bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transverse testicular ectopia
Authors: Yıldız Abdullah , Yiğiter Murat , Oral Akgün , Bakan Vedat 
Published: February 2014

AbstractDescribed herein are six cases of transverse testicular ectopia. All patients who underwent orchidopexy at the one pediatric surgical unit between October 2001 and January 2008 were evaluated. The medical records of all patients diagnosed with transverse testicular ectopia were evaluated retrospectively. Five patients (84%) were admitted with a symptomatic right inguinal hernia and empty scrotum on the left side. Only one child (16%) had left‐sided hernia and right non‐palpable testis (age ranged from 1 month to 3 years). Four patients (66%) were diagnosed in the operating theatre and the last two (33%) on inguinal ultrasound preoperatively. Magnetic resonance imaging was also performed in the last patient. Herniorrhaphy with fixation of the ectopic gonad to the opposite hemiscrotum through a transseptal incision was performed in all patients. Postoperative complications were not observed.
Correlation of mRNA and protein abundance in the developing maize leaf
Authors: Ponnala Lalit , Wang Yupeng , Sun Qi , van Wijk Klaas J. 
Published: February 2014

SummaryTo help understand regulation of maize leaf blade development, including sink‐source transitions and induction of C4 photosynthesis, we compared large‐scale quantitative proteome and transcriptomes collected at specific stages along the developmental maize leaf blade gradient. Proteome data were based on label‐free shotgun proteomics (spectral counting) and transcript data were based on RNA‐seq using the same source materials, and had been published previously (Nat Genet, 42, 2010, 1060–1067; The Plant Cell, 22, 2010, 3509–3542). Transcript and protein abundance followed near normal distributions, in contrast with several studies with other organisms. Protein observability correlated with transcript abundance following a ‘lazy step function’ similar to that in bacteria and yeast. mRNA and protein abundance showed significant positive correlations (up to 0.8) for log‐transformed length‐weighted normalized spectral abundance factor (NSAF) and reads per kilobase of exon model per million mapped reads (RPKM) and non‐weighted abundances (NadjSPC and COV) in dependence of function and development. Correlations were much weaker in the leaf ‘sink‐source’ transition zone, i.e. the zone with massive investments in leaf chloroplast biogenesis and build‐up of photosynthetic capacity. Clustering analyses of gene‐specific protein–mRNA ratios revealed co‐ordinated shifts in control points in gene expression along the leaf blade developmental gradient. The highest protein–mRNA ratio for each gene generally corresponded to leaf developmental stages in which the protein function was most important, with the exception of the 80S ribosome. Specific examples are discussed in the context of C4 photosynthesis, leaf development and sink‐source transitions. This large‐scale mRNA–protein correlation analysis in plants (maize) using label‐free spectral counting for protein quantification and RNA‐seq for mRNA abundance will provide a template for future mRNA–protein correlation studies.
Finite Element Method Oriented Failure Analysis of Medical Implants: Artificial Knee
Authors: Sivarasu Sudesh , James Sam Prasanna , Mathew T. Lazar 
Published: February 2014

The application of Finite Element Modelling in Medical Applications has been evolving as the field of high importance especially in the development of medical devices. The Total Knee Arthroplasty [TKA] has been in existence for over 6 decades till now. The generic artificial knee implants used in the TKA have the restriction in its range of motion with around 90 degrees. A new design allowing flexion extension range of over 120 degrees was designed with a view to facilitate partial squatting and the same is used for the analysis purpose. The new design of the artificial knee has a flexion extension range of 130 degrees. The higher flexion of the knee is obtained by use of the rotating platform knee design principle and also by adopting a multi-radii approach for the femoral component design.
The loading conditions of 10 times the body weight are considered for structural analyses of the novel knee. A maximum load of 700Kg were subjected on the knee implants. The finite element analyses of the designs were carried out based on standard biomaterial used in orthopedic implants. In this paper we have discussed the results of analyses of an artificial knee with Ti alloy. The results of the analyses were used in identifying areas of extreme stresses within the design and the spot prone for higher deformation. Based on these results slight modification on the designs was carried out. The results are also verified whether the body is within the linear deformation levels. As the results obtained were very satisfactory the models have been recommended for prototyping.
Nano-Bio-Cogno Model of Acoustic Patterning for Molecular Neurostimulation
Authors: Lacatus Elena , Savulescu Alexandru Florin 
Published: February 2014

To define a nano-bio-cogno model able to relate acoustic patterning on crystallization of biocompatible colloids to electrolytic molecular neurostimulation, means to functionally relate the in vitro and in vivo experiments aiming to find the key towards some objectively personalized therapies.
For this interdisciplinary research, from the wide spectrum of acoustic frequencies were selected the biologically safe values for in vitro and in vivo experiments, aiming to define a possible relationships between the crystallization patterns of biocompatible colloidal electrolytes and the dynamics of neural activity under the influence of the same acoustic stimuli.
A Novel Ketolide, RBx 14255, with Activity against Multidrug-Resistant Streptococcus pneumoniae
Authors: Raj V. Samuel , Barman Tarani Kanta , Kalia Vandana , Purnapatre Kedar , Dube Smita , G. Ramkumar , Bhateja Pragya , Mathur Tarun , Chaira Tridib , Upadhyay Dilip J. , Surase Yogesh B. , Venkataramanan R. , Chakrabarti Anjan , Das Biswajit , Bhatnagar Pradip K. 
Published: February 2014

ABSTRACTWe present here the novel ketolide RBx 14255, a semisynthetic macrolide derivative obtained by the derivatization of clarithromycin, for itsin vitroandin vivoactivities against sensitive and macrolide-resistantStreptococcus pneumoniae. RBx 14255 showed excellentin vitroactivity against macrolide-resistantS. pneumoniae, including an in-house-generated telithromycin-resistant strain (S. pneumoniae3390 NDDR). RBx 14255 also showed potent protein synthesis inhibition against telithromycin-resistantS. pneumoniae3390 NDDR. The binding affinity of RBx 14255 toward ribosomes was found to be more than that for other tested drugs. Thein vivoefficacy of RBx 14255 was determined in murine pulmonary infection induced by intranasal inoculation ofS. pneumoniaeATCC 6303 and systemic infection withS. pneumoniae3390 NDDR strains. The 50% effective dose (ED50) of RBx 14255 againstS. pneumoniaeATCC 6303 in a murine pulmonary infection model was 3.12 mg/kg of body weight. In addition, RBx 14255 resulted in 100% survival of mice with systemic infection caused by macrolide-resistantS. pneumoniae3390 NDDR at 100 mg/kg four times daily (QID) and at 50 mg/kg QID. RBx 14255 showed favorable pharmacokinetic properties that were comparable to those of telithromycin.
Pharmacokinetics and Safety of Boosted Elvitegravir in Subjects with Hepatic Impairment
Authors: Custodio Joseph M. , Rhee Martin , Shen Gong , Ling Kah Hiing J. , Kearney Brian P. , Ramanathan Srinivasan 
Published: February 2014

ABSTRACT

Elvitegravir (EVG), an HIV strand transfer integrase inhibitor, is metabolized primarily via cytochrome P450 3A4 (CYP3A) and secondarily via glucuronidation. The pharmacokinetics (PK) and safety of cobicistat (COBI)-boosted EVG (EVG/co) were evaluated in subjects with impaired liver function. The enrolled subjects had stable moderate liver impairment (
n
= 10; Child-Pugh-Turcotte [CPT] class B) or were healthy controls (
n
= 10) matched for age (±5 years), gender, and body mass index (±15%). EVG/co (150/150 mg) was administered once daily for 10 days, followed by pharmacokinetic (PK) sampling. Safety was assessed throughout the study. EVG and COBI exposures were compared between the impairment and control groups, with a ≥100% increase considered clinically relevant. EVG and COBI protein binding was also measured. All enrolled subjects completed the study. The treatment-emergent adverse event (AE) incidences were comparable between the groups; all study drug-related AEs were mild. The geometric mean ratio (90% confidence interval [CI]) for EVG area under the concentration-time curve over the dosing interval (AUC
tau
) and maximum observed plasma concentration (
C
max
) were 135% (103%, 177%) and 141% (109%, 183%), respectively. The corresponding values for COBI were 99.8% (76.0%, 131%) and 86.1% (65.4%, 113%), respectively, indicating no clinically relevant change in exposure. No correlations were observed between the EVG and COBI exposures versus CPT score. The EVG- and COBI-free fractions were similar between groups. EVG and COBI do not require dose adjustment in moderate or mild liver impairment, as no clinically relevant PK changes were observed for EVG or COBI in this special population. No PK or safety data are available for EVG or COBI in subjects with severe hepatic impairment.
Oritavancin Activity against Staphylococcus aureus Causing Invasive Infections in U.S. and European Hospitals: a 5-Year International Surveillance Program
Authors: Mendes Rodrigo E. , Sader Helio S. , Flamm Robert K. , Farrell David J. , Jones Ronald N. 
Published: February 2014

ABSTRACT

In this study, oritavancin had modal MIC, MIC
50
, and MIC
90
values of 0.03, 0.03, and 0.06 μg/ml, respectively, against
Staphylococcus aureus
. Similar results (MIC
50/90
, 0.03/0.06 μg/ml) were observed against methicillin-resistant and -susceptible isolates and those demonstrating multidrug-resistant (MDR) and non-MDR phenotypes. When oritavancin (MIC
50/90
, 0.06/0.12 mg/ml) was tested against
S. aureus
with elevated MIC values for daptomycin (i.e., 1 to 4 mg/ml) and vancomycin (i.e., 2 mg/ml), it showed MIC results 2-fold higher than those for the more susceptible vancomycin or daptomycin counterparts (MIC
50/90
, 0.03/0.06 mg/ml), yet it inhibited these isolates at ≤0.25 mg/ml.
Characterization of Heat-Stable (STa) Toxoids of Enterotoxigenic Escherichia coli Fused to Double Mutant Heat-Labile Toxin Peptide in Inducing Neutralizing Anti-STa Antibodies
Authors: Ruan Xiaosai , Robertson Donald C. , Nataro James P. , Clements John D. , Zhang Weiping 
Published: February 2014

ABSTRACT

A long-standing challenge in developing vaccines against enterotoxigenic
Escherichia coli
(ETEC), the most common bacteria causing diarrhea in children of developing countries and travelers to these countries, is to protect against heat-stable toxin type Ib (STa or hSTa). STa and heat-labile toxin (LT) are virulence determinants in ETEC diarrhea. LT antigens are often used in vaccine development, but STa has not been included because of its poor immunogenicity and potent toxicity. Toxic STa is not safe for vaccines, but only STa possessing toxicity is believed to be able to induce neutralizing antibodies. However, recent studies demonstrated that nontoxic STa derivatives (toxoids), after being fused to an LT protein, induced neutralizing antibodies and suggested that different STa toxoids fused to an LT protein might exhibit different STa antigenic propensity. In this study, we selected 14 STa toxoids from a mini-STa toxoid library based on toxicity reduction and reactivity to anti-native STa antibodies, and genetically fused each toxoid to a monomeric double mutant LT (dmLT) peptide for 14 STa
-toxoid
-dmLT toxoid fusions. These toxoid fusions were used to immunize mice and were characterized for induction of anti-STa antibody response. The results showed that different STa toxoids (in fusions) varied greatly in anti-STa antigenicity. Among them, STa
N12S
, STa
N12T
, and STa
A14H
were the top toxoids in inducing anti-STa antibodies.
In vitro
neutralization assays indicated that antibodies induced by the 3×STa
N12S
-dmLT fusion antigen exhibited the greatest neutralizing activity against STa toxin. These results suggested 3×STa
N12S
-dmLT is a preferred fusion antigen to induce an anti-STa antibody response and provided long-awaited information for effective ETEC vaccine development.
Identification of the
Staphylococcus aureus vfrAB
Operon, a Novel Virulence Factor Regulatory Locus
Authors: Bose Jeffrey L. , Daly Seth M. , Hall Pamela R. , Bayles Kenneth W. 
Published: February 2014

ABSTRACT

During a screen of the Nebraska Transposon Mutant Library, we identified 71 mutations in the
Staphylococcus aureus
genome that altered hemolysis on blood agar medium. Although many of these mutations disrupted genes known to affect the production of alpha-hemolysin, two of them were associated with an apparent operon, designated
vfrAB
, that had not been characterized previously. Interestingly, a Δ
vfrB
mutant exhibited only minor effects on the transcription of the
hla
gene, encoding alpha-hemolysin, when grown in broth, as well as on RNAIII, a posttranscriptional regulatory RNA important for alpha-hemolysin translation, suggesting that VfrB may function at the posttranscriptional level. Indeed, a Δ
vfrB
mutant had increased
aur
and
sspAB
protease expression under these conditions. However, disruption of the known secreted proteases in the Δ
vfrB
mutant did not restore hemolytic activity in the Δ
vfrB
mutant on blood agar. Further analysis revealed that, in contrast to the minor effects of VfrB on
hla
transcription when strains were cultured in liquid media, the level of
hla
transcription was decreased 50-fold in the absence of VfrB on solid media. These results demonstrate that while VfrB represses protease expression when strains are grown in broth,
hla
regulation is highly responsive to factors associated with growth on solid media. Intriguingly, the Δ
vfrB
mutant displayed increased pathogenesis in a model of
S. aureus
dermonecrosis, further highlighting the complexity of VfrB-dependent virulence regulation. The results of this study describe a phenotype associated with a class of highly conserved yet uncharacterized proteins found in Gram-positive bacteria, and they shed new light on the regulation of virulence factors necessary for
S. aureus
pathogenesis.
Associations of overall sitting time and TV viewing time with fibrinogen and C reactive protein: the AusDiab study
Authors: Howard Bethany J , Balkau Beverley , Thorp Alicia A , Magliano Dianna J , Shaw Jonathan E , Owen Neville , Dunstan David W 
Published: February 2014

Background/aimSedentary behaviour is associated with increased risk for all-cause and cardiovascular mortality. Plasma fibrinogen and C reactive protein (CRP)—key inflammatory and/or haemostatic markers—may contribute to this association; however, few studies have examined their relationships with sedentary behaviours. We examined associations of overall sitting and TV viewing time with fibrinogen and high-sensitivity CRP (hsCRP).MethodsPlasma fibrinogen and hsCRP were measured in 3086 Australian adults (mean age: 55±12 years) who participated in the 2004–2005 AusDiab (Australian Diabetes, Obesity and Lifestyle) study. Multiple linear regression analyses examined cross-sectional associations of self-reported overall sitting and TV viewing time (h/day) with plasma fibrinogen and hsCRP, adjusting for sociodemographic, behavioural and medical treatments and conditions as potential covariates.ResultsOverall sitting time and TV viewing time were positively associated with plasma fibrinogen (sitting: β: 0.02 g/L, 95% CI (0.01 to 0.02); TV time: 0.03 g/L (0.02 to 0.05)) and hsCRP (sitting: 2.4% (1.2% to 3.6%); TV time: 4.5% (1.7% to 7.4%)). Associations were independent of leisure-time physical activity, but after adjusting for waist circumference, they remained for fibrinogen, but for hsCRP were attenuated to the null. Interactions were observed for gender×TV (p=0.011) with fibrinogen (associations in women only) and for waist circumference×TV (p=0.084) with hsCRP (associations in low-risk only).ConclusionsOverall sitting time was positively associated with plasma fibrinogen and hsCRP in men and women; associations of TV viewing time with fibrinogen were observed in women only. Abdominal adiposity-mediated associations for hsCRP but not for fibrinogen. Prospective and intervention studies are needed to establish likely causality and elucidate potential mechanisms.
Early intervention with tiotropium in Chinese patients with GOLD stages I–II chronic obstructive pulmonary disease (Tie-COPD): study protocol for a multicentre, double-blinded, randomised, controlled trial
Authors: Li Xiaochen , Zhou Yumin , Chen Shuyun , Zheng Jinping , Zhong Nanshan , Ran Pixin 
Published: February 2014

IntroductionOwing to the high and increasing morbidity and mortality, chronic obstructive pulmonary disease (COPD) has become a major public health problem worldwide. Although the majority of patients with COPD are in the early stages, little attention has been paid to them, in particular regarding to early intervention. Tiotropium bromide can significantly relieve symptoms and reduce the incidence of acute exacerbations of COPD. Therefore, we hypothesise that therapy with tiotropium bromide will benefit patients with COPD with early-stage disease.Method/analysisA randomised, double-blinded, placebo-controlled, parallel-group, multicentre clinical trial (Tiotropium In Early COPD study, Tie-COPD study) is being conducted to evaluate the efficacy and safety of long-term intervention with tiotropium in patients with COPD with early-stage disease. A total of 839 patients with COPD who satisfied the eligibility criteria were randomly assigned (1:1) to receive a once daily inhaled capsule of either tiotropium bromide (18 μg) or matching placebo for 2 years. Measurements will include forced expiratory volume in 1 s, health-related quality of life, grade degree of breathlessness related to activities, COPD exacerbations and pharmacoeconomic analysis.Ethics/disseminationThis study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University. Recruitment started in November 2011 and ended in October 2013, with 839 patients randomised. The treatment follow-up of participants with Tie-COPD is currently ongoing and is due to finish in November 2015. The authors will disseminate the findings in peer-reviewed publications, conferences and seminar presentations.Trial registrationClinicalTrials.gov (NCT01455129).
Mortality in chronic kidney disease and renal replacement therapy: a population-based cohort study
Authors: Neovius Martin , Jacobson Stefan H , Eriksson Jonas K , Elinder Carl-Gustaf , Hylander Britta 
Published: February 2014

ObjectiveTo compare mortality in chronic kidney disease (CKD) stages 4 and 5 (estimated glomerular filtration rate <30 mL/min/1.73 m2), peritoneal dialysis, haemodialysis and transplanted patients.DesignPopulation-based cohort study.SettingSwedish national healthcare system.ParticipantsSwedish adult patients with CKD stages 4 and 5 (n=3040; mean age 66 years), peritoneal dialysis (n=725; 60 years), haemodialysis (n=1791; 62 years) and renal transplantation (n=606; 48 years) were identified in Stockholm County clinical quality registers for renal disease between 1999 and 2010. Five general population controls were matched to each patient by age, sex and index year.ExposureCKD status (stage 4 or 5/peritoneal dialysis/haemodialysis/transplanted).Primary outcomeAll-cause mortality was ascertained from the Swedish Causes of Death Register. Mortality HRs were estimated using Cox regression conditioned on age, sex, diabetes status, education level and index year.ResultsDuring 6553 person-years, 766 patients with CKD stages 4 and 5 died (deaths/100 person-years 12, 95% CI 11 to 13) compared with 186 deaths during 1113 person-years in peritoneal dialysis (17, 95% CI 15 to 19), 924 deaths during 3680 person-years in haemodialysis (25, 95% CI 23 to 27) and 53 deaths during 2935 person-years in transplanted patients (1.8, 95% CI 1.4 to 2.4). Against matched general population controls, the mortality HR was 3.6 (95% CI 3.2 to 4.0) for CKD, 5.6 (95% CI 3.5 to 8.9) for transplanted patients, 9.2 (95% CI 6.6 to 12.7) for peritoneal dialysis and 12.6 (95% CI 10.8 to 14.6) for haemodialysis. In direct comparison versus CKD, the mortality HR was 1.7 (95% CI 1.4 to 2.1) for peritoneal dialysis, 2.6 (95% CI 2.3 to 2.9) for haemodialysis and 0.5 (95% CI 0.3 to 0.7) for transplanted patients.ConclusionsWe did not find support for mortality in CKD to be similar to dialysis mortality. The patients with CKD stages 4 and 5 had considerably lower mortality risk than dialysis patients, and considerably higher risk than transplanted patients and matched general population controls.
Postmarket safety in Canada: are significant therapeutic advances and biologics less safe than other drugs? A cohort study
Authors: Lexchin Joel 
Published: February 2014

ObjectivesExamine the probability of new active substances (NASs) approved in Canada between 1 January 1997 and 31 March 2012 acquiring a serious postmarket safety warning.DesignCohort study.Data sourcesAnnual reports of the Therapeutic Products Directorate and the Biologic and Genetic Therapies Directorate; evaluations of therapeutic innovation from the Patented Medicine Prices Review Board and Prescrire International; MedEffect Canada website.InterventionsPostmarket regulatory safety warning or withdrawal from market due to safety reasons.Primary and secondary outcome measuresCompare the probability of acquiring a postmarket safety warning in Canada in four different groups of drugs: (1) traditional medications versus biologics; (2) medications that offer significant new therapeutic benefits versus those that do not. Determine how well the type of review that an NAS received from Health Canada predicted the product's postmarket therapeutic value.ResultsThe probability of a traditional NAS acquiring a serious safety warning and/or being withdrawn was 29.9% (95% CI 21.8% to 40.2%) vs 27.3% (95% CI 18.2% to 39.7%) for an NAS of biological origin (p=0.47, log-rank test). For medications that were significant therapeutic advances the probability was 40.2% (95% CI 24.5% to 60.9%) vs 33.9% (95% CI 26.4% to 42.7%) for those that were not (p=0.18, log-rank test). Health Canada was 77.4% accurate in predicting the therapeutic importance of an NAS.ConclusionsThere was no difference in postmarket regulatory safety action between traditional medications and biologics and no difference between drugs with significant therapeutic benefits and those without. Although these results draw on Canadian data, they are likely to be relevant internationally. Further research should assess whether the current level of premarket safety evaluation is acceptable.