bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutational sources oftrans-regulatory variation affecting gene expression inSaccharomyces cerevisiae
Authors: Duveau Fabien , Zande Petra Vande , Metzger Brian P. H. , Diaz Crisandra J. , Walker Elizabeth A. , Tryban Stephen , Siddiq Mohammad A. , Yang Bing , Wittkopp Patricia J.
Published: February 2021

Heritable variation in a gene’s expression arises from mutations impactingcis- andtrans-acting components of its regulatory network, with expression variation often derived fromtrans-regulatory mutations within species. Here, we investigate howtrans-regulatory mutations are distributed within the genome and within a gene regulatory network by identifying and characterizing 69 mutations withtrans-regulatory effects on expression of the same focal gene inSaccharomyces cerevisiae. Relative to 1766 mutations without effects on expression of this focal gene, we found that thesetrans-regulatory mutations were enriched in coding sequences of transcription factors previously predicted to regulate expression of the focal gene. However, over 90% of thetrans-regulatory mutations identified mapped to other types of genes involved in diverse biological processes including chromatin state, metabolism and signal transduction. Finally, we find that the genomic distribution of these new regulatory mutations significantly overlaps with the genomic distribution oftrans-regulatory variants segregating withinS. cerevisiae.
Oncofusion-drivende novoenhancer assembly promotes malignancy in Ewing sarcomaviaaberrant expression of the stereociliary protein LOXHD1
Authors: Deng Qu , Natesan Ramakrishnan , Cidre-Aranaz Florencia , Arif Shehbeel , Liu Ying , Rasool Reyaz ur , Wang Pei , Cramer Zvi , Chou Margaret , Kumar-Sinha Chandan , Weber Kristy , Eisinger-Mathason T S Karin , Grillet Nicolas , Grünewald Thomas , Asangani Irfan A.
Published: February 2021

Ewing Sarcoma (EwS) is a highly aggressive tumor of bone and soft tissues that mostly affects children and adolescents. The pathognomonic oncofusion EWSR1-ETS (EWSR1-FLI1/EWSR1-ERG) transcription factors drive EwS by orchestrating an oncogenic transcription program throughde novoenhancers. Pharmacological targeting of these oncofusions has been challenged by unstructured prion-like domains and common DNA binding domains in the EWSR1 and ETS protein, respectively. Alternatively, identification and characterization of mediators and downstream targets of EWSR1-FLI1 dependent or independent function could offer novel therapeutic options. By integrative analysis of thousands of transcriptome datasets representing pan-cancer cell lines, primary cancer, metastasis, and normal tissues, we have identified a 32 gene signature (ESS32 - Ewing Sarcoma Specific 32) that could stratify EwS from pan-cancer. Of the ESS32, LOXHD1 – that encodes a stereociliary protein, was the most exquisitely expressed gene in EwS. CRISPR-Cas9 mediated deletion or silencing of EWSR1-FLI1 bound upstreamde novoenhancer elements in EwS cells led to the loss of LOXHD1 expression and altered the EWSR1-FLI1, MYC, and HIF1α pathway genes, resulting in decreased proliferation and invasionin vitroandin vivo. These observations implicate LOXHD1 as a novel biomarker and a major determinant of EwS metastasis and open up new avenues for developing LOXHD1-targeted drugs or cellular therapies for this deadly disease.
Engineering protease-resistant peptides to inhibit human parainfluenza viral respiratory infection
Authors: Outlaw Victor K. , Cheloha Ross W. , Jurgens Eric M. , Bovier Francesca T. , Zhu Yun , Kreitler Dale F. , Harder Olivia , Niewiesk Stefan , Porotto Matteo , Gellman Samuel H. , Moscona Anne
Published: February 2021

The lower respiratory tract infections affecting children worldwide are in large part caused by the parainfluenza viruses (HPIVs), particularly HPIV3, along with human metapneumovirus and respiratory syncytial virus, enveloped negative-strand RNA viruses. There are no vaccines for these important human pathogens, and existing treatments have limited or no efficacy. Infection by HPIV is initiated by viral glycoprotein-mediated fusion between viral and host cell membranes. A viral fusion protein (F), once activated in proximity to a target cell, undergoes a series of conformational changes that first extend the trimer subunits to allow insertion of the hydrophobic domains into the target cell membrane, and then refold the trimer into a stable postfusion state, driving the merger of the viral and host cell membranes. Lipopeptides derived from the C-terminal heptad repeat (HRC) domain of HPIV3 F inhibit infection by interfering with the structural transitions of the trimeric F assembly. Clinical application of this strategy, however, requires improving thein vivostability of antiviral peptides. We show that the HRC peptide backbone can be modified via partial replacement of α-amino acid residues with β-amino acid residues to generate α/β-peptides that retain antiviral activity but are poor protease substrates. Relative to a conventional α-lipopeptide, our best α/β-lipopeptide exhibits improved persistencein vivoand improved anti-HPIV3 antiviral activity in animals.
A G protein-coupled receptor is required in cartilaginous and dense connective tissues to maintain spine alignment
Authors: Liu Zhaoyang , Hussien Amro A. , Wang Yunjia , Heckmann Terry , Gonzalez Roberto , Karner Courtney M. , Snedeker Jess G. , Gray Ryan S.
Published: February 2021

Adolescent idiopathic scoliosis (AIS) is the most common spine disorder affecting children worldwide, yet little is known about the pathogenesis of this disorder. Here, we demonstrate that genetic regulation of structural components of the axial skeleton, the intervertebral discs and dense connective tissues (e.g., ligaments and tendons), are essential for maintenance of spinal alignment. We show that the G-coupled protein receptorAdgrg6, previously implicated in human AIS association studies, is required in these tissues to maintain typical spine morphology. We show thatAdgrg6regulates biomechanical properties of tendon and stimulates CREB signaling governing gene expression in cartilaginous tissues of the spine. Treatment with an cAMP agonist was able to mirror aspects of receptor function in culture defining core pathways for regulation of these axial connective tissues. AsADGRG6is a key gene involved in human AIS, these findings open up novel therapeutic opportunities for human scoliosis.

Highlights

Knockout mice lackingAdgrg6function in the tendons and ligaments of the spine develop perinatal-onset thoracic scoliosis.

Loss ofAdgrg6function in cartilaginous tissues of the discs contribute to the incidence and severity of scoliosis.

The loss ofAdgrg6function in spine tissues provide a model of construct validity for human adolescent idiopathic scoliosis

Fine tuning of the biomechanical properties of dense connective tissues is essential for maintaining spine alignment.
Dominance shifts increase the likelihood of soft selective sweeps
Authors: Muralidhar Pavitra , Veller Carl
Published: February 2021

Genetic models of adaptation to a new environment have typically assumed that the alleles involved maintain a constant fitness dominance across the old and new environments. However, theories of dominance suggest that this should often not be the case. Instead, the alleles involved should frequently shift from recessive deleterious in the old environment to dominant beneficial in the new environment. Here, we study the consequences of these expected dominance shifts for the genetics of adaptation to a new environment. We find that dominance shifts increase the likelihood that adaptation occurs from the standing variation, and that multiple alleles from the standing variation are involved (a soft selective sweep). Furthermore, we find that expected dominance shifts increase the haplotypic diversity of selective sweeps, rendering soft sweeps more detectable in small genomic samples. In cases where an environmental change threatens the viability of the population, we show that expected dominance shifts of newly beneficial alleles increase the likelihood of evolutionary rescue and the number of alleles involved. Finally, we apply our results to a well-studied case of adaptation to a new environment: the evolution of pesticide resistance at theAcelocus inDrosophila melanogaster. We show that, under reasonable demographic assumptions, the expected dominance shift of resistant alleles causes soft sweeps to be the most frequent outcome in this case, with the primary source of these soft sweeps being the standing variation at the onset of pesticide use, rather than recurrent mutation thereafter.
Human basigin (CD147) does not directly interact with SARS-CoV-2 spike glycoprotein
Authors: Ragotte Robert J. , Pulido David , Donnellan Francesca R. , Gorini Giacomo , Davies Hannah , Brun Juliane , King Lloyd D. W. , Skinner Katherine , Draper Simon J.
Published: February 2021

Basigin, or CD147, has been reported as a co-receptor used by SARS-CoV-2 to invade host cells. Basigin also has a well-established role inPlasmodium falciparummalaria infection of human erythrocytes where it is bound by one of the parasite’s invasion ligands, reticulocyte binding protein homolog 5 (RH5). Here, we sought to validate the claim that the receptor binding domain (RBD) of SARS-CoV-2 spike glycoprotein can form a complex with basigin, using RH5-basigin as a positive control. Using recombinantly expressed proteins, size exclusion chromatography and surface plasmon resonance, we show that neither RBD nor full-length spike glycoprotein bind to recombinant human basigin (either expressed inE. colior mammalian cells). Given the immense interest in SARS-CoV-2 therapeutic targets, we would caution the inclusion of basigin in this list on the basis of its reported direct interaction with SARS-CoV-2 spike glycoprotein.

Importance

Reducing the mortality and morbidity associated with COVID-19 remains a global health priority. Critical to these efforts is the identification of host factors that are essential to viral entry and replication. Basigin, or CD147, was previously identified as a possible therapeutic target based on the observation that it may act as a co-receptor for SARS-COV-2, binding to the receptor binding domain of the spike protein. Here, we show that there is no direct interaction between the RBD and basigin, casting doubt on its role as a co-receptor and plausibility as a therapeutic target.
Histone H2Bub1 deubiquitylation is essential for mouse development, but does not regulate global RNA polymerase II transcription
Authors: Wang Fang , El-Saafin Farrah , Ye Tao , Stierle Matthieu , Negroni Luc , Durik Matej , Fischer Veronique , Devys Didier , Vincent Stéphane D. , Tora László
Published: February 2021

Co-activator complexes dynamically deposit post-translational modifications (PTMs) on histones, or remove them, to regulate chromatin accessibility and/or to create/erase docking surfaces for proteins that recognize histone PTMs. SAGA (Spt-Ada-Gcn5 Acetyltransferase) is an evolutionary conserved multisubunit co-activator complex with modular organization. The deubiquitylation module (DUB) of mammalian SAGA complex is composed of the ubiquitin-specific protease 22 (USP22) and three adaptor proteins, ATXN7, ATXN7L3 and ENY2, which are all needed for the full activity of the USP22 enzyme to remove monoubiquitin (ub1) from histone H2B. Two additional USP22-related ubiquitin hydrolases (called USP27X or USP51) have been described to form alternative DUBs with ATXN7L3 and ENY2, which can also deubiquitylate H2Bub1. Here we report that USP22 and ATXN7L3 are essential for normal embryonic development of mice, however their requirements are not identical during this process, asAtxn7l3−/−embryos show developmental delay already at embryonic day (E) 7.5, whileUsp22−/−embryos are normal at this stage, but die at E14.5. Global histone H2Bub1 levels were only slightly affected inUsp22null embryos, in contrast H2Bub1 levels were strongly increased inAtxn7l3null embryos and derived cell lines. Our transcriptomic analyses carried out from wild type andAtxn7l3−/−mouse embryonic stem cells (mESCs), or primary mouse embryonic fibroblasts (MEFs) suggest that the ATXN7L3-related DUB activity regulates only a subset of genes in both cell types. However, the gene sets and the extent of their deregulation were different in mESCs and MEFs. Interestingly, the strong increase of H2Bub1 levels observed in theAtxn7l3−/−mESCs, orAtxn7l3−/−MEFs, does not correlate with the modest changes in RNA Polymerase II (Pol II) occupancy and lack of changes in Pol II elongation observed in the twoAtxn7l3−/−cellular systems. These observations together indicate that deubiquitylation of histone H2Bub1 does not directly regulate global Pol II transcription elongation.
Antiproliferative activity and antioxidative potential of Swiss chard from Montenegro, grown under different irrigation and fertilization regimes
Authors: Ivanović Ljubica , Topalović Ana , Bogdanović Višnja , Đurović Dijana , Mugoša Boban , Jadranin Milka , Tešević Vele , Beškoski Vladimir
Published: February 2021

Purpose

The purpose of this paper is to determine the polyphenol content, antioxidative potential and antiproliferative activity of Swiss chard from Montenegro, grown under different irrigation and fertilization regimes.

Design/methodology/approach

Swiss chard was grown in the open field (Lješkopolje, Montenegro) where it was subjected to different fertilization and irrigation regimes. Chard samples were analyzed for previously identified polyphenols and for antioxidant parameters. Additionally, in order to complete the biological activities, chard extracts were tested for antiproliferative activity against MFC-7 and HT-29 tumor cell lines.

Findings

The polyphenols identified in Swiss chard were flavonoids: vitexin-2?-O-xyloside, vitexin-6?-O-acetyl-2?-O-xyloside, vitexin-6?-O-malonyl-2?-O-xyloside and isorhamnetin-3,7-diglucoside. In the antioxidant tests, DPPH (2,2-diphenyl-1-picrylhydrazyl), and ABTS (2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)), chard extract had values of 7.00 and 8.50 (mean values) µmol Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid) equ/d.w., respectively. The tested chard extracts inhibited cell proliferation at different concentrations (3.125–50.0 µg/mL) against the MCF-7 cell line, after 24 and 48 h of incubation. The antiproliferative activity, expressed in terms of IC50, was 32.97 and 86.45 µg/mL after 24 h of incubation and 20.76 and 23.33 µg/mL after 48 h of incubation, for treated and untreated chard extracts, respectively.

Originality/value

These data suggest Montenegrin Swiss chard grown under different irrigation and fertilization treatments can be considered as a functional food and should be included in an everyday diet. The collected data could help in the growth improvement of chard with functional food properties.
The effects of information technology capability and knowledge base on digital innovation: the moderating role of institutional environments
Authors: Wei Shaobo , Xu Dabao , Liu Hua
Published: February 2021

Purpose

Based on the knowledge-based view, this study investigates how firms' information technology (IT) capability broadens and deepens their knowledge base, which consequently improves digital innovation. By further drawing on the institutional theory perspective, this study examines how the relationships between IT capability and knowledge base are moderated by the institutional environments in which the firm operates.

Design/methodology/approach

This paper uses 170 samples of Chinese firms and an empirical test conducted by the authors following a hierarchical moderated regression analysis.

Findings

The results find that IT capability positively affects knowledge breadth and knowledge depth, which consequently improves digital innovation. Furthermore, the study reveals the negative moderating effects of enforcement inefficiency on IT capability–knowledge breadth relationship, and the negative moderating effects of government support on IT capability–knowledge depth relationship.

Originality/value

This research is one of the earliest attempts to explore the impact of the institutional environment of emerging economies on IT capability. It also clarifies the impact of knowledge breadth and knowledge depth on digital innovation.
A person-situation perspective of informal learning: the role of supervisor feedback environment
Authors: Zia Muhammad Qamar , Bashir Muhammad Adnan , Mangi Riaz Ahmed , Shamsi Aamir Feroz
Published: February 2021

Purpose

Based on trait activation theory, the purpose of the present study is to explore the relationship between the antecedents and outcomes of informal learning with the moderating effect of supervisor feedback environment (SFE) in small- and medium-sized enterprises (SMEs).

Design/methodology/approach

Data (n = 388) were gathered from middle managers of Pakistan’s SME sector by following the purposive sampling technique. The proposed model was examined by means of structural equation modeling analysis with AMOS 24.

Findings

The study results delineate that middle managers with high-level self-efficacy and motivation to learn more actively participate in informal learning activities. The study also found that the SFE is a strong contextual moderator between the nexus of personal factors and informal learning. In addition, informal learning also has significant and positive effect on work engagement.

Practical implications

Human resource practitioners and organizational leaders of small businesses can use informal learning to improve employees’ skills and knowledge with less cost. For instance, management should use different strategies to enhance the effectiveness of informal learning by providing SFE.

Originality/value

There are numerous recent calls for research to ascertain the interaction of individual, contextual factors and outcomes of informal learning. The study addresses these voids by empirically examining antecedents and outcomes of informal learning simultaneously through the person–situation interaction perspective. It demonstrates that informal learning at the workplace becomes more effective in SFE.
Unmanned vehicle dynamic obstacle detection, tracking and recognition method based on laser sensor
Authors: Zhang Hualei , Ikbal Mohammad Asif
Published: February 2021

Purpose

In response to these shortcomings, this paper proposes a dynamic obstacle detection and tracking method based on multi-feature fusion and a dynamic obstacle recognition method based on spatio-temporal feature vectors.

Design/methodology/approach

The existing dynamic obstacle detection and tracking methods based on geometric features have a high false detection rate. The recognition methods based on the geometric features and motion status of dynamic obstacles are greatly affected by distance and scanning angle, and cannot meet the requirements of real traffic scene applications.

Findings

First, based on the geometric features of dynamic obstacles, the obstacles are considered The echo pulse width feature is used to improve the accuracy of obstacle detection and tracking; second, the space-time feature vector is constructed based on the time dimension and space dimension information of the obstacle, and then the support vector machine method is used to realize the recognition of dynamic obstacles to improve the obstacle The accuracy of object recognition. Finally, the accuracy and effectiveness of the proposed method are verified by real vehicle tests.

Originality/value

The paper proposes a dynamic obstacle detection and tracking method based on multi-feature fusion and a dynamic obstacle recognition method based on spatio-temporal feature vectors. The accuracy and effectiveness of the proposed method are verified by real vehicle tests.
Adult children labour migration and parent health: evidence from Indonesian panel data
Authors: Hasanah Alfiah , Kharisma Bayu , Remi Sutyastie Soemitro
Published: February 2021

Purpose

This study aims to explore the impact of adult child labour migration on the health of parents and the possible mechanism that contributes to the health of families left behind.

Design/methodology/approach

Several indicators of parents’ health are analysed and several subgroups – parents of migrant sons, parents of migrant daughters, parents aged 50+ and parents who live in rural areas are investigated. The data from Indonesia Family Life Survey are used and the fixed effects method is used to address potential endogeneity and instrumental variables are applied in the sensitivity analysis.

Findings

The labour out-migration of adult children has a positive and significant association with the health status of the parent left behind. The parents of migrant children are more likely to have a better self-rated health status, fewer episodes of morbidity symptoms, fewer unhealthy days, fewer visits to outpatient care and are less likely to be on medication than the parents of non-migrant children.

Research limitations/implications

The study design in a longitudinal setting, however, there is a relatively many years gap between waves could provide insufficient statistical power for measuring health variations. Future studies should consider to explore possible health outcomes for parents who co-resided with an adult child and the types and severity of various disease conditions.

Practical implications

Highlights challenges in health-care provision for older people in Indonesia and the possible contribution of health disparities in developing countries.

Originality/value

Explores the impact of out-migration of adult children on the health of parents left behind, using very recent data of over a long period of a longitudinal design.
Real-time data integration of an internet-of-things-based smart warehouse: a case study
Authors: Sahara Chelinka Rafiesta , Aamer Ammar Mohamed
Published: February 2021

Purpose

Creating a real-time data integration when developing an internet-of-things (IoT)-based warehouse is still faced with challenges. It involves a diverse knowledge of novel technology and skills. This study aims to identify the critical components of the real-time data integration processes in IoT-based warehousing. Then, design and apply a data integration framework, adopting the IoT concept to enable real-time data transfer and sharing.

Design/methodology/approach

The study used a pilot experiment to verify the data integration system configuration. Radio-frequency identification (RFID) technology was selected to support the integration process in this study, as it is one of the most recognized products of IoT.

Findings

The experimentations’ results proved that data integration plays a significant role in structuring a combination of assorted data on the IoT-based warehouse from various locations in a real-time manner. This study concluded that real-time data integration processes in IoT-based warehousing could be generated into three significant components: configuration, databasing and transmission.

Research limitations/implications

While the framework in this research was carried out in one of the developing counties, this study’s findings could be used as a foundation for future research in a smart warehouse, IoT and related topics. The study provides guidelines for practitioners to design a low-cost IoT-based smart warehouse system to obtain more accurate and timely data to support the quick decision-making process.

Originality/value

The research at hand provides the groundwork for researchers to explore the proposed theoretical framework and develop it further to increase inventory management efficiency of warehouse operations. Besides, this study offers an economical alternate for an organization to implement the integration software reasonably.
How legitimate are the environmental sustainability claims of luxury conglomerates?
Authors: Wells Victoria , Athwal Navdeep , Nervino Esterina , Carrigan Marylyn
Published: February 2021

Purpose

By responding to scholarly calls, this study examines the environmental reports of LVMH and Kering. The study extends legitimacy theory to ascertain the credibility of the aforementioned luxury conglomerates' commitment to environmental sustainability.

Design/methodology/approach

A corpus-assisted discourse analysis centred upon the Global Reporting Initiative (GRI) guidelines is used to examine the environmental disclosures of LVMH and Kering.

Findings

The findings show inconsistencies due to the lack of brand-level reporting and reporting quality falls short of comparable sustainability reporting within each conglomerate and with one another. Selective and unbalanced reporting along with symbolic management undermines the legitimacy of sustainability efforts by LVMH and Kering.

Originality/value

Despite the increased attention paid to sustainable luxury, few studies critically analyse how luxury brands formally report on sustainability.
Learning-based error modeling in FDM 3D printing process
Authors: Charalampous Paschalis , Kostavelis Ioannis , Kontodina Theodora , Tzovaras Dimitrios
Published: February 2021

Purpose

Additive manufacturing (AM) technologies are gaining immense popularity in the manufacturing sector because of their undisputed ability to construct geometrically complex prototypes and functional parts. However, the reliability of AM processes in providing high-quality products remains an open and challenging task, as it necessitates a deep understanding of the impact of process-related parameters on certain characteristics of the manufactured part. The purpose of this study is to develop a novel method for process parameter selection in order to improve the dimensional accuracy of manufactured specimens via the fused deposition modeling (FDM) process and ensure the efficiency of the procedure.

Design/methodology/approach

The introduced methodology uses regression-based machine learning algorithms to predict the dimensional deviations between the nominal computer aided design (CAD) model and the produced physical part. To achieve this, a database with measurements of three-dimensional (3D) printed parts possessing primitive geometry was created for the formulation of the predictive models. Additionally, adjustments on the dimensions of the 3D model are also considered to compensate for the overall shape deviations and further improve the accuracy of the process.

Findings

The validity of the suggested strategy is evaluated in a real-life manufacturing scenario with a complex benchmark model and a freeform shape manufactured in different scaling factors, where various sets of printing conditions have been applied. The experimental results exhibited that the developed regressive models can be effectively used for printing conditions recommendation and compensation of the errors as well.

Originality/value

The present research paper is the first to apply machine learning-based regression models and compensation strategies to assess the quality of the FDM process.
Executive Accountability and National Security
Authors: Woods Lorna , McNamara Lawrence , Townend Judith
Published: February 2021

The protection of national security has traditionally been an exception to general norms of public accountability, based on prerogative powers. The last three decades have seen efforts to bring national security closer to the normal constitutional control mechanisms of parliament and the courts. The design of and changes to mechanisms of accountability have, however, been accepted without discussion of the often narrower purposes for which they were first established (most notably for oversight of surveillance), the extent of their departure from constitutional principles, or their impact in embedding new forms of exceptionalism in the constitutional framework. This article critically assesses these developments, prompted for example by the Law Commission's recommendations to reform official secrets laws, which adopted trusted intermediary and indirect accountability models without full consideration of historical and contemporary concerns or the exceptionalism on which they were based. Though focused on the UK, our account provides a cautionary tale for national security law reform in any modern democracy.
Diagnostic indicators of risk‐prone health behaviors in pregnant adolescents
Authors: Santos Rosely Leyliane dos , Oliveira Antonia Jussara Olinda , de Sampaio Ygor Cleiton Oliveira , Guedes Nirla Gomes , Lopes Marcos Venícios de Oliveira , da Silva Viviane Martins
Published: February 2021

Purpose

This study aimed to identify diagnostic indicators associated with the nursing diagnosis risk‐prone health behaviors in pregnant adolescents.

Methods

We conducted a cross‐sectional study. The sample consisted of 181 pregnant adolescents. A latent class analysis was conducted to verify associations between the defining characteristics of risk‐prone health behaviors and diagnostic accuracy measures. Logistic regression was used to identify factors associated with the manifestation of risk‐prone health behavior.

Findings

The prevalence of risk‐prone health behaviors in this sample was 31.04%. The defining characteristics failure to take action that prevents health problems and inappropriate eating habits achieved a high sensitivity. The related factors such as insufficient social support, stressors, low self‐efficacy, social anxiety, isolated region of residence, and restricted access to health services presented significant associations with risk‐prone health behavior.

Conclusions

The diagnostic indicators associated with the nursing diagnosis of risk‐prone health behavior were failure to take action that prevents health problems inappropriate eating habits, insufficient social support, stressors, low self‐efficacy, social anxiety, isolated region of residence, and restricted access to health services.

Implications for nursing practice

This study contributes to knowledge about the diagnostic indicators of risk‐prone health behavior, which may help nurses reach the proper diagnosis. This will facilitate the application of clinical judgment in nursing care to assist pregnant adolescents.
Sex‐Specific Risk Profiles for Suicide Among Persons with Substance Use Disorders in Denmark
Authors: Adams Rachel Sayko , Jiang Tammy , Rosellini Anthony J. , Horváth‐Puhó Erzsébet , Street Amy E. , Keyes Katherine M. , Cerdá Magdalena , Lash Timothy L. , Sørensen Henrik Toft , Gradus Jaimie L.
Published: February 2021

Background and Aims

Persons with substance use disorders (SUDs) are at elevated risk of suicide death. We identified novel risk factors and interactions that predict suicide among men and women with SUD using machine learning.

Design

Case–cohort study.

Setting

Denmark.

Participants

The sample was restricted to persons with their first SUD diagnosis during 1995 to 2015. Cases were persons who died by suicide in Denmark during 1995 to 2015 (n= 2774) and the comparison subcohort was a 5% random sample of individuals in Denmark on 1 January 1995 (n= 13 179).

Measurements

Suicide death was recorded in the Danish Cause of Death Registry. Predictors included social and demographic information, mental and physical health diagnoses, surgeries, medications, and poisonings.

Findings

Persons among the highest risk for suicide, as identified by the classification trees, were men prescribed antidepressants in the 4 years before suicide and had a poisoning diagnosis in the 4 years before suicide; and women who were 30+ years old and had a poisoning diagnosis 4 years before and 12 months before suicide. Among men with SUD, the random forest identified five variables that were most important in predicting suicide; reaction to severe stress and adjustment disorders, drugs used to treat addictive disorders, age 30+ years, antidepressant use, and poisoning in the 4 prior years. Among women with SUD, the random forest found that the most important predictors of suicide were prior poisonings and reaction to severe stress and adjustment disorders. Individuals in the top 5% of predicted risk accounted for 15% of all suicide deaths among men and 24% of all suicides among women.

Conclusions

In Denmark, prior poisoning and comorbid psychiatric disorders may be among the most important indicators of suicide risk among persons with substance use disorders, particularly among women.
An inguinal hernia that arose after robot‐assisted radical prostatectomy and the repair of an intraoperative external iliac vein injury: A case report
Authors: Nakanishi Ryo , Igarashi Kazuharu , Hosaka Miki , Ishi Satoru , Tsutsui Atsuko , Wakabayashi Go
Published: February 2021

This case involved a 63‐year‐old man. He underwent robot‐assisted radical prostatectomy (RARP) for prostate cancer. One year after the operation, he consulted our hospital about left inguinal swelling. Under a diagnosis of a left external inguinal hernia, transabdominal preperitoneal repair (TAPP) was performed under general anesthesia. The inside of the hernia orifice had been damaged by the RARP, and the resultant fibrosis was so marked that it was difficult to dissect the preperitoneal space. Furthermore, an external iliac vein injury occurred during the operation. The bleeding was controlled, and we used laparoscopic continuous non‐absorbable sutures to repair the external iliac vein injury. The number of TAPP procedures performed after radical prostatectomy has been increasing in recent years, but dissecting the preperitoneal space inside a hernia orifice is difficult. Although external iliac vein injuries are rare complications of TAPP procedures, they can be laparoscopically repaired.
MYD88 L265P mutation and interleukin‐10 detection in cerebrospinal fluid are highly specific discriminating markers in patients with primary central nervous system lymphoma: results from a prospective study
Authors: Ferreri Andrés J. M. , Calimeri Teresa , Lopedote Paolo , Francaviglia Ilaria , Daverio Rita , Iacona Chiara , Belloni Cristina , Steffanoni Sara , Gulino Alessandro , Anghileri Elena , Diffidenti Angelo , Finardi Annamaria , Gagliardi Filippo , Anzalone Nicoletta , Nonis Alessandro , Furlan Roberto , De Lorenzo Daniela , Terreni Maria R. , Martinelli Vittorio , Sassone Marianna , Foppoli Marco , Angelillo Piera , Guggiari Elena , Falini Andrea , Mortini Pietro , Filippi Massimo , Tarantino Vittoria , Eoli Marica , Ciceri Fabio , Doglioni Claudio , Tripodo Claudio , Locatelli Massimo , Cangi Maria Giulia , Ponzoni Maurilio
Published: February 2021

Reliable biomarkers are needed to avoid diagnostic delay and its devastating effects in patients with primary central nervous system (CNS) lymphoma (PCNSL). We analysed the discriminating sensitivity and specificity of myeloid differentiation primary response (88) (MYD88) L265P mutation (mut‐MYD88) and interleukin‐10 (IL‐10) in cerebrospinal fluid (CSF) of both patients with newly diagnosed (n = 36) and relapsed (n = 27) PCNSL and 162 controls (118 CNS disorders and 44 extra‐CNS lymphomas). The concordance of MYD88 mutational status between tumour tissue and CSF sample and the source of ILs in PCNSL tissues were also investigated. Mut‐MYD88 was assessed by TaqMan‐based polymerase chain reaction. IL‐6 and IL‐10 messenger RNA (mRNA) was assessed on PCNSL biopsies using RNAscope technology. IL levels in CSF were assessed by enzyme‐linked immunosorbent assay. Mut‐MYD88 was detected in 15/17 (88%) PCNSL biopsies, with an 82% concordance in paired tissue‐CSF samples. IL‐10 mRNA was detected in lymphomatous B cells in most PCNSL; expression of IL‐6 transcripts was negligible. In CSF samples, mut‐MYD88 and high IL‐10 levels were detected, respectively, in 72% and 88% of patients with newly diagnosed PCNSL and in 1% of controls; conversely, IL‐6 showed a low discriminating sensitivity and specificity. Combined analysis of MYD88 and IL‐10 exhibits a sensitivity and specificity to distinguish PCNSL of 94% and 98% respectively. Similar figures were recorded in patients with relapsed PCNSL. In conclusion, high detection rates of mut‐MYD88 and IL‐10 in CSF reflect, respectively, the MYD88 mutational status and synthesis of this IL in PCNSL tissue. These biomarkers exhibit a very high sensitivity and specificity in detecting PCNSL both at initial diagnosis and relapse. Implications of these findings in patients with lesions unsuitable for biopsy deserve to be investigated.
Using a residency index to estimate the economic value of coastal habitat provisioning services for commercially important fish species
Authors: McCormick Hannah , Salguero‐Gómez Roberto , Mills Morena , Davis Katrina
Published: February 2021

Coastal habitats worldwide face various threats, including sea level rise and land conversion. Coastal habitat loss has important economic consequences, as many of these habitats provide valuable ecosystem services including flood protection, carbon sequestration, and nursery areas for commercially fished species. Quantifying the economic value of these ecosystem services helps target policies for coastal habitat restoration. Here, we demonstrate how to quantify the contribution made by coastal habitats to the revenue (e.g., ex‐vessel values) of commercially fished species by estimating a residency index. This residency index weights the relative importance of a habitat along a species' lifecycle by explicitly incorporating the target species' life histories and the estimated proportion of time the species spends in that habitat at different life stages. We demonstrate how this method can be used to estimate the value of saltmarsh to UK commercial fisheries landings. This analysis suggests that UK saltmarsh contributes annually between 15% and 17.5% of total UK commercial landings for European seabass (Dicentrarchus labrax), European plaice (Pleuronectes platessa), and Common sole (Solea solea). Our findings support an economic argument for saltmarsh protection and restoration. Furthermore, our approach provides a general framework that integrates demographic methods and economic analyses to assess the value of saltmarsh and other coastal habitats for fisheries worldwide.
Outcomes and resource use for liver transplantation in the United States: Insights from the 2009‐2017 National Inpatient Sample
Authors: Aguayo Esteban , Hadaya Joseph , Nakhla Morcos , Williamson Catherine G. , Dobaria Vishal , Mandelbaum Ava , Busuttil Ronald W. , Benharash Peyman , DiNorcia Joseph
Published: February 2021

Introduction

Liver transplantation (LT) is a life‐saving treatment for end‐stage liver disease patients that requires significant resources. We used national data to evaluate LT outcomes and factors associated with hospital resource use.

Methods

Using the National Inpatient Sample, we identified all patients undergoing LT from 2009 to 2017 and defined high‐resource use (HRU) as having costs ≥ 90th percentile. Hierarchical regression models were used to assess factors associated with length of stay (LOS) and HRU.

Results

Over the study period, approximately 53,000 patients underwent LT, increasing from 5,582 in 2009 to 7,095 in 2017 (nptrend < 0.001). Morbidity and mortality were 42.2% and 3.9%, respectively, with a median post‐LT LOS of 10 days. Hospitalization costs increased from $106,866 to $145,868 (nptrend < 0.001). Acute kidney injury (β:4.7 days, P < .001) and end‐stage renal disease (ESRD) with dialysis (β:4.3 days, P < .001) were associated with greater LOS while the Northeast region (AOR:5.2, P < .001), ESRD with dialysis (AOR:3.4, P < .001), heart failure (AOR:2.5, P < .001), and fulminant liver disease (AOR:1.8, P = .01) were associated with HRU.

Conclusion

The cost of LT has increased over time. Renal dysfunction, regional practice patterns, and patient acuity were associated with greater resource use. Transplanting patients before health deterioration may help contain costs, mitigate resource use, and improve LT outcomes.
Metabolic surgery: A clinical update
Authors: Wilson Rickesha , Aminian Ali , Tahrani Abd A.
Published: February 2021

Metabolic and bariatric surgery has grown beyond ‘experimental’ weight‐loss surgery. As techniques have advanced over the last few decades, so has the growing body of research and evidence, proving that both weight‐loss and metabolic health improvement are induced. Metabolic surgery has become the more appropriate term for weight‐loss surgery because of the altered gastrointestinal anatomy and subsequent beneficial metabolic effects. Although the tool of metabolic surgery has been well refined, a large portion of the global population does not have adequate access to it. This clinical update aims to (a) inform healthcare providers from all disciplines about the myriad of benefits of metabolic surgery and (b) equip them with the necessary knowledge to bridge the gap between patients in need of metabolic treatment and the therapies in metabolic surgery available to them.
Aortic valvular stenosis: Novel therapeutic strategies
Authors: Natorska Joanna , Kopytek Magdalena , Undas Anetta
Published: February 2021

Background

Aortic stenosis (AS) prevalence is estimated to reach 4.5 million cases worldwide by the year 2030. AS is a progressive disease without a pharmacological treatment. In the current review, we aimed to investigate novel therapeutic approaches for non‐surgical AS treatment, at least in patients with mild‐to‐moderate AS.

Materials and Methods

The most recent and relevant papers concerned with novel molecular pathways that have potential as therapeutic targets in AS were selected from searches of PubMed and Web of Science up to February 2021.

Results

Growing evidence indicates that therapies using proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, simvastatin/ezetimibe combination, cholesteryl ester transfer protein inhibitors or antisense oligonucleotides targeting apolipoprotein(a) reduce the risk of AS progression. It has been shown that enhanced valvular lipid oxidation may drive AS development by leading to the activation of valvular interstitial cells (VICs), the most abundant valvular cells having a major contribution to valve calcification. Since VICs are able to release pro‐inflammatory cytokines, clotting factors and proteins involved in calcification, strategies targeting these cell activations seem promising as therapeutic interventions. Recently, non‐vitamin K antagonist oral anticoagulants (NOACs) have been shown to inhibit activation of VICs.

Conclusion

Several novel molecular pathways of AS development have been identified over the past few years. Therapies using PCSK9 inhibitors, simvastatin/ezetimibe combination, lipoprotein(a)‐lowering therapy are highly promising candidates as therapeutics in the prevention of mild AS progression, while preclinical studies show that NOACs may inhibit valvular inflammation and coagulation activation and slower the rate of AS progression.
Soil fauna diversity and chemical stressors: a review of knowledge gaps and roadmap for future research
Authors: Beaumelle Léa , Thouvenot Lise , Hines Jes , Jochum Malte , Eisenhauer Nico , Phillips Helen R. P.
Published: February 2021

Soils harbour highly‐diverse invertebrate communities that play important roles for ecosystem services, including the mitigation of environmental pollution. Chemical stressors, such as pesticides, pharmaceuticals and metals, are being increasingly spread into ecosystems due to human activities. While it is crucial to predict the consequences of chemical stressors for soil biodiversity, chemical toxicity is often assessed using individuals or populations in laboratory cultures. There has been no systematic evaluation of the evidence documenting the impacts of chemical stressors on diverse, natural soil communities. Here, we use a comprehensive literature review of 274 studies to evaluate the current state of knowledge about the effects of chemicals on soil fauna communities. Most research has had limited spatial scope, with noteworthy gaps in the regions that are potentially the most threatened by soil pollution (Southern Hemisphere). Furthermore, reports generally were constrained to a few emblematic soil fauna groups (nematodes, collembola and earthworms) and chemical stressors (metals). Future research should address biases in spatial distribution of studies, as well as the taxonomic groups and chemical compounds considered. Specifically, emphasis on indirect effects mediated by species interactions, ecosystem functioning and interactive effects of stressors and climate change, currently lacking in the literature, is needed to improve soil‐biodiversity conservation and restoration efforts, as well as predictions of global diversity change.
Cyclic vomiting syndrome: A narrative review and guide to management
Authors: Kovacic Katja , Li B. U. K.
Published: February 2021

Objectives/Background

Cyclic vomiting syndrome (CVS) is a disabling disorder of gut–brain interaction manifested by stereotypical and severe episodes of nausea and vomiting. Prevalence data indicate that CVS affects 1–2% of children and there has been a recent dramatic rise in diagnosed adults.

Methods

This narrative review summarizes relevant literature pertaining to pediatric and adult CVS and provides a guide to management based on extensive clinical experience.

Results

More timely diagnosis is facilitated by an expert consensus diagnostic approach and limited testing. Some diagnostic tests of exclusion remain essential. These include an upper gastrointestinal (GI) contrast study to exclude intestinal malrotation and basic laboratory screening. An abdominal ultrasound is recommended to exclude renal hydronephrosis in children and biliary disease in adults. Exclusion of metabolic/genetic conditions is warranted in those with specific warning signs, presentation in infants/toddler age, and in those with refractory disease. In the absence of chronic GI symptoms, referral to a GI specialist for upper endoscopy is generally not necessary in children but recommended in adults. A large subset termed migraine‐equivalent CVS display strong clinical and genetic features of migraine. A unifying pathophysiologic core concept involves neuronal hyperexcitability and aberrant central modulation of autonomic signals. This is coupled with multiple susceptibility factors including mitochondrial dysfunction/cellular energy deficits, a hyper‐responsive hypothalamic–pituitary–adrenal axis and many comorbidities that increase vulnerability to triggering events. CVS episodes are frequently triggered by stressors and intercurrent illnesses. Lifestyle and non‐pharmacological interventions thus play a pivotal role in successful management. Pharmacological therapies are categorized into abortive, supportive/rescue, and prophylactic treatments. The majority respond particularly well to migraine‐focused treatment strategies.

Conclusion

Despite improved characterization and understanding, CVS remains classified as a functional disorder of brain–gut interaction that is often disjointly managed by generalists and subspecialists. Early recognition, evaluation, and management will facilitate care and improve outcomes. Further research into its natural history with common progression to migraine headaches, neuroendocrine mechanisms, and the pathophysiologic relation to migraine diathesis is much needed.