bluuebunny/crossref_metadata_2025_split huggingface dataset:
International Pneumococcal Clones Match or Exceed the Fitness of Other Strains despite the Accumulation of Antibiotic Resistance
Authors: Rudolf Daniel , Michaylov Nikolay , van der Linden Mark , Hoy Ludwig , Klugman Keith P. , Welte Tobias , Pletz Mathias W. 
Published: August 2011

ABSTRACT

A few international pneumococcal clones dominate the population of antibiotic-resistant pneumococci. Despite the scientific paradigm that a loss in fitness is the price for acquisition of resistance, these clones spread successfully. One hundred fifty-four isolates from adult patients with community-acquired pneumonia (CAP) were analyzed. Thirty percent showed a close relationship to international clones and had fitness equal to or exceeding that of other strains (
P
= 0.015); these factors may result in the endurance of these strains despite a reduction of antibiotic usage.
Is Cefazolin Inferior to Nafcillin for Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia?
Authors: Lee Shinwon , Choe Pyoeng Gyun , Song Kyoung-Ho , Park Sang-Won , Kim Hong Bin , Kim Nam Joong , Kim Eui-Chong , Park Wan Beom , Oh Myoung-don 
Published: August 2011

ABSTRACT

About 20% of methicillin-susceptible
Staphylococcus aureus
(MSSA) isolates have a substantial inoculum effect with cefazolin, suggesting that cefazolin treatment may be associated with clinical failure for serious MSSA infections. There are no well-matched controlled studies comparing cefazolin with nafcillin for the treatment of MSSA bacteremia. A retrospective propensity-score-matched case-control study was performed from 2004 to 2009 in a tertiary care hospital where nafcillin was unavailable from August 2004 to August 2006. The cefazolin group (
n
= 49) included MSSA-bacteremic patients treated with cefazolin during the period of nafcillin unavailability, while the nafcillin group (
n
= 84) comprised those treated with nafcillin. Treatment failure was defined as a composite outcome of a change of antibiotics due to clinical failure, relapse, and mortality. Of 133 patients, 41 patients from each group were matched by propensity scores. There were no significant differences in baseline characteristics between the matched groups. The treatment failure rates were not significantly different at 4 or 12 weeks (10% [4/41] versus 10% [4/41] at 4 weeks [
P
> 0.99] and 15% [6/41] versus 15% [6/41] at 12 weeks [
P
> 0.99]). Cefazolin treatment was interrupted less frequently than nafcillin treatment due to drug adverse events (0% versus 17%;
P
= 0.02). Cefazolin had clinical efficacy similar to that of nafcillin and was more tolerable than nafcillin for the treatment of MSSA bacteremia.
Development of Peptide-Conjugated Morpholino Oligomers as Pan-Arenavirus Inhibitors
Authors: Neuman Benjamin W. , Bederka Lydia H. , Stein David A. , Ting Joey P. C. , Moulton Hong M. , Buchmeier Michael J. 
Published: August 2011

ABSTRACT

Members of the
Arenaviridae
family are a threat to public health and can cause meningitis and hemorrhagic fever, and yet treatment options remain limited by a lack of effective antivirals. In this study, we found that peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) complementary to viral genomic RNA were effective in reducing arenavirus replication in cell cultures and
in vivo
. PPMO complementary to the Junín virus genome were designed to interfere with viral RNA synthesis or translation or both. However, only PPMO designed to potentially interfere with translation were effective in reducing virus replication. PPMO complementary to sequences that are highly conserved across the arenaviruses and located at the 5′ termini of both genomic segments were effective against Junín virus, Tacaribe virus, Pichinde virus, and lymphocytic choriomeningitis virus (LCMV)-infected cell cultures and suppressed viral titers in the livers of LCMV-infected mice. These results suggest that arenavirus 5′ genomic termini represent promising targets for pan-arenavirus antiviral therapeutic development.
Enteral Tube Feeding Alters the Oral Indigenous Microbiota in Elderly Adults
Authors: Takeshita Toru , Yasui Masaki , Tomioka Mikiko , Nakano Yoshio , Shimazaki Yoshihiro , Yamashita Yoshihisa 
Published: August 2011

ABSTRACT

Enteral tube feeding is widely used to maintain nutrition for elderly adults with eating difficulties, but its long-term use alters the environment of the oral ecosystem. This study characterized the tongue microbiota of tube-fed elderly adults by analyzing the 16S rRNA gene. The terminal restriction fragment length polymorphism (T-RFLP) profiles of 44 tube-fed subjects were compared with those of 54 subjects fed orally (average age, 86.4 ± 6.9 years). Bar-coded pyrosequencing data were also obtained for a subset of the subjects from each group (15 tube-fed subjects and 16 subjects fed orally). The T-RFLP profiles demonstrated that the microbiota of the tube-fed subjects was distinct from that of the subjects fed orally (permutational multivariate analysis of variance [perMANOVA],
P
< 0.001). The pyrosequencing data revealed that 22 bacterial genera, including
Corynebacterium
,
Peptostreptococcus
, and
Fusobacterium
, were significantly more predominant in tube-fed subjects, whereas the dominant genera in the subjects fed orally, such as
Streptococcus
and
Veillonella
, were present in much lower proportions. Opportunistic pathogens rarely detected in the normal oral microbiota, such as
Corynebacterium striatum
and
Streptococcus agalactiae
, were often found in high proportions in tube-fed subjects. The oral indigenous microbiota is disrupted by the use of enteral feeding, allowing health-threatening bacteria to thrive.
Transmission of Intestinal Bifidobacterium longum subsp.
longum
Strains from Mother to Infant, Determined by Multilocus Sequencing Typing and Amplified Fragment Length Polymorphism
Authors: Makino Hiroshi , Kushiro Akira , Ishikawa Eiji , Muylaert Delphine , Kubota Hiroyuki , Sakai Takafumi , Oishi Kenji , Martin Rocio , Ben Amor Kaouther , Oozeer Raish , Knol Jan , Tanaka Ryuichiro 
Published: August 2011

ABSTRACT

The gastrointestinal tracts of neonates are colonized by bacteria immediately after birth. It has been discussed that the intestinal microbiota of neonates includes strains transferred from the mothers. Although some studies have indicated possible bacterial transfer from the mother to the newborn, this is the first report confirming the transfer of bifidobacteria at the strain level. Here, we investigated the mother-to-infant transmission of
Bifidobacterium longum
subsp.
longum
by genotyping bacterial isolates from the feces of mothers before delivery and of their infants after delivery. Two hundred seven isolates from 8 pairs of mothers and infants were discriminated by multilocus sequencing typing (MLST) and amplified fragment length polymorphism (AFLP) analysis. By both methods, 11 strains of
B. longum
subsp.
longum
were found to be monophyletic for the feces of the mother and her infant. This finding confirms that these strains were transferred from the intestine of the mother to that of the infant. These strains were found in the first feces (meconium) of the infant and in the feces at days 3, 7, 30, and 90 after birth, indicating that they stably colonize the infant's intestine immediately after birth. The strains isolated from each family did not belong to clusters derived from any of the other families, suggesting that each mother-infant pair might have unique family-specific strains.
Canopy-scale relationships between foliar nitrogen and albedo are not observed in leaf reflectance and transmittance within temperate deciduous tree species
Authors: Bartlett Megan K. , Ollinger Scott V. , Hollinger David Y. , Wicklein Haley F. , Richardson Andrew D. 
Published: August 2011

Strong positive correlations between the maximum rate of canopy photosynthesis, canopy-averaged foliar nitrogen concentration, and canopy albedo have been shown in previous studies. While leaf-level relationships between photosynthetic capacity and foliar nitrogen are well documented, it is not clear whether leaf-level relationships between solar-weighted reflectance and nitrogen underlie the canopy-scale patterns. Using an integrating sphere, we measured the reflectance and transmittance (350–2500 nm) of both individual leaves and multileaf stacks. Samples were collected from 12 broadleaf species at the Harvard Forest in central Massachusetts, USA. Across all species, foliar nitrogen (both mass-based nitrogen concentration and area-based nitrogen content) and leaf mass / area ratio were negatively, rather than positively, correlated with solar-weighted reflectance and transmittance in ultraviolet–visible and near-infrared wavelength bands (350–700 nm and 700–2500 nm, respectively). Leaf-level anatomy and biochemistry, therefore, do not appear to drive the canopy-level association between increasing foliar nitrogen content and increasing canopy albedo. This suggests that interactions between leaf optical properties and structural canopy-scale traits that correlate with nitrogen content (perhaps some combination of crown shape, leaf area index, leaf angular distribution, or other structural characteristics of the canopy), may instead underlie the previously observed relationship between nitrogen and canopy-level shortwave albedo.
Analysis of genetic diversity of Lactarius hatsudake in South China
Authors: He Li , Liang Guo , Guoying Zhou , Jun-ang Liu 
Published: August 2011

Lactarius hatsudake is a type of ectomycorrhizal fungus that significantly influences the growth of pine trees. It is widely prevalent in Asian countries and has a high economic value. Artificial cultivation of this fungus has not been achieved as yet; therefore, excessive manual harvesting may cause serious damages to the site of its production. In this study, we analyzed 41 samples of L. hatsudake from south China using internal transcribed spacer (ITS) sequences. By comparing the differences among ITS sequences to identify the haplotype diversity within each population, the relationships among local populations, the relationship between the level of genetic differentiation and geographical separation, and the contributions of local and regional geographical separations to the overall ITS haplotype variation were analyzed. Genetic analysis indicates that ITS sequences obtained from these 41 L. hatsudake samples could be identified as 18 haplotypes, of which 13 haplotypes were contained in only a single sample, whereas the remaining sequence types all were contained in two or more samples. The most common sequence type, haplotype 6, was found in 16 samples and was distributed across nearly every region. The Mantel test demonstrated that there is no significant linear relationship between geographical distance and the FST value of genetic difference. Results of this research illustrates that there exists a certain degree of genetic intermixing among natural populations of L. hatsudake. From the group genetic analysis, it appears that there exists genetic differentiation of lower frequencies in natural populations of L. hatsudake; however, the linear relationship between the degree of genetic differentiation and geographical distance is not distinctly apparent.
Relationship between Biomarkers of Cigarette Smoke Exposure and Biomarkers of Inflammation, Oxidative Stress, and Platelet Activation in Adult Cigarette Smokers
Authors: Liu Jianmin , Liang Qiwei , Frost-Pineda Kimberly , Muhammad-Kah Raheema , Rimmer Lonnie , Roethig Hans , Mendes Paul , Sarkar Mohamadi 
Published: August 2011

Abstract
Background: Cigarette smoking is a risk factor for several diseases, including cardiovascular disease, chronic obstructive pulmonary disease, and lung cancer, but the role of specific smoke constituents in these diseases has not been clearly established.
Methods: The relationships between biomarkers of potential harm (BOPH), associated with inflammation [white blood cell (WBC), high sensitivity C-reactive protein (hs-CRP), fibrinogen, and von Willebrand factor (vWF)], oxidative stress [8-epi-prostaglandin F2α (8-epiPGF2α)] and platelet activation [11-dehydro-thromboxin B2 (11-dehTxB2)], and machine-measured tar yields (grouped into four categories), biomarkers of exposure (BOE) to cigarette smoke: nicotine and its five metabolites (nicotine equivalents), 4-methylnitrosamino-1-(3-pyridyl)-1-butanol (total NNAL), carboxyhemoglobin, 1-hydroxypyrene, 3-hydroxypropylmercapturic acid, and monohydroxybutenyl-mercapturic acid, were investigated in 3,585 adult smokers and 1,077 nonsmokers.
Results: Overall, adult smokers had higher levels of BOPHs than nonsmokers. Body mass index (BMI), smoking duration, tar category, and some of the BOEs were significant factors in the multiple regression models. Based on the F value, BMI was the highest ranking factor in the models for WBC, hs-CRP, fibrinogen, and 8-epiPGF2α, respectively, and gender and smoking duration for 11-dehTxB2 and vWF, respectively.
Conclusions: Although several demographic factors and some BOEs were statistically significant in the model, the R2 values indicate that only up to 22% of the variability can be explained by these factors, reflecting the complexity and multifactorial nature of the disease mechanisms.
Impact: The relationships between the BOEs and BOPHs observed in this study may help with the identification of appropriate biomarkers and improve the design of clinical studies in smokers. Cancer Epidemiol Biomarkers Prev; 20(8); 1760–9. ©2011 AACR.
Localized Fibroglandular Tissue as a Predictor of Future Tumor Location within the Breast
Authors: Pereira Snehal M. Pinto , McCormack Valerie A. , Hipwell John H. , Record Carol , Wilkinson Louise S. , Moss Sue M. , Hawkes David J. , dos-Santos-Silva Isabel 
Published: August 2011

Abstract
Background: Mammographic density (MD) is a strong marker of breast cancer risk, but it is unclear whether tumors arise specifically within dense tissue.
Methods: In 231 British women diagnosed with breast cancer after at least one negative annual screening during a mammographic screening trial, we assessed whether tumor location was related to localized MD 5 years prior to diagnosis. Radiologists identified tumor locations on digitised films. We used a validated algorithm to align serial images from the same woman to locate the corresponding point on the prediagnostic film. A virtual 1 cm square grid was overlaid on prediagnostic films and MD calculated for each square within a woman's breast (mean = 271 squares/film). Conditional logistic regression, matching on a woman's breast, was used to estimate the odds of a tumor arising in a square in relation to its prediagnostic square-specific MD.
Results: Median (interquartile range) prediagnostic MD was 98.2% (46.8%–100%) in 1 cm-squares that subsequently contained the tumor and 41.0% (31.5%–53.9%) for the whole breast. The odds of a tumor arising in a 1 cm-square were, respectively, 6.1 (95% CI: 1.9–20.1), 16.6 (5.2–53.2), and 25.5-fold (8.1–80.3) higher for squares in the second, third, and fourth quartiles of prediagnostic MD relative to those in the lowest quartile within that breast (Ptrend &lt; 0.001). The corresponding odds ratios were 2.3 (1.3–4.0), 3.9 (2.3–6.4), and 4.6 (2.8–7.6) if a 3 cm-square grid was used.
Conclusion: Tumors arise predominantly within the radiodense breast tissue.
Impact: Localized MD may be used as a predictor of subsequent tumor location within the breast. Cancer Epidemiol Biomarkers Prev; 20(8); 1718–25. ©2011 AACR.
Assessment of Hepatocyte Growth Factor in Ovarian Cancer Mortality
Authors: Goode Ellen L. , Chenevix-Trench Georgia , Hartmann Lynn C. , Fridley Brooke L. , Kalli Kimberly R. , Vierkant Robert A. , Larson Melissa C. , White Kristin L. , Keeney Gary L. , Oberg Trynda N. , Cunningham Julie M. , Beesley Jonathan , Johnatty Sharon E. , Chen Xiaoqing , Goodman Katelyn E. , Armasu Sebastian M. , Rider David N. , Sicotte Hugues , Schmidt Michele M. , Elliott Elaine A. , Høgdall Estrid , Krüger Kjær Susanne , Fasching Peter A. , Ekici Arif B. , Lambrechts Diether , Despierre Evelyn , Høgdall Claus , Lundvall Lene , Karlan Beth Y. , Gross Jenny , Brown Robert , Chien Jeremy , Duggan David J. , Tsai Ya-Yu , Phelan Catherine M. , Kelemen Linda E. , Peethambaram Prema P. , Schildkraut Joellen M. , Shridhar Vijayalakshmi , Sutphen Rebecca , Couch Fergus J. , Sellers Thomas A. 
Published: August 2011

Abstract
Background: Invasive ovarian cancer is a significant cause of gynecologic cancer mortality.
Methods: We examined whether this mortality was associated with inherited variation in approximately 170 candidate genes/regions [993 single-nucleotide polymorphisms (SNPs)] in a multistage analysis based initially on 312 Mayo Clinic cases (172 deaths). Additional analyses used The Cancer Genome Atlas (TCGA; 127 cases, 62 deaths). For the most compelling gene, we immunostained Mayo Clinic tissue microarrays (TMA, 326 cases) and conducted consortium-based SNP replication analysis (2,560 cases, 1,046 deaths).
Results: The strongest initial mortality association was in HGF (hepatocyte growth factor) at rs1800793 (HR = 1.7, 95% CI = 1.3–2.2, P = 2.0 × 10−5) and with overall variation in HGF (gene-level test, P = 3.7 × 10−4). Analysis of TCGA data revealed consistent associations [e.g., rs5745709 (r2 = 0.96 with rs1800793): TCGA HR = 2.4, CI = 1.4–4.1, P = 2.2 × 10−3; Mayo Clinic + TCGA HR = 1.6, CI = 1.3–1.9, P = 7.0 × 10−5] and suggested genotype correlation with reduced HGF mRNA levels (P = 0.01). In Mayo Clinic TMAs, protein levels of HGF, its receptor MET (C-MET), and phospho-MET were not associated with genotype and did not serve as an intermediate phenotype; however, phospho-MET was associated with reduced mortality (P = 0.01) likely due to higher expression in early-stage disease. In eight additional ovarian cancer case series, HGF rs5745709 was not associated with mortality (HR = 1.0, CI = 0.9–1.1, P = 0.87).
Conclusions: We conclude that although HGF signaling is critical to migration, invasion, and apoptosis, it is unlikely that HGF genetic variation plays a major role in ovarian cancer mortality. Furthermore, any minor role is not related to genetically-determined expression.
Impact: Our study shows the utility of multiple data types and multiple data sets in observational studies. Cancer Epidemiol Biomarkers Prev; 20(8); 1638–48. ©2011 AACR.
Cyclin-Dependent Kinase 5 Is Amplified and Overexpressed in Pancreatic Cancer and Activated by Mutant K-Ras
Authors: Eggers John P. , Grandgenett Paul M. , Collisson Eric C. , Lewallen Michelle E. , Tremayne Jarrod , Singh Pankaj K. , Swanson Benjamin J. , Andersen Judy M. , Caffrey Thomas C. , High Robin R. , Ouellette Michel , Hollingsworth Michael A. 
Published: August 2011

Abstract
Purpose: To evaluate the nature of cyclin-dependent kinase 5 (CDK5) hyperactivity in pancreatic cancer progression.
Experimental Design: We used genetic, biochemical, and molecular biology methods to investigate the nature and function of overexpression of CDK5 and its activators p35 and p39 during the progression of pancreatic cancer.
Results: Amplification of the CDK5 gene or either of its main activators, p35 and p39, was observed in 67% of human pancreatic ductal adenocarcinoma (PDAC). CDK5, p35, and p39 were rarely expressed in pancreatic ducts whereas more than 90% of PDACs had increased levels of CDK5 and p35. Increased levels of CDK5, p35, and p39 protein were observed in several pancreatic cancer cell lines. Inhibition of CDK5 kinase activity using a CDK5 dominant-negative mutant or the drug roscovitine significantly decreased the migration and invasion of pancreatic cancer cells in vitro. Increased CDK5 kinase activity was also observed in immortalized human pancreatic nestin-expressing (HPNE) cells expressing a mutant form of K-Ras (G12D) compared with HPNE cells expressing native K-Ras. G12D K-Ras increased cleavage of p35 to p25, a stable and greater activator of CDK5, thus implicating a role for CDK5 in early progression of PDAC. Inhibition of the signaling cascade downstream of mutant K-Ras (G12D) that involves mitogen-activated protein/extracellular signal–regulated kinase, phosphoinositide 3-kinase, or CDK5 decreased p25 protein levels.
Conclusion: These results suggest that mutant K-Ras acts in concert with CDK5 and its activators to increase malignant progression, migration, and invasion of pancreatic cancer cells. Clin Cancer Res; 17(19); 6140–50. ©2011 AACR.
Autophagy Activation in Hepatocellular Carcinoma Contributes to the Tolerance of Oxaliplatin via Reactive Oxygen Species Modulation
Authors: Ding Zhen-Bin , Hui Bo , Shi Ying-Hong , Zhou Jian , Peng Yuan-Fei , Gu Cheng-Yu , Yang Hua , Shi Guo-Ming , Ke Ai-Wu , Wang Xiao-Ying , Song Kang , Dai Zhi , Shen Ying-Hao , Fan Jia 
Published: August 2011

Abstract
Purpose: Understanding the roles of mammalian autophagy in cancer highlights recent advances in the pharmacologic manipulation of autophagic pathways as a therapeutic strategy for cancer. However, autophagy status and corresponding functions in hepatocellular carcinoma (HCC) after therapeutic stress remain to be clarified. This study was to determine whether the autophagic machinery could be activated after chemotherapy and the contribution of autophagy to tolerance of oxaliplatin in HCC.
Experimental Design: Autophagy activation and cell death induced by oxaliplatin were examined in two HCC cell lines as well as in vivo using an HCC model in nude mice. HCC tissue samples with or without locoregional chemotherapy before surgery were also examined by immunohistochemical and electron microscopic analysis.
Results: Autophagy was functionally activated in HCC cell lines and xenografts after oxaliplatin treatment. Suppression of autophagy using either pharmacologic inhibitors or RNA interference of essential autophagy gene enhanced cell death induced by oxaliplatin in HCC cells. Generation of reactive oxygen species has an important role in the induction of cell death by oxaliplatin in combination with autophagy inhibitors. Critically, the combination of oxaliplatin with autophagy inhibitor chloroquine resulted in a more pronounced tumor suppression in HCC xenografts. Furthermore, autophagy-specific protein LC3 and autophagic autophagosome formation were induced to a significantly higher level in HCC specimens that had been subjected to locoregional chemotherapy.
Conclusions: Autophagy activation under therapy stress contributes to HCC tumor cell survival. Targeting the autophagy pathway is a promising therapeutic strategy to enhance the effects of chemotherapy and improve clinical outcomes in HCC patients. Clin Cancer Res; 17(19); 6229–38. ©2011 AACR.