodeling. We further use different transgenic constructs to silence neuronal activity and report defects in the morphology of the adult-specific dendritic trees. The branching of the presynaptic axonal arbors is regulated by mechanisms that affect axon growth and retrograde transport. The neuron develops its normal morphology in the absence of sensory input to the antennal lobe, or of the mushroom bodies. However, ablation of its presumptive postsynaptic partners, the projection neurons and/or local interneurons, affects the growth and branching of terminal arbors.

Conclusion
Our studies establish a cellular system for studying remodeling of a central neuromodulatory feedback neuron and also identify key elements in this process. Understanding the morphogenesis of such neurons, which have been shown in other systems to modulate the sensitivity and directionality of response to odors, links anatomy to the development of olfactory behavior.