bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishment and characterization of a canine keratinocyte organoid culture system
Authors: Wiener Dominique J. , Basak Onur , Asra Priyanca , Boonekamp Kim E. , Kretzschmar Kai , Papaspyropoulos Angelos , Clevers Hans 
Published: July 2018

BackgroundPerturbations of epidermal and follicular homeostasis have been attributed to a variety of skin diseases affecting dogs. The availability of an in vitro system to investigate these diseases is important to understand underlying pathomechanisms.ObjectivesTo establish an accurate and reliable in vitro 3D system of canine keratinocyte organoids to lay the basis for studying functional defects in interfollicular epidermis (IFE) and hair follicle (HF) morphogenesis, reconstitution and differentiation that lead to alopecic and epidermal diseases.AnimalsSkin biopsies were obtained from freshly euthanized dogs of different breeds with no skin abnormalities.MethodsCells derived from microdissected IFE and HFs were seeded in Matrigel and keratinocyte organoids were grown and characterized using immunohistochemistry, RT‐qPCR and RNA sequencing.ResultsBoth organoid lines develop into a basal IFE‐like cell type. Gene and protein expression analysis revealed high mRNA and protein levels of keratins 5 and 14, IFE differentiation markers and intercellular molecules. Key markers of HF stem cells were lacking. Withdrawal of growth factors resulted in upregulation of markers such as KRT16, Involucrin, KRT17 and SOX9, showing the potential of the organoids to develop towards more differentiated tissue.Conclusion and clinical importanceOur 3D in vitro culture system provides the basis to explore epidermal function, to investigate the culture conditions necessary for the development of organoids with a HF signature and to address cutaneous disorders in dogs. However, for induction of HF signatures or hair growth, addition of different growth factors or co‐culture with dermal papilla will be required.
Evaluation of the secretion of antimicrobial peptides and antimicrobial effect of skin wash in atopic and healthy dogs: a preliminary study
Authors: Santoro Domenico 
Published: July 2018

BackgroundAntimicrobial peptides (AMPs) are an important component of cutaneous innate immunity. The amount of AMPs secreted in healthy and atopic patients is controversial.Hypotheses/ObjectivesTo evaluate the antimicrobial effect of skin wash harvested from healthy and atopic dogs, the amount of AMPs (cBD3‐like/cBD122, cCath, S100A8/9/12) present in the skin washes, and the correlation between AMP levels and severity of the clinical signs.AnimalsFifteen healthy and 15 mildly atopic, privately owned dogs.Methods and materialsSkin washes were performed on a 15 cm2 area of nonlesional abdominal skin. The area was rinsed with 2.7 mL of saline using a sterile tube. Commercially available (S100A8/9/12) or in‐house (cBD3‐like and cCath) canine‐specific ELISAs were performed. Skin washes were incubated with different concentrations (5 × 105 to 4 × 103 cfu/mL) of Staphylococcus pseudintermedius and the bacterial density measured after 24 h of incubation. Severity of clinical signs was assessed by the Canine Atopic Dermatitis Extent and Severity Index, 4th version (CADESI‐04). Data were analysed statistically and significance level was set as P ≤ 0.05.ResultsThere was no significant difference in any of the tested AMPs between healthy and atopic dogs. Strong/moderate positive correlations were seen between total and inguinal CADESI‐04 (r = 0.69; P = 0.0061) and between AMPs [cBD3‐like/cCath (r = 0.69; P = 0.011), S100A8/S100A9 (r = 0.8; P = 0.0016) and S100A9/S100A12 (r = 0.57; P = 0.047)]. Significantly less antimicrobial activity was seen in skin washes from atopic versus healthy dogs (P < 0.05).Conclusions and clinical importanceThis study found no difference in AMP secretion levels between healthy and nonlesional atopic canine skin. However, a significantly lower antimicrobial activity was present in the skin washes from atopic compared to healthy skin.
Additive design: the concept and data analysis
Authors: Oliveira M C , Pereira G A M , Ferreira E A , Santos J B , Knezevic S Z , Werle R 
Published: July 2018

SummaryCrop–weed competition is extensively studied in weed science. The additive design, in which weed density varies and the crop density is kept constant, is the most commonly utilised design in plant competition studies. The additive design is important to calculate economic weed thresholds and improve weed control decision‐making. Crop–weed competition studies are usually conducted by weed scientists, who sometimes report misleading conclusions because of lack of statistical knowledge needed for data analysis of such studies. Therefore, the objective of this manuscript is to provide the concept of additive design and demonstrate the model selection approach for describing crop–weed density relationship to non‐statisticians. We evaluated three models routinely used in the literature to interpret data from additive designs, including polynomial quadratic, sigmoid and rectangular hyperbola curves. Based on the described statistical criteria, we demonstrated the rectangular hyperbola to be the most appropriate model to describe data from an additive design study looking at Richardia brasiliensis and Commelina benghalensis competition with maize (Zea mays). Moreover, we describe step‐by‐step how to perform the statistical analysis in R software and interpret the results of crop–weed competition studies. We suggest the use of the rectangular hyperbola as a standardised model for crop–weed competition in additive design.
Combined Blockade of IL6 and PD-1/PD-L1 Signaling Abrogates Mutual Regulation of Their Immunosuppressive Effects in the Tumor Microenvironment
Authors: Tsukamoto Hirotake , Fujieda Koji , Miyashita Azusa , Fukushima Satoshi , Ikeda Tokunori , Kubo Yosuke , Senju Satoru , Ihn Hironobu , Nishimura Yasuharu , Oshiumi Hiroyuki 
Published: July 2018

AbstractRecently emerging cancer immunotherapies combine the applications of therapeutics to disrupt the immunosuppressive conditions in tumor-bearing hosts. In this study, we found that targeting the proinflammatory cytokine IL6 enhances tumor-specific Th1 responses and subsequent antitumor effects in tumor-bearing mice. IL6 blockade upregulated expression of the immune checkpoint molecule programmed death-ligand 1 (PD-L1) on melanoma cells. This PD-L1 induction was canceled in IFNγ-deficient mice or CD4+ T cell–depleted mice, suggesting that CD4+ T cell–derived IFNγ is important for PD-L1 induction in tumor-bearing hosts. In some patients with melanoma, however, treatment with the anti–PD-1 antibody nivolumab increased systemic levels of IL6, which was associated with poor clinical responses. This PD-L1 blockade-evoked induction of IL6 was reproducible in melanoma-bearing mice. We found that PD-1/PD-L1 blockade prompted PD-1+ macrophages to produce IL6 in the tumor microenvironment. Depletion of macrophages in melanoma-bearing mice reduced the levels of IL6 during PD-L1 blockade, suggesting macrophages are responsible for the IL6-mediated defective CD4+ Th1 response. Combined blockade of the mutually regulated immunosuppressive activities of IL6 and PD-1/PD-L1 signals enhanced expression of T cell–attracting chemokines and promoted infiltration of IFNγ-producing CD4+ T cells in tumor tissues, exerting a synergistic antitumor effect, whereas PD-L1 blockade alone did not promote Th1 response. Collectively, these findings suggest that IL6 is a rational immunosuppressive target for overcoming the narrow therapeutic window of anti–PD-1/PD-L1 therapy.Significance: These findings advance our understanding of IL6-PD1/PD-L1 cross-talk in the tumor microenvironment and provide clues for targeted interventional therapy that may prove more effective against cancer. Cancer Res; 78(17); 5011–22. ©2018 AACR.
High-Throughput Functional Evaluation of Variants of Unknown Significance in ERBB2
Authors: Nagano Masaaki , Kohsaka Shinji , Ueno Toshihide , Kojima Shinya , Saka Kanju , Iwase Hirotaro , Kawazu Masahito , Mano Hiroyuki 
Published: July 2018

Abstract
Purpose: The advent of next-generation sequencing technologies has enabled the identification of several activating mutations of Erb-B2 receptor tyrosine kinase 2 (ERBB2) among various cancers. However, the significance of infrequent mutations has not been fully investigated. Herein, we comprehensively assessed the functional significance of the ERBB2 mutations in a high-throughput manner.
Experimental Design: We evaluated the transforming activities and drug sensitivities of 55 nonsynonymous ERBB2 mutations using the mixed-all-nominated-in-one (MANO) method.
Results: G776V, G778_S779insG, and L841V were newly revealed to be activating mutations. Although afatinib, neratinib, and osimertinib were shown to be effective against most of the ERBB2 mutations, only osimertinib demonstrated good efficacy against L755P and L755S mutations, the most common mutations in breast cancer. In contrast, afatinib and neratinib were predicted to be more effective than other inhibitors for the A775_776insYVMA mutation, the most frequent ERBB2 mutation in lung cancer. We surveyed the prevalence of concurrent ERBB2 mutation with gene amplification and found that approximately 30% of ERBB2-amplified urothelial carcinomas simultaneously carried ERBB2 mutations, altering their sensitivity to trastuzumab, an mAb against ERBB2. Furthermore, the MANO method was applied to evaluate the functional significance of 17 compound mutations within ERBB2 reported in the COSMIC database, revealing that compound mutations involving L755S were sensitive to osimertinib but insensitive to afatinib and neratinib.
Conclusions: Several ERBB2 mutations showed varying sensitivities to ERBB2-targeted inhibitors. Our comprehensive assessment of ERBB2 mutations offers a fundamental database to help customize therapy for ERBB2-driven cancers.
We identified several ERBB2 mutations as activating mutations related to tumorigenesis. In addition, our comprehensive evaluation revealed that several ERBB2 mutations showed varying sensitivities to ERBB2-targeted inhibitors, and thus, the functional significance of each variant should be interpreted precisely to design the best treatment for each patient. Clin Cancer Res; 24(20); 5112–22. ©2018 AACR.
Moral Panic and Power: The Means of Legitimisation of Religious Intolerance & Human Rights Violation against the Bahá’ís in Iran
Authors: Moinipour Shabnam 
Published: July 2018

Abstract
The case of the Bahá’ís of Iran, the country’s largest non-Muslim religious minority, is a “suspended” genocide and hence alarming. The human rights violations against the members of the Bahá’í community have been designed in such a way to draw as little international attention as possible. It is designed to eliminate slowly rather than to eradicate abruptly. Since its inception in 1979, the Islamic Republic has actively pursued the policy of Bahá’í persecution. This paper focuses on one aspect of the tactics used by the Iranian regime to violate the human rights of the Bahá’í community in Iran. To do so, moral panic theory and Foucault’s power discourse have been used to offer an analysis of the Bahá’í persecutions as an underlying feature of Iran’s domestic policy of othering, religious intolerance and Shi’a supremacy.
Endobronchial Non-Tuberculosis Mycobacterium Infection Presenting in a Healthy Child
Authors: Kavookjian Hannah , Jones Joel W. , Shah Sweeti , Escobar Hugo , Swanson Douglas , Nicklaus Pamela 
Published: July 2018

Objectives:To describe a safe and effective treatment for endobronchial Mycobacterium avium complex.Methods:Case report and literature review.Results:We present a case of endobronchial M. avium complex in a healthy child treated with serial carbon-dioxide laser excisions and antibiotic triple therapy using azithromycin, rifampin, and ethambutol. No current guideline for the treatment of these lesions in the pediatric population exists.Conclusions:In patients with airway impingement, serial endoscopic surgical resection combined with antibiotics can provide safe and effective management.
Oral Fluoride Measurements for Estimation of the Anti-caries Efficacy of Fluoride Treatments
Authors: Duckworth R.M. , Morgan S.N. , Gilbert R.J. 
Published: July 2018

The aims of this work were (a) to assess the oral bioavailability of fluoride delivered from dentifrices and (b) to test for a possible link between the results and clinical data obtained with the same dentifrices. Oral fluoride concentrations were measured in samples of saliva and plaque taken from seven subjects, after use of dentifrices which contained 0, 1000, 1500, and 2500 μg F/g as sodium monofluorophosphate. Salivary fluoride in samples obtained within the first few hours after a single dentifrice application, or up to 20 h after four weeks' daily use, increased with increasing F content of the dentifrice. For example, the mean zero-time intercepts of the second phase of salivary fluoride clearance curves for the above dentifrices were 0.46, 1.48, 1.88, and 3.03 μmol F/L, respectively. Plaque fluoride measured after four weeks' daily use of the dentifrices exhibited similar dose-response behavior. Linear regression analysis showed these trends to be statistically significant for both saliva (p < 0.001) and plaque (p < 0.025). Mean saliva and plaque fluoride concentrations were inversely associated with mean three-year caries increments for the three fluoride-containing dentifrices obtained in a recent clinical trial: DMFS scores 6.80, 6.33, and 5.71, respectively (Stephen et al., 1988). This suggests that oral fluoride measurements are a valuable in vivo method for the evaluation of the potential anti-caries efficacy of fluoride-containing dental products.
Pancreatic function and histoarchitecture in Wistar rats following chronic exposure to Bushfire®: the mitigating role of zinc
Authors: Tizhe Emmanuel , Ibrahim Najume , Fatihu Mohammed , Ambali Suleiman , Igbokwe Ikechukwu , Tizhe Ussa 
Published: July 2018

Objectives To assess the toxicopathologic effects of chronic exposure to the glyphosate-based herbicide Bushfire® on the pancreas of Wistar rats and the protective role of zinc. Methods We exposed the rats to daily doses of 14.4 to 750 mg/kg body weight of the glyphosate-based herbicide Bushfire® and to 50 or 100 mg/kg zinc, and measured blood glucose levels and serum insulin levels. Tissue samples were evaluated for histopathological alterations. Results Levels of both blood glucose and serum insulin increased in glyphosate-exposed rats, and moderate to severe degenerative changes were observed in both glandular pancreatic acinar cells and islets of Langerhans in all rats exposed to glyphosate. These effects were prevented by pretreatment with zinc. Conclusion Chronic exposure to glyphosate can alter pancreatic function and histoarchitecture, but zinc supplementation can mitigate these toxicopathologic effects.
Factors Associated with Prescribing Broad-Spectrum Antibiotics for Children with Upper Respiratory Tract Infections in Ambulatory Care Settings
Authors: Alzahrani Mohammad S , Maneno Mary K , Daftary Monika N , Wingate La’Marcus , Ettienne Earl B 
Published: July 2018

Objectives: Broad-spectrum antibiotics are frequently prescribed for children with upper respiratory tract infections (URI). Excessive use of broad-spectrum antibiotics leads to the emergence of resistant bacteria. This study aimed to identify factors associated with prescribing broad-spectrum antibiotics among children younger than 18 years presenting with URI in outpatient settings. Methods: We conducted a cross-sectional analysis of the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey-Outpatient Departments (NHAMCS-OPD) between 2006 and 2010. Descriptive statistics of visits from children with URI were estimated. Simple and multiple logistic regression analyses were used to identify socio-demographic and clinical characteristics associated with broad-spectrum antibiotic prescribing. We also completed a stratified analysis by age (⩽2 vs >2). Results: A total of 4013 outpatient visits for children with URI from both NAMCS and NHAMCS-0PD data were examined. Broad-spectrum antibiotics were prescribed in 39% of the visits, accounting for an estimated 6.8 million visits annually. Multivariable analysis showed that visits in the South region (odds ratio [OR] = 2.38; 95% confidence interval [CI]: 1.38-4.10) compared with the West region and visits with diagnoses of acute sinusitis (OR = 2.77; 95% CI: 1.65-4.63) and acute otitis media (OR = 1.90; 95% CI: 1.32-2.74) compared with those with acute pharyngitis were associated with greater odds of broad-spectrum antibiotic prescribing. Conclusions: The prescribing of broad-spectrum antibiotics is common for children with URI in ambulatory care settings. Diagnosis and management of URI remain a critical area for awareness campaigns promoting judicious use of antibiotics.
Effective Project Management for Strategic Innovation and Change in an Organizational Context
Authors: Kenny John 
Published: July 2018

Projects are a means of implementing strategy; the relationship of project management to strategic implementation in an organization is explored. Some of the recent project management literature is examined and a case study from the education sector is used to consider how to effectively link project management to organizational strategic processes. Project management techniques have been used very successfully in a wide range of areas. They are routinely applied in IT developments, building, government, and education. Recent thinking has raised questions about how to more closely match the techniques to the nature of individual projects. The nature of different types of projects is explored through consideration of projects involving high levels of change, and/or innovation. By their nature, the final outcomes of such projects are not clearly defined and their execution may require many iterations of development. A means of categorizing projects within an organization is developed. This, along with a set process guidelines, will enable an organization's management to more effectively consider the implications of implementing strategic projects. Monitoring such projects can present problems in an organization when management accountability mechanisms demand results and rigid processes are imposed.
A Balanced Scorecard Approach to Project Management Leadership
Authors: Norrie James , Walker Derek H. T. 
Published: July 2018

In this paper, we discuss ways that project managers can use measurement (using a tool such as the balanced scorecard) to improve the operational performance of their project teams. Project managers will see that attaching measures to outcomes clarifies project objectives and supports well-defined and well-communicated links between the project vision and business strategy. These also enable project managers to more effectively monitor and control project activities for the purpose of improving project results. This paper reinforces the importance of strategy as an added dimension to the traditional triple constraint. We present this information through our comparison and survey of two projects undertaken by project teams at a large North American global telecommunications organization. The results of our study provide early evidence of the usefulness of the balanced scorecard (BSC) as a tool for improving project management effectiveness. Our study also shows that balanced performance measurement is an important technique for establishing on-strategy project delivery. We propose using this technique primarily as an extension of current practices by adding a strategic measurement dimension.
Switch Leadership in Projects an Empirical Study Reflecting the Importance of Transformational Leadership on Project Success across Twenty-Eight Nations
Authors: Prabhakar Guru Prakash 
Published: July 2018

“The best way to find yourself is to lose yourself in the service of others.” Mahatma Gandhi This paper documents an empirical analysis of leadership in project management practices on 153 projects across 28 nations. This is a two-phase research study for which 46 projects were studied in phase 1 representing 14 nations and 107 projects were examined in phase 2 originating from 25 nations. The main purpose of this research is to study the importance of project leadership and team related factors and enlist the factors that play a pivotal role in achieving project success. It is a multinational and thus multicultural research study that represents the present day project environment, which is highly multicultural and multidisciplinary. The results from the analysis of data obtained from phase 1 lead to the development of the phase 2 questionnaires that further explores the links between different leadership aspects and project success as pointed out in the phase 1. At the end the author provides a tentative and suggestive list of factors displaying the impact of critical leadership factors on project success
Ferri-fluoro-katophorite from Bear Lake diggings, Bancroft area, Ontario, Canada: a new species of amphibole, ideally Na(NaCa)(Mg4Fe3+)(Si7Al)O22F2
Authors: Oberti Roberta , Boiocchi Massimo , Hawthorne Frank C. , Ball Neil A. , Martin Robert F. 
Published: July 2018

AbstractFerri-fluoro-katophorite is the second species characterised involving the rootname katophorite in the sodium–calcium subgroup of the amphibole supergroup. The mineral and its name were approved by the International Mineralogical Association Commission on New Minerals, Nomenclature and Classification, IMA2015-096. It was found in the Bear Lake diggings, Bancroft area, Ontario, Canada, where coarse euhedral crystals of amphibole, phlogopite, sanidine solid-solution (now coarsely exsolved to microcline perthite), titanite, augite, zircon and fluorapatite crystallised from a low-viscosity silicocarbonatitic magma of crustal origin. Greenish grey prismatic crystals of ferri-fluoro-katophorite generally protrude from the walls into a body of coarsely crystalline calcite, but they also occur away from the walls, completely enclosed by calcite. The empirical formula derived from electron microprobe analysis and single-crystal structure refinement is: A(Na0.55K0.32)Σ0.87B(Na0.79Ca1.18Mn2+0.03)Σ2.00C(Mg3.29Mn2+0.02Fe2+1.19Fe3+0.31Al0.09Ti4+0.08Li0.02)Σ5.00T(Si7.39Al0.61)Σ8.00O22W[F1.23 (OH)0.77]Σ2.00. Ferri-fluoro-katophorite is biaxial (–), with α = 1.640(2), β = 1.652(2), γ = 1.658(2), 2Vmeas. = 68.9(2)° and 2Vcalc.. = 70.1°. The unit-cell parameters are a = 9.887(3), b = 18.023(9), c = 5.292(2) Å, β = 104.66(3)°, V = 912.3(6) Å3, Z = 2 and space group C2/m. The strongest ten lines in the powder X-ray pattern [d values (in Å) I (hkl)] are: 2.708, 100, (151); 2.388, 74, (131); 3.139, 72, (310); 8.449, 69, (110); 2.540, 65, ($\bar{2}$02); 2.591, 53, (061); 2.739, 47, ($\bar{3}$31); 2.165, 45, (261); 3.279, 44, ($\bar{2}$40); 2.341, 43, ($\bar{3}$51).
Extracellular vesicles in DLBCL provide abundant clues to aberrant transcriptional programming and genomic alterations
Authors: Rutherford Sarah C. , Fachel Angela A. , Li Sheng , Sawh Seema , Muley Ashlesha , Ishii Jennifer , Saxena Ashish , Dominguez Pilar M. , Caldas Lopes Eloisi , Agirre Xabier , Chambwe Nyasha , Correa Fabian , Jiang Yanwen , Richards Kristy L. , Betel Doron , Shaknovich Rita 
Published: July 2018

Key Points
EVs derived from DLBCL cells can be traced from and provide insight into cell of origin. Mutated RNAs may be preferentially packaged into EVs, and this could enable disease monitoring through liquid biopsy.