bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics and clinical significance of prostate cancers missed by initial transrectal 12‐core biopsy
Authors: Numao Noboru , Kawakami Satoru , Sakura Mizuaki , Yoshida Soichiro , Koga Fumitaka , Saito Kazutaka , Masuda Hitoshi , Fujii Yasuhisa , Yamamoto Shinya , Yonese Junji , Ishikawa Yuichi , Fukui Iwao , Kihara Kazunori 
Published: September 2011

Study Type – Diagnostic (exploratory cohort)Level of Evidence 3aWhat's known on the subject? and What does the study add?Initial transrectal 12‐core biopsy has a small but definite risk of missing anterior significant prostate cancers irrespective of age, PSA, prostate volume and DRE findings.Our study yields valuable information for diagnosis and treatment decision of prostate cancer based on transrectal 12‐core biopsy.OBJECTIVE
To characterize prostate cancers missed by initial transrectal 12‐core biopsy.
PATIENTS AND METHODS
Between 2002 and 2008, 715 men with prostate‐specific antigen levels in the range 2.5–20 ng/mL or abnormal digital rectal examination underwent three‐dimensional 26‐core prostate biopsy (i.e. a combination of transrectal 12‐core biopsy and transperineal 14‐core biopsy) on initial examination.
Of the 257 patients diagnosed with cancer, 120 patients subsequently underwent radical prostatectomy.
Cancers were grouped into TR12‐negative cancers (i.e. not detected through transrectal 12‐core biopsy but detected through transperineal 14‐core biopsy) and TR12‐positive (i.e. detected through transrectal 12‐core biopsy) cancers.
Clinicopathological characteristics of the TR12‐negative and TR12‐positive cancers were evaluated.
RESULTS
TR12‐negative cancers comprised 21% of the three‐dimensional 26‐core biopsy‐detected cancers.
The frequency of cancers with a biopsy Gleason score ≤6 and that of cancers with a biopsy primary Gleason grade ≤3 was higher in TR12‐negative cancers, at 58% and 83%, respectively, than in TR12‐positive cancers, at 25% (P < 0.001) and 53% (P < 0.001), respectively.
The median number of positive cores in TR12‐negative cancers was two out of 26.
TR12‐negative cancers were more frequently located anteriorly than posteriorly.
The incidence of the TR12‐negative cancers was not associated significantly with any clinical variable.
CONCLUSION
Many of the cancers missed by initial transrectal 12‐core biopsy are probably low‐grade and low‐volume diseases, although initial transrectal 12‐core biopsy has a small but definite risk of missing anterior significant cancers.
Analysis of enquiries to the National Pharmacy Association following major changes to controlled drug legislation in the UK
Authors: Gallagher Cathal T , Hickman Adrienne C , Hannbeck Leyla , Flynn Robert W 
Published: September 2011

Abstract

Objectives
The National Pharmacy Association (NPA) provides an advice service to community pharmacists in the UK, and keeps a database of the enquiries it receives. The aim of this research was to analyse the database for the period of October 2007 to March 2008 to gain an insight into how well pharmacists coped with legislative changes directly affecting pharmacy by identifying which changes generated the most enquiries during these 6 months and ascertaining in which months these queries were at their highest levels.

Methods
Anonymised telephone enquiries regarding controlled drugs (CDs) received by the NPA from pharmacists during a 6-month period were reviewed and categorised according to the legislative change or other CD issue to which they related. A Poisson model was applied to determine whether there was a significant difference in the total number of CD queries generated each month.

Key findings
Altogether 6082 queries regarding CDs were received, of which 57% related to legislative changes. The three legislative changes that took place during the 6-month period all generated a significant increase in numbers of queries around the time of the change. Queries regarding the new form of CD register comprised the largest single category.

Conclusions
Community pharmacists seek information regarding legislative changes when such changes come into force to a greater degree than when the legislation is drafted, consulted upon or enacted. The high number of queries received by the NPA does reflect that there was a difficulty in applying the various legislative changes in practice.
Centenary of the Anglo‐American high‐altitude expedition to Pikes Peak
Authors: West John B. 
Published: September 2011

This year (2011) marks the centenary of one of the most important early research expeditions to high altitude. The principal participants were J. S. Haldane and C. G. Douglas from Oxford, Y. Henderson from Yale and E. C. Schneider from Colorado College. Pikes Peak just outside Colorado Springs proved to be an excellent venue because of its substantial altitude of 4300 m, convenient access via a cog railway and comfortable living accommodation. The expedition had a classical design, with measurements made first at sea level, then on the summit for 5 weeks and then at sea level again. The extensive scientific programme included descriptions of acute mountain sickness, many measurements of partial pressures in alveolar gas and arterial blood, changes in ventilation, including periodic breathing, exercise measurements and a large number of blood studies. One error was the conclusion that the arterial
could considerably exceed the alveolar value, implying oxygen secretion by the lung, but this should not detract from the other important advances. Mabel FitzGerald was invited to be a member of the expedition but did not join the men on the summit. Instead, she visited various mining camps in Colorado at somewhat lower altitudes and carried out classical studies of alveolar gas partial pressures and haemoglobin values. Indeed, her results of alveolar
and
are frequently cited today. The Pikes Peak expedition was a model and it had an extensive influence on later studies.
Salmonella enterica in Swine Production: Assessing the Association between Amplified Fragment Length Polymorphism and Epidemiological Units of Concern
Authors: Wang Bing , Wang Chong , McKean James D. , Logue Catherine M. , Gebreyes Wondwossen A. , Tivendale Kelly A. , O'Connor Annette M. 
Published: September 2011

ABSTRACT

The aims of this study were to determine the ability of amplified fragment length polymorphism (AFLP) to differentiate
Salmonella
isolates from different units of swine production and to demonstrate the relatedness of
Salmonella
between farms and abattoirs by AFLP. Twenty-four farms in the midwestern United States were visited four times from 2006 to 2009. At each farm or abattoir visit, 30 fecal samples or 30 mesenteric lymph nodes were collected, respectively. A total of 220
Salmonella
isolates were obtained, serotyped, and genotyped by multilocus sequence typing (MLST) and AFLP. These 220 isolates clustered into 21 serotypes, 18 MLST types, and 14 predominant AFLP clusters based on a genetic similarity threshold level of 60%. To assess genetic differentiation between farms, harvest cohorts, and pigs, analysis of molecular variance was conducted using AFLP data. The results showed 65.62% of overall genetic variation was attributed to variance among pigs, 27.21% to farms, and 7.17% to harvest cohorts. Variance components at the farm (
P
= 0.003) and pig (
P
= 0.001) levels were significant, but not at the harvest cohort level (
P
= 0.079). A second analysis, a permutation test using AFLP data, indicated that on-farm and at-abattoir
Salmonella
from pigs of the same farms were more related than from different farms. Therefore, among the three subtyping methods, serotyping, MLST, and AFLP, AFLP was the method that was able to differentiate among
Salmonella
isolates from different farms and link contamination at the abattoir to the farm of origin.
Phenotypic Diversity Caused by Differential RpoS Activity among Environmental Escherichia coli Isolates
Authors: Chiang Sarah M. , Dong Tao , Edge Thomas A. , Schellhorn Herb E. 
Published: September 2011

ABSTRACT

Enteric bacteria deposited into the environment by animal hosts are subject to diverse selective pressures. These pressures may act on phenotypic differences in bacterial populations and select adaptive mutations for survival in stress. As a model to study phenotypic diversity in environmental bacteria, we examined mutations of the stress response sigma factor, RpoS, in environmental
Escherichia coli
isolates. A total of 2,040 isolates from urban beaches and nearby fecal pollution sources on Lake Ontario (Canada) were screened for RpoS function by examining growth on succinate and catalase activity, two RpoS-dependent phenotypes. The
rpoS
sequence was determined for 45 isolates, including all candidate RpoS mutants, and of these, six isolates were confirmed as mutants with the complete loss of RpoS function. Similarly to laboratory strains, the RpoS expression of these environmental isolates was stationary phase dependent. However, the expression of RpoS regulon members KatE and AppA had differing levels of expression in several environmental isolates compared to those in laboratory strains. Furthermore, after plating
rpoS
+
isolates on succinate, RpoS mutants could be readily selected from environmental
E. coli
. Naturally isolated and succinate-selected RpoS mutants had lower generation times on poor carbon sources and lower stress resistance than their
rpoS
+
isogenic parental strains. These results show that RpoS mutants are present in the environment (with a frequency of 0.003 among isolates) and that, similarly to laboratory and pathogenic strains, growth on poor carbon sources selects for
rpoS
mutations in environmental
E. coli
. RpoS selection may be an important determinant of phenotypic diversification and, hence, the survival of
E. coli
in the environment.
Membrane Stresses Induced by Overproduction of Free Fatty Acids in Escherichia coli
Authors: Lennen Rebecca M. , Kruziki Max A. , Kumar Kritika , Zinkel Robert A. , Burnum Kristin E. , Lipton Mary S. , Hoover Spencer W. , Ranatunga Don R. , Wittkopp Tyler M. , Marner Wesley D. , Pfleger Brian F. 
Published: September 2011

ABSTRACTMicrobially produced fatty acids are potential precursors to high-energy-density biofuels, including alkanes and alkyl ethyl esters, by either catalytic conversion of free fatty acids (FFAs) or enzymatic conversion of acyl-acyl carrier protein or acyl-coenzyme A intermediates. Metabolic engineering efforts aimed at overproducing FFAs inEscherichia colihave achieved less than 30% of the maximum theoretical yield on the supplied carbon source. In this work, the viability, morphology, transcript levels, and protein levels of a strain ofE. colithat overproduces medium-chain-length FFAs was compared to an engineered control strain. By early stationary phase, an 85% reduction in viable cell counts and exacerbated loss of inner membrane integrity were observed in the FFA-overproducing strain. These effects were enhanced in strains endogenously producing FFAs compared to strains exposed to exogenously fed FFAs. Under two sets of cultivation conditions, long-chain unsaturated fatty acid content greatly increased, and the expression of genes and proteins required for unsaturated fatty acid biosynthesis were significantly decreased. Membrane stresses were further implicated by increased expression of genes and proteins of the phage shock response, the MarA/Rob/SoxS regulon, and thenuoandcyooperons of aerobic respiration. Gene deletion studies confirmed the importance of the phage shock proteins and Rob for maintaining cell viability; however, little to no change in FFA titer was observed after 24 h of cultivation. The results of this study serve as a baseline for future targeted attempts to improve FFA yields and titers inE. coli.
One-Pot Synthesis of Diverse
dl
-Configuration Dipeptides by a Streptomyces
d
-Stereospecific Amidohydrolase
Authors: Arima Jiro , Usuki Hirokazu , Hatanaka Tadashi , Mori Nobuhiro 
Published: September 2011

ABSTRACT

The synthesis of diverse
dl
-configuration dipeptides in a one-pot reaction was demonstrated by using a function of the aminolysis reaction of a
d
-stereospecific amidohydrolase from
Streptomyces
sp., a clan SE, S12 family peptidase categorized as a peptidase with
d
-stereospecificity. The enzyme was able to use various aminoacyl derivatives, including
l
-aminoacyl derivatives, as acyl donors and acceptors. Investigations of the specificity of the peptide synthetic activity revealed that the enzyme preferentially used
d
-aminoacyl derivatives as acyl donors. In contrast,
l
-amino acids and their derivatives were preferentially used as acyl acceptors. Consequently, the synthesized dipeptides had a
dl
-configuration when
d
- and
l
-aminoacyl derivatives were mixed in a one-pot reaction. This report also describes that the enzyme produced cyclo(
d
–Pro-
l
-Arg), a specific inhibitor of family 18 chitinase, with a conversion rate for
d
-Pro benzyl ester and
l
-Arg methyl ester to cyclo(
d
-Pro–
l
-Arg) of greater than 65%. Furthermore, based on results of cyclo(
d
-Pro–
l
-Arg) synthesis, we propose a reaction mechanism for cyclo(
d
-Pro–
l
-Arg) production.
Use of Stable Isotopes To Measure the Metabolic Activity of the Human Intestinal Microbiota
Authors: Reichardt Nicole , Barclay Andrew R. , Weaver Lawrence T. , Morrison Douglas J. 
Published: September 2011

ABSTRACTThe human intestinal microbiota is a complex biological system comprising a vast repertoire of microbes with considerable metabolic activity relevant to both bacterial growth and host health. Greater strides have been made in the analysis of microbial diversity than in the measurement of functional activity, particularlyin vivo. Stable isotope probing offers a new approach by coupling measurements of metabolic activity with microbial identification. Using a low-enrichment labeling strategyin vitro, this study has identified metabolically active bacterial groups via magnetic-bead capture methodology and stable isotope ratio analysis. Using five probes (EUB338, Bac303, Bif164, EREC482, and Clep866), changes in the activities of key intestinal microbial groups were successfully measured by exploiting tracers ofde novoRNA synthesis. Perturbation of the nutrient source with oligofructose generated changes in the activity of bifidobacteria as expected, but also in theBacteroides-Prevotellagroup, theEubacterium rectale-Clostridium coccoidesgroup, and theClostridium leptumsubgroup. Changes in activity were also observed in response to the medium type. This study suggests that changes in the functional activity of the gut microbiota can be assessed using tracers ofde novonucleic acid synthesis combined with measurement of low isotopic enrichment in 16S rRNA. Such tracers potentially limit substrate bias because they are universally available to bacteria. This low-enrichment labeling approach does not depend on the commercial availability of specific labeled substrates and can be easily translated toin vivoprobing experiments of the functional activity of the microbiota in the human gut.
Leaching of Cryptosporidium parvum Oocysts, Escherichia coli, and a Salmonella enterica Serovar Typhimurium Bacteriophage through Intact Soil Cores following Surface Application and Injection of Slurry
Authors: Forslund Anita , Markussen Bo , Toenner-Klank Lise , Bech Tina B. , Jacobsen Ole Stig , Dalsgaard Anders 
Published: September 2011

ABSTRACTIncreasing amounts of livestock manure are being applied to agricultural soil, but it is unknown to what extent this may be associated with contamination of aquatic recipients and groundwater if microorganisms are transported through the soil under natural weather conditions. The objective of this study was therefore to evaluate how injection and surface application of pig slurry on intact sandy clay loam soil cores influenced the leaching ofSalmonella entericaserovar Typhimurium bacteriophage 28B,Escherichia coli, andCryptosporidium parvumoocysts. All three microbial tracers were detected in the leachate on day 1, and the highest relative concentration was detected on the fourth day (0.1 pore volume). Although the concentration of the phage 28B declined over time, the phage was still found in leachate at day 148.C. parvumoocysts and chloride had an additional rise in the relative concentration at a 0.5 pore volume, corresponding to the exchange of the total pore volume. The leaching ofE. coliwas delayed compared with that of the added microbial tracers, indicating a stronger attachment to slurry particles, butE. colicould be detected up to 3 months. Significantly enhanced leaching of phage 28B and oocysts by the injection method was seen, whereas leaching of the indigenousE. coliwas not affected by the application method. Preferential flow was the primary transport vehicle, and the diameter of the fractures in the intact soil cores facilitated transport of all sizes of microbial tracers under natural weather conditions.
Influence of Host Phylogeographic Patterns and Incomplete Lineage Sorting on Within-Species Genetic Variability in Wigglesworthia Species, Obligate Symbionts of Tsetse Flies
Authors: Symula Rebecca E. , Marpuri Ian , Bjornson Robert D. , Okedi Loyce , Beadell Jon , Alam Uzma , Aksoy Serap , Caccone Adalgisa 
Published: September 2011

ABSTRACT

Vertical transmission of obligate symbionts generates a predictable evolutionary history of symbionts that reflects that of their hosts. In insects, evolutionary associations between symbionts and their hosts have been investigated primarily among species, leaving population-level processes largely unknown. In this study, we investigated the tsetse (Diptera: Glossinidae) bacterial symbiont,
Wigglesworthia glossinidia
, to determine whether observed codiversification of symbiont and tsetse host species extends to a single host species (
Glossina fuscipes fuscipes
) in Uganda. To explore symbiont genetic variation in
G. f. fuscipes
populations, we screened two variable loci (
lon
and
lepA
) from the
Wigglesworthia glossinidia
bacterium in the host species
Glossina fuscipes fuscipes
(
W. g. fuscipes
) and examined phylogeographic and demographic characteristics in multiple host populations. Symbiont genetic variation was apparent within and among populations. We identified two distinct symbiont lineages, in northern and southern Uganda. Incongruence length difference (ILD) tests indicated that the two lineages corresponded exactly to northern and southern
G. f. fuscipes
mitochondrial DNA (mtDNA) haplogroups (
P
= 1.0). Analysis of molecular variance (AMOVA) confirmed that most variation was partitioned between the northern and southern lineages defined by host mtDNA (85.44%). However, ILD tests rejected finer-scale congruence within the northern and southern populations (
P
= 0.009). This incongruence was potentially due to incomplete lineage sorting that resulted in novel combinations of symbiont genetic variants and host background. Identifying these novel combinations may have public health significance, since tsetse is the sole vector of sleeping sickness and
Wigglesworthia
is known to influence host vector competence. Thus, understanding the adaptive value of these host-symbiont combinations may afford opportunities to develop vector control methods.
Localization Pattern of Conjugation Machinery in a Gram-Positive Bacterium
Authors: Bauer Theresa , Rösch Thomas , Itaya Mitsuhiro , Graumann Peter L. 
Published: September 2011

ABSTRACT

Conjugation is an efficient way for transfer of genetic information between bacteria, even between highly diverged species, and a major cause for the spreading of resistance genes. We have investigated the subcellular localization of several conserved conjugation proteins carried on plasmid pLS20 found in
Bacillus subtilis
. We show that VirB1, VirB4, VirB11, VirD2, and VirD4 homologs assemble at a single cell pole, but also at other sites along the cell membrane, in cells during the lag phase of growth. Bimolecular fluorescence complementation analyses showed that VirB4 and VirD4 interact at the cell pole and, less frequently, at other sites along the membrane. VirB1 and VirB11 also colocalized at the cell pole. Total internal reflection fluorescence microscopy showed that pLS20 is largely membrane associated and is frequently found at the cell pole, indicating that transfer takes place at the pole, which is a preferred site for the assembly of the active conjugation apparatus, but not the sole site. VirD2, VirB4, and VirD4 started to localize to the pole or the membrane in stationary-phase cells, and VirB1 and VirB11 were observed as foci in cells resuspended in fresh medium but no longer in cells that had entered exponential growth, although at least VirB4 was still expressed. These data reveal an unusual assembly/disassembly timing for the pLS20 conjugation machinery and suggest that specific localization of conjugation proteins in lag-phase cells and delocalization during growth are the reasons why pLS20 conjugation occurs only during early exponential phase.
Probing the Impact of Ligand Binding on the Acyl-Homoserine Lactone-Hindered Transcription Factor EsaR of Pantoea stewartii subsp. stewartii
Authors: Schu Daniel J. , Ramachandran Revathy , Geissinger Jared S. , Stevens Ann M. 
Published: September 2011

ABSTRACT

The quorum-sensing regulator EsaR from
Pantoea stewartii
subsp.
stewartii
is a LuxR homologue that is inactivated by acyl-homoserine lactone (AHL). In the corn pathogen
P. stewartii
, production of exopolysaccharide (EPS) is repressed by EsaR at low cell densities. However, at high cell densities when high concentrations of its cognate AHL signal are present, EsaR is inactivated and derepression of EPS production occurs. Thus, EsaR responds to AHL in a manner opposite to that of most LuxR family members. Depending on the position of its binding site within target promoters, EsaR serves as either a repressor or activator in the absence rather than in the presence of its AHL ligand. The effect of AHL on LuxR homologues has been difficult to study
in vitro
because AHL is required for purification and stability. EsaR, however, can be purified without AHL enabling an
in vitro
analysis of the response of the protein to ligand. Western immunoblots and pulse-chase experiments demonstrated that EsaR is stable
in vivo
in the absence or presence of AHL. Limited
in vitro
proteolytic digestions of a biologically active His-MBP tagged version of EsaR highlighted intradomain and interdomain conformational changes that occur in the protein in response to AHL. Gel filtration chromatography of the full-length fusion protein and cross-linking of the N-terminal domain both suggest that this conformational change does not impact the multimeric state of the protein. These findings provide greater insight into the diverse mechanisms for AHL responsiveness found within the LuxR family.