bluuebunny/crossref_metadata_2025 huggingface dataset:
Recruitment of control and representational components of the semantic system during successful and unsuccessful access to complex factual knowledge
Authors: Ubaldi Silvia , Rabin Giuseppe , Fairhall Scott L.
Published: June 2021

Our ability to effectively retrieve complex semantic knowledge meaningfully impacts our daily lives, yet the neural processes that underly successful access and transient failures in access remain only partially understood. In this fMRI study, we contrast activation during successful semantic access, unsuccessful semantic access due to transient access-failures (i.e., ‘tip-of-the-tongue’, ‘feeling-of-knowing’), and trials where the semantic knowledge was not possessed. Twenty-four human participants (14 female) were presented 240 trivia-based questions relating to person, place, object or scholastic knowledge-domains. Analyses of the recall event indicated a relatively greater role of a dorsomedial section of the prefrontal cortex in unsuccessful semantic access and relatively greater recruitment of the pars orbitalis of the inferior frontal gyrus in successful access. Successful access was also associated with increased activation in knowledge-domain selective areas. Generally, knowledge-domain selective areas showed increased responses for both preferred and non-preferred stimulus classes. The exception was place-selective regions (PPA, TOS and RSC), which were recruited during unsuccessful access attempts for all stimulus domains. Collectively, these results suggest that prefrontal semantic control systems and classical spatial-knowledge selective regions work together to locate relevant information and that access to complex knowledge results in a broad activation of semantic representation extending to regions selective for other knowledge domains.
A Unifying Mechanism Governing Inter-Brain Neural Relationship During Social Interactions
Authors: Zhang Wujie , Yartsev Michael M.
Published: June 2021

A key goal of social neuroscience is to understand the relationship between the neural activity of socially interacting individuals. Decades of research have focused on a single aspect of that relationship: the similarity in neural activity across brains. Here we instead asked how neural activity differs between brains, and how that difference evolves alongside activity patterns shared between brains. Applying this framework to pairs of bats engaged in spontaneous social interactions revealed two complementary phenomena characterizing the inter-brain neural relationship: fast “inter-brain catch-up” unfolding in parallel with slow activity covariation across brains. A model reproduced these observations, generated multiple predictions that we confirmed using experimental data, and provided testable hypotheses for studying the inter-brain relationship in larger social groups. Together, the data and model suggest a parsimonious computational mechanism—opposite feedback to neural activity components reflecting inter-brain difference and similarity—that unifies diverse aspects of the inter-brain neural relationship.
Amyloid beta oligomers modulate neuronal autophagy through the primary cilium
Authors: Pampliega Olatz , Soria Federico N. , Pineda-Ramírez Narayana , Bezard Erwan
Published: June 2021

The major neurodegenerative diseases, like Alzheimer’s disease (AD), accumulate neuropathogenic proteins that compromise autophagic function. In AD, autophagy contributes to intracellular APP processing and amyloid beta (Aβ) generation by mutant presenilin-1 (PS1). However, how extracellular soluble Aβ oligomers (Aβo) impact intracellular autophagy is not well understood. The primary cilium (PC), a signaling organelle on the surface of mature neurons and glia, is able to bind Aβ. Since PC signaling pathways knowingly modify autophagy in non-brain cells, we here investigated the role of neuronal PC in the modulation of autophagy during acute extracellular Aβo overload. Our results show that, in vivo, recombinant Aβo require the presence of neuronal PC to modulate early autophagy and to induce the accumulation of autophagic vacuoles in an age-dependent manner. We show that activated Akt mediates these effects in an age-dependent manner, and that ciliary p75NTR receptor is required to block autophagy by Aβo. These findings demonstrate that neuronal PC in the adult brain participates in the deleterious effects mediated by soluble Aβo. The PC should therefore be considered as a target organelle to modulate autophagy for the treatment of neurodegenerative diseases.

Highlights

Aβo requires the neuronal PC to impair learning in young and old mice.

Autophagy in whole hippocampus differs from autophagy response in hippocampal neurons.

Aβo induce autophagolysosome accumulation through primary cilia- and age-dependent Akt phosphorylation.
Twists and turns from “tumor in tumor” profiling: surveillance of chronic lymphocytic leukemia (CLL) leads to detection of a lung adenocarcinoma, whose genomic characterization alters the original hematologic diagnosis
Authors: Terraf Panieh , Sholl Lynette M. , Davids Matthew S. , Awad Mark M. , Garcia Elizabeth P. , MacConaill Laura E. , Dal Cin Paola , Kim Annette , Lindeman Neal I. , Stachler Matthew , Hwang David H. , Dubuc Adrian M.
Published: June 2021

Comprehensive characterization of somatic genomic alterations has led to fundamental shifts in our understanding of tumor biology. In clinical practice, these studies can lead to modifications of diagnosis and/or specific treatment implications, fulfilling the promise of personalized medicine. Herein, we describe a 78-yr-old woman under surveillance for long-standing untreated chronic lymphocytic leukemia (CLL). Molecular studies from a peripheral blood specimen revealed a TP53 p.V157F mutation, whereas karyotype and fluorescence in situ hybridization (FISH) identified a 17p deletion, trisomy 12, and no evidence of IGH-CCND1 rearrangement. Positron emission tomography-computed tomography scan identified multistation intra-abdominal lymphadenopathy and a pulmonary nodule, and subsequent pulmonary wedge resection confirmed the presence of a concurrent lung adenocarcinoma. Targeted next-generation sequencing of the lung tumor identified an EGFR in-frame exon 19 deletion, two TP53 mutations (p.P152Q, p.V157F), and, unexpectedly, a IGH-CCND1 rearrangement. Follow-up immunohistochemistry (IHC) studies demonstrated a cyclin D1–positive lymphoid aggregate within the lung adenocarcinoma. The presence of the TP53 p.V157F mutation in the lung resection, detection of an IGH-CCND1 rearrangement, and cyclin D1 positivity by IHC led to revision of the patient's hematologic diagnosis and confirmed the extranodal presence of mantle cell lymphoma within the lung mass, thus representing a “tumor in tumor.” Manual review of the sequencing data suggested the IGH-CCND1 rearrangement occurred via an insertional event, whose size precluded detection by original FISH studies. Thus, routine imaging for this patient's known hematologic malignancy led to detection of an unexpected solid tumor, whose subsequent precision medicine studies in the solid tumor redefined the original hematological diagnosis.
The Use of Xenopus for Cell Biology Applications
Authors: Philpott Anna
Published: June 2021

Problems of cell biology and the molecular controls underpinning them have been studied in the remarkably versatile Xenopus systems for many years. This versatility is showcased in several accompanying protocols, which are introduced here. One protocol demonstrates how the Xenopus embryonic ectoderm can be used to study the effects of mechanical cell deformation; another illustrates how the developing eye can be used as a platform for determining cell-cycle length. Two protocols show how extracts from Xenopus embryos can be exploited to characterize the behavior of specific intracellular proteins—specifically, to determine protein phosphorylation status and the ability to bind to chromatin. Finally, because specific antibodies to Xenopus proteins are pivotal reagents for cell biology and biochemistry applications, four protocols describing how to generate, purify, and assay the specificity of antibodies raised against Xenopus proteins are included in hopes of stimulating the expansion of these critical resources across the Xenopus community.
The fast multi-frame X-ray diffraction detector at the Dynamic Compression Sector
Authors: Sinclair N. W. , Turneaure S. J. , Wang Y. , Zimmerman K. , Gupta Y. M.
Published: June 2021

A multi-frame, X-ray diffraction (XRD) detector system has been developed for use in time-resolved XRD measurements during single-event experiments at the Dynamic Compression Sector (DCS) at the Advanced Photon Source (APS). The system is capable of collecting four sequential XRD patterns separated by 153 ns, the period of the APS storage ring in the 24-bunch mode. This capability allows an examination of the temporal evolution of material dynamics in single-event experiments, such as plate impact experiments, explosive detonations, and split-Hopkinson pressure bar experiments. This system is available for all user experiments at the DCS. Here, the system description and measured performance parameters (detective quantum efficiency, spatial and temporal resolution, and dynamic range) are presented along with procedures for synchronization and image post-processing.
Neutron structures of Leishmania mexicana triosephosphate isomerase in complex with reaction-intermediate mimics shed light on the proton-shuttling steps
Authors: Kelpšas Vinardas , Caldararu Octav , Blakeley Matthew P. , Coquelle Nicolas , Wierenga Rikkert K. , Ryde Ulf , von Wachenfeldt Claes , Oksanen Esko
Published: June 2021

Triosephosphate isomerase (TIM) is a key enzyme in glycolysis that catalyses the interconversion of glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. This simple reaction involves the shuttling of protons mediated by protolysable side chains. The catalytic power of TIM is thought to stem from its ability to facilitate the deprotonation of a carbon next to a carbonyl group to generate an enediolate intermediate. The enediolate intermediate is believed to be mimicked by the inhibitor 2-phosphoglycolate (PGA) and the subsequent enediol intermediate by phosphoglycolohydroxamate (PGH). Here, neutron structures of Leishmania mexicana TIM have been determined with both inhibitors, and joint neutron/X-ray refinement followed by quantum refinement has been performed. The structures show that in the PGA complex the postulated general base Glu167 is protonated, while in the PGH complex it remains deprotonated. The deuteron is clearly localized on Glu167 in the PGA–TIM structure, suggesting an asymmetric hydrogen bond instead of a low-barrier hydrogen bond. The full picture of the active-site protonation states allowed an investigation of the reaction mechanism using density-functional theory calculations.
Robust adaptive preview control design for autonomous carrier landing of F/A-18 aircraft
Authors: Bhatia Ajeet Kumar , Ju Jiang , Ziyang Zhen , Ahmed Nigar , Rohra Avinash , Waqar Muhammad
Published: June 2021

Purpose

The purpose of this paper is to design an innovative autonomous carrier landing system (ACLS) using novel robust adaptive preview control (RAPC) method, which can assure safe and successful autonomous carrier landing under the influence of airwake disturbance and irregular deck motion. To design a deck motion predictor based on an unscented Kalman filter (UKF), which predicts the touchdown point, very precisely.

Design/methodology/approach

An ACLS is comprising a UKF based deck motion predictor, a previewable glide path module and a control system. The previewable information is augmented with the system and then latitude and longitudinal controllers are designed based on the preview control scheme, in which the robust adaptive feedback and feedforward gain’s laws are obtained through Lyapunov stability theorem and linear matrix inequality approach, guarantying the closed-loop system’s asymptotic stability.

Findings

The autonomous carrier landing problem is solved by proposing robust ACLS, which is validated through numerical simulation in presence of sea disturbance and time-varying external disturbances.

Practical implications

The ACLS is designed considering the practical aspects of the application, presenting superior performance with extended robustness.

Originality/value

The novel RAPC, relative motion-based guidance system and deck motion compensation mechanism are developed and presented, never been implemented for autonomous carrier landing operations.
Mapping the urban environment using real-time physiological monitoring
Authors: Dritsa Dimitra , Biloria Nimish
Published: June 2021

Purpose

This paper presents a critical review of studies which map the urban environment using continuous physiological data collection. A conceptual model is consequently presented for mitigating urban stress at the city and the user level.

Design/methodology/approach

The study reviews relevant publications, examining the tools used for data collection and the methods used for data analysis and data fusion. The relationship between urban features and physiological responses is also examined.

Findings

The review showed that the continuous monitoring of physiological data in the urban environment can be used for location-aware stress detection and urban emotion mapping. The combination of physiological and contextual data helps researchers understand how the urban environment affects the human body. The review indicated a relationship between some urban features (green, land use, traffic, isovist parameters) and physiological responses, though more research is needed to solidify the existence of the identified links. The review also identified many theoretical, methodological and practical issues which hinder further research in this area.

Originality/value

While there is large potential in this field, there has been no review of studies which map continuously physiological data in the urban environment. This study covers this gap and introduces a novel conceptual model for mitigating urban stress.
Project scheduling and performance prediction: a fuzzy-Bayesian network approach
Authors: Rezakhani Pejman
Published: June 2021

Purpose

Despite the extensive research in project risk management and availability of several techniques and tools, quantifying uncertainty in project schedules remains a challenge. Current risk analysis models suffer from several shortcomings that need to be addressed to provide more reliable and valid schedules. This paper aims to present a dynamic decision support system with the purpose of providing project managers with necessary tool for making real-time informed decisions.

Design/methodology/approach

The proposed approach incorporates the widely accepted critical path method (CPM) calculations in a Bayesian network (BN). BN is employed to conduct inferencing and causal analysis and provide probabilistic results, which can improve the decision-making process. Time parameters of each activity in the CPM network is modeled by a set of simulation nodes in the BN. Prior probability distribution of activities duration is extracted from experts using a fuzzy analytical solution.

Findings

The model proposed in this paper is able to address some key outstanding issues of current project scheduling techniques through: (1) modeling the causality among different sources of schedule uncertainty, (2) minimizing uncertainty in experts' evaluations, (3) assessing effects of unknown risk factors and (4) using actual activity data for learning the behavior of project and predicting crew productivity.

Originality/value

The purposed methodology provides a framework for the new generation of project schedule analysis tools that are better informed by available knowledge and data, and hence, more reliable and useful.
Changes of base-year and Indian GDP growth: an agnostic look
Authors: Chakrabarty Manisha , Ray Partha
Published: June 2021

Purpose

World over, change of base year in the gross domestic product (GDP) is a standard practice of GDP estimation. However, unless a consistent series of GDP is released with respect to the new base for the earlier period, the existence of multiple growth rates creates problems for applied researchers, policymakers and the general public alike. Faced with such a menu of GDP series researchers often try to interpolate a consistent series of GDP. The main purpose of this paper is to analyses the nature of the data generating process of such multiple interpolated series of quarterly growth rates and tries to discern the consistency of such processes.

Design/methodology/approach

The present paper tries to look into the statistical implications and complications of such interpolated quarterly GDP/growth series in India in terms of three series of GDP, namely, with 1999–2000, 2004–2005 and 2011–2012 as its bases.

Findings

The analysis reveals that as a result of a change of base year, the nature of the data generating process of the old and new GDP series could undergo changes and experience different breakpoints. While all these conclusions seem to be valid for GDP growth at quarterly intervals, taking the data at annual frequency is less problematic.

Practical implications

The observation suggests that in most applied work, researchers may not have the luxury of only working with annual data and certain consistency checks will be necessary to check the veracity of the results based on quarterly data with those based on annual data. Second, moving forward it may be useful for the Authorities to make a transition to a chain-based linking method rather than fixed time-period-based bases as is currently done.

Originality/value

The analysis of Indian GDP in this paper is, perhaps, indicative of the fact that usage of quarterly GDP data is to be handled with caution and it is preferable that any serious empirical analysis uses annual GDP data whenever it is available/feasible. The comparison of GDP growth rates at different frequencies and examining the true nature of the process are quite unique in their contribution towards empirical macroeconomic research.
Which search queries are more powerful in tourism demand forecasting: searches via mobile device or PC?
Authors: Hu Mingming , Xiao Mengqing , Li Hengyun
Published: June 2021

Purpose

While relevant research has considered aggregated data from mobile devices and personal computers (PCs), tourists’ search patterns on mobile devices and PCs differ significantly. This study aims to explore whether decomposing aggregated search queries based on the terminals from which these queries are generated can enhance tourism demand forecasting.

Design/methodology/approach

Mount Siguniang, a national geopark in China, is taken as a case study in this paper; another case, Kulangsu in China, is used as the robustness check. The authors decomposed the total Baidu search volume into searches from mobile devices and PCs. Weekly rolling forecasts were used to test the roles of decomposed and aggregated search queries in tourism demand forecasting.

Findings

Search queries generated from PCs can greatly improve forecasting performance compared to those from mobile devices and to aggregate search volumes from both terminals. Models incorporating search queries generated via multiple terminals did not necessarily outperform those incorporating search queries generated via a single type of terminal.

Practical implications

Major players in the tourism industry, including hotels, tourist attractions and airlines, can benefit from identifying effective search terminals to forecast tourism demand. Industry managers can also leverage search indices generated through effective terminals for more accurate demand forecasting, which can in turn inform strategic decision-making and operations management.

Originality/value

This study represents one of the earliest attempts to apply decomposed search query data generated via different terminals in tourism demand forecasting. It also enriches the literature on tourism demand forecasting using search engine data.
Development of a child-rearing promotion of sexual abstinence scale (CPSAS) in Thai female adolescents at two Thai universities
Authors: Wannarit La-Ongdao , Chaiyawat Waraporn , Yunibhand Jintana
Published: June 2021

Purpose

Child-rearing promoting sexual abstinence has strongly predicted sexual abstinence in Thai female adolescents, and it requires a valid and reliable measurement. However, no such instrument exists. This study aimed to develop a child-rearing promotion of sexual abstinence scale (CPSAS) and assess its validity and reliability.

Design/methodology/approach

The scale development consisted of two phases; scale construction and psychometric testing. Phase I included item generation extracted from a literature review and existing measurements. Items were reviewed by five-panel experts and were then selected by considering an inter-item correlation, corrected item-total correlation, factor loading and communality value from the exploratory factor analysis (n = 299). Phase II involved confirmatory factor analysis (CFA) for construct validity and scale reliability (n = 300).

Findings

The CPSAS, first, contained 25 items with four dimensions; assuring daughter to recognize parental love, teaching daughter sexual abstinence, convincing daughter to recognize parent's expectations of sexual abstinence and encouraging daughter sexual abstinence. Two items were then deleted after the experts reviewed, and six items were removed after item analysis. The CPSAS finally contained 17 items with a 4-point Likert scale. Psychometric testing provided acceptable results. CFA reported the fit indices; χ2 = 98.06 p = 0.083, df = 80, χ2/df ratio = 1.220, CFI = 0.996, TLI = 0.992, RMSEA = 0.027 and SRMR = 0.030. The standardized factor loadings were 0.499 to 0.908 (p < 0.05). The S-CVI was 0.96, and Cronbach's alpha coefficient was 0.93.

Originality/value

The CPSAS is a reliable and valid instrument for evaluating child-rearing promoting sexual abstinence in Thai female adolescents.
The value in doing good: perspective from the Indian manufacturing sector
Authors: Jha Ankur
Published: June 2021

Purpose

This study aims to identity the component of corporate social responsibility (CSR) and examine its role in industrial brand equity creation. This study examines the path via value proposition derived by industrial buyers through social performance of suppliers.

Design/methodology/approach

Drawing from the means-end chain paradigm, this study develops a conceptual model illustrating consequences of CSR perception. The model is empirically tested with 404 purchasing managers of manufacturing firms in India.

Findings

This study finds an empirical link between the CSR perception among industry buyers with consumption value and subsequent impact on industrial brand equity of suppliers. This study addresses the conundrum related to the role of social performance of supplier in purchase decision.

Research limitations/implications

The brand preference decision among industrial buyers has majorly focused on price quality conundrum. The supplier groups emphasis on providing the value to customer group across the price quality continuum. However, with growing importance of social accountability, the social performance of suppliers has become integral to decision-making for decision-makers. The supplier groups are expected to create offering with amalgamation of social responsiveness.

Originality/value

To the best of the author’s knowledge, this study is the first to demonstrate the impact of CSR perception on value proposition for industrial buyers. Multiple theories have advanced the importance of value in brand equity; the empirical study is probably first in the context.
Teaching for international mindedness in Chicago Public Schools International Baccalaureate humanities classes
Authors: Tocci Charles , Ryan Ann Marie , Ensminger David C. , Rismiati Catur , Moughania Ahlam Bazzi
Published: June 2021

Purpose

The International Baccalaureate (IB) programme centers on developing students' international mindedness. Central to this effort is the programme's “Learner Profile,” which details ten attributes that teachers seek to cultivate through classroom instruction. This article reports on the ways that middle grades and high school social studies and English teachers in Chicago Public Schools' (CPS) IB programmes are attempting to implement the Learner Profile as part of their classroom practice to support students' international mindedness.

Design/methodology/approach

The project was carried out as a two phase, sequential mixed-methods design. Phase I entailed a survey of IB teachers and programme coordinators across CPS to assess the incorporation of the Learner Profile into instruction. Phase II consisted of mixed-methods case studies of CPS IB programmes selected partially on Phase I data analysis.

Findings

We find that while teachers express high levels of familiarity with the Learner Profile attributes and confidence in incorporating them into practice, we find wide variation in the actual implementation. Taken as a whole, we find CPS programmes take divergent approaches to incorporating the Learner Profile based on differences in understanding of the attributes and its purposes as well as key organizational facets related to implementation.

Originality/value

Ultimately, we argue that the wide variation and lack of explicit incorporation of the Learner Profile into classrooms is related in large part to the broad, indistinct nature of “international mindedness” as a concept. The programme would benefit from creating more space for teacher and students to critique the concept, especially those working from non-Western traditions.
Artificial intelligence and imaging biomarkers for prostate radiation therapy during and after treatment
Authors: Wang Yu‐Feng , Tadimalla Sirisha , Hayden Amy J. , Holloway Lois , Haworth Annette
Published: June 2021

Magnetic resonance imaging (MRI) is increasingly used in the management of prostate cancer (PCa). Quantitative MRI (qMRI) parameters, derived from multi‐parametric MRI, provide indirect measures of tumour characteristics such as cellularity, angiogenesis and hypoxia. Using Artificial Intelligence (AI), relevant information and patterns can be efficiently identified in these complex data to develop quantitative imaging biomarkers (QIBs) of tumour function and biology. Such QIBs have already demonstrated potential in the diagnosis and staging of PCa. In this review, we explore the role of these QIBs in monitoring treatment response during and after PCa radiotherapy (RT). Recurrence of PCa after RT is not uncommon, and early detection prior to development of metastases provides an opportunity for salvage treatments with curative intent. However, the current method of monitoring treatment response using prostate‐specific antigen levels lacks specificity. QIBs, derived from qMRI and developed using AI techniques, can be used to monitor biological changes post‐RT providing the potential for accurate and early diagnosis of recurrent disease.
Coronary heart disease in mothers and fathers of adult children with alcohol use disorders
Authors: Calling Susanna , Ohlsson Henrik , Sundquist Jan , Kendler Kenneth S. , Sundquist Kristina
Published: June 2021

Background and aim

Having a family member with an alcohol use disorder (AUD) may negatively affect a person's health. Our aim was to study the long‐term risk of coronary heart disease (CHD) in parents who have an offspring with AUD.

Design

Cohort study with Cox regression models and co‐sibling analyses.

Setting

Sweden.

Participants

From population registers, we selected all parent‐offspring pairs in which the parent was born in Sweden between 1945 and 1965.

Measurements

Baseline was set when the offspring was 15 years old and AUD was assessed from medical and criminal registers. The parents were followed for CHD during a mean follow‐up of 18 years. Hazard ratios (HRs) in mothers and fathers were calculated and adjusted for potential confounders (year of birth, age at childbirth, sex of the child, parent' AUD, educational level, and marital status).

Findings

In mothers, the adjusted HR for CHD was 1.24 (95% CI = 1.19–1.28) in relation to having a child with AUD. In fathers, the HR for CHD was lower than in mothers but still increased; the adjusted HR was 1.08 (95% CI = 1.05–1.12). In the co‐sibling analyses, the HRs for mothers were similar to the HRs estimated from the population‐based sample, but in fathers the association did not remain significant (HR = 0.98 [0.90–1.06]).

Conclusions

In Sweden, there appears to be an association between having an offspring with alcohol use disorder and increased risk of developing coronary heart disease. For fathers, the association did not remain in co‐sibling analyses.
Effects of various thicknesses and levels of mineral trioxide aggregate coronal plugs on nanoleakage and fracture resistance in revascularization: An in vitro study
Authors: Gunal Esin , Bezgin Tugba , Ocak Mert , Bilecenoglu Burak
Published: June 2021

The aim of this study was to evaluate the effects of mineral trioxide aggregate (MTA) applied at varying levels and thickness in the cervical region of the root on the leakage and fracture resistance of the simulated immature teeth. 3 study groups (n = 16) (Group 1: 2 mm MTA, Group 2: 4 mm MTA, Group 3: 2 mm MTA+2 mm RMGIC below cementoenamel junction) and 2 control groups (Group 4: Complete canal obturation, Group 5: No coronal plug) were used for the study. Nanoleakage was measured using a micro‐computed tomography system. For the fracture resistance test, a universal testing machine was used. The amount of silver nitrate penetration decreased while MTA thicknesses increased (P < 0.001). However, the placement of MTA as a thicker layer did not make any additional contribution on the fracture resistance (P > 0.05). The 4‐mm coronal MTA plug can be suggested in RETs for its superior sealing and reinforcement abilities.
The effect of intracanal medication variations on microhardness of simulated immature root dentin
Authors: Serdar Eymirli Pınar , Eymirli Ayhan , Uzunoğlu Özyürek Emel
Published: June 2021

The effect of different medicaments and irrigation solutions on root dentin microhardness (MH) was evaluated depending on time. After initial measurements, MH of 60 maxillary incisors (n = 15 per group) was measured after 3 steps: irrigation with 2.5% sodium hypochlorite, exposure to medicaments [triple antibiotic (TAP) or calcium hydroxide (CH) pastes, 1 week or 1 month)] and final irrigation [20 mL of 17% EDTA or 20 mL 1% phytic acid (PA)]. The percentage of MH reduction was calculated. Data were analysed statistically atP < 0.05. Treatments caused a significant decrease in MH values compared to baseline and pre‐measurements (P < 0.05). TAP significantly reduced the MH values of the samples over time (P < 0.05). Removal of TAP after 1 month with PA resulted in a significant reduction in MH compared to removing TAP after 1 week and CH removing after 1 month (P < 0.05). Considering the chemical preparation steps, the most hazardous effect on MH was observed after the first irrigation.
Patient‐reported fatigue refines prognosis in higher‐risk myelodysplastic syndromes (MDS): a MDS‐CAN study
Authors: Amitai Irina , Geddes Michelle , Zhu Nancy , Keating Mary‐Margaret , Sabloff Mitchell , Christou Grace , Leber Brian , Khalaf Dina , Leitch Heather A. , St‐Hilaire Eve , Finn Nicholas , Shamy April , Yee Karen , Storring John , Nevill Thomas , Delage Robert , Elemary Mohamed , Banerji Versha , Chodirker Lisa , Mozessohn Lee , Parmentier Anne , Siddiqui Mohammed , Mamedov Alexandre , Zhang Liying , Buckstein Rena
Published: June 2021

The incorporation of patient‐reported outcomes with traditional disease risk classification was found to strengthen survival prediction in patients with myelodysplastic syndromes (MDS). In the present Canadian MDS registry analysis, we validate a recently reported prognostic model, the Fatigue‐International Prognostic Scoring System among higher‐risk patients [FA‐IPSS(h)], which incorporates patients’ reported fatigue, assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life‐Core 30 (QLQ‐C30), with a threshold of ≥45 points, in higher IPSS score, stratifying them into distinct subgroups with different survival outcomes. We further validated this concept, using the Revised IPSS >3·5 as cut‐off for the definition of higher‐risk MDS, and patients’ reported fatigue according to Edmonton Symptom Self‐Assessment Scale (ESAS) Global Fatigue Scale (GFS), a single‐item fatigue rating scale, which is easier to deploy. This emphasises the power of self‐reported fatigue at refining overall survival predictions in higher‐risk MDS and further bolsters the importance of considering patient‐related outcomes in global assessments.
Neutrophil elastase promotes neointimal hyperplasia by targeting toll‐like receptor 4 (TLR4)–NF‐κB signalling
Authors: Yang Mei , Chen Qishan , Mei Li , Wen Guanmei , An Weiwei , Zhou Xinmiao , Niu Kaiyuan , Liu Chenxin , Ren Meixia , Sun Kun , Xiao Qingzhong , Zhang Li
Published: June 2021

Background and Purpose

Neointimal hyperplasia (NIH) is the fundamental cause for vascular diseases and vascular smooth muscle cell (VSMC) dysregulation has been widely implicated in NIH. Neutrophil elastase is a potential therapeutic target for multiple diseases. We investigated the role of neutrophil elastase in VSMC functions and injury‐induced NIH and explored the therapeutic potential of targeting neutrophil elastase in NIH.

Experimental Approach

VSMCs were used to analyse the effects of neutrophil elastase. Proteomic analysis was used to identify potential neutrophil elastase targets. Artery injury model and neutrophil elastase inhibitor GW311616A were used to investigate the role of neutrophil elastase in NIH.

Key Results

TNF‐α up‐regulated neutrophil elastase in VSMCs through modulating GAPBα/Runx1/CEBPα/c‐Myb signalling. Up‐regulated neutrophil elastase promoted VSMC migration, proliferation and inflammation. Toll‐like receptor 4 (TLR4) was identified as a target protein for neutrophil elastase in VSMCs and the TLR4/MyD88/IRAK1/TRAF6/NF‐κB regulatory axis was shown to be the signalling pathway for neutrophil elastase in VSMC pathology. Importantly, TLR4 inhibition abolished neutrophil elastase‐mediated VSMC dysregulation. Injury‐induced NIH was significantly reduced in both neutrophil elastase‐deficient mice and mice treated with GW311616A. The formation of neutrophil extracellular traps was impaired in injured arteries from neutrophil elastase‐deficient mice. Finally, a similar role for neutrophil elastase in human VSMC pathology was confirmed and we observed higher expression levels of neutrophil elastase but lower expression levels of TLR4 in human atherosclerotic lesions.

Conclusion and Implications

We provide new insight into the molecular mechanisms underlying NIH and identify neutrophil elastase as a potential therapeutic target for vascular disease.
A figurational approach to understanding school climate and peer harassment: Possibilities from Norbert Elias’s work
Authors: Webb Andrew
Published: June 2021

Although psychological approaches have been the mainstay of scholarly research on school climate, offering state‐of‐the‐art measurements and methodologies, sociological perspectives remain essential perspectives because violence is essentially a social phenomenon. This paper offers a theoretical consideration of contributions to this field, focusing specifically on those that provide a critical historical lens. I suggest that while Foucault's approach to the disciplining of docile bodies and self‐restraint offers crucial conceptual tools, Norbert Elias's work—which is scarce in scholarly research on school climate—provides a complementary but necessary framework for understanding emotional and relational aspects of peer harassment.
Metabolomic profiling of extraesophageal reflux disease in children
Authors: Mahoney Lisa B. , Esther Charles R. , May Kara , Rosen Rachel
Published: June 2021

Although respiratory symptoms in children are often attributed to gastroesophageal reflux disease, establishing a clear diagnosis of extraesophageal reflux disease (EERD) can be challenging, as there are no sensitive or specific EERD biomarkers. The aim of this study was to evaluate the metabolite profile in bronchoalveolar (BAL) fluid from children with suspected EERD and assess the impact of reflux treatment on these metabolites. In this prospective pilot study, we performed nontargeted global metabolomic profiling on BAL fluid from 43 children undergoing testing with bronchoscopy, upper endoscopy, and multichannel intraluminal impedance with pH (pH‐MII) for evaluation of chronic respiratory symptoms. Twenty‐three (54%) patients had an abnormal pH‐MII study. Seventeen (40%) patients were on proton pump inhibitors (PPIs) for testing. Levels of histamine, malate, adenosine 5′‐monophosphate, and ascorbate were significantly lower in subjects with abnormal pH‐MII studies compared to those normal studies. Furthermore, in children off PPI therapy, those with abnormal pH‐MII studies had robust increases in a number of glycerophospholipids within phospholipid metabolic pathways, including derivatives of glycerophosphorylcholine, glycerophosphoglycerol, and glycerophosphoinositol, compared to those with normal pH‐MII studies. These findings offer insight into the impact of reflux and PPIs on the lungs and provide a foundation for future studies using targeted metabolomic analysis to identify potential biomarkers of EERD.
Developmental changes in auditory‐evoked neural activity underlie infants’ links between language and cognition
Authors: Woodruff Carr Kali , Perszyk Danielle R. , Norton Elizabeth S. , Voss Joel L. , Poeppel David , Waxman Sandra R.
Published: June 2021

The power and precision with which humans link language to cognition is unique to our species. By 3–4 months of age, infants have already established this link: simply listening to human language facilitates infants’ success in fundamental cognitive processes. Initially, this link to cognition is also engaged by a broader set of acoustic stimuli, including non‐human primate vocalizations (but not other sounds, like backwards speech). But by 6 months, non‐human primate vocalizations no longer confer this cognitive advantage that persists for speech. What remains unknown is the mechanism by which these sounds influence infant cognition, and how this initially broader set of privileged sounds narrows to only human speech between 4 and 6 months. Here, we recorded 4‐ and 6‐month‐olds’ EEG responses to acoustic stimuli whose behavioral effects on infant object categorization have been previously established: infant‐directed speech, backwards speech, and non‐human primate vocalizations. We document that by 6 months, infants’ 4–9 Hz neural activity is modulated in response to infant‐directed speech and non‐human primate vocalizations (the two stimuli that initially support categorization), but that 4–9 Hz neural activity is not modulated at either age by backward speech (an acoustic stimulus that doesn't support categorization at either age). These results advance the prior behavioral evidence to suggest that by 6 months, speech and non‐human primate vocalizations elicit distinct changes in infants’ cognitive state, influencing performance on foundational cognitive tasks such as object categorization.
Rodent studies of developmental programming and ageing mechanisms
Authors: Zambrano Elena , Lomas‐Soria Consuelo , Nathanielsz Peter W.
Published: June 2021

Compelling evidence exists indicating that developmental programming influences ageing. Programming alters life‐course phenotype in multiple organs, predisposing to diseases such as diabetes, obesity and cardiovascular disease that shorten lifespan. This review describes studies in rodents, the most commonly studied species, addressing interactions of programming challenges with ageing. We first consider ageing and programming of insulin function that has been clearly shown to decrease with age. It is important to evaluate ageing in pancreatic islets isolated from other systems. Studies discussed show premature pancreatic islet ageing resulting from both maternal under‐ and overnutrition. New ways to determine programming of adipose tissue and effects on fat storage are explored. Oxidative stress is a major factor that regulates ageing in tissues. Oxidative stress is discussed in relation to reproductive and cardiovascular ageing. Premature ageing is associated with both low and high glucocorticoid function. Both over and undernutrition have offspring sex‐specific programming effects on life‐course glucocorticoid concentrations. Evidence is provided that maternal age at conception affects offspring endocrine and metabolism ageing. Finally, the importance of matching foetal nutrition and energy availability with composition and energy content in the post‐weaning diet is demonstrated. This mismatch can lead to a greatly shortened lifespan. General principles are discussed throughout. For example, sexual dimorphism of age‐related outcomes can be marked. Accelerated ageing occurs early in life. Improving knowledge on programming ageing interactions will improve health span as well as lifespan. Finally, there are considerable similarities in outcomes programmed by maternal undernutrition and overnutrition.
Charcot–Marie–Tooth disease misdiagnosed as chronic inflammatory demyelinating polyradiculoneuropathy: An international multicentric retrospective study
Authors: Hauw Fabien , Fargeot Guillaume , Adams David , Attarian Shahram , Cauquil Cécile , Chanson Jean‐Baptiste , Créange Alain , Gendre Thierry , Deiva Kumaran , Delmont Emilien , Francou Bruno , Genestet Steeve , Kuntzer Thierry , Latour Philippe , Le Masson Gwendal , Magy Laurent , Nardin Clotilde , Ochsner François , Sole Guilhem , Stojkovic Tanya , Maisonobe Thierry , Tard Céline , Van den Berghe Peter , Echaniz‐Laguna Andoni
Published: June 2021

Background and purpose

Charcot–Marie–Tooth (CMT) disease, an untreatable hereditary polyneuropathy, may mimic chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), a treatable neuropathy.

Methods

In this retrospective study, we analyzed the characteristics of CMT patients misdiagnosed as CIDP at 16 university hospitals in three countries, compared these patients with a reference group of CIDP patients, and estimated the cost of misdiagnosis.

Results

Among 1104 CIDP cases, we identified 35 CMT patients misdiagnosed as CIDP (3.2%). All were initially diagnosed with definite or probable CIDP (European Federation of Neurological Societies/Peripheral Nerve Society criteria), and mutations in PMP22, MPZ, and 10 other CMT genes were found in 34%, 31%, and 35% of cases, respectively. In comparison with a reference group of 35 CIDP patients, CMT patients were younger (median age at disease onset = 39 vs. 56 years) and more frequently had motor weakness at disease onset (80% vs. 29%), hearing loss (14% vs. 0%), normal brachial plexus imaging (70% vs. 40%), lower cerebrospinal fluid protein content (median = 0.5 vs. 0.8 g/L), and lower treatment response (20% vs. 69%). Treatment cost in these 35 misdiagnosed patients was estimated at 4.6 million euros (M€), whereas the cost of CMT genetic analysis in 1104 patients was estimated at 2.7 M€.

Conclusions

In this study, 35 of 1104 (3.2%) patients initially diagnosed with CIDP had CMT. Importantly, the cost of treating these 35 misdiagnosed patients was significantly higher than the cost of performing CMT genetic analysis in 1104 patients (4.6 M€ vs. 2.7 M€), suggesting that CMT genetic investigations should be more widely used before diagnosing CIDP.
An electron backscatter diffraction investigation on microstructural evolution of pearlite wheel steel near rolling contact fatigue crack tip
Authors: Liu Chun‐Peng , Zhang Guan‐Zhen , Liu Peng‐Tao , Chen Chun‐Huan , Ren Rui‐Ming
Published: June 2021

After rolling contact fatigue (RCF) failure, ultrafine grains are formed in the proeutectoid ferrite (PF) and ferrite grains near the RCF crack tip. During the RCF process, the plastic strain of the samples increases as the cycle increases. When the RCF crack is initiated, a stress field is formed at the RCF crack tip. The accumulation of plastic strain before initiation of the RCF crack is the main reason to result in grain refinement near the RCF crack tip. The stress field also contributes to the grain refinement near the RCF crack tip. The accumulation of plastic strain and the stress field at the RCF crack tip lead to the generation of a large number of dislocations in the PF and ferrite grains in the zone in front of the RCF crack tip. Then, the dislocations are gradually transformed into subboundaries. Finally, the subboundaries evolve into high‐angle grain boundaries, leading to grain refinement. The RCF cracks are mainly propagated at the interface between the grain refinement zone and the unrefined zone at the RCF crack tip. The local grain refinement zone at the RCF crack tip can accelerate the propagation of the RCF cracks.
Perceived ethnic discrimination as a determinant of migrants’ health in Italy
Authors: Quaglia Valeria , Terraneo Marco , Tognetti Mara
Published: June 2021

Discrimination has a negative impact on immigrants’ health and contributes to the (re)production of health inequalities. The aim of this study was to investigate the effect of perceived discrimination on physical and mental health outcomes of migrants living in Italy. Data were taken from the Social Condition and Integration of Foreign Citizens (SCIF) survey, conducted in 2011–2012 in Italy, namely the first national survey that investigates social condition and integration of foreign citizens. In order to assess the association between perceived discrimination and both physical and mental health of immigrants, two binomial logistic regression models were fitted. The main finding of our study is that, also in Italy, perceived ethnic discrimination is associated with worse health outcomes, therefore, policymakers should develop and implement public interventions aimed at reducing health inequalities with the rest of the population and at promoting migrants’ social integration.
A Review of Spatial Causal Inference Methods for Environmental and Epidemiological Applications
Authors: Reich Brian J. , Yang Shu , Guan Yawen , Giffin Andrew B. , Miller Matthew J. , Rappold Ana
Published: June 2021

The scientific rigor and computational methods of causal inference have had great impacts on many disciplines but have only recently begun to take hold in spatial applications. Spatial causal inference poses analytic challenges due to complex correlation structures and interference between the treatment at one location and the outcomes at others. In this paper, we review the current literature on spatial causal inference and identify areas of future work. We first discuss methods that exploit spatial structure to account for unmeasured confounding variables. We then discuss causal analysis in the presence of spatial interference including several common assumptions used to reduce the complexity of the interference patterns under consideration. These methods are extended to the spatiotemporal case where we compare and contrast the potential outcomes framework with Granger causality and to geostatistical analyses involving spatial random fields of treatments and responses. The methods are introduced in the context of observational environmental and epidemiological studies and are compared using both a simulation study and analysis of the effect of ambient air pollution on COVID‐19 mortality rate. Code to implement many of the methods using the popular Bayesian software OpenBUGS is provided.