bluuebunny/crossref_metadata_2025 huggingface dataset:
Anin vitroplatform for the enzymatic characterization of the rhomboid protease RHBDL4
Authors: Bhaduri Satarupa , Braza Mac Kevin E. , Stanchev Stancho , Tauber Marina , Al-Bawab Raghad , Liu Lawrence J. , Trujillo Diego F. , Solorio-Kirpichyan Kristina , Srivastava Ambuj , Sanlley-Hernandez Javier , O’Donoghue Anthony J. , Lemberg Marius K. , Amario Rommie , Strisovsky Kvido , Neal Sonya E.
Published: October 2024

Rhomboid proteases are ubiquitous intramembrane serine proteases that can cleave transmembrane substrates within lipid bilayers. They exhibit many and diverse functions, such as but not limited to, growth factor signaling, immune and inflammatory response, protein quality control, and parasitic invasion. Human rhomboid protease RHBDL4 has been demonstrated to play a critical role in removing misfolded proteins from the Endoplasmic Reticulum and is implicated in severe diseases such as various cancers and Alzheimer’s disease. Therefore, RHBDL4 is expected to constitute an important therapeutic target for such devastating diseases. Despite its critical role in many biological processes, the enzymatic properties of RHBDL4 remain largely unknown. To enable a comprehensive characterization of RHBDL4’s kinetics, catalytic parameters, substrate specificity, and binding modality we expressed and purified recombinant RHBDL4, and employed it in a Förster Resonance Energy Transfer-based cleavage assay. Until now, kinetic studies have been limited mostly to bacterial rhomboid proteases. Ourin vitroplatform offers a new method for studying RHBDL4’s enzymatic function and substrate preferences. Furthermore, we developed and tested potential inhibitors using our assay and successfully identified peptidyl α-ketoamide inhibitors of RHBDL4 that are highly effective against recombinant RHBDL4. We utilize ensemble docking and molecular dynamics (MD) simulations to explore the binding modality of substrate-derived peptides bound to RHBDL4.

Our analysis focused on key interactions and dynamic movements within RHBDL4’s active site that contributed to binding stability, offering valuable insights for optimizing the non-prime side of RHBDL4 ketoamide inhibitors. In summary, our study offers fundamental insights into RHBDL4’s catalytic activities and substrate preferences, laying the foundation for downstream applications such as drug inhibitor screenings and structure-function studies, which will enable the identification of lead drug compounds for RHBDL4.
Evidence for strong cell-scale signalling during planar polarisation in theDrosophilawing
Authors: Carayon Alexandre , Strutt David
Published: October 2024

In developing epithelia, cells become planar polarised with asymmetric localisation of the core planar polarity proteins to opposite cell membranes, where they form stable intercellular complexes. Current models differ regarding the signalling mechanisms required for core protein polarisation. Here, we investigate the existence of cell-intrinsic cell-scale signallingin vivoin theDrosophilapupal wing. We use conditional and restrictive expression tools to spatiotemporally manipulate core protein activity, combined with quantitative measurement of core protein distribution, polarity and stability. Our results provide evidence for a robust cell-scale signal, while arguing against mechanisms that depend on depletion of a limited pool of a core protein or polarised transport of core proteins on microtubules. Furthermore, we show that polarity propagation across a tissue is hard, highlighting the strong intrinsic capacity of individual cells to establish and maintain planar polarity.
Using CRISPR barcoding as a molecular clock to capture dynamic processes at single-cell resolution
Authors: Andres-Lopez Yolanda , Santambrogio Alice , Kafetzopoulos Ioannis , Todd Christopher , Alda-Catalinas Celia , Clark Stephen J. , Reik Wolf , Hernando-Herraez Irene
Published: October 2024

Biological processes are fundamentally dynamic, yet existing methods for capturing these temporal changes are limited. We present scDynaBar, a novel approach that integrates CRISPR-Cas9 dynamic barcoding with single-cell sequencing to enable the recording of temporal cellular events. In this system, genetic barcodes accumulate mutations over a 4-week timeframe and then are sequenced together with the transcriptome of each single cell. We propose that this gradual accumulation of genetic diversity can be exploited to create a time-ordered record of cellular events. To demonstrate this, we apply the system to track the transition from a pluripotent state to a two-cell (2C)–like state in mouse embryonic stem cells (mESCs). The results provide compelling evidence for the transient nature of the 2C-like state. Additionally, our system shows consistent mutation rates across diverse cell types in a mouse gastruloid model, underscoring its robustness and versatility across various biological contexts. This technique not only improves our ability to study cellular dynamics but also creates exciting new opportunities for future applications based on recording temporal signals at the single-cell level—in other words, using dynamic barcoding as a molecular clock.
Sharing channel choices for electric vehicle battery manufacturers when considering range anxiety among heterogeneous consumers
Authors: Chen Ninghao , Li Bin , Zhao Meng , Ren Jiali , Su Jiafu
Published: October 2024

Purpose

This study aims to investigate the optimal pricing decisions and shared channel strategy selection of battery manufacturers considering heterogeneous consumers' range anxiety.

Design/methodology/approach

Amidst the rapid growth of the electric vehicle sector, countries are promoting upgrades in the automotive industry. However, insufficient driving range causes consumer range anxiety. The study utilizes the Stackelberg game model to assess how range anxiety influences battery manufacturers' pricing and channel strategy decisions across three strategies.

Findings

We find that electric vehicle battery manufacturers' decisions to cooperate with third-party sharing platforms (TPSPs) are primarily influenced by fixed costs and consumer range anxiety levels. As range anxiety increases, the cost threshold for joining shared channels rises, reducing cooperation likelihood. However, considering diverse consumer needs, especially a higher proportion of leisure-oriented consumers, increases the likelihood of cooperation. Furthermore, higher battery quality makes direct participation in shared channels more probable.

Originality/value

In the electric vehicle industry, range anxiety is a significant concern. While existing literature focuses on its impact on consumer behavior and charging infrastructure, this study delves into battery manufacturers' strategic responses, offering insights into channel options and pricing strategies amidst diverse consumer segments.
Schools addressing health, wellbeing and sustainability challenges: a literature review of perspectives on social justice, equity and agency
Authors: Carlsson Monica
Published: October 2024

Purpose

This paper explores perspectives on social justice, equity and agency when schools address health, wellbeing and sustainability challenges.

Design/methodology/approach

The paper draws on a literature review of educational research. The analysis is narrative, highlighting how binary conceptions of equity, social justice and agency are explicitly or implicitly evident in the studies included in the review, distinguishing between as well as noting the interplay between the different conceptions.

Findings

Perspectives on social justice and equity are emphasizing the need to address (1) a more equal sharing of resources in education, (2) dominance in education, and (3) community/ies and education as a common good. Perspectives on agency are framed as situated (1) between people (2) between people and structures or social contexts, and (3) between people and nature or the more-than-human. The paper furthermore highlights tendencies and experiences regarding the possibility of addressing these perspectives in different forms of educational practices.

Research limitations/implications

A potential limitation in this review is that 17 out of the 23 included studies are by authors with an Anglo-Saxon background, while a further 3 have a European background. As such, the review mainly represents “Western” perspectives on social justice, equity and agency.

Originality/value

The findings in the paper indicate that despite the fact that social justice, equity and agency are concepts that have been discussed in educational research for a very long time, they cannot be seen as taken-for-granted concepts, and that the research contains a diverse range of perspectives on these concepts — also within research authored by researchers with an Anglo-Saxon or European background.
The international education association of Australia’s first 20 years: strengthening public diplomacy and social licence through professional development, advocacy and research
Authors: Ziguras Christopher , Murray Dennis , Honeywood Phil
Published: October 2024

Purpose

The article examines the ways in which professional associations representing those working in international education are able to shape national systems and thereby change the ways in which the country engages internationally. This is particularly significant for Australia, which has one of the world’s most internationalised higher education systems.

Design/methodology/approach

This paper presents a case study of the International Education Association of Australia, which since 2004 has played a central role in shaping international education policy and practice. It provides an insider account of three authors who have held senior roles in the Association, drawing on first-hand knowledge of institutional history.

Findings

The case study illustrates the ways in which the Association’s professional development, research and policy advocacy activities have helped to broaden Australia’s engagement in international education from a narrow commercial focus. The resulting deeper engagement with a broad range of issues associated with international engagement, including student welfare, outbound mobility, curriculum, migration and transnational education, has transformed policy and practice in Australia.

Originality/value

Although international education is coming to play an increasingly significant role in many systems, little has been written about the role of professional bodies in influencing the character and quality of international engagement. This paper makes a valuable contribution by demonstrating the practical measures that can be employed by international education professional bodies to strengthen public diplomacy and the social licence for global engagement.
Mindfulness matters: unravelling its influence on job demands and emotional exhaustion in remote work
Authors: Deshpande Amruta , Raut Rajesh , Mittal Amit , Kaul Natashaa
Published: October 2024

Purpose

The study aims to investigate the impact of job demands-client-front demands (JDCF) and job demands-office-front demands (JDOF) and family demands (FD) on the perceived competency of work from home (PCWFH) and emotional exhaustion (EE) of remote workers. The study also investigates the impact of mindfulness as a moderator.

Design/methodology/approach

To study the variables, a quantitative survey of 675 remote workers and an interview of 30 remote workers was conducted. The data analysis showed that JDCF, JDOF and FD significantly and negatively affect PCWFH. PCWFH also had a negative impact on EE, supporting the detrimental effect of poor perceived competence on increasing EEs.

Findings

The finding emphasises the value of a supportive work environment and mindfulness training sessions in dealing with the difficulties of remote work. The study concluded that respondents with mindfulness training better manage their emotions to produce better work results.

Practical implications

Managers should include mindfulness practice in their daily routine to enhance their performance and manage EE in remote work.

Originality/value

In augmenting mindfulness literature, this study provides insight into how managers can leverage on mindfulness practice to improve performance.
Profiling consumers for their shopping motivations in modern retail formats in Oman
Authors: Belwal Rakesh , Belwal Shweta , Morgan Zoe , Al Badi Latifa Hamood
Published: October 2024

Purpose

Consumer shopping motivations are evolving in tandem with shifts in products, services and the retail landscape. This paper primarily aims to explore what drives shopping behavior among consumers in Oman. Additionally, the paper aims to profile consumers based on their shopping motivations.

Design/methodology/approach

Based upon the review of literature, we developed a list of 63 items of shopping motivations. Exploratory factor analysis later led to a 12-factor solution involving 50 items, which were refined further into an 11-factor solution involving 44 items using CFA. A combination of hierarchical and k-means cluster analysis was performed for profiling consumers.

Findings

Five distinct segments of consumers that emerged in the Omani food and grocery retail market were derived as Practical Value Seekers, Discerning Shoppers, Selective Online Shoppers, Social Brand Seekers and Instant Gratifiers. Theoretical and managerial implications were discussed.

Practical implications

In theory, this study examines market heterogeneity by considering customer shopping motivations and applies profiling (clustering) techniques to categorize them into distinct market clusters. In practical terms, it provides valuable insights to food and grocery store managers.

Originality/value

This study is novel and the first of its kind, suggesting a typology of food and grocery shoppers in Oman. Research on consumer shopping motivations has primarily focused on consumers in Western countries, particularly in the United States.
Firms financial strength during crisis periods: does “familiness” matter?
Authors: Villagrasa Jorge , Escribá-Esteve Alejandro , Donaldson Colin , Sánchez-Peinado Esther
Published: October 2024

Purpose

In this paper we propose to study the differences among family and non-family-firms in relation to its financial strength, and therefore its potential position to resist in front of financial crisis and receive financial support or conditions by public or private institutions.

Design/methodology/approach

We used multiple hierarchical regressions on a sample of 137 Spanish medium-sized firms (SMEs).

Findings

We observe that the perspectives and idiosyncratic characteristics of family-firms (strongly influenced by their socioemotional wealth) will affect the way these companies invest and operate in the market, which would be more related to efficiency because of their higher willingness to continue the legacy of the business and their weak risk-bearing attributes.

Research limitations/implications

Our study adopts a measure of familiness with a dummy variable, and not as a continuous variable as proposed by recent research. Therefore, our results although relevant and significant for the family firm literature, must be viewed carefully. Additional research could also retest some prior studies to depict differences caused by “real” family firm involvement.

Practical implications

Under a non-munificent environment, the financial strength maintained by firms will be highly relevant since this context could likely stress and influence their immediate future and viability, overcoming and blurring any other characteristic present in the firm or its managers.

Originality/value

This paper contributes to the family firm literature by offering insights into the nuanced dynamics between family and non-family firms during economic downturns, specifically examining their financial strength when different strategic options are pursued and when firms are managed by different type of managers.
Liquidity and credit risks during the COVID-19 pandemic: evidence from a dual banking system
Authors: Rahmadany An Nisaa’ , Risfandy Tastaftiyan , Achsanta Aldy Fariz , Rifai Bahtiar
Published: October 2024

Purpose

The purpose of this paper is to investigate the relationship between liquidity risk and credit risk of Islamic and conventional banks in a predominantly Muslim country (Indonesia) adopting a dual banking system.

Design/methodology/approach

To investigate liquidity-credit risk nexus, this study used a sample of 72 Islamic and conventional banks in Indonesia for a period between 2019 Q4 and 2022 Q1. This paper used a generalized method of moments (GMM) and generalized least square (GLS) estimators.

Findings

This study found that there is a nonlinear (inverted U-shaped) relationship between liquidity risk and credit risk in dual banking system. Liquidity risk was found to increase credit risk if it is below the optimal threshold, and above this optimal threshold, liquidity risk begins to decrease credit risk, both before and during the pandemic. In addition, the impact of liquidity risk on credit risk is higher in Islamic banks compared to conventional banks.

Originality/value

This paper reinvestigates the puzzle between credit risk and liquidity risk by taking a sample of a dual banking system country and by considering the period of the COVID-19 pandemic. To the authors’ knowledge, this approach has not been addressed in prior empirical studies.
To be or not to be? The question of equitable healthcare
Authors: Broadway-Horner Matt
Published: October 2024

Purpose

The purpose of this commentary is to appraise and critically evaluate sexual minorities' mental health provision according to individual and systemic barriers to mental health care. It addresses the issue of health inequity by first exploring the background narrative that informs health inequalities and then moving forward in creating a health equity framework.

Design/methodology/approach

From the focus point of mad studies and queer theory.

Findings

In this critical commentary, the work alongside others will be viewed and discussed in terms of addressing individual and systemic barriers to mental health care. Furthermore, how this has been significantly influenced by the colonisation of mental health with its polarising language and increased marginalisation will be discussed.

Practical implications

Progress world view (PWV) will help sexual minorities receive the care needed.

Social implications

Through the decolonisation of mental health, there will be a new understanding that helps us achieve health equity by using a gay worldview lens called the PWV (Broadway-Horner, 2024).

Originality/value

In closing, recommendations for future research alongside policy implications for service restructuring implementation of a decolonising health service. This will include a national training package to increase self-efficacy levels. It brings together a cohesive understanding of the PWV within a larger body of work on sexual minorities and mental health.
The role of big data analytics in the footwear supply chains: a multiple case study perspective
Authors: Arshad Freeha Maryam , Ramish Asher
Published: October 2024

Purpose

This paper aims to analyze the importance of big data analytics (BDA) and supply chain analytics for sustainable supply chain management in all types of enterprises in the footwear industry. The importance and implementation of BDA in supply chain management have been discussed in this research paper, and a conceptual framework is proposed for the implementation.

Design/methodology/approach

The previous research indicates that the application of BDA and supply chain analytics is the key point to establishing sustainable supply chain management. Even though there are several types of research on the implications of BDA, there is still a gap in practical implications in organizations. For a better understanding, comparison of frameworks has been done for literature support. Further, 11 in-depth, semi-structured interviews have been conducted with four organizations from the footwear industry, and a conceptual framework has been proposed.

Findings

This research demonstrates an important gap in the literature through a thorough investigation of how firms can improve operational efficiency and productivity through the framework application and whether it is feasible to apply this within the global footwear industry or not. In conclusion, the research has denoted that despite lack of understanding related to sustainability agendas and not having proper ERP or BDA systems, the organizations operating in Pakistan still met some standards of sustainability and are moving toward achieving more.

Research limitations/implications

The research has pointed out the importance of the integration of all stakeholders in the supply chain through a proposed framework that aligns and guides the stakeholders so that the policies and other constraints may be taken into consideration while revising sustainable supply chain strategies.

Practical implications

This study will help increase sustainability through the application of BDA technology, which will benefit various stakeholders, particularly those in the footwear industry.

Originality/value

This study has proposed a framework based on three stages of the implementation of BDA in the existing supply chain to maintain and achieve sustainability in the organization in the footwear industry. This three-stage framework covers many aspects that were not covered in the literature before.
Navigating legitimacy: diverse stakeholder perspectives on the IFRS Foundation’s establishment of the ISSB
Authors: Bohn Luciano , Macagnan Clea Beatriz , Kronbauer Clóvis Antônio
Published: October 2024

Purpose

In 2020, the IFRS Foundation’s public consultation on Sustainability Reporting provided an opportunity for stakeholders to share their opinions on the Foundation’s proposals. This paper aims to analyze the comment letters that would legitimize the IFRS Foundation to institutionalize the International Sustainability Standards Board (ISSB).

Design/methodology/approach

This study used Python to develop a model for analyzing all 577 submissions that the IFRS Foundation received, using a combination of quantitative and qualitative content analysis methods.

Findings

Support for the creation of the ISSB was not unanimous but reached 68%. Key supporting arguments were that the IFRS Foundation could harmonize sustainability reporting standards by leveraging its expertise in setting accounting standards, and use its existing relationships to enforce sustainability reporting. Key counterarguments were: the IFRS Foundation lacks expertise in the areas of sustainability and climate; sustainability reporting should be integrated into financial reporting rather than being disclosed separately; the proposals were limited in scope (single materiality, focus on investors’ information needs and climate change centrism); and the IFRS Foundation should aim to endorse already established frameworks instead.

Practical implications

A consensus between supporters and critics was the need to make sustainability reporting mandatory. Endorsed by IOSCO, the ISSB released its inaugural standards, focusing on climate-related disclosures, effective from 2024 in jurisdictions that choose to adopt them.

Originality/value

The findings show that the establishment of the ISSB by the IFRS Foundation only partially fulfilled the demand for the harmonization of sustainability reporting standards. As a result, broader and non-investor-centric sustainability information may continue to be reported under alternative frameworks.
Defiance as an image restoration strategy: refining the reputation risk management framework
Authors: Sathye Milind
Published: October 2024

Purpose

This study aims to develop an understanding of strategies used by two major banks in Australia to manage reputation risk after court proceedings were initiated by the government for serious breaches of the Anti-Money Laundering and Counter-Terrorism Financing Act 2006.

Design/methodology/approach

The study is grounded in the corporate social responsibility (CSR) and image restoration literature. Thematic analysis of court proceedings, banks’ annual report suites (which include sustainability reports) and media reports was undertaken using the conceptual framework of reputation risk management (RRM).

Findings

A major new strategy of image restoration – defiance – emerged. It is contended that the existing RRM framework needs to be refined. Similarly, in the reducing effectiveness strategy, two new sub-strategies need to be included: refusal to acknowledge an incident as reputational damage and acceptance of the statutory penalty without legally challenging it. The banks also used traditional strategies of the RRM framework, such as reducing effectiveness by minimisation, bolstering, corrective action and mortification.

Originality/value

Trustworthiness and confidence are at the core of modern banking. Banks use CSR disclosures as the principal means for image restoration. The present paper explores the link between extant CSR literature and RRM.
Islamic commercial law in action: a look into AAOIFI’s Sharīʿah standard on Waqf
Authors: Alkhan Ahmed M. , Hassan M. Kabir
Published: October 2024

Purpose

The purpose of this paper is to analyse the Sharīʿah Basis of AAOIFI’s Sharīʿah Standard No. (60) – “Waqf” and gain an insight into the Islamic jurisprudential schools of thought depended on while drafting/issuing the standard.

Design/methodology/approach

This research uses a qualitative methodology and AAOIFI’s Sharīʿah Standard No. (60) – “Waqf” as a case study. This is referred to as a single/holistic case study design.

Findings

The findings of this study reveal that while AAOIFI’s Sharīʿah Standard No. (60) – “Waqf” did depend on the Maliki school of fiqh, it certainly referenced other jurisprudential schools of thought, such as Ḥanafī and Shāfiʿī schools of law. This raised a question of legal pluralism and how contemporary Sharīʿah jurisconsults are able to select rulings within particular Islamic jurisprudential schools to fit current needs and for the overall betterment of society.

Research limitations/implications

This research does not delve into the technical aspects of AAOIFI’s waqf standard (furūʿ al-fiqh), but rather, is limited to understanding the basis of rulings therein and the jurisprudential schools of thought heavily depended on.

Originality/value

Given that the (revised) AAOIFI waqf standard is relatively new, limited studies have been conducted particularly focusing on the basis of Sharīʿah rulings therein. This research contributes to knowledge by providing one of the starting points to deliberate on this matter.
Long‐term outcomes of intravenous corticosteroid pulse therapy for rapidly progressive alopecia areata: A single‐center retrospective analysis of 106 cases and usefulness evaluation of a scoring system originally designed for half‐year efficacy prediction for extended periods
Authors: Fukuyama Masahiro , Kinoshita‐Ise Misaki , Ohyama Manabu
Published: October 2024

Intravenous corticosteroid pulse therapy (IVPT) has been preferentially conducted for rapidly progressive alopecia areata (RP‐AA); however, the evaluation of long‐term outcomes has been insufficient. In this study, 106 IVPT‐treated RP‐AA patients (36 males and 70 females) who were followed up for more than 1 year and up to 6.8 years were retrospectively analyzed. The mean observation period was 1137.8 ± 587.9 days (range 380–2490). The mean severity of alopecia tool (SALT) score before IVPT was 21.3 ± 23.4 but whole‐scalp hair loss was observed in all cases after the intervention, suggesting that IVPT was performed soon after the onset. With additional interventions represented by intralesional triamcinolone acetonide injection with or without topical potent corticosteroid for those who insufficiently responded at 6 months after IVPT, 64.2%, 14.2%, and 21.7% of the patients respectively achieved good response (GR; SALT score ≤25), moderate response (MR; 25 < SALT score <75), and poor response (PR; 75 ≤ SALT score) 1 year after IVPT. On the final evaluation, the proportions of patients with GR, MR, and PR were 79 (74.5%), 7 (6.6%), and 20 (18.9%). Sixteen patients achieved and maintained full hair regrowth with IVPT alone until the end of observation. A previously reported scoring system for the short‐term outcome prediction was shown to be useful for distinguishing the final‐point GR responders from PR responders (P = 0.003). Of note, 21 patients were found to have some symptoms suggestive of the existence of preceding infectious diseases and tended to relapse. The revised scoring system adding the absence of preceding infectious diseases as one factor successfully predicted the occurrence of the relapse in our cohort (P = 0.002). Taken together, previously unreported real‐world efficacy of IVPT to RP‐AA was elucidated with the invention of a tool putatively enabling optimal long‐term management.
Seismic fault detection with sliding windowed differential cepstrum–based coherence analysis
Authors: Ran Qi , Chen Kang , Tang Cong , Wen Long , Zeng Ming , Liang Han , Zhang Guang‐rong , Xiao Han , Xue Ya‐juan
Published: October 2024

Cepstral decomposition is beneficial for highlighting certain geological features within the particular quefrency bands which may be deeply buried within the wide quefrency range of the seismic data. Converting seismic traces into the corresponding cepstrum components can better analyse some characteristics of underground strata than the traditional spectral decomposition methods. We propose the sliding windowed differential cepstrum–based coherence analysis approach to delineate the fault features. First, the data are decomposed using a sliding windowed differential cepstrum, which results in multi‐cepstrum data of corresponding quefrency of certain bandwidth. These different multi‐cepstrum data may highlight the different stratigraphic features in a certain quefrency band. We select the first‐order common quefrency volume as the featured attribute. Then, eigenstructure‐based coherence is applied on the first‐order common quefrency data volume to statistically obtain the fault detection result with a finer and sharper image. Synthetic data and field data examples show that the proposed method has the ability to better visualize all the possible subtle and minor faults present in the data more accurately and discernibly than the traditional coherence method. Compared with the ant‐tracking method, the proposed method is more effective in revealing the major faults. It is hoped that this work will complement current fault detection methods with the addition of the cepstral‐based method.
‘It's something that people don't have the knowledge of’: Perceived participation of pupils with Prader‐Willi syndrome in specialist schools and staff preparedness
Authors: Rawlinson Madeleine , Castro‐Kemp Susana
Published: October 2024

There is an abundance of literature on health‐related outcomes for children and young people with Prader‐Willi syndrome and on their lived experiences as well as on their caregivers'. However, little is known about the experiences of education practitioners when providing for them. This study gathered in‐depth evidence of the lived experience of school staff in two secondary specialist schools, on (1) perceptions of functioning and participation of young people with Prader‐Willi syndrome in the setting and (2) how prepared they felt to support them in achieving full participation, including challenges faced. Semi‐structured interviews were conducted with six school staff and transcripts were analysed both deductively (using the ICF classification system) and inductively. School staff perceive the needs of these pupils as mostly related to their body functions, in alignment with a medicalised understanding of disability. However, they recognise the key role of environmental modifications to address these. Staff feel mostly unprepared and perceive their training as limited. Despite wide recognition of the need to conceive disability holistically, medicalised understandings are still present. Training from a biopsychosocial perspective is needed. Future research should address the development of core sets of ICF codes for people with Prader‐Willi syndrome.
Bed bugs, Cimex lectularius: Undercover agents in forensic investigations
Authors: Meiklejohn Kelly A. , Schal Coby , Lodhi Khalid M.
Published: October 2024

Insects have long played a role in forensic investigations and can be used to estimate minimum time since death, corpse translocation, and link an individual to a crime scene. Bed bugs (Cimex lectularius) are wingless ectoparasitic insects of potential forensic utility, given that all mobile life stages feed on vertebrate blood. Successful profiling of autosomal short tandem repeats (STRs) from human DNA isolated from bed bugs has been previously reported. This proof‐of‐concept study looked to expand this work and determine any possible limitations of using bed bugs for both rapid stain identification (RSID™) for human blood and Y‐STR profiling. To achieve this, bed bugs were fed either human male only or human pooled (female:male) blood for 30 min and subsequently collected at 12‐h intervals up to 108 h post‐blood meal (PBM). RSID™ blood testing was successful from the bed bug carcass remaining after DNA isolation, regardless of blood meal type and time of collection PBM. Complete Y‐STR profiles were generated from bed bugs <60 h PBM. As the time PBM increased, DNA quantity decreased, while the degradation index increased. Collection of bed bugs at a crime scene could provide a valuable source of human blood for Y STR profiling and be used to link an individual to a crime scene or for potential male suspect exclusion. Future studies should look to replicate the results of this proof‐of‐concept study with larger numbers of bed bugs, more diverse blood donors, and additional STR profiling kits.
Situational crime prevention as a harm mitigation policy for active shooter incidents
Authors: Greene‐Colozzi Emily A. , Freilich Joshua D.
Published: October 2024

Research summary

Situational crime prevention (SCP) is an environmental crime control perspective with enormous practical and policy relevance due to its practitioner‐friendly theoretical approach. This study examines whether SCP interventions reduce incident casualty outcomes in active shooter incidents. We used an inductive, open‐source data set of 555 active shooter and mass public shooting sites to study the applicability of SCP to active shooter and mass public violence. Our findings suggest a harm mitigation role for SCP: active shooter sites with stronger holistic SCP had fewer casualties. We assessed perpetrator motivation to test displacement, a core critique of SCP, and found that the harm mitigation potential of SCP persists even in the presence of a highly motivated offender.

Policy summary

SCP could be a practical and effective method to decrease casualties in the event of an active shooting, which is a highly motivated crime type that is difficult to predict and prevent. Public locations may select a range of appropriate SCP techniques based on individual resources and needs. The totality and interactions of these techniques may contribute to public safety in general, with diffuse benefits. This policy solution is highly oriented toward practice and real‐life application, and may be used to supplement existing preventative measures like threat assessment and gun legislation.
Screening for compensated advanced chronic liver disease using transient elastography in outpatient addiction clinics
Authors: Karrer Antoine , Pangui Raphael , Le Lan Caroline , Le Texier Sebastien , Le Gruyer Antonia , Moirand Florence , Chalvin Theophile , Moirand Romain
Published: October 2024

Background

Patients with substance use disorders present with many risk factors for liver disease—including alcohol, hepatitis C virus infection, and obesity—and should thus be screened for compensated advanced chronic liver disease (cACLD). Such screening could potentially be performed by outpatient addiction clinics. In this study, we aimed to assess the feasibility, acceptability, and results of cACLD screening using transient elastography (TE) among all patients attending routine follow‐up visits at addiction clinics, regardless of their liver disease risk factors.

Methods

Liver fibrosis evaluation using TE was offered to every patient consulting two different addiction clinics in France, between December 2020 and September 2021, during dedicated half‐day screening sessions. The screening was proposed during the patient's routine care and was performed immediately after the scheduled consultation. Patients with a liver stiffness measurement over 8 kPa were referred to a hepatology visit in the addiction clinic within 2–4 weeks.

Results

Screening was offered to 227 patients and was accepted by 116 (51%) patients. Twelve patients had a liver stiffness over 8 kPa, and nine of these patients attended the recommended specialist hepatology visit. Five patients (4.3% of those screened) were diagnosed with cACLD. Patients' acceptance of the screening was associated with older age, being on one's own or professionally inactive, and presenting with alcohol use disorder.

Conclusion

Overall, our results demonstrated that opportunistic cACLD screening using TE in outpatient addiction clinics was feasible and acceptable, with good results.
An integrated model of care between general surgery and general medicine rationalizes and enhances the care of older surgical patients
Authors: Ferrah Noha , Salomoni Sauro , Turner Richard
Published: October 2024

Backgrounds

There is growing evidence on the benefits of integrated models of care between surgeons and physicians in non‐orthopaedic surgery. We implemented a new General Surgery/General Medicine care model, for all emergency General Surgery patients aged 75 years and older. We compared rates of goals of care (GOC) documentation, hospital‐acquired complications (HAC), mortality, and hospital length of stay (LOS).

Methods

This is a non‐randomized trial, with data collected prospectively in phase 1 (2021–2022), where patients received the traditional standard of care (case‐by‐case referral to a General Physician), and in phase 2 (2022–2023) where patients received integrated care. Variables were compared between phase 1 and phase 2 using Generalized Linear Models (GLMs).

Results

Five hundred and forty‐nine patients, 188 in phase 1 and 361 in phase 2, participated in the study. On univariate analysis, there was a significant increase in patients treated non‐surgically in phase 2 (58.5% vs. 69.0%). Patients treated non‐surgically had significantly shorter LOS, experienced less HACs (P < 0.001). Other variables did not significantly differ after implementation of the service. The multivariate GLM revealed a significant reduction in admissions with undocumented GOC in phase 2 (P = 0.037).

Conclusion

This study showed that an integrated care model resulted in a greater proportion of patients being treated non‐surgically with a comparable rate of HAC and mortality, as well as better documentation of patients' GOC. As the number of older surgical patients will continue to rise, the call for such service to become standard of care in non‐orthopaedic surgery is pressing.
Markers of consciousness in infants: Towards a ‘cluster‐based’ approach
Authors: Frohlich Joel , Bayne Tim
Published: October 2024

As recently as the 1980s, it was not uncommon for paediatric surgeons to operate on infants without anaesthesia. Today, the same omission would be considered criminal malpractice, and there is an increased concern with the possibility of consciousness in the earliest stage of human infancy. This concern reflects a more general trend that has characterised science since the early 1990s of taking consciousness seriously. While this attitude shift has opened minds towards the possibility that our earliest experiences predate our first memories, convincing demonstrations of infant consciousness remain challenging given that infants cannot report on their experiences. Furthermore, while many behavioural and neural markers of consciousness that do not rely on language have been validated in adults, no one specific marker can be confidently translated to infancy. For this reason, we have proposed the ‘cluster‐based’ approach, in which a consensus of evidence across many markers, all pointing towards the same developmental period, could be used to argue convincingly for the presence of consciousness.

Conclusion

We review the most promising markers for early consciousness, arguing that consciousness is likely to be in place by 5 months of age if not earlier.
Early identification and communication in cerebral palsy: Navigating a collaborative approach for neonatal follow‐up programmes
Authors: Church Paige Terrien , Banihani Rudaina , Thomas Karen , Luther Maureen , Agnew Brenda , Makino Amber , Lam‐Damji Sophie , Fehlings Darcy
Published: October 2024

Aim

This article will provide a clinical case demonstrating the implementation of early identification and review the tools and findings and the diagnostic approach. We will review highlighted literature on the subject of communicating a diagnosis. While improved function is a critical goal, the process of communicating the diagnosis of CP can be challenging for both parents and providers. It aims to provide insights on the evidence supporting early identification and discusses strategies for effective communication of crucial information.

Methods

The article reviews the literature on communication of a diagnosis.

Results

Thirteen articles were identified relating to the communication of a diagnosis of CP and parent experience. We examine this evidence, leveraging the knowledge of an interdisciplinary team and incorporating feedback from parents.

Conclusion

Strategies for effective communication include engagement with families, community therapy teams and all medical providers. Consistent, individualised, collaborative communication is critical. Awareness of ableism and use of balanced, value‐neutral terminology is recommended.
Phase I clinical trial evaluating the safety, tolerance, pharmacokinetics and pharmacodynamics of HSK21542 injection in healthy volunteers
Authors: Shao Rong , Wang Hai‐ying , Ruan Zou‐rong , Jiang Bo , Yang Dan‐dan , Hu Yin , Xu Yi‐chao , Yang Jin‐ting , Gao Wei , Zhao Wan‐yun , Yan Min , Lou Honggang
Published: October 2024

HSK21542 injection is a new peripheral kappa opioid receptor (KOR) agonist. To evaluate its safety, tolerability, pharmacokinetics and pharmacodynamics, this study was conducted in healthy volunteers, consisting of two parts: a single ascending dose (0.2–3.375 μg/kg, 15‐min infusion) and different infusion durations (0.2 and 1 μg/kg, 2‐ or 15‐min infusion). The area under the plasma concentration‐time curve (AUC) and peak concentration (Cmax) of HSK21542 were dose‐linear among 0.2–3.375 μg/kg. After intravenous injection, HSK21542 was rapidly eliminated with a half‐life (t1/2) of 1.5 h, and the majority (48.02%) of the dose was excreted unchanged in urine. Pharmacodynamic results showed that HSK21542 increased prolactin release and reached a peak at 1–2 h after administration but had no significant effect on vasopressin levels. There was a brief increase in urine volume within the initial 2 h after administration. HSK21542 was well tolerated; most of the adverse effects (AEs) in the trial group were grade 1, and only 2 cases (4.0%) were grade 2. The main AE was paresthesia, which appeared in 42% (21/50) in the trial group. No serious adverse event (SAE) was observed. No subject withdrew early due to AEs. These results suggest that HSK21542 may be a potential treatment for pain and pruritic conditions.
The value of semiquantitative PET features and end‐of‐therapy PET in grade 3B follicular lymphoma
Authors: Barraclough Allison , Lee Sze Ting , Villa Diego , Hapgood Greg , Wilson Don , Chong Geoffrey , Hawkes Eliza A.
Published: October 2024

Grade 3B follicular lymphoma (G3BFL) is a rare lymphoma thought to sit on a continuum between low‐grade FL and diffuse large B‐cell lymphoma (DLBCL). The prognostic impact of quantitative positron emission tomography (PET) metrics such as total metabolic tumour volume (TMTV), total lesion glycolysis (TLG), and maximum standard uptake value (SUVmax) have been extensively analysed in FL and DLBCL, but G3BFL data are lacking. Here, we describe PET outcomes and radiomic characteristics in 46 G3BFL cases uniformly treated with R‐CHOP (like) chemotherapy. Central semi‐automated PET TMTV, TLG, and SUVmax analyses, using MIM software, were correlated with clinical outcomes and compared with published results in low‐grade FL and DLBCL. In G3BFL, the end‐of‐treatment complete metabolic response was associated with improved progression‐free survival (PFS; p = 0.002) and overall survival (OS; p = 0.04). G3BFL median TLG (1455) and SUVmax (16.50) sit between published values for low‐grade FL (TLG: 1112, SUVmax: 11.3) and DLBCL (TLG: 3004, SUVmax: 24.35). No association between TMTV (>350 cm3) and survival was seen (PFS: p = 0.24; OS: p = 0.40). High SUVmax (>19.2) and TLG (>2760) both conferred inferior PFS but not OS (PFS: SUVmax p = 0.004; TLG p = 0.05). These data support the routine incorporation of PET radiomics at baseline and treatment response for G3BFL.
A Tale of Two Centuries? Expanding Constitutional Labour Rights in Canada and Their Impact on Legislation, Conflict and Wages
Authors: Weinberg Bradley R.
Published: October 2024

Using collective agreement and strike data from the Canadian Federal and provincial jurisdictions for the years 1978–2019, this study examines the effect that various legislative regimes that govern public‐sector bargaining disputes have on the incidence, duration and cost of conflict. This study seeks to replicate and improve previous estimates related to this topic but also extends the analysis to examine changes to the legal environment in Canada in which labour rights have been increasingly enshrined in constitutional law through the Canadian Charter of Rights and Freedoms. This study finds, in contrast to previous studies, that the legislative regime impacts the way agreements are settled when disputes occur but not the likelihood of a directly negotiated agreement prior to impasse. It also highlights some differences in contract and wage settlements prior to and after the constitutionalization of labour rights in Canada.
The p. S178L mutation in Tbc1d24 disrupts endosome‐mediated synaptic vesicle trafficking of cochlear hair cells and leads to hearing impairment in mice
Authors: Chen Penghui , Hou Shule , Li Gen , Lin Yuzhe , Lu Jiawen , Song Lei , Li Geng‐Lin , Pang Xiuhong , Wu Hao , Yang Tao
Published: October 2024

The ribbon synapses of cochlear inner hair cells (IHCs) employ efficient vesicle resupply to enable fast and sustained release rates. However, the molecular mechanisms of these physiological activities remain unelucidated. Previous studies showed that the RAB‐specific GTPase‐activating protein TBC1D24 controls the endosomal trafficking of the synaptic vesicles (SVs) in Drosophila and mammalian neurons, and mutations in TBC1D24 may lead to non‐syndromic hearing loss or hearing loss associated with the DOORS syndrome in humans. In this study, we generated a knock‐in mouse model for the p. S178L mutation in TBC1D24, which leads to autosomal dominant non‐syndromic hearing loss (DFNA65). The p.S178L mutant mice show mild hearing loss and progressively declined wave I amplitude of the auditory brainstem responses. Despite the normal gross and cellular morphology of the cochlea, transmission electron microscopy reveals accumulation of endosome‐like vacuoles and a lower‐than‐normal number of SVs directly associated with the ribbons in the IHCs. Consistently, patch clamp of the IHCs shows reduced exocytosis under prolonged stimulus. ARF6, a TBC1D24‐interacting protein also involved in endosomal membrane trafficking, was underexpressed in the cochleae of the mutant mouse and has weakened in vitro interaction with the p.S178L mutant TBC1D24. Our results suggest an important role of TBC1D24 in maintaining endosomal‐mediated vesicle recycling and sustained exocytosis of hair cell ribbon synapses.