bluuebunny/crossref_metadata_2025 huggingface dataset:
Rhododendrol‐induced leukoderma update II: Pathophysiology, mechanisms, risk evaluation, and possible mechanism‐based treatments in comparison with vitiligo
Authors: Inoue Shintaro , Katayama Ichiro , Suzuki Tamio , Tanemura Atsushi , Ito Shosuke , Abe Yuko , Sumikawa Yasuyuki , Yoshikawa Momoko , Suzuki Kayoko , Yagami Akiko , Masui Yukiko , Ito Akiko , Matsunaga Kayoko
Published: May 2021

A small proportion of individuals utilizing cosmetics containing rhododendrol developed leukoderma with various pathological conditions, in some cases indistinguishable from vitiligo. In this review, we investigate and evaluate the major considerations for developing rhododendrol‐induced leukoderma based on data from original or review articles published in the literature to provide a wide range of information regarding the pathophysiology, mechanisms, risk evaluation, and possible mechanism‐based treatments. We compile and discuss the latest information, including data related to the cytotoxicity of rhododendrol, cytoprotective functions, and involvement of the immune system, and consider the possibility of novel treatments based on the differences between individual patients and on the mechanism underlying the onset of the condition. Understanding the pathophysiology of rhododendrol‐induced leukoderma helps not only elucidate the mechanisms of non‐segmental vitiligo onset and progression, but also suggests prevention and treatment.
Making a (Political) Career: Young Party Members and Career‐Related Incentives for Party Membership
Authors: Fjellman Elin , Rosén Sundström Malena
Published: May 2021

Few empirical studies have investigated career‐related incentives for party membership, including for young party members. Through the lens of rational choice, we ask what career‐related incentives young and active party members consider when calculating costs and benefits of party membership. We argue for a broad understanding of career‐related incentives, including careers outside party politics. The study is based on in‐depth interviews with 25 young party members in Sweden. Our main empirical finding is that the interviewees experience a ‘super‐dilemma’: Although the young party members might consider a political career, they think it is important to leave the party if it departs from their perceived ideology. Hence, these young members must keep non‐political career options open. At the same time, many of the interviewees express concern that their party membership could negatively affect their non‐political career.
What is a compassionate response in the emergency department? Learner evaluation of an End‐of‐Life Essentials online education module
Authors: Rawlings Deb , Winsall Megan , Yin Huahua , Devery Kim
Published: May 2021

Objective

To evaluate the End‐of‐Life Essentials education module ‘Emergency Department End‐of‐Life Care’ and explore learners' views on what constitutes a compassionate response in the ED.

Methods

The present study used a multi‐methods approach. Learners comprised a mix of nurses, doctors and allied health professionals. A quantitative pre‐post evaluation analysis of learners' (n = 959) knowledge, skills, attitude and confidence was conducted, along with a qualitative thematic content analysis on learner responses (n = 538) to the post‐evaluation question, ‘What is a compassionate response for you in the emergency department?’ Data were extracted for a 12‐month period, 6 May 2019 to 6 May 2020.

Results

Learners' post‐evaluation ranks of knowledge, skill, attitude and confidence were significantly higher than the pre‐evaluation ranks (P < 0.001). Emerging themes from the qualitative data were organised into three overarching categories: communication skills (e.g. listening and use of names), care discussion and provision (e.g. provide information and discuss care plans) and humanising healthcare (e.g. emotional support and empathy, taking the time, and offering kindness and comfort).

Conclusion

The ‘Emergency Department End‐of‐Life Care’ module had a significant positive impact on learners in relation to perceived knowledge, skill, attitude and confidence. This evaluation suggests that the End‐of‐Life Essentials ED module could be a useful online learning resource for health professionals.
Development of a risk prediction model of pneumothorax in percutaneous computed tomography guided transthoracic needle lung biopsy
Authors: Weon JangHo , Robson Scott , Chan Ronald , Ussher Simon
Published: May 2021

Introduction

To retrospectively evaluate the incidence of and the risk factors for pneumothorax and intercostal catheter insertion (ICC) after CT‐guided lung biopsy and to generate a risk prediction model for developing a pneumothorax and requiring an ICC.

Methods

255 CT‐guided lung biopsies performed for 249 lesions in 249 patients from August 2014 to August 2019 were retrospectively analysed using multivariate logistic regression analysis. Risk prediction models were established using backward stepwise variable selection and likelihood ratio tests and were internally validated using split‐sample methods.

Results

The overall incidence of pneumothorax was 30.2% (77/255). ICC insertion was required for 8.32% (21/255) of all procedures. The significant independent risk factors for pneumothorax were lesions not in contact with pleura (P < 0.001), a shorter skin‐to‐pleura distance (P = 0.01), the needle crossing a fissure (P = 0.004) and emphysema (P = 0.01); those for ICC insertion for pneumothorax were a needle through emphysema (P < 0.001) and lesions in the upper lobe (P = 0.017). AUC of the predictive models for pneumothorax and ICC insertion were 0.800 (95% CI: 0.745–0.856) and 0.859 (95% CI: 0.779–0.939) respectively. Upon internal validation, AUC of the testing sets of pneumothorax and ICC insertion were 0.769 and 0.822 on average respectively.

Conclusion

The complication rates of pneumothorax and ICC insertion after CT‐guided lung biopsy at our institution are comparable to results from previously reported studies. This study provides highly accurate risk prediction models of pneumothorax and ICC insertion for patients undergoing CT‐guided lung biopsies.
Current status and perspectives of spread through air spaces in lung cancer
Authors: Ikeda Toshihiro , Kadota Kyuichi , Go Tetsuhiko , Haba Reiji , Yokomise Hiroyasu
Published: May 2021

According to the World Health Organization classification of 2015, spread through air spaces (STAS) is a newly recognized pattern of invasion in lung adenocarcinoma. Many researchers have reported that STAS is recognized in all histological subtypes, and there is a strong association between STAS and prognosis in lung cancer. However, there are several technical issues associated with STAS, such as distinction between the actual in vivo phenomenon and an artifact, difficulty in assessing STAS in frozen specimens, and establishing the relationship between morphological and molecular properties of STAS. This review focuses on the current state of knowledge and the outlook of the STAS phenomenon from the perspective of surgeons, pathologists, and radiologists.
Calcification in thymomas can predict invasiveness to surrounding organs
Authors: Yoshida Mitsuteru , Kondo Kazuya , Miyamoto Naoki , Kawakami Yukikiyo , Tangoku Akira
Published: May 2021

Background

Thymomas are the most common type of anterior mediastinal tumors. Calcification is sometimes observed in thymomas using computed tomography (CT), and it is more frequent in invasive thymomas than in noninvasive thymomas. However, the significance of calcification in thymomas remains unknown. This study aimed to evaluate the significance of calcification in thymomas on invasiveness to surrounding organs and investigate the characteristics of thymoma cases with calcification at our institution.

Methods

We included thymoma patients treated at our institution between 2000 and 2016, and evaluated their characteristics, including demographics, calcification on CT, histology, Masaoka stage, and myasthenia gravis status. The patients were categorized into calcification (C) and noncalcification (NC) groups.

Results

Among 51 included patients, 11 (21.6%) had calcification. A higher proportion of group C patients had World Health Organization histological type B2 and B3 tumors (high‐risk) than type A, AB, and B1 tumors (low‐risk; p = 0.0477). The number of patients with Masaoka stages III and IV were significantly higher in the C group than in the NC group (p < 0.0001). The C group patients had significantly higher rates of invasion to the mediastinal pleura, pericardium, lung, phrenic nerve, and chest wall and pleural dissemination than the NC group patients.

Conclusions

Calcification reflects invasiveness of tumors to surrounding organs and tissues, and may thus predict thymoma stage and histologically high‐risk thymomas. Calcification in thymomas may also predict the pathological stage and help decide therapeutic methods and surgical approaches to treat thymomas based on the calcification status according to CT findings.
The Effects of High Estimate Uncertainty in Auditor Negligence Litigation*
Authors: Pickerd Jeffrey , Piercey M. David
Published: May 2021

We examine how jurors' negligence judgments and attorneys' out‐of‐court settlements are differently impacted by two features of a materially misstated accounting estimate—the amount of estimate uncertainty and whether the misstated account is disaggregated into its own line‐item or aggregated with other accounts into a single financial statement line‐item. We predict and find that jurors and attorneys react to estimate uncertainty in opposite directions under common conditions. This finding is important because when jurors' judgments and attorneys' settlements differ, research into juror judgments alone may not capture a complete picture of auditor liability because the vast majority of audit litigation is resolved by attorneys in out‐of‐court settlement without ever going to trial. Consistent with attribution theory, results from our first experiment show that jurors hold auditors more responsible for misstatements of lower estimate uncertainty when the misstated account is disaggregated, as opposed to misstatements that are of higher uncertainty and/or aggregated with other, accurate accounts. However, in a second experiment we find that attorneys negotiate auditor settlements under the incorrect assumption that jurors will hold auditors more responsible for failing to prevent misstatements of higher uncertainty. Our results illustrate that accounting research should not focus solely on juror judgments in the study of how specific factors impact auditor liability, and that attorneys would benefit from a better understanding of juror decision making.
Gain of PITRM1 peptidase in cortical neurons affords protection of mitochondrial and synaptic function in an advanced age mouse model of Alzheimer’s disease
Authors: Du Fang , Yu Qing , Yan Shijun , Zhang Zhihua , Vangavaragu Jhansi Rani , Chen Doris , Yan Shi Fang , Yan Shirley ShiDu
Published: May 2021

Mitochondrial dysfunction is one of the early pathological features of Alzheimer's disease (AD). Accumulation of cerebral and mitochondrial Aβ links to mitochondrial and synaptic toxicity. We have previously demonstrated the mechanism by which presequence peptidase (PITRM1)‐mediated clearance of mitochondrial Aβ contributes to mitochondrial and cerebral amyloid pathology and mitochondrial and synaptic stress in adult transgenic AD mice overexpressing Aβ up to 12 months old. Here, we investigate the effect of PITRM1 in an advanced age AD mouse model (up to 19–24 months) to address the fundamental unexplored question of whether restoration/gain of PITRM1 function protects against mitochondrial and synaptic dysfunction associated with Aβ accumulation and whether this protection is maintained even at later ages featuring profound amyloid pathology and synaptic failure. Using newly developed aged PITRM1/Aβ‐producing AD mice, we first uncovered reduction in PITRM1 expression in AD‐affected cortex of AD mice at 19–24 months of age. Increasing neuronal PITRM1 activity/expression re‐established mitochondrial respiration, suppressed reactive oxygen species, improved synaptic function, and reduced loss of synapses even at advanced ages (up to 19–24 months). Notably, loss of PITRM1 proteolytic activity resulted in Aβ accumulation and failure to rescue mitochondrial and synaptic function, suggesting that PITRM1 activity is required for the degradation and clearance of mitochondrial Aβ and Aβ deposition. These data indicate that augmenting PITRM1 function results in persistent life‐long protection against Aβ toxicity in an AD mouse model. Therefore, augmenting PITRM1 function may enhance Aβ clearance in mitochondria, thereby maintaining mitochondrial integrity and ultimately slowing the progression of AD.
Calcium‐permeable AMPA receptor activity and GluA1 trafficking in the basolateral amygdala regulate operant alcohol self‐administration
Authors: Faccidomo Sara , Cogan Elizabeth S. , Hon Olivia J. , Hoffman Jessica L. , Saunders Briana L. , Eastman Vallari R. , Kim Michelle , Taylor Seth M. , McElligott Zoe A. , Hodge Clyde W.
Published: May 2021

Addiction is viewed as maladaptive glutamate‐mediated neuroplasticity that is regulated, in part, by calcium‐permeable AMPA receptor (CP‐AMPAR) activity. However, the contribution of CP‐AMPARs to alcohol‐seeking behavior remains to be elucidated. We evaluated CP‐AMPAR activity in the basolateral amygdala (BLA) as a potential target of alcohol that also regulates alcohol self‐administration in C57BL/6J mice. Operant self‐administration of sweetened alcohol increased spontaneous EPSC frequency in BLA neurons that project to the nucleus accumbens as compared with behavior‐matched sucrose controls indicating an alcohol‐specific upregulation of synaptic activity. Bath application of the CP‐AMPAR antagonist NASPM decreased evoked EPSC amplitude only in alcohol self‐administering mice indicating alcohol‐induced synaptic insertion of CP‐AMPARs in BLA projection neurons. Moreover, NASPM infusion in the BLA dose‐dependently decreased the rate of operant alcohol self‐administration providing direct evidence for CP‐AMPAR regulation of alcohol reinforcement. As most CP‐AMPARs are GluA1‐containing, we asked if alcohol alters the activation state of GluA1‐containing AMPARs. Immunocytochemistry results showed elevated GluA1‐S831 phosphorylation in the BLA of alcohol as compared with sucrose mice. To investigate mechanistic regulation of alcohol self‐administration by GluA1‐containing AMPARs, we evaluated the necessity of GluA1 trafficking using a TET‐ON AAV encoding a dominant‐negative GluA1 c‐terminus (GluA1ct) that blocks activity‐dependent synaptic delivery of native GluA1‐containing AMPARs. GluA1ct expression in the BLA reduced alcohol self‐administration with no effect on sucrose controls. These results show that CP‐AMPAR activity and GluA1 trafficking in the BLA mechanistically regulate the reinforcing effects of sweetened alcohol. Pharmacotherapeutic targeting these mechanisms of maladaptive neuroplasticity may aid medical management of alcohol use disorder.
Coexistence in an African pastoral landscape: Evidence that livestock and wildlife temporally partition water resources
Authors: Connolly Erin , Allan James , Brehony Peadar , Aduda Alice , Western Guy , Russell Samantha , Dickman Amy , Tyrrell Peter
Published: May 2021

African rangelands support substantial wildlife populations alongside pastoralists and livestock. Recent wildlife declines are often attributed to competition with livestock over water and grazing, in part because livestock are thought to spatially displace wildlife. However, more evidence is needed to understand this interaction and inform rangeland management. Here, we analysed the temporal overlap between wildlife and livestock at water points in a community‐governed area of Kenya's South Rift Valley, which is a dry season refuge where Maasai pastoralists, livestock and wildlife co‐occur. We used camera traps to capture images at water points in two time periods: first, when nearby settlements were unoccupied, and second, as people and their herds moved into the area. We measured wildlife activity (independent detections per hour) and the difference in temporal overlap between livestock and wildlife. We found no evidence that daily wildlife activity declined despite increased human and livestock settlement. However, temporal partitioning between livestock and wildlife at watering points increased with wildlife using water resources more at night. Maasai corral livestock overnight to protect them from predation, allowing wildlife to persist in a livestock‐dominated landscape. Our study demonstrates humans and wildlife co‐adapting to mitigate competition for shared water resources, thereby facilitating spatial coexistence.
Effectiveness of wildlife underpasses and culverts in connecting elephant habitats: a case study of new railway through Kenya’s Tsavo National Parks
Authors: Okita‐Ouma Benson , Koskei Michael , Tiller Lydia , Lala Fredrick , King Lucy , Moller Richard , Amin Rajan , Douglas‐Hamilton Iain
Published: May 2021

Transportation networks can be a major impediment to wildlife movements. We assessed the use of wildlife underpasses and culverts along a newly constructed railway in Kenya's Tsavo National Parks by African elephants (L. africana). We collared ten elephants with GPS satellite transmitters within 20 km of the railway in March 2016 and analysed their movement data to March 2019. Eight elephants used the underpasses although one did not cross the adjacent highway. The remaining two neither used the underpasses nor crossed the highway despite ranging in the vicinity. Their median speed significantly increased to 0.65 km/hr from 0.45 km/hr before crossing the railway, then slowed to 0.32 km/hr after crossing. Females in family groups moved faster than the lone bulls when using the underpasses. Seventy‐eight per cent of all crossings made were at night. The fast speeds and the nocturnal patterns are behavioural responses of elephants in risky landscapes or under stress. Disturbance from vehicles traffic on the adjacent highway and from newly developed human settlements may have limited use of underpasses. Wildlife crossing structures, signage and speed bumps along the highway; relocation of the illegal human settlements; and inter‐agency coordination are requisites for enhancing Tsavos' elephant habitat connectivity.
Glucagon‐like peptide‐1 receptor agonist inhibits aeroallergen‐induced activation of ILC2 and neutrophilic airway inflammation in obese mice
Authors: Toki Shinji , Newcomb Dawn C. , Printz Richard L. , Cahill Katherine N. , Boyd Kelli L. , Niswender Kevin D. , Peebles R. Stokes
Published: May 2021

Background

Obesity is a risk factor for the development of asthma. However, pharmacologic therapeutic strategies that specifically target obese asthmatics have not been identified. We hypothesize that glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) treatment inhibits aeroallergen‐induced early innate airway inflammation in a mouse model of asthma in the setting of obesity.

Methods

SWR (lean) and TALLYHO (obese) mice were challenged intranasally with Alternaria alternata extract (Alt‐Ext) or PBS for 4 consecutive days concurrent with GLP‐1RA or vehicle treatment.

Results

TALLYHO mice had greater Alt‐Ext‐induced airway neutrophilia and lung protein expression of IL‐5, IL‐13, CCL11, CXCL1, and CXCL5, in addition to ICAM‐1 expression on lung epithelial cells compared with SWR mice, and all endpoints were reduced by GLP‐1RA treatment. Alt‐Ext significantly increased BALF IL‐33 in both TALLYHO and SWR mice compared to PBS challenge, but there was no difference in the BALF IL‐33 levels between these two strains. However, TALLYHO, but not SWR, mice had significantly higher airway TSLP in BALF following Alt‐Ext challenge compared to PBS, and BALF TSLP was significantly greater in TALLYHO mice compared to SWR mice following airway Alt‐Ext challenge. GLP‐1RA treatment significantly decreased the Alt‐Ext‐induced TSLP and IL‐33 release in TALLYHO mice. While TSLP or ST2 inhibition with a neutralizing antibody decreased airway eosinophils, they did not reduce airway neutrophils in TALLYHO mice.

Conclusions

These results suggest that GLP‐1RA treatment may be a novel pharmacologic therapeutic strategy for obese persons with asthma by inhibiting aeroallergen‐induced neutrophilia, a feature not seen with either TSLP or ST2 inhibition.
Photograph method fosters direct access to second‐language word meaning: Direct evidence from a word‐picture matching task
Authors: Boddaert Gary , Casalis Séverine , Mahé Gwendoline
Published: May 2021

This experiment was designed to investigate conceptual links directly through a word–picture matching task in children. Participants were asked to indicate between two pictures the one depicting the same concept as the newly learned L2 word (target). One of the two pictures was the target, while the other was either semantically related to it or was unrelated. To investigate whether learning methods modulate L2 word processing, two learning methods were compared: an L2‐photograph method and an L1‐L2 method. Results showed a semantic interference effect only with the L2‐photograph method: Children responded more slowly in the related condition than in the unrelated one. The learning method modulated L2 word processing and L2 word meaning was not necessarily accessed through L1 mediation in the first steps of learning. The method used paves the way for the direct investigation of conceptual links.
Constructionism and AI: A history and possible futures
Authors: Kahn Ken , Winters Niall
Published: May 2021

Constructionism, long before it had a name, was intimately tied to the field of Artificial Intelligence. Soon after the birth of Logo at BBN, Seymour Papert set up the Logo Group as part of the MIT AI Lab. Logo was based upon Lisp, the first prominent AI programming language. Many early Logo activities involved natural language processing, robotics, artificial game players, and generating poetry, art, and music. In the 1970s researchers explored enhancements to Logo to support AI programming by children. In the 1980s the Prolog community, inspired by Logo's successes, began exploring how to adapt logic programming for use by school children. While there have been over 40 years of active AI research in creating intelligent tutoring systems, there was little AI‐flavoured constructionism after the 1980s until about 2017 when suddenly a great deal of activity started. Amongst those activities were attempts to enhance Scratch, Snap!, and MIT App Inventor with new blocks for speech synthesis, speech recognition, image recognition, and the use of pre‐trained deep learning models. The Snap! enhancements also include support for word embeddings, as well as blocks to enable learners to create, train, and use deep neural networks. Student and teacher project‐oriented resources highlighting these new AI programming components appeared at the same time. In this paper, we review this history, providing a unique perspective on AI developments—both social and technical—from a constructionist perspective. Reflecting on these, we close with speculations about possible futures for AI and constructionism.

Practitioner notes

What is already known about this topic

There exist excellent broad surveys of the current status of teaching machine learning in schools, for example Marques et al. (2020). There are historical collections of AI and education research papers that include descriptions of constructionist activities, for example Yazdani (1984).

What this paper adds

This paper adds an in‐depth focus on historical and current efforts on AI and education that support constructionist teaching. This focus enables us to delve deeper than a broad survey. Uniquely, we provide a 50‐year historical perspective on constructionist AI tools, trials, and research. Grounded in this history and our survey of current tools and projects, we provide speculations about future directions.

Implications for practice and/or policy

We hope our descriptions of current AI programming tools for non‐experts placed in a broad historical context will be of use to teachers wishing to introduce AI to their students in a constructionist manner, as well as to developers and researchers aiming to support such teaching.
Developing preservice teachers' understanding of computational thinking: A constructionist approach
Authors: Butler Deirdre , Leahy Margaret
Published: May 2021

Research relating to the development of computational thinking (CT) at primary school level is still in its infancy despite indications that it is most effective when introduced in primary/early secondary education. Teachers are pivotal to ensuring children develop CT, so it is essential they are effectively prepared, starting at preservice level, to incorporate CT into pedagogical practices. Grounded in constructionist principles and adopting the stance that CT be developed as part of subject areas other than computer science, this qualitative study presents findings focused on the understandings of CT of 51 preservice teachers who engaged in a digital learning specialism. Carried out over a 2‐year period, the research investigated preservice teachers' understandings of CT and how the design of the specialism helped to develop their understanding. Findings highlight deep understandings of CT among the preservice teachers who were able to make connections between constructionism and the development of CT. They also demonstrated a high level of pedagogical knowledge, indicating they understood why they designed particular challenges for children as part of their classroom experience. Findings are relevant for the design of teacher preparation programmes illustrating how CT can be effectively embedded to combine theory and practice.

Practitioner notes

What is already known about this topic

Existing research base in relation to preservice teacher education and computational thinking is limited.

When computational thinking is introduced as part of initial teacher education, preservice teachers:

develop more accurate and increased understandings of computational thinking

demonstrate more positive attitudes towards the implementation of computational thinking in the classroom.

Duration of module seems to be a significant factor. A 1‐week module might be enough to develop preservice teachers' surface‐level understanding of computational thinking, but it would not provide them with enough knowledge to embed computational thinking in meaningful ways in the classroom (Yadav et al., 2014).

What this paper adds

Adopting the stance that computational thinking should be developed as part of subject areas other than computer science.

This paper presents and discusses findings from the implementation of a model for preservice teacher education grounded in constructionism, that supports preservice primary teachers in building an understanding of CT as well as the pedagogical knowledge necessary for embedding CT into their classroom practice.

Implications for practice and/or policy

The insights gained from this study are particularly relevant for the design of teacher preparation programmes indicating how CT can be effectively embedded to combine theory and practice.

This will ensure that CT concepts are not developed in a decontexualised manner but are embedded within the prescribed curriculum in a relevant and meaningful manner.
Global meta‐analysis of tree decline impacts on fauna
Authors: Fleming Patricia A. , Wentzel Jacobus J. , Dundas Shannon J. , Kreplins Tracey L. , Craig Michael D. , Hardy Giles E. St.J.
Published: May 2021

Significant portions of the world's forests have been impacted by severe and large‐scale tree declines characterised by gradual but widespread loss of vigour and subsequent death of either single or several tree species. Tree deaths represent a threat for fauna that are dependent on forest habitats for their survival. Although tree declines have received considerable scientific attention, surprisingly, little is known about their impacts on fauna. In total, we calculated 631 effect sizes across 59 studies that quantified the impact of tree declines on animal abundance. Data representing 186 bird species indicated an overall increase in bird abundance in response to tree declines (meta‐analysis mean ± estimationg = 0.172 ± 0.053 [CI 0.069 to 0.275],P = 0.001); however, there was substantial variability in responses (significant heterogeneityP < 0.001) with a strong influence of diet as well as nesting guild on bird responses. Granivores (especially ground‐foraging species, e.g. Passerellidae species), bark‐foraging insectivores (e.g. woodpeckers), as well as ground‐ and cavity‐nesting species apparently benefitted from tree declines, while nectarivorous birds [and, although not significant, aerially foraging insectivores (e.g. flycatchers) and leaf‐gleaning insectivores (canopy‐feeding)] were less common in the presence of tree declines. Data representing 33 mammal species indicate a tendency for detrimental effects of tree declines on mammals that use trees as refuges, while aerial foragers (i.e. bats) may benefit from opening up the canopy. Overall the average effect for mammals was neutral (meta‐analysis mean estimationg = −0.150 ± 0.145 [−0.433 to 0.134],P = 0.302). Data representing 20 reptile species showed an insufficient range of responses to determine any diet or foraging effect on their responses. Data for 28 arthropod taxa should be considered with caution, as we could not adequately separate taxa according to their specialisations and reliance on key habitat. The data broadly suggest a detrimental effect of tree declines (meta‐analysis mean estimationg = −0.171 ± 0.072 [−0.311 to −0.031],P = 0.017) with ground‐foraging arthropods (e.g. detritivores and predators such as spiders and centipedes) more likely to be detrimentally impacted by tree declines. The range of responses to tree declines signifies substantially altered animal communities. In many instances, altered ecosystem function due to loss of key animal services will represent a significant threat to forest health.
Molecular docking‐guided synthesis of NSAID–glucosamine bioconjugates and their evaluation as COX‐1/COX‐2 inhibitors with potentially reduced gastric toxicity
Authors: Jones Lipinski Rachel A. , Thillier Yann , Morisseau Christophe , Sebastiano Christopher S. , Smith Brian C. , Hall C. Dennis , Katritzky Alan R.
Published: May 2021

Non‐steroidal anti‐inflammatory drugs (NSAIDs) are a powerful class of inhibitors targeting two isoforms of the family of cyclooxygenase enzymes (COX‐1 and COX‐2). While NSAIDs are widely used in the management of pain, in particular as a treatment for osteo‐ and rheumatoid arthritis, their long‐term use has been associated with numerous on‐ and off‐target effects. As the carboxylic acid moiety present in common NSAIDs is responsible for some of their adverse effects, but is not required for their anti‐inflammatory activity, we sought to mask this group through direct coupling to glucosamine, which is thought to prevent cartilage degradation. We report herein the conjugation of commonly prescribed NSAIDs to glucosamine hydrochloride and the use of molecular docking to show that addition of the carbohydrate moiety to the parent NSAID can enhance binding in the active site of COX‐2. In a preliminary, in vitro screening assay, the diclofenac‐glucosamine bioconjugate exhibited 10‐fold greater activity toward COX‐2, making it an ideal candidate for future in vivo studies. Furthermore, in an intriguing result, we observed that the mefenamic acid‐glucosamine bioconjugate displayed enhanced activity toward COX‐1 rather than COX‐2.
PD‐L1 and beyond: Immuno‐oncology in cytopathology
Authors: Iaccarino Antonino , Salatiello Maria , Migliatico Ilaria , De Luca Caterina , Gragnano Gianluca , Russo Maria , Bellevicine Claudio , Malapelle Umberto , Troncone Giancarlo , Vigliar Elena
Published: May 2021

Over the past decade, immunotherapy has emerged as one of the most promising cancer treatments. Several monoclonal antibodies targeting the programmed death 1 (PD‐1)/ programmed death ligand‐1 (PD‐L1) pathway have been integrated into standard‐of‐care treatments for a wide range of cancer types. Although all the available PD‐L1 immunohistochemistry (IHC) assays have been developed on formalin‐fixed histological specimens, a growing body of research has recently suggested the feasibility of PD‐L1 testing on cytological samples. Although promising results have been reported, several important issues still need to be addressed. Among these are pre‐analytical issues, cyto‐hystological correlation, and inter‐observer agreement. This review will briefly summarise the knowledge gaps and future directions of cytopathology in the immuno‐oncology scenario.
Environmental DNA of preservative ethanol performed better than water samples in detecting macroinvertebrate diversity using metabarcoding
Authors: Wang Yu , Chen Kai , Gao Jin , Wang Meng , Dong Jie , Xie Yuwei , Giesy John P. , Jin Xiaowei , Wang Beixin
Published: May 2021

Aim

High‐throughput pipelines supported by eDNA metabarcoding have been applied in various freshwater ecosystems. Both eDNA in ethanol (EtOH) samples (ES‐eDNA) and in water samples (WS‐eDNA) can provide comprehensive classification lists with good taxonomic resolution and coverage for determining freshwater biodiversity and biomonitoring. But, the advantages of ES‐eDNA metabarcoding over WS‐eDNA metabarcoding remain unclear for routine assessments of diversity of benthic macroinvertebrates in streams.

Location

Qiantang River Basin, China.

Methods

Here, we compared ES‐eDNA and WS‐eDNA metabarcoding to evaluate the performance of two eDNA workflows in determining biodiversity and recovery of damaged macroinvertebrate communities. All eDNA samples from the environment and bulk specimen of macroinvertebrates were processed into available molecular operational taxonomic units (MOTUs) and identified to the level of genus.

Results

WS‐eDNA detected more exact sequence variants (ESVs) (formerly referred to as operational taxonomic units; OTUs), than did ES‐eDNA (2,866 vs. 2,406), but fewer macroinvertebrate ESVs (381 vs. 481). Among sampling sites, the two eDNA workflows exhibited relatively large dissimilarity on inferred community composition (p < .001). Furthermore, ES‐eDNA metabarcoding exhibited more consistent with morphological identification approaches than did WS‐eDNA metabarcoding (24.24% vs. 17.63%,p = .002), especially for species identified by traditional morphology (morphotaxa).

Main conclusions

Based on the attributes of ES‐eDNA and WS‐eDNA, it is suggested that ES‐eDNA metabarcoding performs better than does WS‐eDNA metabarcoding in detecting local biodiversity and was consistent with morphological results, while WS‐eDNA was more suitable for exploring biodiversity patterns on a broad scale, as it is the easiest and most convenient way to collect samples. Results of this study suggest ES‐eDNA metabarcoding could be an option in building molecular measurement biomonitoring programme based on EtOH sample used for preserving biological samples.
Adapting a Coparenting‐Focused Prevention Program for Latinx Adolescent Parents in a School Context
Authors: Perez‐Brena Norma J. , Toews Michelle L. , Feinberg Mark E. , Anders Kristin M.
Published: May 2021

The current study utilized a three‐step cultural adaptation process to adapt a universal‐coparenting program for Latinx adolescent parents in a school‐based setting. First, focus groups were conducted with adolescent parents (n = 13; 100% Latinx; 69% female), their parents (n = 17; 94% Latinx; 82% female), and school staff (n = 7; 71% White; 100% female) to identify unique needs faced by this population. Second, the program was adapted to include new lesson modules (e.g., coparenting with grandparents, coparenting after breakups) and structural reformatting to fit a school schedule. Third, selected lessons from the adapted program were piloted in four schools with 32 Latinx adolescent parents (97% Latinx; 78% female). Lesson evaluation surveys and focus group data assessed the feasibility and acceptability of the service delivery method and content to show the program was well received. However, implementation challenges emerged when attempting to provide services to adolescent fathers and Spanish‐speaking adolescents. This manuscript provides an example of how to use this cultural adaptation process to tailor prevention programs, highlights a new prevention program that can serve as a resource for adolescent parents, and provides several recommendations for working with Latinx adolescent parents.
Fatigue response dependence of thickness measurement methods for additively manufactured E‐PBF Ti‐6Al‐4 V
Authors: Segersäll Mikael , Kerwin Annie , Hardaker Alex , Kahlin Magnus , Moverare Johan
Published: May 2021

Light weight metal parts produced with additive manufacturing have gained increasing interest from the aerospace industry in recent years. However, light weight parts often require thin walls which can have different material properties compared to thick bulk material. In this work, the fatigue properties of Ti‐6Al‐4 V produced by electron beam powder bed fusion have been investigated for samples with three different wall thicknesses ranging from 1.3 to 2.7 mm and in three different directions; 0°, 45°, and 90° relative to the build plate. Generally, the 90° specimens show worse fatigue life compared to both 0° and 45°. It was found that the fatigue strength is lower for thin samples compared to thicker samples when the stress is calculated from nominal thickness or calliper measurements. However, since materials produced by electron beam powder bed fusion often have a rough as‐built surface, the load bearing area is not easy to determine. In this paper, four different methods for determining the load bearing area are presented. It is shown that if the surface roughness is considered when calculating the stress levels, the influence from specimen thickness decreases or even disappears.
The territorial architecture of government
Authors: Tatham Michaël , Hooghe Liesbet , Marks Gary
Published: May 2021

This article sets the stage for a special issue that examines the interplay between subnational and supranational governance. It begins by discussing how the territorial architecture of government has become more multilevel as national governments have shifted authority both downwards to subnational governments and upwards to international and supranational institutions. Next, we argue that this multilevel structure emanates from a tension between the drive to reap the functional benefits of scale diversity in a globalizing economy and the pressures arising from collective self‐rule. We build on the research in this special issue to highlight some tangible effects of this tension for policy, politics, and polity. Subnational and supranational governance are conventionally perceived as separate phenomena with distinct consequences, and yet they are intimately connected in a fluid territorial architecture of multilevel governance.
The utility of c‐Met as a diagnostic tissue biomarker in primary colorectal cancer
Authors: Armstrong Gemma R. , Khot Mohammed Ibrahim , Tiernan Jim P. , West Nick P. , Perry Sarah L. , Maisey Tom I. , Hughes Thomas A. , Jayne David G.
Published: May 2021

The transmembrane protein, c‐Met, is thought to be overexpressed and activated in colorectal cancer (CRC). This study explored its potential as a diagnostic tissue biomarker for CRC in a large human CRC tissue collection obtained from a randomized clinical trial.

Tissue microarrays of matched normal colorectal epithelium and primary cancer were prepared from specimens obtained from 280 patients recruited to the MRC CLASICC trial (ISRCTN 74883561) and interrogated using immunohistochemistry for c‐Met expression. The distribution and intensity of immunopositivity was graded using a validated, semi‐quantifiable score, and differences in median scores analysed using the Wilcoxon signed‐rank test. A receiver operating characteristic (ROC) curve was plotted to measure the diagnostic accuracy of c‐Met as a biomarker in CRC.

Epithelial cell membrane expression of c‐Met differed significantly between CRC and normal colorectal tissue: median 12.00 (Interquartile range (IQR) 6‐15) versus median 6.00 (IQR 2.70‐12.00) respectively (P = <.0001). ROC‐AUC analysis of c‐Met expression yielded a CRC diagnostic probability of 0.66 (95% CI: 0.61 to 0.70; P < .0001). A score of ≥14.50 showed high specificity at 85.32% (95% CI 80.33%‐89.45%) but sensitivity of only 30.92% (CI 25.37%‐36.90%).

Thus c‐Met is consistently overexpressed in human CRC as compared to normal colorectal epithelium tissue. c‐Met expression may have a role in diagnosis and prognostication if combined with other biomarkers.
Effects of ısotretinoin on the growth rate and thickness of the nail plate
Authors: Özçelik Sinan , Kılıç Fatma A.
Published: May 2021

Background

Isotretinoin has various effects on nails. However, the mechanism of how isotretinoin affects the nail plate is unknown. We aimed to investigate the effects of isotretinoin on morphology, growth rate, and thickness of the nail plate.

Methods

A total of 70 acne vulgaris patients treated with isotretinoin and a control group consisting of 68 healthy volunteers were included in the study. Isotretinoin treatment was started at a dose of 0.5 mg/kg per day. Nail changes were noted; length and thickness of the nail plate were measured in all participants every month.

Results

The medians of nail growth rates in the isotretinoin and control groups were 3.16 (2.87–3.57) mm/month and 2.89 (2.56–3.19) mm/month, respectively. The medians of nail thickness in the isotretinoin and control groups were 0.47 (0.38–0.53) mm and 0.50 (0.40–0.65) mm, respectively. Statistically significant differences were observed between the groups in terms of nail growth rate and thickness (P < 0.01, P = 0.02, respectively). Nail findings were observed in nine out of 70 patients (12.8%), mostly onychoschizia.

Conclusion

Isotretinoin gradually increases the nail growth rate and thins the nail plate over time during the course of isotretinoin treatment. Dermatologists prescribing isotretinoin should also consider the nail changes, which may impact the life quality of patients.
Novel peptides from dried squid head by‐products obtained from snack process
Authors: Sukkhown Pattraporn , Pirak Tantawan , Jangchud Kamolwan , Prinyawiwatkul Witoon
Published: May 2021

The novel peptides were successfully produced with commercial protease hydrolysis (Alcalase® and Flavourzyme®) at the fixed concentration of 3%by weight of protein in substrate. The hydrolysis was performed at various hydrolysis times (0, 300, 450, 600 and 750 min) at the optimal pH and temperature. When the hydrolysis was performed until 750 min, the peptide solutions with high soluble protein content were resulted (47.58 and 42.53 mg protein per mL for Alcalase® and Flavourzyme® hydrolysis, respectively). After freeze drying, the peptide powder from Alcalase® and Flavourzyme® hydrolysis had degree of hydrolysis at 71.87% and 66.39%, respectively. Alcalase® hydrolysis provided the novel peptide fraction with DPPH scavenging, ABTS activity and ACE‐inhibitory activity at 64.20%, 102.50 µg mL−1 and 56.98%, respectively. This peptide fraction possessed the lowest molecular weight (m/z 807.418) as detected by MALDI‐TOF/MS, and the most potent peptide sequence was Arg‐Glu‐Gly‐Tyr‐Phe‐Lys which has the potential as functional ingredient in novel food, snacks and beverages.
Aflatoxins: Occurrence in red chilli and control by gamma irradiation
Authors: Ayob Omeera , Hussain Peerzada Rashid , Naqash Farah , Riyaz Lubna , Kausar Tahreem , Joshi Sweta , Azad Zulfiqarur Rashid Azaz Ahmad
Published: May 2021

Chilli is one of the valuable spices commercialised globally, added as condiments in various cuisines and is easily susceptible to aflatoxin contamination (produced mainly by Aspergillus flavus) during pre‐ and post‐harvesting stages. The important factors such as temperature, moisture content and humidity affect the growth of fungi producing aflatoxins. Chillies contaminated with aflatoxins could be carcinogenic and thus can pose a threat to the general population leading to the loss of international trade market. Therefore, to overcome this problem, there is a need for some effective and novel technologies such as gamma irradiation. Gamma irradiation minimises the toxicological effects of aflatoxins by inhibiting the growth as well as the proliferation of Aspergillus species. In this work, the natural occurrence of aflatoxins including the contribution of gamma irradiation on either eliminating or controlling the aflatoxins in red chilli is reviewed.
Comparative evaluation of the composition of vegetable essential and fixed oils obtained by supercritical extraction and conventional techniques: a chemometric approach
Authors: Piras Alessandra , Piras Cristina , Porcedda Silvia , Rosa Antonella
Published: May 2021

We compared by a chemometric approach the composition of essential (EO) and fixed (FO) oils previously obtained from several vegetable matrices by supercritical CO2 extraction (CO2‐SFE) and conventional techniques (n‐hexane in a Soxhlet apparatus and hydrodistillation). A multivariate approach, by determining the principal components analysis (PCA) applied to data of FO fatty acids and EO volatile compounds, generally indicated that the vegetable oils extracted with CO2‐SFE tightly clustered with those obtained by conventional methods. The graphical distances calculated in the PCA plots between the score of each SFE oil and the corresponding conventional oil revealed that the CO2‐SFE FO and EO profiles were quite similar to conventional oils, with the additional benefit of not having unwanted traces of solvent. SFE FO were more similar to conventional oils than SFE EO (mean values of calculated graphical distances were 0.83 and 1.46 for FO and EO, respectively). Our results strongly corroborate the role of CO2‐SFE as a suitable, environmentally safe and efficient method alternative to the traditional ones for the extraction of natural vegetable oils for food and pharmaceutical applications.
What are the potential strategies to achieve potentially more healthful meat products?
Authors: Guedes‐Oliveira Juliana M. , Brad Kim Yuan H. , Conte‐Junior Carlos A.
Published: May 2021

In recent years, much attention has been paid to the consumption of meat and processed meat, and their relationship with a healthy diet. This review provides an overview of the potential strategies, which can be used to provide the implications for producing healthy, wholesome and consistently high‐quality meat products. Genetic selection, nutrition and feeding management, and gene manipulation techniques have been used as the main strategies to induce beneficial changes in meat and meat composition. Besides, the incorporation of ingredients that play a technological role and are potentially health‐enhancing, such as fibre, fat substitutes, natural antioxidants and the reduction of sodium and nitrites, has a high potential in the development of healthier meat products. In this review, we have observed that many strategies have been successfully used to obtain products with low fat, reduced sodium and nitrite content, low cholesterol and absence of synthetic antioxidants. Another point to be highlighted is that some of these strategies also allow obtaining products with positive health effects that can be potential alternatives to improve consumer acceptance.