bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sputum Cytologic Atypia Predicts Incident Lung Cancer: Defining Latency and Histologic Specificity
Authors: Byers Tim , Wolf Holly J. , Franklin Wilbur A. , Braudrick Sarah , Merrick Daniel T. , Shroyer Kenneth R. , Hirsch Fred R. , Zeng Chan , Barón Anna E. , Bunn Paul A. , Miller York E. , Kennedy Timothy C. 
Published: January 2008

Abstract
Background: There is a need for early detection methods for lung cancer. Radiologic imaging may be more sensitive for peripheral cancers than for cancers arising in the central airways, from which bronchial epithelial cells are exfoliated into the sputum.
Methods: Sputum samples were collected at baseline and periodically thereafter in a cohort of smokers and former smokers with chronic obstructive lung disease. The association between cytologic atypia and incident lung cancer was assessed by hazard ratios (HR; 95% confidence intervals) using Cox regression and by odds ratios (95% confidence intervals) using logistic regression, adjusting for potential confounding factors.
Results: We observed 174 incident lung cancers in a cohort of 2,521 people over 9,869 person-years of observation. Risk for incident lung cancer was increased among those with cytologic atypia graded as moderate or worse (adjusted HR, 2.37; 1.68-3.34). The association between sputum atypia and lung cancer incidence was greatest for those sputum samples collected 5 months or less before the diagnosis of lung cancer (odds ratio, 10.32; 5.34-19.97). The association was substantially stronger for squamous cell lung cancers (HR, 5.13; 2.89-9.10) than for adenocarcinomas (HR, 1.85; 0.94-3.65).
Conclusion: Cytologic atypia is a marker for increased lung cancer risk. These cytologic changes seem to arise from late events that are most apparent for cancers arising in the central respiratory airways. Whether cytologic atypia might complement radiologic imaging in a combined approach to lung cancer, early detection requires additional evaluation of those two methods used together. (Cancer Epidemiol Biomarkers Prev 2008;17(1):158–63)
Profiling Tumor-Associated Markers for Early Detection of Malignant Mesothelioma: An Epidemiologic Study
Authors: Amati Monica , Tomasetti Marco , Scartozzi Mario , Mariotti Laura , Alleva Renata , Pignotti Elettra , Borghi Battista , Valentino Matteo , Governa Mario , Neuzil Jiri , Santarelli Lory 
Published: January 2008

Abstract
Improved detection methods for diagnosis of asymptomatic malignant mesothelioma (MM) are essential for an early and reliable detection and treatment of this type of neoplastic disease. Thus, focus has been on finding tumor markers in the blood that can be used for noninvasive detection of MM. Ninety-four asbestos-exposed subjects defined at high risk, 22 patients with MM, and 54 healthy subjects were recruited for evaluation of the clinical significance of 8-hydroxy-2′-deoxyguanosine (8OHdG) in WBCs and plasma concentrations of soluble mesothelin-related peptides (SMRPs), angiogenic factors [platelet-derived growth factor β, hepatocyte growth factor, basic fibroblast growth factor, and vascular endothelial growth factor β (VEGFβ)], and matrix proteases [matrix metalloproteinase (MMP) 2, MMP9, tissue inhibitor of metalloproteinase (TIMP) 1, and TIMP2] for potential early detection of MM. The area under receiver operating characteristic (ROC) curves indicate that 8OHdG levels can discriminate asbestos-exposed subjects from healthy controls but not from MM patients. Significant area under ROC curve values were found for SMRPs, discriminating asbestos-exposed subjects from MM patients but not from healthy controls. Except for platelet-derived growth factor β, the hepatocyte growth factor, basic fibroblast growth factor, and VEGFβ can significantly differentiate high-risk individuals from healthy control and cancer groups. No diagnostic value was observed for MMP2, MMP9, TIMP1, and TIMP2. In addition to the diagnostic performance defined by the ROC analysis, the sensitivity and specificity results of markers with clinical significance were calculated at defined cutoffs. The combination of 8OHdG, VEGFβ, and SMRPs best distinguished the individual groups, suggesting a potential indicator of early and advanced MM cancers. The combination of blood biomarkers and radiographic findings could be used to stratify the risk of mesothelioma in asbestos-exposed populations. (Cancer Epidemiol Biomarkers Prev 2008;17(1):163–70)
Exfoliated Buccal Mucosa Cells as a Source of DNA to Study Oxidative Stress
Authors: Borthakur Gayatri , Butryee Chaniphun , Stacewicz-Sapuntzakis Maria , Bowen Phyllis E. 
Published: January 2008

AbstractThe extent of oxidative DNA damage is considered a biomarker of carcinogenic process and could be investigated in population studies using easily obtained cells. The oxidized DNA base adduct 8-hydroxy-2-deoxyguanosine (8-OHdG) released by enzymatic hydrolysis of DNA is commonly assayed by high performance liquid chromatography with electrochemical detection. It is expressed as a ratio of 8-OHdG to unoxidized deoxyguanosine. We modified and improved this method, determined the optimal time for harvesting buccal mucosa cells (BMC), assessed whether they mirror peripheral circulating blood cell DNA damage, and compared the anticoagulants, heparin, and EDTA for consistency in measurement of leukocyte 8-OHdG. Thirty-one healthy participants, randomized into two groups, donated BMC and blood samples. Samples were collected at baseline and either 3 or 7 days after baseline. Results showed no correlation between 8-OHdG/deoxyguanosine ratios in BMC and peripheral blood leukocytes at any time point regardless of harvest time. BMC had much higher oxidative DNA damage, but displayed a 25.6% reduction in the oxidized DNA adduct level (P &lt; 0.04) at 3 days after baseline. Leukocytes collected in heparin and EDTA had similar 8OHdG/deoxyguanosine ratios; however, EDTA was preferred, as it produced a clean nuclear pellet without hemoglobin contamination, and the results were less variable. This improved assay shows within subject stability over time in both leukocyte and BMC DNA damage, increasing the probability that small intervention differences can be detected in healthy subjects. Buccal cells provide an accessible pool of epithelial cells that represents higher levels of DNA damage than circulating leukocytes. (Cancer Epidemiol Biomarkers Prev 2008;17(1):212–9)
Properties of the Wind Field within the Oklahoma City Park Avenue Street Canyon. Part I: Mean Flow and Turbulence Statistics
Authors: Nelson M. A. , Pardyjak E. R. , Klewicki J. C. , Pol S. U. , Brown M. J. 
Published: January 2008

Abstract
Velocity data were obtained from sonic anemometer measurements within an east–west-running street canyon located in the urban core of Oklahoma City, Oklahoma, during the Joint Urban 2003 field campaign. These data were used to explore the directional dependence of the mean flow and turbulence within a real-world street canyon. The along-canyon vortex that is a key characteristic of idealized street canyon studies was not evident in the mean wind data, although the sensor placement was not optimized for the detection of such structures. Instead, surface wind measurements imply that regions of horizontal convergence and divergence exist within the canopy, which are likely caused by taller buildings diverting the winds aloft down into the canopy. The details of these processes appear to be dependent on relatively small perturbations in the prevailing wind direction. Turbulence intensities within the canyon interior appeared to have more dependence on prevailing wind direction than they did in the intersections. Turbulence in the intersections tended to be higher than was observed in the canyon interior. This behavior implies that there are some fundamental differences between the flow structure found in North American–style cities where building heights are typically heterogeneous and that found in European-style cities, which generally have more homogeneous building heights. It is hypothesized that the greater three-dimensionality caused by the heterogeneous building heights increases the ventilation of the urban canopy through mean advective transport as well as enhanced turbulence.
The Aberrant Anterior Tibial Artery
Authors: Klecker Rosemary J. , Winalski Carl S. , Aliabadi Piran , Minas Tom 
Published: January 2008

Background Injury of a popliteal fossa artery during orthopaedic knee surgery is very rare but has serious consequences. The risk of vascular trauma during orthopaedic procedures may be increased when there is abnormal branching of the popliteal artery with an aberrant anterior tibial artery originating above the popliteus muscle and coursing between the posterior tibial cortex and ventral margin of the popliteus muscle. Preoperative identification of this anatomical variant may help avoid these injuries. Hypothesis The aberrant anterior tibial artery is present in a substantial portion of the population and can be visualized by magnetic resonance imaging. Study Design Cross-sectional study; Level of evidence, 3. Methods Retrospective review of 1116 consecutive knee magnetic resonance imaging studies was performed to evaluate the prevalence of an aberrant anterior tibial artery. Images were reviewed by 3 musculoskeletal radiologists. Results The aberrant anterior tibial artery was present in 23 of 1116 extremities for a prevalence of 2.1 %. The aberrant artery was most easily identified on axial and sagittal magnetic resonance imaging scans. Conclusion The aberrant anterior tibial artery is a relatively common normal variant, and magnetic resonance is an excellent modality for detection of the artery close to the posterior joint capsule and tibial cortex. Clinical Relevance The anatomy suggests the aberrant anterior tibial artery may be at greater risk of injury in orthopaedic procedures such as high tibial osteotomy, revision total knee arthroplasty, lateral meniscal repair, posterior cruciate ligament reconstruction, and screw fixation for tibial tubercle osteotomy. Careful inspection of preoperative magnetic resonance imaging studies may alert the surgeon to the presence of this anatomical variant.
A Randomized Controlled Trial Comparing the Effectiveness of Functional Knee Brace and Neoprene Sleeve Use after Anterior Cruciate Ligament Reconstruction
Authors: Birmingham Trevor B. , Bryant Dianne M. , Giffin J. Robert , Litchfield Robert B. , Kramer John F. , Donner Allan , Fowler Peter J. 
Published: January 2008

Background Despite a lack of evidence for their effectiveness, functional knee braces are commonly prescribed to patients after anterior cruciate ligament (ACL) reconstruction. Purpose This trial was conducted to compare postoperative outcomes in patients using an ACL functional knee brace and patients using a neoprene knee sleeve. Hypothesis Patients using a brace will have superior outcomes than those using a sleeve. Study Design Randomized controlled clinical trial; Level of evidence, 1. Methods One hundred fifty patients were randomized to receive a brace (n = 76) or neoprene sleeve (n = 74) at their 6-week postoperative visit after primary ACL reconstruction with hamstring autograft. Patients were assessed preoperatively, then 6 weeks and 6, 12, and 24 months postoperatively. Outcome measures included disease-specific quality of life (Anterior Cruciate Ligament–Quality of Life [ACL-QOL] Questionnaire), anterior tibial translation (KT-1000 arthrometer side-to-side difference), the single-limb forward hop test (limb symmetry index), and Tegner Activity Scale. Outcomes at 1 and 2 years were compared after adjusting for baseline scores. Subjective ratings of how patients felt while using the brace/sleeve were also collected for descriptive purposes using a questionnaire. Four a priori directional subgroup hypotheses were evaluated using tests for interactions. Results There were no significant differences between brace (n = 62) and sleeve (n = 65) groups for any of the outcomes at 1- and 2-year follow-ups. Adjusted mean differences at 2 years were as follows: −0.94 (95% confidence interval [CI], −7.52 to 5.64) for the ACL-QOL Questionnaire, −0.10 mm (95% CI, −0.99 to 0.81) for KT-1000 arthrometer side-to-side difference, −0.87% (95% CI, −8.89 to 7.12) for hop limb symmetry index, and −0.05 (95% CI, −0.72 to 0.62) for the Tegner Activity Scale. Subjective ratings of confidence in the knee provided by the brace/sleeve were higher for the brace group than the sleeve group. Subgroup findings were minimal. Adverse events were few and similar between groups. Conclusions A functional knee brace does not result in superior outcomes compared with a neoprene sleeve after ACL reconstruction. Current evidence does not support the recommendation of using an ACL functional knee brace after ACL reconstruction.
Flavopiridol causes early mitochondrial damage in chronic lymphocytic leukemia cells with impaired oxygen consumption and mobilization of intracellular calcium
Authors: Hussain Syed-Rehan A. , Lucas David M. , Johnson Amy J. , Lin Thomas S. , Bakaletz Alan P. , Dang Vinh X. , Viatchenko-Karpinski Serge , Ruppert Amy S. , Byrd John C. , Kuppusamy Periannan , Crouser Elliott D. , Grever Michael R. 
Published: January 2008

AbstractEffective administration of flavopiridol in advanced-stage chronic lymphocytic leukemia (CLL) is often associated with early biochemical evidence of tumor cell lysis. Previous work using other cell types showed that flavopiridol impacts mitochondria, and in CLL cells flavopiridol down-regulates the mitochondrial protein Mcl-1. We therefore investigated mitochondrial structure and function in flavopiridol-treated CLL patient cells and in the lymphoblastic cell line 697 using concentrations and times at which tumor lysis is observed in treated patients. Mitochondrial membrane depolarization was detected in flavopiridol-treated CLL cells by 6 hours, well before the onset of cell death. Flavopiridol-induced mitochondrial depolarization was not blocked by caspase inhibitors or by the calcium chelator EGTA, but was reduced by Bcl-2 overexpression. Intracellular calcium mobilization was noted at early time points using fluorescence microscopy. Furthermore, electron paramagnetic resonance oximetry showed a gradual but significant reduction in cellular oxygen consumption rate by 6 hours, corresponding with ultrastructural mitochondrial damage detected by electron microscopy. These observations suggest that in CLL and 697 cells, flavopiridol mediates its cytotoxic effects via induction of the mitochondrial permeability transition and changes in intracellular calcium.
Profiling quality of care for patients with chronic headache in three different German hospitals – a case study
Authors: Melchart Dieter , Wessel Anne , Brand Ronald , Hager Stefan , Weidenhammer Wolfgang 
Published: January 2008

Abstract

Background
Legal requirements for quality assurance in German rehabilitation hospitals include comparisons of providers. Objective is to describe and to compare outcome quality of care offered by three hospitals providing in-patient rehabilitative treatment exemplified for patients with chronic headache.

Methods
We performed a prospective three center observational study on patients suffering from chronic headache. Patients underwent interventions commonly used according to internal guidelines of the hospitals. Measurements were taken at three points in time (at admission, at discharge and 6 months after discharge). Indicators of outcome quality included pain intensity and frequency of pain, functional ability, depression, quality of life and health related behavior. Analyses of differences amongst the hospitals were adjusted by covariates due to case-mix situation.

Results
306 patients from 3 hospitals were included in statistical analysis. Amongst the hospitals, patients differed significantly in age, education, diagnostic subgroups, beliefs, and with respect to some pain-related baseline values (covariates). Patients in all three hospitals benefited from intervention to a clinically relevant degree. At discharge from hospital, outcome quality differed significantly after adjustment according to case-mix only in terms of patients' global assessment of treatment results. Six months after discharge, the only detectable significant differences were for secondary outcomes like improved coping with stress or increased use of self-help. The profiles for satisfaction with the hospital stay showed clear differences amongst patients.

Conclusion
The results of this case study do not suggest a definite overall ranking of the three hospitals that were compared, but outcome profiles offer a multilayer platform of reliable information which might facilitate decision making.
Selective blockade of lymphopoiesis induced by kalanchosine dimalate: inhibition of IL-7-dependent proliferation
Authors: de Paiva Luciana S , Nobrega Alberto , De Melo Giany O , Hayashi Elize A , Carvalho Vinicius , Rodrigues e Silva Patricia M , Bellio Maria , Teixeira Gerlinde P , Rumjanek Vivian , Costa Sonia S , Koatz Vera Lúcia G 
Published: January 2008

AbstractLymphopoiesis and myelopoiesis continuously generate mature cells from hematopoietic cell progenitors during the lifetime of the organism. The identification of new endogenous or exogenous substances that can act specifically on the differentiation of distinct cell lineages is of relevance and has potential therapeutical use. Kalanchoe brasiliensis (Kb) is a medicinal plant from the Crassulaceae family, used in folk medicine to treat inflammatory and infectious diseases. Here, we show that short-term treatment of naïve mice with Kb led to a strong and selective inhibition of lymphopoiesis, affecting B and T cell lineages without reduction of the myeloid lineage development. Similar effects were observed after treatment with the highly purified compound kalanchosine dimalate (KMC), obtained from Kb. Numbers of mature lymphocytes in secondary lymphoid organs were preserved in Kb(KMC)-treated mice. The effect of Kb(KMC) was not a result of secondary augmentation of plasma levels of endogenous corticoids; neither involves TNF-α, type-I IFN, or TLR2/TLR4 ligands, which have all been described as selective inhibitors of lymphopoiesis. Flow cytometry analysis of the phenotypes of T and B cell precursors indicate a blockade of maturation on IL-7-dependent, proliferative stages. In vitro, Kb(KMC) inhibited the IL-7-dependent proliferation of pre-B cells and does not induce massive apoptosis of B and T cell precursors. These results suggest that Kb(KMC) is selectively blocking lymphopoiesis through a mechanism that does not involve the previously characterized substances, possibly acting on the IL-7 signaling pathway, opening new perspectives for a potential therapeutic use of Kb-derived drugs.
Murine β-defensin 2 promotes TLR-4/MyD88-mediated and NF-κB-dependent atypical death of APCs via activation of TNFR2
Authors: Biragyn Arya , Coscia Marta , Nagashima Kunio , Sanford Michael , Young Howard A , Olkhanud Purevdorj 
Published: January 2008

AbstractMammalian antimicrobial peptides, including β-defensins, represent an ancient arm of innate immunity designed to directly neutralize invading microbes. Previously, we demonstrated that murine β-defensin 2 (mDF2β) also acted as an endogenous ligand for TLR-4-activating maturation of dendritic cells (DCs). Herein, we report that this TLR-4 –dependent activation leads to induction of an atypical cell death that is unexpectedly exaggerated by the inhibition of caspases. Experiments using APCs with nonfunctional TNF-α or its receptors suggest that this is a NF-κB- and TNF-α-dependent process that does not require TNFR1. We demonstrate that mDF2β triggers a TNFR2-mediated signaling cascade of “self-destruction” through up-regulation of membrane-bound TNF-α and TNFR2. This appears not to be an isolated phenomenon, as human synthetic β-defenisn 3 was also able to activate and kill DCs. We propose that β-defenins may play an important immunoregulatory role as controllers of the natural process of elimination of activated APCs.
Functional Structure of Adipocytes Differentiated from Human Umbilical Cord Stroma-Derived Stem Cells
Authors: Karahuseyinoglu Sercin , Kocaefe Cetin , Balci Deniz , Erdemli Esra , Can Alp 
Published: January 2008

Abstract
It has been previously demonstrated that human umbilical cord stroma-derived stem cells (HUCSCs) are competent to differentiate into adipocytes. However, controversies have arisen as to whether HUCSCs can become mature adipocytes or not, and to what extent these cells can be induced in adipogenic pathway. Here, we extensively analyzed their adipogenic potency with a structural and functional approach by determining lipid formation dynamics in concordance to adipocyte-specific markers. During a 35-day period, HUCSCs respond to adipogenic induction, at which point 88% of cells exhibited multilocular lipid granules (LGs) having a mean diameter of 3 μm in round-shaped, F-actin-poor cells. Although the 1st week of induction did not generally display typical lipidogenic phenotypes, the degree of adipogenesis was dissected and confirmed by mRNA expressions of peroxisome proliferator-activated receptor γ, C/EBP-β, sterol regulatory element-binding transcription factor 1, adipophilin, stearoyl-CoA desaturase, glycerol 3-phosphate dehydrogenase 1, LIPE, adiponectin, and leptin. All markers tested were found elevated in various amounts (3–70-fold) around day 7 and reached a plateau after day 14 or 21 (5–335-fold). Perilipin as a surface protein around the LGs was confined exclusively to the enlarging LGs. Conclusively, we propose that after the termination of proliferation, HUCSCs possess the biochemical and cellular machinery to successfully differentiate into maturing adipocytes under adipogenic conditions, and this feature will ultimately allow these fetus-derived stem cells to be used for various therapeutic or esthetic purposes.
Disclosure of potential conflicts of interest is found at the end of this article.
Bone Marrow-Derived Cells Exhibiting Lung Epithelial Cell Characteristics Are Enriched In Vivo Using Methylguanine DNA Methyltransferase-Mediated Drug Resistance
Authors: Reese Jane S. , Roth Justin C. , Gerson Stanton L. 
Published: January 2008

Abstract
Previous studies have suggested that donor bone marrow-derived cells can differentiate into lung epithelial cells at low frequency. We investigated whether we could enrich the number of donor-derived hematopoietic cells that have type II pneumocyte characteristics by overexpression of the drug resistance gene methylguanine DNA methyltransferase (MGMT). MGMT encodes O6-alkylguanine DNA alkyltransferase (AGT), a drug resistance protein for DNA damage induced by N,N′-bis(2-chloroethyl)-N-nitrosourea (BCNU), and the mutant P140K MGMT confers resistance to BCNU and the AGT inactivator O6-benzylguanine (BG). For this study, we used two MGMT selection models: one in which donor cells had a strong selection advantage because the recipient lung lacked MGMT expression, and another in which drug resistance was conferred by gene transfer of P140K MGMT. In both models, we saw an increase in the total number of donor-derived cells in the lung after BCNU treatment. Analysis of single-cell suspensions from 28 mice showed donor-derived cells with characteristics of type II pneumocytes, determined by surfactant protein C (SP-C) expression. Furthermore, an increase in the percentage of donor-derived SP-C cells was noted after BCNU or BG and BCNU treatment. This study demonstrates that bone marrow cells expressing MGMT can engraft in the lung and convert into cells expressing the type II pneumocyte protein SP-C. Furthermore, these cells can be enriched in response to alkylating agent-mediated lung injury. These results suggest that expression of MGMT could enhance the capacity of bone marrow-derived cells to repopulate lung epithelium, and when used in combination with a gene of interest, MGMT could have therapeutic applications.