bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the representational power of pre-trained DNA language models for regulatory genomics
Authors: Tang Ziqi , Somia Nirali , Yu Yiyang , Koo Peter K
Published: March 2024

The emergence of genomic language models (gLMs) offers an unsupervised approach to learning a wide diversity ofcis-regulatory patterns in the non-coding genome without requiring labels of functional activity generated by wet-lab experiments. Previous evaluations have shown that pre-trained gLMs can be leveraged to improve predictive performance across a broad range of regulatory genomics tasks, albeit using relatively simple benchmark datasets and baseline models. Since the gLMs in these studies were tested upon fine-tuning their weights for each downstream task, determining whether gLM representations embody a foundational understanding ofcis-regulatory biology remains an open question. Here we evaluate the representational power of pre-trained gLMs to predict and interpret cell-type-specific functional genomics data that span DNA and RNA regulation. Our findings suggest that probing the representations of pre-trained gLMs do not offer substantial advantages over conventional machine learning approaches that use one-hot encoded sequences. This work highlights a major gap with current gLMs, raising potential issues in conventional pre-training strategies for the non-coding genome.
Beta Cells Deficient forRenalaseCounteract Autoimmunity by Shaping Natural Killer Cell Activity
Authors: Bode Kevin , Wei Siying , Gruber Isabella , Kissler Stephan , Yi Peng
Published: March 2024

Type 1 diabetes (T1D) arises from autoimmune-mediated destruction of insulin-producing pancreatic beta cells. Recent advancements in the technology of generating pancreatic beta cells from human pluripotent stem cells (SC-beta cells) have facilitated the exploration of cell replacement therapies for treating T1D. However, the persistent threat of autoimmunity poses a significant challenge to the survival of transplanted SC-beta cells. Genetic engineering is a promising approach to enhance immune resistance of beta cells as we previously showed by inactivating of theRenalase(Rnls) gene. Here we demonstrate thatRnlsloss-of-function in beta cells shape autoimmunity by mediating a regulatory Natural Killer (NK) cell phenotype important for the induction of tolerogenic antigen presenting cells.Rnls-deficient beta cells mediate cell-cell-contact-independent induction of hallmark anti-inflammatory cytokine Tgfβ1 in NK cells. In addition, surface expression of key regulatory NK immune checkpoints CD47 and Ceacam1 are markedly elevated on beta cells deficient forRnls. Enhanced glucose metabolism inRnlsmutant beta cells is responsible for upregulation of CD47 surface expression. These findings are crucial to a better understand how genetically engineered beta cells shape autoimmunity giving valuable insights for future therapeutic advancements to treat and cure T1D.

Graphical summary
A novel method for fine-scale retrospective isotope analysis in mammals using eye lenses
Authors: Miura Kazuki , Matsubayashi Jun , Yoshimizu Chikage , Takafumi Hino , Shirane Yuri , Mano Tsutomu , Tsuruga Hifumi , Tayasu Ichiro
Published: March 2024

1. Investigating individual behavioural variations in mammals is essential for understanding their ecology and evolution, and plays a critical role in conservation and management practices. However, the reconstruction of long-term individual behaviour, such as via bio-logging, remains challenging owing to cost constraints and limitations of battery life and the impact of device size for smaller animals. This study proposed and tested a novel and cost-effective method for retrospective isotope analysis using mammalian eye lenses, specifically focusing on brown bears (Ursus arctos).

2. Seven pairs of bear eye lenses were collected from southwestern Hokkaido, Japan. One or both lenses of each bear were segregated into small fragments from the outermost to the core tissues, and the nitrogen and carbon stable isotope ratios (δ15N and δ13C) of each eye lens fragment were measured. These isotope ratios in the eye lenses were compared with the δ15N and δ13C of potential brown bear diets in the study region (C3herbs, C3fruits, terrestrial animals, and corn). Additionally, we compared the isotopic patterns in both the right and left lenses of the same bear in two individuals to evaluate the consistency of our preparation protocol.

3. In all eye lenses, high δ15N values were identified near the core, which gradually decreased towards the outer tissues, indicating ontogenetic dietary shifts related to lactation and weaning in the early life stage. Bears from study areas with high corn availability exhibited substantial increases in δ13C and δ15N in the outer lens tissues, suggesting a dietary shift toward corn consumption after weaning. Isotopic patterns between lens pairs from the same individual were similar, although discrepancies increased in tissues located 1.00 to 2.25 mm from the core, highlighting the need for standardisation in sample processing.

4. This study demonstrates a novel and simple technique for retrospective isotope analysis in wild mammals using eye lenses, effectively reconstructing the feeding histories of brown bears. Our findings provide a new avenue for studying individual time-series behavioural patterns, with important implications for the fields of mammalian ecology, evolution, conservation, and management.
Regulation of immune signal integration and memory by inflammation-induced chromosome conformation
Authors: Daniel Bence , Chen Andy Y. , Sandor Katalin , Zhang Wenxi , Miao Zhuang , Lareau Caleb A. , Yost Kathryn E. , Chang Howard Y. , Satpathy Ansuman T.
Published: March 2024

3-dimensional (3D) genome conformation is central to gene expression regulation, yet our understanding of its contribution to rapid transcriptional responses, signal integration, and memory in immune cells is limited. Here, we study the molecular regulation of the inflammatory response in primary macrophages using integrated transcriptomic, epigenomic, and chromosome conformation data, including base pair-resolution Micro-Capture C. We demonstrate that interleukin-4 (IL-4) primes the inflammatory response in macrophages by stably rewiring 3D genome conformation, juxtaposing endotoxin-, interferon-gamma-, and dexamethasone-responsive enhancers in close proximity to their cognate gene promoters. CRISPR-based perturbations of enhancer-promoter contacts or CCCTC-binding factor (CTCF) boundary elements demonstrated that IL-4-driven conformation changes are indispensable for enhanced and synergistic endotoxin-induced transcriptional responses, as well as transcriptional memory following stimulus removal. Moreover, transcriptional memory mediated by changes in chromosome conformation often occurred in the absence of changes in chromatin accessibility or histone modifications. Collectively, these findings demonstrate that rapid and memory transcriptional responses to immunological stimuli are encoded in the 3D genome.
Correlation measures in metagenomic data: the blessing of dimensionality
Authors: Fuschi Alessandro , Merlotti Alessandra , Binh Tran Thi Dong , Nguyen Hoan , Weinstock George M. , Remondini Daniel
Published: March 2024

Microbiome analysis has revolutionized our understanding of various biological processes, spanning human health, epidemiology (including antimicrobial resistance and horizontal gene transfer), as well as environmental and agricultural studies. At the heart of microbiome analysis lies the characterization of microbial communities through the quantification of microbial taxa and their dynamics. In the study of bacterial abundances, it is becoming more relevant to consider their relationship, to embed these data in the framework of network theory, allowing characterization of features like node relevance, pathway and community structure. In this study, we address the primary biases encountered in reconstructing networks through correlation measures, particularly in light of the compositional nature of the data, within-sample diversity, and the presence of a high number of unobserved species. These factors can lead to inaccurate correlation estimates. To tackle these challenges, we employ simulated data to demonstrate how many of these issues can be mitigated by applying typical transformations designed for compositional data. These transformations enable the use of straightforward measures like Pearson’s correlation to correctly identify positive and negative relationships among relative abundances, especially in high-dimensional data, without having any need for further corrections. However, some challenges persist, such as addressing data sparsity, as neglecting this aspect can result in an underestimation of negative correlations.
Stabilization of AMPK/PFKL/RPIA in the Glycolytic Bodies Transduces IL6/STAT3 Signal in Hepatocarcinogenesis
Authors: Hsiao He-Yun , Cheng Chun-Chia , Chou Yu-Ting , Kuo Cheng-Chin , Wang Wen-Ching , Sampurna Bonifasius Putera , Wang Yi-Wen , Hsiao Chun-Ling , Wu Jing-Yiing , Lin Kuan-Hao , Yang Wan-Yu , Lin Yu-Hsuan , Gwee Kong-Huai , Wang Horng-Dar , Yuh Chiou-Hwa
Published: March 2024

Metabolic reprogramming is a pivotal characteristic of cancer, yet the intricate interplay between glycolysis and the pentose phosphate pathway (PPP) remains elusive. This study unveils the pivotal role of 6-phosphofructokinase liver type (PFKL) in glycolysis and ribose 5-phosphate isomerase A (RPIA) in PPP, orchestrating liver tumorigenesis. PFKL, the rate-limiting enzyme in glycolysis, stabilizes RPIA by impeding ubiquitination/proteasome activity. The pro-inflammatory and tumor cytokine interleukin 6 activates pSTAT3 which binds to the promoter region and activates AMPK and PFKL transcription. Furthermore, pAMPK stabilizes PFKL protein by preventing proteasome degradation in hepatoma cells. Inhibiting PFKL, AMPK, and STAT3 genetically or pharmacologically can reduce glycolysis, ATP production, resulting in reduction of hepatoma cell proliferation and migration. Intriguingly, the PFKL, AMPK, RPIA, and PKM2 are co-localized in the Glycolytic body (G-body) which starts forming at chronic hepatitis, dramatically increases during active hepatitis, and the size of G-bodies becomes bigger from cirrhosis to hepatocellular carcinoma. Furthermore, using Bimolecular fluorescence complementation (BiFC) assay, we demonstrated that PFKL and RPIA direct interacts. Targeting AMPK or STAT3 significantly reduced tumor formation and lipid accumulation in zebrafish models, suggesting the STAT3/AMPK/PFKL axis as a potential therapeutic avenue for liver cancer treatment.
Student Cognitive Enhancement with Non-Prescribed Modafinil. Is it Cheating?
Authors: Kesta Alexia , Newton Philip M.
Published: March 2024

Modafinil, a prescription-only drug, it is mainly used to treat narcolepsy and sleep disorders, but it is also used, without a prescription, as a cognitive enhancer by ∼10% of UK University students. Previous research has focused on the prevalence of, and motivations for, these behaviours. Here we focused specifically on determining whether students view this behaviour as cheating. We used a scenario-based approach to quantify, and qualitatively understand, student views on this topic. Most students did not view this behaviour as cheating, in part due to similarities with freely available stimulants such as caffeine, and a view that cognitive enhancement does not confer new knowledge or understanding. Although a minority of students did view it as cheating, they also expressed strong views, based in part on basic questions of fairness and access. Few students did not have a view either way. These views remained largely unchanged even when presented with considerations of other moderators of the ethics of cognitive enhancement with modafinil.
Assessment of Stiffness-Dependent Autophagosome Formation and Apoptosis in Embryonal Rhabdomyosarcoma Tumor Cells
Authors: Sezen Serap , Adiguzel Sevin , Zareour Atefeh , Khosravi Arezoo , Gordon Joseph W , Ghavami Saeid , Zarrabi Ali
Published: March 2024

Summary/Abstract

Remodeling of the extracellular matrix (ECM) eventually causes the stiffening of tumors and changes to the microenvironment. The stiffening alters the biological processes in cancer cells due to altered signaling through cell surface receptors. Autophagy, a key catabolic process in normal and cancer cells, is thought to be involved in mechano-transduction and the level of autophagy is probably stiffness-dependent. Here, we provide a methodology to study the effect of matrix stiffness on autophagy in embryonal rhabdomyosarcoma cells. To mimic stiffness, we seeded cells on GelMA hydrogel matrices with defined stiffness and evaluated autophagy-related endpoints. We also evaluated autophagy dependent pathways, apoptosis, and cell viability. Specifically, we utilized immunocytochemistry and confocal microscopy to track autophagosome formation through LC3 lipidation. This approach suggests that the use GelMA hydrogels with defined stiffness represent a novel method to evaluate the role of autophagy in embryonal rhabdomyosarcoma and other cancer cells.

Workflow
LHP1 and INO80 cooperate with ethylene signaling for warm ambient temperature response by activating specific bivalent genes
Authors: Shao Zhengyao , Bai Yanan , Huq Enamul , Qiao Hong
Published: March 2024

Ethylene signaling has been indicated as a potential positive regulator of plant warm ambient temperature response but its underlying molecular mechanisms are largely unknown. Here, we show that LHP1 and INO80 cooperate with ethylene signaling for warm ambient temperature response by activating specific bivalent genes. We found that the presence of warm ambient temperature activates ethylene signaling through EIN2 and EIN3, leading to an interaction between LHP1 and accumulated EIN2-C to co-regulate a subset of LHP1-bound genes marked by H3K27me3 and H3K4me3 bivalency. Furthermore, we demonstrate that INO80 is recruited to bivalent genes by interacting with EIN2-C and EIN3, promoting H3K4me3 enrichment and facilitating transcriptional activation in response to warm ambient temperature. Together, our findings illustrate a novel mechanism wherein ethylene signaling orchestrates LHP1 and INO80 to regulate warm ambient temperature response through activating specific bivalent genes in Arabidopsis.
Time-course transcriptome data of silk glands in day 0–7 last-instar larvae ofBombyx mori(w1 pndstrain)
Authors: Masuoka Yudai , Jouraku Akiya , Tsubota Takuya , Ono Hiromasa , Chiba Hirokazu , Sezutsu Hideki , Bono Hidemasa , Yokoi Kakeru
Published: March 2024

Time-course transcriptome expression data were constructed for four parts of the silk gland (anterior, middle, and posterior parts of the middle silk gland, along with the posterior silk gland) in the domestic silkworm,Bombyx mori, from days 0 to 7 of the last-instar larvae. For sample preparation, silk glands were extracted from one female and one male larva every 24 hours accurately after the fourth ecdysis. The reliability of these transcriptome data was confirmed by comparing the transcripts per million (TPM) values of the silk gene and quantitative reverse transcription PCR results. Hierarchical cluster analysis results supported the reliability of transcriptome data. These data are likely to contribute to the progress in molecular biology and genetic research usingB. mori, such as elucidating the mechanism underlying the massive production of silk proteins, conducting entomological research using a meta-analysis as a model for lepidopteran insect species, and exploring medical research usingB. morias a model for disease species by utilising transcriptome data.
Toxic eburicol accumulation drives the antifungal activity of azoles againstAspergillus fumigatus
Authors: Elsaman Hesham , Golubtsov Evgeny , Brazil Sean , Ng Natanya , Klugherz Isabel , Dichtl Karl , Müller Christoph , Wagener Johannes
Published: March 2024

Azole antifungals inhibit the sterol C14-demethylase (CYP51/Erg11), a key enzyme in the ergosterol biosynthesis pathway. They have fungistatic effects against yeasts but fungicidal effects against molds. The molecular basis for this difference remained unknown. The sequence of enzymatic steps required for ergosterol biosynthesis is different in yeasts and molds. Here we show that the azole-induced synthesis of fungicidal cell wall carbohydrate patches in the pathogenic moldAspergillus fumigatusstrictly correlates with the accumulation of the CYP51 substrate eburicol. A lack of other essential ergosterol biosynthesis enzymes, such as sterol C24-methyltransferase (Erg6A), squalene synthase (Erg9) or squalene epoxidase (Erg1) does not result in comparable cell wall alterations. Partial repression of Erg6A, which converts lanosterol into eburicol, increases azole resistance. The sterol C5-desaturase (ERG3)-dependent conversion of eburicol into 14-methylergosta-8,24(28)-dien-3β,6α-diol, the “toxic diol” responsible for the antifungal effects of azoles in yeasts, is not required for the fungicidal effects inA. fumigatus. In contrast to yeast, where a lack of ERG3 functionality causes azole resistance,A. fumigatuslacking ERG3 becomes more azole susceptible. Mutants lacking mitochondrial complex III functionality, which are less susceptible to the fungicidal effects of azoles, but get strongly inhibited in growth, convert eburicol much more efficiently into the supposedly “toxic diol”. Our results support a mechanistic model where the mode of action of azoles against the pathogenic moldA. fumigatus, other than in yeast, relies on the accumulation of eburicol which exerts fungicidal effects by triggering the formation of cell wall carbohydrate patches.
Trabectedin Enhances Oncolytic Virotherapy by Reducing Barriers to Virus Spread and Cytotoxic Immunity in Preclinical Pediatric Bone Sarcoma
Authors: Ringwalt Emily M. , Currier Mark A. , Glaspell Andrea M. , Chen Chun-Yu , Cannon Matthew V. , Cam Maren , Gross Amy C. , Gust Matthew , Wang Pin-Yi , Boon Louis , Biederman Laura E. , Schwarz Emily , Rajappa Prajwal , Lee Dean A. , Mardis Elaine R. , Carson William E. , Roberts Ryan D. , Cripe Timothy P.
Published: March 2024

We previously reported that the DNA alkylator and transcriptional-blocking chemotherapeutic agent trabectedin enhances oncolytic herpes simplex viroimmunotherapy in human sarcoma xenograft models, though the mechanism remained to be elucidated. Here we report trabectedin disrupts the intrinsic cellular anti-viral response which increases viral transcript spread throughout the human tumor cells. We also extended our synergy findings to syngeneic murine sarcoma models, which are poorly susceptible to virus infection. In the absence of robust virus replication, we found trabectedin enhanced viroimmunotherapy efficacy by reducing immunosuppressive macrophages and stimulating granzyme expression in infiltrating T and NK cells to cause immune-mediated tumor regressions. Thus, trabectedin enhances both the direct virus-mediated killing of tumor cells and the viral-induced activation of cytotoxic effector lymphocytes to cause tumor regressions across models. Our data provide a strong rationale for clinical translation as both mechanisms should be simultaneously active in human patients.
Two PYRIDOXAL PHOSPHATE HOMEOSTASIS PROTEINs are essential for management of the coenzyme in plants
Authors: Farkas Peter , Fitzpatrick Teresa B.
Published: March 2024

Coenzyme management is believed to be important for the required pool of active enzymes driving metabolic routes to facilitate homeostasis and match environmental circumstance. The coenzyme pyridoxal 5’-phosphate (PLP) (a vitamin B6derivative) is involved in a diverse array of enzyme reactions spanning amino acid to hormone metabolism. However, dedicated proteins that contribute to PLP homeostasis have not yet been studied in plants. Here we demonstrate the importance of proteins annotated PLP HOMEOSTASIS PROTEINs (PLPHPs) for control of PLP in Arabidopsis. A systematic analysis indicates that while most kingdoms have a singlePLPHPhomolog, Angiosperms within the plant kingdom have two. PLPHPs from Arabidopsis bind PLP and exist as monomers in solution in contrast to reported PLP-dependent enzymes from all kingdoms. Disrupting functionality of both homologs perturbs vitamin B6content including a PLP deficit accompanied by impaired and light hypersensitive root growth, unlike biosynthesis mutants. Micrografting studies show that the PLP deficit can be relieved distally between shoots and roots. Yet, supplementation experiments do not restore vitamin B6homeostasis in the absence of PLPHP. A series of chemical treatments probing PLP-dependent reactions, notably those for auxin and ethylene, provide evidence that the physiological role of PLPHPs is dynamic management of PLP. Assays in vitro show that Arabidopsis PLPHP can coordinate both PLP transfer and withdrawal. This study expands our broader knowledge of vitamin B6biology and highlights the importance of PLP coenzyme homeostasis in plants, providing a platform for further investigations in boosting adaptive responses.

One sentence summary

PLPHPs contribute to surveillance of vitamin B6homeostasis, likely acting as a rheostat in adaptive responses as a function of the use of the coenzyme PLP.
Yellow Fever Emergence: Role of Heterologous Flavivirus Immunity in Preventing Urban Transmission
Authors: Shinde Divya P. , Plante Jessica A. , Scharton Dionna , Mitchell Brooke , Walker Jordyn , Azar Sasha R. , Campos Rafael K. , Sacchetto Lívia , Drumond Betânia P. , Vasilakis Nikos , Plante Kenneth S. , Weaver Scott C.
Published: March 2024

During major, recent yellow fever (YF) epidemics in Brazil, human cases were attributed only to spillover infections from sylvatic transmission with no evidence of human amplification. Furthermore, the historic absence of YF in Asia, despite abundant peridomesticAedes aegyptiand naive human populations, represents a longstanding enigma. We tested the hypothesis that immunity from dengue (DENV) and Zika (ZIKV) flaviviruses limits YF virus (YFV) viremia and transmission byAe. aegypti. Prior DENV and ZIKV immunity consistently suppressed YFV viremia in experimentally infected macaques, leading to reductions inAe. aegyptiinfection when mosquitoes were fed on infected animals. These results indicate that, in DENV- and ZIKV-endemic regions such as South America and Asia, flavivirus immunity suppresses YFV human amplification potential, reducing the risk of urban outbreaks.

One-Sentence Summary

Immunity from dengue and Zika viruses suppresses yellow fever viremia, preventing infection of mosquitoes and reducing the risk of epidemics.
A binary trait model reveals the fitness effects of HIV-1 escape from T cell responses
Authors: Gao Yirui , Barton John P.
Published: March 2024

Natural selection often acts on multiple traits simultaneously. For example, the virus HIV-1 faces pressure to evade host immunity while also preserving replicative fitness. While past work has studied selection during HIV-1 evolution, as in other examples where selection acts on multiple traits, it is challenging to quantitatively separate different contributions to fitness. This task is made more difficult because a single mutation can affect both immune escape and replication. Here, we develop an evolutionary model that disentangles the effects of escaping CD8+T cell-mediated immunity, which we model as a binary trait, from other contributions to fitness. After validation in simulations, we applied this model to study within-host HIV-1 evolution in a clinical data set. We observed strong selection for immune escape, sometimes greatly exceeding past estimates, especially early in infection. Conservative estimates suggest that roughly half of HIV-1 fitness gains during the first months to years of infection can be attributed to T cell escape. Our approach is not limited to HIV-1 or viruses, and could be adapted to study the evolution of quantitative traits in other contexts.
Landau Singularities Revisited: Computational Algebraic Geometry for Feynman Integrals
Authors: Fevola Claudia , Mizera Sebastian , Telen Simon
Published: March 2024

We reformulate the analysis of singularities of Feynman integrals in a way that can be practically applied to perturbative computations in the standard model in dimensional regularization. After highlighting issues in the textbook treatment of Landau singularities, we develop an algorithm for classifying and computing them using techniques from computational algebraic geometry. We introduce an algebraic variety called the principal Landau determinant, which captures the singularities even in the presence of massless particles or UV/IR divergences. We illustrate this for 114 example diagrams, including a cutting-edge 2-loop 5-point nonplanar QCD process with multiple mass scales.

Published by the American Physical Society
2024
“I can almost recognize its voice”: AI and its impact on ethical teacher-centaur labor
Authors: Fassbender William Joseph
Published: March 2024

Purpose

This study builds on previous theoretical work that considered artificial intelligence (AI) and its potential for creating “teacher-centaurs” whose labor could be accelerated through the use of generative AI (Fassbender, in review). The purpose of this paper is to use empirical methods to study centaur teachers and the division of labor (Durkheim, 1893/2013) that arise from outsourcing teaching tasks to AI.

Design/methodology/approach

Multiple case study (Stake, 2006) was used to collect data on two secondary English teachers who were early adopters of generative AI. Data included semi-structured interviews as well as ChatGPT chat logs, which helped in describing how teaching approaches evolved using AI technology.

Findings

Results showed that teachers used AI for planning, instruction and assessment. AI-augmented teaching practices allowed teachers to complete tasks with greater speed, which in turn increased stamina and short-term work–life balance. Given the novelty of AI, concerns about data privacy and academic integrity raised ethical questions.

Originality/value

ChatGPT’s rise to popularity in 2023 brought with it significant discussions about education, specifically how students would use AI primarily as a tool for plagiarism. This study takes a different focus, considering how early adoption of AI has begun changing teacher labor, offering implications for the future of the teaching profession.
The impact of environmental, social and governance (ESG) reporting on corporate profitability: evidence from Thailand
Authors: Treepongkaruna Sirimon , Suttipun Muttanachai
Published: March 2024

Purpose

The United Nations' sustainable development goals (SDGs) put together a global framework in an attempt to address environmental, social and governance (ESG) concerns. Measuring a company’s contribution to the SDGs relies heavily on ESG reporting. This paper aims to examine the impact of ESG reporting on the corporate profitability of listed companies in Thailand over the period of 2019–2021.

Design/methodology/approach

Using 147 listed firms in the ESG group, content analysis was used to quantify the ESG reporting (within 11 themes), while corporate profitability was measured by return on asset and return on equity. Descriptive analysis, correlation matrix and panel regression are used to analyze the data of this study.

Findings

Consistent with the legitimacy, stakeholder and signaling theories, the authors found a statistically significant and positive impact of ESG reporting on corporate profitability in Thailand.

Originality/value

The findings highlight the importance of incorporating ESG considerations into companies’ reporting and decision-making processes, as these can enhance firm profitability and performance, attract stakeholders, improve their competitive advantage and step toward sustainability.
Does the healthcare decentralization provide better public health security capacity and health services satisfaction? An analysis of OECD countries
Authors: Durmuş Veli
Published: March 2024

Purpose

Decentralization has profound implications for many health systems. This study investigates the effect of health system decentralization in Organization for Economic Co-operation and Development (OECD) countries on public health security capacity and health service satisfaction.

Design/methodology/approach

Multiple linear regression analyses were employed for variables related to the level of health security capacity and satisfaction with the healthcare system while controlling for all socio-demographic variables from the European Social Survey, including over 44,000 respondents from 25 OECD countries. The Health Systems in Transition series of countries were used for assessing the decentralization level.

Findings

The result of multiple linear regression analyses showed that the level of decentralization in health systems was significantly associated with higher health security capacity (ß-coefficient 3.722, 95% confidence interval (CI) [3.536 3.908]; p=<0.001) and health service satisfaction (ß-coefficient 1.463, 95% CI [1.389 1.536]; p=<0.001) in the study. Countries with a higher level of decentralization in health policy tasks and areas were significantly likely to have higher health services satisfaction, whereas this satisfaction had a significant negative relation with the lower level of decentralization status of secondary/tertiary care services in OECD countries (ß-coefficient −5.250, 95% CI [−5.757–4.743]; p = 0.001).

Originality/value

This study contributes to a better understanding of the extent to which decentralization of health services affects public health safety capacity and satisfaction with health services, whereas the level of decentralization in OECD countries varies considerably. Overall, the findings highlight the importance of public health security and satisfaction with health care delivery in assessing the effects of decentralization in health services.
The effects of corporate social responsibility on innovation and performance of firms in China: a structural equation model analysis
Authors: Li Xiufeng , Zhang Zhen
Published: March 2024

Purpose

This study aims to analyze and discuss the impact of corporate social responsibility (CSR) on firms’ performance, as well as to examine the interplay between CSR and the economy, society and innovation.

Design/methodology/approach

This paper collects data from 420 manufacturing firms across various geographical regions in China. By using a structural equation model, the paper investigates the impact of CSR on enterprise innovation, customer management capability, market competitiveness (MC) and firm financial performance.

Findings

The findings demonstrate that CSR performance positively contributes to enhancing the level of enterprise innovation, as well as customer management capability and market competitiveness. Furthermore, it assists enterprises in improving market competitiveness and elevating customer management capabilities. Thus, CSR can have a positive effect on the firm financial performance.

Originality/value

The outcomes presented in this paper offer valuable evidence regarding the influence of implementing CSR on different aspects of enterprise performance and innovation. Moreover, it provides practical recommendations for enterprises seeking to transition towards low-carbon practices and upgrade their manufacturing industry.
The dilemma of leadership development
Authors: Phillips Patti P. , Phillips Jack J.
Published: March 2024

Purpose

In the field of leadership development, a dilemma exists with many executives, who often support and fund leadership development programs. Executives know that great leaders are needed to drive results, and for the most part, they must develop those leaders internally. At the same time, the leadership development providers are content with showing executives that they have changed leader behavior. The same providers are reluctant to connect behavior change to meaningful and important business measures. Yet, when used properly, leader behavior will drive all types of important impact measures in an organization. That is what executives want to see. This purpose of this article is to show how leadership development providers can connect their programs to important business measures and deliver value at the Impact and ROI Levels using the ROI Methodology.

Design/methodology/approach

Executives prefer to have leader behavior connected to impact, which is their No. 1 measure and return on investment (ROI), their No. 2 measure. Impact and ROI is the world they live in. Executives know that new leader behavior is necessary for impact and often have input into the behaviors they would like to see. When it comes to measuring success, they want to see how the program connects to the organization and the value the new behavior delivers. To avoid the possibility of disappointing results, implement the ROI Methodology framework to design the leadership development program to deliver the desired results and make sure that everyone involved is helping to deliver the needed success.

Findings

Leadership development providers must address the challenge of showing the value of leadership development. It is not that difficult to show the impact and ROI of major programs. Literally, hundreds of organizations are doing this now. The authors have published four books with different publishers on the value of leadership development, with case studies, and more will be published.

Originality/value

This level of evaluation can set the leadership development program apart from the others.
The interaction effect of goal orientation and mindfulness of entrepreneurs on firm innovation capability and its impact on firm performance
Authors: Ratanavanich Muanfhun , Charoensukmongkol Peerayuth
Published: March 2024

Purpose

Grounded in the resource-based view of the firm, this study aims to examine the effects of goal orientation and the mindfulness of entrepreneurs on firm innovation capability and analyzes that capability’s subsequent impact on firm performance. The authors also analyze whether mindfulness interacts with goal orientation to intensify its effect on firm innovation capability.

Design/methodology/approach

Simple random sampling was used to obtain the sample of Thai firms listed in the Department of Business Development database (n = 304). The data analysis was done by using partial least square structural equation modeling.

Findings

Goal orientation and mindfulness are positively associated with firm innovation capability. The analysis also supports the interaction effect of goal orientation and mindfulness on firm innovation capability. Moreover, firm innovation capability is positively associated with firm performance.

Practical implications

Goal orientation and mindfulness should be considered two essential soft skills that entrepreneurs must develop to build up their firms’ innovation capability. Because entrepreneurs are the key drivers of economic growth and sustainable development, the government agencies responsible for the entrepreneurship development should consider goal orientation and mindfulness as parts of their entrepreneurship training program and development policy.

Originality/value

The finding about the interaction effect of goal orientation and mindfulness on firm innovation capability provides new evidence that was not documented in previous research. The authors clarify that these are entrepreneurial characteristics that could supplement each other to maximize the potential of entrepreneurs and strengthen the innovation capability of their firms.
Novel therapeutic targets in dermatomyositis
Authors: Bax Christina , Aghdasi Carmel , Fiorentino David
Published: March 2024

Dermatomyositis (DM) is a systemic autoimmune disease with variable clinical presentations, including inflammation in the skin, muscle, lungs, and/or joints. Current therapeutic strategies in DM typically include broad immunosuppression; however, the currently used modalities are not universally effective and are associated with various side effects, including risk of infection. There is currently a highly unmet need for more effective and well‐tolerated therapies. Recent years have witnessed increased interest in pharmaceutical development of new therapeutic strategies for DM. This review aims to summarize the landscape of therapies that are currently being tested or planned in patients with DM. These therapies have a wide variety of immunological targets, including T cells, B cells, inflammatory signaling pathways, type I interferons, autoantibodies, and other targets.
Soluble PD‐L1 predicts tumor response and immune‐related adverse events in patients with advanced melanoma treated with anti–PD‐1 antibodies
Authors: Oya Kazumasa , Nakamura Yoshiyuki , Shen Larina Tzu‐Wei , Ishizuki Shoichiro , Matsusaka Satoshi , Fujisawa Yasuhiro
Published: March 2024

Immune checkpoint inhibitors (ICIs) bring prognostic benefits to patients with malignancies. However, there is a substantial number of patients whose lesions are not improved by ICIs. In addition, ICIs may cause immune‐related adverse events (irAEs), which could lead to an unfavorable prognosis with fatal consequences. Therefore, we conducted a retrospective study to evaluate the utility of circulating sPD‐L1 (soluble programmed cell death 1 ligand 1) as a biomarker in patients with advanced melanoma treated with anti–PD‐1 (programmed cell death 1 protein) antibodies. Sera from 31 consecutive patients were prospectively collected before and after anti–PD‐1 antibody treatment and the serum level of sPD‐L1 was evaluated. We found that high sPD‐L1 levels before treatment were associated with better prognosis, and this association was observed only in patients with a low tumor burden. We also found that sPD‐L1 levels were elevated in patients who developed severe irAEs after treatment, and the patients with severe irAEs had significantly higher fluctuations in sPD‐L1 (delta sPD‐L1) than those without severe irAEs. Our study suggests that serum sPD‐L1 level is a useful biomarker to predict tumor response and irAE development in patients with advanced melanoma treated with anti–PD‐1 antibodies.
Listening to experts is not always wise: Unravelling the dynamics of decision‐making in the crisis cell
Authors: De Vittoris Raphael G. , Lebrument Norbert , Bousquet Carole
Published: March 2024

The study challenges the conventional belief that expertise enhances crisis decision‐making. Analyzing crisis simulations, it reveals that crisis cells with minimal expertise achieved a commendable 69% decision quality, surpassing those with specialists. The research underscores the importance of collective intelligence and adherence to fundamental ‘metarules’ in decision‐making, irrespective of expertise. It questions the presumed benefits of expertise, suggesting that excessive reliance on experts may hinder information processing and flexibility during crises. The findings advocate for a reconsideration of the role of expertise in crisis management, emphasizing the significance of collective decision‐making and adherence to metarules. The study calls for further exploration of expert leaders' potential influence within crisis cells.
Expectation versus reality: How crisis statement essentials are evaluated by Gen Z stakeholders and crisis communication practitioners
Authors: Karinshak Elise , Voges Taylor , Jin Yan
Published: March 2024

At the onset of a crisis, an initial organizational statement sets the tone for subsequent discussion. While existing literature provides strategic guidance, it offers limited insight into the message‐level execution of such statements. This study synthesizes insights from literature and trade publications to complement strategic literature by proposing a practical set of ‘crisis essentials’ which practitioners can leverage in composing an initial crisis statement. Upon identification of these elements from scholarly and industry literature, two online surveys presenting a hypothetical crisis scenario are released to Gen Z stakeholders and crisis communication practitioners in the United States; respondents rate the relative importance of each element. Gen Z was selected as the stakeholder population of interest due to their high activity on social media, their role as the talent which will be entering the workforce and eventually leadership roles, and the more limited existing analysis of this segment. Comparative analysis is conducted, based on two online surveys among adult individuals from these two populations, to evaluate whether gaps exist in stakeholder expectations and practitioner approaches. Findings reveal: the proposed elements (e.g., statement of the crisis, attribution, expert quote; 11 in total) were of nonzero importance to both Gen Z stakeholder respondents and crisis communication practitioner respondents, essentials related to the assuring stakeholders (e.g., action steps) were rated more highly than informational essentials (e.g., timeline), and importance ratings across survey samples were generally consistent. Practitioners should consider each of these proposed essentials when developing communication materials, and that while stakeholders expect sufficient information to understand a crisis event, they ultimately care about what the crisis means for the future of the organization. This study, grounded in crisis communication theory, provides a relevant, practical contribution to the implementation of effective strategic crisis communication in situations concerning Gen Z stakeholders.
Increased relative incidence of maternal death by suicide
Authors: Griffiths Malcolm
Published: March 2024

Linked article: This is a mini commentary on Lommerse et al., pp. 1392–1398 in this issue. To view this article visit https://doi.org/10.1111/1471‐0528.17784.
Eco‐friendly chitosan polymer mitigates disease severity and mediates plant resistance against Beet curly top Iran virus in tomato
Authors: Tokhmechi Kimia , Eini Omid , El Gamal Ahmed , Koolivand Davoud
Published: March 2024

A tomato‐infecting virus known as Beet curly top Iran virus (BCTIV) cause a significant disease for tomato plants and several other plant species around the world. Chitosan polysaccharide is a natural biopolymer that has been utilised as an exo‐elicitor to enhance plant defence mechanisms against a variety of plant diseases. This study investigates the efficacy of chitosan in combating BCTIV disease on tomato plants and modulating the host–virus interaction under greenhouse conditions. Twenty‐four hours before the virus inoculation, tomato plants were sprayed with a protective chitosan solution at different concentrations (0.5, 1, 1.5, and 2 mg/mL). Tomato plants were inoculated with a BCTIV infectious clone using an Agrobacterium‐inoculation method. The findings clearly demonstrated a reduction in the severity of the disease in chitosan‐treated plants as compared to Mock‐plants, with the percentage decreasing from 61.53% to 75.28% in 1.5 mg/mL treated plants and from 9.01% to 28.43% in 0.5 mg/mL treated plants. In addition, the utilisation of chitosan has the potential to deactivate the accumulation of BCTIV within the host tissues. The virus accumulation was greatly alleviated in 1, 1.5, and 2 mg/mL‐treated plants by 71.29%, 90.11%, and 93.14%, respectively, and over the mock plants. Furthermore, it was found that chitosan applied at all tested concentrations increased the relative expression and mRNA accumulation of genes related to resistance, including the pathogenesis‐related protein gene PR‐1, the HSP90 gene, and the AGO2a antiviral gene. These genes reached their maximum by 22.9‐, 12.93‐, and 4.44‐fold increases, respectively, over the untreated control. According to gas chromatography–mass spectroscop (GC‐MS) fractionation profile, chitosan increased 28 bioactive metabolic components, such as n‐hexadecanoic acid, heptanone, 1,2‐dimethylbenzene, dicarboxylic acid, and cis‐11‐octadecenoic acid methyl‐ester, to improve metabolic pathways. Results reported here revealed that foliar application of chitosan decreases the rate of the disease severity and virus accumulation in BCTIV‐infected tomato plants. This effect is associated with increased gene expression and defence‐related factors, enhancing tomato resistance to BCTIV infection. Consequently, chitosan treatments could be part of an integrated approach for reducing the severity of BCTIV disease in tomato and other host plants.
Multi‐proteomic analyses of 5xFAD mice reveal new molecular signatures of early‐stage Alzheimer's disease
Authors: Lee Seulah , Jang Kuk‐In , Lee Hagyeong , Jo Yeon Suk , Kwon Dayoung , Park Geuna , Bae Sungwon , Kwon Yang Woo , Jang Jin‐Hyeok , Oh Yong‐Seok , Lee Chany , Yoon Jong Hyuk
Published: March 2024

An early diagnosis of Alzheimer's disease is crucial as treatment efficacy is limited to the early stages. However, the current diagnostic methods are limited to mid or later stages of disease development owing to the limitations of clinical examinations and amyloid plaque imaging. Therefore, this study aimed to identify molecular signatures including blood plasma extracellular vesicle biomarker proteins associated with Alzheimer's disease to aid early‐stage diagnosis. The hippocampus, cortex, and blood plasma extracellular vesicles of 3‐ and 6‐month‐old 5xFAD mice were analyzed using quantitative proteomics. Subsequent bioinformatics and biochemical analyses were performed to compare the molecular signatures between wild type and 5xFAD mice across different brain regions and age groups to elucidate disease pathology. There was a unique signature of significantly altered proteins in the hippocampal and cortical proteomes of 3‐ and 6‐month‐old mice. The plasma extracellular vesicle proteomes exhibited distinct informatic features compared with the other proteomes. Furthermore, the regulation of several canonical pathways (including phosphatidylinositol 3‐kinase/protein kinase B signaling) differed between the hippocampus and cortex. Twelve potential biomarkers for the detection of early‐stage Alzheimer's disease were identified and validated using plasma extracellular vesicles from stage‐divided patients. Finally, integrin α‐IIb, creatine kinase M‐type, filamin C, glutamine γ‐glutamyltransferase 2, and lysosomal α‐mannosidase were selected as distinguishing biomarkers for healthy individuals and early‐stage Alzheimer's disease patients using machine learning modeling with approximately 79% accuracy. Our study identified novel early‐stage molecular signatures associated with the progression of Alzheimer's disease, thereby providing novel insights into its pathogenesis.
Genomic characterization of dryland adaptation in endangered Anxi cattle in China
Authors: Lyu Yang , Yao Tingting , Chen Zhefu , Huangfu Ruiyao , Cheng Haijian , Ma Weidong , Qi Xingshan , Li Fuqiang , Chen Ningbo , Lei Chuzhao
Published: March 2024

Local species exhibit distinctive indigenous characteristics while showing unique productive and phenotypic traits. However, the advent of commercialization has posed a substantial threat to the survival of indigenous species. Anxi cattle, an endangered native breed in China, have evolved unique growth and reproductive characteristics in extreme desert and semidesert ecosystems. In this study, we conducted a genomic comparison of 10 Anxi cattle genomes with those of five other global populations/breeds to assess genetic diversity and identify candidate genomic regions in Anxi cattle. Population structure and genetic diversity analyses revealed that Anxi cattle are part of the East Asian cattle clade, exhibiting higher genetic diversity than commercial breeds. Through selective sweep analysis, we identified specific genetic variations linked to the environmental adaptability of Anxi cattle. Notably, we identified several candidate genes, including CERS3 involved in regulating skin permeability and antimicrobial functions, RBFOX2 associated with cardiac development, SLC16A7 participated in the regulation of pancreatic endocrine function, and SPATA3 related to reproduction. Our findings revealed the distinctive genomic features of Anxi cattle in dryland environments, provided invaluable insights for further research and breed preservation, and had important significance for enriching the domestic cattle breeding gene bank.