bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Oral Ribavirin in Hematologic Disease Patients with Paramyxovirus Infection: Analytic Strategy Using Propensity Scores
Authors: Park So-Youn , Baek Seunghee , Lee Sang-Oh , Choi Sang-Ho , Kim Yang Soo , Woo Jun Hee , Sung Heungsup , Kim Mi-Na , Kim Dae-Young , Lee Jung-Hee , Lee Je-Hwan , Lee Kyoo-Hyung , Kim Sung-Han 
Published: December 2012

ABSTRACT

Few antiviral agents are available for treating paramyxovirus infections, such as those involving respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV). We evaluated the effect of oral ribavirin on clinical outcomes of paramyxovirus infections in patients with hematological diseases. All adult patients with paramyxovirus were retrospectively reviewed over a 2-year period. Patients who received oral ribavirin were compared to those who received supportive care without ribavirin therapy. A propensity-matched case-control study and a logistic regression model with inverse probability of treatment weighting (IPTW) were performed to reduce the effect of selection bias in assignment for oral ribavirin therapy. A total of 145 patients, including 64 (44%) with PIV, 60 (41%) with RSV, and 21 (15%) with hMPV, were analyzed. Of these 145 patients, 114 (78%) received oral ribavirin and the remaining 31 (21%) constituted the nonribavirin group. Thirty-day mortality and underlying respiratory death rates were 31% (35/114) and 12% (14/114), respectively, for the oral ribavirin group versus 19% (6/31) and 16% (5/31), respectively, for the nonribavirin group (
P
= 0.21 and
P
= 0.56). In the case-control study, the 30-day mortality rate in the ribavirin group was 24% (5/21) versus 19% (4/21) in the nonribavirin group (
P
= 0.71). In addition, the logistic regression model with IPTW revealed no significant difference in 30-day mortality (adjusted hazard ratio of 1.3; 95% confidence interval [95% CI] of 0.3 to 5.8) between the two groups. Steroid use (adjusted odds ratio, 5.67;
P
= 0.01) and upper respiratory tract infection (adjusted odds ratio, 0.07;
P
= 0.001) was independently associated with mortality. Our data suggest that oral ribavirin therapy may not improve clinical outcomes in hematologic disease patients infected with paramyxovirus.
Association with Soil Bacteria Enhances p38-Dependent Infection Resistance in Caenorhabditis elegans
Authors: Montalvo-Katz Sirena , Huang Hao , Appel Michael David , Berg Maureen , Shapira Michael 
Published: December 2012

ABSTRACT

The importance of our inner microbial communities for proper immune responses against invading pathogens is now well accepted, but the mechanisms underlying this protection are largely unknown. In this study, we used
Caenorhabditis elegans
to investigate such mechanisms. Since very little is known about the microbes interacting with
C. elegans
in its natural environment, we began by taking the first steps to characterize the
C. elegans
microbiota. We established a natural-like environment in which initially germfree, wild-type larvae were grown on enriched soil. Bacterial members of the adult
C. elegans
microbiota were isolated by culture and identified using 16S rRNA gene sequencing. Using pure cultures of bacterial isolates as food, we identified two,
Bacillus megaterium
and
Pseudomonas mendocina
, that enhanced resistance to a subsequent infection with the Gram-negative pathogen
Pseudomonas aeruginosa
. Whereas protection by
B. megaterium
was linked to impaired egg laying, corresponding to a known trade-off between fecundity and resistance, the mechanism underlying protection conferred by
P. mendocina
depended on weak induction of immune genes regulated by the p38 MAPK pathway. Disruption of the p38 ortholog,
pmk-1
, abolished protection.
P. mendocina
enhanced resistance to
P. aeruginosa
but not to the Gram-positive pathogen
Enterococcus faecalis
. Furthermore, protection from
P. aeruginosa
was similarly induced by a
P. aeruginosa
gacA
mutant with attenuated virulence but not by a different
C. elegans
-associated
Pseudomonas
sp. isolate. Our results support a pivotal role for the conserved p38 pathway in microbiota-initiated immune protection and suggest that similarity between microbiota members and pathogens may play a role in such protection.
Carbidopa/levodopa dose elevation and safety concerns in Parkinson's patients: a cross-sectional and cohort design
Authors: Brodell David W , Stanford Nicole T , Jacobson Charles E , Schmidt Peter , Okun Michael S 
Published: December 2012

ObjectiveSinemet, a combination drug containing carbidopa and levodopa is considered the gold standard therapy for the treatment of Parkinson's disease (PD). When approved by the Food and Drug Administration (FDA) in 1988, a maximum daily dosage limit of 800 mg (eight tablets) of the 25/100 carbidopa/levodopa formulation was introduced. Overall, the FDA approval was a historic success; however, the pill limit has been hardcoded into many online medical record systems. This study investigates the 800 mg threshold by using a prospectively collected database of patient information.DesignA retrospective cohort study: (Part I) cross-sectional, (Part II) longitudinal.Setting and participantsPD patients at a Movement Disorders Center in a large academic, tertiary medical setting.Outcome measuresAn analysis was performed using carbidopa/levodopa at dosages below and above the 800 mg threshold. A secondary analysis was then performed using two consecutive clinic visits to determine the effects of crossing the 800 mg threshold. Comparisons were made on standardised scales.ResultsThere was no significant difference in motor, mood and quality-of-life scores in patients consuming below and above the 800 mg carbidopa/levodopa threshold, though a mild worsening in dyskinesia duration was noted without worsening in dyskinesia pain and disability. In PD patients who crossed the 800 mg threshold between two consecutive clinic visits, a significant improvement in depressive symptoms and quality-of-life measures was demonstrated, and in these patients there was no worsening of motor fluctuations or dyskinesia.ConclusionsThe data suggest that PD patients have the potential for enhanced clinical benefits when eclipsing the 800 mg carbidopa/levodopa threshold. Many patients will likely need to eclipse the 800 mg threshold and pharmacies and insurance companies should be aware of the requirements that may extend beyond approval limits.
Sexual dimorphism in floral traits of gynodioecious Lobelia siphilitica (Lobeliaceae) is consistent across populations
Authors: Caruso Christina M. 
Published: December 2012

In angiosperms, the evolution of gender dimorphism is often correlated with the evolution of sexual dimorphism in floral traits. The magnitude of sexual dimorphism will reflect both sex-specific selection and constraints on evolution in response to this selection. If the evolution of sexual dimorphism is constrained by genetic correlations, then trait means are predicted to evolve more quickly than the magnitude of sexual dimorphism in the same traits. To test whether mean floral traits evolve more quickly than sexual dimorphism in these traits, I measured flower size and flower number of gynodioecious Lobelia siphilitica L. from 10–14 populations across the species’ range. Females produced more flowers than hermaphrodites, but neither mean flower number nor the magnitude of dimorphism in flower number varied among populations. Pistillate flowers were smaller than perfect flowers, and mean flower size varied among populations. However, the magnitude of dimorphism in flower size did not vary. My results suggest that the evolution of sexual dimorphism in flower size, but not necessarily flower number, could be constrained by within- or between-sex genetic correlations in L. siphilitica.
Internet nuggets
Authors: Thorson Mark 
Published: December 2012

This column consists of selected traffic from the comp.arch newsgroup, a forum for discussion of computer architecture on the Internet---an international computer network.
As always, the opinions expressed in this column are the personal views of the authors, and do not necessarily represent the institutions to which they are affiliated.
Text which sets the context of a message appears underlined or in italics; this is usually text the author has quoted from earlier messages. The code-like expressions below the authors' names are their addresses on Internet.
MDA-9/Syntenin and IGFBP-2 Promote Angiogenesis in Human Melanoma
Authors: Das Swadesh K. , Bhutia Sujit K. , Azab Belal , Kegelman Timothy P. , Peachy Leyla , Santhekadur Prasanna K. , Dasgupta Santanu , Dash Rupesh , Dent Paul , Grant Steven , Emdad Luni , Pellecchia Maurizio , Sarkar Devanand , Fisher Paul B. 
Published: December 2012

Abstract
Melanoma differentiation–associated gene-9 (mda-9/syntenin) encodes an adapter scaffold protein whose expression correlates with and mediates melanoma progression and metastasis. Tumor angiogenesis represents an integral component of cancer metastasis prompting us to investigate a possible role of mda-9/syntenin in inducing angiogenesis. Genetic (gain-of-function and loss-of-function) and pharmacologic approaches were used to modify mda-9/syntenin expression in normal immortal melanocytes, early radial growth phase melanoma, and metastatic melanoma cells. The consequence of modifying mda-9/syntenin expression on angiogenesis was evaluated using both in vitro and in vivo assays, including tube formation assays using human vascular endothelial cells, chorioallantoic membrane (CAM) assays and xenograft tumor animal models. Gain-of-function and loss-of-function experiments confirm that MDA-9/syntenin induces angiogenesis by augmenting expression of several proangiogenic factors/genes. Experimental evidence is provided for a model of angiogenesis induction by MDA-9/syntenin in which MDA-9/syntenin interacts with the extracellular matrix (ECM), activating Src and FAK resulting in activation by phosphorylation of Akt, which induces hypoxia inducible factor 1-α (HIF-1α). The HIF-1α activates transcription of insulin growth factor–binding protein-2 (IGFBP-2), which is secreted thereby promoting angiogenesis and further induces endothelial cells to produce and secrete VEGF-A augmenting tumor angiogenesis. Our studies delineate an unanticipated cell nonautonomous function of MDA-9/syntenin in the context of angiogenesis, which may directly contribute to its metastasis-promoting properties. As a result, targeting MDA-9/syntenin or its downstream-regulated molecules may provide a means of simultaneously impeding metastasis by both directly inhibiting tumor cell transformed properties (autonomous) and indirectly by blocking angiogenesis (nonautonomous). Cancer Res; 73(2); 844–54. ©2012 AACR.
Sorafenib Inhibits Cell Migration and Stroma-Mediated Bortezomib Resistance by Interfering B-cell Receptor Signaling and Protein Translation in Mantle Cell Lymphoma
Authors: Xargay-Torrent Sílvia , López-Guerra Mónica , Montraveta Arnau , Saborit-Villarroya Ifigènia , Rosich Laia , Navarro Alba , Pérez-Galán Patricia , Roué Gaël , Campo Elias , Colomer Dolors 
Published: December 2012

AbstractPurpose: We evaluated the antitumoral properties of the multikinase inhibitor sorafenib in mantle cell lymphoma (MCL), an aggressive B lymphoma for which current therapies have shown limited efficacy.Experimental Design: Sensitivity to sorafenib was analyzed in MCL cell lines and primary samples in the context of BCR and microenvironment simulation. Sorafenib signaling was characterized by quantitative PCR, Western blotting, immunofluorescence, and protein immunoprecipitation. Migration analysis included flow cytometric counting, actin polymerization assays, and siRNA-mediated knockdown of focal adhesion kinase (FAK). In vivo antitumor effect of sorafenib and bortezomib was analyzed in an MCL xenograft mouse model.Results: Sorafenib rapidly dephosphorylates the BCR-associated kinases, Syk and Lyn, as well as FAK, an Src target involved in focal adhesion. In this line, sorafenib displays strong synergy with the Syk inhibitor, R406. Sorafenib also blocks Mcl-1 and cyclin D1 translation, which promotes an imbalance between pro- and antiapoptotic proteins and facilitates Bax release from cyclin D1, leading to the induction of mitochondrial apoptosis and caspase-dependent and -independent mechanisms. Moreover, sorafenib inhibits MCL cell migration and CXCL12-induced actin polymerization. FAK knockdown partially prevents this inhibitory effect, indicating that FAK is a relevant target of sorafenib. Furthermore, sorafenib enhances the antitumoral activity of bortezomib in an MCL xenograft mouse model as well as overcomes stroma-mediated bortezomib resistance in MCL cells.Conclusion: We show for the first time that sorafenib interferes with BCR signaling, protein translation and modulates the microenvironment prosurvival signals in MCL, suggesting that sorafenib, alone or in combination with bortezomib, may represent a promising approach to treat patients with MCL. Clin Cancer Res; 19(3); 586–97. ©2012 AACR.
Prolonged Biologically Active Colonic Tissue Levels of Curcumin Achieved After Oral Administration—A Clinical Pilot Study Including Assessment of Patient Acceptability
Authors: Irving Glen R.B. , Howells Lynne M. , Sale Stewart , Kralj-Hans Ines , Atkin Wendy S. , Clark Susan K. , Britton Robert G. , Jones Donald J.L. , Scott Edwina N. , Berry David P. , Hemingway David , Miller Andrew S. , Brown Karen , Gescher Andreas J. , Steward William P. 
Published: December 2012

AbstractCurcumin, the main constituent of turmeric, is suspected to possess cancer chemopreventive properties. Pharmacokinetic and pharmacodynamic parameters have been reported, but few data exist describing whether methodologies are suitably robust for curcuminoid detection in colonic biopsy specimens. Information on the acceptability of prolonged administration of daily curcumin is not available. This is of vital importance to implement chemoprevention strategies. This study aimed to quantify levels of curcuminoids in colorectal mucosa of patients undergoing colorectal endoscopy or surgical resection and to obtain information on the acceptability and compliance with daily curcumin. Curcumin C3 complex (2.35 g) was administered to patients once daily for 14 days before endoscopic biopsy or colonic resection. Safety and tolerance were monitored. Analysis of curcuminoids in plasma, urine, and colonic mucosa was conducted by ultraperformance liquid chromatography (UPLC)-UV with characterization by liquid chromatography/tandem mass spectrometry (LC/MS-MS). Twenty-four of 26 patients commencing curcumin completed the course. Six patients reported mild gastrointestinal adverse events. Curcuminoids were detectable in nine of 24 plasma samples, 24 of 24 urine samples, and in the colonic mucosa of all 23 biopsied participants. Mean tissue levels were 48.4 μg/g (127.8 nmol/g) of parent curcuminoids. The major conjugate, curcumin glucuronide, was detectable in 29 of 35 biopsies. High levels of topical curcumin persisted in the mucosa for up to 40 hours postadministration. Sixteen participants (67%) stated that they would take curcumin long-term should it be of proven benefit. In summary, pharmacologically active levels of curcumin were recovered from colonic mucosa. The regimen used here seems safe, and patients support its use in long-term trials. Cancer Prev Res; 6(2); 119–28. ©2012 AACR.
Admixture Mapping of Coronary Artery Calcified Plaque in African Americans With Type 2 Diabetes Mellitus
Authors: Divers Jasmin , Palmer Nicholette D. , Lu Lingyi , Register Thomas C. , Carr J. Jeffrey , Hicks Pamela J. , Hightower R. Caresse , Smith S. Carrie , Xu Jianzhao , Cox Amanda J. , Hruska Keith A. , Bowden Donald W. , Lewis Cora E. , Heiss Gerardo , Province Michael A. , Borecki Ingrid B. , Kerr Kathleen F. , Chen Y.-D. Ida , Palmas Walter , Rotter Jerome I. , Wassel Christina L. , Bertoni Alain G. , Herrington David M. , Wagenknecht Lynne E. , Langefeld Carl D. , Freedman Barry I. 
Published: December 2012

Background—
The presence and severity of coronary artery calcified plaque (CAC) differs markedly between individuals of African and European descent, suggesting that admixture mapping may be informative for identifying genetic variants associated with subclinical cardiovascular disease.

Methods and Results—

Admixture mapping of CAC was performed in 1040 unrelated African Americans with type 2 diabetes mellitus from the African American-Diabetes Heart Study, Multi-Ethnic Study of Atherosclerosis and Family Heart Study using the Illumina custom ancestry informative marker panel. All cohorts obtained computed tomography scanning of the coronary arteries using identical protocols. For each ancestry informative marker, the probability of inheriting 0, 1, and 2 copies of a European-derived allele was determined. Linkage analysis was performed by testing for association between each ancestry informative marker using these probabilities and CAC, accounting for global ancestry, age, sex, and study. Markers on 1p32.3 in the
GLIS1
gene (rs6663966, logarithm of odds [LOD]=3.7), 1q32.1 near CHIT1 (rs7530895, LOD=3.1), 4q21.2 near PRKG2 (rs1212373, LOD=3.0), and 11q25 in the
OPCML
gene (rs6590705, LOD=3.4) had statistically significant LOD scores, whereas markers on 8q22.2 (rs6994682, LOD=2.7), 9p21.2 (rs439314, LOD=2.7), and 13p32.1 (rs7492028, LOD=2.8) manifested suggestive evidence of linkage. These regions were uniformly characterized by higher levels of European ancestry associating with higher levels or odds of CAC. Findings were replicated in 1350 African Americans without diabetes mellitus and 2497 diabetic European Americans from Multi-Ethnic Study of Atherosclerosis and the Diabetes Heart Study.

Conclusions—
Fine mapping these regions will likely identify novel genetic variants that contribute to CAC and clarify racial differences in susceptibility to subclinical cardiovascular disease.
Low Numeracy Is Associated With Increased Odds of 30-Day Emergency Department or Hospital Recidivism for Patients With Acute Heart Failure
Authors: McNaughton Candace D. , Collins Sean P. , Kripalani Sunil , Rothman Russell , Self Wesley H. , Jenkins Cathy , Miller Karen , Arbogast Patrick , Naftilan Allen , Dittus Robert S. , Storrow Alan B. 
Published: December 2012

Background—
More than 25% of Medicare patients hospitalized for heart failure are readmitted within 30 days. The contributions of numeracy and health literacy to recidivism for patients with acute heart failure (AHF) are not known.

Methods and Results—

A cohort of patients with acute heart failure who presented to 4 emergency departments between January 2008 and September 2011. Research assistants administered subjective measures of numeracy and health literacy; 30-day follow-up was performed by phone interview. Recidivism was defined as any unplanned return to the emergency department or hospital within 30 days of the index emergency department visit for AHF. Multivariable logistic regression adjusting for patient age, sex, race, insurance status, hospital site, days eligible for recidivism, chronic kidney disease, abnormal hemoglobin, and low ejection fraction evaluated the relation between numeracy and health literacy with 30-day recidivism. Of the 709 patients included in the analysis, 390 (55%) had low numeracy skills and 258 (37%) had low literacy skills. Low numeracy was associated with increased odds of recidivism within 30 days (adjusted odds ratio, 1.41; 95% confidence interval, 1.00–1.98;
P
=0.048). For low health literacy, adjusted odds ratio of recidivism was 1.17 (95% confidence interval, 0.83–1.65;
P
=0.37).

Conclusions—
Low numeracy was associated with greater odds of 30-day recidivism. Further investigation is warranted to determine whether addressing numeracy and health literacy may reduce 30-day recidivism for patients with acute heart failure.
Assessing Appropriateness of Lipid Management Among Patients With Diabetes Mellitus
Authors: Beard Ashley J. , Hofer Timothy P. , Downs John R. , Lucatorto Michelle , Klamerus Mandi L. , Holleman Rob , Kerr Eve A. ,   for the Diabetes Clinical Action Measures Workgroup
Published: December 2012

Background—
Performance measures that emphasize only a treat-to-target approach may motivate overtreatment with high-dose statins, potentially leading to adverse events and unnecessary costs. We developed a clinical action performance measure for lipid management in patients with diabetes mellitus that is designed to encourage appropriate treatment with moderate-dose statins while minimizing overtreatment.

Methods and Results—

We examined data from July 2010 to June 2011 for 964 818 active Veterans Affairs primary care patients ≥18 years of age with diabetes mellitus. We defined 3 conditions as successfully meeting the clinical action measure for patients 50 to 75 years old: (1) having a low-density lipoprotein (LDL) <100 mg/dL, (2) taking a moderate-dose statin regardless of LDL level or measurement, or (3) receiving appropriate clinical action (starting, switching, or intensifying statin therapy) if LDL is ≥100 mg/dL. We examined possible overtreatment for patients ≥18 years of age by examining the proportion of patients without ischemic heart disease who were on a high-dose statin. We then examined variability in measure attainment across 881 facilities using 2-level hierarchical multivariable logistic models. Of 668 209 patients with diabetes mellitus who were 50 to 75 years of age, 84.6% passed the clinical action measure: 67.2% with LDL <100 mg/dL, 13.0% with LDL ≥100 mg/dL and either on a moderate-dose statin (7.5%) or with appropriate clinical action (5.5%), and 4.4% with no index LDL on at least a moderate-dose statin. Of the entire cohort ≥18 years of age, 13.7% were potentially overtreated. Facilities with higher rates of meeting the current threshold measure (LDL <100 mg/dL) had higher rates of potential overtreatment (
P
<0.001).

Conclusions—
Use of a performance measure that credits appropriate clinical action indicates that almost 85% of diabetic veterans 50 to 75 years of age are receiving appropriate dyslipidemia management. However, many patients are potentially overtreated with high-dose statins.
Finescale Vertical Structure of the Upwelling System off Southern Peru as Observed from Glider Data
Authors: Pietri Alice , Testor Pierre , Echevin Vincent , Chaigneau Alexis , Mortier Laurent , Eldin Gerard , Grados Carmen 
Published: December 2012

Abstract
The upwelling system off southern Peru has been observed using an autonomous underwater vehicle (a Slocum glider) during October–November 2008. Nine cross-front sections have been carried out across an intense upwelling cell near 14°S. During almost two months, profiles of temperature, salinity, and fluorescence were collected at less than 1-km resolution, between the surface and 200-m depth. Estimates of alongshore absolute geostrophic velocities were inferred from the density field and the glider drift between two surfacings. In the frontal region, salinity and biogeochemical fields displayed cross-shore submesoscale filamentary structures throughout the mission. Those features presented a width of 10–20 km, a vertical extent of ~150 m, and appeared to propagate toward the shore. They were steeper than isopycnals and kept an aspect ratio close to f/N, the inverse of the Prandtl ratio. These filamentary structures may be interpreted mainly as a manifestation of submesoscale turbulence through stirring of the salinity gradients by the mesoscale eddy field. However, meandering of the front or cross-frontal wind-driven instabilities could also play a role in inducing vertical velocities.