bluuebunny/crossref_metadata_2025 huggingface dataset:
A Transfection-Free Approach of Gene Editing via a gold-based nanoformulation of the Cas9 protein
Authors: Konstantinidou Soultana , Lindstaedt Agnieszka , Schmidt Tiziana Julia Nadjeschda , Nocilla Francesco , Maltinti Giovanni , Rocco Mafalda Angelica , Landi Elena , Carli Alessandro De , Crucitta Stefania , Lai Michele , Pistello Mauro , Cappello Valentina , Witt Dariusz , Gabellini Chiara , Barski Piotr , Raffa Vittoria
Published: July 2024

In recent years, the CRISPR/Cas9 technology has emerged as a highly efficient tool for cell gene editing. However, the delivery of the CRISPR/Cas9 system into cells remains a significant challenge, drastically limitingin vivogene therapy applications. In this study, we present a transfection/transduction-free tool for intracellular delivery of the Cas9:gRNA ribonucleoprotein. The Cas9 enzyme is conjugated to a 12 nm gold nanoparticle through affinity binding between the 6x His-tag of the protein and the NTA-Ni²LJ groups on the nanoparticles. This link chemistry allows a fine control of the density of the enzymes decorating the particle surface, the orientation of the bonding and the stability of the interaction. Importantly, the surface chemistry of this nanoformulation has been precisely engineered to modulate the cellular internalization and localization. Thanks to this approach of precision chemistry, this nanoformulation demonstrated the ability to spontaneously enter human melanoma cells as monodispersed particles that localize in cell cytoplasm, endosomes, and nucleus. It also shows effective gene editing efficiency similarly to conventional transfection tools. This gold-based formulation of Cas9 represents a ready-to-use biotech editing tool, and a promising solution for directin vivogene editing applications.
An Agent-Based Simulation Using Extensive Real Datasets: the Case of COVID-19 in Catalonia
Authors: Bosman M. , Cordon Y. , Duran M. , Gabbanelli L. , García-Pérez C. , Jordan X. , Manera M. , Masjuan P. , Medina A. , Mir Ll.M. , Oròs A. , Vitagliano V.
Published: July 2024

During the COVID-19 pandemic, effective public policy interventions have been crucial in combating virus transmission, sparking extensive debate on crisis management strategies and emphasizing the necessity for reliable models to inform governmental decisions, particularly at the local level. Leveraging disaggregated socio-demographic microdata, including social determinants, age-specific strata, and mobility patterns, we design a comprehensive network model of Catalonia’s population and, through numerical simulation, assess its response to the outbreak of COVID-19 over the two-year period 2020-21. Our findings underscore the critical importance of timely implementation of broad non-pharmaceutical measures and effective vaccination campaigns in curbing virus spread; in addition, the identification of high-risk groups and their corresponding maps of connections within the network paves the way for tailored and more impactful interventions.
Loss ofcped1does not affect bone and lean mass in zebrafish
Authors: Alvarado Kurtis , Tang W. Joyce , Watson Claire J , Ahmed Ali R , Gomez Arianna Ericka , Donaka Rajashekar , Amemiya Chris T , Karasik David , Hsu Yi-Hsiang , Kwon Ronald Y
Published: July 2024

Human genetic studies have nominated Cadherin-like and PC-esterase Domain-containing 1 (CPED1) as a candidate target gene mediating bone mineral density (BMD) and fracture risk heritability. Recent efforts to define the role ofCPED1in bone in mouse and human models have revealed complex alternative splicing and inconsistent results arising from gene targeting, making its function in bone difficult to interpret. To better understand the role ofCPED1in adult bone mass and morphology, we conducted a comprehensive genetic and phenotypic analysis ofcped1in zebrafish, an emerging model for bone and mineral research. We analyzed two differentcped1mutant lines and performed deep phenotyping to characterize more than 200 measures of adult vertebral, craniofacial, and lean tissue morphology. We also examined alternative splicing of zebrafishcped1and gene expression in various cell/tissue types. Our studies fail to support an essential role ofcped1in adult zebrafish bone. Specifically, homozygous mutants for bothcped1mutant alleles, which are expected to result in loss-of-function and impact allcped1isoforms, exhibited no significant differences in the measures examined when compared to their respective wildtype controls, suggesting thatcped1does not significantly contribute to these traits. We identified sequence differences in critical residues of the catalytic triad between the zebrafish and mouse orthologs of CPED1, suggesting that differences in key residues, as well as distinct alternative splicing, could underlie different functions ofCPED1orthologs in the two species. Our studies fail to support a requirement ofcped1in zebrafish bone and lean tissue, adding to evidence that variants at 7q31.31 can act independently ofCPED1to influence BMD and fracture risk.
NMR Reveals the Synergistic Roles of Bivalent Metal Ions in Norovirus Infections
Authors: Maass Thorben , Westermann Leon Torben , Sharotri Linda , Blankenhorn Leon , Lane Miranda Sophie , Chaika Maryna , Taube Stefan , Peters Thomas , Mallagaray Alvaro
Published: July 2024

Norovirus is the most common cause of acute gastroenteritis worldwide. Murine noroviruses (MNV) are often used as model systems for human noroviruses (HuNoV). Therefore, it is important to identify common and divisive properties. Here, we compare the interactions of human and murine norovirus P-domains with bivalent metal ions. Binding of bivalent metal ions and bile acids to MNV P-domains have been shown to stabilize a contracted (“resting”) as opposed to an extended (“raised”) capsid conformation. This conformational change has been linked to infectivity, diarrheagenic potential, and immune escape. Likewise, the interaction of bivalent metal ions with human norovirus capsids results in contraction, suggesting a similar underlying mechanism. We used methyl TROSY NMR experiments to study the thermodynamics and kinetics of metal ion binding to P-domains, revealing a highly synergistic interaction with the bile acid glycochenodeoxycholic acid (GCDCA) for MNV. Neutralization assays support this synergistic behavior. It turns out that bivalent metal ion binding to MNV and HuNoV P-domains differs significantly. Therefore, although the transition between “raised” and “resting” capsid conformations and consequential modulation of infectivity appears to be triggered by bivalent metal ions in murine and human noroviruses, the underlying mechanisms must be different.
Striatal endocannabinoid-long-term potentiation mediates one-shot learning
Authors: Piette Charlotte , Hubert Arnaud , Perez Sylvie , Berry Hugues , Touboul Jonathan , Venance Laurent
Published: July 2024

One-shot learning, the ability to form memories after a single, brief salient event, is essential to adapt one’s behaviour in a dynamic world. However, how one-shot learning unfolds in the brain remains unknown. Challenges to elucidate its neural underpinnings stem experimentally from the scarcity of behavioral assays recapitulating one-shot learning in the laboratory, and conceptually from the limited number of neuronal plasticity mechanisms that could support learning after a small number of action potentials, as is common during a one-shot experience. Here, we overcome these challenges and identify a new mechanism for one-shot learning in dorsal striatum that relies on a non-classical form of plasticity, the endocannabinoid-mediated long-term potentiation (eCB-LTP). To do so, we develop a novel one-shot behavioral test, in which mice learn to avoid a sticky tape after a single, spontaneous and brief contact with the uncomfortable substrate, and maintain this memory for more than one month. We use the sticky tape avoidance test to demonstrate that striatal LTP emerges in vivo after one-shot learning; the observed patterns of activity in vivo suggest that eCB-LTP mediates one-shot learning, which we corroborate bothex vivoand through computational modeling. Consistent with this hypothesis, conditional knock-out mice abolishing eCB-LTP show impaired one-shot learning. These results highlight the importance of non-classical plasticity mechanisms in supporting memory formation after a single brief experience.
Free cortisol and free 21-deoxycortisol in the clinical evaluation of congenital adrenal hyperplasia
Authors: Adriaansen Bas P.H. , Utari Agustini , Olthaar André J. , van der Steen Rob C.B.M. , Pijnenburg-Kleizen Karijn J. , Berkenbosch Lizanne , Span Paul N. , Sweep Fred C.G.J. , Claahsen-van der Grinten Hedi L. , van Herwaarden Antonius E.
Published: July 2024

Context

Some patients with classic congenital adrenal hyperplasia (CAH) survive without glucocorticoid treatment. Increased precursor concentrations in these patients might lead to higher free (biological active) cortisol concentrations by influencing the cortisol-protein binding. In 21-hydroxylase deficiency (21OHD), the most common CAH form, accumulated 21-deoxycortisol (21DF), a precursor steroid, may further increase glucocorticoid activity. Both mechanisms could explain the low occurrence of symptoms in some untreated classic CAH patients.

Objective

Establishment and validation of an LC-MS/MS method for (free) cortisol and (free) 21DF to quantify these steroids in untreated patients with classic CAH (n=29), non-classic CAH (NCCAH, n=5), other forms of adrenal insufficiency (AI, n=3), and controls (n=11) before and 60 minutes after Synacthen® administration.

Results

Unstimulated total cortisol levels of untreated classic CAH patients (median 109 nmol/L) were lower compared to levels in untreated NCCAH patients (249 nmol/L, p=0.010) and controls (202 nmol/L, p=0.016), but free cortisol concentrations were similar. Basal free 21DF levels were high in 21OHD patients (median 5.32 nmol/L) and undetectable in AI patients and controls (<0.19 nmol/L). After Synacthen® administration, free concentrations of 21DF -but not cortisol-increased only in patients with 21OHD.

Conclusions

Free cortisol levels were similar in classic CAH compared to controls and NCCAH patients, suggesting a comparable availability of cortisol. Additionally, 21OHD patients produce high levels of the glucocorticoid 21DF, possibly explaining the low occurrence of symptoms in some classic 21OHD patients. Free cortisol and (free) 21DF levels should be considered in the clinical evaluation of adrenal insufficiency in patients with CAH.
Does motivation differ across generations? A two-wave study
Authors: Kothari Tanvi Paras , Pingle Sameer Sudhakar , Karani Mehta Anushree
Published: July 2024

Purpose

The main objective of the study was to understand the impact of intrinsic and extrinsic motivation on productivity at two different times: before and after the pandemic era, among middle and top-level professionals across India.

Design/methodology/approach

The study has adopted a shortitudinal approach. The data were collected two times from the same respondents: before the pandemic (T1) and after the pandemic (T2) following the convenience sampling. At T1, we received responses from 321 respondents. At T2, we received only 203 responses while contacting the same respondents. Thus, the final sample size was only 203 respondents.

Findings

The results revealed that in the pre-pandemic times, both intrinsic and extrinsic motivation impacted the productivity of middle and top-level professionals. Further, the study also revealed that only intrinsic motivation impacted productivity after the pandemic. Moreover, generational cohorts (pre-liberalization, early-liberalization and rapid growth generations) moderated the relationship between intrinsic and extrinsic motivation and Productivity at T1 and T2.

Research limitations/implications

Woven in the multiple theories, the study has some practical and theoretical nuances. The intrinsic and extrinsic motivations were rooted in the self-determination theory. The results also supported that extrinsic reward cannot increase intrinsic motivation in difficult times, and only intrinsic motivation is constant at all times, contributing to productivity. The HR department should understand the importance of intrinsic motivation and design employee benefits and policies.

Practical implications

The results also supported that extrinsic reward cannot increase intrinsic motivation in difficult times, and only intrinsic motivation is constant at all times, contributing to productivity. The HR department should understand the importance of intrinsic motivation and design employee benefits and policies.

Originality/value

Following the generational view, the study added that different generation reacts differently to the turbulent times.
The effect of early life care on childhood cognitive development in Ghana
Authors: Ofori Adofo Josephine
Published: July 2024

Purpose

In most Sub-Saharan African countries, a widely adopted policy to increase access to healthcare is the complete or partial removal of health user fees. This paper examines the effect of removing health user fees on the cognitive development of children in Ghana.

Design/methodology/approach

The study uses the Ghana Socioeconomic Panel Survey (GSPS) and a difference-in-differences method to analyze the impacts of free healthcare.

Findings

The findings show that improved access to healthcare enhances the cognitive ability of children. More importantly, children who received free healthcare in early life experienced significant improvement in their cognitive ability. The benefits are also huge for girls and children from low-income families. The findings further show that maternal health, the timely receipt of vaccinations and regular infant health visits are important operative channels through which improved access to healthcare affects children’s cognitive ability.

Originality/value

There are several studies on the effects of eliminating health user fees on various outcomes, but only a few focus on children’s outcomes. This study contributes to the literature by focusing on a vital child outcome, cognitive ability and exploring the timing and pathways through which abolishing health user fees affect cognitive development in children. Because cognitive ability is crucial for educational and labor market outcomes, the findings are useful for policymakers in determining the population to target and the timing of interventions that yield huge impacts when designing health intervention programs in developing countries.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/IJSE-11-2022-0739.
CEO social media celebrity status and credit rating assessment
Authors: Fang Yue , Bao Xin , Sun Baiqing , Lau Raymond Yiu Keung
Published: July 2024

Purpose

This paper aims to investigate the effect of CEO social media celebrity status on credit ratings and to determine whether potential threats on the CEO celebrity status negatively moderate the above association.

Design/methodology/approach

The authors collected tweets for 874 CEOs from 513 unique S&P 1500 firms. A panel data analysis was conducted on a panel with 4,235 observations from 2009 to 2020. We then tested the hypothesis with the ordinal logit model.

Findings

The empirical findings confirmed that CEO social media celebrity status is positively associated with corporate credit rating outcomes. Our path analyses revealed that CEOs with higher social media celebrity status have less incentive to conduct risk-taking behaviors and thus benefit credit ratings. When the rating agencies perceive potential threats to CEO celebrity status, including CEO myopia and CEO overconfidence, the association between CEO social media celebrity status and credit rating is weakened.

Practical implications

This study provides an in-depth understanding of CEO social media perception on credit ratings for firms' managers and capital market participants. Findings can help managers and firms improve their strategies for leveraging social media to release credit constraints. The debt market participants could adopt the CEO social media celebrity status and its concerned threats to setting debt contracts with an adequate price.

Originality/value

This is likely to be the first study that examines the effect of CEO social media celebrity status on credit ratings. The findings of this study also reveal that social media certificated celebrity CEOs tend to be capable of enhancing firm revenue and have lower risk-taking incentives, unlike mass media certificated celebrity CEOs.
Bricolage and the entrepreneurial process in times of crisis: insights from new ventures in the Philippines
Authors: Francisco Jamil Paolo
Published: July 2024

Purpose

How does entrepreneurship flourish amidst persistent resource scarcity, market imperfections, underdeveloped infrastructure and institutional voids? In recent years, bricolage has emerged in the entrepreneurship literature as an effective form of resource mobilization in resource-constrained environments and crisis situations. The purpose of this study is to investigate the role of bricolage in new venture creation by examining the use of bricolage at each stage of the entrepreneurial process of opportunity discovery, development and exploitation.

Design/methodology/approach

The author conducted a qualitative analysis of 10 new business ventures established in the Philippines during the COVID-19 pandemic.

Findings

The author found a prevalence of bricolage at every stage of the entrepreneurial process in all cases, showing that bricolage was embedded in the behavior and decision-making of entrepreneurs throughout the process.

Practical implications

The finding have implications for policymakers aiming to support entrepreneurship in emerging economies.

Originality/value

This paper contributes to the literature by providing empirical evidence of bricolage behavior identified at every step of the entrepreneurial process in a specific emerging economy context.
AI adoption in supply chain management: a systematic literature review
Authors: Shahzadi Gulnaz , Jia Fu , Chen Lujie , John Albert
Published: July 2024

Purpose

This systematic literature review (SLR) aims to critically analyze the current academic research on the adoption of artificial intelligence (AI) in supply chain management (SCM) and develop a theoretical framework and future research agenda.

Design/methodology/approach

Through a comprehensive review of 68 relevant papers, this study synthesizes the findings to identify key themes based on extended technology-organization-environment (TOE) theory.

Findings

This study analyzes AI integration in SCM based on the TOE framework, identifying drivers (technological, organizational, environmental and human), barriers (technical, organizational, economic and human) and outcomes (operational, environmental, social and economic) of AI adoption. It emphasizes AI's potential in improving SCM practices like resilience, process improvement and sustainable operations, contributing to better decision-making, efficiency and sustainable practices. The study also provided a novel framework that offers insights for strategic AI integration in SCM, aiding policymakers and managers in understanding and leveraging AI's multifaceted impact.

Originality/value

The originality of the study lies in the development of a theoretical framework that not only elucidates the drivers and barriers of AI in SCM but also maps the operational, financial, environmental and social outcomes of AI-enabled practices. This framework serves as a novel tool for policymakers and managers, offering specific, actionable insights for the strategic integration of AI in supply chains (SCs). Furthermore, the study's value is underscored by its potential to guide policy formulation and managerial decision-making, with a focus on optimizing SC efficiency, sustainability and resilience through AI adoption.
Publication performance and trends in psychological capital research: a bibliometric analysis
Authors: Pham Van-Chien , Wong Wing-Keung , Bui Xuan Thi
Published: July 2024

Purpose

This research aims to provide a comprehensive understanding of the evolution and trends in psychological capital (PsyCap) research and related issues.

Design/methodology/approach

This research uses bibliometric analysis. A total of 2,244 journal articles were extracted from the Scopus database using relevant keywords, covering the period from 1997 to 2023. The data analysis was conducted utilizing VOSviewer software, Microsoft Excel, and an online text analysis tool.

Findings

There is a rapid rise in the quantity of PsyCap publications, especially from 2017, with significant contribution of research from Chinese scholars with 577 articles in the period 2019–2023. The antecedents of PsyCap have a stagnation of leadership-related topics and increased focus on social support and perceived organizational support. The attention has been specifically directed toward well-being and mental health, with special emphasis on work engagement, job satisfaction, and job performance.

Research limitations/implications

The exclusion of certain publications in this research may overlook emerging trends. Thus, future research endeavors should adopt a multifaceted approach that combines bibliometric analysis with qualitative and quantitative methods to glean comprehensive insights into PsyCap research.

Originality/value

PsyCap research is growing rapidly, with more publications in the last three years than in all the previous years combined. This study, updating data until the end of 2023, provides the most up-to-date insights on research trends in PsyCap to aid scholars in discerning suitable avenues for their research endeavors.
Multi-stakeholder recommendations system with deep learning-based diversity personalization and multi-objective optimization for establishing trade-off among competing preferences
Authors: Shrivastava Rahul , Sisodia Dilip Singh , Nagwani Naresh Kumar
Published: July 2024

Purpose

The Multi-Stakeholder Recommendation System learns consumer and producer preferences to make fair and balanced recommendations. Exclusive consumer-focused studies have improved the recommendation accuracy but lack in addressing producers' priorities for promoting their diverse items to target consumers, resulting in minimal utility gain for producers. These techniques also neglect latent and implicit stakeholders' preferences across item categories. Hence, this study proposes a personalized diversity-based optimized multi-stakeholder recommendation system by developing the deep learning-based diversity personalization model and establishing the trade-off relationship among stakeholders.

Design/methodology/approach

The proposed methodology develops the deep autoencoder-based diversity personalization model to investigate the producers' latent interest in diversity. Next, this work builds the personalized diversity-based objective function by evaluating the diversity distribution of producers' preferences in different item categories. Next, this work builds the multi-stakeholder, multi-objective evolutionary algorithm to establish the accuracy-diversity trade-off among stakeholders.

Findings

The experimental and evaluation results over the Movie Lens 100K and 1M datasets demonstrate that the proposed models achieve the minimum average improvement of 40.81 and 32.67% over producers' utility and maximum improvement of 7.74 and 9.75% over the consumers' utility and successfully deliver the trade-off recommendations.

Originality/value

The proposed algorithm for measuring and personalizing producers' diversity-based preferences improves producers' exposure and reach to various users. Additionally, the trade-off recommendation solution generated by the proposed model ensures a balanced enhancement in both consumer and producer utilities.
Exploring consumer engagement and satisfaction in health and wellness tourism through text-mining
Authors: Balcioglu Yavuz Selim
Published: July 2024

Purpose

This study aims to deepen the understanding of consumer engagement and satisfaction within the health and wellness tourism sector, a rapidly growing niche in the global tourism industry. It focuses on identifying key elements that influence consumer perceptions and experiences in this domain.

Design/methodology/approach

Employing a quantitative approach, this research utilizes Dynamic Correlated Topic Models (DCTM) and sentiment analysis techniques to analyze user-generated content from TripAdvisor. The methodology involves parsing through extensive online reviews to extract thematic patterns and emotional sentiments related to various wellness tourism experiences.

Findings

The findings reveal that wellness and relaxation, spa and therapy services, and cultural immersion are significant factors influencing consumer satisfaction in health and wellness tourism. These elements contribute to a more profound and emotionally satisfying tourist experience, highlighting the shift from traditional tourism to more holistic, wellness-focused travel.

Research limitations/implications

The study is limited by its focus on user-generated content from a single platform, which may not fully represent the diverse range of consumer experiences in health and wellness tourism. Future research could expand to include other platforms and cross-reference with qualitative data.

Practical implications

The study offers valuable implications for destination managers and marketers in the health and wellness tourism industry, suggesting that enhancing and promoting wellness-centric experiences can significantly improve consumer satisfaction and engagement.

Social implications

The research underscores the growing importance of health and wellness in societal values, reflecting a shift in consumer preferences towards travel experiences that offer mental, physical, and spiritual benefits. This has broader implications for how destinations can cater to the evolving demands of socially conscious travelers.

Originality/value

This research contributes original insights into the evolving field of health and wellness tourism by integrating advanced text mining techniques to analyze consumer feedback, offering a novel perspective on what drives engagement and satisfaction in this sector.
Commentary on “Stakeholder experiences of deprescribing psychotropic medicines for challenging behaviour in people with intellectual disabilities”
Authors: Clifford Adam , Omokanye Mariam , Bagalkote Deval
Published: July 2024

Purpose

This paper aims to provide a commentary response to “Stakeholder experiences of deprescribing psychotropic medicines for challenging behaviour in people with intellectual disabilities”.

Design/methodology/approach

The commentary provides some evidence-based perspectives on the risks and challenges of psychiatric drug-withdrawal, emphasising the importance of the patient experience in deprescribing decisions. It also makes the case for clinical clarity and carer-engagement in optimising deprescribing outcomes for individuals. Some clinical reflections are provided.

Findings

Whilst efforts to reduce the overmedication of people with learning disabilities are welcomed, there is lacking evidence around this population’s experience of adverse effects from psychiatric deprescribing decisions, including differentiating between withdrawal and relapse effects. Clinical clarity and carer engagement are key to safe and effective prescribing, although in reality, this can be challenging.

Originality/value

This paper will be of value to all professionals with a role in the effective deprescribing of psychiatric medications with and/or for people with intellectual disability. It provides perspectives on aspects of stakeholder experience that warrant further consideration and research.
Evaluation of the extended Japan NBI expert team classification of subtype 2B in laterally spreading colorectal tumors based on blue laser imaging
Authors: Zheng Lin Fu , Chen Long Ping , Zhou Lin Xin , Zheng Jin , Jiang Chuan Shen , Peng Shi Rui , Li Da Zhou , Wang Wen
Published: July 2024

Objectives

The Japan NBI Expert Team (JNET) classification has good diagnostic potential for colorectal diseases. We aimed to explore the diagnostic value of the JNET classification type 2B (JNET2B) criteria for colorectal laterally spreading tumors (LSTs) based on magnifying endoscopy with blue laser imaging (ME‐BLI) examination.

Methods

Between January 2017 and June 2023, 218 patients who were diagnosed as having JNET2B‐type LSTs using ME‐BLI were included retrospectively. Endoscopic images were reinterpreted to categorize the LSTs as JNET2B‐low (n = 178) and JNET2B‐high (n = 53) LSTs. The JNET2B‐low and JNET2B‐high LSTs were compared based on their histopathological and morphological classifications.

Results

Among the 178 JNET2B‐low LSTs, 86 (48.3%) were histopathologically classified as low‐grade intraepithelial neoplasia, 54 (30.3%) as high‐grade intraepithelial neoplasia (HGIN), 37 (20.8%) as intramucosal carcinoma (IMC), and one (0.6%) as superficial invasive submucosal carcinoma (SMC1). Among the 53 JNET2B‐high LSTs, five (9.4%) were classified as HGIN, 28 (52.9%) as IMC, 15 (28.3%) as SMC1, and 5 (9.4%) as deep invasive submucosal carcinoma. There were significant differences in this histopathological classification between the two groups (P < 0.001). However, there was no significant difference between JNET2B‐low and JNET2B‐high LSTs based on their morphological classification (granular vs nongranular) or size (<20 mm vs ≥20 mm). Besides, the κ value for JNET2B subtyping was 0.698 (95% confidence interval 0.592–0.804) between the two endoscopists who reassessed the endoscopic images.

Conclusion

The JNET2B subtyping of LSTs has a diagnostic potential in the preoperative setting, and may be valuable for treatment decision‐making.
The efficacy of almonertinib and anlotinib combination therapy for advanced non‐small‐cell lung cancer patients who continued to experience cancer progression during third‐generation EGFR‐TKI treatment: a retrospective study
Authors: Zhang Yu , Wang Chengmeng , Zhao Jing , Wang Meng
Published: July 2024

Background

Epidermal growth factor receptor (EGFR) mutations are key drivers in a significant portion of non‐small‐cell lung cancer (NSCLC) patients. While third‐generation EGFR‐tyrosine kinase inhibitors (TKIs) such as osimertinib have demonstrated efficacy, the management of patients who continue to experience disease progression during treatment remains challenging. The emergence of drug resistance, including the development of secondary mutations, necessitates exploration of alternative treatment strategies. This study aims to evaluate and observe the efficacy and safety of almonertinib combined with anlotinib in patients after cancer progression during third‐generation EGFR‐TKI therapy.

Methods

In this retrospective analysis, we included EGFR‐mutated NSCLC patients who were resistant to third‐generation EGFR‐TKIs. All patients were treated with almonertinib combined with anlotinib. The clinical characteristics, treatment history, clinical benefits, and adverse events of these patients were retrospectively collected.

Results

A total of 16 eligible patients were included in the analysis. The results revealed that combination therapy with almonertinib and anlotinib was effective in this patient cohort. The overall response rate was 25% and the disease control rate was 93.75%. The 6 and 12 months of PFS rates were 92.9% (95% confidence interval [CI] 80.3%, 100.0%) and 84.4% (95% CI 66.6%, 100.0%), respectively. Moreover, this combination therapy was generally well‐tolerated, with manageable adverse events.

Conclusion

Our retrospective analysis suggests that almonertinib and anlotinib combination therapy may represent a viable option for EGFR‐mutated NSCLC patients who have progressed on third‐generation EGFR‐TKIs, especially for those with posterior lines and no standard treatment options. Further investigation and larger clinical trials are warranted to validate these observations and refine treatment guidelines.
Methodological reflections on radio and podcast listenership in political geography
Authors: Watson Alice
Published: July 2024

This paper makes a novel intervention in political geography by offering methodological reflections on contemporary radio and podcast listenership. It begins from the starting point that radio and podcasts are important and popular sites of geographical knowledge production with the power to shape how audiences understand, imagine and engage in the world. The paper heeds calls in critical and popular geopolitics to move away from the site of representation towards audience reception and presents the ‘playlist‐diary’ method as an innovative way of exploring listener responses to BBC radio journalism on migration. This method is then used as a springboard to think more broadly about everyday encounters with radio and podcasts. It argues that situating audience engagements within specific spatialities and temporalities, and considering the digital technologies and platforms though which audio is discovered, consumed and circulated, is critical to developing a nuanced understanding of radio and podcast geopolitics. This discussion reflects growing interest in materialities, networks and assemblages of popular geopolitics and points to a blurring of visual and aural media. Overall, the paper makes the case for amplifying methodologies of listening in political geography and aims to be a catalyst to future scholarship on radio and podcasts.
A characterization of patients with low soluble urokinase plasminogen activator receptor who died within 90 days of hospital discharge
Authors: Christensen Louise Westberg Strejby , Iversen Esben , Andersen Aino Leegaard , Walls Anne Byriel , Rasmussen Line Jee Hartmann , Andersen Ove , Kallemose Thomas , Houlind Morten Baltzer
Published: July 2024

Soluble urokinase plasminogen activator receptor (suPAR) is a marker of systemic chronic inflammation. Elevated suPAR levels are associated with adverse clinical outcomes, but a small subset of patients with low suPAR also experience poor outcomes. Therefore, we aimed to characterize patients presenting to the emergency department with low suPAR (<3 ng/mL) who died within 90 days after discharge in a registry‐based study. Compared to patients with low suPAR who survived (n = 15 122), those who died within 90 days (n = 87) had higher age (75.4 years), higher medication use (7.0; 71.3% with polypharmacy) and more blood tests outside reference intervals (5.0) (including C‐reactive protein, neutrophils and albumin), and the most common diagnoses were chronic pulmonary disease (27.6%), cerebrovascular disease (18.4%) and dementia (11.5%). Patients with low suPAR were more morbid than what was reflected by suPAR alone. Future studies must determine which factors that contribute the most to potential algorithms when stratifying patients based on their risk of adverse clinical outcomes. These data indicate that inclusion of medication data could be relevant.
Debate: How the business model of social media fuels the need for greater moderation
Authors: Graham Richard
Published: July 2024

The current business model of social media companies is to keep users engaged and on screen, so that data can be obtained from them, and targeted advertisements sold. To maintain user engagement, recommender systems (algorithms) promote content, which can be extreme, and includes mental health content. Extreme mental health content, such as self‐harm images, can be pushed to any user and then more and more extreme content can be pushed to them. The normalisation, amplification or glamorisation of harmful content can have negative impacts upon the user, who may struggle to express what is happening online to anyone. In contrast with the views of Zhang et al. (Child and Adolescent Mental Health, 2024, 29, 104), without greater, timely moderation of harmful content, the promotion of self‐harm, suicide and eating disorders will continue on social media, with potentially devastating consequences.
MRPL35 Induces Proliferation, Invasion, and Glutamine Metabolism in NSCLC Cells by Upregulating SLC7A5 Expression
Authors: Hou Wei , Chen Juan , Wang Yaoyuan
Published: July 2024

Background

Mitochondrial ribosomal protein L35 (MRPL35) has been reported to contribute to the growth of non–small cell lung cancer (NSCLC) cells. However, the functions and mechanisms of MRPL35 on glutamine metabolism in NSCLC remain unclear.

Methods

The detection of mRNA and protein of MRPL35, ubiquitin‐specific protease 39 (USP39), and solute carrier family 7 member 5 (SLC7A5) was conducted using qRT‐PCR and western blotting. Cell proliferation, apoptosis, and invasion were evaluated using the MTT assay, EdU assay, flow cytometry, and transwell assay, respectively. Glutamine metabolism was analyzed by detecting glutamine consumption, α‐ketoglutarate level, and glutamate production. Cellular ubiquitination analyzed the deubiquitination effect of USP39 on MRPL35. An animal experiment was conducted for in vivo analysis.

Results

MRPL35 was highly expressed in NSCLC tissues and cell lines, and high MRPL35 expression predicted poor outcome in NSCLC patients. In vitro analyses suggested that MRPL35 knockdown suppressed NSCLC cell proliferation, invasion, and glutamine metabolism. Moreover, MRPL35 silencing hindered tumor growth in vivo. Mechanistically, USP39 stabilized MRPL35 expression by deubiquitination and then promoted NSCLC cell proliferation, invasion, and glutamine metabolism. In addition, MRPL35 positively affected SLC7A5 expression in NSCLC cells in vitro and in vivo. Moreover, the anticancer effects of MRPL35 silencing could be rescued by SLC7A5 overexpression in NSCLC cells.

Conclusion

MRPL35 expression was stabilized by USP39‐induced deubiquitination in NSCLC cells, and knockdown of MRPL35 suppressed NSCLC cell proliferation, invasion, and glutamine metabolism in vitro and impeded tumor growth in vivo by upregulating SLC7A5, providing a promising therapeutic target for NSCLC.
Dalzanemdor (SAGE‐718), a novel, investigational N‐methyl‐D‐aspartate receptor positive allosteric modulator: Safety, tolerability, and clinical pharmacology in randomized dose‐finding studies in healthy participants and an open‐label study in participants with Huntington's disease
Authors: Koenig Aaron , Lewis Michael , Wald Jeff , Li Sigui , Varoglu Mustafa , Dai Jing , Sankoh Abdul , Paumier Katrina , Doherty James , Quirk Mike
Published: July 2024

N‐methyl‐D‐aspartate receptor (NMDAR)‐positive allosteric modulators (PAMs) represent a potential therapeutic strategy for cognitive impairment in disorders associated with NMDAR hypofunction, including Huntington's disease (HD) and Alzheimer's disease. Dalzanemdor (SAGE‐718) is a novel, investigational NMDAR PAM being evaluated for the potential treatment of cognitive impairment in these disorders. We report first‐in‐human, phase I, double‐blind, dose‐finding studies to assess the safety, tolerability, and clinical pharmacology of dalzanemdor. A single‐ascending dose study (dalzanemdor 0.35, 0.75, 1.5, or 3.0 mg vs. placebo) was conducted in healthy participants and included food effects. A multiple‐ascending dose study (14 days) was conducted in healthy participants (dalzanemdor 0.5 or 1.0 mg vs. placebo) and HD participants (open‐label dalzanemdor 1.0 mg) and included exploratory pharmacodynamics on cognitive performance. Dalzanemdor was generally well tolerated with no adverse events leading to discontinuation. Dalzanemdor exhibited pharmacokinetic parameters appropriate for once‐daily dosing. Following single and multiple doses in healthy participants, median terminal half‐life was 8–118 h, and the median time to reach maximum plasma concentration was 4–7 h. Exposures were dose‐proportional after single dose (6–46 ng/mL) and more than dose‐proportional after multiple doses (6–41 ng/mL). With multiple dosing, a steady state was achieved after 11 days in healthy participants and 13 days in HD participants. Dalzanemdor exposure decreased slightly with food. In HD participants, results suggest that dalzanemdor may improve cognitive performance on tests of executive function. These results support continued clinical development of dalzanemdor for the potential treatment of cognitive impairment in disorders of NMDAR hypofunction.
Contribution of initial lymphatics to oral wound healing after tooth extraction
Authors: Virtej Anca , Marti Larissa , Wagner Marek , Wiig Helge , Xue Ying , Bletsa Athanasia , Berggreen Ellen
Published: July 2024

Lymphatics are involved in the resolution of inflammation and wound healing, but their role in the oral wound healing process after tooth extraction has never been investigated. We therefore sought to evaluate the healing process following the extraction of maxillary molars in two transgenic mouse models: K14‐VEGFR3‐Ig mice, which lack initial mucosal lymphatic vessels, and K14‐VEGFC mice, which have hyperplastic mucosal lymphatics. Maxillary molars were extracted from both transgenic mouse types and their corresponding wild‐type (WT) controls. Mucosal and alveolar bone healing were evaluated. A delayed epithelialization and bone regeneration were observed in K14‐VEGFR3‐Ig mice compared with their WT littermates. The hampered wound closure was accompanied by decreased levels of epidermal growth factor (EGF) and persistent inflammation, characterized by infiltrates of immune cells and elevated levels of pro‐inflammatory markers in the wounds. Hyperplastic mucosal lymphatics did not enhance the healing process after tooth extraction in K14‐VEGFC mice. The findings indicate that initial mucosal lymphatics play a major role in the initial phase of the oral wound healing process.
Incomplete resection of the intracranial electroencephalographic seizure onset zone is not associated with postsurgical outcomes
Authors: Gascoigne Sarah J. , Evans Nathan , Hall Gerard , Kozma Csaba , Panagiotopoulou Mariella , Schroeder Gabrielle M. , Simpson Callum , Thornton Christopher , Turner Frances , Woodhouse Heather , Blickwedel Jess , Chowdhury Fahmida A. , Diehl Beate , Duncan John S. , Faulder Ryan , Thomas Rhys H. , Wilson Kevin , Taylor Peter N. , Wang Yujiang
Published: July 2024

Delineation of seizure onset regions using intracranial electroencephalography (icEEG) is vital in the surgical workup of drug‐resistant epilepsy cases. However, it is unknown whether the complete resection of these regions is necessary for seizure freedom, or whether postsurgical seizure recurrence can be attributed to the incomplete removal of seizure onset regions. To address this gap, we retrospectively analyzed icEEG recordings from 63 subjects, identifying seizure onset regions visually and algorithmically. We assessed onset region resection and correlated this with postsurgical seizure control. The majority of subjects had more than half of their onset regions resected (82.46% and 80.65% of subjects using visual and algorithmic methods, respectively). There was no association between the proportion of the seizure onset zone (SOZ) that was subsequently resected and better surgical outcomes (area under the receiver operating characteristic curve [AUC] < .7). Investigating the spatial extent of onset regions, we found no substantial evidence of an association with postsurgical seizure control (all AUC < .7). Although seizure onset regions are typically resected completely or in large part, incomplete resection is not associated with worse postsurgical outcomes. We conclude that postsurgical seizure recurrence cannot be attributed to an incomplete resection of the icEEG SOZ alone. Other network mechanisms beyond icEEG seizure onset likely contribute.
The impact of involuntary job displacement on participation in gig work: A causal analysis
Authors: Jeon Sung‐Hee , Ostrovsky Yuri
Published: July 2024

We used rich Canadian administrative data linked to census records to examine the impact of firm closures and involuntary job displacement on entry into gig work. Similar to several recent studies, we identified gig workers as unincorporated self‐employed freelancers, independent consultants and on‐demand workers. We found that individuals displaced from closing firms are about 24% (1.1 p.p.) more likely to be gig workers in the year following the displacement year than the control group. We show that displaced workers remain strongly attached to traditional employment, and those who take up gig work often combine it with earning wages and salaries.
The independent and combined effects of physical activity and depressive symptoms on frailty in community‐dwelling older adults: A cross‐sectional study
Authors: Yang Lingli , Xue Benli , Zheng Xiao , Zhang Xinyi , Xiao Shujuan , Zhou Chunlan , Zhang Chichen
Published: July 2024

Aims

To investigate the independent and combined effects of physical activity (PA) and depressive symptoms on the risk of frailty in community‐dwelling older adults.

Background

Older adults face a high risk of frailty which is commonly used to predict adverse health outcomes in older patients. Engaging in PA and without depressive symptoms are crucial factors to prevent frailty. It is essential to investigate the independent and combined effects of these two variables on the risk of frailty.

Methods

We included 3392 community‐dwelling older adults. The FRAIL Scale was used to assess older adults' frail status (robust, prefrail and frail). Multiple logistic regression was utilized to examine the independent and combined effects of PA and depressive symptoms on the risk of prefrailty and frailty. The combined effects were visualized by marginal plots.

Results

The prevalence of prefrailty and frailty in older adults were 42.16% and 10.58%. Compared with the group of “Light physical activity and With depressive symptoms”, “Vigorous physical activity and Without depressive symptoms” had the lowest risk of prefrailty and frailty.

Conclusions

Older adults who do not engage in PA or have depressive symptoms increased the risk of frailty, but older adults with depressive symptoms could lower the risk of frailty through PA.

Relevance to Clinical Practice

It is effective to reduce the risk of frailty by directing older adults to do moderate physical activity, although they have depressive symptoms. The focus should also be on older adults with depressive symptoms, who have at least more than twice and fourfold risk of prefrailty and frailty compared to those without.

Impact

This study offers insights for future interventions aimed at preventing frailty in older adults.

Reporting Method

This study adhered to the STROBE checklist.

Patient or Public Contributions

Older adults participated in this study and completed questionnaires.