bluuebunny/crossref_metadata_2025 huggingface dataset:
The dynamic properties of B4C/6061Al neutron absorber composites fabricated by power metallurgy
Authors: Chen Hongsheng , Wang Wenxian , Nie Huihui , Zhou Jun , Li Yuli , Zhang Peng
Published: December 2017

The dynamic compression properties of B4C/6061Al neutron absorber composites (NACs) with three B4C volume fractions (20–40%), fabricated by power metallurgy, were studied. Compression tests were conducted at strain rates ranging from 760 to 1150 s−1, using a split Hopkinson pressure bar. The damage mechanism was studied through microstructural analysis. Results show that the B4C particles exhibited a uniform distribution in the 6061Al matrix. The NACs dynamic strength was found to improve with increasing quantities of B4C particles, and with strain rate. The damage mechanisms include particle fracture and interface debonding. Dislocation pile-up was observed at grain boundaries and at the interface between particles and the matrix. A constitutive model under dynamic compression was developed based on the Johnson–Cook model.

This paper is part of a thematic issue on Nuclear Materials.
Sharp edge cutting technology - a review of hand held and machine knives/blades and their sharp edge retention
Authors: Gregory G. , Hamby R.
Published: December 2017

The cutlery & Trades Research Association (CATRA) has recently concluded a two year research project, funded by the Department of Trade and Industry Focus Technology Programme, to review the sharp edge retention of hand held and machine knives and blades. Results for sharpness and wear performance of cutting edges, ranging from small thin razor blades to large paper shear blades, are reported and compared with those having undergone a variety of hard, wear resistant surface treatments, i.e. physical vapour deposition, plasma nitriding, case hardening, and electrodeposition processes.
Role of interfacial reaction on the mechanical performance of Al/steel dissimilar refill friction stir spot welds
Authors: Shen Z. , Chen J. , Ding Y. , Hou J. , Shalchi Amirkhiz B. , Chan K. , Gerlich A. P.
Published: December 2017

Al/steel welds were successfully fabricated by refill friction stir spot welding. The welding parameters were optimised based on the clamping ring temperature and weld strength. 85.7% of welds achieve a strength which exceeds the American Welding Society requirement when the clamping ring temperature ranges from 230 to 265°C. Cracks are formed under the pin and sleeve in the Al substrate at the Al/steel interface, which are associated with the tool sleeve plunging period and attributed to the α-Al + Al–Zn eutectic structure. The interdiffusion between Al and Zn at the steel surface produced an Al–Zn eutectic structure layer at the Al/steel interface, while part of the zinc coating materials is squeezed out of the sleeve periphery, leading to a brazing effect which contributes to weld strength. Nanoscale discontinuous Fe4Al13 and FeAl intermetallics form as a layer localised at the Al–Zn layer/steel substrate interface.
Control of microtubule dynamics using an optogenetic microtubule plus end–F-actin cross-linker
Authors: Adikes Rebecca C. , Hallett Ryan A. , Saway Brian F. , Kuhlman Brian , Slep Kevin C.
Published: December 2017

We developed a novel optogenetic tool, SxIP–improved light-inducible dimer (iLID), to facilitate the reversible recruitment of factors to microtubule (MT) plus ends in an end-binding protein–dependent manner using blue light. We show that SxIP-iLID can track MT plus ends and recruit tgRFP-SspB upon blue light activation. We used this system to investigate the effects of cross-linking MT plus ends and F-actin in Drosophila melanogaster S2 cells to gain insight into spectraplakin function and mechanism. We show that SxIP-iLID can be used to temporally recruit an F-actin binding domain to MT plus ends and cross-link the MT and F-actin networks. Cross-linking decreases MT growth velocities and generates a peripheral MT exclusion zone. SxIP-iLID facilitates the general recruitment of specific factors to MT plus ends with temporal control enabling researchers to systematically regulate MT plus end dynamics and probe MT plus end function in many biological processes.
Estrogen Stimulation Differentially Impacts Human Male and Female Antigen-Specific T Cell Anti-Tumor Function and Polyfunctionality
Authors: Navarro Flor C. , Watkins Stephanie K.
Published: December 2017

Sex-specific differences exist in innate and adaptive immune responses and are mediated by hormone signaling. Estrogen is able to differentially modulate the development and differentiation of immune cells, including T cells. However, the effect of estrogen on T cell function, especially at concentrations other than physiological, remains controversial and incompletely understood. Immunotherapy is one of the most promising cancer treatments to date with a high probability of future enhancements. The adoptive transfer of genetically modified T cells can mediate tumor regression but there are still many hurdles to enhancing the proficiency of this treatment. This study demonstrates for the first time that one major aspect to consider for designing potent immunotherapies for cancer is the impact of the patient's sex. Herein, using two different Ag-specific T cell groups, we investigated the effect of sex and estrogen in antitumor effector responses, T helper cytokine secretion, and, importantly, on T cell whole polyfunctionality important for memory T cell development and survival. Major differences were observed in T cell function and polyfunctionality between sexes and on E2 treatment. The findings of this study may be critical to understand the results of immunotherapy on different patients and for the enhancement of immunotherapy for cancer.
Ordinary pseudorepresentations and modular forms
Authors: Wake Preston , Wang-Erickson Carl
Published: December 2017

In this note, we observe that the techniques of our paper “Pseudo-modularity and Iwasawa theory” can be used to provide a new proof of some of the residually reducible modularity lifting results of Skinner and Wiles. In these cases, we have found that a deformation ring of ordinary pseudorepresentations is equal to the Eisenstein local component of a Hida Hecke algebra. We also show that Vandiver’s conjecture implies Sharifi’s conjecture.
TCGA-assembler 2: software pipeline for retrieval and processing of TCGA/CPTAC data
Authors: Wei Lin , Jin Zhilin , Yang Shengjie , Xu Yanxun , Zhu Yitan , Ji Yuan
Published: December 2017

Motivation

The Cancer Genome Atlas (TCGA) program has produced huge amounts of cancer genomics data providing unprecedented opportunities for research. In 2014, we developed TCGA-Assembler, a software pipeline for retrieval and processing of public TCGA data. In 2016, TCGA data were transferred from the TCGA data portal to the Genomic Data Commons (GDCs), which is supported by a different set of data storage and retrieval mechanisms. In addition, new proteomics data of TCGA samples have been generated by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) program, which were not available for downloading through TCGA-Assembler. It is desirable to acquire and integrate data from both GDC and CPTAC.

Results

We develop TCGA-assembler 2 (TA2) to automatically download and integrate data from GDC and CPTAC. We make substantial improvement on the functionality of TA2 to enhance user experience and software performance. TA2 together with its previous version have helped more than 2000 researchers from 64 countries to access and utilize TCGA and CPTAC data in their research. Availability of TA2 will continue to allow existing and new users to conduct reproducible research based on TCGA and CPTAC data.

Availability and implementation

http://www.compgenome.org/TCGA-Assembler/ or https://github.com/compgenome365/TCGA-Assembler-2

Supplementary information

Supplementary data are available at Bioinformatics online.
Missing value imputation for LC-MS metabolomics data by incorporating metabolic network and adduct ion relations
Authors: Jin Zhuxuan , Kang Jian , Yu Tianwei
Published: December 2017

Motivation

Metabolomics data generated from liquid chromatography-mass spectrometry platforms often contain missing values. Existing imputation methods do not consider underlying feature relations and the metabolic network information. As a result, the imputation results may not be optimal.

Results

We proposed an imputation algorithm that incorporates the existing metabolic network, adduct ion relations even for unknown compounds, as well as linear and nonlinear associations between feature intensities to build a feature-level network. The algorithm uses support vector regression for missing value imputation based on features in the neighborhood on the network. We compared our proposed method with methods being widely used. As judged by the normalized root mean squared error in real data-based simulations, our proposed methods can achieve better accuracy.

Availability and implementation

The R package is available at http://web1.sph.emory.edu/users/tyu8/MINMA.

Supplementary information

Supplementary data are available at Bioinformatics online.
Personal Cancer Genome Reporter: variant interpretation report for precision oncology
Authors: Nakken Sigve , Fournous Ghislain , Vodák Daniel , Aasheim Lars Birger , Myklebost Ola , Hovig Eivind
Published: December 2017

Individual tumor genomes pose a major challenge for clinical interpretation due to their unique sets of acquired mutations. There is a general scarcity of tools that can (i) systematically interrogate cancer genomes in the context of diagnostic, prognostic, and therapeutic biomarkers, (ii) prioritize and highlight the most important findings and (iii) present the results in a format accessible to clinical experts. We have developed a stand-alone, open-source software package for somatic variant annotation that integrates a comprehensive set of knowledge resources related to tumor biology and therapeutic biomarkers, both at the gene and variant level. Our application generates a tiered report that will aid the interpretation of individual cancer genomes in a clinical setting.

Availability and implementation

The software is implemented in Python/R, and is freely available through Docker technology. Documentation, example reports, and installation instructions are accessible via the project GitHub page: https://github.com/sigven/pcgr.

Supplementary information

Supplementary data are available at Bioinformatics online.
Predicting Hospitalization and Outpatient Corticosteroid Use in Inflammatory Bowel Disease Patients Using Machine Learning
Authors: Waljee Akbar K , Lipson Rachel , Wiitala Wyndy L , Zhang Yiwei , Liu Boang , Zhu Ji , Wallace Beth , Govani Shail M , Stidham Ryan W , Hayward Rodney , Higgins Peter D R
Published: December 2017

Background

Inflammatory bowel disease (IBD) is a chronic disease characterized by unpredictable episodes of flares and periods of remission. Tools that accurately predict disease course would substantially aid therapeutic decision-making. This study aims to construct a model that accurately predicts the combined end point of outpatient corticosteroid use and hospitalizations as a surrogate for IBD flare.

Methods

Predictors evaluated included age, sex, race, use of corticosteroid-sparing immunosuppressive medications (immunomodulators and/or anti-TNF), longitudinal laboratory data, and number of previous IBD-related hospitalizations and outpatient corticosteroid prescriptions. We constructed models using logistic regression and machine learning methods (random forest [RF]) to predict the combined end point of hospitalization and/or corticosteroid use for IBD within 6 months.

Results

We identified 20,368 Veterans Health Administration patients with the first (index) IBD diagnosis between 2002 and 2009. Area under the receiver operating characteristic curve (AuROC) for the baseline logistic regression model was 0.68 (95% confidence interval [CI], 0.67–0.68). AuROC for the RF longitudinal model was 0.85 (95% CI, 0.84–0.85). AuROC for the RF longitudinal model using previous hospitalization or steroid use was 0.87 (95% CI, 0.87–0.88). The 5 leading independent risk factors for future hospitalization or steroid use were age, mean serum albumin, immunosuppressive medication use, and mean and highest platelet counts. Previous hospitalization and corticosteroid use were highly predictive when included in specified models.

Conclusions

A novel machine learning model substantially improved our ability to predict IBD-related hospitalization and outpatient steroid use. This model could be used at point of care to distinguish patients at high and low risk for disease flare, allowing individualized therapeutic management.
Plasma microRNA Profile Differentiates Crohn’s Colitis From Ulcerative Colitis
Authors: Netz Uri , Carter Jane , Eichenberger M Robert , Feagins Kayla , Galbraith Norman J , Dryden Gerald W , Pan Jianmin , Rai Shesh N , Galandiuk Susan
Published: December 2017

Background

Inflammatory bowel disease (IBD) is commonly divided into 2 entities: Crohn’s disease (CD) and ulcerative colitis (UC). Differentiating between these entities when dealing with IBD confined to the colon is important, especially when planning surgical treatment. Due to ambiguous histological or endoscopic findings, accurate diagnosis is not possible in up to 15% of cases. The aim of this study was to determine whether plasma microRNAs (miRNAs) can help differentiate Crohn’s colitis (CC) from ulcerative colitis.

Methods

Patients with isolated CC and with UC were enrolled in our study from January 2010 to May 2016. Peripheral blood was collected, and total RNA was isolated from plasma. Screening was performed for 380 common miRNAs. miRNAs that were differentially expressed between these 2 groups were chosen, and their differential expression was confirmed using single miRNA assays in a larger sample size. A predictive model was generated using these data. Significantly differentially expressed miRNAs were then validated utilizing the predictive model to assess blinded data from the single assays.

Results

Screening was performed on 8 patients from each group. Seven differentially expressed miRNAs were chosen for single assay confirmation. Two miRNAs (miR-598, miR-642) were consistently different between the patient groups (P = 0.013, P = 0.005). Using blinded data, these 2 miRNAs were validated using the predictive model, achieving an overall accuracy of 75% (95% confidence interval, 40.7–92.9).

Conclusions

We identified 2 plasma miRNAs that differentiated CC from UC. Our data indicate the promise and feasibility of a plasma miRNA–based assay to distinguish between these 2 conditions.
Development and Validation of a Confocal Laser Endomicroscopy-Based Score for In Vivo Assessment of Mucosal Healing in Ulcerative Colitis Patients
Authors: Hundorfean Gheorghe , Chiriac Mircea T , Mihai Sidonia , Hartmann Arndt , Mudter Jonas , Neurath Markus F
Published: December 2017

Background

Endoscopic monitoring is fundamental for evaluating the therapeutic response in IBD, but a validated endomicroscopic mucosal healing (MH) score is not available to date. However, confocal laser endomicroscopy (CLE) might define MH more precisely than conventional endoscopy. The major aim was to establish and validate an MH score for ulcerative colitis (UC), based on CLE.

Methods

In an initial pilot study (n = 10), various CLE changes were analyzed for identification of reproducible criteria for establishing a CLE score. Four reproducible CLE criteria were implemented in a following validation study. Subsequently, active UC patients (n = 23, Mayo score ≥6) were prospectively included and underwent colonoscopy with CLE before and after 3 anti-TNF applications. Patients were clinically followed over a period of 3 years. The endomicroscopic MH score (eMHs; range, 0–4) was compared with histopathology and endoscopy scores from the same colonic location.

Results

The eMHs showed high sensitivity, specificity, and accuracy values (100% with 95% confidence interval [CI] of 15.81%–100%; 93.75% with 95% CI of 69.77%–99.84%, and 94.44%, respectively). The eMHs showed a good correlation with the histological Gupta score (rs = 0.82, P < 0.0001) and the endoscopic Mayo subscore (rs = 0.81%, P < 0.0001). Sixty percent of therapy responders presented an eMHs <1, which translated into long-lasting clinical remission and reduced hospitalization, steroid, and surgery need.

Conclusions

CLE can accurately assess MH based on the newly developed and statistically validated eMHs in UC, and it is superior in predicting the long-lasting clinical outcome based on both descriptive and functional barrier imaging (NCT01417728).
Indeterminate QuantiFERON-TB Gold Increases Likelihood of Inflammatory Bowel Disease Treatment Delay and Hospitalization
Authors: Vajravelu Ravy K , Osterman Mark T , Aberra Faten N , Roy Jason A , Lichtenstein Gary R , Mamtani Ronac , Goldberg David S , Lewis James D , Scott Frank I
Published: December 2017

Background

QuantiFERON-TB Gold (QFTG) is a blood test used to diagnose latent tuberculosis infection (LTBI) prior to TNF-α inhibitor (anti-TNF) initiation. We sought to determine factors associated with indeterminate QFTG results in inflammatory bowel disease (IBD) patients and whether indeterminate results are associated with IBD-related morbidity.

Methods

This nested case-control study included IBD patients who underwent QFTG testing. Cases were patients with indeterminate QFTG and controls were those with negative QFTG. The association of demographic and clinical data with indeterminate QFTG result was assessed using logistic regression. We examined the clinical impact of indeterminate QFTG results on risk of hospitalization and delay in anti-TNF initiation using inverse probability-of-treatment weighting (IPTW) regression.

Results

We identified 411 patients with QFTG testing (320 negative, 80 indeterminate, and 11 positive results). No patient with an indeterminate result subsequently had LTBI. Systemic corticosteroid use (OR, 4.4; 95% CI, 2.0–9.6) and hospitalization at the time of QFTG (OR, 3.8; 95% CI, 1.9–7.7) were associated with indeterminate QFTG, while immunomodulator use was nearly statistically significant (OR, 3.1; 95% CI, 0.9–9.8) and anti-TNF use was not (OR, 0.9; 95% CI, 0.2–4.6). After IPTW adjustment, indeterminate QFTG was associated with a 23.1% (95% CI, 8.2%–37.9%) greater probability of delay in anti-TNF initiation beyond 30 days and an 11.9% (95% CI, 0.6%–23.1%) greater probability of hospitalization within 60 days.

Conclusions

Systemic corticosteroid use and hospitalization were associated with an indeterminate QFTG result. Indeterminate QFTG results were associated with delayed anti-TNF initiation and subsequent hospitalization.

10.1093/ibd/izx019_video1 izx019.video1 5732754519001
IBD Serology and Disease Outcomes in African Americans With Crohn’s Disease
Authors: Bertha Madeline , Vasantharoopan Arthi , Kumar Archana , Bruce Beau B , Prince Jarod , Hofmekler Tatyana , Okou David , Chopra Pankaj , Wang Gabriel , Sauer Cary , Landers Carol J , Hussain Sunny Z , Cross Raymond K , Baldassano Robert N , Kappelman Michael D , Katz Jeffrey , Alexander Jonathan S , Kirschner Barbara S , Moulton Dedrick E , Osuntokun Bankole O , Patel Ashish , Saeed Shehzad , Klapproth Jan-Michael A , Dhere Tanvi A , Dubinsky Marla C , McGovern Dermot , Kugathasan Subra
Published: December 2017

Backgrounds

Recent studies have identified the role of serologic markers in characterizing disease phenotype, location, complications, and severity among Northern Europeans (NE) with Crohn’s disease (CD). However, very little is known about the role of serology in CD among African Americans (AA). Our study explored the relationship between serology and disease phenotype in AA with CD, while controlling for genetic ancestry.

Methods

AAs with CD were enrolled as participants through multicenter collaborative efforts. Serological levels of IgA anti-Saccharomyces cervisiae antibody (ASCA), IgG ASCA, E. coli outermembrane porin C, anti-CBir1, and ANCA were measured using enzyme-linked immunosorbent assays. Genotyping was performed using Illumina immunochip technology; an admixture rate was calculated for each subject. Multiple imputation by chained equations was performed to account for data missing at random. Logistic regression was used to calculate adjusted odds ratio (OR) for associations between serological markers and both complicated disease and disease requiring surgery.

Results

A total of 358 patients were included in the analysis. The majority of our patients had inflammatory, noncomplicated disease (58.4%), perianal disease (55.7%), and documented colonic inflammation (86.8%). On multivariable analysis, both IgG ASCA and OmpC were associated with complicated disease (OR, 2.67; 95% CI, 1.67–4.28; OR, 2.23; 95% CI, 1.41–3.53, respectively) and disease requiring surgery (OR, 2.51; 95% CI, 1.49–4.22; OR, 3.57; 95% CI, 2.12–6.00). NE admixture to the African genome did not have any associations or interactions in relation to clinical outcome.

Conclusions

Our study comprises the largest cohort of AAs with CD. The utility of serological markers for the prognosis of CD in NE applies equally to AA populations.
Validation of Neutrophil CD64 Blood Biomarkers to Detect Mucosal Inflammation in Pediatric Crohn’s Disease
Authors: Minar Phillip , Jackson Kimberly , Tsai Yi-Ting , Sucharew Heidi , Rosen Michael J , Denson Lee A
Published: December 2017

Background

In a pilot study, neutrophil CD64 surface expression was significantly elevated in newly diagnosed, pediatric-onset Crohn’s disease. We aimed to test the CD64 biomarkers (neutrophil CD64 surface expression and soluble CD64) as determinates for mucosal inflammation in a larger pediatric Crohn’s cohort with the hypotheses that the CD64 biomarkers would reliably detect intestinal inflammation and correlate with endoscopic severity scores.

Methods

We enrolled patients referred for colonoscopy for either suspected inflammatory bowel disease or with established Crohn’s. Neutrophil CD64 index was determined by flow cytometry using a commercial kit (Leuko64, Trillium) and soluble CD64 by ELISA (LifeSpan).

Results

A total of 209 patients (72 controls, 76 new inflammatory bowel disease patients, and 61 established Crohn’s) were enrolled. Both neutrophil CD64 index and soluble CD64 were significantly elevated in new Crohn’s compared with controls. The area under the curve (AUC) for neutrophil CD64 index ≥1 was 0.85 (95% confidence interval, 0.77–0.92), 75% sensitive and 89% specific for new Crohn’s. Comparatively, soluble CD64 ≥39 ng/mL was 92% sensitive and 85% specific (AUC, 0.93) for new Crohn’s. Neutrophil CD64 index, soluble CD64, and fecal calprotectin discriminated endoscopic inactive from moderate and severe activity while soluble CD64 differentiated endoscopic mild from moderate and severe activity. Neutrophil CD64 index (r = 0.46, P < 0.001) and fecal calprotectin (r = 0.55, P < 0.001) correlated well with the Simple Endoscopic Score–Crohn’s disease. Spearman correlation between the CD64 index and calprotectin was 0.39 (P < 0.001).

Conclusions

In a large Crohn’s disease cohort, we found that neutrophil CD64 index and soluble CD64 were significantly elevated during active gastrointestinal inflammation.

10.1093/ibd/izx022_video1 izx022.video1 5732761255001
Thiopurine Treatment in Ulcerative Colitis: A Critical Review of the Evidence for Current Clinical Practice
Authors: van Gennep Sara , de Boer Nanne K , D’Haens Geert R , Löwenberg Mark
Published: December 2017

Background

Due to toxicity problems and controversial evidence, thiopurine use in ulcerative colitis (UC) has faced a lot of criticism. We present a critical review of the literature on efficacy of thiopurines in UC.

Methods

Studies evaluating therapeutic efficacy of thiopurine remission induction and/or maintenance treatment in UC were identified using the Cochrane Library, MEDLINE, and EMBASE.

Results

Out of 5 randomized trials on thiopurine induction treatment, 3 demonstrated a significant effect of thiopurine treatment vs mesalamine or placebo in steroid-dependent UC patients: (1) lower endoscopic activity scores, (2) higher clinical remission rates, and (3) more patients who discontinued steroids. Two found no significant difference in clinical and endoscopic remission of azathioprine compared with sulfasalazine or placebo in patients with active UC. Out of 7 randomized trials on thiopurine maintenance treatment, 4 demonstrated significant higher clinical and endoscopic remission rates in thiopurine-treated patients compared with placebo or mesalamine. Three found no significant difference in clinical and endoscopic remission of thiopurine maintenance treatment compared with sulfasalazine or placebo.

Conclusions

All studies that investigated thiopurine treatment in UC had shortcomings, such as lack of sufficient power, no use of blinding, allowed concomitant treatment with steroids, and no endoscopy to confirm active disease at study entry or to evaluate therapeutic efficacy. Hence, current clinical practice of thiopurine treatment in UC is based on minimal and controversial evidence. This underscores the need for clinical studies with sufficient power and objective end points in order to determine efficacy of thiopurines in UC.

10.1093/ibd/izx025_video1 izx025.video1 5732762967001
Capsule Endoscopy, Magnetic Resonance Enterography, and Small Bowel Ultrasound for Evaluation of Postoperative Recurrence in Crohn’s Disease: Systematic Review and Meta-Analysis
Authors: Yung Diana E , Har-Noy Ofir , Tham Yuen Sau , Ben-Horin Shomron , Eliakim Rami , Koulaouzidis Anastasios , Kopylov Uri
Published: December 2017

Background

Anastomotic recurrence is frequent in patients with Crohn’s disease (CD) following ileocecal resection. The degree of endoscopic recurrence, quantified by the Rutgeerts score (RS), is correlated with the risk of clinical and surgical recurrence. Noninvasive modalities such as capsule endoscopy (CE), magnetic resonance enterography (MRE), and intestinal ultrasound (US) may yield similar information without the need for ileocolonoscopy (IC). The aim of our meta-analysis was to evaluate the accuracy of those modalities for detection of endoscopic recurrence in postoperative CD patients.

Methods

We performed a systematic literature search for studies comparing the accuracy of CE, MRE, and US with IC for detection of postoperative recurrence in CD. We calculated pooled diagnostic sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC) for each comparison.

Results

A total of 135 studies were retrieved; 14 studies were eligible for analysis. For CE, the pooled sensitivity was 100% (95% CI, 91%–100%), specificity was 69% (95% CI, 52%–83%), DOR was 30.8 (95% CI, 6.9–138), and AUC was 0.94. MRE had pooled sensitivity of 97% (95% CI, 89%–100%), specificity of 84% (95% CI, 62%–96%), DOR of 129.5 (95% CI, 16.4–1024.7), and AUC of 0.98. US had pooled sensitivity of 89% (95% CI, 85%–92%), specificity of 86% (95% CI, 78%–93%), DOR of 42.3 (95% CI, 18.6–96.0), and AUC 0.93.

Conclusions

CE, MRE, and US provide accurate assessment of postoperative endoscopic recurrence in CD. These modalities should gain wider use for detection of postoperative recurrence; the prognostic value of those diagnostic findings merits evaluation in further prospective studies.
Long-Term Outcomes After Primary Bowel Resection in Pediatric-Onset Crohn’s Disease
Authors: Rinawi Firas , Zevit Noam , Eliakim Rami , Niv Yaron , Shamir Raanan , Assa Amit
Published: December 2017

Background

There is limited evidence on the long-term outcome of intestinal resection in pediatric-onset Crohn’s disease (POCD) with no established predictors of adverse outcomes. We aimed to investigate clinical outcomes and predictors for adverse outcome following intestinal resection in POCD.

Methods

The medical records of patients with POCD who underwent at least 1 intestinal resection between 1990 and 2014 were reviewed retrospectively. Main outcome measures included time to first flare, hospitalization, second intestinal resection, and response to nonprophylactic biologic therapy.

Results

Overall, 121 patients were included. Median follow-up was 6 years (range 1–23.6). One hundred and seven (88%) patients experienced at least 1 postsurgical exacerbation, 52 (43%) were hospitalized, and 17 (14%) underwent second intestinal resection. Of 91 patients who underwent surgery after the year 2000, 37 (41%) were treated with antitumor necrosis factor ɑ (anti-TNFɑ) (nonprophylactic) following intestinal resection. Time to hospitalization and to second intestinal resection were shorter among patients with extraintestinal manifestations (EIMs) (HR 2.7, P = 0.006 and HR = 3.1, P = 0.03, respectively). Time to initiation of biologic treatment was shorter in patients with granulomas (HR 2.1, P = 0.038), whereas being naïve to anti-TNFɑ treatment before surgery was a protective factor for biologic treatment following surgery (HR 0.3, P = 0.005). Undergoing intestinal resection beyond the year 2000 was associated with shorter time to first flare (HR 1.9, P = 0.019) and hospitalization (HR 2.6, P = 0.028).

Conclusion

Long-term risk for flares, hospitalization, or biologic treatment is significant in POCD following bowel resection. EIMs increase the risk for hospitalization and second intestinal resection.
Genetic and Pharmacological Dissection of the Role of Spleen Tyrosine Kinase (Syk) in Intestinal Inflammation and Immune Dysfunction in Inflammatory Bowel Diseases
Authors: Biagioli Michele , Mencarelli Andrea , Carino Adriana , Cipriani Sabrina , Marchianò Silvia , Fiorucci Chiara , Donini Annibale , Graziosi Luigina , Baldelli Franco , Distrutti Eleonora , Costantino Gabriele , Fiorucci Stefano
Published: December 2017

Background

The DNAX adaptor protein 12 (DAP12) is a transmembrane adaptor molecule that signals through the activation of Syk (Spleen Tyrosine Kinase) in myeloid cells. The purpose of this study is to investigate the role of DAP12 and Syk pathways in inflammatory bowel diseases (IBDs).

Methods

DAP12 deficient and DAP12 transgenic, overexpressing an increased amount of DAP12, mice and Syk deficient mice in the C57/BL6 background were used for these studies. Colitis was induced by administering mice with dextran sulfate sodium (DSS), in drinking water, or 2,4,6-trinitrobenzene sulfonic acid (TNBS), by intrarectal enema.

Results

Abundant expression of DAP12 and Syk was detected in colon samples obtained from Crohn’s disease patients with expression restricted to immune cells infiltrating the colonic wall. In rodents development of DSS colitis as measured by assessing severity of wasting diseases, global colitis score,and macroscopic and histology scores was robustly attenuated in DAP12-/- and Syk-/- mice. In contrast, DAP12 overexpression resulted in a striking exacerbation of colon damage caused by DSS. Induction of colon expression of proinflammatory cytokines and chemokines in response to DSS administration was attenuated in DAP12-/- and Syk-/- mice, whereas opposite results were observed in DAP12 transgenic mice. Treating wild-type mice with a DAP-12 inhibitor or a Syk inhibitor caused a robust attenuation of colitis induced by DSS and TNBS.

Conclusions

DAP12 and Syk are essential mediators in inflammation-driven immune dysfunction in murine colitides. Because DAP12 and Syk expression is upregulated in patients with active disease, present findings suggest a beneficial role for DAP12 and Syk inhibitors in IBD.
Clinoptilolite in Dextran Sulphate Sodium-Induced Murine Colitis: Efficacy and Safety of a Microparticulate Preparation
Authors: Nizet Stéphane , Muñoz Eduardo , Fiebich Bernd L , Abuja Peter M , Kashofer Karl , Zatloukal Kurt , Tangermann Simone , Kenner Lukas , Tschegg Cornelius , Nagl Dietmar , Scheichl Laurenz , Meisslitzer-Ruppitsch Claudia , Freissmuth Michael , Berger Thomas
Published: December 2017

Background

Clinoptilolite is an aluminium silicate of natural origin; the microporous structure and the net negative charge of its crystal lattice allows for adsorption of ions, toxins, inflammatory mediators, and some microorganisms. We generated 2 preparations of purified clinoptilolite, which differed by about 10-fold in particle size, ie, a standard powder (GHC1) and a microparticulate fraction (GHC2) with a size of 3.6 µm and 0.39 µm (d50) respectively. These were examined for their ability to accelerate the recovery of mice from DSS (dextran sulphate sodium)-induced intestinal inflammation.

Methods

Efficacy of clinoptilolite preparations was investigated by administering DSS-treated mice twice daily with 30 mg GHC2 or GHC1 for 5 consecutive days, followed by 5 days of recovery without DSS. To explore the safety of the microparticulate preparation (GHC2), mice were subjected to 4 cycles of DSS-exposure. We specifically verified that clinoptilolite microparticles were not systemically bioavailable by examining the gut tissue and the liver for the accumulation of microparticles by transmission electron microscopy.

Results

Treatment of mice with GHC2 was superior to GHC1 and as effective as the reference compound 5-aminosalicylic acid in ameliorating the damage induced by the exposure to DSS. In addition, no clinoptilolite particle was observed in the intestinal epithelial layer, gut-associated lymph follicles, or in the liver.

Conclusion

Our observations confirm that a microparticulate preparation of clinoptilolite is safe and effective in a murine model of inflammatory bowel disease and supports the hypothesis that the adsorptive capacity of clinoptilolite is of potential therapeutic relevance.
A detached stellar-mass black hole candidate in the globular cluster NGC 3201
Authors: Giesers Benjamin , Dreizler Stefan , Husser Tim-Oliver , Kamann Sebastian , Anglada Escudé Guillem , Brinchmann Jarle , Carollo C Marcella , Roth Martin M , Weilbacher Peter M , Wisotzki Lutz
Published: December 2017

As part of our massive spectroscopic survey of 25 Galactic globular clusters with MUSE, we performed multiple epoch observations of NGC 3201 with the aim of constraining the binary fraction. In this cluster, we found one curious star at the main-sequence turn-off with radial velocity variations of the order of 100 km s− 1, indicating the membership to a binary system with an unseen component since no other variations appear in the spectra. Using an adapted variant of the generalized Lomb–Scargle periodogram, we could calculate the orbital parameters and found the companion to be a detached stellar-mass black hole with a minimum mass of 4.36 ± 0.41 M⊙. The result is an important constraint for binary and black hole evolution models in globular clusters as well as in the context of gravitational wave sources.
Welfare state structure, inequality, and public attitudes towards progressive taxation
Authors: Berens Sarah , Gelepithis Margarita
Published: December 2017

Recent research indicates that while higher tax levels are politically unpopular, greater tax progressivity is not. However, there remain unanswered questions regarding public support for more progressive taxation. In particular, little is known about how individual attitudes towards tax progressivity are affected by their institutional context. Building on existing theories of redistribution, this article develops the argument that the structure of the welfare state shapes public attitudes towards progressive taxation—support for progressive taxation among both average and high-income households is undermined by ‘pro-poor’ welfare spending. We support our argument with a cross-sectional analysis of rich democracies, interacting household income with country-level indicators of welfare state structure. In doing so, we contribute a micro-level explanation for the paradoxical macro-level phenomenon that larger, more redistributive welfare states tend to be financed by less progressive tax systems.
Interprofessional Education and Team-Based Learning in a Research Methods Course
Authors: Schug Vicki , Finch-Guthrie Patricia , Benz Janet
Published: December 2017

This article describes team-based pedagogical strategies for a hybrid, four-credit research methods course with students from nursing, exercise, and nutrition science. The research problem of concussion in football, a socially relevant and controversial topic, was used to explore interprofessional perspectives and develop shared problem solving. The course was designed using permanent teams, readiness assurance, application exercises, and peer evaluation to facilitate student achievement of competencies related to interprofessional collaboration and research application. Feedback from students, faculty, and the Readiness for Interprofessional Learning Scale was used to evaluate the learning innovation.
Visual Acuity and Cognition in Older Adults With and Without Hearing Loss: Evidence For Late-Life Sensory Compensation?
Authors: Wettstein Markus , Wahl Hans-Werner , Heyl Vera
Published: December 2017

Objectives:

Relationships between cognitive and sensory functioning become stronger with advancing age, and the debate on underlying mechanisms continues. Interestingly, the potential mechanism of compensation by the unaffected sensory modality has so far been investigated in younger age groups with congenital sensory impairment but not in older adults with late-life sensory loss. We compared associations between visual acuity and cognitive functioning in hearing-impaired older adults (HI), and sensory-unimpaired controls (UI). We expected stronger associations in the HI group as compared with the UI group.

Design:

Our study sample was drawn from the pools of outpatients from regional university clinics and city registries and consisted of n = 266 older adults (mean age = 82.45 years, SD = 4.76 years; HI: n = 116; UI: n = 150). For the assessment of cognitive performance, multiple established tests (e.g., subtests of the revised Wechsler Adult Intelligence Scale) were used. Moreover, objective visual acuity (distance vision) was assessed.

Results:

As expected, bivariate correlations between vision and cognitive abilities were stronger in the HI group compared with the UI group. In regression models controlling for age, sex, education, subjective health and number of chronic diseases, distance visual acuity was a significant predictor of general cognitive ability in the HI group only.

Conclusions:

Our findings suggest that visual acuity may play an important compensatory role for maintaining cognitive ability when hearing impairment sets in, which may reflect an adaptive process of late-life sensory compensation.
Cardioprotective Mechanisms of Exenatide in Isoprenaline-induced Myocardial Infarction: Novel Effects on Myocardial α-Estrogen Receptor Expression and IGF-1/IGF-2 System
Authors: Darwesh Ahmed M. , El-Azab Mona F. , Abo-Gresha Noha M. , El-Sayed Norhan M. , Moustafa Yasser M.
Published: December 2017

Myocardial infarction (MI) is one of the main causes of morbidity and mortality in diabetic patients. The antidiabetic glucagon-like polypeptide-1 receptor (GLP-1R) agonists, such as exenatide, proved to confer cardioprotection; however, their exact mechanisms are not fully elucidated. Although the cardioprotective effect of α-estrogen receptor (ERα) activation is well established, its involvement in exenatide-induced cardioprotection has never been investigated. Moreover, modulation of insulin-like growth factor-1/2 (IGF-1/IGF-2) system by exenatide, and the consequent effect on cardiomyocyte apoptosis, is yet to be established. Current study aimed to investigate the cardioprotective potential of exenatide versus the standard cardioprotective agent, 17β-estradiol, against isoprenaline (ISO)-induced MI in rats. MI-insulted group showed electrocardiographic abnormalities, elevated serum cardiac markers, higher serum IGF-2 level along with histopathological abnormalities. Treatment with exenatide and/or 17β-estradiol, commenced 8 weeks before ISO insult, ameliorated these anomalies with maximum cardioprotection achieved with combined treatment. This was associated with upregulation of both ERα and IGF-1R, and downregulation of IGF-2R in left ventricles. Inhibition of ERs in Langendorff preparations confirmed their involvement in mediating exenatide-induced cardioprotective effect. Current study showed that the GLP-1R agonist exenatide exerted cardioprotection associated with upregulation of ERα and modulation of IGF-1/IGF-2 signaling in favor of antiapoptosis.
Reconsidering Sequential Double Running Suture Removal After Penetrating Keratoplasty: A Prospective Randomized Study Comparing Excimer Laser and Motor Trephination
Authors: Seitz Berthold , Hager Tobias , Langenbucher Achim , Naumann Gottfried O. H.
Published: December 2017

Purpose:

We assessed the impact of sequential double running suture removal on corneal curvature after penetrating keratoplasty (PK), comparing mechanical and nonmechanical excimer laser trephination.

Methods:

PK was performed in 134 patients (mean age 51 ± 18 yrs) using either the excimer laser [excimer, n = 60 (37 keratoconus and 23 Fuchs dystrophy)] or motor trephination [control, n = 74 (44 keratoconus and 30 Fuchs dystrophy)] and a double running cross-stitch suture. Refractometry, Zeiss keratometry, and Tomey corneal topography were performed before removal of the first suture (15.2 ± 4.2 mo) and immediately before and at least 6 weeks after removal of the second suture (21.4 ± 5.6 mo).

Results:

Keratometry before removal of the first (−1.7 ± 2.3 D vs. −3.1 ± 2.8 D) and second (−2.3 ± 2.6 D vs. −3.8 ± 2.8 D) sutures showed that the change in the corneal base curve was significantly smaller in the excimer group than the control group (P < 0.004). After complete suture removal, astigmatism decreased in 52% and 11%, remained stable (±0.5 D) in 27% and 9%, and increased in 21% and 80% of eyes in the excimer and control groups, respectively, resulting in significantly lower astigmatism in the excimer (3.1 ± 2.1 D) group compared with the control group (6.2 ± 2.9 D) with “all-sutures-out” (P < 0.0001). The change in vector-corrected astigmatism (Jaffe) was significantly smaller in the excimer group (4.3 ± 3.5 D) than in the control group (6.9 ± 4.5 D; P < 0.001).

Conclusions:

In conclusion, less change in astigmatism and the base curve after sequential removal of a double running suture indicates better alignment of the graft in the recipient bed after excimer laser trephination. After double running suture removal, astigmatism decreases or remains unchanged in 79% of patients after excimer laser keratoplasty and increases in 80% of patients after conventional motor trephination.
Endoscopic Lung Volume Reduction in COPD
Authors: Hsu Kelvin , Williamson Jonathan P. , Peters Matthew J. , Ing Alvin J.
Published: December 2017

Background:

Endoscopic lung volume reduction (ELVR) has been shown to improve lung function, quality of life, and exercise tolerance in patients with severe heterogeneous emphysema. Our study aims to determine the effect of ELVR on gas transfer capacity corrected for alveolar volume (KCO) and investigate the relationship between KCO and ventilation and perfusion (VQ) matching. We speculate on possible mechanisms for the observed changes

Methods:

Patients with severe chronic obstructive pulmonary disease were prospectively recruited and underwent unilateral upper lobe ELVR between 2012 and 2014. Each had respiratory function test and differential VQ scans at baseline, 1-, 3-, and 12-month post-ELVR.

Results:

In total, 11 patients had 3 sets of respiratory function test (at baseline, 1, and 3 mo), whereas 7 had 4 sets (at baseline, 1, 3, and 12 mo). KCO improved by 10.3 (±7.5)% at 1 month (P=NS) and 39.8 (±15.4)% at 12 months (P<0.05). VQ of the nontargeted lung increased by 12.8 (±5.6)% and 7.9 (±2.3)%, respectively at 1 month, whereas those of the targeted lung both decreased (P<0.05). At 3 and 12 months, the VQ changes were similar to those at 1 month, though some were not statistically significant.

Conclusions:

ELVR results in improved KCO for at least 12 months. This may be explained by the VQ redistribution to the nontargeted and less emphysematous lung with improved VQ matching.
Diagnostic Yield of 2 Strategies for Adult Celiac Disease Identification in Primary Care
Authors: Scoglio Riccardo , Trifirò Gianluca , Sandullo Antonino , Marangio Giovanni , D’Agate Cinzia , Costa Stefano , Pellegrino Salvatore , Alibrandi Angela , Aiello Andrea , Currò Giovanni , Cuzzupè Chiara , Comisi Fabrizio , Amato Salvatore , Conti Nibali Roberto , Oteri Sergio , Magazzu Giuseppe , Carroccio Antonio
Published: December 2017

Goals:

To compare the diagnostic yield and cost-consequences of 2 strategies, screening regardless of symptoms versus case finding (CF), using a point-of-care test (POCT), for the detection of celiac disease (CD) in primary care, to bridge the diagnostic gap of CD in adults.

Materials and Methods:

All subjects under 75 years of age who consecutively went to their general practitioners’ offices were offered POCT for anti-transglutaminase immunoglobulin A antibodies. The POCT was performed on all subjects who agreed, and then a systematic search for symptoms or conditions associated with higher risk for CD was performed, immediately after the test but before knowing the test results. The 2 resulting groups were: (a) POCT positive and (b) symptomatic subject at CF. Subjects were defined as symptomatic at CF in the presence of 1 or more symptoms. All POCT-positive or symptomatic subjects at CF were referred to the CD Centers for confirmation of CD. Data on resource consumption were gathered from patients’ charts. Cost of examinations, and diagnostic and laboratory tests were estimated with regional outpatient tariffs (Sicily), and a price of €2.5 was used for each POCT.

Results:

Of a total of 2197 subjects who agreed to participate in the study, 36 (1.6%) and 671 (30.5%) were POCT positive and symptomatic at CF, respectively. The yield from the screening and CF was 5 new celiac patients. The total cost and mean cost for each new CD case were €7497.35 and €1499.47 for the POCT screening strategy, and €9855.14 and €1971.03 for the CF strategy, respectively. Assuming consecutive use of both strategies, performing POCT only in symptomatic subjects at CF, the calculated yield would be 4 new diagnoses with a total cost of €2345.84 and a mean cost of €586.46 for each newly diagnosed patient. Only 1 patient was celiac despite a negative POCT.

Conclusions:

Testing symptomatic subjects at CF only by POCT seems the most cost-effective strategy to bridge the diagnostic gap of adult CD in primary care.