bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining National Health Insurance Fund Members’ preferences and trade-offs for the attributes of contracted outpatient facilities in Kenya: a discrete choice experiment
Authors: Kazungu Jacob , Barasa Edwine , Nonvignon Justice , Quaife Matthew
Published: July 2024

Patient choice of health facilities is increasingly gaining recognition for potentially enhancing the attainment of health system goals globally. In Kenya, National Health Insurance Fund (NHIF) members are required to choose an NHIF-contracted outpatient facility before accessing care. Understanding their preferences could support resource allocation decisions, enhance the provision of patient-centered care, and deepen NHIF’s purchasing decisions. We employed a discrete choice experiment to examine NHIF members’ preferences for attributes of NHIF-contracted outpatient facilities in Kenya. We developed a d-efficient experimental design with six attributes, namely availability of drugs, distance from household to facility, waiting time at the facility until consultation, cleanliness of the facility, attitude of health worker, and cadre of health workers seen during consultation. Data were then collected from 402 NHIF members in six out of 47 counties. Choice data were analysed using panel mixed multinomial logit and latent class models. NHIF members preferred NHIF-contracted outpatient facilities that always had drugs [β=1.572], were closer to their households [β=-0.082], had shorter waiting times [β=-0.195], had respectful staff [β=1.249] and had either clinical officers [β=0.478] or medical doctors [β=1.525] for consultation. NHIF members indicated a willingness to accept travel 17.8km if drugs were always available, 17.7km to see a medical doctor for consultation, and 14.6km to see respectful health workers. Furthermore, NHIF members indicated a willingness to wait at a facility for 8.9 hours to ensure the availability of drugs, 8.8 hours to see a doctor for consultation, and 7.2 hours to see respectful health workers. Understanding NHIF member preferences and trade-offs can inform resource allocation at counties, service provision across providers, and purchasing decisions of purchasers such as the recently formed social health insurance authority in Kenya as a move towards UHC.
Assessing the clinical meaningfulness of slowing CDR-SB progression with disease-modifying therapies for Alzheimer disease
Authors: Hartz Sarah M. , Schindler Suzanne E. , Streitz Marissa L. , Moulder Krista L. , Mozersky Jessica , Wang Guoqiao , Xiong Chengjie , Morris John C.
Published: July 2024

INTRODUCTION

For many patients and caregivers, a major goal of disease-modifying treatments (DMT) for Alzheimer disease (AD) dementia is to extend independence in instrumental and basic activities of daily living (IADLs and BADLs). The goal of this study was to estimate the effect of treatments on the time remaining independent in IADLs and BADLs.

METHODS

Participants at the Knight Alzheimer Disease Research Center were selected who were potentially eligible for recent DMT trials: age ≥ 60 years at baseline, clinical diagnosis of very mild or mild AD dementia (global Clinical Dementia Rating® (CDR®) score 0.5 or 1), biomarker confirmation of amyloid pathology, and at least one follow-up CDR assessment within 5 years. For IADLs, a subset of the Functional Assessment Questionnaire (FAQ) was examined that rated the degree of independence in the following: paying bills, driving, remembering medications and appointments, and preparing meals. For BADLs, the Personal Care domain of the CDR was used. Mixed-effects logistic and ordinal regression models were used to examine the relationship between CDR Sum Boxes (CDR-SB) and the individual functional outcomes and their components. The change in CDR-SB over time was estimated with linear mixed effects models.

RESULTS

282 participants were followed for an average of 2.9 years (SD 1.3 years). For 50% of individuals, loss of independence in IADLs occurred at CDR-SB>4.5 and in BADLs at CDR-SB>11.5. For individuals with a baseline CDR-SB=2, treatment with lecanemab would extend independence in IADLs for 10 months (95% CI 4-18 months) and treatment with donanemab in the low/medium tau group would extend independence in IADLs by 13 months (95% CI 6-24 months).

DISCUSSION

Independence in ADLs can be related to CDR-SB and used to demonstrate the effect of AD treatments in extending the time of independent function, a meaningful outcome for patients and their families.
Allosteric regulation of the tyrosine phosphatase PTP1B by a protein-protein interaction
Authors: Chartier Cassandra A. , Woods Virgil A. , Xu Yunyao , van Vlimmeren Anne E. , Johns Andrew C. , Jovanovic Marko , McDermott Ann E. , Keedy Daniel A. , Shah Neel H.
Published: July 2024

The rapid identification of protein-protein interactions has been significantly enabled by mass spectrometry (MS) proteomics-based methods, including affinity purification-MS, crosslinking-MS, and proximity-labeling proteomics. While these methods can reveal networks of interacting proteins, they cannot reveal how specific protein-protein interactions alter protein function or cell signaling. For instance, when two proteins interact, there can be emergent signaling processes driven purely by the individual activities of those proteins being co-localized. Alternatively, protein-protein interactions can allosterically regulate function, enhancing or suppressing activity in response to binding. In this work, we investigate the interaction between the tyrosine phosphatase PTP1B and the adaptor protein Grb2, which have been annotated as binding partners in a number of proteomics studies. This interaction has been postulated to co-localize PTP1B with its substrate IRS-1 by forming a ternary complex, thereby enhancing the dephosphorylation of IRS-1 to suppress insulin signaling. Here, we report that Grb2 binding to PTP1B also allosterically enhances PTP1B catalytic activity. We show that this interaction is dependent on the proline-rich region of PTP1B, which interacts with the C-terminal SH3 domain of Grb2. Using NMR spectroscopy and hydrogen-deuterium exchange mass spectrometry (HDX-MS) we show that Grb2 binding alters PTP1B structure and/or dynamics. Finally, we use MS proteomics to identify other interactors of the PTP1B proline-rich region that may also regulate PTP1B function similarly to Grb2. This work presents one of the first examples of a protein allosterically regulating the enzymatic activity of PTP1B and lays the foundation for discovering new mechanisms of PTP1B regulation in cell signaling.

Significance Statement

Protein-protein interactions are critical for cell signaling. The interaction between the phosphatase PTP1B and adaptor protein Grb2 co-localizes PTP1B with its substrates, thereby enhancing their dephosphorylation. We show that Grb2 binding also directly modulates PTP1B activity through an allosteric mechanism involving the proline-rich region of PTP1B. Our study reveals a novel mode of PTP1B regulation through a protein-protein interaction that is likely to be exploited by other cellular interactors of this important signaling enzyme.
Titration-WB: A methodology for accurate quantitative protein determination overcoming reproducibility errors
Authors: Maestri Alice , Ehrenborg Ewa , Werngren Olivera , Olin Maria , Hagberg Carolina E. , Pedrelli Matteo , Parini Paolo
Published: July 2024

Western blot (WB) technique is widely used to identify and quantify proteins in biological samples, but it is poorly accurate and precise for quantitative purposes. Merging the WB with the titration assay, we established a reliable method for protein quantification based on the slope of the linear function for signal-intensity/total protein loaded. Titration-WB unravels systematic and operator errors, compensates for problems in antibody affinity/avidity, and permits trustworthy inter-WB comparison.
Molecular basis of FIGNL1 in dissociating RAD51 from DNA and chromatin
Authors: Carver Alexander , Yu Tai-Yuan , Yates Luke A , White Travis , Wang Raymond , Lister Katie , Jasin Maria , Zhang Xiaodong
Published: July 2024

Maintaining genome integrity is an essential and challenging process. RAD51 recombinase, the central player of several crucial processes in repairing and protecting genome integrity, forms filaments on DNA. RAD51 filaments are tightly regulated. One of these regulators is FIGNL1, that prevents persistent RAD51 foci post-damage and genotoxic chromatin association in cells. The cryogenic electron microscopy structure of FIGNL1 in complex with RAD51 reveals that the FIGNL1 forms a non-planar hexamer and RAD51 N-terminus is enclosed in the FIGNL1 hexamer pore. Mutations in pore loop or catalytic residues of FIGNL1 render it defective in filament disassembly and are lethal in mouse embryonic stem cells. Our study reveals a unique mechanism for removing RAD51 from DNA and provides the molecular basis for FIGNL1 in maintaining genome stability.
Multi-ion Frequency Reference Using Dynamical Decoupling
Authors: Pelzer Lennart , Dietze Kai , Martínez-Lahuerta Víctor José , Krinner Ludwig , Kramer Johannes , Dawel Fabian , Spethmann Nicolas C. H. , Hammerer Klemens , Schmidt Piet O.
Published: July 2024

We present the experimental realization of a continuous dynamical decoupling scheme which suppresses leading frequency shifts in a multi-ion frequency reference based on Ca+40. By near-resonant magnetic coupling of the S21/2 and D25/2 Zeeman sublevels using radio-frequency dressing fields, engineered transitions with reduced sensitivity to magnetic-field fluctuations are obtained. A second stage detuned dressing field reduces the influence of amplitude noise in the first stage driving fields and decreases 2nd-rank tensor shifts, such as the electric quadrupole shift. Suppression of the quadratic dependence of the quadrupole shift to 3(2)  mHz/μm2 and coherence times of 290(20) ms on the optical transition are demonstrated even within a laboratory environment with significant magnetic field noise. Besides removing inhomogeneous line shifts in multi-ion clocks, the demonstrated dynamical decoupling technique may find applications in quantum computing and simulation with trapped ions by a tailored design of decoherence-free subspaces.

Published by the American Physical Society
2024
Kilonova light-curve interpolation with neural networks
Authors: Peng Yinglei , Ristić Marko , Kedia Atul , O'Shaughnessy Richard , Fontes Christopher J. , Fryer Chris L. , Korobkin Oleg , Mumpower Matthew R. , Villar V. Ashley , Wollaeger Ryan T.
Published: July 2024

Kilonovae are the electromagnetic transients created by the radioactive decay of freshly synthesized elements in the environment surrounding a neutron star merger. To study the fundamental physics in these complex environments, kilonova modeling requires, in part, the use of radiative transfer simulations. The microphysics involved in these simulations results in high computational cost, prompting the use of emulators for parameter inference applications. Utilizing a training set of 22 248 high-fidelity simulations (composed of 412 unique ejecta parameter combinations evaluated at 54 viewing angles), we use a neural network to efficiently train on existing radiative transfer simulations and predict light curves for new parameters in a fast and computationally efficient manner. Our neural network can generate millions of new light curves in under a minute. We discuss our emulator's degree of off-sample reliability and parameter inference of the AT2017gfo observational data. Finally, we discuss tension introduced by multiband inference in the parameter inference results, particularly with regard to the neural network's recovery of viewing angle.

Published by the American Physical Society
2024
Inverse Hamiltonian design of highly entangled quantum systems
Authors: Inui Koji , Motome Yukitoshi
Published: July 2024

Solving inverse problems to identify Hamiltonians with desired properties holds promise for the discovery of fundamental principles. In quantum systems, quantum entanglement plays a pivotal role in not only characterizing the quantum nature but also developing quantum technology such as quantum computing. Nonetheless, the design principles of the quantum entanglement are yet to be clarified. Here we apply an inverse design framework using automatic differentiation to quantum spin systems, aiming to construct Hamiltonians with large quantum entanglement. We show that the method automatically finds the Kitaev model with bond-dependent anisotropic interactions, whose ground state is a quantum spin liquid, on both honeycomb and square-octagon lattices. On triangular and maple-leaf lattices with geometrical frustration, it generates numerous solutions with spatially inhomogeneous interactions rather than converging to a specific model, but it still helps to construct unprecedented models. The comparative study reveals that bond-dependent anisotropic interactions, rather than isotropic Heisenberg interactions, amplify quantum entanglement, even in the systems with geometrical frustration. The present study paves the way for the automatic design of new quantum systems with desired quantum nature and functionality.

Published by the American Physical Society
2024
Modeling the unphysical pseudomode model with physical ensembles: Simulation, mitigation, and restructuring of non-Markovian quantum noise
Authors: Cirio Mauro , Luo Si , Liang Pengfei , Nori Franco , Lambert Neill
Published: July 2024

The influence of a Gaussian environment on a quantum system can be described by effectively replacing the continuum with a discrete set of ancillary quantum and classical degrees of freedom. This defines a pseudomode model which can be used to classically simulate the reduced system dynamics. Here we consider an alternative point of view and analyze the potential benefits of an analog or digital quantum simulation of the pseudomode model itself. Superficially, such a direct experimental implementation is, in general, impossible due to the unphysical properties of the effective degrees of freedom involved. However, we show that the effects of the unphysical pseudomode model can still be reproduced using measurement results over an ensemble of physical systems involving ancillary harmonic modes and an optional stochastic driving field. This is done by introducing an extrapolation technique whose efficiency is limited by stability against imprecision in the measurement data. We examine how such a simulation would allow us to (i) perform a quantum simulation of the effects of complex nonperturbative and non-Markovian environments in regimes that are challenging for classical simulation; (ii) conversely, mitigate potential unwanted non-Markovian noise present in quantum devices; and (iii) restructure some of the properties of a given physical bath, such as its temperature.

Published by the American Physical Society
2024
Rapid detection of rare events from in situ X-ray diffraction data using machine learning
Authors: Zheng Weijian , Park Jun-Sang , Kenesei Peter , Ali Ahsan , Liu Zhengchun , Foster Ian , Schwarz Nicholas , Kettimuthu Rajkumar , Miceli Antonino , Sharma Hemant
Published: July 2024

High-energy X-ray diffraction methods can non-destructively map the 3D microstructure and associated attributes of metallic polycrystalline engineering materials in their bulk form. These methods are often combined with external stimuli such as thermo-mechanical loading to take snapshots of the evolving microstructure and attributes over time. However, the extreme data volumes and the high costs of traditional data acquisition and reduction approaches pose a barrier to quickly extracting actionable insights and improving the temporal resolution of these snapshots. This article presents a fully automated technique capable of rapidly detecting the onset of plasticity in high-energy X-ray microscopy data. The technique is computationally faster by at least 50 times than the traditional approaches and works for data sets that are up to nine times sparser than a full data set. This new technique leverages self-supervised image representation learning and clustering to transform massive data sets into compact, semantic-rich representations of visually salient characteristics (e.g. peak shapes). These characteristics can rapidly indicate anomalous events, such as changes in diffraction peak shapes. It is anticipated that this technique will provide just-in-time actionable information to drive smarter experiments that effectively deploy multi-modal X-ray diffraction methods spanning many decades of length scales.
Do many options result in listening to oneself or others during boycott campaigns?
Authors: Yan Xiuyan , Kim Changju , Kim Jungkeun , Inoue Masato
Published: July 2024

Purpose

This study empirically investigates whether and how boycott attitudes and subjective norms influence the impact of the perceived behavioral control of boycotts on boycott intention.

Design/methodology/approach

To test our hypotheses, we perform a hierarchical linear regression analysis using data from Japanese (n = 500) and South Koreans (n = 571).

Findings

Boycott attitudes strengthen the positive effect of perceived behavioral control on boycott intentions for Japanese and South Koreans. Contrary to our assumptions, while the direct impact of perceived behavioral control on boycott intention is not significant, there is a negative moderating effect of subjective norms for Japanese consumers.

Originality/value

We argue that when perceived behavioral control is evident in boycotts, consumers listen more to themselves than to others. Our cross-national analysis of actual boycott campaigns is the first study on boycott research to offer implications for the interaction effects among the three key antecedents of psychological motivation factors in the theory of planned behavior.
The psychedelic mind: Current user perceptions of psychedelic drugs and their use
Authors: McGruddy Sarah , Whelan Jai , Mills Ethan , Boardman Alexander , Ward Ryan D.
Published: July 2024

Purpose

Psychedelic drugs can induce altered states of consciousness characterised by changes in visual perception, tactile sensation, cognition, and emotion. Although there is a history of misinformation surrounding these drugs, recent investigation has reinvigorated interest. However, little research has assessed the attitudes of psychedelic consumers regarding these substances. The current study aims to explore the attitudes and perceptions of people with experience with psychedelic drugs, specifically surrounding psychedelic drugs themselves and their use within Aotearoa New Zealand.

Design/methodology/approach

Nineteen individuals with experience of psychedelic use were recruited to participate across eight groups in semi-structured, exploratory interviews, where a range of topics associated with psychedelics were discussed. Reflexive thematic analysis of the data focussed on participants’ current perceptions and attitudes.

Findings

Four themes were produced: (1) a negative historical influence on current perceptions of psychedelics; (2) knowledge is key but not everyone has it; (3) prohibition is not working, policy needs to change; (4) psychedelics have therapeutic potential. These themes emphasise key features of people with experience of psychedelic drugs’ current views and highlight potential areas for future investigation and intervention.

Social implications

Findings indicate a need for greater public knowledge and awareness of psychedelics in Aotearoa society. Findings also inform information, education and policy, which in turn will reduce the stigma and associated harm that those who have used or use psychedelic drugs may experience.

Originality/value

To the best of the authors’ knowledge, qualitative research aiming to understand attitudes and perspectives surrounding psychedelic drugs and their use from a drug users’ perspective have not yet been assessed.
The new pluralism: interests, identity and social change
Authors: McGovern Patrick
Published: July 2024

Purpose

The paper reviews Fox’s frames of reference against subsequent changes in the composition of the labour force, shifts in social values and the arrival of the politics of identity.

Design/methodology/approach

A close reading of the frames of reference is placed in the context of Fox’s writing on the search for managerial legitimacy. That search is then considered in relation to the subsequent revolution in equal opportunities and contemporary efforts to promote equality, diversity and inclusion (EDI).

Findings

At the core of Fox’s frames lies the fundamental question of whether employers accept trade unions as a legitimate expression of employee interests. Changes in the composition of the labour force and the related arrival of identity politics has led to the emergence of a new set of interests based on social identity. These interests exist because of state legislation, social pressure from campaign groups and the awareness of the right to equal treatment regardless of gender, race, sexuality etc. It follows that the emergence of these identity-based interests means that employers are all pluralists now. This new pluralism has the ideological challenge of gaining approval not only from employees but also from the public in a world where errant employers are vulnerable to hashtag activism.

Originality/value

By revisiting Fox’s frames of reference, and emphasizing the role of employee interests, the paper shows that Fox's original insights on managerial authority and the need for “legitimising sentiments” are still relevant even if his frames are now outdated.
Crafting gender into meaningful work: experiences of women engaging in social entrepreneurship in China
Authors: Han Ling
Published: July 2024

Purpose

Social entrepreneurship, leveraging economic activities to achieve social benefits, offers women the opportunity to freely and actively shape the contours of their work in meaningful ways. This study aims to examine how Chinese women use job crafting in social entrepreneurship to align their gender identity, forge meaningful work and new relationships and navigate mixed gender expectations.

Design/methodology/approach

The study is based on 19 in-depth interviews with young women engaging in social entrepreneurship in China. Using a grounded theory approach, the study explores how women craft their gender identity into the unconventional career path of creating their social venture, focusing on the creative combination of task, relational and cognitive crafting in shaping social entrepreneurship.

Findings

The findings suggest that women make social entrepreneurship meaningful by actively aligning their gender experiences to delineate a relational and cognitive causal path between their social enterprise, their identity as women and their moral values. By working for a larger social cause, women may cognitively reframe their gender identity to compromise financial performance for social impact.

Originality/value

Current studies on social entrepreneurship in China have yet to examine its development through a gender lens. This study uses job crafting to highlight the distinctive gender meaning-making process for Chinese women to enhance their work identity and to challenge normative gender expectations. The study shows that job crafting enables women to view their social ventures as a means of gender empowerment, helping them to reconcile the paradoxical pressures of normative gender expectations and scaling up their businesses.
Effects of travel vlogs on travel intention of slow tourism in China: an evaluation of resonance and destination image
Authors: Wang Meng , Abd Rahman Azmawani , Aziz Yuhanis Abdul , Adzharuddin Nor Azura
Published: July 2024

Purpose

The distinct characteristics of slow tourism compared to mass tourism determine the differences between slow travelers and mass travelers. This transformation is essential for potential tourists to transition into slow travelers when promoting slow tourism to them. Can travel vlogs, a “fast” way of promoting, achieve such a “slow” transformation? To address this question, the purpose of this paper is to introduce the resonance theory and investigate the impact of resonance with slow tourism vlogs on potential travelers’ destination image and travel intention.

Design/methodology/approach

Through the distribution of online questionnaires on site, this study collected a total of 349 valid questionnaires. Subsequently, the researcher used partial least squares structural equation modeling to analyze the data and test the hypotheses.

Findings

The research findings indicate that cognitive resonance only positively affected cognitive image, while emotional resonance was positively associated with both cognitive image and affective image. In addition, it was observed that cognitive image and affective image played a positive mediating role between resonance with slow tourism vlogs and travel intention.

Originality/value

This research is pioneering in quantitatively validating the structure linking resonance, destination image and travel intention in the context of slow tourism. By validating the second-order structure of cognitive and emotional resonance, this study underscores the crucial role of resonance in shaping tourists’ transition toward a slow mindset in slow tourism.
Value co-creation on social attachment toward social platforms: evidence from developing countries
Authors: Yang Maosheng , Xu Shaobao , Chen Shih-Chih , Li Juan , Zhou Yajun , Tseng Ming-Lang
Published: July 2024

Purpose

As a high-reward strategy to differentiate social platforms, value co-creation is increasingly becoming a tool to enhance customers' social attachment. However, there is still a lack of academic understanding of the value co-creation that enables users to build social attachment with social platforms. To address this challenge, we develop and then examine a theoretical model grounded in value co-creation theory considering the relationship between value co-creation and social attachment, and also explore the mediating effect of user experience and the moderating effect of self-disclosure.

Design/methodology/approach

This study takes representative social platform users as the research object, chooses Questionnaire Star as the platform for questionnaire distribution and collection and collects 531 eligible data through the snowball sampling questionnaire method. And then, MPLUS7.4 is used to analyze the data and thus examine our proposed theoretical model.

Findings

The results of structural equation modeling analysis suggest that two dimensions of value co-creation (i.e. initiated value co-creation and spontaneous value co-creation) affect social attachment not only directly but also indirectly (i.e. the mediating role of user experience) and that self-disclosure moderates the impact of value co-creation affecting social attachment.

Originality/value

This study verifies the impact of different dimensions of value co-creation toward social platforms on social attachment, showing that value co-creation plays an important role in developing users' social attachment and provides practical implications for promoting the sustainable development of social platforms and building users' psychological well-being.
An integrated academic library supply chain (IALSC) model
Authors: Hye A.K. Mahbubul , Ahmad Nurakmal Ahmad , Habib Md. Mamun
Published: July 2024

Purpose

This exploratory study illustrated an integrated academic library supply chain (IALSC) model to design the strategic planning management tool of the academic library. The supply chain (SC) model has been widely used in manufacturing industries and has also been applied in many service industries with the same objectives. However, very few studies for academic libraries, particularly the implementation of the integrated SC model, are being executed, although it has been proven that SC management in practice can enhance stakeholder satisfaction, increase revenues and decrease total costs. The academic library also needs to be successful in providing quality products, services and information to fulfil the library users’ needs within the library budget. This research aims to develop a verified model of the integrated SC for the academic library.

Design/methodology/approach

This research used both qualitative and quantitative approaches to achieve its objectives. The proposed conceptual SC model, named as IALSC, for the academic library has been developed using the system thinking method; eventually, it has been validated through the fuzzy Delphi method, an expert judgement technique.

Findings

The research findings could contribute to academic library management in planning and formulating a roadmap for the library to increase its quality services for all stakeholders.

Originality/value

The conceptual model would have a high potential to be proposed as the strategic decision-making tool for an academic library, i.e. the flow of funds through the operations of the library, the library stakeholders’ satisfaction measurement, the decision process currently made by the library management team on the purchase of new library resources, the library resource suppliers, etc.
“African root and American fruit”: African American families and culture in college choice
Authors: Donatto Teranda
Published: July 2024

Purpose

Research shows that family is influential to African Americans in college choice (Chapman et al., 2018; Chapman et al., 2020; Freeman, 2005; Hines et al., 2019; Lowry, 2017; Williams, 2018). However, it often overlooks unique, African-rooted characteristics of African American families and culture. This study aimed to explore whether and how these characteristics shape college choice for these students.

Design/methodology/approach

Data were collected through semi-structured interviews with six, first-year African American students at an urban university. The data were analyzed using theoretical thematic analysis.

Findings

The major themes showed the influence of family, community and spirituality in shaping participants’ college choice decisions and perception of higher education.

Originality/value

In addition to identifying specific family members who were influential to African Americans in college choice, this work highlighted the role of communities as a whole in shaping these students’ decisions and creating supportive environments. It also showed the importance of these students’ relationship with God through the college choice process. The work can guide researchers and educators in considering African American families and culture as strengths in helping these students through college choice.
How does Labour intend to achieve Economic Growth? A Response to Rachel Reeves's Mais Lecture
Authors: Bhattacharya Aveek
Published: July 2024

The new Labour government's overriding priority is economic growth—and chancellor Rachel Reeves's March 2024 Mais lecture is the clearest statement of how they intend to achieve it. The anticipated ‘dullness dividend’ from being more stable than recent Conservative governments is likely to be small, while the incoming government will have to confront trade‐offs—for example, accepting lower consumption—to increase investment. Planning reform is at the heart of Labour's proposed supply side reforms, but it remains unclear whether the party will be bold enough to follow through on its rhetoric. Labour also believes that stronger worker protections will increase productivity. By contrast, education, migration and trade are more marginal in Labour's growth narrative. It is to be seen how far Labour has made a virtue of necessity by prioritising cheaper and apparently less politically contentious growth measures.
Potential mechanisms implied in tick infection by arboviruses and their transmission to vertebrate hosts
Authors: YUAN Chuanfei , XU Qiong , NING Yunjia , XIA Qianfeng
Published: July 2024

Ticks can transmit many pathogens, including arboviruses, to their vertebrate hosts. Arboviruses must overcome or evade defense mechanisms during their passage from the tick gut to the hemolymph, salivary glands, and the feeding site in the host skin. This review summarizes current knowledge of defense mechanisms in specific tick tissues and at the feeding site in the host skin. We discuss the possible roles of these defense mechanisms in viral infection and transmission. The responses of tick salivary proteins to arbovirus infection are also discussed. This review provides information that may help accelerate research on virus–tick interactions.
Akkermansia muciniphila outer membrane protein regulates recruitment of CD8+ T cells in lung adenocarcinoma and through JAK–STAT signalling pathway
Authors: Xu Yufen , Tan Xiaoli , Yang Qi , Fang Zhixian , Chen Wenyu
Published: July 2024

As a Gram‐negative anaerobic bacterium, Akkermansia muciniphila (AKK) participates in the immune response in many cancers. Our study focused on the factors and molecular mechanisms of AKK affecting immune escape in lung adenocarcinoma (LUAD). We cultured AKK bacteria, prepared AKK outer membrane protein Amuc_1100 and constructed a subcutaneous graft tumour mouse model. A549, NCI‐H1395 cells and mice were respectively treated with inactivated AKK, Amuc_1100, Ruxolitinib (JAK inhibitor) and RO8191 (JAK activator). CD8+ T cells that penetrated the membrane were counted in the Transwell assay. The toxicity of CD8+ T cells was evaluated by lactate dehydrogenase assay. Western blot was applied to determine JAK/STAT‐related protein and PD‐L1 expression, whilst CCL5, granzyme B and INF‐γ expression were assessed through enzyme‐linked immunosorbent assay (ELISA). The proportion of tumour‐infiltrating CD8+ T cells and the levels of granzyme B and INF‐γ were determined by flow cytometry. AKK markedly accelerated A549 and NCI‐H1395 recruiting CD8+ T cells and enhanced CD8+ T cell toxicity. Amuc_1100 purified from AKK exerted the same promoting effects. Besides, Amuc_1100 dramatically suppressed PD‐L1, p‐STAT and p‐JAK expression and enhanced CCL5, granzyme B and INF‐γ expression. Treatment with Ruxolitinib accelerated A549 and NCI‐H1395 cells recruiting CD8+ T cells, enhanced CD8+ T cell toxicity, CCL5, granzyme B and INF‐γ expression, and inhibited PD‐L1 expression. In contrast, the RO8191 treatment slowed down the changes induced by Amuc_1100. Animal experiments showed that Amuc_1100 was found to increase the number of tumour‐infiltrating CD8+ T cells, increase the levels of granzyme B and INF‐γ and significantly inhibit the expression of PD‐L1, p‐STAT and p‐JAK, which exerted an antitumour effect in vivo. In conclusion, through inhibiting the JAK/STAT signalling pathway, AKK outer membrane protein facilitated the recruitment of CD8+ T cells in LUAD and suppressed the immune escape of cells.
Hormonal male contraception
Authors: Wang Christina , Meriggiola Maria Cristina , Behre Hermann M. , Page Stephanie T.
Published: July 2024

Introduction

Male contraception with exogenously administered hormones suppresses both luteinizing hormone and follicle stimulating hormone leading to low intratesticular testosterone concentration. This results in reversible suppression of spermatogenesis and marked decrease in sperm output in the ejaculate and preventing pregnancy in the female partner.

Prior Studies

Studies of testosterone administered alone or in combination of another gonadotropin suppressive agent such as a progestin or gonadotropin releasing hormone (GnRH) analog showed decisively that the exogenous hormone administrations are effective in suppressing sperm output with few adverse events that are not anticipated. In contraceptive efficacy studies, testosterone alone or combined with a progestin are as effective in preventing pregnancies as female contraceptive methods.

Conclusion

Hormone combinations for male contraception are in late‐phase clinical trials and hold the promise of being the new, reversible contraception method for men in over half a century. Lessons learned from the male hormonal contraceptive development pave the way for new targeted approached to regulate male fertility.
HIF‐1α limits myocardial infarction by promoting mitophagy in mouse hearts adapted to chronic hypoxia
Authors: Alanova Petra , Alan Lukas , Opletalova Barbora , Bohuslavova Romana , Abaffy Pavel , Matejkova Katerina , Holzerova Kristyna , Benak Daniel , Kaludercic Nina , Menabo Roberta , Di Lisa Fabio , Ostadal Bohuslav , Kolar Frantisek , Pavlinkova Gabriela
Published: July 2024

Aim

The transcriptional factor HIF‐1α is recognized for its contribution to cardioprotection against acute ischemia/reperfusion injury. Adaptation to chronic hypoxia (CH) is known to stabilize HIF‐1α and increase myocardial ischemic tolerance. However, the precise role of HIF‐1α in mediating the protective effect remains incompletely understood.

Methods

Male wild‐type (WT) mice and mice with partial Hif1a deficiency (hif1a
+/−) were exposed to CH for 4 weeks, while their respective controls were kept under normoxic conditions. Subsequently, their isolated perfused hearts were subjected to ischemia/reperfusion to determine infarct size, while RNA‐sequencing of isolated cardiomyocytes was performed. Mitochondrial respiration was measured to evaluate mitochondrial function, and western blots were performed to assess mitophagy.

Results

We demonstrated enhanced ischemic tolerance in WT mice induced by adaptation to CH compared with their normoxic controls and chronically hypoxic hif1a
+/− mice. Through cardiomyocyte bulk mRNA sequencing analysis, we unveiled significant reprogramming of cardiomyocytes induced by CH emphasizing mitochondrial processes. CH reduced mitochondrial content and respiration and altered mitochondrial ultrastructure. Notably, the reduced mitochondrial content correlated with enhanced autophagosome formation exclusively in chronically hypoxic WT mice, supported by an increase in the LC3‐II/LC3‐I ratio, expression of PINK1, and degradation of SQSTM1/p62. Furthermore, pretreatment with the mitochondrial division inhibitor (mdivi‐1) abolished the infarct size‐limiting effect of CH in WT mice, highlighting the key role of mitophagy in CH‐induced cardioprotection.

Conclusion

These findings provide new insights into the contribution of HIF‐1α to cardiomyocyte survival during acute ischemia/reperfusion injury by activating the selective autophagy pathway.
Clinical utility of investigations in triple‐negative thrombocytosis: A real‐world, multicentre evaluation of UK practice
Authors: Godfrey Anna L. , Sousos Nikolaos , Frewin Rebecca , Prahladan Mahesh , Green Anna C. , McGregor Andrew , Khan Alesia , Milne Kate , Amin Faisal , Torre Elena , Gudgin Emma J. , Lambert Jonathan , Wilson Andrew J. , Royston Daniel , Harrison Claire N. , Mead Adam J.
Published: July 2024

Diagnosis of essential thrombocythaemia (ET) is challenging in patients lacking JAK2/CALR/MPL mutations. In a retrospective evaluation of 320 patients with ‘triple‐negative thrombocytosis’, we assessed utility of bone marrow histology (90.9% of patients) and myeloid gene panel (MGP, 55.6%). Supportive histology (‘myeloproliferative neoplasm‐definite/probable’, 36.8%) was associated with higher platelet counts and varied between centres. 14.6% MGP revealed significant variants: 3.4% JAK2/CALR/MPL and 11.2% other myeloid genes. Final clinical diagnosis was strongly predicted by histology, not MGP. 23.7% received cytoreduction (17.6% under 60 years). Real‐world ‘triple‐negative’ ET diagnosis currently depends heavily on histology; we advocate caution in MGP‐negative cases and that specific guidelines are needed.
Protein phosphatase 6 promotes stemness of colorectal cancer cells
Authors: Fujiwara Nobuyuki , Tsunedomi Ryouichi , Kimura Yuta , Nakajima Masao , Tomochika Shinobu , Enjoji Shuhei , Ohama Takashi , Sato Koichi , Nagano Hiroaki
Published: July 2024

Colorectal cancer (CRC) remains a significant global health concern, demanding a more profound comprehension of its molecular foundations for the development of improved therapeutic strategies. This study aimed to elucidate the role of protein phosphatase 6 (PP6), a member of the type 2A protein phosphatase family, in CRC. Protein phosphatase 6 functions as a heterotrimer with a catalytic subunit (PP6c), regulatory subunits (PP6Rs; PP6R1, PP6R2, and PP6R3), and scaffold subunits (ANKRD28, ANKRD44, and ANKRD52). Elevated PP6c expression has been identified in CRC tissues compared to normal mucosa, aligning with its potential involvement in CRC pathogenesis. PP6c knockdown resulted in decreased colony‐forming ability and in vivo proliferation of various CRC cell lines. Transcriptome analysis revealed that PP6c knockdown resulted in altered expression of genes associated with cancer stemness. Notably, the PP6c‐PP6R3 complex is a key player in regulating cancer stem cell (CSC) markers. Additionally, increased PP6c expression was observed in CSC‐like cells induced by sphere formation, implicating the role of PP6c in CSC maintenance. This study highlights the role of PP6c in CRC and suggests that it is a potential therapeutic target disrupting a pathway critical for CRC progression and stem cell maintenance.
The dynamic feasibility of resisting (R), accepting (A), or directing (D) ecological change
Authors: Cravens Amanda E. , Clifford Katherine R. , Knapp Corrine , Travis William R.
Published: July 2024

Ecological transformations are occurring as a result of climate change, challenging traditional approaches to land management decision‐making. The resist–accept–direct (RAD) framework helps managers consider how to respond to this challenge. We examined how the feasibility of the choices to resist, accept, and direct shifts in complex and dynamic ways through time. We considered 4 distinct types of social feasibility: regulatory, financial, public, and organizational. Our commentary is grounded in literature review and the examples that exist but necessarily has speculative elements because empirical evidence on this newly emerging management strategy is scarce. We expect that resist strategies will become less feasible over time as managers encounter situations where resisting is ecologically, by regulation, financially, or publicly not feasible. Similarly, we expect that as regulatory frameworks increasingly permit their use, if costs decrease, and if the public accepts them, managers will increasingly view accept and direct strategies as more viable options than they do at present. Exploring multiple types of feasibility over time allows consideration of both social and ecological trajectories of change in tandem. Our theorizing suggested that deepening the time horizon of decision‐making allows one to think carefully about when one should adopt different approaches and how to combine them over time.
The Novel Fusion Protein Melittin‐MIL‐2 Exhibits Strong Antitumor Immune Effect in Lung Adenocarcinoma Cell A549
Authors: Gao Weize , Li Wenshuai , Wang Zhan , Li Yongxin , Liu Mingjun
Published: July 2024

In previous studies, we developed a novel fusion protein named “melittin‐MIL‐2” which exhibited more anti‐tumor activity. However, it remains unclear whether melittin‐MIL‐2 possesses antitumor immune effect on lung adenocarcinoma. In this study, the immune effect and mechanism of melittin‐MIL‐2 inhibiting the growth and invasion of lung adenocarcinoma will be investigated, in order to provide novel perspectives for the immunotherapy of lung cancer. The results indicated that melittin‐MIL‐2 promoted T cell proliferation, enhanced NK cell cytotoxicity, and boosted IFN‐γ secretion in PBMCs. After melittin‐MIL‐2 stimulation, perforin expression and LAK/NK‐like killing activities of human PBMCs and NK cells were significantly enhanced. Melittin‐MIL‐2 is capable of hampering the development and proliferation of lung adenocarcinoma cell A549. ICAM‐1 and Fas expression in A549 cells exposed to melittin‐MIL‐2 rose significantly. The expression levels of TLR8 and VEGF in A549 cells decreased significantly after melittin‐MIL‐2 stimulation. In vivo, melittin‐MIL‐2 substantially impeded the growth of lung adenocarcinoma and formed an immune‐stimulating microenvironment locally in tumor tissues. In conclusion, the novel fusion protein melittin‐MIL‐2 exhibits strong anti‐tumor immune effect in lung adenocarcinoma cell A549 via activating the LFA‐1/ICAM‐1 and Fas/FasL pathways to enhance cytolytic activity, upregulating the secretion of IFN‐γ and perforin, and boosting LAK/NK‐like killing activities. Immuno‐effector cells and their secreted cytokines can form immune stimulation microenvironment locally in lung adenocarcinoma Lewis mice tissue.
Strategic boundary management in university‐based living labs
Authors: Tercanli Hacer , Jongbloed Ben , van der Meulen Barend
Published: July 2024

University‐based boundary organisations provide academics with an environment where they can interact with a wide variety of societal partners to produce knowledge and work on research projects, often of a transdisciplinary nature. This environment, however, implies that their researchers may be confronted with multiple and sometimes conflicting demands coming from various stakeholders. In this study, we focus on one such case, a Real‐world Laboratory (RwL), set up by the Karlsruhe Institute of Technology. This RwL focuses on urban sustainable development challenges. Drawing on boundary work literature, we analyse the boundary work strategies employed by the lab's leading researchers to manage such demands as part of a RwL research project. We observe that the managing researchers buffer several types of boundaries in order not to compromise the transdisciplinary nature of the RwL. They appear to utilise four types of boundary devices when managing boundaries: language, people, objects, and spaces. We conclude that, to reduce tensions, the managing researchers should acknowledge the presence of boundaries early on in their RwL research project, that is, during its conception phase.
Online space for learning: Perceived educational environment typology, interpersonal interaction typology, and their relationship to international students' ability development in Chinese universities
Authors: Tian Mei , Lu Genshu
Published: July 2024

The ways in which learning environments are spatially conceived have undergone a significant transformation from space as “a realm without meaning” into place as “a meaningful location.” In this context, the relevance of online interactions and the significance of online space and place in facilitating positive learning are worth exploration. Drawing on a nationwide survey involving 1010 international students at 41 Chinese HEIs in the COVID‐19 pandemic, this research applied k‐means cluster analyses which produced a typology of international students' perceived online educational environments and another typology of their online interpersonal interactions. The logistic regression results indicated the predictive power of both typologies on ability development. The discussion highlights the importance of considering spatial dimensions of international students' online learning. Promoting international students' online interactions and supporting inclusive, engaging learning experiences require both space for hosting and place enabling intercultural learning. The research holds implications for the sustainable development of online international education in the post‐COVID‐19 era.