bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breaking the Invulnerability of Cancer Stem Cells: Two-Step Strategy to Kill the Stem-like Cell Subpopulation of Multiple Myeloma
Authors: Morgenroth Agnieszka , Vogg Andreas T.J. , Zlatopolskiy Boris D. , Siluschek Monika , Oedekoven Caroline , Mottaghy Felix M. 
Published: October 2013

Abstract
In multiple myeloma, the presence of highly resistant cancer stem cells (CSC) that are responsible for tumor metastasis and relapse has been proven. Evidently, for achieving complete response, new therapeutic paradigms that effectively eradicate both, CSCs and bulk cancer populations, need to be developed. For achieving that goal, an innovative two-step treatment combining targeting of thymidine de novo synthesis pathway and a nanoirradiation by the Auger electron emitting thymidine analogue 123/125I-5-iodo-4′-thio-2′-deoxyuridine (123/125I-ITdU) could be a promising approach. The pretreatment with thymidylate synthase inhibitor 5-fluoro-2′-deoxyuridine (FdUrd, 1 μmol/L for 1 hour) efficiently induced proliferation and terminal differentiation of isolated myeloma stem-like cells. Moreover, FdUrd stimulation led to a decreased activity of a functional CSC marker, aldehyde dehydrogenase (ALDH). The metabolic conditioning by FdUrd emerged to be essential for enhanced incorporation of 125I-ITdU (incubation with 50 kBq/2 × 104 cells for 4 days) and, consequently, for the induction of irreparable DNA damage. 125I-ITdU showed a pronounced antimyeloma effect on isolated tumor stem-like cells. More than 85% of the treated cells were apoptotic, despite activation of DNA repair mechanisms. Most important, exposure of metabolically conditioned cells to 125I-ITdU resulted in a complete inhibition of clonogenic recovery. This is the first report showing that pretreatment with FdUrd sensitizes the stem-like cell compartment in multiple myeloma to apoptosis induced by 125I-ITdU–mediated nanoirradiation of DNA. Mol Cancer Ther; 13(1); 144–53. ©2013 AACR.
Serum neutrophil gelatinase-associated lipocalin (NGAL) in patients with Shiga toxin mediated haemolytic uraemic syndrome (STEC-HUS)
Authors: Beneke Jan , Menne Jan , Vetter Frank , Schmidt Bernhard M. W. , Schiffer Mario , Haller Hermann , Kümpers Philipp , Kielstein Jan T. , Lukasz Alexander 
Published: October 2013

SummaryNeutrophil gelatinase-associated lipocalin (NGAL) is an increasingly used biomarker for acute kidney injury (AKI). Its utility in adult patients with AKI caused by Shiga toxin producing Escherichia coli infection (STEC)-associated haemolytic-uraemic syndrome (HUS), remains unknown. We aimed to evaluate the prognostic value of serum NGAL admission levels for the need of renal replacement therapy (RRT) in STEC-HUS patients. Baseline serum NGAL was determined by ELISA in 39 patients with STEC O104:H4 infection cared for at Hannover Medical School during the outbreak in Germany through May-July 2011. Patients with HUS had significant higher NGAL levels than healthy controls (379 [248 – 540] vs 39.0 [37.5–45] ng/ml, p < 0.0001). During clinical course, 24 patients required RRT at a median of five days after admission. NGAL admission levels were higher in patients requiring RRT (476 (344–639) ng/ml) compared to patients not requiring RRT (257 (196–426) ng/ml; p < 0.001). Unadjusted and adjusted logistic regression analyses identified NGAL as an independent predictor for need of RRT. In a combined model, a joint NGAL/AKIN classification approach improved the predictive accuracy for need of RRT over either marker alone. The combined categorical cut-off point defined by NGAL ≥ 330 ng/ml and presence of AKI (AKIN ≥ I) on admission correctly identified 20 of 24 patients requiring RRT (odds ratio 20, sensitivity 83%, specificity 80%, negative predictive value 75%, positive predictive value 87%). NGAL may serve as an adjunctive tool to improve risk prediction in patients with STEC-HUS.
Anti-prothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies and the risk of thrombosis in the antiphospholipid syndrome
Authors: Sciascia Savino , Sanna Giovanni , Murru Veronica , Roccatello Dario , Khamashta Munther A. , Bertolaccini Maria Laura 
Published: October 2013

SummaryAntibodies to prothrombin are detected by directly coating prothrombin on irradiated ELISA plates (aPT) or by using the phosphatidylserine/ prothrombin complex as antigen (aPS/PT). Although these antibodies have both been associated with antiphospholipid syndrome (APS) and a correlation between the two assays have been reported, it seems that aPT and aPS/PT belong to different populations of autoantibodies. It was our objective to systematically review the available evidence on aPT and aPS/PT antibodies and the risk of thrombosis in APS. Medline-reports published between 1988 and 2013 investigating aPT and aPS/PT as a risk factor for thrombosis were included. Whenever possible, antibody isotype(s) and site of thrombosis were analysed. This systematic review is based on available data from more than 7,000 patients and controls from 38 studies analysing aPT and 10 aPS/PT. Antibodies to prothrombin (both aPT and aPS/PT) increased the risk of thrombosis (odds ratio [OR] 2.3; 95% confidence interval [CI] 1.72–3.5). aPS/PT seemed to represent a stronger risk factor for thrombosis, both arterial and/or venous than aPT (OR 5.11; 95%CI 4.2–6.3 and OR 1.82; 95%CI 1.44–2.75, respectively). In conclusion, routine measurement of aPS/PT (but not aPT) might be useful in establishing the thrombotic risk of patients with previous thrombosis and/or systemic lupus erythematosus. Their inclusion as laboratory criteria for the APS should be indisputably further explored.
Validation of Noninvasive Indices of Global Systolic Function in Patients With Normal and Abnormal Loading Conditions
Authors: Yotti Raquel , Bermejo Javier , Benito Yolanda , Sanz-Ruiz Ricardo , Ripoll Cristina , Martínez-Legazpi Pablo , del Villar Candelas Pérez , Elízaga Jaime , González-Mansilla Ana , Barrio Alicia , Bañares Rafael , Fernández-Avilés Francisco 
Published: October 2013

Background—
Noninvasive indices based on Doppler echocardiography are increasingly used in clinical cardiovascular research to evaluate left ventricular global systolic chamber function. Our objectives were to clinically validate ultrasound-based methods of global systolic chamber function to account for differences between patients in conditions of abnormal load, and to assess their sensitivity to load confounders.

Methods and Results—

Twenty-seven patients (8 dilated cardiomyopathy, 10 normal ejection fraction, and 9 end-stage liver disease) underwent simultaneous echocardiography and left heart catheterization with pressure-conductance instrumentation. The reference index, maximal elastance (
E
max
), was calculated from pressure–volume loop data obtained during acute inferior vena cava occlusion. A wide range of values were observed for left ventricular systolic chamber function (
E
max
: 2.8±1.0 mm Hg/mL), preload, and afterload. Among the noninvasive indices tested, the peak ejection intraventricular pressure difference showed the best correlation with
E
max
(
R
=0.75). A significant but weaker correlation with
E
max
was observed for ejection fraction (
R
=0.41), midwall fractional shortening (
R
=0.51), global circumferential strain (
R
=−0.53), and strain rate (
R
=−0.46). Longitudinal strain and strain rate failed to correlate with
E
max
, as did noninvasive single-beat estimations of this index. Principal component and multiple regression analyses demonstrated that peak ejection intraventricular pressure difference was less sensitive to load, whereas ejection fraction and longitudinal strain and strain rate were heavily influenced by afterload.

Conclusions—
Current ultrasound methods have limited accuracy to characterize global left ventricular systolic chamber function in a given patient. The Doppler-derived peak ejection intraventricular pressure difference should be preferred for this purpose because it best correlates with the reference index and is more robust in conditions of abnormal load.
Preventable Readmissions Within 30 Days of Ischemic Stroke Among Medicare Beneficiaries
Authors: Lichtman Judith H. , Leifheit-Limson Erica C. , Jones Sara B. , Wang Yun , Goldstein Larry B. 
Published: October 2013

Background and Purpose—
The Centers for Medicare and Medicaid Services proposes to use 30-day hospital readmissions after ischemic stroke as part of the Hospital Inpatient Quality Reporting Program for payment determination beginning in 2016. The proportion of poststroke readmissions that is potentially preventable is unknown.

Methods—

Thirty-day readmissions for all Medicare fee-for-service beneficiaries aged ≥65 years discharged alive with a primary diagnosis of ischemic stroke (
International Classification of Diseases
,
Ninth Revision
, Clinical Modification 433, 434, 436) between December 2005 and November 2006 were analyzed. Preventable readmissions were identified based on 14 Prevention Quality Indicators developed for use with administrative data by the US Agency for Healthcare Research and Quality. National, hospital-level, and regional preventable readmission rates were estimated. Random-effects logistic regression was also used to determine patient-level factors associated with preventable readmissions.

Results—
Among 307 887 ischemic stroke discharges, 44 379 (14.4%) were readmitted within 30 days; 5322 (1.7% of all discharges) were the result of a preventable cause (eg, pneumonia), and 39 057 (12.7%) were for other reasons (eg, cancer). In multivariate analysis, older age and cardiovascular-related comorbid conditions were strong predictors of preventable readmissions. Preventable readmission rates were highest in the Southeast, Mid-Atlantic, and US territories and lowest in the Mountain and Pacific regions.

Conclusions—
On the basis of Agency for Healthcare Research and Quality Prevention Quality Indicators, we found that a small proportion of readmissions after ischemic stroke were classified as preventable. Although other causes of readmissions not reflected in the Agency for Healthcare Research and Quality measures could also be avoidable, hospital-level programs intended to reduce all-cause readmissions and costs should target high-risk patients.
The Media-Entertainment Industry and the “War on Drugs” in Mexico
Authors: Mercille Julien 
Published: October 2013

Since 2006, Mexico has militarized its “war on drugs,” backed by the United States. Examination of this drug war from a critical political economic angle suggests that the neoliberal reforms implemented in Mexico over the past several decades have increased the size of the drug industry and that drug war rhetoric facilitates the containment of popular opposition to neoliberal policies. U.S. popular culture has contributed to legitimizing the drug war and making it more acceptable to the U.S. public. An analysis of selected movies, television series, and a video game shows that the themes presented in these productions are very similar to those conveyed by U.S. government officials and mainstream analysts. Indeed, popular culture messages reflect elite views of U.S. foreign policy because the media-entertainment industry is itself part of the corporate establishment. Desde 2006, México, con el apoyo de los Estados Unidos, ha militarizado su “guerra contra el narcotráfico.” Una crítica de esta guerra contra el narco de un punto de vista político-económico sugiere que las reformas neoliberales implementadas en México durante ya varias décadas han agrandado la industria de estupefacientes, y que la retórica de la guerra contra el narco facilita la contención de la oposición popular que se opone a la política neoliberal. Mientras tanto, en los Estados Unidos, la cultura popular ha contribuido a legitimar y hacer más aceptable la guerra contra el narco. Un análisis de películas y series de televisión seleccionadas, más un juego de video, muestra que los temas presentados en estas producciones son muy parecidos a los difundidos por oficiales del gobierno de Estados Unidos y analistas convencionales. De hecho, los mensajes de la cultura popular reflejan las perspectivas de la élite con respecto a la política exterior de los Estados Unidos porque los mismos medios de entretenimiento forman parte del establecimiento corporativo.
In vivo leukemogenic potential of an interleukin 7 receptor α chain mutant in hematopoietic stem and progenitor cells
Authors: Yokoyama Kazuaki , Yokoyama Nozomi , Izawa Kiyoko , Kotani Ai , Harashima Akira , Hozumi Katsuto , Tojo Arinobu 
Published: October 2013

Key Points
Gain-of function mutation of IL7Rα induces lymphoid leukemia as well as myeloproliferative disease. In vivo oncogenicity of mutant IL7Rα is influenced by the differentiation stage at which it occurs.
Angiogenic capacity of M1- and M2-polarized macrophages is determined by the levels of TIMP-1 complexed with their secreted proMMP-9
Authors: Zajac Ewa , Schweighofer Bernhard , Kupriyanova Tatyana A. , Juncker-Jensen Anna , Minder Petra , Quigley James P. , Deryugina Elena I. 
Published: October 2013

Key PointsAcquisition of high angiogenesis-inducing capacity by human and murine macrophages requires their polarization toward the M2 phenotype. M2-polarized macrophages shutdown their TIMP1 gene expression and initiate production of highly angiogenic TIMP-deficient proMMP-9.
Human and viral interleukin-6 and other cytokines in Kaposi sarcoma herpesvirus-associated multicentric Castleman disease
Authors: Polizzotto Mark N. , Uldrick Thomas S. , Wang Victoria , Aleman Karen , Wyvill Kathleen M. , Marshall Vickie , Pittaluga Stefania , O’Mahony Deirdre , Whitby Denise , Tosato Giovanna , Steinberg Seth M. , Little Richard F. , Yarchoan Robert 
Published: October 2013

Key PointsHuman IL-6 and a viral IL-6 homolog encoded by KSHV/HHV8 can independently or together lead to flares of KSHV-associated MCD. KSHV-MCD disease flares were more severe where both human and viral IL-6 were elevated, suggesting they jointly contribute to severity.
Association between winter season and risk of death from cardiovascular diseases: a study in more than half a million inpatients in Beijing, China
Authors: Xu Beibei , Liu Hui , Su Naifang , Kong Guilan , Bao Xiaoyuan , Li Jiong , Wang Jing , Li Yi , Ma Xiemin , Zhang Jun , Yu Guo-Pei , Zhao Lueping 
Published: October 2013

Abstract

Background
Seasonal associations of cardiovascular mortality have been noted in most populations of European origin years ago, but are not well evaluated in Asian populations recently.

Methods
Utilizing the electronic Hospitalization Summary Reports (HSRs) from 32 top-ranked hospitals in Beijing, China, we evaluated the association between winter season and the risk of cardiovascular death among hospitalized individuals. General additive models and logistic regression models were adjusted for confounding factors.

Results
Older patients who were admitted to the hospital in the winter months (January, February, November and December) had a death risk that was increased by approximately 30% to 50% (P < 0.01) over those who were admitted in May. However, younger patients did not seem to experience the same seasonal variations in death risk. The excess winter deaths among older patients were associated with ischemic heart disease (RR = 1.22; 95% CI 1.13 to 1.31), pulmonary heart disease (RR = 1.42; 95% CI 1.10 to 1.83), cardiac arrhythmias (RR = 1.67; 95% CI 1.36 to 2.05), heart failure (RR = 1.30; 95% CI 1.09 to 1.54), ischemic stroke (RR = 1.30; 95% CI 1.17 to 1.43), and other cerebrovascular diseases (RR = 1.78; 95% CI 1.40 to 2.25). The risks of mortality were higher in winter months than in the month of May, regardless of the presence or absence of respiratory disease.

Conclusions
Winter season was associated with a substantially increased risk of cardiovascular death among older Chinese cardiovascular inpatients.
Distraction test of the posterior superior iliac spine (PSIS) in the diagnosis of sacroiliac joint arthropathy
Authors: Werner Clément M L , Hoch Armando , Gautier Lucienne , König Matthias A , Simmen Hans-Peter , Osterhoff Georg 
Published: October 2013

AbstractBackgroundThe sacroiliac joint (SIJ) is a frequently underestimated cause of lower back (LBP). A simple clinical test of sufficient validity would be desirable. The aim of this study was to evaluate the diagnostic value of a new PSIS distraction test for the clinical detection of SIJ arthropathy and to compare it to several commonly used clinical tests.MethodsConsecutive patients, where a SIJ pathology had been confirmed by an SIJ infiltration were enrolled (case group, 61 SIJs in 46 patients). Before infiltration, patients were tested for pain with PSIS distraction by a punctual force on the PSIS in medial-to-lateral direction (PSIS distraction test), pain with pelvic compression, pelvic distraction, Gaenslen test, Thigh Thrust, and Faber (or Patrick’s) test. In addition, these clinical tests were applied to both SIJs of a population of individuals without history of LBP (control group, 64 SIJs in 32 patients).ResultsWithin the investigated cohort, the PSIS distraction test showed a sensitivity of 100% and a specificity of 89% for SIJ pathology. The accuracy of the test was 94%, the positive predictive value (PPV) was 90% and the negative predictive value (NPV) was 100%. Pelvic compression, pelvic distraction, Gaenslen test, Thigh Thrust, and Faber test were associated with a good specificity (> 90%) but a poor sensitivity (< 35%).ConclusionsWithin our population of patients with confirmed SIJ arthropathy the PSIS distraction test was found to be of high sensitivity, specificity and accuracy. In contrast, common clinical tests showed a poor sensitivity. The PSIS distraction test seems to be an easy-to-perform and clinically valuable test for SIJ arthropathy.
Socioeconomic and psychosocial predictors of dental healthcare use among Brazilian preschool children
Authors: Machry Rômulo Vaz , Tuchtenhagen Simone , Agostini Bernardo Antonio , da Silva Teixeira Carlos Roberto , Piovesan Chaiana , Mendes Fausto Medeiros , Ardenghi Thiago Machado 
Published: October 2013

Abstract

Background
Disparities in utilization of oral healthcare services have been attributed to socioeconomic and individual behavioral factors. Parents’ socioeconomic status, demographics, schooling, and perceptions of oral health may influence their children’s use of dental services. This cross-sectional study assessed the relationships between socioeconomic and psychosocial factors and the utilization of dental health services by children aged 1–5 years.

Methods
Data were collected through clinical exams and a structured questionnaire administered during the National Day of Children’s Vaccination. A Poisson regression model was used to estimate prevalence ratios and 95% confidence intervals.

Results
Data were collected from a total of 478 children. Only 112 (23.68%) were found to have visited a dentist; 67.77% of those had seen the dentist for preventive care. Most (63.11%) used public rather than private services. The use of dental services varied according to parental socioeconomic status; children from low socioeconomic backgrounds and those whose parents rated their oral health as “poor” used dental services less frequently. The reason for visiting the dentist also varied with socioeconomic status, in that children of parents with poor socioeconomic status and who reported their child’s oral health as “fair/poor” were less likely to have visited the dentist for preventive care.

Conclusion
This study demonstrated that psychosocial and socioeconomic factors are important predictors of the utilization of dental care services.
Functional conservation of HIV-1 Gag: implications for rational drug design
Authors: Li Guangdi , Verheyen Jens , Rhee Soo-Yon , Voet Arnout , Vandamme Anne-Mieke , Theys Kristof 
Published: October 2013

Abstract

Background
HIV-1 replication can be successfully blocked by targeting gag gene products, offering a promising strategy for new drug classes that complement current HIV-1 treatment options. However, naturally occurring polymorphisms at drug binding sites can severely compromise HIV-1 susceptibility to gag inhibitors in clinical and experimental studies. Therefore, a comprehensive understanding of gag natural diversity is needed.

Findings
We analyzed the degree of functional conservation in 10862 full-length gag sequences across 8 major HIV-1 subtypes and identified the impact of natural variation on known drug binding positions targeted by more than 20 gag inhibitors published to date. Complete conservation across all subtypes was detected in 147 (29%) out of 500 gag positions, with the highest level of conservation observed in capsid protein. Almost half (41%) of the 136 known drug binding positions were completely conserved, but all inhibitors were confronted with naturally occurring polymorphisms in their binding sites, some of which correlated with HIV-1 subtype. Integration of sequence and structural information revealed one drug binding pocket with minimal genetic variability, which is situated at the N-terminal domain of the capsid protein.

Conclusions
This first large-scale analysis of full-length HIV-1 gag provided a detailed mapping of natural diversity across major subtypes and highlighted the considerable variation in current drug binding sites. Our results contribute to the optimization of gag inhibitors in rational drug design, given that drug binding sites should ideally be conserved across all HIV-1 subtypes.
HIV-TAT mediated protein transduction of Cu/Zn-superoxide dismutase-1 (SOD1) protects skin cells from ionizing radiation
Authors: Gu Qing , Feng Tienan , Cao Han , Tang Yiting , Ge Xin , Luo Judong , Xue Jiao , Wu Jinyong , Yang Hongying , Zhang Shuyu , Cao Jianping 
Published: October 2013

AbstractBackgroundRadiation-induced skin injury remains a serious concern during radiotherapy. Cu/Zn-superoxide dismutase (Cu/Zn-SOD, SOD1) is a conserved enzyme for scavenging superoxide radical in cells. Because of the integrity of cell membranes, exogenous molecule is not able to be incorporated into cells, which limited the application of natural SOD1. The aim of this study was to evaluate the protective role of HIV-TAT protein transduction domain mediated protein transduction of SOD1(TAT-SOD1) against ionizing radiation.MethodsThe recombinant TAT-SOD1and SOD1were obtained by prokaryotic–based protein expression system. The transduction effect and biological activity of TAT-SOD1was measured by immunofluorescence and antioxidant capability assays in human keratinocyte HaCaT cells. Mito-Tracker staining, reactive oxygen species (ROS) generation assay, cell apoptosis analysis and malondialdehyde (MDA) assay were used to access the protective effect of TAT- SOD1.ResultsUptake of TAT-SOD1by HaCaT cells retained its biological activity. Compared with natural SOD1, the application of TAT-SOD1significantly enhanced the viability and decreased the apoptosis induced by X-ray irradiation. Moreover, TAT-SOD1reduced ROS and preserved mitochondrial integrity after radiation exposure in HaCaT cells. Radiation-induced γH2AX foci, which are representative of DNA double strand breaks, were decreased by pretreatment with TAT-SOD1. Furthermore, subcutaneous application of TAT-SOD1resulted in a significant decrease in 45 Gy electron beam-induced ROS and MDA concentration in the skins of rats.ConclusionsThis study provides evidences for the protective role of TAT-SOD1in alleviating radiation-induced damage in HaCaT cells and rat skins, which suggests a new therapeutic strategy for radiation-induced skin injury.