bluuebunny/crossref_metadata_2025 huggingface dataset:
Shaken to the core: trust trajectories in the aftermaths of adverse cyber events
Authors: Searle Rosalind , Renaud Karen V. , van der Werff Lisa
Published: October 2024

Purpose

Adverse cyber events, like death and taxes, have become inevitable. They are an increasingly common feature of organisational life. Their aftermaths are a critical and under-examined context and dynamic space within which to examine trust. In this paper, we address this deficit.

Design/methodology/approach

Drawing on pertinent theory and reports of empirical studies, we outline the basis of two alternative subsequent trajectories, drawing out the relationships between trust, vulnerability and emotion, both positive and negative, in the aftermath of an adverse cyber event.

Findings

We combine stage theory and social information processing theories to delineate the dynamics of trust processes and their multilevel trajectories during adverse cyber event aftermaths. We consider two response trajectories to chart the way vulnerability arises at different levels within these social systems to create self-reinforcing trust and distrust spirals. These ripple out to impact multiple levels of the organisation by either amplifying or relieving vulnerability.

Research limitations/implications

The way adverse cyber events aftermaths are managed has immediate and long-term consequences for organisational stakeholders. Actions impact resilience and the ability to preserve the social fabric of the organisations. Subsequent trajectories can be “negative” or “positive”. The “negative” trajectory is characterised by efforts to identify and punish the employee whose actions facilitated the adverse events, i.e. the “who”. Public scapegoating might follow thereby amplifying perceived vulnerability and reducing trust across the board. By contrast, the “positive” trajectory relieves perceived vulnerability by focusing on, and correcting, situational causatives. Here, the focus is on the “what” and “why” of the event.

Practical implications

We raise the importance of responding in a constructive way to adverse cyber events.

Originality/value

The aftermaths of cyber attacks in organisations are a critical, neglected context. We explore the interplay between trust and vulnerability and its implications for management “best practice”.
Non-optimality of intellectual capital inputs: a new avenue for research
Authors: Barajas Angel , Shakina Elena
Published: October 2024

Purpose

This paper aims to initiate new avenues of research by examining optimal intellectual capital (IC) inputs, introducing three theories into the discussion: diminishing returns to scale, transaction costs economics and efficiency wage theory. In the second part, it advocates for demonstrating the existence of such non-optimality through empirical tests.

Design/methodology/approach

This paper is divided into two parts. The first part provides a theoretical justification for the necessity of observing nonlinear relationships between IC inputs and firm performance. In the empirical section, the research design follows a four-step process, each progressively building on insights gained from the preceding phase: (1) establishing a baseline linear regression model; (2) introducing the logarithm of the IC inputs; (3) incorporating the square terms of the IC inputs and (4) investigating the phenomena of over- and under-input in IC.

Findings

The background theories and the obtained results highlight the necessity for firms to adopt a strategic approach to IC, acknowledging the diverse effects of IC components on different outcomes. They emphasize the nonlinear nature of IC returns, underscoring the importance of investing up to an optimal level to maximize benefits.

Practical implications

The study’s discovery of optimal levels for the components of IC highlights the importance for practitioners to identify and invest up to these optimal levels. This ensures that IC initiatives are strategically aligned to maximize their positive impact on firm performance.

Originality/value

The integration of theories such as diminishing returns to scale, transaction costs economics and efficiency wage theory, alongside traditional frameworks like the resource-based view, the theory of dynamic capabilities and the knowledge-based theory of the firm, opens up new avenues for research on IC. The proposed methodology and measures – from financial reports – provide opportunities for replicating this type of study.
Comparative assessment of the progress of employee financial participation in the member states of the EU
Authors: Hashi Iraj , Lowitzsch Jens
Published: October 2024

Purpose

This article provides an overview of the different measures promoting EFP schemes that are in place across the EU-27 and the United Kingdom and classifies Member States according to a “success score” given to each measure. “Success” is measured by the degree to which both soft and hard criteria have contributed to promotion of EFP in different countries.

Design/methodology/approach

The article assesses the progress of EFP in EU 27 and the UK using three indicators: (i) legal framework, (ii) fiscal incentives and (iii) political support and social dialogue to obtain an overall score for each country both for ESO and PS. Countries are then grouped into clusters, showing that a significant number of countries have made progress in the spread of both ESO and PS.

Findings

ESO is much less frequently used in Europe than e.g. in the US. If this still largely unexploited potential is to be harnessed, further development of financial participation, ESO in particular, should be part of an overall European strategy for stimulating sustainable and inclusive growth of the EU economy. A generally favourable attitude in some countries has usually led to supportive legislation for EFP schemes, which, in turn, have led to the spread of these schemes. Tax incentives are important tools for enhancing and broadening financial participation. When properly designed, they promote the spread of EFP effectively.

Originality/value

Assessing the progress of EFP schemes in EU 27 and the UK using the three indicators (i) legal framework, (ii) fiscal incentives and (iii) political support and social dialogue, we obtain an overall score for each country both for ESO and PS and compare it with those produced in 2014. We can show that in as many as twelve countries, i.e. 44% of MS, there was a positive change in their overall score between 2014 and 2024.
The future of tourism: an interview with Dr Daniel Wright about the genre of science fiction
Authors: Yeoman Ian Seymour , Wright Daniel William Mackenzie
Published: October 2024

Purpose

As the Journal of Tourism Futures celebrates its 10th Anniversary, Dr Ian Yeoman (Hotel Management School Leeuwarden) interviews Dr Daniel Wright (University of Central Lancashire) about the future genre of science fiction and his publications.

Design/methodology/approach

A personal interview.

Findings

Science fiction research is about asking difficult questions, the questions we feel uncomfortable asking and answering. Science fiction is a powerful medium to imagine the future, which students love as it is provocative. In the interview, Dr Wright reflects upon his own writing from immortality to the end of the world.

Originality/value

The power of science fiction, as a genre of transformation, skepticism and thinking out of the box, is often missing in futures studies and scenario planning.
Aircraft joint structure lightweight design
Authors: Zhu Liang , Qu Hongzhang , Zhang Di , Bao Fei
Published: October 2024

Purpose

The purpose of this article is to carry out a lightweight design of the joint structure according to the service condition of the joint.

Design/methodology/approach

The finite element analysis techniques are used along with the variable density structure topology optimization method, the multi-island genetic algorithm for structural dimension optimization and the fatigue life analysis method.

Findings

Utilizing the topology optimization method and size optimization method, the mass of the optimized model for the A100 material model is 9.67 kg. Compared to the pre-optimized model, the mass decreases by 8.23 kg, representing a weight reduction of 46.0% in the optimized model; the fatigue life of the aircraft joint is predicted to be a maximum of 1,460,017 cycles.

Originality/value

The originality of this study is that it provides new design ideas for the lightweight design of aircraft load-bearing structures.
Indigenous communities, collectives and organizations advancing decolonizing methodologies: perspectives from British Columbia Network Environment for Indigenous Health Research in Canada
Authors: Barry Julianne Cecile , Erb Tara Lise , Stelkia Krista
Published: October 2024

Purpose

The British Columbia Network Environment for Indigenous Health Research (BC NEIHR) aims to support and advance research leadership among Indigenous communities, collectives and organizations (ICCOs) within British Columbia, Canada. The BC NEIHR provides support and funding to ICCOs for research development and knowledge sharing. This funding model supports ICCOs' self-determined health research by providing funds that are fully controlled by ICCOs, without the requirement of a non-Indigenous host organization.

Design/methodology/approach

We conducted a critical analysis of 35 ICCO research development and knowledge-sharing grant applications to identify how ICCOs are decolonizing research and methodologies.

Findings

Six themes were identified from ICCO decolonizing methodologies: (1) identified, driven, and led by Indigenous Peoples and community; (2) guidance from advisors, ethical guidelines, and local protocols; (3) follow traditional and cultural practices; (4) determine what is knowledge and ways to share knowledge; (5) celebrating the sharing and returning of knowledge and (6) advancing relationality: building and strengthening relationships.

Originality/value

This paper highlights the impact of how the BC NEIHR and ICCOs are advancing decolonizing methodologies to support self-determined Indigenous health research led by, and grounded in, Indigenous communities. It reflects on the work of Maori scholar Linda Tuhiwai Smith’s Decolonizing Methodologies: Research and Indigenous Peoples and contributes to the literature of decolonizing methodologies.
Downregulation of CD86 in HCMV‐infected THP‐1 cells
Authors: Koshizuka Tetsuo , Sasaki Yuta , Kondo Hiroki , Koizumi Juri , Takahashi Keita
Published: October 2024

Monocytes and macrophages are at the frontline of defense against pathogens. Human cytomegalovirus (HCMV) uses myeloid cells as vehicles to facilitate viral dissemination. HCMV infection in monocytes and macrophages leads to the downregulation of several cell surface markers via an undefined mechanism. Previously, we showed that HCMV pUL42 associates with the Nedd4 family ubiquitin E3 ligases through the PPXY motif on pUL42 and downregulates Nedd4 and Itch proteins in HCMV‐infected fibroblasts. Homologous proteins of HCMV pUL42, such as HHV‐6 U24, downregulate cell surface markers. To reveal the downregulation property of pUL42, we focused on CD86, the key costimulatory factor for acquired immunity. Here, we constructed CD86‐expressing THP‐1 cells using a retroviral vector and analyzed the effects of HCMV infection and pUL42 on CD86 downregulation. Disruption of the PPXY motifs of pUL42 (UL42PA) decelerated the degradation of CD86 in recombinant virus‐infected cells, indicating the involvement of Nedd4 family functions. However, no direct interactions were observed between CD86 and Itch. Interestingly, unlike fibroblast infection, the expression of Nedd4 and Itch proteins increased in HCMV‐infected THP‐1 cells, accompanied by an increase in their transcript levels. Although the function of pUL42 did not relate to the increase of Nedd4 and Itch proteins, pUL42 should affect these Nedd4 proteins to downregulate CD86.
Productivity costs of the green energy transition in Africa
Authors: Sene Ligane , Fall El Hadji
Published: October 2024

Transitioning to renewable energy generates tangible benefits in terms of the environment and emissions of greenhouse gases. However, the economic productivity costs of switching to clean energy cannot be overlooked, in addition to the large resource requirements, potential disruption in energy systems, risks of job losses, and emergence of new inequalities. Therefore, it is crucial to identify and quantify synergies and trade‐offs. This paper investigates the productivity cost of abandoning the use of fossil fuels in African countries, using econometric techniques applied to panel data, including the fully modified ordinary least square. The paper finds that, while renewable energy supply is beneficial to increase total factor productivity, in general, a shift toward a higher share of renewables in the power mix is not without productivity cost on the economy. The analysis accounts for other sources of productivity, such as human capital and the diffusion of embodied technology imported from abroad into local markets. The data also reveal that the energy transition could have heterogeneous effects depending on the regions' and countries' characteristics and stages of transition.
Institutional (ante)narratives of anticipatory entrepreneurial resilience: COVID‐19 and the global entrepreneurship monitor
Authors: Lucas Allison , Mitra Rahul
Published: October 2024

The COVID‐19 crisis severely impacted entrepreneurs worldwide, so that policy dispatches like the Global Entrepreneurship Monitor's (GEM) September 2020 special report, Diagnosing COVID‐19 Impacts on Entrepreneurship: Exploring Policy Remedies for Recovery, were crucial for governments devising economic policies. Our paper examines how the GEM used institutional storytelling to craft anticipatory resilience, by drawing on the Communication Theory of Resilience and (ante)narrative approaches to anticipatory resilience. Findings demonstrated intersections of the GEM's role of resilience storyteller, as well as how resilience action by entrepreneurs and policymakers was narrated by the GEM. We uncover key tensions within the GEM's positioning as diagnostician and fortuneteller, between the resilient processes of normalizing and pivoting for everyday entrepreneurs, and in the institutionalizing work of policymakers through reacting and prospecting. We end by discussing key implications of our narrative approach to how institutions craft anticipatory resilience in response to global crises.
Prioritization of chemical food safety hazards in the European feed supply chain
Authors: van der Fels‐Klerx H. J. , van Asselt E. D. , van Leeuwen S. P. J. , Dorgelo F. O. , Hoek ‐ van den Hil E. F.
Published: October 2024

Extensive monitoring programs of chemical hazards in the animal feed chain are in place, both organized by public and private organizations. The objective of this review was to prioritize chemical hazards for monitoring in the European animal feed supply chain. A step‐wise approach was designed for the prioritization, based on: historical occurrence of the chemicals in animal feed ingredients and animal feeds (in relation to European guidance values or maximum limits in feed); information on transfer of the chemical to edible animal products, and; the extent of human dietary intake of the products and possible adverse human health effects of the chemical. Possible prioritization outcomes were: high (H), medium (M), or low (L) priority for monitoring, or classification not possible (NC) because of limited available data on the transfer of the chemical to edible animal tissues. The selection of chemicals included (with results in parentheses): dioxins and polychlorinated biphenyls (H); brominated flame retardants (H); per‐ and polyfluorinated alkyl substances (H); the heavy metals arsenic (H) and cadmium (H) as well as lead (M) and mercury (M); aflatoxins (H), ochratoxin A (NC), and other mycotoxins (L); pyrrolizidine alkaloids (H) and other plant toxins (NC); organochlorine pesticides (H) and other pesticides (L); pharmaceutically active substances (M); hormones (NC); polycyclic aromatic hydrocarbons (L), heat‐induced processing contaminants (NC), and mineral oils (NC). Results of this study can be used to support risk‐based monitoring by food safety authorities and feed‐producing companies in Europe.
Antibiotic‐producing plant‐associated bacteria, anti‐virulence therapy and microbiome engineering: Integrated approaches in sustainable agriculture
Authors: Roca Amalia , Monge‐Olivares Laura , Matilla Miguel A.
Published: October 2024

Plant health is crucial for maintaining the well‐being of humans, animals and the environment. Plant pathogens pose significant challenges to agricultural production, global food security and ecosystem biodiversity. This problem is exacerbated by the impact of climate change, which is expected to alter the emergence and evolution of plant pathogens and their interaction with their plant hosts. Traditional approaches to managing phytopathogens involved the use of chemical pesticides, but alternative strategies are needed to address their ongoing decline in performance as well as their negative impact on the environment and public health. Here, we highlight the advancement and effectiveness of biocontrol strategies based on the use of antimicrobial‐producing plant‐associated bacteria, anti‐virulence therapy (e.g. quorum quenching) and microbiome engineering as sustainable biotechnological approaches to promote plant health and foster sustainable agriculture. Notably, Enterobacterales are emerging as important biocontrol agents and as a source of new antimicrobials for potential agricultural use. We analysed here the genomes of over 250 plant‐associated enterobacteria to examine their potential to synthesize secondary metabolites. Exploration of the plant microbiome is of major interest in the search for eco‐friendly alternatives for reducing the use of chemical pesticides.
Alterations in peripheral T‐cell and B‐cell subsets in the ankylosing spondylitis patients with gut inflammation
Authors: Luo Xiqing , Li Jinwei , Yang Mingcan , Tu Liudan , Xie Ya , Lv Qing , Wen Shenghui , Wen Xianghui , Zhou Liuzhong , Gu Jieruo
Published: October 2024

Aim

This study investigates changes in immune cell subsets in peripheral blood of ankylosing spondylitis (AS) patients with colitis or terminal ileitis. It aims to explore the connection between changes in lymphocyte subsets and gut inflammation, providing insights for early detection.

Methods

Overall, 50 AS patients undergoing colonoscopy were enrolled. Flow cytometry was employed to analyze lymphocyte subsets, including T and B cells, in peripheral blood. Disease activity was assessed using CRP, ESR, BASDAI, ASDAS‐CRP, and ASDAS‐ESR.

Results

Compared to AS patients without gut inflammation, those with colorectal inflammation showed a significant increase in total T cells (p < .05), an increase in exhausted CD4+ T cells (p < .05), and a decrease in Th2 cells and total Tc cells (p < .05). Notably, in AS patients with terminal ileitis, there was an increase in total B cells and classic switched B cells (p < .05), with a decrease in double‐positive T cells (p < .05). However, no significant differences were observed in the distribution of Tfh‐cell subpopulations (Tfh1, Tfh2, Tfh17) and Tc‐cell subpopulations (Tc1, Tc2, Tc17) between AS patients with either colorectal inflammation or terminal ileitis (p > .05). We explored the relationship between disease activity scores, ESR, CRP, and lymphocyte subsets, but found no statistically significant correlation between them.

Conclusion

Distinct immune patterns may exist in AS with different types of intestinal inflammation. Colitis in AS is primarily characterized by a significant increase in exhausted CD4+ T cells, along with a decrease in Th2 cells. In contrast, terminal ileum inflammation in AS is marked by an increase in total B cells and classic switched B cells. These findings offer new insights for early detection and therapeutic intervention.
Biologic and targeted synthetic disease‐modifying anti‐rheumatic drugs improve body composition in rheumatoid arthritis patients more than conventional synthetic disease‐modifying anti‐rheumatic drugs: Results from the PRESENT study
Authors: Tada Masahiro , Matsumoto Yoshinari , Koike Tatsuya , Mamoto Kenji , Nakamura Tomoyuki , Anno Shohei , Iida Takahiro , Goto Hitoshi , Hidaka Noriaki
Published: October 2024

Introduction

The effects of biologic and targeted synthetic disease‐modifying anti‐rheumatic drugs (b/tsDMARDs) and conventional synthetic disease‐modifying anti‐rheumatic drugs (csDMARDs) on body composition and muscle function in rheumatoid arthritis (RA) patients requiring treatment enhancement were compared.

Methods

This multicenter, prospective, observational study (PRESENT Study) divided RA patients non‐randomly into a csDMARD group (n = 100) and a b/tsDMARD group (n = 100). Changes in body composition and muscle function were examined in 80 patients in each group followed for 52 weeks. The percentages of new‐onset and improved sarcopenia over 1 year were investigated. Patients in the b/tsDMARD group were divided into three groups by drug type: TNF inhibitors (n = 30), non‐TNF inhibitors (n = 23), and JAK inhibitors (n = 27).

Results

Baseline median age and disease duration were 70.0 and 4.0 years, respectively. Changes in weight (24 and 52 weeks) and muscle mass (52 weeks) were significantly higher in the b/tsDMARD group (p = .035, p < .001, and p = .002, respectively). On multivariate logistic regression analysis, b/tsDMARD treatment (OR 3.21, p = .002), DAS28‐ESR (OR 0.65 p = .011), and muscle mass (OR 0.90, p = .023) were independently associated with increased muscle mass at 52 weeks. The percentages of new‐onset and improved sarcopenia were almost equal. There were no significant differences in the time‐dependent changes (52 weeks) of clinical status, body composition, muscle function, and status of sarcopenia among TNF inhibitors, non‐TNF inhibitors, and JAK inhibitors.

Conclusions

Weight and muscle mass increased significantly more with b/tsDMARD than with csDMARD treatment. There were no differences in body composition changes by mode of action with b/tsDMARDs.
MicroRNA‐1307‐3p contributes to breast cancer progression through PRM2
Authors: Estupiñan‐Jiménez José Roberto , Villarreal‐García Valeria , Gonzalez‐Villasana Vianey , Vivas‐Mejia Pablo E. , Vazquez‐Guillen Jose Manuel , Zapata‐Morin Patricio Adrián , Flores‐Colón Marienid , Altamirano‐Torres Claudia , Viveros‐Valdez Ezequiel , Ivan Cristina , Rashed Mohammed H. , Bayraktar Recep , Rodríguez‐Padilla Cristina , Lopez‐Berestein Gabriel , Resendez‐Perez Diana
Published: October 2024

Background

Despite advances in screening and therapy, breast cancer (BC) remains the predominant cancer in women globally. Dysregulation of microRNAs (miRNAs) is pivotal in carcinogenesis across various cancers, including BC. Evidence indicates that miR‐1307‐3p is upregulated in BC tumors, yet its target genes are not fully elucidated. This study aimed to explore how miR‐1307‐3p regulates BC proliferation, migration, invasion, and angiogenesis and to identify potential target genes.

Methods

Basal miR‐1307‐3p levels were quantified in BC cell lines MDA‐MB‐231 and MCF‐7, as well as MCF‐10A using quantitative real‐time reverse transcription‐PCR (RT‐qPCR). The impact of miR‐1307‐3p inhibition on BC cell proliferation, migration, invasion, and angiogenesis was assessed. Nine miRNA‐target prediction databases identified potential miR‐1307‐3p targets. Target expression was validated using RT‐qPCR, Western blot, and dual‐luciferase reporter assays. MiR‐1307‐3p was overexpressed in MDA‐MB‐231 and MCF‐7 compared to MCF‐10A.

Results

Inhibiting miR‐1307‐3p significantly reduced BC cell proliferation, migration, invasion, and angiogenesis. Bioinformatics analysis identified 17 potential miR‐1307‐3p targets, with protamine 2 (PRM2) overexpression confirmed via Western blot and dual‐luciferase assays.

Conclusion

MiR‐1307‐3p overexpression in BC promotes proliferation, migration, invasion, and angiogenesis. PRM2 emerges as a novel miR‐1307‐3p target in BC.
Investing in Netflix: Accounting for Content Assets*
Authors: Henderson Darren
Published: October 2024

This case describes an equity investment scenario in the context of the COVID‐19 pandemic. A fictional decision‐maker, Amandeep Singh, is considering whether or not to invest in Netflix, Inc. (Netflix). Netflix has benefited from changing habits during the pandemic, but Singh questions whether those benefits will persist post‐pandemic. To make his decision, Singh needs to perform a qualitative analysis of the video streaming industry and Netflix itself before moving to a quantitative analysis of Netflix's performance. To properly assess performance, Singh needs to fully understand Netflix's accounting methods and estimates for content assets—especially original content. The case is ideally suited to an MBA or Executive MBA audience. Students can easily engage with the case since they will be familiar with the company and industry. This familiarity allows for a general discussion about the industry's future and key success factors. The case provides an opportunity to cover core financial statement analysis concepts and drives home the importance of understanding accounting judgments when assessing firm performance.
Orbitofrontal cortex to dorsal striatum circuit is critical for incubation of oxycodone craving after forced abstinence
Authors: Lin Hongyu , Olaniran Adedayo , Luo Xiang , Strauch Jessica , Burke Megan A. M. , Matheson Chloe L. , Li Xuan
Published: October 2024

Relapse is a major challenge in treating opioid addiction, including oxycodone. During abstinence, oxycodone seeking progressively increases, a phenomenon termed incubation of oxycodone craving. We previously demonstrated a causal role of orbitofrontal cortex (OFC) in this incubation. Here, we studied the interaction between glutamatergic projections from OFC and dopamine 1‐family receptor (D1R) signaling in dorsal striatum (DS) in this incubation in male rats. We first examined the causal role of D1R signalling in DS in incubated oxycodone seeking. Next, we combined fluorescence‐conjugated cholera toxin subunit B (CTb‐555, a retrograde tracer) with Fos (a neuronal activity marker) to assess whether the activation of OFC→DS projections was associated with incubated oxycodone seeking. We then used a pharmacological asymmetrical disconnection procedure to examine the role of the interaction between projections from OFC and D1R signalling in DS in incubated oxycodone seeking. We also tested the effect of unilateral pharmacological inactivation of OFC or unilateral D1R blockade of DS on incubated oxycodone seeking. Finally, we assessed whether contralateral disconnection of OFC→DS projections impacted non‐incubated oxycodone seeking on abstinence day 1. We found that D1R blockade in DS decreased incubated oxycodone seeking and OFC→DS projections were activated during incubated oxycodone seeking. Moreover, anatomical disconnection of OFC→DS projections, but not unilateral inactivation of OFC or unilateral D1R blockade in DS, decreased incubated oxycodone seeking. Lastly, contralateral disconnection of OFC→DS projections had no effect on oxycodone seeking on abstinence day 1. Together, these results demonstrated a causal role of OFC→DS projections in incubation of oxycodone craving.
Weather shocks affect trade policy: Evidence from preferential trade agreements
Authors: Amodio Francesco , Baccini Leonardo , Chiovelli Giorgio , Di Maio Michele
Published: October 2024

We show that weather shocks affect government trade policy decisions. We exploit variation in rainfall during the growing season within and across countries to show that weather shocks impact agricultural output and trade. Using information on tariff cuts by commodity from preferential trade agreements signed between 1995 and 2014, we then show that weather shocks that happen during the negotiation period correlate strongly with the size of tariff cuts. When weather shocks increase (decrease) a country's capacity to produce a given crop, its government negotiates a smaller (larger) tariff cut. These results are consistent with a political economy trade model with sector‐specific inputs in which the government places more weight on producers relative to consumers in its objective function. They also reveal that governments update their beliefs about domestic agricultural production capacity in response to weather shocks.
Correlation of adenomyosis features to live birth rates after the first IVF/ICSI treatment, when using the revised Morphological Uterus Sonographic Assessment group definitions
Authors: Alson Sara , Henic Emir , Hansson Stefan R. , Sladkevicius Povilas
Published: October 2024

Introduction

Data regarding the impact of adenomyosis on the outcomes after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment are conflicting. Standardized diagnostic criteria are prerequisites for studying a potential association between adenomyosis and IVF/ICSI treatment outcomes. This study aims to examine the cumulative live birth rate (CLBR) after the first IVF/ICSI treatment in women with or without direct or indirect features of adenomyosis, using the revised Morphological Uterus Sonographic Assessment (MUSA) group definitions.

Material and Methods

This was a prospective cohort study of 1037 women aged 25–≤39 years, undergoing their first IVF/ICSI treatment between January 2019 and October 2022. The presence of MUSA features of adenomyosis was assessed prior to treatment start.

Results

The CLBR after the first IVF/ICSI treatment was 424/1037 (40.9%, 95% CI, 37.9–43.8) in the total cohort. Women with direct features of adenomyosis had lower CLBR, 25/102 (24.5%; 95% CI, 17.5–31.5) than women without, 399/935 (42.7%; 95% CI, 39.5–45.8), p < 0.001. The adjusted relative risk (aRR) for live birth for women with direct features of adenomyosis compared to women without was 0.62 (95% CI, 0.43–0.88), p = 0.007. Direct features were associated with a higher risk of miscarriage after frozen embryo transfer, aRR 2.88 (95% CI, 1.49–5.57), p = 0.002. Women with indirect features had a lower CLBR [50/188 (26.6%, 95% CI, 20.3–32.9)] than women without [399/935, (42.7%, 95% CI, 39.5–45.8)], aRR 0.58 (95% CI, 0.45–0.75), p < 0.001. For features located in the inner myometrium, the aRR for live birth was 0.29 (95% CI 0.11–0.74), p = 0.010 and for the outer myometrium 2.61 (95% CI 1.42–4.8), p = 0.002. An interrupted junctional zone was the single feature that impacted CLBR the most.

Conclusions

The presence of direct or indirect MUSA features of adenomyosis correlates to reduced live birth rates in women undergoing their first IVF/ICSI treatment. Features located in the inner myometrium, particularly an interrupted junctional zone, reduced the chance of live birth the most, whereas location in the outer myometrium was associated with higher chances of live birth. Systematic ultrasound examinations should be considered for women scheduled for IVF/ICSI treatment, for adequate counseling on the chances of successful treatment.
Impact of early detection and steroid treatment on fetal ventricular heart rate and pacemaker implantation in anti‐Ro/SSA positive congenital heart block
Authors: Sonesson Sven‐Erik , Ambrosi Aurelie , Nordenstam Felicia , Eliasson Håkan , Wahren‐Herlenius Marie
Published: October 2024

Introduction

We investigated the effects of timing of detection and transplacental fluorinated steroid treatment on ventricular heart rate (HR) and age at pacemaker implantation in fetal third‐degree atrioventricular block (AVB).

Material and Methods

Twenty‐five of 31 fetuses diagnosed with Ro/SSA autoantibody‐positive AVB II‐III at our tertiary fetal cardiology center (2000–2020) and AVB III as final feto‐neonatal outcome were reviewed.

Results

AVB was detected approximately 5 weeks earlier in pregnancy if followed in a surveillance program compared to cases referred from primary care for bradycardia (20.6 [2.3] [mean (SD)] vs. 25.4 [3.2] weeks, p = 0.001). AVB detected before 24 weeks had higher HR than those detected later in gestation (63.3 [6.9] vs. 57.2 [6.9] bpm, p = 0.042), with a larger proportion having HR >60 bpm (80% vs. 33%, p = 0.041). The 17/25 cases that received treatment with fluorinated steroid were diagnosed earlier in gestation, with higher HR at diagnosis (61.7 [7.1] vs. 54.7 [6.3] bpm, p = 0.026), 1–2 weeks after diagnosis/treatment start, and before birth (65.4 [12.4] vs. 54.9 [5.7] bpm, p = 0.030) than untreated cases. Overall, 11 cases were commenced on betamimetics: three at diagnosis and eight at or after the examination made 1–2 weeks after diagnosis/treatment start, without any HR improvement. Two of 24 surviving babies were born preterm, and 4/24 received a neonatal pacemaker. Age at pacemaker implantation correlated significantly with HR before birth (Spearman R 0.57, p = 0.004), and fetuses with HR >60 bpm had a higher rate of pacemaker‐free survival at three (90% vs. 40%, p = 0.018) and 12 months of age (80% vs. 13%, p = 0.002). The same trend was observed in pacemaker‐free survival at 3 months of age in fluorinated steroid‐treated compared to untreated cases (71% vs. 38%, ns).

Conclusions

Our data confirm that AVB III detected earlier in gestation have a higher HR, and suggest that this higher HR can be successfully maintained to the end of gestation in cases treated with fluorinated steroids. Fetuses with HR >60 bpm before birth had a lower rate of pacemaker implantation at 3 and 12 months of age.
Hyperreflective ganglion cell layer band in a large cohort of non‐syndromic retinitis pigmentosa: Frequency and clinical correlations
Authors: Dias Margarida Q. , Gouveia Nuno , Franca Maria , Murta Joaquim , Silva Rufino , Marques João Pedro
Published: October 2024

Purpose

Recently, an ‘hyperreflective ganglion cell layer band’ (HGB) has been described on spectral‐domain optical coherence tomography (SD‐OCT) in a subset of patients with retinitis pigmentosa (RP). This study aims to validate and describe the frequency of HGB in a large cohort of Portuguese patients with RP.

Methods

This single‐centre, cross‐sectional cohort study included consecutive patients with a genetic diagnosis of RP. SD‐OCT images were reviewed to identify the presence of the HGB and other retinal comorbidities. The HGB was defined as a continuous hyperreflective band within the thickness of the ganglion cell layer (GCL). We built mixed‐effects regression models, accounting for inter‐eye correlations, to investigate features predictive of visual acuity. Subsequently, a reduced model was fitted.

Results

A total of 398 eyes from 201 patients were included. HGB was identified in 69 (17.3%) eyes from 39 (19.4%) patients. Patients presenting with the HGB were significantly younger at diagnosis and at symptom onset. Median BCVA [ETDRS (IQR)] was 65 (29) letters in eyes with the HGB and 70 (21) letters in eyes without HGB (p < 0.001). In both the full and reduced mixed‐effects models, the presence of HGB and macular hole (MH) was significantly associated with worse BCVA.

Conclusions

This study validates the recent description of HGB within the GCL in a subset of patients with RP. Eyes with HGB demonstrated significantly worse BCVA compared to those without HGB, suggesting that the presence of HGB may serve as an SD‐OCT biomarker of worse visual prognosis in these patients.
Letter: Zinc and Selenium—Potential Biomarkers for Chronic Liver Disease? Authors' Reply
Authors: Dominik Nina , Balcar Lorenz , Semmler Georg , Simbrunner Benedikt , Schwarz Michael , Hofer Benedikt S. , Hartl Lukas , Jachs Mathias , Scheiner Bernhard , Pinter Matthias , Trauner Michael , Mandorfer Mattias , Pilger Alexander , Reiberger Thomas
Published: October 2024

LINKED CONTENT

This article is linked to Dominik et al papers. To view these articles, visit https://doi.org/10.1111/apt.18179 and https://doi.org/10.1111/apt.18293.
Coping strategies employed by transgender youth with higher and lower quality of life
Authors: Chinazzo Ítala Raymundo , Vaitses Fontanari Anna Martha , Riva Annelise , de Brito Silva Bruno , Rodrigues Lucca P. , Trajano Ana Carolina , Feijó Marina , Brandelli Costa Angelo , Lobato Maria Inês Rodrigues
Published: October 2024

Understanding transgender youth coping mechanisms may help create strategies that reduce the influence of stress on quality of life. Our study aims to measure the quality of life of Brazilian transgender youth and analyse the association with their coping strategies used for dealing with general and gender‐related stress. The sample consisted of 185 participants (μ = 18.49 years; SD 2.42); of which 95 (46.34%) transgender boys, 45 (21.95%) transgender girls, 65 (31.71%) non‐binary. Better quality of life was related to social support, whereas lower quality of life was related to the use of avoidance coping style in the context of general stress. The study found no association between coping strategies for gender‐related stress and quality of life. Thus, the increase in quality of life in the context of gender distress among transgender youth should involve other mechanisms than promoting coping skills.
Combined MEK1/2 and ATR inhibition promotes myeloma cell death through a STAT3‐dependent mechanism in vitro and in vivo
Authors: Li Lin , Hu Xiaoyan , Nkwocha Jewel , Kmieciak Maciej , Meads Mark B. , Shain Kenneth H. , Alugubelli Raghunandan R. , Silva Ariosto S. , Mann Hashim , Sudalagunta Praneeth R. , Canevarolo Rafael R. , Zhou Liang , Grant Steven
Published: October 2024

Mechanisms underlying potentiation of the anti‐myeloma (MM) activity of ataxia telangiectasia Rad3 (ATR) antagonists by MAPK (Mitogen‐activated protein kinases)‐related extracellular kinase 1/2 (MEK1/2) inhibitors were investigated. Co‐administration of the ATR inhibitor (ATRi) BAY1895344 (BAY) and MEK1/2 inhibitors, for example, cobimetinib, synergistically increased cell death in diverse MM cell lines. Mechanistically, BAY and cobimetinib blocked STAT3 Tyr705 and Ser727 phosphorylation, respectively, and dual dephosphorylation triggered marked STAT3 inactivation and downregulation of STAT3 (Signal transducer and activator of transcription 3) downstream targets (c‐Myc and BCL‐XL). Similar events occurred in highly bortezomib‐resistant (PS‐R) cells, in the presence of patient‐derived conditioned medium, and with alternative ATR (e.g. M1774) and MEK1/2 (trametinib) inhibitors. Notably, constitutively active STAT3 c‐MYC or BCL‐XL ectopic expression significantly protected cells from BAY/cobimetinib. In contrast, transfection of cells with a dominant‐negative form of STAT3 (Y705F) sensitized cells to cobimetinib, as did ATR shRNA knockdown. Conversely, MEK1/2 knockdown markedly increased ATRi sensitivity. The BAY/cobimetinib regimen was also active against primary CD138+ MM cells, but not normal CD34+ cells. Finally, the ATR inhibitor/cobimetinib regimen significantly improved survival in MM xenografts, including bortezomib‐resistant models, with minimal toxicity. Collectively, these findings suggest that combined ATR/MEK1/2 inhibition triggers dual STAT3 Tyr705 and Ser727 dephosphorylation, pronounced downregulation of cytoprotective targets and MM cell death, warranting attention as a novel therapeutic strategy in MM.
The Diversity of Voices in Universities: A Critical Reflection on Representation Based on Two University Projects in Iceland and Germany
Authors: Leonhardt Nico , Björnsdóttir Kristín , Goldbach Anne , Smára Ragnar , Martick Steffen , Schlothauer Beate
Published: October 2024

Background

Universities are deeply rooted in a tradition of exclusivity. However, for the past several years, they have been called upon to develop in an inclusive and socially responsible manner that does justice to the plurality of society. This has led to the emergence of diverse practices and projects around the world that are intended to open up universities to previously excluded and marginalised groups of people. At the same time, findings from postcolonial studies, such as Spivak's discussions on the topic of representation, show that such processes of change must always be accompanied by critical reflection. This article offers a reflexive analysis of two university projects—one in Iceland and one in Germany—where people with learning difficulties are employed as academic staff, engaged in both teaching and research.

Methods

This article is a result of a collaboration between three nondisabled lecturers and three lecturers with learning disabilities, co‐written across three languages—German, Icelandic and English. The authors worked together to explore theories of representation, ensuring that their discussions and writing were accessible to all members, regardless of language or disability. The article discusses two projects from Iceland and Germany.

Findings

The article shows that inclusive higher education developments are necessary. The projects presented in the article have created work opportunities for people with learning disabilities in the previously exclusive setting of the university. The article provides descriptions of the exemplary life paths of the three lecturers with learning disabilities who co‐authored this article. They have had to navigate the precarious balance between being reduced to mere representatives of their disability and contributing valuable academic knowledge. The findings suggest that an inclusive university can foster equitable academic environments, contributing to the transformation of higher education by reflecting diverse viewpoints and experiences.

Conclusions

Initiatives in Iceland and Germany highlight significant progress towards more inclusive universities by integrating individuals with learning disabilities into academic roles, challenging traditional power dynamics. Spivak's (2008) concept of representation emphasises the need to include marginalised voices in academic discourse, ensuring they are genuinely reflected. While these efforts are crucial, continuous critical reflection is necessary to avoid reinforcing inequalities. Moving forward, universities must embed inclusion into all aspects of their structures, creating meaningful opportunities for marginalised groups to influence decision‐making. This approach will ensure that representation is transformative and drives genuine social change.
Beneficial effects of CHF6467, a modified human nerve growth factor, in experimental neonatal hypoxic–ischaemic encephalopathy
Authors: Landucci Elisa , Mango Dalila , Carloni Silvia , Mazzantini Costanza , Pellegrini‐Giampietro Domenico E. , Saidi Amira , Balduini Walter , Schiavi Elisa , Tigli Laura , Pioselli Barbara , Imbimbo Bruno P. , Facchinetti Fabrizio
Published: October 2024

Background and Purpose

Therapeutic hypothermia (TH) has become the standard care to reduce morbidity and mortality in neonates affected by moderate‐to‐severe hypoxic–ischaemic encephalopathy (HIE). Despite the use of TH for HIE, the incidence of mortality and disabilities remains high.

Experimental Approach

Nerve growth factor (NGF) is a potent neurotrophin, but clinical use is limited by its pain eliciting effects. CHF6467 is a recombinant modified form of human NGF devoid of algogenic activity (painless NGF).

Key Results

In rodent hippocampal slices exposed to oxygen and glucose deprivation, CHF6467 protected neurons from death and reverted neurotransmission impairment when combined with hypothermia. In a model of rat neonatal HIE, intranasal CHF6467 (20 μg kg−1) significantly reduced brain infarct volume versus vehicle when delivered 10 min or 3 h after the insult. CHF6467 (20 and 40 μg kg−1, i.n.), significantly decreased brain infarct volume to a similar extent to TH and when combined, showed a synergistic neuroprotective effect. CHF6467 (20 μg kg−1, i.n.) per se and in combination with hypothermia reversed locomotor coordination impairment (Rotarod test) and memory deficits (Y‐maze and novel object recognition test) in the neonatal HIE rat model. Intranasal administration of CHF6467 resulted in meaningful concentrations in the brain, blunted HIE‐induced mRNA elevation of brain neuroinflammatory markers and, when combined to TH, significantly counteracted the increase in plasma levels of neurofilament light chain, a peripheral marker of neuroaxonal damage.

Conclusion and Implications

CHF6467 administered intranasally is a promising therapy, in combination with TH, for the treatment of HIE.
Computational Insights Into the Mechanism of EGCG's Binding and Inhibition of the TDP‐43 Aggregation
Authors: Meshram Vini D. , Balaji Ramkumar , Saravanan Preethi , Subbamanda Yashashwini , Deeksha Waghela , Bajpai Akarsh , Joshi Himanshu , Bhargava Anamika , Patel Basant K.
Published: October 2024

Misfolding and aggregation of TAR DNA‐binding protein, TDP‐43, is linked to devastating proteinopathies such as ALS. Therefore, targeting TDP‐43's aggregation is significant for therapeutics. Recently, green tea polyphenol, EGCG, was observed to promote non‐toxic TDP‐43 oligomer formation disallowing TDP‐43 aggregation. Here, we investigated if the anti‐aggregation effect of EGCG is mediated via EGCG's binding to TDP‐43. In silico molecular docking and molecular dynamics (MD) simulation suggest a strong binding of EGCG with TDP‐43's aggregation‐prone C‐terminal domain (CTD). Three replicas, each having 800 ns MD simulation of the EGCG‐TDP‐43‐CTD complex, yielded a high negative binding free energy (ΔG) inferring a stable complex formation. Simulation snapshots show that EGCG forms close and long‐lasting contacts with TDP‐43's Phe‐313 and Ala‐341 residues, which were previously identified for monomer recruitment in CTD's aggregation. Notably, stable physical interactions between TDP‐43 and EGCG were also detected in vitro using TTC staining and isothermal titration calorimetry which revealed a high‐affinity binding site of EGCG on TDP‐43 (Kd, 7.8 μM; ΔG, −6.9 kcal/mol). Additionally, TDP‐43 co‐incubated with EGCG was non‐cytotoxic when added to HEK293 cells. In summary, EGCG's binding to TDP‐43 and blocking of residues important for aggregation can be a possible mechanism of its anti‐aggregation effects on TDP‐43.
Reactive Gaze during Locomotion in Natural Environments
Authors: Melgare J. K. , Rohmer D. , Musse S. R. , Cani M‐P.
Published: October 2024

Animating gaze behavior is crucial for creating believable virtual characters, providing insights into their perception and interaction with the environment. In this paper, we present an efficient yet natural‐looking gaze animation model applicable to real‐time walking characters exploring natural environments. We address the challenge of dynamic gaze adaptation by combining findings from neuroscience with a data‐driven saliency model. Specifically, our model determines gaze focus by considering the character's locomotion, environment stimuli, and terrain conditions. Our model is compatible with both automatic navigation through pre‐defined character trajectories and user‐guided interactive locomotion, and can be configured according to the desired degree of visual exploration of the environment. Our perceptual evaluation shows that our solution significantly improves the state‐of‐the‐art saliency‐based gaze animation with respect to the character's apparent awareness of the environment, the naturalness of the motion, and the elements to which it pays attention.