bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparison of Nephrotoxicity in Non–Intensive Care Unit Medical-Surgical Patients Receiving Vancomycin Alone Versus Vancomycin With Piperacillin-Tazobactam
Authors: Eberle Hannah , Rogers Maegan , Lee Marilyn , Hill David , Cross Sara
Published: July 2017

Background

Recent studies have identified an increase in nephrotoxicty in patients receiving vancomycin plus piperacillin-tazobactam (PT) when compared with vancomycin monotherapy. To date, studies have evaluated all hospitalized patients or intensive care unit patients only. The purposes of this study were to examine the incidence of acute kidney injury (AKI) in patients who received vancomycin either as monotherapy or with PT in a non–intensive care unit medical-surgical setting and to identify potential risk factors for the development of AKI.

Methods

A retrospective chart review was performed to identify patients who received vancomycin either as monotherapy or in combination with PT for at least 48 hours. Patients were evaluated for development of AKI, defined as serum creatinine increase of 50% from baseline. Statistical analysis included demographic, univariate, and multivariable analyses.

Results

One hundred eighty-nine patients met inclusion criteria. More patients in the vancomycin + PT group developed AKI than in the vancomycin monotherapy group (18.4% vs 5.6%,P= 0.008). After multivariable logistic regression of patients receiving vancomycin, PT, African American, and perioperative patients remained statistically associated with AKI. These risk factors gave odds ratios of 3.9, 3.8, and 4.0, respectively.

Conclusions

Patients receiving PT in addition to vancomycin were more likely to develop AKI compared with those receiving vancomycin monotherapy. African American and perioperative patients may have a higher risk.
Lung Abscess Due to Aspergillus lentulus and Pseudomonas aeruginosa in a Patient With Granulomatosis With Polyangiitis
Authors: Ilieva Valeria , Thomas Elaine , Walraven Carla , Sutton Deanna A. , Wiederhold Nathan , Lee Samuel A.
Published: July 2017

Aspergillus lentulus has been recognized within Aspergillus section Fumigati as a phenotypically similar but genetically distinct species, displaying reduced susceptibility to antifungal agents. It has been described as a cause of invasive aspergillosis in patients who underwent hematopoietic stem cell transplantation, solid organ transplant recipients, those on prolonged corticosteroid therapy, or in patients with structural lung disease including chronic obstructive pulmonary disease. We report a case of successful treatment of probable invasive pulmonary aspergillosis due to A. lentulus and polymicrobial infection with Pseudomonas aeruginosa in a patient with relapsing granulomatosis with polyangiitis and recent high-dose steroid therapy.
Is the rationale more important than deception? A randomized controlled trial of open-label placebo analgesia
Authors: Locher Cosima , Frey Nascimento Antje , Kirsch Irving , Kossowsky Joe , Meyer Andrea , Gaab Jens
Published: July 2017

Research on open-label placebos questions whether deception is a necessary characteristic of placebo effects. Yet, comparisons between open-label and deceptive placebos (DPs) are lacking. We therefore assessed effects of open-label placebos and DPs in comparison with no treatment (NT) with a standardized experimental heat pain paradigm in a randomized controlled trial in healthy participants. Participants (N = 160) were randomly assigned to NT, open-label placebo without rationale (OPR-), open-label placebo with rationale (OPR+), and DP. We conducted baseline and posttreatment measurements of heat pain threshold and tolerance. Apart from the NT, all groups received an application of a placebo cream. Primary outcomes were planned comparisons of heat pain tolerance and the corresponding intensity and unpleasantness ratings. Objective posttreatment pain tolerance did not differ among groups. However, for subjective heat pain ratings at the posttreatment tolerance level, groups with a rationale (OPR+ and DP) reported diminished heat pain intensity (t(146) = −2.15, P = 0.033, d = 0.43) and unpleasantness ratings (t(146) = −2.43, P = 0.016, d = 0.49) compared with the OPR-group. Interestingly, the OPR+ and the DP groups did not significantly differ in heat pain intensity (t(146) = −1.10, P = 0.272) or unpleasantness ratings (t(146) = −0.05, P = 0.961) at the posttreatment tolerance level. Our findings reveal that placebos with a plausible rationale are more effective than without a rationale. Even more, open-label placebos did not significantly differ in their effects from DPs. Therefore, we question the ubiquitously assumed necessity of concealment in placebo administration.
Evaluation and Minimization of the Pseudohepatic Anisotropy Artifact in Liver Intravoxel Incoherent Motion
Authors: Wong Oi Lei , Goh Lo Gladys , Yuan Jing , Chung Wai Kit , Ho Wing Hung Benny , Noseworthy Michael D.
Published: July 2017

Purpose

The aim of this study was to evaluate the effect of the pseudohepatic anisotropy artifact on liver intravoxel incoherent motion (IVIM) metrics and whether the use of multiple gradient directions in the IVIM acquisition minimizes the artifact.

Materials and Methods

Multiple breath-holding and forced shallow free-breathing IVIM scans were performed on 8 healthy volunteers using 1 and 6 gradient directions. Cluster analysis was carried out to separate motion-contaminated parenchyma from liver parenchyma and vessels. Nonlinear motion analysis was also performed to look for a possible link between IVIM metrics and nonlinear liver motion.

Results

On the basis of the resulted clusters, motion-contaminated parenchyma is often noted in the left liver lobe, where the prominent pseudohepatic artifact has previously been identified. A significant reduction in outliers was obtained with the acquisition of 6 noncoplanar gradient directions and when using forced shallow free-breathing.

Conclusion

The pseudohepatic anisotropy artifact can be minimized when using multiple diffusion-encoding gradient directions and forced free-breathing during IVIM acquisition.
Differentiating Primary Central Nervous System Lymphomas From Glioblastomas and Inflammatory Demyelinating Pseudotumor Using Relative Minimum Apparent Diffusion Coefficients
Authors: Wen Jian-Bo , Huang Wei-Yuan , Xu Wei-Xing-Zi , Wu Gang , Geng Dao-Ying , Yin Bo
Published: July 2017

Objective

Our purpose was to evaluate the diagnostic performance of diffusion-weighted imaging, the relative minimum apparent diffusion coefficient (rADCmin) in differentiating primary central nervous system lymphomas (PCNSLs) from glioblastomas (GBMs) and inflammatory demyelinating pseudotumors (IDPs).

Materials and Methods

Magnetic resonance images were reviewed retrospectively in 82 patients including 39 PCNSLs, 35 GBMs, and 8 IDPs. Regions of interest were drawn around the tumor on contrast-enhanced axial images; these images were transferred onto coregistered ADC maps to obtain the ADCmin, and the normalized ADCmin ratios (rADCmin) were calculated using the formula rADCmin = ADCmin of the lesion / ADCmin of the normal white matter. The rADCmin values were compared between PCNSLs, GBMs, and IDPs using the analysis of variance test. Receiver operating characteristic curves were constructed to evaluate the diagnostic performance of rADCmin values and to determine the optimum thresholds. Simple logistic regression was analyzed to evaluate the relationship between ADCs and tumor cellularity.

Results

The rADCmin value was significantly lower in PCNSLs (0.675 ± 0.113) than GBMs (0.765 ± 0.059) and IDPs (0.834 ± 0.067) (PCNSL vs GBM, P < 0.001; PCNSL vs IDP, P < 0.001). Relative ADCmin was a significant assessor for differentiating PCNSLs from non-PCNCLs (P < 0.001). The optimal cutoff value was 0.722 (sensitivity, 74.5%; specificity, 74.1%; area under the curve, 0.803) on receiver operating characteristic analysis. A stronger negative correlation (r = −0.755, P = 0.000) was obtained between the cytoplasm and rADCmin.

Conclusions

Relative ADCmin value is helpful in differentiating PCNSL from GBM and IDP. Thus, ADC values may provide a useful supplement to the information obtained from conventional contrast-enhanced magnetic resonance imaging and assist in future treatment planning.
Impact of SSF on Diagnostic Performance of Coronary Computed Tomography Angiography Within 1 Heart Beat in Patients With High Heart Rate Using a 256-Row Detector Computed Tomography
Authors: Liang Junfu , Wang Hui , Xu Lei , Dong Li , Fan Zhanming , Wang Rui , Sun Zhonghua
Published: July 2017

Objective

The aim of this study was to investigate the impact of a motion-correction algorithm on diagnostic accuracy of coronary computed tomography angiography (CCTA) within 1 heart beat in patients with high heart rate (HR) using a 256-row detector CT.

Method

Sixty-four consecutive patients with known or suspected coronary artery disease (symptomatic) and with HR of 75 beats per minute or greater (mean [SD] HR, 82.6 [7.3] beats per minute) undergoing CCTA and invasive coronary angiography within 4 weeks were prospectively enrolled. Coronary computed tomography angiography was performed with a 256-row detector CT (Revolution CT, GE Healthcare) using prospectively electrocardiography-triggered volume scan in 1 heart beat. All images were reconstructed using standard (STD) algorithm and a motion-correction algorithm reconstruction (Snapshot Freeze SSF; GE Healthcare) technique. The image quality of coronary artery segments was evaluated by 2 experienced radiologists using a 4-point scale based on the 18-segment model. Diagnostic accuracy was compared between STD and SSF for significant lumen stenosis (≥50%) of each segment with invasive coronary angiography as the reference standard for determining significant stenosis.

Results

The diagnostic sensitivity, specificity, positive predictive value, and negative predictive value with STD and SSF were 93.7%, 85.1%, 50.2%, and 98.8% versus 91.9%, 95.8%, 77.9%, and 98.7% on per-segment assessment; 98.7%, 74.0%, 62.9%, and 99.2% versus 96.2%, 94.4%, 77.9%, and 98.7% on per-artery assessment; and 100%, 14.3%, 70.5%, and 100% versus 100%, 85.7%, 93.5%, and 100% on per-patient assessment, respectively. There was a significant difference in accuracy between STD and SFF on per-patient level 71.9% versus 95.3%, on per-artery level 81.6% versus 94.9%, and per-segment level 86.3% versus 95.3%, respectively. The area under receiver operating characteristics curve analysis also showed a significant improvement on diagnostic performance with the SSF technique versus with the STD algorithm on per-patient level (P < 0.001), with corresponding area under the curve being 0.91 (95% confidence interval, 0.79–1.00) and 0.60 (95% confidence interval, 0.44–0.75). The mean effective dose was 2.0 mSv.

Conclusions

Coronary computed tomography angiography can be performed in patients with high HR within 1 heart beat yielding low radiation dose. The use of SSF technique reconstruction for 1 heart beat CCTA achieves significant improvements in image quality and diagnostic value.
Predicting Neoadjuvant Chemotherapy in Nonconcentric Shrinkage Pattern of Breast Cancer Using 1H-Magnetic Resonance Spectroscopic Imaging
Authors: Zhou Juan , Qiao Peng-Gang , Zhang Hong-Tao , Li Gong-Jie , Jiang Ze-Fei
Published: July 2017

Objective

The aim of this study was to explore the response to neoadjuvant chemotherapy (NAC) in nonconcentric shrinkage pattern of breast cancer (BC) patients using1H–magnetic resonance spectroscopy.

Methods

Twenty-five BC patients were the study cohort. All patients received AT-based regimen as first-line treatment. Tumor response to chemotherapy was evaluated after the second and fourth cycles using magnetic resonance imaging and magnetic resonance spectroscopy. Final histopathology following surgery after 4 to 8 cycles of NAC served as a reference. Changes in total choline integral* (tCho) and tumor size in response versus nonresponse groups were compared using the 2-way Mann-Whitney nonparametric test. Receiver operating characteristic (ROC) analyses were undertaken, and the area under the ROC curve compared among them.

Results

1H–magnetic resonance spectroscopy revealed a negative tCho integral* in 6 cases at the first follow-up and 14 cases at the second follow-up. Based on pathology (Miller-Payne system), there were 16 cases of response, and 9 cases of nonresponse. The tCho integral* was significantly different between the response and nonresponse groups at the second follow-up (P= 0.027). The tumor size changes were not significantly different in the response and nonresponse groups at the second follow-up study (P> 0.05). The comparison of ROC curves among the change in tCho integral* and tumor size at baseline and both follow-ups revealed the maximum area under the ROC curve of the change in tCho integral* to be 0.747 at the second follow-up, sensitivity to be 93.75%, and positive predictive value to be 78.9%.

Conclusions

In nonconcentric shrinkage pattern after NAC of BC, when tumor size is difficult to reflect the response, tCho integral* reduction may be a predictive marker.
The rumen microbiome: an underexplored resource for novel antimicrobial discovery
Authors: Oyama Linda B , Girdwood Susan E , Cookson Alan R , Fernandez-Fuentes Narcis , Privé Florence , Vallin Hannah E , Wilkinson Toby J , Golyshin Peter N , Golyshina Olga V , Mikut Ralf , Hilpert Kai , Richards Jennifer , Wootton Mandy , Edwards Joan E , Maresca Marc , Perrier Josette , Lundy Fionnuala T , Luo Yu , Zhou Mei , Hess Matthias , Mantovani Hilario C , Creevey Christopher J , Huws Sharon A
Published: July 2017

Antimicrobial peptides (AMPs) are promising drug candidates to target multi-drug resistant bacteria. The rumen microbiome presents an underexplored resource for the discovery of novel microbial enzymes and metabolites, including AMPs. Using functional screening and computational approaches, we identified 181 potentially novel AMPs from a rumen bacterial metagenome. Here, we show that three of the selected AMPs (Lynronne-1, 2 and 3) were effective against numerous bacterial pathogens, including methicillin resistantStaphylococcus aureus(MRSA). No decrease in MRSA susceptibility was observed after 25 days of sub-lethal exposure to these AMPs. The AMPs bound preferentially to bacterial membrane lipids and induced membrane permeability leading to cytoplasmic leakage. Topical administration of Lynronne-1 (10% w/v) to a mouse model of MRSA wound infection elicited a significant reduction in bacterial counts, which was comparable to treatment with 2% mupirocin ointment. Our findings indicate that the rumen microbiome may provide viable alternative antimicrobials for future therapeutic application.
CRISPR/Cas9-mediated Knock-in of an Optimized TetO Repeat for Live Cell Imaging of Endogenous Loci
Authors: Tasan Ipek , Sustackova Gabriela , Zhang Liguo , Kim Jiah , Sivaguru Mayandi , HamediRad Mohammad , Wang Yuchuan , Genova Justin , Ma Jian , Belmont Andrew S. , Zhao Huimin
Published: July 2017

Nuclear organization has an important role in determining genome function; however, it is not clear how spatiotemporal organization of the genome relates to functionality. To elucidate this relationship, a high-throughput method for tracking any locus of interest is desirable. Here, we report an efficient and scalable method named SHACKTeR (Short Homology and CRISPR/Cas9-mediated Knock-in of a TetO Repeat) for live cell imaging of specific chromosomal regions. Compared to alternatives, our method does not require a nearby repetitive sequence and it requires only two modifications to the genome: CRISPR/Cas9-mediated knock-in of an optimized TetO repeat and its visualization by TetR-EGFP expression. Our simplified knock-in protocol, utilizing short homology arms integrated by PCR, was successful at labeling 9 different loci in HCT116 cells with up to 20% efficiency. These loci included both nuclear speckle-associated, euchromatin regions and nuclear lamina-associated, heterochromatin regions. We anticipate the general applicability and scalability of our method will enhance causative analyses between gene function and compartmentalization in a high-throughput manner.
Genomic analysis of an infant with intractable diarrhea and dilated cardiomyopathy
Authors: Bodian Dale L. , Vilboux Thierry , Hourigan Suchitra K. , Jenevein Callie L. , Mani Haresh , Kent Kathleen C. , Khromykh Alina , Solomon Benjamin D. , Hauser Natalie S.
Published: July 2017

We describe a case of an infant presenting with intractable diarrhea who subsequently developed dilated cardiomyopathy, for whom a diagnosis was not initially achieved despite extensive clinical testing, including panel-based genetic testing. Research-based whole-genome sequences of the proband and both parents were analyzed by the SAVANNA pipeline, a variant prioritization strategy integrating features of variants, genes, and phenotypes, which was implemented using publicly available tools. Although the intestinal morphological abnormalities characteristic of congenital tufting enteropathy (CTE) were not observed in the initial clinical gastrointestinal tract biopsies of the proband, an intronic variant, EPCAM c.556-14A>G, previously identified as pathogenic for CTE, was found in the homozygous state. A newborn cousin of the proband also presenting with intractable diarrhea was found to carry the same homozygous EPCAM variant, and clinical testing revealed intestinal tufting and loss of EPCAM staining. This variant, however, was considered nonexplanatory for the proband's dilated cardiomyopathy, which could be a sequela of the child's condition and/or related to other genetic variants, which include de novo mutations in the genes NEDD4L and GSK3A and a maternally inherited SCN5A variant. This study illustrates three ways in which genomic sequencing can aid in the diagnosis of clinically challenging patients: differential diagnosis despite atypical clinical presentation, distinguishing the possibilities of a syndromic condition versus multiple conditions, and generating hypotheses for novel contributory genes.
Integration of learning organization ideas and Islamic core values principle at university
Authors: Ahmad Aini , Sulan Norrihan , Abdul Rani Anita
Published: July 2017

Purpose

The concept of learning organization has been inspiring both public and private sectors since the early 90s. This paper discusses the implementation of learning organization ideas along with the organization’s core values at one of the public universities in Malaysia. The purpose of this paper is to identify the components of core values that support the development and maintenance of learning organization ideas. It also aims to examine the potential integration of the learning organization idea with organizational core values.

Design/methodology/approach

The study analyses the application of learning organization principles based on Örtenblad’s (2002) four understandings of learning organization, which are organizational learning, learning at work, learning climate and learning structure, along with the five core values initiatives at the university.

Findings

This study suggests that the university core values and the learning organization idea work harmoniously with each other. This paper provides examples of the application of the learning organization idea and the core values attribute and how both fit into each other in one of the Malaysian public universities. A learning organization–core values matrix is proposed at the end of the paper.

Research limitations/implications

This research uses the specific case of organizational core values that are established based on Islamic principles. Opportunities for further research can be a study of learning organizations in other core values environment and also from a different belief system.

Practical implications

Learning organization is relevant and in harmony with Islamic environment.

Originality/value

The paper provides real examples of learning organization practices within the core values agenda in a Malaysian university.
Bibliotherapeutic book club intervention to promote reading skills and social–emotional competencies in low SES community‐based high schools: A randomised controlled trial
Authors: Tijms Jurgen , Stoop Mirthe A. , Polleck Jody N.
Published: July 2017

Reading skills and social–emotional competencies are two important skills for both academic achievement and long‐term quality of life. The present study evaluated the effects of a school‐based intervention to promote reading skills and social–emotional competencies in young adolescents from urban, low socioeconomic status (SES) communities in their first year of secondary education. A small group intervention was conducted, using book clubs in which students read and discussed literature with the objective to enhance reading attitude, reading comprehension and social–emotional competencies. Participants were randomly allocated to either the book club intervention condition (n = 50) or a business‐as‐usual control condition (n = 40). Results revealed that the intervention group accrued significant greater gains than the control group in (recreational) reading attitude, reading comprehension and social emotional competences.

Highlights

What is already known about this topic

The transition from primary to secondary education is accompanied by a sharp decline in reading attitude and a rise in demands on young adolescents' social–emotional competencies.

Qualitative research suggests book clubs can be an educational tool to enhance both reading behaviour and social–emotional skills.

What this paper adds

A bibliotherapeutic book club intervention can be an effective tool to improve reading attitudes, reading comprehension and to strengthen social–emotional competencies in young adolescents from low SES areas.

Implications for theory, policy or practice

This study supports the inclusion of bibliotherapeutic book clubs in the secondary education curriculum as a mean to address both reading behaviour and social–emotional competencies, two skills that are important for adolescents' academic success.
Perceptions of HR practices, person–organisation fit, and affective commitment: The moderating role of career stage
Authors: Kooij Dorien T.A.M. , Boon Corine
Published: July 2017

In a three‐wave survey study among 487 Dutch university employees, we examined how and when employees' perceptions of high‐performance work practices (HPWP) affect employee affective commitment. We proposed that perceived person–organisation (PO) fit mediates this relationship and that the relationships among perceptions of HPWP, perceived PO fit, and affective commitment differ across career stages. Our results confirm that perceptions of HPWP enhance PO fit perceptions and, in turn, strengthen affective commitment. Moreover, the relationship between perceptions of HPWP and perceived PO fit is only significant among employees in the advancement stage of their careers; however, direct comparison across different career stages reveals no significant differences in the HPWP–PO fit relationship. Furthermore, career stage partly moderates the relationship between PO fit and affective commitment, which is only significant among employees in the maintenance career stage. These findings have important implications for the literature on strategic Human Resource Management and PO fit.
Information disclosure quality: correlation versus precision
Authors: Cheung Adrian (Wai‐Kong) , Hu Wei
Published: July 2017

We investigate how a multidimensional disclosure quality (i.e., correlation and precision) determines an optimal information disclosure strategy. We find that, for an infinitely lived, unlevered firm with market perfection, a truth‐telling disclosure is optimal at increasing the expected firm value. However, for a finitely lived, levered firm in the presence of market imperfections (e.g., bankruptcy cost), the optimal disclosure quality depends negatively on the level of imperfections. Once we consider the agency problem, such dependence can become positive, thereby highlighting the importance of a proper managerial‐incentive scheme to align the information disclosure interests of managers and shareholders.
The OregonHeart Total Artificial Heart: Design and Performance on a Mock Circulatory Loop
Authors: Glynn Jeremy , Song Howard , Hull Bryan , Withers Stanley , Gelow Jill , Mudd James , Starr Albert , Wampler Richard
Published: July 2017

Widespread use of heart transplantation is limited by the scarcity of donor organs. Total artificial heart (TAH) development has been pursued to address this shortage, especially to treat patients who require biventricular support. We have developed a novel TAH that utilizes a continuously spinning rotor that shuttles between two positions to provide pulsatile, alternating blood flow to the systemic and pulmonary circulations without artificial valves. Flow rates and pressures generated by the TAH are controlled by adjusting rotor speed, cycle frequency, and the proportion of each cycle spent pumping to either circulation. To validate the design, a TAH prototype was placed in a mock circulatory loop that simulates vascular resistance, pressure, and compliance in normal and pathophysiologic conditions. At a systemic blood pressure of 120/80 mm Hg, nominal TAH output was 7.4 L/min with instantaneous flows reaching 17 L/min. Pulmonary artery, and left and right atrial pressures were all maintained within normal ranges. To simulate implant into a patient with severe pulmonary hypertension, the pulmonary vascular resistance of the mock loop was increased to 7.5 Wood units. By increasing pump speed to the pulmonary circulation, cardiac output could be maintained at 7.4 L/min as mean pulmonary artery pressure increased to 56 mm Hg while systemic blood pressures remained normal. This in vitro testing of a novel, shuttling TAH demonstrated that cardiac output could be maintained across a range of pathophysiologic conditions including pulmonary hypertension. These experiments serve as a proof‐of‐concept for the design, which has proceeded to in vivo testing.
Laparoendoscopic single‐site surgery in inguinal hernia repair
Authors: Buenafe Alfred Allen E. , Lee‐Ong Alembert C.
Published: July 2017

Laparoendoscopic single‐site surgery (LESS) for laparoscopic inguinal hernia repair (IHR) offers the potential for excellent cosmetic outcomes and maximization of the inherent advantages of minimally invasive surgery. LESS IHR is associated with a steep learning curve, which is attributable to both the IHR technique itself and the single‐site technique. The technical obstacles in the single‐site technique may be mitigated by employing certain maneuvers and strategies that minimize clashing between instruments and improve freedom of movement. The current literature consistently points out the inherent challenges in LESS IHR, with its longer operative time compared to that of conventional laparoscopic IHR. LESS IHR performed by capable operators has comparable complication rates, duration of hospital stay, and incidence of recurrence as conventional laparoscopic IHR. LESS IHR is both feasible and safe. Given its excellent cosmetic outcome, it is likely to be sought by younger patients who are concerned with scar formation. The use of robotics may bypass the technical challenges in LESS, but cost considerations in their usage will likely persist.
Identification of unique proteomic signatures in allergic and non‐allergic skin disease
Authors: Wang J. , Suárez‐Fariñas M. , Estrada Y. , Parker M. L. , Greenlees L. , Stephens G. , Krueger J. , Guttman‐Yassky E. , Howell M. D.
Published: July 2017

Background

Atopic dermatitis (AD), psoriasis (PS), and contact dermatitis (CD) are common skin diseases, characterized by barrier disruption and systemic inflammation, with unique epidermal signatures and common inflammatory pathways identified by transcriptomic profiling. This study profiled proteomic signatures in serum from subjects with AD, PS, and CD compared with healthy controls (HC).

Objective

Identify unique proteomic signatures to distinguish between inflammatory diseases with similar epidermal disruption and overlapping epithelial inflammation.

Methods

Sera from 20 subjects with moderate to severe AD, 10 subjects with CD, 12 subjects with moderate to severe PS, 10 subjects with both AD and CD, and 10 HC with no history of skin disease was analysed using high‐throughput proteomic analysis that detects expression of 1129 protein targets. Protein expression was compared between disease and HC, and across diseases for statistical significance (fold change≥1.5 and false discovery rate≤0.05), to identify unique proteomic signatures for each disease.

Results

Complement C5A anaphylatoxin (C5A), lipopolysaccharide binding protein (LBP), C‐reactive protein (CRP), ILT‐4, C‐C motif ligand 18 (PARC), and sialic acid‐binding Ig‐like lectin 14 (SIG14) were significantly modulated in all three diseases compared with HC. We identified unique signatures for AD (Immunoglobulin E (IgE), thymus‐ and activation‐regulated chemokine (TARC) and macrophage‐derived chemokine (MDC)), CD (10 proteins), and PS (kynureninase (KYNU)). Proteomic profiling in subjects with both AD and CD identified additional dysregulated proteins compared with subjects with either condition alone, indicating an exacerbated inflammation reaction.

Conclusions and Clinical Relevance

Unique sera proteomic signatures may distinguish between inflammatory skin diseases despite similar epidermal barrier disruption and epithelial inflammation. This may provide insight into disease pathogenesis, diagnosis, and therapeutic intervention in difficult‐to‐treat subjects.
Tissue dynamics and regenerative outcome in two resorbable non‐cross‐linked collagen membranes for guided bone regeneration: A preclinical molecular and histological study in vivo
Authors: Omar Omar , Dahlin Anna , Gasser Angelines , Dahlin Christer
Published: July 2017

Objectives

To investigate the molecular and structural patterns of bone healing during guided bone regeneration (GBR), comparing two resorbable non‐cross‐linked collagen membranes.

Materials and methods

Trabecular bone defects in rat femurs were filled with deproteinized bovine bone (DBB) and covered with either a membrane comprising collagen and elastin (CXP) or collagen (BG). Samples were harvested after 3 and 21 days for histology/histomorphometry and gene expression analysis. Gene expression analysis was performed on the membrane (at 3 days) and the underlying defect compartment (at 3 and 21 days).

Results

At the total defect level, no differences in bone area percentage were found between the CXP and BG. When evaluating the central area of the defect, a higher percentage of de novo bone formation was seen for the CXP membrane (34.9%) compared to BG (15.5%) at 21 days (p = .01). Gene expression analysis revealed higher expression of bone morphogenetic protein‐2 (Bmp2) in the membrane compartment at 3 days in the BG group. By contrast, higher Bmp2 expression was found in the defect compartment treated with the CXP membrane, both at 3 and 21 days. A significant temporal increase (from 3 to 21 days) in the remodeling activity, cathepsin K (Catk) and calcitonin receptor (Calcr), was found in the CXP group. Molecular analysis demonstrated expression of several growth factors and cytokines in the membrane compartment irrespective of the membrane type. Bmp2 expression in the membrane correlated positively with Bmp2 expression in the defect, whereas fibroblast growth factor‐2 (Fgf2) expression in the membrane correlated positively with inflammatory cytokines, tumor necrosis factor‐alpha (Tnfa) and interleukin‐6 (Il6) in the defect.

Conclusions

The results provide histological and molecular evidence that different resorbable collagen membranes contribute differently to the GBR healing process. In the BG group, bone formation was primarily localized to the peripheral part of the defect. By contrast, the CXP group demonstrated significantly higher de novo bone formation in the central portion of the defect. This increase in bone formation was reflected by triggered expression of potent osteogenic growth factor, Bmp2, in the defect. These findings suggest that the CXP membrane may have a more active role in regulating the bone healing dynamics.
Effectiveness of protected areas for vertebrates based on taxonomic and phylogenetic diversity
Authors: Quan Qing , Che Xianli , Wu Yongjie , Wu Yuchun , Zhang Qiang , Zhang Min , Zou Fasheng
Published: July 2017

Establishing protected areas is the primary goal and tool for preventing irreversible biodiversity loss. However, the effectiveness of protected areas that target specific species has been questioned for some time because targeting key species for conservation may impair the integral regional pool of species diversity and phylogenetic and functional diversity are seldom considered. We assessed the efficacy of protected areas in China for the conservation of phylogenetic diversity based on the ranges and phylogenies of 2279 terrestrial vertebrates. Phylogenetic and taxonomic diversity were strongly and positively correlated, and only 12.1–43.8% of priority conservation areas are currently protected. However, the patterns and coverage of phylogenetic diversity were affected when weighted by species richness. These results indicated that in China, protected areas targeting high species richness protected phylogenetic diversity well overall but failed to do so in some regions with more unique or threatened communities (e.g., coastal areas of eastern China, where severely threatened avian communities were less protected). Our results suggest that the current distribution of protected areas could be improved, although most protected areas protect both taxonomic and phylogenetic diversity.
Scaling range sizes to threats for robust predictions of risks to biodiversity
Authors: Keith David A. , Akçakaya H. Resit , Murray Nicholas J.
Published: July 2017

Assessments of risk to biodiversity often rely on spatial distributions of species and ecosystems. Range‐size metrics used extensively in these assessments, such as area of occupancy (AOO), are sensitive to measurement scale, prompting proposals to measure them at finer scales or at different scales based on the shape of the distribution or ecological characteristics of the biota. Despite its dominant role in red‐list assessments for decades, appropriate spatial scales of AOO for predicting risks of species’ extinction or ecosystem collapse remain untested and contentious. There are no quantitative evaluations of the scale‐sensitivity of AOO as a predictor of risks, the relationship between optimal AOO scale and threat scale, or the effect of grid uncertainty. We used stochastic simulation models to explore risks to ecosystems and species with clustered, dispersed, and linear distribution patterns subject to regimes of threat events with different frequency and spatial extent. Area of occupancy was an accurate predictor of risk (0.81<|r|<0.98) and performed optimally when measured with grid cells 0.1–1.0 times the largest plausible area threatened by an event. Contrary to previous assertions, estimates of AOO at these relatively coarse scales were better predictors of risk than finer‐scale estimates of AOO (e.g., when measurement cells are <1% of the area of the largest threat). The optimal scale depended on the spatial scales of threats more than the shape or size of biotic distributions. Although we found appreciable potential for grid‐measurement errors, current IUCN guidelines for estimating AOO neutralize geometric uncertainty and incorporate effective scaling procedures for assessing risks posed by landscape‐scale threats to species and ecosystems.
Trait‐dependent distributional shifts in fruiting of common British fungi
Authors: Gange A. C. , Heegaard E. , Boddy L. , Andrew C. , Kirk P. , Halvorsen R. , Kuyper T. W. , Bässler C. , Diez J. , Heilman‐Clausen J. , Høiland K. , Büntgen U. , Kauserud H.
Published: July 2017

Despite the dramatic phenological responses of fungal fruiting to recent climate warming, it is unknown whether spatial distributions of fungi have changed and to what extent such changes are influenced by fungal traits, such as ectomycorrhizal (ECM) or saprotrophic lifestyles, spore characteristics, or fruit body size.

Our overall aim was to understand how climate and fungal traits determine whether and how species‐specific fungal fruit body abundances have shifted across latitudes over time, using the UK national database of fruiting records. The data employed were recorded over 45 yr (1970–2014), and include 853 278 records of Agaricales, Boletales and Russulales, though we focus only on the most common species (with more than 3000 records each). The georeferenced observations were analysed by a Bayesian inference as a Gaussian additive model with a specification following a joint species distribution model. We used an offset, random contributions and fixed effects to isolate different potential biases from the trait‐specific interactions with latitude/climate and time. Our main aim was assessed by examination of the three‐way‐interaction of trait, predictor (latitude or climate) and time.

The results show a strong trait‐specific shift in latitudinal abundance through time, as ECM species have become more abundant relative to saprotrophic species in the north. Along precipitation gradients, phenology was important, in that species with shorter fruiting seasons have declined markedly in abundance in oceanic regions, whereas species with longer seasons have become relatively more common overall. These changes in fruit body distributions are correlated with temperature and rainfall, which act directly on both saprotrophic and ECM fungi, and also indirectly on ECM fungi, through altered photosynthate allocation from their hosts. If these distributional changes reflect fungal activity, there will be important consequences for the responses of forest ecosystems to changing climate, through effects on primary production and nutrient cycling.
Aggregate strength in calcareous soil fertilized with pig slurries
Authors: Bosch‐Serra À. D. , Yagüe M. R. , Poch R. M. , Molner M. , Junyent B. , Boixadera J.
Published: July 2017

Effects of applications of pig slurry on soil aggregate stability are not well understood in dryland agriculture. This research aims to (i) identify aggregate stability tests that give a reliable description of the soil's behaviour when pig slurry (PS) is applied to calcareous soil and (ii) interpret them in terms of chemical, biological, morphological and physical soil properties for soil quality assessments. Soil samples from eight fertilizer treatments (mineral fertilizers and PS), applied over seven growing seasons were analysed. We applied five methodologies to examine different mechanisms of aggregate breakdown. Porosity was characterized by image analyses. There was minimum resistance to the mechanical breakdown of aggregates when slurries had been applied 12 months before analysis. Recent applications of slurry (3 months before the analysis) improved resistance to implosion caused by the penetration of water into dry aggregates (slaking), although the opposite result can occur if the method of evaluation is not chosen properly. Recent applications of PS also enhanced soil respiration and increased soil porosity in the 25–100‐µm size range (packing pores between aggregates) and in the 100–400‐µm size range (interaggregate or faunal pores). In dryland systems and in the winter cereal cropping season, the resistance of dry aggregates to slaking is improved temporarily if PS is applied at N rates equivalent to around 1.7 Mg OM ha−1 year−1.

Highlights

How does soil aggregate strength change in response to pig slurry (PS) applications?

Improve understanding of PS as a fertilizer and its effect on soil quality assessments

Changes in aggregate stability are controlled by time since pig slurry application

The effects of PS on the increase in packing pores between aggregates are transient
Structure of the adenylation domain Thr1 involved in the biosynthesis of 4‐chlorothreonine in Streptomyces sp. OH‐5093—protein flexibility and molecular bases of substrate specificity
Authors: Scaglione Antonella , Fullone Maria Rosaria , Montemiglio Linda Celeste , Parisi Giacomo , Zamparelli Carlotta , Vallone Beatrice , Savino Carmelinda , Grgurina Ingeborg
Published: July 2017

We determined the crystal structure of Thr1, the self‐standing adenylation domain involved in the nonribosomal‐like biosynthesis of free 4‐chlorothreonine in Streptomyces sp. OH‐5093. Thr1 shows two monomers in the crystallographic asymmetric unit with different relative orientations of the C‐ and N‐terminal subdomains both in the presence of substrates and in the unliganded form. Cocrystallization with substrates, adenosine 5′‐triphosphate and l‐threonine, yielded one monomer containing the two substrates and the other in complex with l‐threonine adenylate, locked in a postadenylation state. Steady‐state kinetics showed that Thr1 activates l‐Thr and its stereoisomers, as well as d‐Ala, l‐ and d‐Ser, albeit with lower efficiency. Modeling of these substrates in the active site highlighted the molecular bases of substrate discrimination. This work provides the first crystal structure of a threonine‐activating adenylation enzyme, a contribution to the studies on conformational rearrangement in adenylation domains and on substrate recognition in nonribosomal biosynthesis.

Database

Structural data are available in the Protein Data Bank under the accession number 5N9W and 5N9X.
Fatigue crack growth of multiple interacting cracks: Analytical models and experimental validation
Authors: Galatolo R. , Lazzeri R.
Published: July 2017

This article deals with the fatigue propagation of multiple cracks in finite width holed panels, which are typical of aircraft structural components. Theoretical studies in the literature have been considered and critically analyzed. Some of them have been translated into analytical models and implemented in a computer code. To check the effectiveness of the used models, a fatigue testing campaign has been conducted on six different configurations of notches and cracks. The comparison between experimental results and those obtained from the implemented models has shown a good agreement.
Molecular cloning and characterization of a short peptidoglycan recognition protein from silkworm Bombyx mori
Authors: Yang P.‐J. , Zhan M.‐Y. , Ye C. , Yu X.‐Q. , Rao X.‐J.
Published: July 2017

Peptidoglycan is the major bacterial component recognized by the insect immune system. Peptidoglycan recognition proteins (PGRPs) are a family of pattern‐recognition receptors that recognize peptidoglycans and modulate innate immune responses. Some PGRPs retain N‐acetylmuramoyl‐L‐alanine amidase (Enzyme Commission number: 3.5.1.28) activity to hydrolyse bacterial peptidoglycans. Others have lost the enzymatic activity and work only as immune receptors. They are all important modulators for innate immunity. Here, we report the cloning and functional analysis of PGRP‐S4, a short‐form PGRP from the domesticated silkworm, Bombyx mori. The PGRP‐S4 gene encodes a protein of 199 amino acids with a signal peptide and a PGRP domain. PGRP‐S4 was expressed in the fat body, haemocytes and midgut. Its expression level was significantly induced by bacterial challenges in the midgut. The recombinant PGRP‐S4 bound bacteria and different peptidoglycans. In addition, it inhibited bacterial growth and hydrolysed an Escherichia coli peptidoglycan in the presence of Zn2+. Scanning electron microscopy showed that PGRP‐S4 disrupted the bacterial cell surface. PGRP‐S4 further increased prophenoloxidase activation caused by peptidoglycans. Taken together, our data suggest that B. mori PGRP‐S4 has multiple functions in immunity.
Neither eosinophils nor neutrophils require ATG5‐dependent autophagy for extracellular DNA trap formation
Authors: Germic Nina , Stojkov Darko , Oberson Kevin , Yousefi Shida , Simon Hans‐Uwe
Published: July 2017

The importance of extracellular traps (ETs) in innate immunity is well established, but the molecular mechanisms responsible for their formation remain unclear and in scientific dispute. ETs have been defined as extracellular DNA scaffolds associated with the granule proteins of eosinophils or neutrophils. They are capable of killing bacteria extracellularly. Based mainly on results with phosphoinositide 3‐kinase (PI3K) inhibitors such as 3‐methyladenine (3‐MA) and wortmannin, which are commonly used to inhibit autophagy, several groups have reported that autophagy is required for neutrophil extracellular trap (NET) formation. We decided to investigate this apparent dependence on autophagy for ET release and generated genetically modified mice that lack, specifically in eosinophils or neutrophils, autophagy‐related 5 (Atg5), a gene encoding a protein essential for autophagosome formation. Interestingly, neither eosinophils nor neutrophils from Atg5‐deficient mice exhibited abnormalities in ET formation upon physiological activation or exposure to low concentrations of PMA, although we could confirm that human and mouse eosinophils and neutrophils, after pre‐treatment with inhibitors of class III PI3K, show a block both in reactive oxygen species (ROS) production and in ET formation. The so‐called late autophagy inhibitors bafilomycin A1 and chloroquine, on the other hand, were without effect. These data indicate that ET formation occurs independently of autophagy and that the inhibition of ROS production and ET formation in the presence of 3‐MA and wortmannin is probably owing to their additional ability to block the class I PI3Ks, which are involved in signalling cascades initiated by triggers of ET formation.