bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilizing High-fidelity Simulators in Improving Trainee Confidence and Competency in Code Management
Authors: Tufts Lauren M. , Hensley Christina A. , Frazier Marie D. , Hossino Deena , Domanico Renee S. , Harris Jeffrey K. , Flesher Susan L.
Published: December 2021

Introduction:

Simulation training is central in preparing practitioners for code management that is free from patient harm.
1
The purpose of this study was to determine if using a high-fidelity simulator in pediatric code education would improve trainee confidence and competency compared with the use of a traditional mannequin in the same setting.

Methods:

Fifty-third-year medical students participated in Pediatric Advanced Life Support code training, including a mock code scenario. Students were randomized into two groups and assigned to a simulator group: high-fidelity simulator (Group 1) or traditional mannequin (Group 2). To assess competency, trainees were evaluated using a checklist of required verbalized items or performed during the mock code scenario. To assess confidence, trainees completed pre- and postintervention confidence surveys, which were collected and compared.

Results:

Both Group 1 and Group 2 reported increased overall confidence in code management upon completion of their training. Although confidence increased universally, Group 1 reported increased confidence over that of Group 2 in three specific areas: ability to treat respiratory arrest, ability to run a code, and knowledge of the Pediatric Advanced Life Support algorithm. Group 1 also demonstrated increased competency in code management compared with Group 2 in four key code components: checking airway, checking breathing, checking pulses, and checking capillary refill.

Conclusions:

Trainee confidence increases after completion of Pediatric Advanced Life Support code training, regardless of simulator type utilized. However, trainees were more competent in code management when trained using a high-fidelity simulator compared with a traditional mannequin.
The numerical unified transform method for the nonlinear Schrödinger equation on the half-line
Authors: Yang Xin , Deconinck Bernard , Trogdon Thomas
Published: December 2021

We implement the numerical unified transform method to solve the nonlinear Schrödinger equation on the half-line. For the so-called linearizable boundary conditions, the method solves the half-line problems with comparable complexity as the numerical inverse scattering transform solves whole-line problems. In particular, the method computes the solution at any

x

and

t

without spatial discretization or time stepping. Contour deformations based on the method of nonlinear steepest descent are used so that the method’s computational cost does not increase for large

x
,
t

and the method is more accurate as

x
,
t

increase. Our ideas also apply to some cases where the boundary conditions are not linearizable.
The contribution of plastic sink-in to the static friction of single asperity microscopic contacts
Authors: Brazil Owen , Pethica John B. , Pharr George M.
Published: December 2021

We report microscale friction experiments for diamond/metal and diamond/silica contacts under gigapascal contact pressures. Using a new nanoprobe technique that has a sufficient dynamic range of force and stiffness, we demonstrate the processes involved in the transition from purely interface sliding at the nanoscale to the situation where at least one of the sliding bodies undergoes some plastic deformation. For sliding of micrometre-sized tips on metallic substrates, additional local plastic yielding of the substrate resulting from tangential tractions causes the tip to sink into the surface, increasing the contact area in the direction of loading and resulting in a static friction coefficient higher than the kinetic during ploughing. This sink-in is largely absent in fused silica, and no friction drop is observed, along with lower friction in general. The transition from sink-in within the static friction regime to ploughing in the sliding friction regime is mediated by failure of the contact interface, indicated by a sharp increase in energy dissipation. At lower contact pressures, the elastic interfacial sliding behaviour characteristic of scanning probe or surface force apparatus experiments is recovered, bridging the gap between the exotic realm of nanotribology and plasticity-dominated macroscale friction.
Resilience of cold-water coral holobionts to thermal stress
Authors: Chapron Leila , Galand Pierre E. , Pruski Audrey M. , Peru Erwan , Vétion Gilles , Robin Sarah , Lartaud Franck
Published: December 2021

Cold-water corals are threatened by global warming, especially in the Mediterranean Sea where they live close to their upper known thermal limit (i.e. 13°C), yet their response to rising temperatures is not well known. Here, temperature effects onLophelia pertusaandMadrepora oculataholobionts (i.e. the host and its associated microbiome) were investigated. We found that at warmer seawater temperature (+2°C),L. pertusashowed a modification of its microbiome prior to a change in behaviour, leading to lower energy reserves and skeletal growth, whereasM. oculatawas more resilient. At extreme temperature (+4°C), both species quickly lost their specific bacterial signature followed by lower physiological activity prior to death. In addition, our results showing the holobionts' negative response to colder temperatures (−3°C), suggest that Mediterranean corals live close to their thermal optimum. The species-specific response to temperature change highlights that global warming may affect dramatically the main deep-sea reef-builders, which would alter the associated biodiversity and related ecosystem services.
Population size impacts host–pathogen coevolution
Authors: Papkou Andrei , Schalkowski Rebecca , Barg Mike-Christoph , Koepper Svenja , Schulenburg Hinrich
Published: December 2021

Ongoing host–pathogen interactions are characterized by rapid coevolutionary changes forcing species to continuously adapt to each other. The interacting species are often defined by finite population sizes. In theory, finite population size limits genetic diversity and compromises the efficiency of selection owing to genetic drift, in turn constraining any rapid coevolutionary responses. To date, however, experimental evidence for such constraints is scarce. The aim of our study was to assess to what extent population size influences the dynamics of host–pathogen coevolution. We usedCaenorhabditus elegansand its pathogenBacillus thuringiensisas a model for experimental coevolution in small and large host populations, as well as in host populations which were periodically forced through a bottleneck. By carefully controlling host population size for 23 host generations, we found that host adaptation was constrained in small populations and to a lesser extent in the bottlenecked populations. As a result, coevolution in large and small populations gave rise to different selection dynamics and produced different patterns of host–pathogen genotype-by-genotype interactions. Our results demonstrate a major influence of host population size on the ability of the antagonists to co-adapt to each other, thereby shaping the dynamics of antagonistic coevolution.
The genetic basis of phage susceptibility, cross-resistance and host-range in Salmonella
Authors: Adler Benjamin A. , Kazakov Alexey E. , Zhong Crystal , Liu Hualan , Kutter Elizabeth , Lui Lauren M. , Nielsen Torben N. , Carion Heloise , Deutschbauer Adam M. , Mutalik Vivek K. , Arkin Adam P.
Published: December 2021

Though bacteriophages (phages) are known to play a crucial role in bacterial fitness and virulence, our knowledge about the genetic basis of their interaction, cross-resistance and host-range is sparse. Here, we employed genome-wide screens in

Salmonella enterica

serovar Typhimurium to discover host determinants involved in resistance to eleven diverse lytic phages including four new phages isolated from a therapeutic phage cocktail. We uncovered 301 diverse host factors essential in phage infection, many of which are shared between multiple phages demonstrating potential cross-resistance mechanisms. We validate many of these novel findings and uncover the intricate interplay between RpoS, the virulence-associated general stress response sigma factor and RpoN, the nitrogen starvation sigma factor in phage cross-resistance. Finally, the infectivity pattern of eleven phages across a panel of 23 genome sequenced

Salmonella

strains indicates that additional constraints and interactions beyond the host factors uncovered here define the phage host range.
Single Molecule Analysis of differential functional mechanisms of MtRecG while being exposed to variants of stalled replication-fork
Authors: Bandyopadhyay Debolina , Mishra Padmaja P
Published: December 2021

Helicases are motor proteins involved in multiple activities to carry out manipulation of the nucleic acids for efficient gene regulation. In case of roadblocks that can lead the replication machinery to get halted, a complex molecular surveillance system utilizing helicases as its key player ensures the halted fork to resume its duplication process. RecG, belonging to the category of Superfamily-2 plays a vital role in rescuing different kinds of stalled fork. Here, through adoption of single-molecule techniques we have attempted to probe the DNA unwinding features by RecG and tried to capture several stages of genetic rearrangement. An elevated processivity of RecG has been observed for the kinds of stalled fork where progression of lagging daughter strand is ahead than that of the leading strand. Through precise alteration of its function in terms of unwinding, depending upon the substrate DNA, RecG catalyzes the formation of Holliday junction from a stalled fork DNA. In summary, we have featured that RecG adopts asymmetric mode of locomotion to unwind the lagging daughter strand to facilitate Holliday junction creation which acts as a suitable intermediate for recombinational repair pathway.
NeuroXNet: Creating A Novel Deep Learning Architecture that Diagnoses Neurological Disorders, Finds New Blood Biomarkers, and Assesses Surgical, Drugs, and Radiation Treatment Plans Using Medical Imaging and Genomic Data
Authors: Mishra Vaibhav
Published: December 2021

Neurodegenerative diseases and cancerous brain tumors cause millions of patients worldwide to be fatally ill and face cognitive impairment each year. Current diagnosis and treatment of these neurological conditions take many days, are sometimes inaccurate, and use invasive approaches that could endanger the patient’s life. Thus, this study’s purpose is the creation of a novel deep learning model called NeuroXNet, which uses MRI images and genomic data to diagnose both neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, and Mild Cognitive Impairment as well as cancerous brain tumors, including glioma, meningioma, and pituitary tumors. Moreover, the model helps find novel blood biomarkers of differentially expressed genes to aid in diagnosing the six neurological conditions. Furthermore, the model uses patient genomic data to give additional recommendations for treatment plans that include various treatment approaches, including surgical, radiation, and drugs for higher patient survival for each class of the disease. The NeuroXNet model achieves a training accuracy of 99.70%, a validation accuracy of 100%, and a test accuracy of 94.71% in multi-class classification of the six diseases and normal patients. Thus, NeuroXNet reduces the chances of misdiagnosis, helps give the best treatment options, and does so in a time/cost-efficient manner. Moreover, NeuroXNet efficiently diagnoses diseases and recommends treatment plans based on patient data using relatively few parameters causing it to be more cost and time-efficient in providing non-invasive approaches to diagnosis and treatment for neurological disorders than current procedures.
RANK is an independent biomarker of poor prognosis in estrogen receptor-negative breast cancer and a therapeutic target in patient-derived xenografts
Authors: Ciscar Marina , Trinidad Eva M. , Perez-Montoyo Hector , Alsaleem Mansour , Jimenez-Santos Maria J. , Toss Michael , Sanz-Moreno Adrian , Vethencourt Andrea , Perez-Chacon Gema , Petit Anna , Soler-Monso Maria T. , Gomez-Miragaya Jorge , Gomez-Aleza Clara , Jimenez Maria , Dobrolecki Lacey E. , Lewis Michael T. , Bruna Alejandra , Mouron Silvana , Quintela-Fandino Miguel , Al-Shahrour Fatima , Martinez-Aranda Antonio , Sierra Angels , Green Andrew R. , Rakha Emad , Gonzalez-Suarez Eva
Published: December 2021

Despite strong preclinical data, the therapeutic benefit of the RANKL inhibitor denosumab in BC patients, beyond its bone-related effects, is unclear. Here, we investigated the prognostic value of RANK expression and its functionality in human BC. We analyzed RANK and RANKL expression in more than 1500 BC cases (777 being estrogen receptor-negative (ER-)) from four independent cohorts. We confirmed that RANK is more frequently expressed in ER- tumors, but it is also found in a subset of ER+ tumors. In ER- BC, RANK expression was independently associated with poor outcome, especially in postmenopausal patients and those who received adjuvant chemotherapy. Gene expression analyses unraveled distinct biology associated with RANK in relation to ER expression and menopause, and evidenced enhanced RANK activation in ER- postmenopausal tumors, together with regulation of metabolic pathways. Functional studies and transcriptomic analyses in ER- RANK+ patients-derived orthoxenografts demonstrated that activation of RANK signaling pathway promotes tumor cell proliferation and stemness, and regulates multiple biological processes including tumor immune surveillance and metabolism. Our results demonstrate that RANK expression is an independent poor prognosis biomarker in postmenopausal ER- BC patients and support the rational of using RANK pathway inhibitors in combination with chemotherapy in ER- BC.
ADAP’s intrinsically disordered region is an actin sponge regulating T cell motility
Authors: Dadwal Nirdosh , Degen Janine , Sticht Jana , Hilal Tarek , Wegner Tatjana , Reichardt Peter , Lyck Ruth , Abadier Michael , Hons Miroslav , Mix Charlie , Kuropka Benno , Stephanowitz Heike , Liu Fan , Schraven Burkhart , Wülfing Christoph , Kliche Stefanie , Freund Christian
Published: December 2021

Intrinsically disordered proteins (IDPs) play a vital role in biological processes that rely on transient molecular compartmentation1. In T cells, the dynamic switching between migration and adhesion mandates a high degree of plasticity in the interplay of adhesion and signaling molecules with the actin cytoskeleton2,3. Here, we show that the N-terminal intrinsically disordered region (IDR) of adhesion- and degranulation-promoting adapter protein (ADAP) acts as a multipronged scaffold for G- and F-actin, thereby promoting actin polymerization and bundling. Positively charged motifs, along a sequence of at least 200 amino acids, interact with both longitudinal sides of G-actin in a promiscuous manner. These polymorphic interactions with ADAP become constrained to one side once F-actin is formed. Actin polymerization by ADAP acts in synergy with a capping protein but competes with cofilin. In T cells, ablation of ADAP impairs adhesion and migration with a time-dependent reduction of the F-actin content in response to chemokine or T cell receptor (TCR) engagement. Our data suggest that IDR-assisted molecular crowding of actin above the critical concentration defines a new mechanism to regulate cytoskeletal dynamics. The principle of IDRs serving as molecular sponges to facilitate regulated self-assembly of filament-forming proteins might be a general phenomenon.
The barriers and facilitators of radical innovation implementation in secondary healthcare: a systematic review
Authors: Thijssen Salina V. , Jacobs Maria J.G. , Swart Rachelle R. , Heising Luca , Ou Carol X.J. , Roumen Cheryl
Published: December 2021

Purpose

This study aimed to identify the barriers and facilitators related to the implementation of radical innovations in secondary healthcare.

Design/methodology/approach

A systematic review was conducted and presented in accordance with a PRISMA flowchart. The databases PubMed and Web of Science were searched for original publications in English between the 1st of January 2010 and 6th of November 2020. The level of radicalness was determined based on five characteristics of radical innovations. The level of evidence was classified according to the level of evidence scale of the University of Oxford. The Consolidated Framework for Implementation Research was used as a framework to classify the barriers and facilitators.

Findings

Based on the inclusion and exclusion criteria, nine publications were included, concerning six technological, two organizational and one treatment innovation. The main barriers for radical innovation implementation in secondary healthcare were lack of human, material and financial resources, and lack of integration and organizational readiness. The main facilitators included a supportive culture, sufficient training, education and knowledge, and recognition of the expected added value.

Originality/value

To our knowledge, this is the first systematic review examining the barriers and facilitators of radical innovation implementation in secondary healthcare. To ease radical innovation implementation, alternative performance systems may be helpful, including the following prerequisites: (1) Money, (2) Added value, (3) Timely knowledge and integration, (4) Culture, and (5) Human resources (MATCH). This study highlights the need for more high-level evidence studies in this area.
A review on the identification of total productive maintenance critical success factors for effective implementation in the manufacturing sector
Authors: Chaurey Sudhir , Kalpande Shyamkumar D. , Gupta R.C. , Toke Lalit K.
Published: December 2021

Purpose

The purpose of this paper is to carry out the literature search on manufacturing organizations and total productive maintenance (TPM). This research aims at studying TPM attributes and barriers in line with the TPM framework for effective implementation of TPM. This study identifies the barriers in TPM implementation and the critical success factors (CSFs) for effective TPM implementation.

Design/methodology/approach

In this manuscript, the study of TPM in the manufacturing sector has been considered a broad area of the research and emphasis on the TPM literature review, which primarily relates to the contribution of manufacturing sector and employment availability. Next sections covers TPM history, importance, justification, pillars, obstacles and TPM implementation procedure and models. Thereafter author identified the gaps in existing literature.

Findings

The existing literature shows that very few TPM implementation models are available for the manufacturing sector. The study also found that there is no systematically conducted large-scale empirical research which deals with TPM implementation. In order to bridge this gap, an investigation into the successful implementation of TPM in is truly needed. The finding of the literature shows that there is a need of TPM model specially developed for the manufacturing sector. The identified critical factors derived from the extensive literature review help to overcome the barriers for effective TPM implementation.

Research limitations/implications

This review study is limited to Indian manufacturing industries. The identified TPM CSFs are based on the TPM pillars and their sub-factors. This cross-sectional study was based on the existing TPM model.

Practical implications

This paper can increase the significance of TPM strategy, which could help managers of organizations to have a better understanding of the benefits of implementing TPM and therefore enable patient satisfaction within their organizations.

Originality/value

The literature review covers methodical identification of TPM barriers and critical factors for maintenance performance improvements. It allows the practitioners to apply these identified CSFs for TPM implementation to achieve an improvement in industrial performance and competitiveness.
Spurring inclusive entrepreneurship and student development post-C19: synergies between research and business plan competitions
Authors: Gonzalez Laura
Published: December 2021

Purpose

Academic innovation strives to benefit from an ample talent pool, and entrepreneurship and research competitions constitute an integral part of the effort. This prompts discussions about how to optimize the impact of interdisciplinary learning, especially for less-traditional participants. The main purpose of this article is to describe how synergies between research and business plan competitions can facilitate inclusive engagement and enhanced development of transferable skills.

Design/methodology/approach

A case illustration addresses the following questions: (1) what skills can be enhanced through a single project toward parallel participation in research and business plan competitions? (2) How can synergies between research and business plan competitions support more inclusive student development? The case illustration outlines the process and outcomes of an initiative with three first-gen business students, two female and two international.

Findings

The case illustration describes how synergies and alignments of deadliness between research and business plan competitions enhanced the learning process by facilitating more opportunities to showcase learning and receive feedback. In addition, the parallel preparation facilitated student inclusion by providing purposeful authentic practice in a project envisioned by the students. As a result of the 2019 learning experience, students and their employers continue to value in 2021 the effective development of transferable skills.

Originality/value

Previous studies examine independently entrepreneurship initiatives, science technology engineering arts and mathematics (STEAM) initiatives, transferable skills and pedagogy that support inclusive education. This manuscript describes the option of synergies between research and entrepreneurship competitions to support more inclusive student development. In addition, it provides recommendations for impact when scaling-up synergies.
Assessment of non-linear behavior and ductility of reinforced concrete structures
Authors: Belhocine Malika , Bouafia Youcef , Kachi Mohand Said , Benyahi Karim
Published: December 2021

Purpose

The calculation and design of the structures are carried out with the aim of obtaining a sufficiently ductile behavior to allow the structure to undergo displacements, without risk of sudden breaks or loss of stability. The purpose of this study is to develop and validate a computer program (Thin beam2), allowing the modeling and simulation of the nonlinear behavior of reinforced concrete elements, on the other part, it is estimating the local and global ductility of the sections or elements constituting these structures.

Design/methodology/approach

The authors present two nonlinear analysis methods to carry out a parametric study of the factors influencing the local and global ductility of reinforced concrete structures. The first consists in evaluating the nonlinear behavior at the level of the cross-section of the reinforced concrete elements used in the elaborate Sectenol 1 program, it allows us to have the local ductility. The second, allows us to evaluate the nonlinear behavior of the element used in the modified thin beam 2 program, it allows us to estimate the overall ductility of the element.

Findings

The validation results of the Thin beam2 program are very satisfactory, by conferring the analytic and experimental results obtained by various researchers and the parametric study shows that each factor such as the compressive strength of the concrete has a favorable effect on ductility. Conversely, the normal compression force and the high resistance of tensioned reinforcements adversely affect ductility.

Originality/value

The reliability of the two programs lies in obtaining the local and global ductility of reinforced concrete structures because the calculation and design of the structures are carried out with the aim of obtaining ductile behavior without risk of breakage and instability.
Bottom‐up effect of host protective symbionts on parasitoid diversity: Limited evidence from two field experiments
Authors: Narayan Karthik Sankar , Vorburger Christoph , Hafer‐Hahmann Nina
Published: December 2021

Protective symbionts can provide effective and specific protection to their hosts. This protection can differ between different symbiont strains with each strain providing protection against certain components of the parasite and pathogen community their host faces. Protective symbionts are especially well known from aphids where, among other functions, they provide protection against different parasitoid wasps. However, most of the evidence for this protection comes from laboratory experiments.

Our aim was to understand how consistent protection is across different symbiont strains under natural field conditions and whether symbiont diversity enhanced the species diversity of colonizing parasitoids, as could be expected from the specificity of their protection.

We used experimental colonies of the black bean aphid Aphis fabae to investigate symbiont‐conferred protection under natural field conditions over two seasons. Colonies differed only in their symbiont composition, carrying either no symbionts, a single strain of the protective symbiont Hamiltonella defensa, or a mixture of three H. defensa strains. These aphid colonies were exposed to natural parasitoid communities in the field. Subsequently, we determined the parasitoids hatched from each aphid colony.

The evidence for a protective effect of H. defensa was limited and inconsistent between years, and aphid colonies harbouring multiple symbiont strains did not support a more diverse parasitoid community. Instead, parasitoid diversity tended to be highest in the absence of H. defensa.

Symbiont‐conferred protection, although a strong and repeatable effect under laboratory conditions may not always cause the predicted bottom‐up effects under natural conditions in the field.
Best person or best mix? How public sector managers understand the merit principle
Authors: Foley Meraiah , Cooper Rae , Colley Linda , Williamson Sue
Published: December 2021

As public sector organisations around the world enact strategies to progress gender equality, managers are forced to navigate the apparent conflict between making employment decisions on individual‐level ‘merit’ and considering the collective constraints and disadvantage that occur along gender lines. In this paper, we investigate how managers’ understandings of merit contribute to this tension. Analysing data collected in focus groups with 273 mid‐level public sector managers in four Australian jurisdictions where efforts to promote gender equality were actively under way, we found that many managers adhered to a highly individualised understanding of merit which precluded them from considering gender or addressing gendered inequality in their employment decisions. Only a small proportion of managers who believed that creating a more representative bureaucracy was a legitimate public sector objective were able to justify considering a candidate's gender as a source of merit. We argue that public sector organisations seeking to promote gender equality should focus managers’ attention on the benefits of achieving a more representative bureaucracy and give managers greater normative and regulatory certainty about how to assess and apply merit in that context.
Noninvasive, visual examination for the presence of gunshot residue on human skin
Authors: Husak Jennifer
Published: December 2021

When a firearm is discharged, the highest concentration of gunshot residue (GSR) is located on a shooter's hands, forearms, and clothing. Currently, collecting GSR from an individual's hands is accomplished with a carbon disk that is submitted for confirmatory analysis in a forensic laboratory. Presumptive chemical tests can be performed in the field, but these tests consume a portion of the GSR particles leaving a reduced amount of evidence available to be collected and sent to a forensic laboratory. An abundance of research exists for detecting GSR particles instantly on different fabrics using an alternate light source (ALS). This study expanded on that research and developed a noninvasive, visual examination to detect GSR on a suspected shooter's hands without destroying or removing any particles prior to collection. The hands of individuals who recently discharged a firearm were examined under a light source between 475 and 530 nm and an infrared (IR) camera. The fluorescent particles observed on a shooter's hands under 520 nm were similar in size and appearance to GSR particles observed on fabrics under an ALS. The fluorescent particles were collected and analyzed for GSR, and the results indicated that GSR particles were present. More testing needs to be conducted to determine if the fluorescent particles observed are inorganic or organic GSR particles. There is also potential to detect GSR under IR light; however, more research needs to be conducted to determine the composition of the particles observed after image enhancement.
Hip and stifle joint anatomy of the Saimaa (Pusa hispida saimensis) and Baltic ringed seals (Pusa hispida botnica)
Authors: Laakkonen Juha , Vedrines Alixia
Published: December 2021

The anatomical architecture of the hip and stifle joints of the Saimaa ringed seal was determined by dissection to be similar to that of the Baltic ringed seal. There was no ligament of the femoral head in the hip joint. The lateral side of the stifle joint lacked a collateral ligament but the collateral ligament on the medial side was of considerable size. The medial meniscus was larger and thicker than the lateral meniscus. The asymmetrical anatomical architecture allows for much lateral movement during aquatic motion, but it is poorly adapted to terrestrial locomotion.
Editorial: don’t forget basic performance measures in the endoscopic assessment of ulcerative colitis
Authors: Laharie David , Rivière Pauline
Published: December 2021

LINKED CONTENT

This article is linked to Feagan et al papers. To view these articles, visit https://doi.org/10.1111/apt.16626
Editorial: sporadic early‐onset colorectal cancer—appreciating aetiologic complexity
Authors: Maratt Jennifer K. , Imperiale Thomas F.
Published: December 2021

LINKED CONTENT

This article is linked to Vuik et al papers. To view these articles, visit https://doi.org/10.1111/apt.16638
Editorial: targeting liver biopsy in NAFLD – the need to expand non‐invasive tools
Authors: Calzadilla Bertot Luis
Published: December 2021

LINKED CONTENT

This article is linked to Kim et al papers. To view these articles, visit https://doi.org/10.1111/apt.16674 and https://doi.org/10.1111/apt.16711
Validation of self‐reported medication use applying untargeted mass spectrometry‐based metabolomics techniques in the Rhineland study
Authors: Alaeddin Nersi , Stingl Julia C. , Breteler Monique M. B. , de Vries Folgerdiena M.
Published: December 2021

Aims

To assess the validity of self‐reported continuous medication use with drug metabolites measured in plasma by using untargeted mass spectrometric techniques.

Methods

In a population‐based cohort in Bonn, Germany, we compared interview‐based, self‐reported medication intake with drug‐specific metabolites measured in plasma (based on participants who completed their study visits between March 2016 and February 2020). Analyses were done stratified by sex and age (<65 years vs ≥65 years). Cohen's kappa (κ) statistics with 95% confidence intervals (CI) were calculated.

Results

A total of 13 drugs used to treat hypertension, gout, diabetes, epilepsy and depression were analysed in a sample of 4386 individuals (mean age 55 years, 56.1% women). Eleven drugs showed almost perfect agreement (κ > 0.8), whereas sitagliptin and hydrochlorothiazide showed substantial (κ = 0.8, 95% CI 0.71–0.90) and moderate agreement (κ = 0.61, 95% CI 0.56–0.66), respectively. Frequency of use allowed sex‐ and age‐stratified analyses for eight and nine drugs, respectively. For five drugs, concordance tended to be higher for women than for men. For most drugs, concordance was higher among individuals aged ≥65 years than among individuals aged <65 years, but these age‐related differences were not statistically significant.

Conclusion

High concordance rates between self‐reported drug use and metabolites measured in plasma suggest that self‐reported drug use is reliable and accurate for assessing drug use.
Structure‐based survey of ligand binding in the human insulin receptor
Authors: Kumar Lokender , Vizgaudis Whitney , Klein‐Seetharaman Judith
Published: December 2021

The insulin receptor is a membrane protein responsible for the regulation of nutrient balance; and therefore, it is an attractive target in the treatment of diabetes and metabolic syndrome. Pharmacology of the insulin receptor involves two distinct mechanisms: (1) activation of the receptor by insulin mimetics that bind in the extracellular domain and (2) inhibition of the receptor TK enzymatic activity in the cytoplasmic domain. While a complete structural picture of the full‐length receptor comprising the entire sequence covering extracellular, transmembrane, juxtamembrane and cytoplasmic domains is still elusive, recent progress through cryoelectron microscopy has made it possible to describe the initial insulin ligand binding events at atomistic detail. We utilize this opportunity to obtain structural insights into the pharmacology of the insulin receptor. To this end, we conducted a comprehensive docking study of known ligands to the new structures of the receptor. Through this approach, we provide an in‐depth, structure‐based review of human insulin receptor pharmacology in light of the new structures.

LINKED ARTICLES

This article is part of a themed issue on Structure Guided Pharmacology of Membrane Proteins (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.14/issuetoc
Global rarity of intact coastal regions
Authors: Williams Brooke A. , Watson James E.M. , Beyer Hawthorne L. , Klein Carissa J. , Montgomery Jamie , Runting Rebecca K. , Roberson Leslie A. , Halpern Benjamin S. , Grantham Hedley S. , Kuempel Caitlin D. , Frazier Melanie , Venter Oscar , Wenger Amelia
Published: December 2021

Management of the land–sea interface is essential for global conservation and sustainability objectives because coastal regions maintain natural processes that support biodiversity and the livelihood of billions of people. However, assessments of coastal regions have focused strictly on either the terrestrial or marine realm. Consequently, understanding of the overall state of Earth's coastal regions is poor. We integrated the terrestrial human footprint and marine cumulative human impact maps in a global assessment of the anthropogenic pressures affecting coastal regions. Of coastal regions globally, 15.5% had low anthropogenic pressure, mostly in Canada, Russia, and Greenland. Conversely, 47.9% of coastal regions were heavily affected by humanity, and in most countries (84.1%) >50% of their coastal regions were degraded. Nearly half (43.3%) of protected areas across coastal regions were exposed to high human pressures. To meet global sustainability objectives, all nations must undertake greater actions to preserve and restore the coastal regions within their borders.
Plant naturalizations are constrained by temperature but released by precipitation
Authors: Häkkinen Henry , Hodgson Dave , Early Regan
Published: December 2021

Aim

During naturalization, many species undergo climatic niche expansion, in which they spread into climates with which they have not been associated previously. This suggests that species are absent from some climatically suitable areas in their native range, but the reason for this is unknown. We aimed to evaluate whether the climatic conditions in which expansion occurs provide information about the causes of niche expansion.

Location

Global.

Time period

Contemporary.

Major taxa studied

Terrestrial plants.

Methods

We compiled native and naturalized occurrence data for 606 terrestrial plant species and compared their native and naturalized climatic niches to detect evidence of climatic niche expansion. Where species showed evidence of niche expansion, we used a variety of circular modelling techniques to investigate further whether species were more likely to expand, or expand further, along some climatic axes than others. We also asked, with or without expansion, whether species were more successful at colonizing the hottest, coldest, wettest or driest portions of their potential niche.

Results

We found climatic niche expansion in 45% of naturalizations of 606 terrestrial plants. Species expanded predominantly into wetter climate than their native niche, somewhat less frequently into drier climate, and only in rare instances into hotter or colder climate. Species were least likely to naturalize in the hottest or coldest portions of their native climatic niche.

Main conclusions

Our results could suggest that the wetter margins of native niches are limited by biotic interactions that are relaxed in the naturalized range. Our results could also suggest that evolutionary adaptation to novel precipitation regimes is occurring, and/or there are time lags caused by slow population growth rates in cold and hot conditions. Regardless of the explanation, range margins associated with precipitation might be the least predictable during naturalization or environmental change.
THINKING ON LOCATION: AN ESSAY IN THE VULNERABILITY OF THE SUBJECT
Authors: LOCK CHARLES
Published: December 2021

This essay addresses problems of how and what we know in an attempt to distinguish what's inside from what's outside and to figure out whether acts of knowing can be plotted on either side of any boundary that might claim to separate inside from outside. Moving beyond the familiar dialectics derived from Hegel's theory of history, the essay reflects on the author's experience as a teacher of English literature “abroad” who has tried to disclaim any privileged access to the interpretation of texts written in English. It was possible to maintain a status as outsider when teaching texts written across the postcolonial world, but such a position was not sustainable when teaching literature by authors from the First Nations of North America. Throughout, various theoretical alternatives are posited, from Mikhail M. Bakhtin's “outsidedness” to Alain Badiou's pursuit (following Saint Paul) of “universal singularity.” None of these theories seems adequate, and the essay's argument finds itself circling around the intractable. That figure of “circling around” would suggest that the outside had been attained, but one can always think of a theme, a context, or a relation in which the subject would find itself again inhabiting the inside. Structuring the argument is the notion of place and location and the Viconian yearning for the strictly geometrical representation of history, and thence of entities in fixed places, and of constant spatial relations between entities—and of metonymy as the figure by whose suppression, alone, space and time have been enabled to persist in their Kantian sovereignty as the a priori categories that ground all our knowing.
Non‐coding RNA‐associated competitive endogenous RNA regulatory networks: Novel diagnostic and therapeutic opportunities for hepatocellular carcinoma
Authors: Khashkhashi Moghadam Sattar , Bakhshinejad Babak , Khalafizadeh Ali , Mahmud Hussen Bashdar , Babashah Sadegh
Published: December 2021

Hepatocellular carcinoma (HCC), as the most prevalent liver malignancy, is annually diagnosed in more than half a million people worldwide. HCC is strongly associated with hepatitis B and C viral infections as well as alcohol abuse. Obesity and nonalcoholic fatty liver disease (NAFLD) also significantly enhance the risk of liver cancer. Despite recent improvements in therapeutic approaches, patients diagnosed in advanced stages show poor prognosis. Accumulating evidence provides support for the regulatory role of non‐coding RNAs (ncRNAs) in cancer. There are a variety of reports indicating the regulatory role of microRNAs (miRNAs) in different stages of HCC. Long non‐coding RNAs (LncRNAs) exert their effects by sponging miRNAs and controlling the expression of miRNA‐targeted genes. Circular RNAs (circRNAs) perform their biological functions by acting as transcriptional regulators, miRNA sponges and protein templates. Diverse studies have illustrated that dysregulation of competing endogenous RNA networks (ceRNETs) is remarkably correlated with HCC‐causing diseases such as chronic viral infections, nonalcoholic steatohepatitis and liver fibrosis/cirrhosis. The aim of the current article was to provide an overview of the role and molecular mechanisms underlying the function of ceRNETs that modulate the characteristics of HCC such as uncontrolled cell proliferation, resistance to cell death, metabolic reprogramming, immune escape, angiogenesis and metastasis. The current knowledge highlights the potential of these regulatory RNA molecules as novel diagnostic biomarkers and therapeutic targets in HCC.
Getting your House in Order for EU Negotiations: When Domestic Constraints Condition Italy's Performance at the EU Level*
Authors: Lovato Marianna
Published: December 2021

Despite being one of the founding members of the European Community and the third largest economy in the EU, Italy does not stand out as a particularly influential negotiator when it comes to day‐to‐day EU decision‐making. Why is it that a country with Italy's political weight, economic resources and administrative capacity has such a patchy record in terms of negotiation success? Examining Italy's negotiation of two key EU policies (2008–16) and relying on an original set of interviews with EU officials and Italian politicians, this paper contends that the answer lies in a set of domestic factors that have largely been neglected by negotiation theory: namely, political, administrative and individual domestic constraints.

This contribution explains Italy's inconsistent performance in EU negotiations, while also developing a broader theoretical framework accounting for the ways in which domestic factors moderate member states' bargaining power and, ultimately, their likelihood of achieving negotiation success.
A prospective study on vulvovaginal candidiasis: multicentre molecular epidemiology of pathogenic yeasts in China
Authors: Song N. , Kan S. , Pang Q. , Mei H. , Zheng H. , Li D. , Cui F. , Lv G. , An R. , Li P. , Xiong Z. , Fan S. , Zhang M. , Chen Y. , Qiao Q. , Liang X. , Cui M. , Li D. , Liao Q. , Li X. , Liu W.
Published: December 2021

Background

Vulvovaginal candidiasis (VVC) is frequent in women of reproductive age, but very limited data are available on the epidemiology in cases of VVC in China.

Objectives

The current study has been conducted to reveal the prevalence, species distribution of yeast causing VVC and molecular genetics of Candida albicans in China.

Methods

Vaginal swabs were collected from 543 VVC outpatients recruited in 12 hospitals in China between September 2017 and March 2018. They were preliminarily incubated on Sabouraud dextrose agar and then positive subjects of which were then transmitted to our institute for further identification. CHROMagar™ was used to isolate Candida species, and all isolates were finally identified by DNA sequencing. Multilocus sequence typing (MLST) was used to analyse phylogenetic relationships of the various C. albicans isolates.

Results

Eleven different yeast species were identified in 543 isolates, among which C. albicans (84.7%) was the most frequent, followed by C. glabrata (8.7%). We obtained 117 unique diploid sequence types from 451 clinical C. albicans isolates and 92 isolates (20.4%) belonged to a New Clade. All the strains appearing in the New Clade were from northern China and they were isolated from non‐recurrent VVC.

Conclusions

Our findings suggest that C. albicans are still the main cause of VVC in China and the majority of C. albicans isolates belongs to Clade 1 with DST 79 and DST 45 being two most common. Moreover, the New Clade revealed in our study seems to be specific to northern China.
Cholecystectomy reduces the risk of cholangiocarcinoma in patients with complicated gallstones, but has negligible effect on hepatocellular carcinoma
Authors: Ahn Hyeong Sik , Kim Hyun Jung , Kang Tae Uk , Park Seon Mee
Published: December 2021

Background and Aim

Gallstones have been reported to be positively associated with hepatobiliary cancers. However, risks of these cancers by cholecystectomy or in patients with complicated gallstones are controversial. We studied the effect of cholecystectomy on the risk of cholangiocarcinoma (CCA) or hepatocellular carcinoma (HCC) in patients with gallstones and subgroup of complicated gallstones.

Methods

Patients with gallstone disease (n = 958 677) and age‐matched and sex‐matched controls (n = 9 586 770) were identified using the Korean National Health Insurance database. Complicated gallstones were defined as gallstones associated with acute cholecystitis or acute cholangitis. Adjusted hazard ratios (adjusted hazard ratios, 95% confidence interval) of CCA and HCC incidences were evaluated in patients with gallstones who received cholecystectomy compared to the controls. We also analyzed these effects in patients with complicated gallstones.

Results

Patients with gallstones showed increased risks of CCA (1.80, 1.67–1.93) and HCC (1.03, 1.00–1.07) compared with controls. Cholecystectomy had minimal effects on the risks of CCA (1.94, 1.76–2.14) and HCC (0.93, 0.87–0.99) compared with those without cholecystectomy. However, patients with complicated gallstones showed highly increased CCA risk (5.62, 4.89–6.46) and a 30% risk reduction after cholecystectomy (3.91, 3.43–4.46). Risk reduction by cholecystectomy was greater for extrahepatic CCA than for intrahepatic CCA or ampulla of Vater cancer. However, the risk of HCC was not different in patients with complicated gallstones and those who underwent cholecystectomy compared to controls.

Conclusion

The risk of CCA was markedly increased in patients with complicated gallstones and was partially reduced by cholecystectomy. The risk change of HCC was minimal with gallstones or cholecystectomy.
(Dis)Solving the Zero Lower Bound Equilibrium through Income Policy
Authors: ASCARI GUIDO , BONCHI JACOPO
Published: December 2021

We investigate the possibility to reflate an economy experiencing a long‐lasting zero lower bound episode with subdued or negative inflation by imposing a minimum level of wage inflation. The income policy under investigation is formalized as a downward nominal wage growth rigidity, such that wage inflation cannot be lower than a fraction of the inflation target. This policy allows dissolving the zero lower bound steady‐state equilibrium in an Overlapping Generations (OLG) model featuring “secular stagnation” and in an infinite‐life model, where this equilibrium emerges due to deflationary expectations.