bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased IL‐6 and Potential IL‐6 trans‐signalling in the airways after an allergen challenge
Authors: Esnault Stephane , Khosravi Mehdi , Kelly Elizabeth A. , Liu Lin Ying , Bochkov Yury A. , Tattersall Matthew C. , Jarjour Nizar N.
Published: January 2021

Background

In asthma, IL‐6 is a potential cause of enhanced inflammation, tissue damage and airway dysfunction. IL‐6 signalling is regulated by its receptor, which is composed of two proteins, IL‐6R and GP130. In addition to their membrane form, these two proteins may be found as extracellular soluble forms. The interaction of IL‐6 with soluble IL‐6R (sIL‐6R) can trigger IL‐6 trans‐signalling in cells lacking IL‐6R. Conversely, the soluble form of GP130 (sGP130) competes with its membrane form to inhibit IL‐6 trans‐signalling.

Objectives

We aimed to analyse IL‐6 trans‐signalling proteins in the airways of subjects after an allergen challenge.

Methods

We used a model of segmental bronchoprovocation with an allergen (SBP‐Ag) in human subjects with allergy. Before and 48 h after SBP‐Ag, bronchoalveolar lavages (BALs) allowed for the analysis of proteins in BAL fluids (BALFs) by ELISA, and membrane proteins on the surface of BAL cells by flow cytometry. In addition, we performed RNA sequencing (RNA‐seq) and used proteomic data to further inform on the expression of the IL‐6R subunits by eosinophils, bronchial epithelial cells and lung fibroblasts. Finally, we measured the effect of IL‐6 trans‐signalling on bronchial fibroblasts, in vitro.

Results

IL‐6, sIL‐6R, sGP130 and the molar ratio of sIL‐6R/sGP130 increased in the airways after SBP‐Ag, suggesting the potential for enhanced IL‐6 trans‐signalling activity. BAL lymphocytes, monocytes and eosinophils displayed IL‐6R on their surface and were all possible providers of sIL‐6R, whereas GP130 was highly expressed in bronchial epithelial cells and lung fibroblasts. Finally, bronchial fibroblasts activated by IL‐6 trans‐signalling produced enhanced amounts of the chemokine, MCP‐1 (CCL2).

Conclusion and Clinical relevance

After a bronchial allergen challenge, we found augmentation of the elements of IL‐6 trans‐signalling. Allergen‐induced IL‐6 trans‐signalling activity can activate fibroblasts to produce chemokines that can further enhance inflammation and lung dysfunction.
Whole blood interleukin-2 release test to detect and characterize rare circulating gluten-specific T cell responses in coeliac disease
Authors: Anderson R P , Goel G , Hardy M Y , Russell A K , Wang S , Szymczak E , Zhang R , Goldstein K E , Neff K , Truitt K E , Williams L J , Dzuris J L , Tye-Din J A
Published: January 2021

Whole blood cytokine release assays (CRA) assessing cellular immunity to gluten could simplify the diagnosis and monitoring of coeliac disease (CD). We aimed to determine the effectiveness of electrochemiluminescence CRA to detect responses to immunodominant gliadin peptides. HLA-DQ2·5+ CD adults (cohort 1, n = 6; cohort 2, n = 12) and unaffected controls (cohort 3, n = 9) were enrolled. Cohort 1 had 3-day gluten challenge (GC). Blood was collected at baseline, and for cohort 1 also at 3 h, 6 h and 6 days after commencing 3-day GC. Gliadin peptide-stimulated proliferation, interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) and 14- and 3-plex electrochemiluminescence CRA were performed. Poisson distribution analysis was used to estimate responding cell frequencies. In cohort 1, interleukin (IL)-2 dominated the gliadin peptide-stimulated cytokine release profile in whole blood. GC caused systemic IL-2 release acutely and increased gliadin peptide-stimulated IFN-γ ELISPOT and whole blood CRA responses. Whole blood CRA after GC was dominated by IL-2, but also included IFN-γ, C-X-C motif chemokine ligand 10/IFN-γ-induced protein 10 (CXCL10/IP-10), CXCL9/monokine induced by IFN-γ (MIG), IL-10, chemokine (C-C motif) ligand 3/macrophage inflammatory protein 1-alpha (CCL3/MIP-1α), TNF-α and IL-8/CXCL8. In cohorts 2 and 3, gliadin peptide-stimulated whole blood IL-2 release was 100% specific and 92% sensitive for CD patients on a gluten-free diet; the estimated frequency of cells in CD blood secreting IL-2 to α-gliadin peptide was 0·5 to 11 per ml. Whole blood IL-2 release successfully mapped human leucocyte antigen (HLA)-DQ2·5-restricted epitopes in an α-gliadin peptide library using CD blood before and after GC. Whole blood IL-2 release assay using electrochemiluminescence is a sensitive test for rare gliadin-specific T cells in CD, and could aid in monitoring and diagnosis. Larger studies and validation with tetramer-based assays are warranted.
Implementing steroid profiling by liquid chromatography‐tandem mass spectrometry improves newborn screening for congenital adrenal hyperplasia in New Zealand
Authors: de Hora Mark R. , Heather Natasha L. , Patel Tejal , Bresnahan Lauren G. , Webster Dianne , Hofman Paul L.
Published: January 2021

Objective

To evaluate the impact of a liquid chromatography‐tandem mass spectrometry (LCMSMS) second‐tier test on newborn screening for congenital adrenal hyperplasia due to 21‐hydroxylase deficiency (CAH) in New Zealand.

Design

In a prospective study, a LCMSMS method to measure 17‐hydroxyprogesterone (17OHP) was adapted to measure four additional steroids. Steroid concentrations were collected on all second‐tier CAH screening tests while protocols remained unchanged. Steroid ratio parameters with recommended or published screening cuts‐offs were evaluated for their impact on newborn screening performance.

Measurements

Precision, accuracy, linearity and recovery of the second‐tier LCMSMS method were evaluated. Second‐tier specimens were divided in 3 groups; newborn screening bloodspots from neonates with confirmed CAH (n = 7) and 2 groups specimens from neonates with a birthweight (BW) ≤1500 g (n = 795) and with a BW > 1500 g (n = 806) with a negative newborn screening test. Six protocols using four steroid ratio parameters were evaluated. The sensitivity, specificity, false positive rate and positive predictive value of screening was calculated for each protocol.

Results

The LCMSMS method was sufficiently accurate and precise to be used as a second‐tier test for CAH. Screening sensitivity remained at 100% for each protocol apart from (17OHP + androstenedione)/cortisol when the highest cut‐off of 3.75 was applied. The false positive rate was significantly improved when (17OHP + androstenedione)/cortisol and (17OHP + 21‐deoxycortisol)/cortisol were evaluated with cut‐offs of 2.5 and 1.5 respectively (P < .01) and both with a positive predictive value of 64%.

Conclusions

A second‐tier LCMSMS newborn screening test for CAH offers significant improvements to screening specificity without any other changes to screening protocols.
Using expert knowledge to support Endangered Species Act decision‐making for data‐deficient species
Authors: Fitzgerald Daniel B. , Smith David R. , Culver David C. , Feller Daniel , Fong Daniel W. , Hajenga Jeff , Niemiller Matthew L. , Nolfi Daniel C. , Orndorff Wil D. , Douglas Barbara , Maloney Kelly O. , Young John A.
Published: January 2021

Many questions relevant to conservation decision‐making are characterized by extreme uncertainty due to lack of empirical data and complexity of the underlying ecologic processes, leading to a rapid increase in the use of structured protocols to elicit expert knowledge. Published ecologic applications often employ a modified Delphi method, where experts provide judgments anonymously and mathematical aggregation techniques are used to combine judgments. The Sheffield elicitation framework (SHELF) differs in its behavioral approach to synthesizing individual judgments into a fully specified probability distribution for an unknown quantity. We used the SHELF protocol remotely to assess extinction risk of three subterranean aquatic species that are being considered for listing under the U.S. Endangered Species Act. We provided experts an empirical threat assessment for each known locality over a video conference and recorded judgments on the probability of population persistence over four generations with online submission forms and R‐shiny apps available through the SHELF package. Despite large uncertainty for all populations, there were key differences between species’ risk of extirpation based on spatial variation in dominant threats, local land use and management practices, and species’ microhabitat. The resulting probability distributions provided decision makers with a full picture of uncertainty that was consistent with the probabilistic nature of risk assessments. Discussion among experts during SHELF's behavioral aggregation stage clearly documented dominant threats (e.g., development, timber harvest, animal agriculture, and cave visitation) and their interactions with local cave geology and species’ habitat. Our virtual implementation of the SHELF protocol demonstrated the flexibility of the approach for conservation applications operating on budgets and time lines that can limit in‐person meetings of geographically dispersed experts.
An atypical chondroid syringoma with malignant degeneration: Utility of comparative genomic hybridization in confirming the diagnosis
Authors: Zia Shereen , Shaw Brandon , Chapman Stephanie , Friedman Ben J.
Published: January 2021

Chondroid syringoma (CS) represents the cutaneous counterpart of mixed tumor (pleomorphic adenoma) of salivary glands. Definitive diagnosis is made on histopathology and is based on the presence of characteristic epithelial and stromal components. We report a case of an atypical CS arising on the extremity of an elderly male patient. Histomorphologic features of necrosis and cellular atypia raised suspicion for malignant degeneration, an exceptionally rare circumstance in this context. To further support the diagnosis of malignancy, array comparative genomic hybridization was performed from both low and higher grade areas of the tumor. Both regions demonstrated multiple copy number gains and losses, with additional loss of q7p (TP53), loss of 19p, and loss of heterozygosity on16q demonstrated in the more atypical foci. To our knowledge, this is the first case description of malignant degeneration of a CS with correlative microarray analysis. The findings in this case may prove useful in confirming the diagnosis in future ambiguous cases.
Effects of hypertension on cancer survival: A meta‐analysis
Authors: Petrelli Fausto , Ghidini Antonio , Cabiddu Mary , Perego Gianluca , Lonati Veronica , Ghidini Michele , Oggionni Emanuela , Galli Emilio , Moleri Giovanna , Barni Sandro , Bossi Antonio Carlo , Colombelli Paolo Luigi , Dognini Giuseppina , Sganzerla Paolo
Published: January 2021

Background

Hypertension is usually associated with increased cardiovascular mortality. Uncertainty exists about the possible role of hypertension as a poor prognostic factor for cancer‐specific mortality (CSM). To assess the association between pre‐existing hypertension and the risk of mortality and relapse after a diagnosis of cancer, we performed a systematic review and meta‐analysis of published studies.

Methods

PubMed, Scopus, Web of Science, the Cochrane Library and EMBASE were searched from inception until May 2020, without language restrictions, for observational studies reporting the prognosis of patients with hypertension and cancer. The primary outcome of the study refers to CSM in hypertensive vs nonhypertensive patients, and secondary endpoints were overall mortality (OM) and progression‐ or relapse‐free survival. The effect size was reported as hazard ratios (HRs) with 95% CIs.

Results

Mortality and relapse associated with hypertension in patients with various cancers were evaluated among 1 603 437 participants (n = 66 studies). Overall, diagnosis of cancer and hypertension was associated with an increased independent risk of OM (HR = 1.2 [95% CI, 1.13‐1.27], P < .01) and CSM (HR = 1.12 [95% CI, 1.04‐1.21], P < .01) but not of relapse (HR = 1.08 [95% CI, 0.98‐1.19], P = .14).

Conclusions

Among cancer patients, those with pre‐existing hypertension have a poorer outcome, probably due to multifactorial reasons. Adequate control of lifestyle, more intensive follow‐ups, monitoring for hypertension‐ and anticancer‐related cardiovascular complications, and establishing multidisciplinary cardio‐oncology units can be useful measures for reducing mortality and improving care in this setting.
Impact of biochar on nutrient supply, crop yield and microbial respiration on sandy soils of northern Germany
Authors: Knoblauch Christian , Priyadarshani S.H. Renuka , Haefele Stephan M. , Schröder Nicola , Pfeiffer Eva‐Maria
Published: January 2021

The application of biochar to agricultural soils to increase nutrient availability, crop production and carbon sequestration has gained increasing interest but data from field experiments on temperate, marginal soils are still under‐represented. In the current study, biochar, produced from organic residues (digestates) from a biogas plant, was applied with and without digestates at low (3.4 t ha−1) and intermediate (17.1 t ha−1) rates to two acidic and sandy soils in northern Germany that are used for corn (Zea mays L.) production. Soil nutrient availability, crop yields, microbial biomass and carbon dioxide (CO2) emissions from heterotrophic respiration were measured over two consecutive years. The effects of biochar application depended on the intrinsic properties of the two tested soils and the biochar application rates. Although the soils at the fallow site, with initially low nutrient concentrations, showed a significant increase in pH, soil nutrients and crop yield after low biochar application rates, a similar response was found at the cornfield site only after application of substantially larger amounts of biochar. The effect of a single dose of biochar at the beginning of the experiment diminished over time but was still detectable after 2 years. Whereas plant available nutrient concentrations increased after biochar application, the availability of potentially phytotoxic trace elements (Zn, Pb, Cd, Cr) decreased significantly, and although slight increases in microbial biomass carbon and heterotrophic CO2 fluxes were observed after biochar application, they were mostly not significant. The results indicate that the application of relatively small amounts of biochar could have positive effects on plant available nutrients and crop yields of marginal arable soils and may decrease the need for mineral fertilizers while simultaneously increasing the sequestration of soil organic carbon.

Highlights

A low rate of biochar increased plant available nutrients and crop yield on marginal soils.

Biochar application reduced the availability of potentially harmful trace elements.

Heterotrophic respiration showed no clear response to biochar application.

Biochar application may reduce fertilizer need and increase carbon sequestration on marginal soils.
Poor performance due to epiglottic retroversion in a Standardbred trotter
Authors: Burns J. J. , MacMillan K. M.
Published: January 2021

A 3‐year‐old Standardbred trotting gelding presented to the Atlantic Veterinary College for diagnostic work‐up of poor performance and abnormal respiratory noise during exercise. Physical examination was unremarkable, and no significant findings were identified on standing endoscopic examination of the upper respiratory tract. Treadmill endoscopy was utilised for dynamic evaluation of the upper respiratory tract; a diagnosis of epiglottic retroversion was confirmed. The owner requested euthanasia of the gelding, and a post‐mortem evaluation was completed. Despite thorough gross and histological examination of the head and neck on post‐mortem examination, no evidence was identified to support the postulated aetiologies for epiglottic retroversion currently found in the literature. This case represents the first reported findings from a post‐mortem examination of a horse with epiglottic retroversion.
Angular orientations derived from a portable media device to assess postural stability during quiet standing in the horse
Authors: Moorman V. J. , King M. R.
Published: January 2021

Background

Body‐mounted sensors have been increasingly popular to measure horse movement with the majority of investigations examining linear movement. Many of these devices can also determine angular orientations, and measuring angular movements may increase the ability to differentiate treatment conditions.

Objective

To determine if angular orientations utilising the sensors within a portable media device (PMD) could be used to differentiate stance conditions in standing horses.

Study design

Cross‐over.

Methods

A PMD was mounted over the withers (thoracic vertebra 8‐10) using a surcingle. Seven healthy horses were examined during quiet standing, and five trials were collected in a square stance, base‐narrow stance, and at 5 and 10 min following sedation with xylazine hydrochloride (IV). Angular orientations around the mediolateral (ML), craniocaudal (CC), and vertical axes, and range of motion and standard deviations (SD) were extracted. Mixed‐model ANOVAs, with stance condition as a fixed effect and horse as a random effect, were performed with significance at P<0.05.

Results

There was no significant difference in any angular orientation variable when comparing the base‐narrow to square stance condition. At 5 minutes following sedation with xylazine hydrochloride, there were significant differences in the range of motion and SDs for all three angular orientations (pitch, roll and yaw) compared to square stance (P<0.005). At 10 minutes following sedation with xylazine hydrochloride, there were significant differences in the range of motion and SDs, respectively, for rotation around the ML (pitch) (0.91°, 0.21°) and CC (roll) (1.07°, 0.25°) axes compared to square stance (pitch: 0.71°, 0.16°; roll: 0.73°, 0.18°) (P<0.036).

Main limitations

No gold standard was utilised to determine the accuracy of the angular orientations.

Conclusions

Use of angular orientations derived from sensors within the PMD may be another avenue for evaluating horses’ postural sway during stance.
Potassium permanganate assisted organosolv pretreatment enhances enzymatic hydrolysis of corn stover
Authors: Chen Haiyan , Li Xuezhi , Yu Shaoyang , Qin Yuqi , Qu Yinbo , Zhao Jian
Published: January 2021

High efficiency enzymatic hydrolysis of lignocellulose to produce fermentable sugar is important for bioconversion of lignocellulosic biomass to liquid fuels and chemicals. In this study, a simple pretreatment with potassium permanganate is used to enhance the efficiency of organosolv pretreatment of corn stover. It is testified that, compared to the single organosolv pretreatment, the KMnO4 assisted organosolv pretreatment significantly increase yields of carbohydrates through decreasing degradation of hemicellulose, decrease formation of inhibitors and enhance enzymatic hydrolysis of corn stover pretreated at a low pretreatment temperature. Process conditions of the KMnO4 assisted organosolv pretreatment are optimized and the conversion of glucan and xylan in pretreated corn stover at 72 h of enzymatic hydrolysis reach to 89.45% and 85.30% respectively when corn stover is firstly treated with 1% (w/w) KMnO4 at 40°C for 60 min prior to ethanol‐water pretreatment with 50% ethanol concentration at 185°C for 90 min. The differences in morphological feature, fiber surface chemical compositions, crystallinity degree and thermostability of pretreated corn stover by ethanol‐water with and without KMnO4 are characterized by scanning electron microscope, X‐ray photoelectron spectroscopy, X‐ray diffraction and thermogravimetry to explore the underlying reasons of KMnO4 strengthening ethanol‐water pretreatment process.
What does safety in mental healthcare transitions mean for service users and other stakeholder groups: An open‐ended questionnaire study
Authors: Tyler Natasha , Wright Nicola , Panagioti Maria , Grundy Andrew , Waring Justin
Published: January 2021

Background

Historically, safety mental health research has tended to focus on risks of homicide, suicide and deaths. Although wider safety issues are now recognized in regards to mental health services, the safety of mental health transitions, a key research and policy priority according to World Health Organisation, has not been explored.

Objective

The purpose of this study was to investigate perceptions of safety in mental health transitions (hospital to community) amongst five stakeholder groups.

Design and setting

An online, international cross‐sectional, open‐ended questionnaire.

Participants

There were five stakeholder participant groups: service users; families/carers; mental health‐care professionals; researchers; and end users of research.

Results

Ninety‐three participants from 12 different countries responded. Three overarching themes emerged: ‘individual/clinical’, ‘systems/services’ and ‘human, behavioural and social’ elements of safe mental health transitions. Whilst there was a great focus on clinical elements from researchers and healthcare professionals, service users and carers considered safety in terms of human, behavioural and social elements of transitional safety (ie loneliness, emotional readiness for discharge) and systems/services (ie inter‐professional communication).

Discussion

Safety in mental health‐care transitions is perceived differently by service users and families compared to healthcare professionals and researchers. Traditional safety indicators for care transitions such as suicide, self‐harm and risk of adverse drug events are raised as important. However, service users and families in particular have a much wider perception of transitions safety.

Conclusion

Future quality and safety research and policy should consider including a service user voice and consider integration of psychosocial elements in discharge interventions.
Integration policy and refugees’ economic performance: Evidence from Sweden’s 2010 reform of the introduction programme
Authors: Qi Haodong , Irastorza Nahikari , Emilsson Henrik , Bevelander Pieter
Published: January 2021

In this paper, we investigate whether integration policy improves refugees’ economic performance, specifically examining the effects on refugees’ income of Sweden's 2010 reform of the introduction programme (or IP). We also evaluate how the reform effects vary depending on refugees’ gender and educational attainment. Our key finding shows a strong positive effect of the reform on refugees’ income, immediately after the completion of the IP. More importantly, this positive effect intensifies over time, with no signs of diminishing, which implies a longer‐term effect of the reform. Furthermore, the effects of the reform do not significantly vary between men and women or between the highly educated and the less‐educated, suggesting that the new Swedish IP benefits refugees to the same extent, regardless of their gender and educational attainment.
Placing the future: Onward migration, education and citizenship among Portuguese‐Bangladeshi in London
Authors: Mapril José
Published: January 2021

Based on a longitudinal ethnography with Bangladeshis in Lisbon and in London, this article unravels the ways my interlocutors perceive their onward migration projects to the UK. Their decision to migrate once again was intimately connected with the education of their children. This would not only make them fluent in English language, a global language of power and prestige according to many but would give them access to better opportunities in the labour market. Simultaneously, these new mobilities had a tremendous emotional/affective price and were seen by the parents as a sacrifice and a new beginning. This article argues that these new beginnings are not about the accumulation of diverse forms of capital per se but rather the creation of largerhorizon of expectationsbased on the redistribution logic ofrelatedness, kinship and domestic units; in sum, onward migration was a future‐making strategy in contexts of economic uncertainty.
Meta‐analysis of efficacy and safety of inhaled ciprofloxacin in non‐cystic fibrosis bronchiectasis patients
Authors: Wang Sumei , Zhang Aiping , Yao Xin
Published: January 2021

Background

No antibiotic therapies have been approved for reducing exacerbations and preventing disease progression in non‐cystic fibrosis bronchiectasis (NCFB) patients. Several recent clinical studies have investigated the feasibility of inhaled ciprofloxacin in NCFB, whereas the results were controversial.

Aim

No antibiotic therapies have been approved for reducing exacerbations and preventing disease progression in non‐cystic fibrosis bronchiectasis (NCFB) patients. Several recent clinical studies have investigated the feasibility of inhaled ciprofloxacin in NCFB, whereas the results were controversial. We conducted the present meta‐analysis to comprehensively evaluate the feasibility of inhalation of ciprofloxacin in NCFB.

Methods

Electrical databases Medline and Cochrane library were retrieved from inception through December 2019. Randomised controlled trials (RCT) comparing inhaled ciprofloxacin and placebo were selected. The primary outcomes were time to first exacerbation, frequency of exacerbations and the change in sputum Pseudomonas aeruginosa density.

Results

A total of five articles involving six RCT was finally included in the analysis. The time to first exacerbation was significantly prolonged by inhaled ciprofloxacin (hazard ratio: 0.72, 95% confidence interval (CI): 0.63–0.82), with low heterogeneity (I2 = 23%). Inhalation of ciprofloxacin significantly reduced frequency of exacerbations (risk ratio: 0.70, 95% CI: 0.61–0.79) and decreased density of sputum P. aeruginosa (weighted mean difference: −2.11 log10CFU/g, 95% CI: −2.96 to −1.27 log10CFU/g) compared with placebo. No significant between‐group differences in mortality, adverse events and discontinuation rate were observed. Further indirect treatment comparison showed no differences between the two types of inhaled ciprofloxacin in all outcomes of interest.

Conclusions

Ciprofloxacin inhalation treatment significantly prolonged the time to first exacerbation, reduced the frequency of exacerbations and decreased sputum P. aeruginosa density and was well tolerated. Ciprofloxacin inhalation is promising in the treatment of NCFB.
Attachment and joint attention in infants: The role of expectation
Authors: Mohammadzade Naghashan Neda , Mazaheri M.Ali , Gustafsson Erik , Sadeghi‐Firoozabadi Vahid , Zabihzadeh Abbas
Published: January 2021

Previous research highlighted the correlation between parent–infant's attachment quality and joint attention skills. However, the underlying mechanisms of this relationship are still unclear. The aim of this study was to assess whether it is by mediating the expectation component in Internal Working Models that the quality of attachment style can affect joint attention. At first, 12‐ to 20‐month‐old infants were classified into secure and insecure groups using the Strange Situation Procedure. On a following day, using a violation‐of‐expectation paradigm, infants were habituated to two joint attention videos. Finally, the mean looking time duration of secure and insecure infants were compared with each other between two “divergent attention” and “joint attention” videos. Infants looked longer for divergent attention videos suggesting they did have expectation regarding the appropriate response in triadic interactions. In line with our main hypothesis, secure infants, but not insecure ones, looked longer in the divergent attention situation when an attachment‐related context was present, revealing the possible mediating role of “expectations” in the correlation between attachment and joint attention.
Neuregulin‐1 alleviate oxidative stress and mitigate inflammation by suppressing NOX4 and NLRP3/caspase‐1 in myocardial ischaemia‐reperfusion injury
Authors: Wang Fuhua , Wang Huan , Liu Xuejing , Yu Haiyi , Huang Xiaomin , Huang Wei , Wang Guisong
Published: January 2021

Neuregulin‐1 (NRG‐1) is reported to be cardioprotective through the extracellular‐regulated protein kinase (ERK) 1/2 pathway in myocardial ischaemia‐reperfusion injury (MIRI). NOX4‐induced ROS activated NLRP3 inflammasome and exacerbates MIRI. This study aims to investigate whether NRG‐1 can suppress NOX4 by ERK1/2 and consequently inhibit the NLRP3/caspase‐1 signal in MIRI. The myocardial infarct size (IS) was measured by TTC‐Evans blue staining. Immunohistochemical staining, real‐time quantitative PCR (RT‐qPCR) and Western blotting were used for detection of the factors, such as NOX4, ERK1/2, NLRP3, caspase‐1 and IL‐1β .The IS in the NRG‐1 (3 μg/kg, intravenous) group was lower than that in the IR group. Immunohistochemical analysis revealed NRG‐1 decreased 4HNE and NOX4. The RT‐qPCR and Western blot analyses revealed that NRG‐1 mitigated the IR‐induced up‐regulation of NOX4 and ROS production. Compared with the IR group, the NRG‐1 group exhibited a higher level of P‐ERK1/2 and a lower level of NLRP3. In the Langendorff model, PD98059 inhibited ERK1/2 and up‐regulated the expression of NOX4, NLRP3, caspase‐1 and IL‐1β, which exacerbated oxidative stress and inflammation. In conclusion, NRG‐1 can reduce ROS production by inhibiting NOX4 through ERK1/2 and inhibit the NLRP3/caspase‐1 pathway to attenuate myocardial oxidative damage and inflammation in MIRI.
Dental software classification and dento‐facial interdisciplinary planning platform
Authors: Coachman Christian , Blatz Markus Bernhard , Bohner Lauren , Sesma Newton
Published: January 2021

Objective

Despite all advantages provided by the digital workflow, its application in clinical practice is still more focused on device manufacturing and clinical execution than on treatment planning and communication. The most challenging phases of treatment, comprehensive planning, diagnosis, risk assessment, and decision‐making, are still performed without significant assistance from digital technologies. This article proposes a new dental software classification based on the digital workflow timeline, considering the moment of patient's case acceptance as key in this classification, and presents the ideal software tools for each phase.

Clinical Considerations

The proposed classification will help clinicians and dental laboratories to choose the most appropriate software during the treatment planning phase and integrate virtual plans with other software platforms for digitally guided execution. A dento‐facial interdisciplinary planning platform virtually simulates interdisciplinary clinical procedures and assists in the decision‐making process.

Conclusions

The suggested classification assists professionals in different phases of the digital workflow and provides guidelines for improvement and development of digital technologies before treatment plan acceptance by the patient.

Clinical Significance

Three‐dimensional interdisciplinary simulations allow clinicians to visualize how each dental procedure influences further treatments. With this treatment planning approach, predictability of different procedures in restorative dentistry, orthodontics, implant dentistry, periodontal, and oral maxillofacial surgery is improved.
The esthetic biological contour concept for implant restoration emergence profile design
Authors: Gomez‐Meda Ramon , Esquivel Jonathan , Blatz Markus B.
Published: January 2021

Objective

Emergence profile design is important for stable peri‐implant tissues and esthetically pleasing results with dental implant restorations, influenced by factors, such as, implant position and surrounding soft tissues. Different aspects of the emergence profile have been described, but detailed explanations of the different zones and corresponding designs are missing. This article describes the esthetic biological contour concept (EBC), differentiating important areas of the emergence profile and recommending particular designs for those zones.

Overview

The EBC concept considers specific parameters for proper design of the emergence profile of implant‐supported restorations. Understanding the different zones of the emergence profile and their relation to factors like implant position, implant design, and soft tissue thickness is key. The suggested guidelines are geared toward providing more stable and esthetic results when restoring dental implants in the esthetic zone.

Conclusions

Each of the zones described in the EBC concept have a specific function in the design of the emergence profile. Understanding the importance and specific design features of the EBC zones facilitates esthetic and biologically sound treatment outcomes with interim and definitive implant restorations.

Clinical significance

Proper emergence profile design supports esthetic outcomes and provides favorable biological response to implant‐supported restorations.
Validation of Perceived Mental Fatigability Using the Pittsburgh Fatigability Scale
Authors: Renner Sharon W. , Bear Todd M. , Brown Patrick J. , Andersen Stacy L. , Cosentino Stephanie , Gmelin Theresa , Boudreau Robert M. , Cauley Jane A. , Qiao Yujia (Susanna) , Simonsick Eleanor M. , Glynn Nancy W.
Published: January 2021

Objectives

Establish reliability, concurrent and convergent validity of the Pittsburgh Fatigability Scale (PFS) Mental subscale.

Design

Cross‐sectional.

Setting

Older adults from two University of Pittsburgh registries, Baltimore Longitudinal Study of Aging (BLSA), and Long Life Family Study (LLFS).

Participants

PFS Mental subscale validation was conducted using three cohorts: (1) Development Sample (N = 664, 59.1% women, age 74.8 ± 6.4 years, PFS Mental scores 10.3 ± 9.1), (2) Validation Sample I—BLSA (N = 430, 51.9% women, age 74.5 ± 8.2 years, PFS Mental scores 9.4 ± 7.9), and (3) Validation Sample II—LLFS (N = 1,917, 54.5% women, age 72.2 ± 9.3 years, PFS Mental scores 7.5 ± 8.2).

Measurements

Development Sample, Validation Sample I—BLSA, and Validation Sample II—LLFS participants self‐administered the 10‐item Pittsburgh Fatigability Scale. Validation Sample II—LLFS completed cognition measures (Trail Making Tests A and B), depressive symptomatology (Center for Epidemiologic Studies—Depression Scale, CES‐D), and global fatigue from two CES‐D items.

Results

In the Development Sample and Validation Sample I—BLSA, confirmatory factor analysis showed all 10 items loaded on two factors: social and physical activities (fit indices: SRMSR = 0.064, RMSEA = 0.095, CFI = 0.91). PFS Mental scores had strong internal consistency (Cronbach's α = 0.85) and good test‐retest reliability (ICC = 0.78). Validation Sample II—LLFS PFS Mental scores demonstrated moderate concurrent and construct validity using Pearson (r) or Spearman (ρ) correlations against measures of cognition (Trail Making Tests A (r = 0.14) and B (r = 0.17) time), depressive symptoms (r = 0.31), and global fatigue (ρ = 0.21). Additionally, the PFS Mental subscale had strong convergent validity, discriminating according to established clinical or cognitive testing cut points, with differences in PFS Mental scores ranging from 3.9 to 7.6 points (all P < .001). All analyses were adjusted for family relatedness, field center, age, sex, and education.

Conclusions

The validated PFS Mental subscale may be used in clinical and research settings as a sensitive, one‐page self‐administered tool of perceived mental fatigability in older adults.
Psychotherapeutic processes associated with couple therapy discontinuance: An observational analysis using the rapid marital interaction coding system
Authors: D’Aniello Carissa , Anderson Shayne R. , Tambling Rachel R.
Published: January 2021

Premature discontinuation presents challenges to couple clients and therapists alike. Although couple therapy has demonstrated efficacy and effectiveness, little is known about the mechanisms that contribute to couple therapy completion. This study presents the results of an observational inquiry into the psychotherapeutic processes associated with treatment discontinuance using clinical data. Using observational coding of the Rapid Marital Interaction Coding System (RMICS) researchers sought to examine differences in in‐session interactions between couple members in a matched sample of therapy continuers and discontinuers. Results indicate that specifically for female partners, the absence of positive interactions is linked to therapy discontinuation. Clinical implications of these findings are presented and discussed.
Experimental test of the geometric model of image formation in bright‐field microscopy
Authors: Clements RJ , Davidson M , Model MA
Published: January 2021

In the geometric optics approximation, an image formed by an objective lens replicates the distribution of intensity at the front focal plane of the objective. Although this fact represents a fundamental optical principle, its application to analysis of bright‐field microscopic images was developed only recently and has not been tested experimentally. In this paper, we applied simple ray tracing to compute an image of a glass cylinder at various positions of the objective and to compare it to the experiment. We obtained a close match between theory and observation, except for a slight underestimation of the intensity in the middle part of the cylinder. The likely reason for this minor difference was constructive interference due to lens‐like properties of a cylinder, which could not be accounted for by geometric approximation. We expect that such artefacts would be negligible in imaging of live cells, and the geometric approach would successfully complement the existing quantitative phase methods.
The emerging role of the advanced practice epilepsy nurse: A comparative study between two countries
Authors: Manzanares Isabel , Sevilla Guerra Sonia , Peña‐Ceballos Javier , Carreño Mar , Palanca María , Lombraña María , Conde‐Blanco Estefanía , Centeno María , Donaire Antonio , Gil‐Lopez Francisco , Khawaja Mariam , López Poyato Mireia , Zabalegui Adelaida
Published: January 2021

Aims and objectives

The aim of the study was to compare advanced practice in epilepsy nurses in Spain and United Kingdom, identifying differences in the domains of standard advanced practice.

Background

Europe has recently faced the challenge of providing high‐quality care for patients with epilepsy, a disease that generates many health demands. In some countries, such as the United Kingdom, advanced practice nursing is well established and could serve as a guide for implantation in countries where it is still in development, as is the case of Spain.

Design

A multicentre cross‐sectional descriptive cohort study compared differences in the roles of advanced practice nurses in Spain and the United Kingdom.

Methods

The Advanced Practice Role Delineation Tool and its validated Spanish version were administered using an online questionnaire in a cohort of advanced practice epilepsy nurses in both countries. A convenience sample was recruited between January to December 2019. The study complied with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist.

Results

Most United Kingdom nurses in our sample came from community environments, in contrast to Spanish nurses who worked in hospital. All domains analysed in the survey had significantly higher scores in the United Kingdom than in the Spanish cohort, especially in the research and leadership domains.

Conclusions

The advanced practice role in Spain is underdeveloped compared with the United Kingdom. Differences in the settings of advanced roles in epilepsy nurses may be explained by greater community practice in the United Kingdom and differences in organisational and health systems.

Relevance to clinical practice

Our study showed the need to implement specific policies to develop advance practice nurse roles in Spain to improve the quality of care of patients with epilepsy.
Translation and Validation of the Japanese Version of the Trait and State Post‐Event Processing Inventory
Authors: Maeda Shunta , Sato Tomoya , Kanai Yoshihiro , Blackie Rebecca A. , Kocovski Nancy L.
Published: January 2021

In this study, we translated the Trait and State versions of the Post‐Event Processing Inventory (PEPI) into Japanese and examined their psychometric properties. One thousand participants, comprising three subsamples, completed the questionnaires. Confirmatory factor analyses supported a bi‐factor model, comprising one general factor and three theoretically derived subfactors (“Frequency,” “Self‐judgment,” and “Intensity”), for the State and Trait versions of the scale. However, both versions were essentially unidimensional, and scoring based on subfactors lacked support. Additionally, we found preliminary evidence for the test–retest reliability; internal consistency; and concurrent, convergent, divergent, incremental, and predictive validity of both versions. Furthermore, participants with self‐reported diagnoses of social anxiety disorder exhibited higher scores on both the PEPI‐Trait and PEPI‐State than healthy controls. Our findings suggest that the Japanese versions of the PEPI‐Trait and PEPI‐State may become useful alternatives to existing measures of post‐event processing in Japan.
Characterization of the intestinal mucosal proteome in cats with inflammatory bowel disease and alimentary small cell lymphoma
Authors: Marsilio Sina , Dröes Floris C. , Dangott Lawrence , Chow Betty , Hill Steve , Ackermann Mark , Estep J. Scott , Lidbury Jonathan A. , Suchodolski Jan S. , Steiner Jörg M.
Published: January 2021

Background

Current tests for diagnosis and differentiation of lymphoplasmacytic enteritis (LPE) and small cell lymphoma (SCL) in cats are expensive, invasive, and lack specificity. The identification of less invasive, more reliable biomarkers would facilitate diagnosis.

Objectives

To characterize the mucosal proteome in endoscopically obtained, small intestinal tissue biopsy specimens. We hypothesized that differentially expressed proteins could be identified and serve as biomarker candidates for the differentiation of LPE and SCL in cats.

Animals

Six healthy control cats, 6 cats with LPE, and 8 cats with SCL.

Methods

The mucosal proteome was analyzed using 2‐dimensional fluorescence difference gel electrophoresis (2D DIGE) and nanoflow liquid chromatography tandem mass spectrometry. For 5 proteins, results were verified by Western blot analysis.

Results

A total of 2349 spots were identified, of which 9 were differentially expressed with a ≥2‐fold change between healthy cats and cats with LPE and SCL (.01 < P < .001). Eight of these 9 spots were also differentially expressed between cats with LPE and cats with SCL (P .001 < P < .04). However, Western blot analysis for malate dehydrogenase‐1, malate dehydrogenase‐2, apolipoprotein, annexin IV, and annexin V did not confirm significant differential protein expression for any of the 5 proteins assessed.

Conclusions and Clinical Importance

Two‐D DIGE did not identify potential biomarker candidates in the intestinal mucosa of cats with LPE and SCL. Future studies should focus on different techniques to identify biomarker candidates for cats with chronic enteropathies (CE).
Stratification regimes and thermodynamic modelling of a subtropical African reservoir
Authors: Nhiwatiwa Tamuka , Mungenge Chipo , Mhlanga Lindah , Dalu Tatenda
Published: January 2021

The stratification of a lentic water system is an important factor regulating its biotic activities and processes. The present study investigated changes in temperature and oxygen stratification regimes in Mazvikadei Reservoir 27 years after the first study was conducted during its filling phase. The FLake‐Global model was also tested as a predictive tool for the first time to analyse annual limnological trends in a subtropical reservoir. The lake‐modelling tool FLake‐Global enables an instantaneous estimation of the seasonal cycle of temperature and mixing conditions in shallow freshwater lakes around the world. The results of the present study illustrate that the reservoir was weakly stratified, with the overall thermal stratification patterns somewhat similar to those recorded during the filling phase (1992). The oxygen stratification patterns observed in the present study correspond well to those of thermal stratification. The depth‐integrated oxygen profiles for both the deep and shallow sampling sites exhibited the same pattern, with higher concentrations from July to September. The water column was well oxygenated, indicating the reservoir has matured since its filling phase in 1992, when there was significant hypolimnetic deoxygenation. The FLake‐Global model exhibited good results in predicting annual trends, with the results also indicating no differences in stratification levels in the reservoir for the current and Masundire (1992) filling phase studies. The model predicted lower surface and bottom temperatures, however, compared to those measured in the reservoir. There was lowering of the mixed layer depth from the hot‐wet (November–April) months through the cool‐dry (May–August) season. Latent heat fluxes agreed with the net longwave (LW) predictions for Mazvikadei Reservoir, which exhibited an overall net cooling effect. The stratification has not changed significantly since the previous study in 1988. The FLake‐Global model proved a useful predictive tool when tested in a subtropical system.
Esophageal pH increments associated with post‐reflux swallow‐induced peristaltic waves show the occurrence and relevance of esophago‐salivary reflex in clinical setting
Authors: Frazzoni Marzio , Frazzoni Leonardo , Ribolsi Mentore , De Bortoli Nicola , Tolone Salvatore , Conigliaro Rita , Arsiè Elena , Penagini Roberto , Cicala Michele , Savarino Edoardo
Published: January 2021

Background

Following acid perfusion, esophageal pH is restored by swallowed bicarbonate‐containing saliva secreted in response to a vagal esophago‐salivary reflex. At impedance‐pH monitoring, the post‐reflux swallow‐induced peristaltic wave (PSPW) index puts into relationship timely post‐reflux swallows with the number of reflux events: Low values typify reflux‐related heartburn (RRH) and lack of on‐therapy improvement characterizes proton pump inhibitor (PPI) failure. Considerable esophageal pH increments associated with PSPWs could demonstrate the occurrence of esophago‐salivary reflex in clinical setting, while its relevance could be shown by lower esophageal pH increments in PPI‐refractory RRH.

Methods

Prospective multicenter study in patients with PPI‐refractory or PPI‐responsive RRH evaluated with off‐PPI impedance‐pH monitoring. Increments in pH associated with PSPWs were measured and the mean calculated to obtain the PSPW‐associated ∆pH.

Key Results

The mean PSPW‐associated ∆pH in 294 RRH patients was 1.2 ± 0.7 and was lower in 137 PPI‐refractory (1.0 ± 0.6) than in 157 PPI‐responsive (1.5 ± 0.6) cases (p < 0.0001). Lower PSPW‐associated ∆pH was independently related to PPI failure at multivariable logistic regression analysis (OR 0.16, 95% CI 0.09–0.26). At ROC analysis, comparing PPI‐refractory to PPI‐responsive cases the AUC for PSPW‐associated ∆pH was 0.76 (95% CI 0.71–0.82), the best cutoff value being 1.2.

Conclusions and Inferences

Considerable PSPW‐associated pH increments demonstrate the occurrence of esophago‐salivary reflex in clinical setting. Lower increments in PPI‐refractory RRH cases show the clinical relevance of esophago‐salivary reflex, confirming that PSPW represents a defense mechanism against reflux. PSPW‐associated ∆pH can efficiently predict PPI response in patients undergoing off‐therapy impedance‐pH monitoring.