bluuebunny/crossref_metadata_2025 huggingface dataset:
Neither alpha-synuclein-preformed fibrils derived from patients withGBA1mutations nor the host murine genotype significantly influence seeding efficacy in the mouse olfactory bulb
Authors: Walton Sara , Fenyi Alexis , Tittle Tyler , Sidransky Ellen , Pal Gian , Choi Solji , Melki Ronald , Killinger Bryan A. , Kordower Jeffrey H.
Published: August 2023

Parkinson’s disease (PD) is a neurodegenerative disease characterized by progressive motor symptoms and alpha-synuclein (αsyn) aggregation in the nervous system. For unclear reasons, PD patients with certain GBA mutations (GBA-PD) have a more aggressive clinical progression. Two testable hypotheses that can potentially account for this phenomenon are thatGBA1mutations promote αsyn spread or drive the generation of highly pathogenic αsyn polymorphs (i.e., strains). We tested these hypotheses by treating homozygousGBA1D409V knockin (KI) mice with human α-syn-preformed fibrils (PFFs) and treating wild-type mice (WT) with several αsyn-PFF polymorphs amplified from brain autopsy samples collected from patients with idiopathic PD and GBA-PD patients with either homozygous or heterozygousGBA1mutations. Robust phosphorylated-αsyn (PSER129) positive pathology was observed at the injection site (i.e., the olfactory bulb granular layer) and throughout the brain six months following PFF injection. The PFF seeding efficiency and degree of spread were similar regardless of the mouse genotype or PFF polymorphs. We found that PFFs amplified from the human brain, regardless of patient genotype, were generally more effective seeders than wholly synthetic PFFs (i.e., non-amplified); however, PFF concentration differed between these two studies, and this might also account for the observed differences. To investigate whether the molecular composition of pathology differed between different seeding conditions, we permed Biotinylation by Antibody Recognition on PSER129 (BAR-PSER129). We found that for BAR-PSER129, the endogenous PSER129 pool dominated identified interactions, and thus, very few potential interactions were explicitly identified for seeded pathology. However, we found Dctn2 interaction was shared across all PFF conditions, and Nckap1 and Ap3b2 were unique to PFFs amplified from GBA-PD brains of heterozygous mutation carriers. In conclusion, both the genotype and αsyn strain had little effect on overall seeding efficacy and global PSER129-interactions.
The genome of the Wollemi pine, a critically endangered “living fossil” unchanged since the Cretaceous, reveals extensive ancient transposon activity
Authors: Stevenson Dennis Wm. , Ramakrishnan Srividya , Alves Cristiane de Santis , Coelho Laís Araujo , Kramer Melissa , Goodwin Sara , Ramos Olivia Mendevil , Eshel Gil , Sondervan Veronica M. , Frangos Samantha , Zumajo-Cardona Cecilia , Jenike Katherine , Ou Shujun , Wang Xiaojin , Lee Yin Peng , Loke Stella , Rossetto Maurizio , McPherson Hannah , Nigris Sebastiano , Moschin Silvia , Little Damon P. , Katari Manpreet S. , Varala Kranthi , Kolokotronis Sergios-Orestis , Ambrose Barbara , Croft Larry J. , Coruzzi Gloria M. , Schatz Michael , McCombie W. Richard , Martienssen Robert A.
Published: August 2023

We present the genome of the living fossil,Wollemia nobilis, a southern hemisphere conifer morphologically unchanged since the Cretaceous. Presumed extinct until rediscovery in 1994, the Wollemi pine is critically endangered with less than 60 wild adults threatened by intensifying bushfires in the Blue Mountains of Australia. The 12 Gb genome is among the most contiguous large plant genomes assembled, with extremely low heterozygosity and unusual abundance of DNA transposons. Reduced representation and genome re-sequencing of individuals confirms a relictual population since the last major glacial/drying period in Australia, 120 ky BP. Small RNA and methylome sequencing reveal conservation of ancient silencing mechanisms despite the presence of thousands of active and abundant transposons, including some transferred horizontally to conifers from arthropods in the Jurassic. A retrotransposon burst 8-6 my BP coincided with population decline, possibly as an adaptation enhancing epigenetic diversity.Wollemia, like other conifers, is susceptible toPhytophthora, and a suite of defense genes, similar to those in loblolly pine, are targeted for silencing by sRNAs in leaves. The genome provides insight into the earliest seed plants, while enabling conservation efforts.
Cell-extrinsic effects ofIrf2on cDC2 development
Authors: O’Connor Kevin W. , Liu Tiantian , Kim Sunkyung , Murphy Theresa L. , Murphy Kenneth M.
Published: August 2023

Characterization of the functional effects of cDC2s in vivo requires model systems in which cDC2s are depleted. Previous literature has reported a loss of cDC2s in mice lacking the transcription factor IRF21,2. We sought to further characterize the cDC2 defect in these animals. Here, we find that the requirement for IRF2 in cDC2 development and survival is cell-extrinsic and correlated to the development of dermatitis in theIrf2-/-model system. We also find that Flt3L-mediated in vitro development of cDC1s and cDC2s, but not pDCs, is abrogated inIrf2-/-bone marrow, as well as in wild-type bone marrow cultured with IFNα. Loss of interferon α (IFNα) signaling inIrf2-/-mice restored cDC2 development in vivo and cDC1 and cDC2 development in vitro. We therefore conclude that IRF2 is required for cDC2 development in a cell-extrinsic manner dependent on IFNα signaling.
(p)ppGpp is required for Virulence ofShigella flexneri
Authors: Kago Grace , Turnbough Charles L. , Payne Shelley M.
Published: August 2023

Infection by the enteric pathogenShigella flexnerirequires transit through the gastrointestinal tract and invasion of and replication within the cells of the host colonic epithelium. This process exposes the pathogen to a range of diverse microenvironments. Further, the unique composition and physical environment of the eukaryotic cell cytosol represents a stressful environment forS. flexneri, and extensive physiological adaptations are needed for the bacterium to thrive. In this work, we show that disrupting synthesis of the stringent response alarmone (p)ppGpp inS. flexneridiminished expression of key virulence genes, includingipaA, ipaB, ipaCandicsA, and it reduced bacterial invasion and intercellular spread. Deletion of the (p)ppGpp synthase generelAalone had no effect onS. flexnerivirulence, but disruption of bothrelAand the (p)ppGpp synthase/hydrolase genespoTresulted in loss of (p)ppGpp synthesis and virulence. While therelA spoTdeletion mutant was able to invade a cultured human epithelial cell monolayer, albeit at reduced levels, it was unable to maintain the infection and spread to adjacent cells, as indicated by loss of plaque formation. Complementation withspoTon a plasmid vector restored plaque formation. Thus, SpoT alone is sufficient to provide the necessary level of (p)ppGpp for virulence. These results indicate that (p)ppGpp is required forS. flexnerivirulence and adaptation to the intracellular environment, adding to the repertoire of signaling pathways that affectShigellapathogenesis.
A Standardized Protocol for Sample Preparation for Scanning Electron Microscopy (SEM) to Visualize Extrachromosomal DNA (ecDNA)
Authors: Madren Jillann , Chen Jingting , Dennis William , Ford Christina , White Kristen , Brunk Elizabeth
Published: August 2023

Extrachromosomal DNA (ecDNA) are large (∼kilo to megabase) acentric, atelomeric, circular DNAs that are established cytogenetic markers for malignancy, hard-to-treat tumors and drug resistance. Often referred to as double minute chromosomes, ecDNA have been studied since the 1960s, primarily through molecular biology techniques, such as cytogenetics and fluorescence microscopy. More recently, next generation sequencing technologies present novel opportunities for identifying ecDNA. However, none of these approaches adequately address the architecture, size and composition of ecDNA within single cells. Developing an approach to systematically visualize ecDNA, confirm their circular architecture and determine their ultrastructure and composition is an urgent, unmet need. This work presents a protocol for visualizing ecDNA at high resolution using scanning electron microscopy (SEM). To this end, we have optimized an end-to-end procedure that involves preparing, processing and visualizing metaphase spread samples. This protocol was tested on five human cancer cell lines (COLO320DM, NCIH716, NCIH2170, SKGT2, SNU16), four of which express ecDNA in various amounts and one amplifies DNA via a homogeneous staining region (HSR). This work presents a standardized approach to preparing samples and visualizing ecDNA using SEM.

Significance

Extrachromosomal DNA (ecDNA) are proposed to have unique molecular traits, which include acentric, atelomeric and circular DNA. Standardized, high resolution microscopy approaches are in high demand to better understand structure-function relationships of ecDNA.
Tumor suppressor let-7 acts as a key regulator for maintaining pluripotency gene expression in Muse cells
Authors: Li Gen , Wakao Shohei , Kitada Masaaki , Dezawa Mari
Published: August 2023

In embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), the expression of an RNA-binding pluripotency-relevant protein, LIN28, and the absence of its antagonist, the tumor-suppressor microRNA (miRNA) let-7, play a key role in maintaining pluripotency. Muse cells are non-tumorigenic pluripotent-like stem cells residing in the bone marrow, peripheral blood, and organ connective tissues as pluripotent surface marker SSEA-3(+). They express pluripotency genes, differentiate into triploblastic-lineage cells, and self-renew at the single cell level. Muse cells do not express LIN28 but do express let-7 at higher levels than in iPSCs. In Muse cells, we demonstrated that let-7 inhibited the PI3K-AKT pathway, leading to sustainable expression of the key pluripotency regulator KLF4 as well as its downstream genes,POU5F1,SOX2, andNANOG. Let-7 also suppressed proliferation and glycolysis by inhibiting the PI3K-AKT pathway, suggesting its involvement in non-tumorigenicity. Furthermore, the MEK/ERK pathway is not controlled by let-7 and may have a pivotal role in maintaining self-renewal and suppression of senescence. The system found in Muse cells, in which the tumor suppressor let-7, but not LIN28, tunes the expression of pluripotency genes, might be a rational cell system conferring both pluripotency-like properties and a low risk for tumorigenicity.
SUMOnet: Deep Sequential Prediction of SUMOylation Sites
Authors: Dilekoglu Berke , Tastan Oznur
Published: August 2023

SUMOylation is a reversible post-translational protein modification in which SUMOs (small ubiquitin-like modifiers) covalently attach to a specific lysine residue of the target protein. This process is vital for many cellular events. Aberrant SUMOylation is associated with several diseases, including Alzheimer’s, cancer, and diabetes. Therefore, accurate identification of SUMOylation sites is essential to understanding cellular processes and pathologies that arise with their disruption. We present three deep neural architectures, SUMOnets, that take the peptide sequence centered on the candidate SUMOylation site as input and predict whether the lysine could be SUMOylated. Each of these models, SUMOnet-1, -2, and -3 relies on different compositions of deep sequential learning architectural units, such as bidirectional Gated Recurrent Units(biGRUs) and convolutional layers. We evaluate these models on the benchmark dataset with three different input peptide representations of the input sequence. SUMOnet-3 achieves 75.8% AUPR and 87% AUC scores, corresponding to approximately 5% improvement over the closest state-of-the-art SUMOylation predictor and 16% improvement over GPS-SUMO, the most widely adopted tool. We also evaluate models on a challenging subset of the test data formed based on the absence and presence of known SUMOylation motifs. Even though the performances of all methods degrade in these cases, SUMOnet-3 remains the best predictor in these challenging cases.

Availability and Implementation

The SUMOnet-3 framework is available as an open-source project and a Python library athttps://github.com/berkedilekoglu/SUMOnet.
Reinforcing resilience on the supply side: the role of supplier capabilities
Authors: Akbar Bilal , Aslam Haris
Published: August 2023

Purpose

This research study aims to investigate supplier integration's (SI) impact on supply-side resilience (SSR) while considering the intervening role of supplier sustainability and supplier flexibility (SF).

Design/methodology/approach

Grounded in the dynamic capabilities view (DCV), the study posits that integration of the focal firm with firm's suppliers leads to sustainability on the supplier's side, which makes the firms more flexible to work with during disruptive circumstances, resulting in resilience on the supply side. The hypotheses are tested on the data of 181 manufacturing firm supply chain managers from a developing country.

Findings

The research findings confirmed the hypothesized model suggesting that SI positively impacts SSR. The results also confirm the existence of sequential mediation of supplier sustainability and SF between the SI–SSR relationship.

Practical implications

The results of this study show that SI is the primary capability for organizations seeking SSR. Furthermore, the supply-side capabilities, to be effective, are developed in a specific order.

Originality/value

This research advances the body of knowledge by identifying the underlying mechanisms through which SI augments SSR.
A hedonic analysis of the determinants of hotel room rates in the Greater Gaborone Region (Botswana) using quantile regression
Authors: Chatibura Delly Mahachi
Published: August 2023

Purpose

The purpose of this study is to examine the influence of key hotel attributes on the room rates of selected hotels in the Greater Gaborone Region, Botswana.

Design/methodology/approach

Using hedonic pricing analysis, the effect of eight attributes collected from 80 standard double rooms on Booking.com in the area was analysed using quantile regression.

Findings

The estimated results from quantile regression suggested the importance of the 10th quantile as the best predictor of hotel room price distribution. Overall, the presence of a fitness centre and the availability of meeting and conference facilities were positively significant for the lowest- and premium-priced hotels, respectively.

Research limitations/implications

The study advanced the literature in hedonic pricing models by confirming the applicability of hotel room rate attribute research in unexplored environments.

Practical implications

Hotel managers should be aware of the influence of key attributes, such as meeting and conference space availability and locational factors, on the pricing decisions of room rates in the Greater Gaborone Region. The study also presented opportunities for business-to-business marketing between hotel and tour operators in the region.

Originality/value

The study is one of the few that uses quantile regression in the hedonic pricing analysis of hotel room rates.
Key performance indicators in short-term rental accommodation
Authors: Pardinha João , Mota Jorge , Costa Rui Augusto
Published: August 2023

Purpose

The boom of new players in the accommodation sector has led to an increase in the level of competitiveness and has highlighted the importance of using key performance indicators (KPIs) in organisational decision-making processes as efficient tools for thriving in the growingly competitive environment. This study aims to assess the use of KPIs by owner-managers of small and medium-sized short-term rental accommodation (STRA) units.

Design/methodology/approach

To achieve this aim, this research encompasses two different primary data collection methods conducted in 2021. Firstly, from April to May, a set of exploratory interviews with experts within the STRA domain was planned. Secondly, an intensive data collection, from June to September, included an online questionnaire with close-ended questions to a sample of all the companies that manage STRA units in Portugal.

Findings

These managers tend to use more widely financial and operational KPIs that depict relationships with guests and reflect the activity of the STRA units, the external environment and the innovation level. Moreover, younger managers and those with higher levels of education tend to use a “monitoring review of digital platforms” KPI, while less experienced managers use financial and operational KPIs and senior and higher experienced managers place greater value on KPIs associated with customer relationships.

Originality/value

STRA units hold a very relevant position in the hospitality industry, and it is urgent to generate more information to better understand this growing subsector. This research contributes to the literature providing evidence on the importance of KPI to STRA units, for owner-managers and for urban tourism, considering their growth, proliferation and importance for the planning of cities by destination management organisations.
Understanding the role of Instagram in young adult consumers' purchase and post-purchase evaluation behaviors
Authors: Hood Sara Lewis , Thoney-Barletta Kristin Anne , Rothenberg Lori
Published: August 2023

Purpose

This study explored the role that Instagram, a prominent social media platform, plays in the consumer decision-making process of young adults (age 18–27 years) in the United States as they shop online for apparel and interact with the digital profiles of apparel brands. Specifically, this study compared consumers' purchase and post-purchase evaluation behaviors on Instagram between Millennials and Generation Z, and investigated the role of consumers' trust of Instagram on these behaviors.

Design/methodology/approach

A survey instrument was developed to explore critical variables, including consumers' purchase and post-purchase evaluation behaviors on Instagram, consumers' trust of Instagram, and demographic factors, adapting previous works from Ko (2018), Djafarova and Rushworth (2017), and Herrando et al. (2019). Survey responses were collected via the Qualtrics participant panel service (N = 226), then coded and analyzed using JMP Pro (Version 14.2).

Findings

Results indicated that statistically significant mean differences were present among several key variables, including between Millennial and Generation Z post-purchase behaviors on Instagram, willingness to share feedback about a brand experience on Instagram, and trust of content on Instagram. Additionally, it was determined that purchase and post-purchase behaviors on Instagram are significantly different depending on whether or not a consumer trusts Instagram and the content therein.

Originality/value

While online consumer behaviors have been previously studied, the impact of young adults' Instagram usage on their purchase and post-purchase evaluation behaviors in the apparel sector had not been thoroughly examined. The findings from this study provide meaningful insights on the purchase and post-purchase behaviors on Instagram of young adult consumers from different generational cohorts. They demonstrate that developing trust with young adults is critical to the success of brands trying to reach this demographic on Instagram.
Trust, pandemic and communication: an analysis of the COVID-19 pandemic from an autopoietic systems perspective
Authors: Wahyuni Hermin Indah
Published: August 2023

Purpose

This article seeks to discuss trust within the context of public health crises using an autopoietic systems perspective that positions communication as one of its core concepts. This article will explore trust studies conducted during public health crises in this Millennium (from SARS to COVID-19 pandemics), including their problems; briefly summarize Luhmann's concept of Vertrauen; and use this concept to analyze trust issues during the COVID-19 pandemic.

Design/methodology/approach

This article will explore trust studies conducted during public health crises from SARS to COVID-19 pandemics, including their problems. The perspective used is an explication of Niklas Luhmann's theory regarding Vertrauen which was derived as a framework for reading empirical facts on trust issues during the COVID-19 pandemic. The research design and exploration stages were inspired by the theory of autopoiesis systems by Niklas Luhmann.

Findings

From a systems perspective, the COVID-19 pandemic has highlighted the extraordinary complexity of the linkages between social systems. Trust will continue to evolve dynamically as new variants emerge in society. Consequently, the pandemic has provided the momentum necessary for maximally exploring the concept of trust. Indonesia thus experienced significant obstacles when making and implementing disaster mitigation policies. Owing to the lack of a trust system, greater emphasis was given to control and power. There has been little preparedness to create and reinforce public trust, and this in turn has stifled efforts to stop the spread of COVID-19.

Originality/value

This study of trust, communication and public health crises has provided space to reflect on the development of trust within the social system. This study shows that trust can prove to be a very important factor in resolving a crisis. However, the complexity of the interrelationships of the social system can affect the quality of trust. The context of Indonesia's social system which is very complex due to population density and the dynamics of the development of its social system which is very diverse as an archipelagic country has contributed to the originality of the study of trust in times of crisis in a growing contemporary society.
Application of biosensors in aflatoxins detection in food: a review
Authors: Narjabadi Fam Shakiba , Massoud Ramona
Published: August 2023

Purpose

Food safety is among the most important topics in the world. According to WHO guidelines, aflatoxins are one of the most hazardous food toxins. Therefore, their detection in food products seems crucial due to health problems. The purpose of this paper is to discuss the different types of biosensors in aflatoxin determination.

Design/methodology/approach

Traditional detection methods are time consuming and expensive. As fast and accurate detection is important in monitoring food contaminants, alternative analytical methods would be essential. Biosensors are the intelligent design of sensitive sensors for precise detection of toxins in a short time. Various biosensors are being applied for aflatoxins detection in food products with many advantages over the traditional methods.

Findings

Biosensors are cost-effective, stable and have possessed high selectivity, specificity and accuracy in aflatoxins detection. Applying biosensors has been increased recently, so biosensing methods (optical, electrochemical, piezoelectrical, immunosensors, surface plasmon resonance and calorimetric) are discussed along with their advantages in this article.

Research limitations/implications

More efforts should be occurred to detect and decrease the aflatoxins by biosensors, and some traits like accuracy and selectivity would be the purpose of future projects. The combination of various techniques would also help in toxin detection issue in food products, so high efforts in this regard are also required for the upcoming years.

Originality/value

This article also reviews different types of biosensors simultaneously and explains their specificity for aflatoxin determination in different food products and also the future trends and requirements.
Natural and synthetic drugs as eco-friendly and sustainable corrosion inhibitors for metals: a review
Authors: Njoku Chigoziri N. , Maduoma Temple Uzoma , Emori Wilfred , Odey Rita Emmanuel , Unimke Beshel M. , Yakubu Emmanuel , Anorondu Cyril C. , Udunwa Daniel I. , Njoku Onyinyechi C. , Oyoh Kechinyere B.
Published: August 2023

Purpose

Corrosion is a major concern for many industries that use metals as structural or functional materials, and the use of corrosion inhibitors is a widely accepted strategy to protect metals from deterioration in corrosive environments. Moreover, the toxic nature, non-biodegradability and price of most conventional corrosion inhibitors have encouraged the application of greener and more sustainable options, with natural and synthetic drugs being major actors. Hence, this paper aims to stress the capability of natural and synthetic drugs as manageable and sustainable, environmentally friendly solutions to the problem of metal corrosion.

Design/methodology/approach

In this review, the recent developments in the use of natural and synthetic drugs as corrosion inhibitors are explored in detail to highlight the key advancements and drawbacks towards the advantageous utilization of drugs as corrosion inhibitors.

Findings

Corrosion is a critical issue in numerous modern applications, and conventional strategies of corrosion inhibition include the use of toxic and environmentally harmful chemicals. As greener alternatives, natural compounds like plant extracts, essential oils and biopolymers, as well as synthetic drugs, are highlighted in this review. In addition, the advantages and disadvantages of these compounds, as well as their effectiveness in preventing corrosion, are discussed in the review.

Originality/value

This survey stresses on the most recent abilities of natural and synthetic drugs as viable and sustainable, environmentally friendly solutions to the problem of metal corrosion, thus expanding the general knowledge of green corrosion inhibitors.
Study of parametric interaction during fused filament fabrication (FFF) using interpretive structural modelling (ISM) followed by experimental analysis
Authors: Sharma Shekhar , Datta Saurav , Roy Tarapada , Mahapatra Siba Sankar
Published: August 2023

Purpose

Fused filament fabrication (FFF) is a type of additive manufacturing (AM) based on materials extrusion. It is the most widely practiced AM route, especially used for polymer-based rapid prototyping and customized product fabrication in relation to aerospace, automotive, architecture, consumer goods and medical applications. During FFF, part quality (surface finish, dimensional accuracy and static mechanical strength) is greatly influenced by several process parameters. The paper aims to study FFF parametric influence on aforesaid part quality aspects. In addition, dynamic analysis of the FFF part is carried out.

Design/methodology/approach

Interpretive structural modelling is attempted to articulate interrelationships that exist amongst FFF parameters. Next, a few specimens are fabricated using acrylonitrile butadiene styrene plastic at varied build orientation and build style. Effects of build orientation and build style on part’s ultimate tensile strength, flexure strength along with width build time are studied. Prototype beams (of different thickness) are fabricated by varying build style. Instrumental impact hammer Modal analysis is performed on the cantilever beams (cantilever support) to obtain the natural frequencies (first mode). Parametric influence on natural frequencies is also studied.

Findings

Static mechanical properties (tensile and flexure strength) are greatly influenced by build style and build orientation. Natural frequency (NF) of prototype beams is highly influenced by the build style and beam thickness.

Originality/value

FFF built parts when subjected to application, may have to face a variety of external dynamic loads. If frequency of induced vibration (due to external force) matches with NF of the component part, resonance is incurred. To avoid occurrence of resonance, operational frequency (frequency of externally applied forces) must be lower/ higher than the NF. Because NF depends on mass and stiffness, and boundary conditions, FFF parts produced through varying build style may definitely correspond to varied NF. This aspect is explained in this work.
Managing change in the face of a pandemic: the case of Cargills (Ceylon) PLC
Authors: Senaratne Sanduni Ishara , Deyalage Piruni , Wickremasinghe Hashini T. , Navaratne Thilini , Piyasena Kinchigune Gamaralalage Chanaka Chameera
Published: August 2023

Research methodology

This case study has been developed based on the primary data obtained through a series of interviews held with the senior management of Cargills, and the secondary data obtained from the company’s corporate website www.cargillsceylon.com/,annual reports and publicly available sources of information such as newspaper articles.

Case overview/synopsis

This case study focuses on the strategic responses employed by Cargills (Ceylon) PLC – a leading business conglomerate in Sri Lanka – in response to the challenges posed by the COVID-19 pandemic. The duration of this case study is from January 2020 to September 2021. The case study particularly examines the key business sectors of Cargills (Ceylon) PLC – retail, food manufacturing and quick service restaurants – which elaborate on the change management practices and strategies deployed by the company in each of these sectors during this challenging period. This study is based on the primary data gathered from the interviews held with the Cargills (Ceylon) PLC team, and the secondary data obtained from the corporate website of Cargills (Ceylon) PLC. This case study is most suitable to be taught in academic courses related to strategic change management.

Complexity academic level

The case is most suited to be discussed with undergraduates (3rd year and 4th year) following business and management studies related disciplines. While the pivotal area around which the case has been developed is strategic change management, covering environmental analysis, strategic analysis and process of change management, the case could also be used in strategic management classes, to discuss environmental analysis, strategic planning approaches and business and corporate level strategies.

Subject code

CSS 11: Strategy.
Neuro‐behavioural changes after acquired brain injury: The role of the occupational therapist; the interventions they use and why
Authors: Brown Anahita , Tse Tamara , Fortune Tracy
Published: August 2023

Introduction

Almost half of the people living with acquired brain injury experience behavioural changes, yet there is lack of clarity both in the literature, and through major stakeholders internationally, regarding how occupational therapists contribute to neuro‐behavioural rehabilitation and what their role is in this context.

Methods

This study answers the research question: What do occupational therapists perceive as their role in behavioural rehabilitation with adults living with acquired brain injury, and what treatment approaches, if any, are they using to promote occupation? A national, qualitative, bounded case study design using semi‐structured interviews was used to explore what the role of the occupational therapist is in neuro‐behavioural rehabilitation across subacute brain injury units in Australia.

Findings

Four themes were identified which provide clarification on the role of the occupational therapist in neuro‐behavioural rehabilitation: You change the task, you change the environment, change the person; build a safe rapport; the sensory stuff is huge and, finally, owning how we think.

Conclusion

This bounded case study provides insight into how occupational therapists perceive their role and the interventions they use to promote occupational engagement. The lack of recognition of the occupational therapist role is a barrier to providing appropriate neuro‐behavioural rehabilitation. This case study identified sensory approaches, building safe rapport and adapting the environment as the main interventions used in neuro‐behavioural rehabilitation by occupational therapists.
Suppression of hypothalamic–pituitary–gonadal function by linzagolix in benign prostatic hyperplasia and polycystic ovary syndrome animal models
Authors: Tezuka Motohiro , Yonekubo‐Awaka Saori , Tamai Yasuaki , Tsuchioka Kumi , Kobayashi Kaoru , Kuramochi Yu , Tatemichi Satoshi , Nagasawa Tatsuya , Kiguchi Sumiyoshi
Published: August 2023

The hypothalamic–pituitary–gonadal (HPG) axis is an important regulatory mechanism involved primarily in the development and regulation of the reproductive systems. The suppression of the HPG axis by gonadotropin‐releasing hormone (GnRH) analogues is expected to be effective for the treatment of sex hormone‐dependent diseases, such as endometriosis, uterine fibroid, prostate cancer, benign prostatic hyperplasia (BPH) and polycystic ovary syndrome (PCOS). Despite the established involvement of GnRH signalling in these disorders, the therapeutic efficacy of small molecular GnRH antagonists for BPH and PCOS has not been adequately evaluated in non‐clinical studies. Therefore, the purpose of the present study was to evaluate the potential of linzagolix, a small molecular GnRH antagonist, as a potential new treatment option for BPH and PCOS. Dogs and rats exhibiting normal prostates and dogs diagnosed with prostatic hyperplasia were used to evaluate the effects of linzagolix in BPH. The effects of linzagolix were also examined in a rat model of PCOS induced by repeated administration of letrozole, an aromatase inhibitor. Linzagolix reduced serum luteinizing hormone and testosterone levels in male rats and normal or BPH model dogs and suppressed prostate weight without testosterone depletion, suggesting the existence of an optimal therapeutic testosterone level for BPH treatment. In a PCOS rat model, linzagolix improved both insulin resistance and ovarian dysfunction. Treatment with linzagolix decreased follicle‐stimulating hormone levels, but did not alter serum luteinizing hormone and testosterone levels. These results indicate that linzagolix may provide a new treatment option for GnRH‐related disorders, such as BPH and PCOS.
Teaching economics as though values matter
Authors: Angner Erik
Published: August 2023

Economics is permeated with value judgements, and removing them would be neither possible nor desirable. They are consequential, in the sense that they have a sizeable impact on economists’ output. Yet many economists may not even realise they are there. This paper surveys ways in which values influence economic theory and practice and explores some implications for the manner in which economics – especially welfare economics – is taught, practised and communicated. Explicit attention to values needs to be embedded in the teaching of economics at all levels.
The interaction of e‐cigarette use and mental health symptoms on risk of cigarette smoking initiation among young adults in the United States
Authors: Harlow Alyssa F. , Han Dae‐Hee , Eckel Sandrah P. , McConnell Rob , Leventhal Adam M. , Barrington‐Trimis Jessica L.
Published: August 2023

Background and Aims

It is unknown whether young adults who vape nicotine and have poor mental health have greater risk of smoking initiation than expected based on individual risks of vaping and mental health alone. This study aimed to estimate the joint association of vaping and mental health symptoms with smoking initiation among young adults, and test for additive interaction between vaping and mental health in smoking initiation risk.

Design

Using five waves of the Population Assessment of Tobacco and Health (wave 1, 2013–2014; wave 2, 2014–2015; wave 3, 2015–2016; wave 4, 2016–2018; wave 5, 2018–2019), we estimated risk differences (RD) for the association of time‐varying and time‐lagged vaping and internalizing (e.g., anxiety, depressive) and externalizing (e.g., inattention/hyperactivity) mental health symptoms with cigarette smoking initiation at follow‐up, over four 1‐year intervals. We calculated interaction contrasts (IC) to estimate the excess risk of smoking initiation attributable to the interaction of vaping and mental health symptoms.

Setting

United States.

Participants

A total of 6908 cigarette‐naïve individuals aged 18–24 years.

Measurements

Exposures included current (past‐30 day) vaping and internalizing and externalizing mental health symptoms (high vs moderate/low symptoms). The outcome was smoking initiation (ever cigarette use) after 1 year.

Findings

The per‐interval risk of smoking initiation was 7.6% (1039 cases/13 712 person‐intervals). Compared with noncurrent vaping and moderate/low mental health symptoms, adjusted RDs for current vaping and high mental health symptoms were 17.2% (95% confidence interval [CI]: 7.2% to 27.3%) for internalizing and 18.7% (95%CI: 8.1% to 29.2%) for externalizing symptoms. The excess risk attributed to interaction of current vaping and high externalizing symptoms was IC = 11.3% (95%CI: 1.3% to 21.2%; P = 0.018), with inconclusive findings for internalizing symptoms (IC = 7.7% [95%CI: −2.2% to 17.7%; P = 0.097]).

Conclusions

There is possible, but inconclusive, superadditivity between vaping and mental health in risk of smoking initiation among young adults in the United States.
Parental perceptions of social and emotional well‐being of young children from Australian military families
Authors: Rogers Marg , Johnson Amy , Coffey Yumiko , Fielding Jill , Harrington Ingrid , Bhullar Navjot
Published: August 2023

Introduction

Many Australian Defence Force (ADF) and Veteran families are affected by the stressors of Defence family life, including frequent and prolonged parental deployments, and frequent relocations.

Objective

To address a gap in information about Defence and Veteran (hereafter Defence) parents' knowledge, confidence and resources to support their young children's well‐being and build their resilience.

Design

This study used a mixed methods design to explore Defence parent's perceptions of their young children's (aged 2–8 years) social and emotional well‐being and understanding of their children's responses to unique stressors as well as their confidence in providing support. Data from 41 parents were available.

Findings

Overall, parents reported positive well‐being evaluation of their children. However, just over a third of parents also reported that their children rarely cope well on two indicators combined (adapting to new situations and sharing negative emotions with others). Significantly, more than half of the parents (61%) were only partially confident in their ability to assist their children to cope with unique stressors in military families. Qualitative data provided further insights into children's struggle with relocations and parental absence and the challenges parents face in supporting them. Parents reported having limited access to effective age‐ and culturally appropriate resources to support their young children.

Discussion

In a first‐of‐its kind study, we found that Australian Defence parents reported their young children were coping on most of the key well‐being indicators. However, awareness of currently available supports for children remains a barrier as well as access to contextualised, age‐ and culturally appropriate resources are lacking.

Conclusion

There is a need for access to free, quality, online, research‐based Australian resources to support young children from Defence families, especially for those living in regional and rural locations and are less likely to have access to mental health and other specialist supports.
Commentary: Climate‐Related Risks Disclosures in the Notes to Financial Statements: Descriptive Evidence from Australia
Authors: Li Ao , Lee Eric C.T.
Published: August 2023

This paper aims to provide background information about the International Accounting Standards Board's Climate‐Related Risks in the Financial Statements project. Further, we provide some observations of related disclosures in the notes to the 2022 financial statements of the top 75 Australian Securities Exchange‐listed entities. Overall, we find that there has been improvement in the disclosures and considerations of climate‐related risks in the financial statements in recent years. However, the disclosures appear to be generic, which may not meet the needs of financial statement users. We suggest that further research is needed to provide evidence about how such risks are considered and disclosed in the financial statements and whether such information meets user needs. Evidence will help standard setters to consider appropriate action, such as providing educational material or amending the Accounting Standards, to enhance the quality of financial reporting.
Key factors associated with 6‐thioguanine and 6‐methylmercaptopurine nucleotide concentrations in children treated by thiopurine for acute leukaemia and inflammatory bowel disease
Authors: de Beaumais Tiphaine Adam , Lorrain Simon , Mamhoudi Naura , Simonin Mathieu , Martinez Vinson Christine , Medard Yves , Petit Arnaud , Jacqz‐Aigrain Evelyne
Published: August 2023

Aims

Azathioprine (AZA) and 6‐mercaptopurine are prescribed in acute lymphoblastic leukaemia (ALL) and inflammatory bowel diseases (IBD). Metabolism to active 6‐thioguanine (6TGN) and 6‐methylmercaptopurine nucleotides (6MMPN) is variable but therapeutic drug monitoring (TDM) remains debatable. This study reports on factors impacting on red blood cell (RBC) metabolites concentrations in children to facilitate TDM interpretation.

Methods

The first paediatric TDM samples received during year 2021 were analysed, whatever indication and thiopurine drug. Target concentration ranges were 200–500, <6000 pmol/8 × 108 RBC for 6TGN and 6MMPN.

Results

Children (n = 492) had IBD (64.8%), ALL (22.6%) or another autoimmune disease (12.6%): mean ages at TDM were 7.5 in ALL and 13.7 years in IBD (P < .0001). ALL received 6‐mercaptopurine (mean dose 1.7 mg/kg/d with methotrexate), IBD received AZA (1.9 mg/kg/d with anti‐inflammatory drugs and/or monoclonal antibodies). Median 6TGN and 6MMPN concentrations were 213.7 [interquartile range: 142.5; 309.6] and 1144.6 [419.4; 3574.3] pmol/8 × 108 RBC, 38.8% of patients were in the recommended therapeutic range for both compounds. Aminotransferases and blood tests were abnormal in 57/260 patients: 8.1% patients had high alanine aminotransaminase, 3.4% of patients had abnormal blood count. Factors associated with increased 6TGN were age at TDM and thiopurine methyltransferase genotype in ALL and AZA dose in IBD. The impact of associated treatment in IBD patients was also significant.

Conclusion

TDM allowed identification of children who do not reach target levels or remain over treated. Including TDM in follow‐up may help physicians to adjust dosage with the aim of reducing adverse effects and improve treatment outcome.
Life motion signals bias the perception of apparent motion direction
Authors: Ge Yiping , Yu Yiwen , Huang Suqi , Huang Xinyi , Wang Li , Jiang Yi
Published: August 2023

Walking direction conveyed by biological motion (BM) cues, which humans are highly sensitive to since birth, can elicit involuntary shifts of attention to enhance the detection of static targets. Here, we demonstrated that such intrinsic sensitivity to walking direction could also modulate the direction perception of simultaneously presented dynamic stimuli. We showed that the perceived direction of apparent motion was biased towards the walking direction even though observers had been informed in advance that the walking direction of BM did not predict the apparent motion direction. In particular, rightward BM cues had an advantage over leftward BM cues in altering the perception of motion direction. Intriguingly, this perceptual bias disappeared when BM cues were shown inverted, or when the critical biological characteristics were removed from the cues. Critically, both the perceptual direction bias and the rightward advantage persisted even when only local BM cues were presented without any global configuration. Furthermore, the rightward advantage was found to be specific to social cues (i.e., BM), as it vanished when non‐social cues (i.e., arrows) were utilized. Taken together, these findings support the existence of a specific processing mechanism for life motion signals and shed new light on their influences in a dynamic environment.
Folate trapping is lethal to cancer cells
Authors: Rather Gulam Mohmad
Published: August 2023

Regulation of formate flux by a key folate enzyme, MTHFD2 (methylene tetrahydrofolate dehydrogenase 2) in cancer cells remains poorly understood. Green et al. (Nature Metabolism, 2023; 5: 642–659) showed an interesting phenomenon of “folate trapping” toxicity leads to cancer cell kill using a potent inhibitor (TH9619) against the dehydrogenase and cyclohydrolase (DC) activities of cytosolic methylenetetrahydrofolate dehydrogenase 1 (cMTHFD1) and nuclear methylenetetrahydrofolate dehydrogenase 2 (nMTHFD2), but not the mitochondrial MTHFD2 (mTHFD2). But, mMTHFD2 is required for formate flow to cytosol which leads to the trapping of 10‐formyl tetrahydrofolate and causes toxicity by TH9619 treatment, to kill cancer cells expressing mMTHFD2. This article opens new avenues to be evaluated for therapeutic benefits of cancer patients where MTHFD2 shows overexpression viz‐a‐viz breast, prostate, colorectal, acute myeloid leukemia, and other cancer types.
Design and characterization of a novel tumor‐homing cell‐penetrating peptide for drug delivery in TGFBR3 high‐expressing tumors
Authors: Wu Yi‐Jie , Lei Jin , Zhao Jian , Cao Xue‐Wei , Wang Fu‐Jun
Published: August 2023

Targeted therapy has attracted more and more attention in cancer treatment in recent years. However, due to the diversity of tumor types and the mutation of target sites on the tumor surface, some existing targets are no longer suitable for tumor therapy. In addition, the long‐term administration of a single targeted drug can also lead to drug resistance and attenuate drug potency, so it is important to develop new targets for tumor therapy. The expression of Type III transforming growth factor β receptor (TGFBR3) is upregulated in colon, breast, and prostate cancer cells, and plays an important role in the occurrence and development of these cancers, so TGFBR3 may be developed as a novel target for tumor therapy, but so far there is no report on this research. In this study, the structure of bone morphogenetic protein 4 (BMP4), one of the ligands of TGFBR3 was analyzed through the docking analysis with TGFBR3 and sequence charge characteristic analysis, and a functional tumor‐targeting penetrating peptide T3BP was identified. The results of fluorescent labeling experiments showed that T3BP could target and efficiently enter tumor cells with high expression of TGFBR3, especially A549 cells. When the expression of TGFBR3 on the surface of tumor cells (HeLa) was knocked down by RNA interference, the high delivery efficiency of T3BP was correspondingly reduced by 40%, indicating that the delivery was TGFBR3‐dependent. Trichosanthin (TCS, a plant‐derived ribosome inactivating protein) fused with T3BP can enhance the inhibitory activity of the fusion protein on A549 cells by more than 200 times that of TCS alone. These results indicated that T3BP, as a novel targeting peptide that can efficiently bind TGFBR3 and be used for targeted therapy of tumors with high expression of TGFBR3. This study enriches the supply of tumor‐targeting peptides and provides a new potential application option for the treatment of tumors with high expression of TGFBR3.