bluuebunny/crossref_metadata_2025_split huggingface dataset:
The membrane anchor of penicillin‐binding protein PBP2a from Streptococcus pneumoniae influences peptidoglycan chain length
Authors: Helassa Nordine , Vollmer Waldemar , Breukink Eefjan , Vernet Thierry , Zapun André 
Published: April 2012

The pneumococcus is an important Gram‐positive pathogen, which shows increasing resistance to antibiotics, including β‐lactams that target peptidoglycan assembly. Understanding cell‐wall synthesis, at the molecular and cellular level, is essential for the prospect of combating drug resistance. As a first step towards reconstituting pneumococcal cell‐wall assembly in vitro, we present the characterization of the glycosyltransferase activity of penicillin‐binding protein (PBP)2a from Streptococcus pneumoniae. Recombinant full‐length membrane‐anchored PBP2a was purified by ion‐exchange chromatography. The glycosyltransferase activity of this enzyme was found to differ from that of a truncated periplasmic form. The full‐length protein with its cytoplasmic and transmembrane segment synthesizes longer glycan chains than the shorter form. The transpeptidase active site was functional, as shown by its reactivity towards bocillin and the catalysis of the hydrolysis of a thiol‐ester substrate analogue. However, PBP2a did not cross‐link the peptide stems of glycan chains in vitro. The absence of transpeptidase activity indicates that an essential component is missing from the in vitro system.Structured digital abstract
PBP2a and PBP2a bind by cross‐linking study (View interaction)
Performance of the New South Wales Ambulance Service major trauma transport protocol (T1) at an inner city trauma centre
Authors: Dinh Michael M , Oliver Matthew , Bein Kendall J , Roncal Susan , Byrne Christopher M 
Published: April 2012

AbstractObjective: To evaluate the performance of a newly implemented prehospital trauma triage (T1) protocol in New South Wales for patients transported to an inner city major trauma centre.Methods: An observational study was conducted over 1 year. Prehospital data and injury characteristics were collected prospectively for all hospital trauma team activations and injury presentations transported by Ambulance Service of New South Wales. Univariate comparison of T1‐ and non‐T1‐transported patients was performed and sensitivity, specificity, overtriage and undertriage rates were calculated. The outcomes studied were Injury Severity Score >15 and major outcome (composite of in‐hospital death and/or transferred from the ED to operating theatre or intensive care unit). Factors associated with undertriage were determined with univariate analysis.Results: A total of 2664 ambulance arrivals for trauma were studied with 767(29%) transported on the T1 protocol. T1‐transported patients were associated with more severe injury (23% vs 6%, P < 0.001) and major outcomes (30% vs 10%, P < 0.001) compared with non‐T1‐transported patients. The sensitivity of the T1 protocol for severe injury was 63% with a positive predictive value of 23%. The undertriage and overtriage rates for severe injury were 12% and 77%, respectively. Undertriaged patients were elderly with falls as the predominant mechanism of injury.Conclusion: The sensitivity and undertriage rates associated with the T1 protocol indicate the ongoing need for secondary triage at designated trauma centres and refinement of the protocol to include age as a criterion.
Inter‐industry Technology Spillover Effects in China: Evidence from 35 Industrial Sectors
Authors: Pan Wenqing , Yang Delin , Lin Min 
Published: April 2012

AbstractThe present paper calculates 35 industrial sectors' similarity matrices for the period of 1997–2008 using China's input–output tables for 1997, 2002 and 2007, and uses these to measure inter‐industry technology spillover to analyze the spillover effects on industrial sectors' labor productivity. The empirical analysis shows that inter‐industry technology spillover has a significant positive effect on the labor productivity of each industry. The elasticity of productivity effects of inter‐industry technology spillover is not only larger than that of direct R&D input, but also increases over time. We group the industries into four major categories and find that the inter‐industry technology spillover effect within the categories is, on average, greater than that between the four categories, indicating that technology spillover occurs more easily between similar industries. This research shows that the interindustry technology spillover effect in China has begun to increase, and the government should take advantage of this effect.
Light chain deposition disease: novel biological insights and treatment advances
Authors: JIMENEZ‐ZEPEDA V. H. 
Published: April 2012

SummaryLight chain deposition disease (LCDD) is a monoclonal gammopathy characterized by nonamyloid deposition of immunoglobulin light chains in various organs. Most cases present with renal dysfunction, a ubiquitous feature of this disease, and in some instances, it may progress to end‐stage renal disease. Unfortunately, until now, no standard treatment has been established. The use of alkylating agents and steroids has been extensively reported. However, conventional chemotherapy response is generally limited with minor effects on kidney function. The use of novel agents such as bortezomib has shown a more rapid response with a dramatically important reduction of light chains in serum and/or urine in small series of cases. Furthermore, autologous stem cell transplantation has been reported as a feasible strategy in LCDD, able to prolong the dialysis‐free survival. Nonetheless, toxicity from these therapies should be considered carefully because most of patients might present with kidney dysfunction that could limit the use of some agents.
Grazing management in saltmarsh ecosystems drives invertebrate diversity, abundance and functional group structure
Authors: FORD HILARY , GARBUTT ANGUS , JONES LAURENCE , JONES DAVEY L. 
Published: April 2012

Abstract.  1. Saltmarsh conservation management often involves livestock grazing to maximise plant diversity and provide suitable breeding habitat for over‐wintering coastal birds. The effect of grazing on invertebrates is rarely quantified, but results from limited studies of terrestrial and coastal grasslands demonstrate greater abundance and species richness in un‐grazed grassland.2. The impact of short sward (<8 cm) cattle grazing on the ground dwelling invertebrate community was assessed on an English inter‐tidal upper salt marsh using pitfall traps. Abundance, species richness, functional group structure, abundance of coastal specialists, environmental factors that influence invertebrate habitat choice and food web composition were compared for grazed and un‐grazed marsh.3. In total, 90 000 invertebrates were sampled. Predatory, zoophagus and detritivorous Coleoptera were significantly more abundant on the un‐grazed marsh. In contrast, predatory Hemiptera and Araneae were significantly more abundant on the grazed marsh. Sheet weaver spiders were significantly more abundant on the grazed marsh, foliage running hunters and space web builders more abundant on the un‐grazed marsh. Most inter‐tidal coastal specialist species exhibited clear habitat preference for the grazed marsh. Total species richness was not significantly different between grazing treatments.4. Linear direct gradient analysis showed that two environmental variables influenced by grazing intensity, soil temperature and vegetation height, significantly explained the composition of invertebrate functional groups. Larger bodied invertebrates dominated the un‐grazed food web.5. We conclude that both short sward cattle grazed and un‐grazed saltmarsh habitat should be maintained to maximise invertebrate abundance and diversity and provide suitable habitat for coastal specialists.
Comparison of the feasibility of three flood‐risk extent delineation techniques using Geographic Information System: case study in Tavoliere delle Puglie, Italy
Authors: Strobl R.O. , Forte F. , Lonigro T. 
Published: April 2012

AbstractDelineation of flood‐risk extent is a tedious task which normally requires the expertise of trained hydrologists. In order to provide a quicker and more automated approach for estimating flood‐risk extent, three straightforward methods (Mahalanobis distance, Maximin and Equally likely decision methods) which are easily executed in Geographic Information System were investigated and applied to a study area in the so‐called ‘Tavoliere delle Puglie’ (southern Italy). The delineated areas were then visually and statistically confronted with a methodology based on hydrologic expertise that can be considered up to date with current flood‐risk zone delineation knowledge. Two major problems associated with flood‐risk extent estimation are firstly the overwhelming complexity of the wide variety of spatially relevant flood‐related data and the amount of information contained within these data that are not easily interpreted without often costly and time consuming hydrologic expertise, and secondly, the wide variety of criteria usually considered in flood‐risk analysis, yielding a broad spectrum of different units involved. The comparative analysis has revealed that of the three alternative methods, only the Mahalanobis distance technique gave moderately comparable results with the methodology based on hydrologic expert knowledge. The results suggest and confirm that hydrologic expertise cannot be bypassed in flood‐risk extent analysis.
Treatment extension may benefit female genotype 1 chronic hepatitis C patients with complete early virological response to peginterferon‐alpha‐2b and ribavirin combination therapy
Authors: Nishimura Takeshi , Yamaguchi Kanji , Hashimoto Hiroaki , Niimi Toshihisa , Yokomizo Chihiro , Fujii Hideki , Minami Masahito , Sakamoto Masafumi , Ohnish Naoki , Nagao Yasuyuki , Okita Mika , Umemura Atsushi , Shima Toshihide , Okanoue Takeshi , Itoh Yoshito 
Published: April 2012

Aim:  Little is known about the appropriate use of peginterferon‐α‐2b (PEG IFN‐α‐2b) or ribavirin (RBV) in genotype 1 chronic hepatitis C (CH‐C) patients with complete early virological response (cEVR). Female patients, especially the older, are known to experience inferior treatment outcomes.Method:  A total of 150 CH‐C patients with cEVR treated for 48 weeks (n = 104) or 52–64 weeks (n = 46) with PEG IFN‐α‐2b and RBV combination therapy were retrospectively analyzed to evaluate the benefits of extended treatment.Results:  In the 48‐week group, patients without a sustained virological response (SVR) were more often female (P = 0.004) and had received a significantly lower total RBV dose (P = 0.003) than those with SVR. The SVR rate in these female patients was similar to males with hepatitis C virus (HCV) RNA negativity at treatment week 8 (P = 0.413); however, it was lower than that in males with HCV RNA negativity at treatment week 12 (P = 0.005). In the 52–64‐week group, although the total RBV dose (mg/kg) after treatment week 48 was less in females than in males (P = 0.027), the SVR rate in females was equivalent to that in males (P = 0.604).Conclusion:  Genotype 1 CH‐C patients treated with PEG IFN‐α‐2b and RBV combination therapy without SVR were more often female and had received a lower total RBV dose than males. The smaller SVR rate in female patients with cEVR compared to males may be overcome by extending treatment even if the RBV dose is lowered due to anemia.
Concurrent use of complementary and alternative medicine with antiretroviral therapy reduces adherence to HIV medications
Authors: Ekwunife Obinna Ikechukwu , Oreh Chinekwu , Ubaka Chukwuemeka Micheal 
Published: April 2012

Abstract

Objective
Antiretroviral therapy requires strict adherence to ensure therapeutic success. Concurrent use of complementary and alternative medicine (CAM) could alter the adherence to and thereby effectiveness of antiretroviral drugs. This study examined the association of CAM use with adherence to antiretroviral therapy (ART) and CD4 count.

Methods
The study was conducted in two HIV clinics: one in a semi-urban, the other in a rural area. Adherence to ART was assessed using the Morisky Medication Adherence Scale (MMAS). Data on type of CAM used and MMAS adherence were collected by patient interview and demographic; clinical data were collected from hospital records.

Results
Altogether 212 HIV patients participated in the exit study conducted over 3 months. Almost half (47.9%) used CAM concurrently with antiretroviral drugs. Dietary supplements (40.3%), healing systems (36.5%) and exercise (23.2%) were mainly used. The use of CAM significantly lowered adherence to ART (89.4% in non-CAM users versus 82.5% in CAM users, P = 0.01). Improvement in CD4 count was less in patients using CAM compared to non-CAM users although the difference was not statistically significant (310.5 ± 294.0 cells/L in CAM users versus 224.5 ± 220.0 cells/L in non-CAM users, P = 0.13). Patients attending the rural HIV clinic were more likely to use CAM compared to patients attending semi-urban hospital (χ2 test = 7.0; P &lt; 0.01).

Conclusion
Use of CAM could lower adherence to antiretroviral therapy. There is need to develop protocol which could help in monitoring CAM use in HIV patients especially those from rural settings.
Response and Stability Analysis of Periodic Delayed Systems With Discontinuous Distributed Delay
Authors: Bobrenkov Oleg A. , Nazari Morad , Butcher Eric A. 
Published: April 2012

AbstractIn this paper, the analysis of delay differential equations with periodic coefficients and discontinuous distributed delay is carried out through discretization by the Chebyshev spectral continuous time approximation (ChSCTA). These features are introduced in the delayed Mathieu equation with discontinuous distributed delay which is used as an illustrative example. The efficiency of stability analysis is improved by using shifted Chebyshev polynomials for computing the monodromy matrix, as well as the adaptive meshing of the parameter plane. An idea for a method for numerical integration of periodic DDEs with discontinuous distributed delay based on existing MATLAB functions is proposed.
Pseudomonas
Biofilms, Cystic Fibrosis, and Phage: a Silver Lining?
Authors: Brüssow Harald 
Published: April 2012

ABSTRACT

In contrast to usual laboratory conditions, most bacteria in the human body grow in biofilms. Encased in a structured matrix, many pathogens display heightened resistance to antibiotics.
Pseudomonas aeruginosa
lung infections in cystic fibrosis patients represent a prime example of the clinical challenges that antibiotic resistance in biofilms can represent. In the March 6, 2012 issue of
mBio
, Colin Hill and his colleagues report on experiments that add to the evidence that
Pseudomonas
phages are a potential treatment option for these infections.
A potential role of Escherichia coli pathobionts in the pathogenesis of pediatric inflammatory bowel disease
Authors: Schippa Serena , Iebba Valerio , Totino Valentina , Santangelo Floriana , Lepanto Mariastefania , Alessandri Claudia , Nuti Federica , Viola Franca , Di Nardo Giovanni , Cucchiara Salvatore , Longhi Catia , Conte Maria Pia 
Published: April 2012

Through genomic analysis of mucosa-associated Escherichia coli strains, we found a close genetic association among isolates from pediatric inflammatory bowel disease (IBD) patients. A specific E. coli pathovar, adherent–invasive E. coli (AIEC), was found in Crohn’s disease (CD) adult patients — this pathovar has enhanced adhesive and invasive properties, mainly due to the mannose-bonding FimH protein. We aimed to characterize 52 mucosa-associated E. coli strains isolated from pediatric IBD and non-IBD patients. Eleven E. coli strains, showing a strong similarity in fimH gene sequence to that of E. coli AIEC LF82, were characterized for fimH gene sequence, genomic profiling, adhesive and invasive ability, and phylogrouping. The results were compared with E. coli strains AIEC LF82 and MG1655. The 11 E. coli isolates showed 82.4% ± 1.4% fimH sequence similarity and 80.6% ± 1.3% genomic similarity to strain AIEC LF82. All these strains harbored V27A and S78N FimH mutations, as found in LF82. Nine of them belonged to the more virulent B2 and D phylogroups. Neuraminidase treatment, mimicking inflamed mucosa, enhanced adhesion of all 11 strains by 3.5-fold, but none showed invasion ability. It could be argued that the 11 selected strains could be a branch of an E. coli subpopulation (pathobionts), that could take advantage in an inflamed context because of a suitable genomic and (or) genetic backdrop.
Inhibiting Systemic Autophagy during Interleukin 2 Immunotherapy Promotes Long-term Tumor Regression
Authors: Liang Xiaoyan , De Vera Michael E. , Buchser William J. , de Vivar Chavez Antonio Romo , Loughran Patricia , Stolz Donna Beer , Basse Per , Wang Tao , Van Houten Bennett , Zeh Herbert J. , Lotze Michael T. 
Published: April 2012

Abstract
Administration of high-dose interleukin-2 (HDIL-2) has durable antitumor effects in 5% to 10% of patients with melanoma and renal cell carcinoma. However, treatment is often limited by side effects, including reversible, multiorgan dysfunction characterized by a cytokine-induced systemic autophagic syndrome. Here, we hypothesized that the autophagy inhibitor chloroquine would enhance IL-2 immunotherapeutic efficacy and limit toxicity. In an advanced murine metastatic liver tumor model, IL-2 inhibited tumor growth in a dose-dependent fashion. These antitumor effects were significantly enhanced upon addition of chloroquine. The combination of IL-2 with chloroquine increased long-term survival, decreased toxicity associated with vascular leakage, and enhanced immune cell proliferation and infiltration in the liver and spleen. HDIL-2 alone increased serum levels of HMGB1, IFN-γ, IL-6, and IL-18 and also induced autophagy within the liver and translocation of HMGB1 from the nucleus to the cytosol in hepatocytes, effects that were inhibited by combined administration with chloroquine. In tumor cells, chloroquine increased autophagic vacuoles and LC3-II levels inhibited oxidative phosphorylation and ATP production and promoted apoptosis, which was associated with increased Annexin-V+/propidium iodide (PI)− cells, cleaved PARP, cleaved caspase-3, and cytochrome c release from mitochondria. Taken together, our findings provide a novel clinical strategy to enhance the efficacy of HDIL-2 immunotherapy for patients with cancer. Cancer Res; 72(11); 2791–801. ©2012 AACR.
SSBP2 Variants Are Associated with Survival in Glioblastoma Patients
Authors: Xiao Yuanyuan , Decker Paul A. , Rice Terri , McCoy Lucie S. , Smirnov Ivan , Patoka Joseph S. , Hansen Helen M. , Wiemels Joe L. , Tihan Tarik , Prados Michael D. , Chang Susan M. , Berger Mitchel S. , Kosel Matthew L. , Fridley Brooke L. , Lachance Daniel H. , O'Neill Brian Patrick , Buckner Jan C. , Thompson Reid C. , Nabors Louis Burt , Olson Jeffrey J. , Brem Steve , Madden Melissa H. , Browning James E. , Wiencke John K. , Egan Kathleen M. , Jenkins Robert B. , Wrensch Margaret R. 
Published: April 2012

Abstract
Purpose: Glioblastoma is a devastating, incurable disease with few known prognostic factors. Here, we present the first genome-wide survival and validation study for glioblastoma.
Experimental Design: Cox regressions for survival with 314,635 inherited autosomal single-nucleotide polymorphisms (SNP) among 315 San Francisco Adult Glioma Study patients for discovery and three independent validation data sets [87 Mayo Clinic, 232 glioma patients recruited from several medical centers in Southeastern United States (GliomaSE), and 115 The Cancer Genome Atlas patients] were used to identify SNPs associated with overall survival for Caucasian glioblastoma patients treated with the current standard of care, resection, radiation, and temozolomide (total n = 749). Tumor expression of the gene that contained the identified prognostic SNP was examined in three separate data sets (total n = 619). Genotype imputation was used to estimate hazard ratios (HR) for SNPs that had not been directly genotyped.
Results: From the discovery and validation analyses, we identified a variant in single-stranded DNA-binding protein 2 (SSBP2) on 5q14.1 associated with overall survival in combined analyses (HR, 1.64; P = 1.3 × 10−6). Expression of SSBP2 in tumors from three independent data sets also was significantly related to patient survival (P = 5.3 × 10−4). Using genotype imputation, the SSBP2 SNP rs17296479 had the strongest statistically significant genome-wide association with poorer overall patient survival (HR, 1.79; 95% CI, 1.45-2.22; P = 1.0 × 10−7).
Conclusion: The minor allele of SSBP2 SNP rs17296479 and the increased tumor expression of SSBP2 were statistically significantly associated with poorer overall survival among glioblastoma patients. With further confirmation, previously unrecognized inherited variations influencing survival may warrant inclusion in clinical trials to improve randomization. Unaccounted for genetic influence on survival could produce unwanted bias in such studies. Clin Cancer Res; 18(11); 3154–62. ©2012 AACR.
Association of Cardiorespiratory Fitness With Total, Cardiovascular, and Noncardiovascular Mortality Across 3 Decades of Follow-Up in Men and Women
Authors: Vigen Rebecca , Ayers Colby , Willis Benjamin , DeFina Laura , Berry Jarett D. 
Published: April 2012

Background—
The inverse, dose-dependent association between cardiorespiratory fitness and mortality is well-established; however, the pattern of the association between low fitness and mortality across short- (0 to 10 years), intermediate- (10 to 20 years), and long-term (>20 years) follow-up has not been studied.

Methods and Results—
We included 46 575 men and 16 151 women (mean age 44 years) from the Cooper Center Longitudinal Study. Participants were categorized as either “low fit” or “not low fit,” based on age- and sex- adjusted treadmill times, and were followed for mortality, determined from the National Death Index. Multivariable-adjusted Cox proportional hazards models were constructed to compare the association between fitness and traditional risk factors, with mortality outcomes across short-, intermediate-, and long-term follow-up. After a median follow-up of 16 years, there were 1295 cardiovascular disease and 2840 noncardiovascular disease deaths. Low fitness was associated with all-cause mortality across all periods in men [0 to 10 years: hazard ratios (HR), 1.99 (95% confidence interval [CI], 1.66 to 2.40); 10 to 20 years: HR, 1.61 (95% CI, 1.41 to 1.84); and >20 years: HR, 1.42 (95% CI, 1.27 to 1.60)] and in women [0 to 10 years: HR, 1.98 (95% CI, 1.27 to 3.10); 10 to 20 years: HR, 1.90 (95% CI, 1.40 to 2.56); and >20 years: HR, 1.54 (95% CI, 1.15 to 2.07)]. Similar results were seen for both cardiovascular disease and noncardiovascular disease mortality. Although these associations were also consistent across most subgroups, low fitness appeared to be most strongly associated with mortality in the short term among individuals at highest short-term risk (ie, older age, abnormal exercise test).

Conclusions—
Similar to traditional risk factors, fitness is associated with mortality across short-, intermediate-, and long-term follow-up.
Precreation Discourse in Psalms 74 and 77: Struggling with Chaoskämpfe
Authors: Sylva Dennis 
Published: April 2012

AbstractThe way in which Psalms 74 and 77 deal with historical turmoil in the psalmists’ lives is to weave together reflections on the concrete problems being experienced with succinct myths about God’s precreative struggle with chaos:Chaoskämpfe. The cultural intertextural background for these myths is to be found in Near Eastern accounts about the divine battle against chaotic sea gods. Each psalmist tailors this component in ways that fit the theodicy and the basis of appeal for divine intervention in their own lives that they are attempting to construct. In the interplays of these overarching constructions and the roles of theChaoskämpfein them the larger functions of the precreative discourses in these psalms are to be found.