bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining machine learning and propensity score weighting to estimate causal effects in multivalued treatments
Authors: Linden Ariel , Yarnold Paul R 
Published: July 2016

AbstractRationale, aims and objectivesInterventions with multivalued treatments are common in medical and health research; examples include comparing the efficacy of competing interventions and contrasting various doses of a drug. In recent years, there has been growing interest in the development of methods that estimate multivalued treatment effects using observational data. This paper extends a previously described analytic framework for evaluating binary treatments to studies involving multivalued treatments utilizing a machine learning algorithm called optimal discriminant analysis (ODA).MethodWe describe the differences between regression‐based treatment effect estimators and effects estimated using the ODA framework. We then present an empirical example using data from an intervention including three study groups to compare corresponding effects.ResultsThe regression‐based estimators produced statistically significant mean differences between the two intervention groups, and between one of the treatment groups and controls. In contrast, ODA was unable to discriminate between distributions of any of the three study groups.ConclusionsOptimal discriminant analysis offers an appealing alternative to conventional regression‐based models for estimating effects in multivalued treatment studies because of its insensitivity to skewed data and use of accuracy measures applicable to all prognostic analyses. If these analytic approaches produce consistent treatment effect P values, this bolsters confidence in the validity of the results. If the approaches produce conflicting treatment effect P values, as they do in our empirical example, the investigator should consider the ODA‐derived estimates to be most robust, given that ODA uses permutation P values that require no distributional assumptions and are thus, always valid.
A low percentage of HER‐2 amplification whereas indicates poor prognosis in salivary carcinoma ex pleomorphic adenoma: a study of 140 cases
Authors: Xia Liang , Hu Yuhua , Li Jiang , Gu Ting , Zhang Chunye , Wang Lizhen , Tian Zhen 
Published: July 2016

BackgroundHuman epidermal growth factor receptor 2 (HER‐2) has been found in many malignant tumours including salivary malignancy. HER‐2‐targeted therapy has been applied in the treatment of HER‐2‐overexpressing carcinoma. The aim of this study was to determine the status of HER‐2 in salivary invasive carcinoma ex pleomorphic adenoma (ICXPA) in a relatively large Chinese sample, which may provide HER‐2‐targeted therapy with profound support in the future.Methods and resultsWe collected 140 ICXPAs and their related clinicopathological and follow‐up data. All cases were examined for HER‐2 expression by immunohistochemistry and gene amplification by fluorescence in situ hybridization, if necessary. The study showed that the ratio of HER‐2 positivity was only 25% (35/140) in all cases, but the positive ratio in ICXPAs with luminal differentiation for malignant component (32/79, 40.5%) was much higher than that in cases with non‐luminal differentiation (3/61, 4.9%). The overexpression of HER‐2 was closely associated with gender, histological grade and N stage. HER‐2‐positive tumours conferred short overall survival time (P = 0.036) and short disease‐specific survival time (P = 0.042) in patients, but HER‐2 status was not an independent predictor of prognosis.ConclusionsHuman epidermal growth factor receptor 2 amplification is significantly associated with cell differentiation of the malignant component in ICXPA and it implies an unfavourable prognosis. Although HER‐2 positivity is not common in the tumour, HER‐2‐targeted therapy for those HER‐2‐positive patients is still worth expecting.
Carbon source–sink limitations differ between two species with contrasting growth strategies
Authors: Burnett Angela C. , Rogers Alistair , Rees Mark , Osborne Colin P. 
Published: July 2016

AbstractUnderstanding how carbon source and sink strengths limit plant growth is a critical knowledge gap that hinders efforts to maximize crop yield. We investigated how differences in growth rate arise from source–sink limitations, using a model system comparing a fast‐growing domesticated annual barley (Hordeum vulgare cv. NFC Tipple) with a slow‐growing wild perennial relative (Hordeum bulbosum). Source strength was manipulated by growing plants at sub‐ambient and elevated CO2 concentrations ([CO2]). Limitations on vegetative growth imposed by source and sink were diagnosed by measuring relative growth rate, developmental plasticity, photosynthesis and major carbon and nitrogen metabolite pools. Growth was sink limited in the annual but source limited in the perennial. RGR and carbon acquisition were higher in the annual, but photosynthesis responded weakly to elevated [CO2] indicating that source strength was near maximal at current [CO2]. In contrast, photosynthetic rate and sink development responded strongly to elevated [CO2] in the perennial, indicating significant source limitation. Sink limitation was avoided in the perennial by high sink plasticity: a marked increase in tillering and root:shoot ratio at elevated [CO2], and lower non‐structural carbohydrate accumulation. Alleviating sink limitation during vegetative development could be important for maximizing growth of elite cereals under future elevated [CO2].
Health‐related quality of life in Japanese children with acute lymphoblastic leukemia during and after chemotherapy
Authors: Kobayashi Kyoko , Nakagami‐Yamaguchi Etsuko , Hayakawa Akira , Adachi Souichi , Hara Junichi , Tokimasa Sadao , Ohta Hideaki , Hashii Yoshiko , Rikiishi Takeshi , Sawada Machiko , Kuriyama Kikuko , Kohdera Urara , Kamibeppu Kiyoko , Kawasaki Hirohide , Oda Megumi , Hori Hiroki 
Published: July 2016

AbstractBackgroundQuality of life (QOL) as a treatment outcome has not yet been evaluated among patients receiving a specific treatment regimen by treatment phase in a consistent manner. This exploratory cross‐sectional study evaluated the QOL of children with acute lymphoblastic leukemia (ALL) receiving one of the most popular treatment regimens in Japan (Japan Association of Childhood Leukemia Study ALL‐02 revised protocol).MethodsChildren aged 5–18 years with newly diagnosed B‐cell precursor ALL were included. The Pediatric Quality of Life Inventory™ 4.0 Generic Core Scales (PedsQL‐J) were completed by children with ALL and their siblings, as well as by age‐ and sex‐matched healthy controls. PedsQL Cancer Module (PedsQL‐C) scores were also collected from children with ALL.ResultsQOL in children with ALL of the consolidation phase group was significantly decreased compared with that of healthy controls, except in the area of emotional functioning. Regarding the maintenance phase group, QOL impairment was noted in the physical and school functioning, but no differences were noted in social functioning. The off‐treatment group had a large effect size only for physical functioning, and the social functioning score was even better in children with ALL than in matched controls. QOL of children with ALL differed with treatment phase. Effect size varied with function and treatment phase.ConclusionsQOL may change with the progression of treatment, and the timing of these changes varied according to function and problem.
Physical behaviour of Cretaceous calcareous nannofossil ooze: Insight from flume studies of disaggregated chalk
Authors: Buls Toms , Anderskouv Kresten , Friend Patrick L. , Thompson Charlotte E. L. , Stemmerik Lars 
Published: July 2016

AbstractGeomorphic features such as drifts, sediment waves and channels have been documented in the Upper Cretaceous of north‐west Europe. These features are interpreted to result from bottom currents and have been used to refine chalk depositional models and quantify palaeocirculation patterns. Chalk was first deposited as calcareous nannofossil ooze and geomorphic features are the result of sediment reworking after deposition. There is limited knowledge on the processes that govern nannofossil ooze mobility, thus forcing uncertainty onto numerical models based on sedimentological observations. This article provides an extensive view of the erosional and depositional behaviour of calcareous nannofossil ooze based on experimental work using annular flumes. A fundamental observation of this study is the significant decrease of nannofossil ooze mobility with decreasing bed porosity. Erosion characteristics, labelled as erosion types, vary with total bed porosity (φ) and applied shear stress (τ0). High‐porosity ooze (φ >80%) is characterized by constant erosion rates (Em). At φ <77%, however, erosion characteristics showed greater variance. Surface erosion was typically followed by transitional erosion (with asymptotically decreasing Em), and stages of erosion with constant, and exponential erosion rates. The estimated erosion thresholds (τc) vary from ca 0·05 to 0·08 Pa for the onset of surface erosion and up to ca 0·19 Pa for the onset of constant erosion (φ of 60 to 85%). Variability of deposition thresholds (τcd) from ca 0·04 to 0·13 Pa reflects the influence of variable suspended sediment concentration and τ0 on settling particle size due to the identified potential for chalk ooze aggregation and flocculation. Additionally, deposition thresholds seem to be affected by the size of eroded aggregates whose size correlates with bed porosity. Lastly, slow sediment transport without resuspension occurred in high‐porosity ooze as surface creep, forming low‐relief sedimentary features resembling ripples. This process represents a previously undescribed mode of fine‐grained nannofossil ooze transport.
Comparative Analysis of Microbial Communities in Iron-Dominated Flocculent Mats in Deep-Sea Hydrothermal Environments
Authors: Makita Hiroko , Kikuchi Sakiko , Mitsunobu Satoshi , Takaki Yoshihiro , Yamanaka Toshiro , Toki Tomohiro , Noguchi Takuroh , Nakamura Kentaro , Abe Mariko , Hirai Miho , Yamamoto Masahiro , Uematsu Katsuyuki , Miyazaki Junichi , Nunoura Takuro , Takahashi Yoshio , Takai Ken 
Published: July 2016

ABSTRACT

It has been suggested that iron is one of the most important energy sources for photosynthesis-independent microbial ecosystems in the ocean crust. Iron-metabolizing chemolithoautotrophs play a key role as primary producers, but little is known about their distribution and diversity and their ecological role as submarine iron-metabolizing chemolithotrophs, particularly the iron oxidizers. In this study, we investigated the microbial communities in several iron-dominated flocculent mats found in deep-sea hydrothermal fields in the Mariana Volcanic Arc and Trough and the Okinawa Trough by culture-independent molecular techniques and X-ray mineralogical analyses. The abundance and composition of the 16S rRNA gene phylotypes demonstrated the ubiquity of zetaproteobacterial phylotypes in iron-dominated mat communities affected by hydrothermal fluid input. Electron microscopy with energy-dispersive X-ray microanalysis and X-ray absorption fine structure (XAFS) analysis revealed the chemical and mineralogical signatures of biogenic Fe-(oxy)hydroxide species and the potential contribution of
Zetaproteobacteria
to the
in situ
generation. These results suggest that putative iron-oxidizing chemolithoautotrophs play a significant ecological role in producing iron-dominated flocculent mats and that they are important for iron and carbon cycles in deep-sea low-temperature hydrothermal environments.

IMPORTANCE
We report novel aspects of microbiology from iron-dominated flocculent mats in various deep-sea environments. In this study, we examined the relationship between
Zetaproteobacteria
and iron oxides across several hydrothermally influenced sites in the deep sea. We analyzed iron-dominated mats using culture-independent molecular techniques and X-ray mineralogical analyses. The scanning electron microscopy–energy-dispersive X-ray spectroscopy SEM-EDS analysis and X-ray absorption fine structure (XAFS) analysis revealed chemical and mineralogical signatures of biogenic Fe-(oxy)hydroxide species as well as the potential contribution of the zetaproteobacterial population to the
in situ
production. These key findings provide important information for understanding the mechanisms of both geomicrobiological iron cycling and the formation of iron-dominated mats in deep-sea hydrothermal fields.
A Tetrahydrofolate-Dependent Methyltransferase Catalyzing the Demethylation of Dicamba in Sphingomonas sp. Strain Ndbn-20
Authors: Yao Li , Yu Lin-Lu , Zhang Jun-Jie , Xie Xiang-Ting , Tao Qing , Yan Xin , Hong Qing , Qiu Ji-Guo , He Jian , Ding De-Rong 
Published: July 2016

ABSTRACT

Sphingomonas
sp. strain Ndbn-20 degrades and utilizes the herbicide dicamba as its sole carbon and energy source. In the present study, a tetrahydrofolate (THF)-dependent dicamba methyltransferase gene,
dmt
, was cloned from the strain, and three other genes,
metF
,
dhc
, and
purU
, which are involved in THF metabolism, were found to be located downstream of
dmt
. A transcriptional study revealed that the four genes constituted one transcriptional unit that was constitutively transcribed. Lysates of cells grown with glucose or dicamba exhibited almost the same activities, which further suggested that the
dmt
gene is constitutively expressed in the strain. Dmt shared 46% and 45% identities with the methyltransferases DesA and LigM from
Sphingomonas paucimobilis
SYK-6, respectively. The purified Dmt catalyzed the transfer of methyl from dicamba to THF to form the herbicidally inactive metabolite 3,6-dichlorosalicylic acid (DCSA) and 5-methyl-THF. The activity of Dmt was inhibited by 5-methyl-THF but not by DCSA. The introduction of a codon-optimized
dmt
gene into
Arabidopsis thaliana
enhanced resistance against dicamba. In conclusion, this study identified a THF-dependent dicamba methyltransferase, Dmt, with potential applications for the genetic engineering of dicamba-resistant crops.

IMPORTANCE
Dicamba is a very important herbicide that is widely used to control more than 200 types of broadleaf weeds and is a suitable target herbicide for the engineering of herbicide-resistant transgenic crops. A study of the mechanism of dicamba metabolism by soil microorganisms will benefit studies of its dissipation, transformation, and migration in the environment. This study identified a THF-dependent methyltransferase, Dmt, capable of catalyzing dicamba demethylation in
Sphingomonas
sp. Ndbn-20, and a preliminary study of its enzymatic characteristics was performed. Introduction of a codon-optimized
dmt
gene into
Arabidopsis thaliana
enhanced resistance against dicamba, suggesting that the
dmt
gene has potential applications for the genetic engineering of herbicide-resistant crops.
Enrichment of Root Endophytic Bacteria from Populus deltoides and Single-Cell-Genomics Analysis
Authors: Utturkar Sagar M. , Cude W. Nathan , Robeson Michael S. , Yang Zamin K. , Klingeman Dawn M. , Land Miriam L. , Allman Steve L. , Lu Tse-Yuan S. , Brown Steven D. , Schadt Christopher W. , Podar Mircea , Doktycz Mitchel J. , Pelletier Dale A. 
Published: July 2016

ABSTRACT

Bacterial endophytes that colonize
Populus
trees contribute to nutrient acquisition, prime immunity responses, and directly or indirectly increase both above- and below-ground biomasses. Endophytes are embedded within plant material, so physical separation and isolation are difficult tasks. Application of culture-independent methods, such as metagenome or bacterial transcriptome sequencing, has been limited due to the predominance of DNA from the plant biomass. Here, we describe a modified differential and density gradient centrifugation-based protocol for the separation of endophytic bacteria from
Populus
roots. This protocol achieved substantial reduction in contaminating plant DNA, allowed enrichment of endophytic bacteria away from the plant material, and enabled single-cell genomics analysis. Four single-cell genomes were selected for whole-genome amplification based on their rarity in the microbiome (potentially uncultured taxa) as well as their inferred abilities to form associations with plants. Bioinformatics analyses, including assembly, contamination removal, and completeness estimation, were performed to obtain single-amplified genomes (SAGs) of organisms from the phyla
Armatimonadetes
,
Verrucomicrobia
, and
Planctomycetes
, which were unrepresented in our previous cultivation efforts. Comparative genomic analysis revealed unique characteristics of each SAG that could facilitate future cultivation efforts for these bacteria.

IMPORTANCE
Plant roots harbor a diverse collection of microbes that live within host tissues. To gain a comprehensive understanding of microbial adaptations to this endophytic lifestyle from strains that cannot be cultivated, it is necessary to separate bacterial cells from the predominance of plant tissue. This study provides a valuable approach for the separation and isolation of endophytic bacteria from plant root tissue. Isolated live bacteria provide material for microbiome sequencing, single-cell genomics, and analyses of genomes of uncultured bacteria to provide genomics information that will facilitate future cultivation attempts.
Efficient and Regioselective Synthesis of β-GalNAc/GlcNAc-Lactose by a Bifunctional Transglycosylating β-
N
-Acetylhexosaminidase from Bifidobacterium bifidum
Authors: Chen Xiaodi , Xu Li , Jin Lan , Sun Bin , Gu Guofeng , Lu Lili , Xiao Min 
Published: July 2016

ABSTRACT

β-
N
-Acetylhexosaminidases have attracted interest particularly for oligosaccharide synthesis, but their use remains limited by the rarity of enzyme sources
, low efficiency, and relaxed regioselectivity of transglycosylation. In this work, genes of 13 β-
N
-acetylhexosaminidases, including 5 from
Bacteroides fragilis
ATCC 25285, 5 from
Clostridium perfringens
ATCC 13124, and 3 from
Bifidobacterium bifidum
JCM 1254, were cloned and heterogeneously expressed in
Escherichia coli
. The resulting recombinant enzymes were purified and screened for transglycosylation activity. A β-
N
-acetylhexosaminidase named BbhI, which belongs to glycoside hydrolase family 20 and was obtained from
B. bifidum
JCM 1254, possesses the bifunctional property of efficiently transferring both GalNAc and GlcNAc residues through β1-3 linkage to the Gal residue of lactose. The effects of initial substrate concentration, pH, temperature, and reaction time on transglycosylation activities of BbhI were studied in detail. With the use of 10 mM
p
NP-β-GalNAc or 20 mM
p
NP-β-GlcNAc as the donor and 400 mM lactose as the acceptor in phosphate buffer (pH 5.8), BbhI synthesized GalNAcβ1-3Galβ1-4Glc and GlcNAcβ1-3Galβ1-4Glc at maximal yields of 55.4% at 45°C and 4 h and 44.9% at 55°C and 1.5 h, respectively. The model docking of BbhI with lactose showed the possible molecular basis of strict regioselectivity of β1-3 linkage in β-
N
-acetylhexosaminyl lactose synthesis.

IMPORTANCE
Oligosaccharides play a crucial role in many biological events and therefore are promising potential therapeutic agents. However, their use is limited because large-scale production of oligosaccharides is difficult. The chemical synthesis requires multiple protecting group manipulations to control the regio- and stereoselectivity of glycosidic bonds. In comparison, enzymatic synthesis can produce oligosaccharides in one step by using glycosyltransferases and glycosidases. Given the lower price of their glycosyl donor and their broader acceptor specificity, glycosidases are more advantageous than glycosyltransferases for large-scale synthesis. β-
N
-Acetylhexosaminidases have attracted interest particularly for β-
N
-acetylhexosaminyl oligosaccharide synthesis, but their application is affected by having few enzyme sources, low efficiency, and relaxed regioselectivity of transglycosylation. In this work, we describe a microbial β-
N
-acetylhexosaminidase that exhibited strong transglycosylation activity and strict regioselectivity for β-
N
-acetylhexosaminyl lactose synthesis and thus provides a powerful synthetic tool to obtain biologically important GalNAcβ1-3Lac and GlcNAcβ1-3Lac.
Polydiglycosylphosphate Transferase PdtA (SCO2578) of Streptomyces coelicolor A3(2) Is Crucial for Proper Sporulation and Apical Tip Extension under Stress Conditions
Authors: Sigle Steffen , Steblau Nadja , Wohlleben Wolfgang , Muth Günther 
Published: July 2016

ABSTRACT

Although anionic glycopolymers are crucial components of the Gram-positive cell envelope, the relevance of anionic glycopolymers for vegetative growth and morphological differentiation of
Streptomyces coelicolor
A3(2) is unknown. Here, we show that the LytR-CpsA-Psr (LCP) protein PdtA (SCO2578), a TagV-like glycopolymer transferase, has a dual function in the
S. coelicolor
A3(2) life cycle. Despite the presence of 10 additional LCP homologs, PdtA is crucial for proper sporulation. The integrity of the spore envelope was severely affected in a
pdtA
deletion mutant, resulting in 34% nonviable spores.
pdtA
deletion caused a significant reduction in the polydiglycosylphosphate content of the spore envelope. Beyond that, apical tip extension and normal branching of vegetative mycelium were severely impaired on high-salt medium. This growth defect coincided with the mislocalization of peptidoglycan synthesis. Thus, PdtA itself or the polydiglycosylphosphate attached to the peptidoglycan by the glycopolymer transferase PdtA also has a crucial function in apical tip extension of vegetative hyphae under stress conditions.

IMPORTANCE
Anionic glycopolymers are underappreciated components of the Gram-positive cell envelope. They provide rigidity to the cell wall and position extracellular enzymes involved in peptidoglycan remodeling. Although
Streptomyces coelicolor
A3(2), the model organism for bacterial antibiotic production, is known to produce two distinct cell wall-linked glycopolymers, teichulosonic acid and polydiglycosylphosphate, the role of these glycopolymers in the
S. coelicolor
A3(2) life cycle has not been addressed so far. This study reveals a crucial function of the anionic glycopolymer polydiglycosylphosphate for the growth and morphological differentiation of
S. coelicolor
A3(2). Polydiglycosylphosphate is attached to the spore wall by the LytR-CpsA-Psr protein PdtA (SCO2578), a component of the
Streptomyces
spore wall-synthesizing complex (SSSC), to ensure the integrity of the spore envelope. Surprisingly, PdtA also has a crucial role in vegetative growth under stress conditions and is required for proper peptidoglycan incorporation during apical tip extension.