bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of Life and Healthcare Resource Use Associated With Angiographic Vasospasm After Aneurysmal Subarachnoid Hemorrhage
Authors: Macdonald R. Loch , Hunsche Elke , Schüler René , Wlodarczyk John , Mayer Stephan A. 
Published: February 2012

Background and Purpose—
In this analysis of data from a large clinical trial in aneurysmal subarachnoid hemorrhage, the impact of angiographic vasospasm (aVSP) on specific patient outcomes and inpatient healthcare resource use was assessed.

Methods—
This was a post hoc analysis of exploratory end points collected for 409 patients with aneurysmal subarachnoid hemorrhage in the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) trial. Central reviewers graded severity of aVSP as none, mild, moderate, or severe based on comparison of catheter angiograms obtained at baseline and 7 to 11 days after aneurysmal subarachnoid hemorrhage. Assessments of cognitive status (Mini-Mental State Examination) and patient-relevant outcomes (EuroQol total score and visual analog scale and Functional Status Examination) were administered at Week 12. The relationship between severity of aVSP and these end points as well as inpatient healthcare resource use (intensive care, general ward, and total hospital lengths of stay) was assessed using univariate and multivariate analyses.

Results—

Cognitive status and all patient-relevant outcome measures varied significantly (
P
<0.0001) with severity of aVSP (mean for severe aVSP versus no aVSP, respectively: Mini-Mental State Examination, 18.0 versus 27.6; EuroQol total, 0.38 versus 0.74; EuroQol visual analog scale, 50.9 versus 75.5; Functional Status Examination, 20.5 versus 11.7). A significant inverse relationship with severity of aVSP was observed for total hospital days (
P
=0.008) and days in the intensive care unit (
P
<0.0001). On average, patients with severe aVSP stayed in the hospital 5 days longer than those with no aVSP.

Conclusions—
Severe aVSP is associated with poor cognition, worse patient-relevant outcomes, and greater inpatient healthcare resource use. Future studies assessing new aVSP treatments should include outcome measures that evaluate quality of recovery among survivors.
The Feasibility of Cardiopulmonary Exercise Testing for Prescribing Exercise to People After Stroke
Authors: Marzolini Susan , Oh Paul , McIlroy William , Brooks Dina 
Published: February 2012

Background and Purpose—
Despite the importance of exercise training in mitigating cardiovascular risk, the development of exercise programs for people poststroke has been limited by lack of feasibility data concerning cardiopulmonary exercise testing (CPET) to inform the exercise prescription. Therefore, we examined the feasibility of CPETs for developing an exercise prescription in people ≥3 months poststroke.

Methods—
CPET results from 98 consecutively enrolled patients poststroke with motor impairments and 98 age- and sex-matched patients with coronary artery disease were examined at baseline and after 6 months of exercise training.

Results—

The proportion of patients with stroke and coronary artery disease attaining an intensity sufficient for prescribing exercise at baseline was 68.4% versus 82.7%, respectively (
P
=0.02) and 84.7% versus 83.8% (
P
=0.9) at 6 months. Women were less likely than men poststroke to achieve a sufficient intensity at baseline (40% versus 80.9%,
P
<0.001) but not at 6 months (78.3% versus 87.1,
P
=0.3). A clinically relevant abnormality occurred in 11.2% of stroke and 12.2% of patients with coronary artery disease on baseline CPETs (
P
=0.8) and 10.6% of stroke and 5.9% of patients with coronary artery disease on the 6-month CPET (
P
=0.4). No serious cardiovascular events occurred during 349 CPETs.

Conclusions—
Most patients after stroke achieved a level of exertion during the CPET sufficient to inform an exercise prescription. At least 1 of 10 patients poststroke developed a clinically relevant abnormality on baseline and postprogram CPETs with no serious cardiovascular events. These data support the feasibility and safety of CPETs for prescribing exercise poststroke. Strategies to improve use of baseline CPETs for women poststroke require further investigation.
Age-Dependent Lethality in Novel Transgenic Mouse Models of Central Nervous System Arteriovenous Malformations
Authors: Milton Ian , Ouyang Dan , Allen Caitlin J. , Yanasak Nathan E. , Gossage James R. , Alleyne Cargill H. , Seki Tsugio 
Published: February 2012

Background and Purpose—
The lack of an appropriate animal model has been a limitation in studying hemorrhage from arteriovenous malformations (AVMs) in the central nervous system.

Methods—

Novel mouse central nervous system AVM models were generated by conditionally deleting the activin receptor-like kinase (
Alk1
;
Acvrl1
) gene with the SM22-Cre transgene. All mice developed AVMs in their brain and/or spinal cord, and >80% of them showed a paralysis or lethality phenotype due to internal hemorrhages during the first 10 to 15 weeks of life. The mice that survived this early lethal period, however, showed significantly reduced lethality rates even though they carried multiple AVMs.

Results—
The age-dependent change in hemorrhage rates allowed us to identify molecular factors uniquely upregulated in the rupture-prone AVM lesions.

Conclusions—
Upregulation of angiopoietin 2 and a few inflammatory genes were identified in the hemorrhage-prone lesions, which may be comparable with human pathology. These models will be an exceptional tool to study pathophysiology of AVM hemorrhage.
A review of the use of clozapine levels to guide treatment and determine cause of death
Authors: Stark Anne , Scott James 
Published: February 2012

Objective: To review the literature to examine the use of clozapine levels to (i) guide therapy and prevent toxicity in clinical care and (ii) determine cause of death in post-mortem examination of patients who were treated with clozapine. Methods: MEDLINE was searched in December 2010 using the following keywords: ‘clozapine levels’, ‘clozapine and toxicity’, ‘clozapine and death’, ‘clozapine and mortality’ and ‘post-mortem redistribution’. Data was also collected from the 2010 MIMS Annual. Results: The literature reported significant variation in clozapine levels attained with any given dose, and considerable variability in the clinical response achieved at any given clozapine level. The lowest effective clozapine levels ranged from 250 to 550 µg/L, while the recommended upper limit to prevent toxicity varied from 600 to 2000 µg/L. There was minimal correlation between clozapine levels and side effects, with the exception of sedation, hypotension and seizure activity. The risk of seizures increased with plasma clozapine levels greater than 600 µg/L or rapid upward titration. In addition to prescribed dose, there are many factors that influence plasma clozapine levels. After death, the process of post-mortem drug redistribution resulted in 3.00 to 4.89 times increases in clozapine levels in central blood vessels and 1.5 fold increases in peripheral vessels compared to ante-mortem levels. Conclusions: The exact range of clozapine levels that corresponds to toxicity remains unclear. However, levels between 350 µg/L and 1000 µg/L achieved with gradual upward titration are more likely to be effective and less likely to cause toxicity. Ongoing clozapine level monitoring is indicated, especially when (i) prescribing higher doses (> 600 mg/day) of clozapine, (ii) there has been a change in a patient’s concomitant pharmacotherapy or cigarette use and (iii) there has been a suboptimal response to treatment. The use of post-mortem clozapine levels to determine clozapine toxicity as a cause of death is unreliable.
Measurable Progress in Female Authorship in Otolaryngology
Authors: Bergeron Jennifer L. , Wilken Reason , Miller Mia E. , Shapiro Nina L. , Bhattacharyya Neil 
Published: February 2012

ObjectiveTo identify contemporary trends in female authorship in the otolaryngology literature.Study DesignAnalysis of 4 otolaryngology journals.SettingAll articles published in Annals of Otology, Rhinology and Laryngology, Archives of Otolaryngology–Head and Neck Surgery, Laryngoscope, and Otolaryngology–Head and Neck Surgery in 2008 were reviewed and compared with prior data from 1978, 1988, and 1998.Subjects and MethodsEach published article’s authorship panel was examined for the number of authors and each author’s sex, degree, and the subspecialty area of publication. Year‐to‐year comparisons were conducted for the rates and characteristics of female authorship.ResultsA total of 544, 629, 713, and 785 articles from 1978, 1988, 1998, and 2008, respectively, were analyzed. From 1998 to 2008, the overall percentage of female authors increased from 14.5% to 22.5% (P <. 001). Similarly, the percentage of articles with a female first author increased from 12.9% to 21.3% (P <. 001). Whereas previously pediatric otolaryngology had the highest female first author percentage (range, 6.9%‐19.4%), in 2008 all other subspecialties demonstrated significant increases in female first author percentages: otology (18.6%), general (22.3%), head and neck (22.2%), plastics (18.9%), and pediatrics (19.4%) (P =. 885). A significant number of female first authors continue to be nonphysicians (19.2% in 2008, P <. 001).ConclusionsFemale authorship has shown significant and steady increases in the otolaryngology literature, particularly in the past decade. Increased rates of publication from female otolaryngologists within most subspecialties have resulted in similar rates of publication across the subspecialties.
Associations Between Abnormal Ultrasound Color Doppler Measures and Tendon Pain Symptoms in Badminton Players During a Season
Authors: Boesen Anders Ploug , Boesen Morten Ilum , Torp-Pedersen Soren , Christensen Robin , Boesen Lars , Hölmich Per , Nielsen Michael Bachmann , Koenig Merete Juhl , Hartkopp Andreas , Ellegaard Karen , Bliddal Henning , Langberg Henning 
Published: February 2012

Background: Color Doppler ultrasound is widely used to examine intratendinous flow in individuals with overuse tendon problems, but the association between color Doppler and pain is still unclear. Hypothesis: Intratendinous flow is present and associated with pain in badminton players, and intratendinous flow and pain increase during a badminton season. Study Design: Cohort study (prognosis); Level of evidence, 2. Methods: Ninety-five semiprofessional badminton players were included in the study at a tournament at the start of the badminton season. All players were interviewed regarding pain. The anterior knee tendons and Achilles tendons were studied. Each tendon was scored using a quantitative grading system (grades 0-5) and a qualitative scoring system (color fraction) using color Doppler ultrasound. Eight months later, 86 of the players (91%) were retested by the same investigators during an equivalent badminton tournament (including 1032 tendon regions; 86 players with 4 tendons each with 3 regions), thus forming the study group. Results: At the start of the season, 24 players (28%) experienced pain in 37 tendons (11%), and at the end of the season, 31 players (36%) experienced pain in 51 tendons (15%), which was a statistically significant increase ( P = .0002). Abnormal flow was found in 230 tendon regions in 71 players (83%) at the start of the season compared with 78 tendon regions in 41 players (48%) at the follow-up. The decrease in abnormal flow was statistically significant ( P < .0001). Of the 37 painful tendons at the start of the season, 25 had abnormal flow (68%). In contrast, 131 tendons (85%) with abnormal flow at the start of the season were pain free. At the end of the season, 18 of the 51 painful tendons (35%) had abnormal flow. Ninety-six of the 131 pain-free tendons (73%) with abnormal flow at the start of the season were normalized (no pain and normal flow) at the end of the season. Conclusion: It was not possible to verify any association between intratendinous flow and pain at the start of the season or at the follow-up (end of the season). Intratendinous flow at the start of the season could not predict symptomatic outcome at the end of the season. The decrease in Doppler flow during the season might suggest that intratendinous flow could be part of a physiological adaptive response to loading and that intratendinous flow as previously believed is not always a sign of pathological changes.
Rising prevalence of vascular comorbidities in multiple sclerosis: validation of administrative definitions for diabetes, hypertension, and hyperlipidemia
Authors: Marrie Ruth Ann , Yu Bo Nancy , Leung Stella , Elliott Lawrence , Caetano Patricia , Warren Sharon , Wolfson Christina , Patten Scott B , Svenson Lawrence W , Tremlett Helen , Fisk John , Blanchard James F ,   for the CIHR Team in the Epidemiology and Impact of Comorbidity on Multiple Sclerosis
Published: February 2012

Background: Despite the importance of comorbidity in multiple sclerosis (MS), methods for comorbidity assessment in MS are poorly developed. Objective: We validated and applied administrative case definitions for diabetes, hypertension, and hyperlipidemia in MS. Methods: Using provincial administrative data we identified persons with MS and a matched general population cohort. Case definitions for diabetes, hypertension, and hyperlipidemia were derived using hospital, physician, and prescription claims, and validated in 430 persons with MS. We examined temporal trends in the age-adjusted prevalence of these conditions from 1984–2006. Results: Agreement between various case definitions and medical records ranged from kappa (κ) =0.51–0.69 for diabetes, κ =0.21–0.71 for hyperlipidemia, and κ =0.52–0.75 for hypertension. The 2005 age-adjusted prevalence of diabetes was similar in the MS (7.62%) and general populations (8.31%; prevalence ratio [PR] 0.91; 0.81–1.03). The age-adjusted prevalence did not differ for hypertension (MS: 20.8% versus general: 22.5% [PR 0.91; 0.78–1.06]), or hyperlipidemia (MS: 13.8% versus general: 15.2% [PR 0.90; 0.67–1.22]). The prevalence of all conditions rose in both populations over the study period. Conclusion: Administrative data are a valid means of tracking diabetes, hypertension, and hyperlipidemia in MS. The prevalence of these comorbidities is similar in the MS and general populations.
A Comparative Study of Oral Candidal Carriage and Its Association with CD4 Count between HIV-Positive and Healthy Individuals
Authors: Kamtane Smita , Subramaniam Arun , Suvarna Prashant 
Published: February 2012

Aims and Objectives: To correlate asymptomatic oral candidal carriage in HIV-positive patients and normal individuals and determine its association with CD4 count. Material and Methods: Forty HIV-positive patients and forty healthy individuals were included in this study. Saliva from both groups was collected by the spitting method. The saliva from each individual was incubated aerobically on Sabouraud Dextrose agar with antibiotics at 37°C. The germ tube method was used for differentiation of candidal species, whether the Candida albicans or non- Candida albicans. Surface count method was used to count the number of colonies of candida species. Data were analyzed by chi square and Mann-Whitney test. Results: Oral candidal carriage was found in 22 out of 40 (55%) HIV-positive patients. In healthy volunteers, oral candidal carriage was found in 6 out of 40 (15%) individuals ( p value = 0.0002), which is significantly higher. Similarly, density carriage in the HIV-positive patients was found to be significantly higher than that in the HIV-negative group ( p value = 0.002). However, oral yeast carriage was not associated with CD4 count (correlation coefficient r = −0.087). Conclusion: Within the limits of the study, we concluded oral candidal carriage rate and density carriage higher in HIV-positive patients than in healthy individuals.
Polycombs and microRNA-223 regulate human granulopoiesis by transcriptional control of target gene expression
Authors: Zardo Giuseppe , Ciolfi Alberto , Vian Laura , Starnes Linda M. , Billi Monia , Racanicchi Serena , Maresca Carmen , Fazi Francesco , Travaglini Lorena , Noguera Nelida , Mancini Marco , Nanni Mauro , Cimino Giuseppe , Lo-Coco Francesco , Grignani Francesco , Nervi Clara 
Published: February 2012

Abstract
Epigenetic modifications regulate developmental genes involved in stem cell identity and lineage choice. NFI-A is a posttranscriptional microRNA-223 (miR-223) target directing human hematopoietic progenitor lineage decision: NFI-A induction or silencing boosts erythropoiesis or granulopoiesis, respectively. Here we show that NFI-A promoter silencing, which allows granulopoiesis, is guaranteed by epigenetic events, including the resolution of opposing chromatin “bivalent domains,” hypermethylation, recruitment of polycomb (PcG)–RNAi complexes, and miR-223 promoter targeting activity. During granulopoiesis, miR-223 localizes inside the nucleus and targets the NFI-A promoter region containing PcGs binding sites and miR-223 complementary DNA sequences, evolutionarily conserved in mammalians. Remarkably, both the integrity of the PcGs-RNAi complex and DNA sequences matching the seed region of miR-223 are required to induce NFI-A transcriptional silencing. Moreover, ectopic miR-223 expression in human myeloid progenitors causes heterochromatic repression of NFI-A gene and channels granulopoiesis, whereas its stable knockdown produces the opposite effects. Our findings indicate that, besides the regulation of translation of mRNA targets, endogenous miRs can affect gene expression at the transcriptional level, functioning in a critical interface between chromatin remodeling complexes and the genome to direct fate lineage determination of hematopoietic progenitors.
The combination of valproic acid and lithium delays hematopoietic stem/progenitor cell differentiation
Authors: Walasek Marta A. , Bystrykh Leonid , van den Boom Vincent , Olthof Sandra , Ausema Albertina , Ritsema Martha , Huls Gerwin , de Haan Gerald , van Os Ronald 
Published: February 2012

AbstractDespite increasing knowledge on the regulation of hematopoietic stem/progenitor cell (HSPC) self-renewal and differentiation, in vitro control of stem cell fate decisions has been difficult. The ability to inhibit HSPC commitment in culture may be of benefit to cell therapy protocols. Small molecules can serve as tools to manipulate cell fate decisions. Here, we tested 2 small molecules, valproic acid (VPA) and lithium (Li), to inhibit differentiation. HSPCs exposed to VPA and Li during differentiation-inducing culture preserved an immature cell phenotype, provided radioprotection to lethally irradiated recipients, and enhanced in vivo repopulating potential. Anti-differentiation effects of VPA and Li were observed also at the level of committed progenitors, where VPA re-activated replating activity of common myeloid progenitor and granulocyte macrophage progenitor cells. Furthermore, VPA and Li synergistically preserved expression of stem cell–related genes and repressed genes involved in differentiation. Target genes were collectively co-regulated during normal hematopoietic differentiation. In addition, transcription factor networks were identified as possible primary regulators. Our results show that the combination of VPA and Li potently delays differentiation at the biologic and molecular levels and provide evidence to suggest that combinatorial screening of chemical compounds may uncover possible additive/synergistic effects to modulate stem cell fate decisions.
Recruitment of monocytes/macrophages by tissue factor-mediated coagulation is essential for metastatic cell survival and premetastatic niche establishment in mice
Authors: Gil-Bernabé Ana M. , Ferjančič Špela , Tlalka Monika , Zhao Lei , Allen Philip D. , Im Jae Hong , Watson Karla , Hill Sally A. , Amirkhosravi Ali , Francis John L. , Pollard Jeffrey W. , Ruf Wolfram , Muschel Ruth J. 
Published: February 2012

Abstract
Tissue factor (TF) expression by tumor cells correlates with metastasis clinically and supports metastasis in experimental settings. However, the precise pathways coupling TF to malignancy remain incompletely defined. Here, we show that clot formation by TF indirectly enhances tumor cell survival after arrest in the lung, during experimental lung metastasis, by recruiting macrophages characterized by CD11b, CD68, F4/80, and CX3CR1 (but not CD11c) expression. Genetic or pharmacologic inhibition of coagulation, by either induction of TF pathway inhibitor ex-pression or by treatment with hirudin, respectively, abrogated macrophage recruitment and tumor cell survival. Furthermore, impairment of macrophage function, in either Mac1-deficient mice or in CD11b-diphtheria toxin receptor mice in which CD11b-positive cells were ablated, decreased tumor cell survival without altering clot formation, demonstrating that the recruitment of functional macrophages was essential for tumor cell survival. This effect was independent of NK cells. Moreover, a similar population of macrophages was also recruited to the lung during the formation of a premetastatic niche. Anticoagulation inhibited their accumulation and prevented the enhanced metastasis associated with the formation of the niche. Our study, for the first time, links TF induced coagulation to macrophage recruitment in the metastatic process.
Optimizing the thermoelectric performance of zigzag and chiral carbon nanotubes
Authors: Tan Xiaojian , Liu Huijun , Wen Yanwei , Lv Hongyan , Pan Lu , Shi Jing , Tang Xinfeng 
Published: February 2012

Abstract
Using nonequilibrium molecular dynamics simulations and nonequilibrium Green's function method, we investigate the thermoelectric properties of a series of zigzag and chiral carbon nanotubes which exhibit interesting diameter and chirality dependence. Our calculated results indicate that these carbon nanotubes could have higher ZT values at appropriate carrier concentration and operating temperature. Moreover, their thermoelectric performance can be significantly enhanced via isotope substitution, isoelectronic impurities, and hydrogen adsorption. It is thus reasonable to expect that carbon nanotubes may be promising candidates for high-performance thermoelectric materials.
Obese mice exhibit an altered behavioural and inflammatory response to lipopolysaccharide
Authors: Lawrence Catherine B. , Brough David , Knight Elysse M. 
Published: February 2012

SummaryObesity is associated with an increase in the prevalence and severity of infections. Genetic animal models of obesity (ob/ob and db/db mice) display altered centrally-mediated sickness behaviour in response to acute inflammatory stimuli such as lipopolysaccharide (LPS). However, the effect of diet-induced obesity (DIO) on the anorectic and febrile response to LPS in mice is unknown. This study therefore determined how DIO and ob/ob mice respond to a systemic inflammatory challenge. C57BL/6 DIO and ob/ob mice, and their respective controls, were given an intraperitoneal (i.p.) injection of LPS. Compared to controls, DIO and ob/ob mice exhibited an altered febrile response to LPS (100 μg/kg) over 8 h. LPS caused a greater and more prolonged anorexic effect in DIO mice, and in ob/ob mice, LPS induced a reduction in food intake and body weight at an earlier time point. These effects of LPS in obese mice were also seen after a fixed dose of LPS (5 μg). LPS (100 μg/kg) induced c-Fos protein expression in several brain nuclei of control mice, with fewer c-Fos-positive cells observed in the brains of obese mice. An altered inflammatory response to LPS was also observed in obese mice as changes in cytokine expression and release were detected in the plasma, spleen, liver and peritoneal macrophages. In summary, DIO and ob/ob mice displayed an altered behavioural response and cytokine release to systemic inflammatory challenge. These findings could help explain why obese humans show an increased sensitivity to infections.