bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term Quality of Life Following Vestibular Schwannoma Excision Via the Translabyrinthine Approach
Authors: Broomfield Stephen J. , Mandavia Ashish K. , Nicholson Jack S. , Mahmoud Osama , King Andrew T. , Rutherford Scott A. , Ramsden Richard T. 
Published: August 2017

Objective:
To assess postoperative quality of life (QOL) and other patient-reported outcomes following surgery for vestibular schwannoma.

Study Design:
Cross-sectional retrospective case review using postal questionnaires.

Setting:
Tertiary referral center.

Patients:
Five hundred consecutive patients undergoing surgery for vestibular schwannoma.

Intervention(s):
Patients undergoing surgery via the translabyrinthine approach (excluding neurofibromatosis type 2) under the senior author, with a minimum of 5 years follow-up, were included.

Main Outcome Measure(s):
QOL was assessed using the Short Form 36 (SF-36) questionnaire and a disease-specific survey to assess patients’ subjective outcomes.

Results:
The SF-36 scores in this group were significantly lower than the general UK population, though 24% of respondents reported a subjective improvement in overall QOL. Tumors larger than 4 cm were related to a reduced SF-36 total mental component score (p = 0.037). Increased age at time of surgery correlated with a reduced physical component of QOL (correlation coefficient = −0.26) and an improved mental component (correlation coefficient = 0.26). Subjective reports of postoperative symptoms and return to work, driving and social activities were similar to other published studies. 35% of patients reported vivid dreams or nightmares following surgery; the first reported incidence of this phenomenon in a large group of vestibular schwannoma patients.

Conclusions:
Generic measures of QOL in patients following translabyrinthine surgery for vestibular schwannoma do not always match subjective reports, reflecting the complexity of QOL assessment and the range of outcomes in this group. Increased time since surgery appears to be associated with an improvement in mental health.
Perceptions of Support Groups Among Older Breast Cancer Survivors
Authors: Green Emily K. , Wodajo Amelework , Yang Yajuan , Sleven Miriam , Pieters Huibrie C. 
Published: August 2017

Background:
Cancer survivors transitioning from active treatment to posttreatment may lack critical support and information about their posttreatment care. Support groups have the potential to address this gap.

Objective:
The aim of this study was to describe how breast cancer survivors 65 years and older perceived professionally led, in-person support groups.

Methods:
Individual interviews with 54 women were analyzed using grounded theory informed by constructivism.

Results:
Strong negative assumptions about cancer support groups were described. Tension existed between two opposing categories: participants' preconceptions of support groups and characterizations of their members and the women's perceptions of their own informational and emotional needs. Participants also described what sources of support they used in lieu of professionally led support groups.

Conclusions:
Despite awareness and availability, most participants did not use support groups as a resource during their primary or post–cancer treatment.

Implications for Practice:
Structural changes can benefit existing models of support groups including how and when support needs and services are discussed with survivors and a shift toward the inclusion of practical information.
Dimensions of Posttraumatic Growth in Patients With Cancer
Authors: Heidarzadeh Mehdi , Rassouli Maryam , Brant Jeannine M. , Mohammadi-Shahbolaghi Farahnaz , Alavi-Majd Hamid 
Published: August 2017

Background:
Posttraumatic growth (PTG) refers to positive outcomes after exposure to stressful events. Previous studies suggest cross-cultural differences in the nature and amount of PTG.

Objective:
The aim of this study was to explore different dimensions of PTG in Iranian patients with cancer.

Methods:
A mixed method study with convergent parallel design was applied to clarify and determine dimensions of PTG. Using the Posttraumatic Growth Inventory (PTGI), confirmatory factor analysis was used to quantitatively identify dimensions of PTG in 402 patients with cancer. Simultaneously, phenomenological methodology (in-depth interview with 12 patients) was used to describe and interpret the lived experiences of cancer patients in the qualitative part of the study.

Results:
Five dimensions of PTGI were confirmed from the original PTGI. Qualitatively, new dimensions of PTG emerged including “inner peace and other positive personal attributes,” “finding meaning of life,” “being a role model,” and “performing health promoting behaviors.”

Conclusion:
Results of the study indicated that PTG is a 5-dimensional concept with a broad range of subthemes for Iranian cancer patients and that the PTGI did not reflect all growth dimensions in Iranian cancer patients.

Implications for Practice:
Awareness of PTG dimensions can enable nurses to guide their use as coping strategies and provide context for positive changes in patients to promote quality care.
The Dynamic and Transient Immune Microenvironment in Locally Advanced Esophageal Adenocarcinoma Post Chemoradiation
Authors: Kelly Ronan J. , Zaidi Ali H. , Smith Matthew A. , Omstead Ashten N. , Kosovec Juliann E. , Matsui Daisuke , Martin Samantha A. , DiCarlo Christina , Werts E. Day , Silverman Jan F. , Wang David H. , Jobe Blair A. 
Published: August 2017

Objective:
The aim of this study was to assess the impact of chemoradiation on the immune microenvironment to influence and optimally design future neoadjuvant clinical trials.

Summary Background Data:
Programmed death (PD)-1 inhibitors in metastatic gastroesophageal cancer have demonstrated response rates of approximately 25% in programmed death ligand-1 (PD-L1+) tumors. Unfortunately, the majority of patients do not respond. Therefore, a rationale strategy of combining immunotherapeutic agents with chemoradiation in earlier stage esophageal cancer may prevent metastatic disease in patients.

Methods:
To determine the effects of chemoradiation on resected esophageal adenocarcinomas, we examined the immune microenvironment pre- and post-chemoradiation using immunohistochemistry, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and functional analysis of tumor-infiltrating lymphocytes. Additionally, to assess the duration and dependency of radiation-induced PD-L1 upregulation, a surgical rat reflux model of esophageal adenocarcinoma is used. First, tumor-bearing animals were dosed with single-fraction 13Gy or 16Gy radiation to determine safety, dose correlation, and PD-L1 upregulation using qRT-PCR post-radiation. Next, longitudinal PD-L1 expression levels within individual animals were determined using serial endoscopic biopsies at baseline, 1, 5, and 9 weeks post 16Gy radiation.

Results:
The majority of cancers displayed enhanced interferon γ and activated CD8+ T lymphocytes at the tumor stroma interface. These tumors also demonstrated enhanced upregulation of PD-L1 and multiple other immune checkpoints including TIM3, GITR, IDO1, LAG3, OX40, and KIR. The animal model results indicated PD-L1 upregulation is dose-dependent and transiently elevated post radiation exposure.

Conclusions:
Collectively, these findings provide insights into the evolving immune landscape after chemoradiation and have significant implications for neoadjuvant trial designs that will combine radiotherapy with immune checkpoint inhibitors.
Multiscale Model Within-host and Between-host for Viral Infectious Diseases
Authors: Almocera Alexis Erich S. , Nguyen Van Kinh , Hernandez-Vargas Esteban A. 
Published: August 2017

AbstractMultiscale models possess the potential to uncover new insights into infectious diseases. Here, a rigorous stability analysis of a multiscale model within-host and between-host is presented. The within-host model describes virus replication and the respective immune response while disease transmission is represented by a simple susceptible-infected (SI) model.The bridge of within-to between-host is by considering transmission as a function of the viral load of the within-host level. Consequently, stability and bifurcation analyses were developed coupling the two basic reproduction numbersandfor the within- and the between-host subsystems, respectively. Local stability results for each subsystem, such as a unique stable equilibrium point, recapitulate classical approaches to infection and epidemic control.Using a Lyapunov function, global stability of the between-host system was obtained. A main result was the derivation of theas a general increasing function of. Numerical analyses reveal that a Michaelis-Menten form based on the virus is more likely to recapitulate the behavior between the scales than a form directly proportional to the virus. Our work contributes basic understandings of the two models and casts light on the potential effects of the coupling function on linking the two scales.
Patterns of thaumarchaeal gene expression in culture and diverse marine environments
Authors: Carini Paul , Dupont Christopher L. , Santoro Alyson E. 
Published: August 2017

AbstractThaumarchaea are ubiquitous in marine habitats where they participate in carbon and nitrogen cycling. Although metatranscriptomes suggest thaumarchaea are active microbes in marine waters, we understand little about how thaumarchaeal gene expression patterns relate to substrate utilization and activity. Here, we report the global transcriptional response of the marine ammonia-oxidizing thaumarchaeon ‘CandidatusNitrosopelagicus brevis’ str. CN25 to ammonia limitation using RNA-Seq. We further describe the genome and transcriptome ofCa. N. brevis str. U25, a new strain capable of urea utilization. Ammonia limitation in CN25 resulted in reduced expression of transcripts coding for ammonia oxidation proteins, and increased expression of a gene coding an Hsp20-like chaperone. Despite significantly different transcript abundances across treatments, two ammonia monooxygenase subunits (amoAB), a nitrite reductase (nirK), and both ammonium transporter genes were always among the most abundant transcripts, regardless of growth state.Ca. N. brevis str. U25 cells expressed a urea transporter 139-fold more than the urease catalytic subunitureC. Gene co-expression networks derived from culture transcriptomes and ten thaumarchaea-enriched metatranscriptomes revealed a high degree of correlated gene expression across disparate environmental conditions and identified a module of genes, includingamoABCandnirK, that we hypothesize to represent the core ammonia oxidation machinery.Originality-Significance StatementDiscovering gene function in fastidious or uncultivated lineages remains one of the biggest challenges in environmental microbiology. Here, we use an approach that combines controlled laboratory experiments within situtranscript abundance data from the environment to identify genes that share similar transcription patterns in marine ammonia-oxidizing thaumarchaea. These findings demonstrate how transcriptomes from microbial cultures can be used together with complex environmental samples to identify suites of co-expressed genes that are otherwise enigmatic and provide new insights into the mechanism of ammonia oxidation. Our results add to the growing body of literature showing that relatively small changes in transcript abundance are linked to large changes in growth in organisms with reduced genomes, suggesting they have limited capacity for metabolic regulation or that they rely on mechanisms other than transcriptional regulation to deal with a fluctuating environment.
Chlorinated electron acceptor availability selects for specificDehalococcoidespopulations in dechlorinating enrichment cultures and in groundwater
Authors: Pérez-de-Mora A. , Lacourt A. , McMaster M.L. , Liang X. , Dworatzek S.M. , Edwards E.A. 
Published: August 2017

AbstractIndividualDehalococcoides mccartyi (Dhc)strains differ primarily from one another by the number and identity of the reductive dehalogenase homologous catalytic subunit A (rdhA) genes contained within their respective genomes. While thousands ofrdhAgenes have been sequenced, the activity of the corresponding proteins have been identified in only a handful of cases. Most effort has focused on identifying the enzymes that dechlorinate substrates including trichloroethene (TCE), cis-dichloroethene (cDCE) and vinyl chloride (VC) relevant to groundwater remediation. The associatedrdhAgenes, namelytceA, bvcA,andvcrA, along with theD. mccartyi16S rRNA gene are often used to track growth and dechlorinating activity in DNA extracted from field samples. In this study, we augmented the typical suite of three characterizedrdhAgenes to include an additional 12 uncharacterizedrdhAsequences identified in the metagenome in the mixedDhc-containing culture KB-1 to track population shifts within the culture and at two bioaugmented field sites. Quantitative PCR assays were developed for the 15 selectedD. mccartyi rdhAgenes and evaluated using 11 different sub-cultures of KB-1, each enriched on different chlorinated ethenes and ethanes. The proportion ofrdhAgene copies relative toDhc16S gene copies indicated the presence of multiple distinctDhcpopulations in each culture. The specific electron acceptor amended to each culture had a major influence on the distribution ofD. mccartyipopulations and their associatedrdhAgenes. We also surveyed the abundance ofrdhAgenes in samples obtained from two bioaugmented field sites. Growth of the dominantD. mccartyipopulation in the KB-1 inoculum was detected in the UK site samples. At both field sites, the measurement of relativerdhAabundances revaled significantD. mccartyipopulation shifts over time as dechlorination progressed from TCE through cDCE to VC and ethene, indicating that the selective pressure of the most abundant chlorinated electron acceptor that was observed in lab cultures was also occurring in the populations in the field. Understanding driving forces behindD. mccartyipopulation selection and activity is improving predictability of remediation performance at chlorinated solvent contaminated sites.
Immunologic Effect of Polysaccharides Extracted fromSipunculus nudus(SNP) on Hepatoma HepG2-bearing Mice
Authors: Su Jie , Jiang Linlin , Wu Jingna , Liu Zhiyu , Wu Yuping 
Published: August 2017

AbstractSince many studies have clarified the biological activity of polysaccharides, we investigated the effect of SNP which was the water-soluble polysaccharides extracted fromSipunculus nuduson Hepatoma HepG2-bearing Mice to verify the potential of SNP as an effective clinical agent for liver cancer therapy. SNP were administered at the doses of 50,100, and 200 mg/kg to HepG2-bearing mice to determine their antitumor effects. SNP had an inhibitory effect on the growth of HepG2 cells and enhanced the immunological effect on HepG2 tumor-bearing mice. SNP increased the expression of IL-2, IFN-γ, and TNF-α cytokines in serum, suggesting that SNP can strengthen the antitumor immune response. In addition, SNP increased ATF4, DDIT3, and IkBα expression and decreased CYR61, HSP90, and VEGF expression, all of which are proteins involved in antitumor activity and cell death/survival. our results suggested that SNP may be a novel antitumor agent.Summary statementSNP(polysaccharides extracted fromSipunculus nudus) mediates anti-tumor activity through influencing immunoregulation, and SNP can be explored as a promising candidate for future anticancer drug.
The role of a single non-coding nucleotide in the evolution of an epidemic African clade ofSalmonella
Authors: Hammarlöf Disa L. , Kröger Carsten , Owen Siân V. , Canals Rocío , Lora Lizeth Lacharme , Wenner Nicolas , Wells Timothy J. , Henderson Ian R. , Wigley Paul , Hokamp Karsten , Feasey Nicholas A. , Gordon Melita A. , Hinton Jay C. D. 
Published: August 2017

Introductory ParagraphSalmonella entericaserovar Typhimurium ST313 is a relatively newly emerged sequence type that is causing a devastating epidemic of bloodstream infections across sub-Saharan Africa. Analysis of hundreds ofSalmonellagenomes has revealed that ST313 is closely-related to the ST19 group ofS. Typhimurium that cause gastroenteritis across the world. The core genomes of ST313 and ST19 vary by just 1000 single-nucleotide polymorphisms (SNPs). We hypothesised that the phenotypic differences that distinguish AfricanSalmonellafrom ST19 are caused by certain SNPs that directly modulate the transcription of virulence genes.Here we identified 3,597 transcriptional start sites (TSS) of the ST313 strain D23580, and searched for a gene expression signature linked to pathogenesis ofSalmonella. We identified a SNP in the promoter of thepgtEgene that caused high expression of the PgtE virulence factor in AfricanS.Typhimurium, increased the degradation of the factor B component of human complement, contributed to serum resistance and modulated virulence in the chicken infection model. The PgtE protease is known to mediate systemic infection in animal models. We propose that high levels of expression PgtE of by AfricanS. Typhimurium ST313 promotes bacterial survival and bacterial dissemination during human infection.Our finding of a functional role for an extra-genic SNP shows that approaches used to deduce the evolution of virulence in bacterial pathogens should include a focus on non-coding regions of the genome.
A Next Generation Clustering Tool Enables Identification of Functional Cancer Subtypes with Associated Biological Phenotypes
Authors: Nyamundanda Gift , Eason Katherine , Sadanandam Anguraj 
Published: August 2017

AbstractOne of the major challenges faced in defining clinically applicable and homogeneous molecular tumor subtypes is assigning biological and/or clinical interpretations to etiological (intrinsic) subtypes. The conventional approach involves at least three steps: Firstly, identify subtypes using unsupervised clustering of patient tumours with molecular (etiological) profiles; secondly associate the subtypes with clinical or phenotypic information (covariates) to infer some biological meaning to the redefined subtypes; and thirdly, identify clinically relevant biomarkers associated with the subtypes. Here, we report the implementation of a tool, phenotype mapping (phenMap), which combines these three steps to definefunctional subtypeswith associated phenotypic information and molecular signatures.phenMapmodels meta (unobserved) variables as a function of covariates to expose any underlying clustering structure within the data and discover associations between subtypes and phenotypes. We demonstrate how this tool can more avidly identify functional subtypes that are an improvement over already existing etiological subtypes by analysing published breast cancer gene expression data.
Performance-optimized partitioning of clonotypes from high-throughput immunoglobulin repertoire sequencing data
Authors: Nouri Nima , Kleinstein Steven H. 
Published: August 2017

AbstractMotivationDuring adaptive immune responses, activated B cells expand and undergo somatic hypermutation of their immunoglobulin (Ig) receptor, forming a clone of diversified cells that can be related back to a common ancestor. Identification of B cell clonotypes from high-throughput Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) data relies on computational analysis. Recently, we proposed an automate method to partition sequences into clonal groups based on single-linkage clustering of the Ig receptor junction region with length-normalized hamming distance metric. This method could identify clonally-related sequences with high confidence on several benchmark experimental and simulated data sets. However, this approach was computationally expensive, and unable to provide estimates of accuracy for new data. Here, a new method is presented that address this computational bottleneck and also provides a study-specific estimation of performance, including sensitivity and specificity. The method uses a finite mixture modeling fitting procedure for learning the parameters of two univariate curves which fit the bimodal distributions of the distance vector between pairs of sequences. These distribution are used to estimate the performance of different threshold choices for partitioning sequences into clonotypes. These performance estimates are validated using simulated and experimental datasets. With this method, clonotypes can be identified from AIRR-seq data with sensitivity and specificity profiles that are user-defined based on the overall goals of the study.AvailabilitySource code is freely available at the Immcantation Portal:www.immcantation.comunder the CC BY-SA 4.0 license.Contactsteven.kleinstein@yale.edu
Increased anxiety and decreased sociability in adulthood following paternal deprivation involve oxytocin in the mPFC
Authors: He Zhixiong , Wang Limin , Luo luo , Jia Rui , Yuan Wei , Hou Wenjuan , Yang Jinfeng , Yang Yang , Tai Fadao 
Published: August 2017

AbstractEarly adverse experiences often have devastating consequences on adult emotional and social behavior. However, whether paternal deprivation (PD) during the pre-weaning period affects brain and behavioral development remains unexplored in socially mandarin vole (Microtus mandarinus). We found that PD increased anxiety-like behavior and attenuated social preference in adult males and females; decreased prelimbic cortex OT-immunoreactive fibers and paraventricular nucleus OT positive neurons; reduced levels of medial prefrontal cortex (mPFC) OT receptor protein in females and OT receptor and V1a receptor protein in males. Intra-prelimbic cortical OT injections reversed anxiety-like behavior and social preferences affected by PD, whereas injections of OT and OT receptor antagonist blocked this reversal. These findings demonstrate that PD leads to increased anxiety-like behavior and attenuated social preferences with involvement of the mPFC OT system. The prelimbic cortex OT system may be an important target for the treatment of disorders related to early adverse experiences.
Estimation of complex effect-size distributions using summary-level statistics from genome-wide association studies across 32 complex traits and implications for the future
Authors: Zhang Yan , Qi Guanghao , Park Ju-Hyun , Chatterjee Nilanjan 
Published: August 2017

AbstractSummary-level statistics from genome-wide association studies are now widely used to estimate heritability and co-heritability of traits using the popular linkage-disequilibrium-score (LD-score) regression method. We develop a likelihood-based approach for analyzing summary-level statistics and external LD information to estimate common variants effect-size distributions, characterized by proportion of underlying susceptibility SNPs and a flexible normal-mixture model for their effects. Analysis of summary-level results across 32 GWAS reveals that while all traits are highly polygenic, there is wide diversity in the degrees of polygenicity. The effect-size distributions for susceptibility SNPs could be adequately modeled by a single normal distribution for traits related to mental health and ability and by a mixture of two normal distributions for all other traits. Among quantitative traits, we predict the sample sizes needed to identify SNPs which explain 80% of GWAS heritability to be between 300K-500K for some of the early growth traits, between 1-2 million for some anthropometric and cholesterol traits and multiple millions for body mass index and some others. The corresponding predictions for disease traits are between 200K-400K for inflammatory bowel diseases, close to one million for a variety of adult onset chronic diseases and between 1-2 million for psychiatric diseases.