bluuebunny/crossref_metadata_2025 huggingface dataset:
SAPID: a Strategy to Analyze Plant Extracts Taste In Depth. Application to the complex taste ofSwertia chirayita(Roxb.) H.Karst.
Authors: Rutz Adriano , Deneulin Pascale , Tonutti Ivano , Bach Benoît , Wolfender Jean-Luc
Published: January 2025

Bitterness is challenging to analyze due to the diversity of bitter compounds, variability in sensory perception, and its interplay with other tastes. To address this, we developed an untargeted approach to deconvolute the taste and molecular composition of complex plant extracts. We applied our methodology to an ethanolic extract ofSwertia chirayita(Roxb.) H.Karst., a plant known for its unique bitterness. Chemical characterization was performed through nuclear magnetic resonance spectroscopy experiments together with untargeted liquid chromatography-high resolution tandem mass spectrometry analysis coupled to a charged aerosol detector. After clustering the fractions based on chemical similarity, we performed free sensory analysis and classical descriptive analysis on each cluster. Our results confirmed the attribution of bitterness to iridoids and highlighted the role of other important compounds in the overall taste. This method offers a systematic approach to analyzing and enhancing the taste profiles of plant-based beverages.

Highlights

An untargeted method to analyze in depth plant extracts’ taste and chemical composition has been developed.

The attribution of the bitterness of an ethanolic extract ofSwertia chirayita(Roxb.) H.Karst. to well-known bitter major and minor iridoids was confirmed using untargeted methods.

Chemically informed tastingallowed to highlight other less pronounced tastes within the extract, contributing to its overall complexity.

Chemically informed tastingled to interesting insights into the sub-threshold impact on taste and taste modulating properties.

Graphical Abstract
Cholesterol deficiency directs autophagy-dependent secretion of extracellular vesicles
Authors: Yaeger Jazmine D. W. , Sengupta Sonali , Walz Austin L. , Morita Mayu , Morgan Terry K. , Vermeer Paola D. , Francis Kevin R.
Published: January 2025

Extracellular vesicle (EV) secretion is an important, though not fully understood, intercellular communication process. Lipid metabolism has been shown to regulate EV activity, though the impact of specific lipid classes is unclear. Through analysis of small EVs (sEVs), we observe aberrant increases in sEV release within genetic models of cholesterol biosynthesis disorders, where cellular cholesterol is diminished. Inhibition of cholesterol synthesis at multiple synthetic steps mimics genetic models in terms of cholesterol reduction and sEVs secreted. Further analyses of sEVs from cholesterol-depleted cells revealed structural deficits and altered surface marker expression, though these sEVs were also more easily internalized by recipient cells. Transmission electron microscopy of cells with impaired cholesterol biosynthesis demonstrated multivesicular and multilamellar structures potentially associated with autophagic defects. We further found autophagic vesicles being redirected toward late endosomes at the expense of autophagolysosomes. Through CRISPR-mediated inhibition of autophagosome formation, we mechanistically determined that release of sEVs after cholesterol depletion is autophagy dependent. We conclude that cholesterol imbalance initiates autophagosome-dependent secretion of sEVs, which may have pathological relevance in diseases of cholesterol disequilibrium.
Improvement in the enzymatic efficiency of a zinc metalloprotease through random mutagenesis approach: Studies on the enzymatic and structural properties of the mutant
Authors: Srivastava Nitin , Khare Sunil Kumar
Published: January 2025

Microbial proteases are significant enzymes acquiring 60% of the enzyme market. The heterologous expression provides higher enzymatic yield, yet such proteases possess less stability and low catalytic efficiency. A directed evolution strategy could improve protease’s properties to meet industrial demands. This study attempted the directed evolution of a recombinant metalloprotease (rsep) gene by a single round of error-prone PCR, wherein four hundred PCR were performed for random mutant gene library preparation. Eighteen amplicons (1230 bp) originated from modified PCR conditions were selected, cloned into pET22b+ plasmid, and overexpressed inEscherichia coliBL21(DE3). The recombinants showing soluble expression were screened, and one of the mutants (rsepA1) showed an 8.04-fold enhancement in the relative protease activity. It was purified to homogeneity with 92kDa molecular size. Its enzymatic properties like pH, temperature optima, and stability were comparable torsep(WT). Furthermore, it exhibited improved enzymatic efficiency (∼ 4.2-fold towards casein) and better substrate affinity. The structural elucidation studies through bioinformatic tools, sequencing data, and comparative biophysical studies (Fluorescence-CD spectra-DSC) of the wild and mutantrsepshowed increased histidine in the mutant. This probably resulted in enhanced substrate affinity and catalytic efficiency ofrsepA1, which were well correlated with the ICP-MS analysis.

Graphical Abstract
Tke5 is a novelPseudomonas putidatoxin that depolarises membranes killing plant pathogens
Authors: Velázquez Carmen , Arce-Rodríguez Alejandro , Altuna-Alvarez Jon , Rojas-Palomino Jessica , Flores-Cerón Andony , Ruiz Adrián , González-Magaña Amaia , Queralt-Martín María , Alcaraz Antonio , Albesa-Jové David , Bernal Patricia
Published: January 2025

The soil bacteriumPseudomonas putidainjects toxic proteins into neighbouring competitors including resilient phytopathogens using the Type VI secretion system (T6SS). The secretion of toxins endowsP. putidaa significant fitness advantage, allowing this biocontrol agent to thrive in plant-related polymicrobial environments and prevent phytopathogen infections. However, despite the significance ofP. putidain agriculture and biotechnology, the identity and mechanisms of action of most of its toxins remain largely unexplored. This is in part because only one of the three T6SSs identified inP. putida(K1-T6SS) is active under laboratory conditions, limiting the study of toxins secreted through the K2- and K3-T6SSs. We present the first comprehensive molecular characterisation of Tke5, a potent toxin encoded within the K3-T6SS, which represents the first functional analysis of the BTH_I2691 protein family within the cl49522 superfamily. Our findings reveal that Tke5 is a novel pore-forming toxin that disrupts bacterial membranes through selective ion transport rather than by forming large, non-specific membrane disruptions. This mechanism leads to membrane depolarisation and bacterial cell death while preserving overall membrane integrity, distinguishing it from conventional detergent-like pore-forming toxins. This discovery not only contributes to our fundamental understanding of a widespread yet understudied toxin family, but also introduces a powerful new mechanism for targeting even the most resilient phytopathogens, potentially revolutionising the biocontrol capabilities ofP. putida. Our work highlights the importance of studying bacterial toxins in the context of biocontrol, offering alternatives to combat plant pathogens without relying on traditional chemical pesticides.
Dynamic interactions of retroviral Gag condensates with nascent viral RNA at transcriptional burst sites: implications for genomic RNA packaging
Authors: Kaddis Maldonado Rebecca J. , Parent Leslie J.
Published: January 2025

Retroviruses are responsible for significant pathology in humans and animals, including the acquired immunodeficiency syndrome and a wide range of malignancies. A crucial yet poorly understood step in the replication cycle is the recognition and selection of unspliced viral RNA (USvRNA) by the retroviral Gag protein, which binds to the psi (Ψ) packaging sequence in the 5’ leader, to package it as genomic RNA (gRNA) into nascent virions. It was previously thought that Gag initially bound gRNA in the cytoplasm. However, previous studies demonstrated that the Rous sarcoma virus (RSV) Gag protein traffics transiently through the nucleus, which is necessary for efficient gRNA packaging. These data formed a strong premise for the hypothesis that Gag selects nascent gRNA at transcription sites in the nucleus, the location of the highest concentration of USvRNA molecules in the cell. In support of this model, previous studies using fixed cells infected with RSV revealed that Gag co-localizes with large USvRNA nuclear foci representing viral transcriptional burst sites. To test this idea, we used single molecule labeling and imaging techniques to visualize fluorescently-tagged, actively transcribing viral genomes, and Gag proteins in living cells. Gag condensates were observed in the nucleus, transiently co-localized with USvRNA at transcriptional burst sites, forming co- localized viral ribonucleoprotein complexes (vRNPs). These results support a novel paradigm for retroviral assembly in which Gag traffics to transcriptional burst sites and interacts through a dynamic kissing interaction to capture nascent gRNA for incorporation into virions.
Sparse modeling of interactions enables fast detection of genome-wide epistasis in biobank-scale studies
Authors: Stamp Julian , Smith Samuel Pattillo , Weinreich Daniel , Crawford Lorin
Published: January 2025

The lack of computational methods capable of detecting epistasis in biobanks has led to uncertainty about the role of non-additive genetic effects on complex trait variation. The marginal epistasis framework is a powerful approach because it estimates the likelihood of a SNP being involved in any interaction, thereby reducing the multiple testing burden. Current implementations of this approach have failed to scale to large human studies. To address this, we present the sparse marginal epistasis (SME) test, which concentrates the scans for epistasis to regions of the genome that have known functional enrichment for a trait of interest. By leveraging the sparse nature of this modeling setup, we develop a novel statistical algorithm that allows SME to run 10 to 90 times faster than state-of-the-art epistatic mapping methods. In a study of blood traits measured in 349,411 individuals from the UK Biobank, we show that reducing searches of epistasis to variants in accessible chromatin regions facilitates the identification of genetic interactions associated with regulatory genomic elements.
A temporal coordination between Nodal and Wnt signalling governs the emergence of the mammalian body plan
Authors: Dias André , Pascual-Mas Pau , Torregrosa-Cortés Gabriel , McNamara Harold M. , Wehmeyer Alexandra E. , Arnold Sebastian J. , Martinez Arias Alfonso
Published: January 2025

Nodal and Wnt signalling play an important role in the emergence of the mammalian body plan, primarily by orchestrating gastrulation and primitive streak formation. While the literature suggests that these pathways cooperate to build the primitive streak, their individual contributions remain poorly understood, largely due to pleiotropic effects observed when key pathway components are knocked out in mouse embryos. In this study, we used gastruloids - a non-integrated stem cell model of mammalian gastrulation - to dissect the roles of Wnt and Nodal signalling. We found that Wnt/β-catenin signalling drives a genetic program characteristic of the late primitive streak, promoting the development of posterior body structures in a time and dose-dependent manner. Conversely, Nodal signalling activates a distinct developmental module resembling the early primitive streak. By engineering gastruloids with elevated Nodal signalling, we demonstrate that the decreasing temporal gradient of Nodal activity in the mouse primitive streak likely plays a pivotal role in establishing the anterior body plan, with higher Nodal levels producing more anterior structures in a concentration-dependent manner. Our findings suggest that rather than cooperating, Nodal and Wnt signalling act antagonistically, initiating distinct developmental modules within the primitive streak. This antagonism is likely the core mechanism driving the early body plan in mammals. Additionally, our results also lead to the suggestion that the gastruloid system models the primitive streak and reveals its self-organizing potential.
Epigenetic phase variation in the gut microbiome enhances bacterial adaptation
Authors: Ni Mi , Fan Yu , Liu Yujie , Li Yangmei , Qiao Wanjin , Davey Lauren E. , Zhang Xue-Song , Ksiezarek Magdalena , Mead Edward , Touracheau Alan , Jiang Wenyan , Blaser Martin J. , Valdivia Raphael H. , Fang Gang
Published: January 2025

The human gut microbiome within the gastrointestinal tract continuously adapts to variations in diet, medications, and host physiology. A central strategy for genetic adaptation is epigenetic phase variation (ePV) mediated by bacterial DNA methylation, which can regulate gene expression, enhance clonal heterogeneity, and enable a single bacterial strain to exhibit variable phenotypic states. Genome-wide and site-specific ePV have been well characterized in human pathogens’ antigenic variation and virulence factor production. However, the role of ePV in facilitating adaptation within the human microbiome remains poorly understood. Here, we comprehensively cataloged genome-wide and site-specific ePV in human infant and adult gut microbiomes. First, using long-read metagenomic sequencing, we detected genome-wide ePV mediated by complex structural variations of DNA methyltransferases, highlighting the ones associated with antibiotics or fecal microbiota transplantation. Second, we analyzed an extensive collection of public short-read metagenomic sequencing datasets, uncovering a greater prevalence of genome-wide ePV in the human gut microbiome. Third, we quantitatively detected site-specific ePVs using single-molecule methylation analysis to identify dynamic variations associated with antibiotic treatment or probiotic engraftment. Finally, we performed an in-depth assessment of anAkkermansia muciniphilaisolate from an infant, highlighting that ePV can regulate gene expression and enhance the bacterial adaptive capacity by employing a bet-hedging strategy to increase tolerance to differing antibiotics. Our findings indicate that epigenetic modifications are a common and broad strategy used by bacteria in the human gut to adapt to their environment.
Digital Health Technologies for Accessing Contraceptive Services among Young People in Sub-Saharan Africa: A Scoping Review Protocol
Authors: Kyamulabi Agnes , Oberle Eva , Olisaeloka Lotenna , Kamya Innocent , Nyesigire Ingrid , Abdulai Abdul-Fatawu , Norman Wendy
Published: January 2025

Objective

This scoping review aims to examine and synthesize existing literature on the use of digital health technologies, with a focus on the extent and types of technologies used to access contraceptive services among young people in Sub-Saharan Africa (SSA).

Introduction

Globally, digital health technologies have emerged as pivotal tools in addressing contraceptive needs among young people. In SSA, where traditional healthcare systems often face numerous challenges, these technologies offer innovative solutions to improve access to contraceptive services. Despite growing interest in digital health technologies, comprehensive reviews on contraceptive access among young people in SSA are still lacking. Most existing studies focus broadly on sexual and reproductive health (SRH) or adult populations, leaving a gap in understanding the unique needs and experiences of young people using digital technologies for contraception services. It is unclear how much research has been conducted to examine how these technologies can facilitate contraceptive use, which technologies are used and why, where this evidence is concentrated within SSA, and the prevailing gaps. Therefore, we propose to undertake a scoping review.

Inclusion criteria

This scoping review will include studies focusing on young people aged 10-24 years in SSA, addressing access challenges to contraceptive services within this age group. The review will consider client-facing digital health technologies. All methodological approaches and designs will be included. Reviews, protocols, conference papers, policy briefs and studies conducted outside SSA will be excluded.

Methods

The review will apply the comprehensive search strategy recommended by JBI. The initial limited search of MEDLINE (Ovid) and CINAHL Complete (EBSCOhost) was conducted with guidance from the University Librarian. This informed the selection of keywords, along with index terms, to develop a full search strategy for MEDLINE (Ovid), CINAHL Complete (EBSCOhost), Scopus, Compendix Engineering Village, and IEEE Xplore. The scoping review shall also use supplementary resources such as google scholar, and African Journal online (AJOL). We will also review the reference lists of articles that meet the inclusion criteria to ascertain articles that were not returned by the search criteria. Data will be presented using tables and charts, accompanied by a narrative summary. This scoping review was registered in Open Science Framework:https://doi.org/10.17605/OSF.IO/5QJ6P
Identification of critical factors of the replication stress response in human cells
Authors: Janssen Louise M.E. , Baltasar Perez Empar , Vaarting Chantal , Mazouzi Abdelghani , Raaben Matthijs , Brummelkamp Thijn R. , Medema René H. , Raaijmakers Jonne A.
Published: January 2025

High fidelity of replication is important to preserve genomic integrity and ensure healthy progeny. Perturbations of replication, also known as replication stress, is frequently observed in cancer cells and is considered a cancer cell-specific trait. Although replication stress drives genomic instability and tumor progression, it also generates a targetable cancer-specific vulnerability. In order to identify potential therapeutic targets in cancer cells that experience replication stress, we performed a genome wide genetic screen in human HAP1 cells challenged with low doses of replication stress-inducing drugs. We identified a large set of genes that specifically hamper cell survival in the context of replication stress. In addition to well-known players in the replication stress response and DNA repair, such as RNASEH1, BRIP1, and MDC1, we identified several genes with no prior described role in DNA replication, damage tolerance or repair. We validated that the loss of GIGYF2, HNRNPA2B1, and SUMO2 renders cells more vulnerable to replication stress. For GIGYF2 and SUMO2, we could implicate a role in homologous recombination. Taken together, our replication stress screen identified several known as well as some novel factors that protect against the toxic implications of replication stress. These factors could entail potential therapeutic targets for cancer cells experiencing replication stress.
Gut microbiota-derived lithocholic acid leads to intestinal barrier dysfunction via LPCAT1 in irritable bowel syndrome
Authors: Zhai Lixiang , Li Baohua , Xu Shujun , Peng Jiao , Zhang Yingdi , He Jiayu , Bao Gengyu , Li Yunlyu , Deng Huan , Zhao Ling , Ning Ziwan , Lyu Junfang , Lin Chengyuan , Xavier Wong Hoi Leong , Bian Zhaoxiang , Xiao Haitao
Published: January 2025

Intestinal barrier dysfunction is widely observed in patients with irritable bowel syndrome (IBS) and significantly contributes to the persistence of IBS symptoms. The association between gut dysbiosis and the pathogenesis of IBS, as well as its connection to intestinal barrier dysfunction, has been established. However, the precise roles of gut bacteria in inducing intestinal barrier dysfunction and the underlying mechanisms of IBS remain unclear. In the present study, we showed that microbiota-derived lithocholic acid (LCA) is positively associated with intestinal barrier dysfunction biomarkers in patients with IBS-D. We found excessive LCA disrupts intestinal barrier function in normal mice and aggravates colonic inflammation in a mouse model of experimental colitis. Mechanistically, LCA modulates phospholipid metabolism and compromises the intestinal barrier by directly activating lysophosphatidylcholine acyltransferase 1 (LPCAT1). Our results demonstrated that LCA significantly upregulates LPCAT1 expression, and its overexpression leads to intestinal barrier dysfunction and promotes colonic inflammation via the activation of matrix metalloproteinase-1 (MMP1). Furthermore, we found inhibition of LPCAT1 ameliorates intestinal barrier dysfunction, diarrhea symptoms and colonic inflammation in LCA-treated mice and those with experimental colitis, highlighting LPCAT1 as a potential therapeutic target for gastrointestinal diseases characterized by intestinal barrier dysfunction and colonic inflammation. Additionally, our findings showed a positive correlation between LPCAT1 and biomarkers of intestinal barrier dysfunction and colonic inflammation in patients with ulcerative colitis. Collectively, these findings reveal the essential role of gut microbiota-derived LCA in the development of intestinal barrier dysfunction by activating LPCAT1, which worsens diarrhea symptoms in IBS and colonic inflammation in IBD. Inhibiting LPCAT1, therefore, presents a promising therapeutic strategy for both IBS-D and ulcerative colitis. This study provides insights into the molecular mechanisms involving LCA and an associated gut dysbiosis pattern in the pathogenesis of IBS-D, while also identifying new therapeutic targets aimed at maintaining intestinal homeostasis in gastrointestinal diseases, particularly in reducing IBD risks among the IBS-D population.
Comparing Clinicopathologic Features and Outcomes Between Young Children, Adolescents, and Adults with Rhabdomyosarcoma at a Single Institution
Authors: Boyd Karla , Leelatian Nalin , Morotti Raffaella , Deshpande Hari , Christison-Lagay Emily , McCollum Sarah , Shabanova Veronika , Pashankar Farzana , Vasquez Juan C.
Published: January 2025

Background

There are limited data comparing clinical and pathologic features and outcomes of rhabdomyosarcoma (RMS) between young children, adolescent/young adults (AYAs), and adults.

Design/Methods

We performed a retrospective chart review of patients with RMS treated at our institution between 2000 and 2017. We compared clinical and pathologic features, treatment modalities, and outcomes among three different age groups (young children: <15 years of age, AYA: 15-39 years of age, and older adults: >39 years of age).

Results

Among 65 patients, 33 (50.8%) were young children, 14 (21.5%) were AYAs, and 18 (27.7%) were older adults. Head and neck was the most common tumor site among young children, AYAs tumor sites were variable, while extremities were the most frequent location for adults. AYAs were more likely to have stage 4 disease at presentation (64.3% vs. 21.2% in children, p=0.01, and vs. 27.8% in adults, p=0.08). Similarly, clinical group and risk classifications were higher among AYAs as compared to the other two age groups. Tumors in children were alveolar and embryonal histology, while AYAs primarily developed alveolar RMS. Older adults had tumors with diverse histologies, including pleiomorphic and spindle cell. Children and AYAs received multimodal therapy, but a subset of adults did not. Five-year overall survival (OS) varied by age at diagnosis (p=0.001), with highest OS among young children (81.8%) following by adults (50.0%), with the lowest OS among AYAs (14.29%).

Conclusion

This study highlights the need for ongoing collaboration between pediatric and adult multidisciplinary teams to improve outcomes for patients with RMS across the age spectrum.
INSIGHTFUL: Insight Generation through Clinical Annotation, Analysis, and Modeling of Suicide-Related Factors towards Understanding and Lifesaving
Authors: Li Zehan , Vieira Rodrigo M , Fu Sunyang , Hu Yan , Wang Wanjing , Wen Andrew , Lane Scott , Selek Salih , Shahani Lokesh , Xu Hua , Soares Jair C , Liu Hongfang , Huang Ming
Published: January 2025

Objective

Suicide is a critical medical and public health challenge, particularly among individuals with mental illnesses in safety-net hospitals. To uncover insights about suicidality embedded in unstructured clinical notes, we propose to annotate, analyze, and model a corpus for suicidality understanding and lifesaving.

Methods

A multidisciplinary panel developed an annotation guideline to capture four key suicide-related factors: Suicidal Ideation (SI), Suicide Attempt (SA), Exposure to Suicide (ES), and Non-Suicidal Self-Injury (NSSI). We created an annotated corpus of 500 notes through a clinically validated annotation process and performed cohort analysis to characterize demographic and suicidal distributions. A large language model was deployed for automatic classification.

Results

The annotated corpus was created with a Cohen’s Kappa of 0.95 and further de-identified for data sharing. Most notes (79.4%) contained one (34.4%) or more (45%) suicide-related labels, with SI and SA co-occurrence as the most frequent combination (35.6%), which demonstrates significant overlap. The cohort was characterized with a mean age of 33.4, 51.7% male, and 75.8% singles. Prevalent stressors included unemployment (24.2%), homelessness (12.0%), limited healthcare access (5.4%), and legal challenges (5.0%). We identified four key insights to improve documenting suicidality, including implicitness, confliction, ambiguity, and definition coverage incompleteness. The baseline model achieved a micro-averaged F1 score of 0.70, demonstrating satisfying performance in multi-label classification.

Conclusion

The near-perfect inter-annotator agreement underscores the proposed annotation process and data quality. Cohort analysis highlights the distribution and documentation insights of suicidality. Data modeling demonstrates the potential of insight generation via AI-powered methods for mining large-scale clinical notes.
Evaluation of the Prognostic Value of Four ECM-Associated Genes in Recurrence and Metastasis of Colorectal Cancer
Authors: Avcıoğlu Seçil Durel , Charyeva Sulgun , Erdoğan Beyza Doğanay , Kaymaz Özlem , Durhan Abdullah , Aksel Bülent , Yazıcı Ozan , Savaş Berna , Ensari Arzu , Kıvrak Hale , Engin Evren Doruk , Belder Nevin , Özdağ Hilal
Published: January 2025

Colorectal cancer is a significant public health issue due to its high incidence and high mortality rate, especially when diagnosed late. Identifying new biomarkers that can predict the diagnosis and prognosis of CRC is critical to reducing the mortality rate of the disease. This study tested the relationship of four extracellular matrix genes (COL1A1, COL5A1, THBS2 and FN1) with CRC prognosis at the mRNA and protein levels. Our previous studies identified these genes as candidate prognostic biomarkers for CRC. They were analysed in two cohorts: retrospective (130 CRC tumours and 70 healthy colon tissues) and prospective (160 paired tumours and normal tissues with 180 CRC serum samples).

Accordingly, in the retrospective cohort, COL1A1 (p>0.0001), COL5A1 (p>0.0001), THBS2 (0.0001) and FN1 (0.001) were expressed at higher levels in tumours compared to controls by qRT-PCR and in metastatic cases compared to non-metastatic cases. In the same cohort, immunohistochemistry analysis showed that increasing protein levels of COL1A1 and FN1 correlated with mRNA levels. In addition, high COL1A1 mRNA levels were associated with OS (p>0.011), RFS (p>0.0001), and DMFS (p>0.0001), high COL5A1 mRNA levels were associated with OS (0.042), RFS (0.013), DMFS (p>0.003) and high FN1 levels were associated with DMFS (p>0.039). In the prospective cohort, COL1A1, COL5A1 and THBS2 were found to be higher in tumour tissue compared to matched normal tissue and in metastatic tumours compared to primary tumours by qRT-PCR in 160 tumours and matched normal tissues. In this cohort, FN1 levels were unexpectedly higher in normal tissues than in tumour tissues. In the prospective cohort, where 180 CRC serum samples were also tested by ELISA, COL1A1 (p>0.0001), COL5A1 (p>0.05), and THBS2 (p>0.05) levels were higher in metastatic cases than in the sera of non-metastatic cases. As a result, this study associated COL1A1, COL5A1 and THBS2 genes, which have different data on their prognostic effects in the literature, with poor prognosis of CRC at both mRNA and protein levels.
Genetic variants within silencer elements contribute to human blood cell traits
Authors: Tan Minkang , van Weerd Jan , Yavas Alper , Pang Baoxu
Published: January 2025

Genome-wide association studies (GWAS) have identified numerous non-coding loci associated with human complex traits and diseases. However, assigning the functional impacts to the underlying variants remains challenging. In this study, we performed high-throughput ReSE screening to characterize the effects of 14,720 fine-mapped causal non-coding SNPs associated with 15 diverse blood traits on the potential silencer activity. By prioritizing non-coding variants that confer allelic imbalances in silencer activity, we identified epigenomic signatures of silencer-related variants and assessed their heritability contributions to specific blood traits. We conducted mechanistic studies on individual silencer variants and characterized the transcriptional factors (TF) that may recognize the silencer elements harboring the blood traits-related GWAS variants. We showed the silencer activity of GWAS variantsrs4808806which is related to red blood cell distribution width (RDW) andrs10758656which is associate with mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) traits. Our study underscores the importance of investigating the silencer-activity-related variants in post-GWAS functional studies.
Placental Nutrient Transport and Signaling in a Guinea Pig Model of Fetal Growth Restriction with Repeated Placental Nanoparticle-mediated IGF1 Treatment
Authors: Davenport Baylea N , Wilson Rebecca L , Williams Alyssa A , Jones Helen N
Published: January 2025

Roughly 10% of all pregnancies are affected by fetal growth restriction (FGR). The primary etiology of FGR is placental insufficiency: the placenta not providing the appropriate amount of nutrients and oxygen to the fetus. There is currently no treatment for FGR or placental insufficiency. Because of the placentas pivotal role in FGR and supplying nutrients to the fetus, it offers an excellent target for therapeutic intervention. Using a guinea pig maternal nutrient restriction model and a repeated placental nanoparticle-mediated IGF1 treatment, placental IGF1 signaling and nutrient transport pathways were characterized to understand changes with FGR and treatment. This study elucidates the signaling mechanisms in which repeated placental nanoparticle-mediated IGF1 treatment leads to correct fetal growth. Overall, this study resulted in sex-specific kinase signaling and nutrient transporter changes within the placenta in both FGR and treatment groups. Combined with our previous studies using this treatment, we demonstrate the basic molecular signaling of this treatment and recapitulate the plausibility of this therapy for future human translation.
Selective Targeting of Pathogenic Tau Seeds via a Novel VHH
Authors: Gupta Ankit , Liu Richard , Keely Devin , Sunderman Victoria , Tak Yogesh , Kostantoulea Katerina , Terpack Sandi Jo , White Charles L. , Russ William P. , Rizo Josep , Louros Nikolaos , Vaquer-Alicea Jaime , Diamond Marc I.
Published: January 2025

In Alzheimer’s disease (AD) and related tauopathies, progressive pathology has been linked to prion mechanisms, whereby ordered tau assemblies, or “seeds,” form in one cell and transit to neighboring or connected cells where they serve as templates for their own replication. Despite intensive efforts to develop early diagnosis and effective treatment, none has emerged. This is due partly to the structural heterogeneity of tau seeds and limitations in selectively targeting their pathogenic conformations. Here we report the discovery of a camelid variable heavy domain of heavy chain (VHH) that preferentially binds tau seeds of AD, corticobasal degeneration (CBD), and PS19 tauopathy mouse brains. From a published synthetic VHH yeast display library, we identified VHH clones that bound 2N4R tau monomer. After counter-screening for immunoprecipitation of seeding from human brain, we identified two seed-selective anti-tau VHH—VHH(510) and VHH(50)—that preferentially bound pathological tau. We enhanced the stability of these VHHs through framework mutations without affecting their seed-binding characteristics. We characterized VHH(510) in detail, determining that it binds the carboxy terminus of tau, maintains robust seed avidity even in the presence of competing monomer, and stains pathological tau inclusions in mouse and human AD tissues. These results highlight the power of seed-selective VHH to bind pathogenic tau, paving the way for future therapeutic and diagnostic applications across a wide range of neurodegenerative disorders.
Unveiling the dark side of virtual work climate: the mediating role of blurred work-nonwork boundaries
Authors: Li Rui-Xiao , Lim Yet-Mee , Tan Garry Wei-Han
Published: January 2025

Purpose

This research investigates the dark sides of virtual work climate by examining how blurred work-nonwork boundaries serve as a turning point leading to amotivation at work.

Design/methodology/approach

This quantitative study involved 487 employees from small and medium-sized enterprises in China who completed a self-administered questionnaire. Data were analyzed using the partial least squares structural equation modeling (PLS-SEM) method.

Findings

The study found that virtual work climate positively influences workplace flexibility. However, blurred work-nonwork boundaries mediate the relationship between workplace flexibility and psychological demands, transforming the positive effects of virtual work climate in terms of flexibility into negative outcomes. Psychological demands from both work and nonwork domains contribute to amotivation at work.

Practical implications

The study provides practical insights for managers on satisfying employees’ needs for flexible working arrangements within a virtual work climate by advocating for clear policies that establish distinct work-nonwork boundaries, thereby ensuring employee motivation is not compromised.

Originality/value

This research unveils the dark sides of the virtual work climate, extending the self-determination through the lens of the “too-much-of-a-good-thing” theory. The findings suggest that blurred work-nonwork boundaries may be the turning point where the virtual work climate leads to amotivation at work.
Driving regional advancement: exploring the impact of science and technology parks in the outermost regions of Europe
Authors: Lopes João M. , Gomes Sofia , Ferreira João J.M. , Dabic Marina
Published: January 2025

Purpose

Europe’s outermost regions are often geographically isolated, and they face challenges when it comes to fostering innovation. This study aims to evaluate the impact of Science and Technology Parks (STPs) on the stimulation of innovation performance and the regional development of innovation in the outermost European regions. This study contributes to the development and interpretation of STP literature, which is especially relevant for policymakers operating within these regions.

Design/methodology/approach

We collected the data from six Regional Innovation Scoreboard reports (RIS, 2012; RIS, 2014; RIS, 2016; RIS, 2017; RIS, 2019; and RIS 2021), available at https://ec.europa.eu, for the following outermost regions of Europe: the Autonomous Regions of Azores and Madeira (Portugal), the Canary Islands (Spain) and the Outermost Regions of France, which encompass Martinique, Mayotte, Guadeloupe, French Guiana, Saint-Martin and Reunion Island.

Findings

The results demonstrate that, for STPs to positively impact regional policies for innovation and regional development, policymakers must make significant investments into research and development (R&D). The outermost European regions display characteristics that negatively affect innovation performance and regional development. Furthermore, we found that innovative products and services are negatively affected by these regions, as they deploy only a limited number of resources. We also conclude that the impact of STPs on the outermost European regions depends on the policies of regional governments. STPs represent important inputs to formulating and implementing innovation strategies for regional development.

Research limitations/implications

This study has some limitations. This research only analyses the European Union's (EU’s) outermost regions, and we have only included data extracted from the Regional Innovation Scoreboard from 2007 to 2021. Disaggregated data for the five outermost regions in France was not available. This would have increased the sample and made the results even more robust, had the information been available.

Practical implications

The results propose that regional actors in the outermost regions (industry–government–academia) better articulate their resources (which are more scarce) and their priorities with regard to Science, Technology and Innovation, thus accelerating innovation and development of their regions.

Originality/value

In this panel data study, we adopt a methodology that enables the evaluation of STP performance under different levels of intensity of gross domestic expenditure on research and development activities in the context of the RIS. In this study, the RIS refers to the peripheral regions of the EU. This study therefore aims to evaluate the impact of STPs in stimulating innovation performance and regional development in the outermost regions of Europe.
Historical geopolitical risk acts and world crude oil production: evidence from the international level
Authors: Sweidan Osama D.
Published: January 2025

Purpose

The purpose of this study is to empirically investigates the influence of geopolitical risk acts (GPR) on world crude oil production. GPRs are a proxy for waging wars and military actions, thus it is expected to have a clear impact on world crude oil production (WCOP).

Design/methodology/approach

The current study formulates a theoretical model, and its parameters are estimated using three methodologies – traditional autoregressive distributed lag (ARDL) model, Dynamic ARDL model, and Frequency domain causality test – across the period 1973–2023 to ensure robust findings.

Findings

The results illustrate that GPRs constrain the global crude oil supply. The final impact relies on the positive interaction term between GPRs and international economic activity from one side and the negative interaction term with crude oil prices from the other. Likewise, the findings show that geopolitical threats reduce producing crude oil. Furthermore, this research deliberates on policy implications stemming from these findings.

Originality/value

Examining existing literature reveals a gap in understanding the relationship between geopolitical risk and crude oil production. Most of the studies in this research strand focus on investigating the impact on oil price volatility.
Artificial intelligence for personalized learning: a systematic literature review
Authors: Hardaker Glenn , Glenn Liyana Eliza
Published: January 2025

Purpose

The purpose of this systematic literature review is to identify the antecedents that have enabled the adoption of artificial intelligence (AI) in Higher Education (HE) institutions at both a macro and micro level. The term adoption is in reference to the diffusion of technology that is actively chosen for use by the targeted demographic. Within the context of this paper, adoption is largely referring to the factors that influence the acceptance and use of AI as a tool for personalized learning.

Design/methodology/approach

To develop our understanding and appreciation of the valuable impact that AI potentially has upon personalized learning the following systematic literature review was conducted. An acceptable systematic literature review is a comprehensive method of fully analysing and evaluating all available research in the chosen area or specific research query.

Findings

The findings from this study have particular implications for personalized learning in the adoption and diffusion of AI and an increasing integration of macro, structural, and micro, individual. Developing and managing AI in education is seen, from the literature, to becoming more embedded in the teaching and learning process. The paper identifies the following: antecedents that supports the adoption of AI for personalized learning; application of AI technologies in the teaching and learning process; AI technologies that enable personalized instruction and learning; generative AI that supports intuitive learning through tracking data.

Originality/value

Personalized learning remains focused on customizable “choice-driven” learning and education. In addition, personalized learning and instruction is defined as being a responsive and structured method that adapts to each individual learner’s method of learning so that all may achieve their capabilities and actively participate. This solidifies the intrinsic connection between teaching and learning through personalized technologies such as AI.
Regional heterogeneities in returns to education in Zambia: a quantile regression analysis
Authors: Nsokolo Denny S. , Simo-Kengne Beatrice , Chama-Chiliba Chitalu Miriam
Published: January 2025

Purpose

This study determines the existence of regional heterogeneities in returns to education in Zambia. It seeks to analyse the differential impact of education on wages across different geographical regions of Zambia. Adopting a regional approach, the study employs novel empirical methods to understand the pecuniary benefits of education at the sub-national level.

Design/methodology/approach

The study analyses data from Zambia’s 2021 Labour Force Survey. It employs modified human capital models and quantile regression techniques to examine how returns to education differ across regions and the wage distribution.

Findings

Results show a distinctive heterogeneous pattern in which returns to education are higher in urban regions, followed by peri-urban, and lowest in the rural region. Results further show that returns to education increase with the level of education and are highest at the tertiary level. Quantile regression estimates reveal that returns to education vary across income levels within regions, suggesting a necessity for tailored policy interventions. Additionally, individuals’ health conditions display direct effects on their earnings potential.

Originality/value

This study adopts a modified human capital model to account for the health dimension, which has received less attention in past returns to education research. Furthermore, a regional approach is employed to capture within-country variations necessary for designing policy interventions aimed at addressing region-specific challenges.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/IJSE-03-2024-0262
The GreenComp Evaluation Roadmap: a roadmap for in-depth holistic evaluation of the integration of the GreenComp framework in higher-education curricula
Authors: Mertens Anouk , Eppinga Maarten B. , Arens Patrick , de Scisciolo Tobia , John Nigel , Sultan Salys , Buys Nadine , Mijts Eric N.
Published: January 2025

Purpose

The GreenComp framework identifies 12 competences for sustainability as common ground for higher-education curricula. The framework can be used for self-assessment and the review of curricula. However, a step-by-step method to conduct such a self-assessment is not yet available for the GreenComp framework specifically. Therefore, the authors present the GreenComp Evaluation Roadmap allowing to evaluate the extent to which the frameworks’ competences for sustainability are integrated in higher-education curricula. The application of the GreenComp Evaluation Roadmap to a curriculum taught at the University of Aruba, allows to report on the benefits, limitations and future potential of the approach.

Design/methodology/approach

The proposed mixed-method approach combines hybrid qualitative and quantitative data collection on the integration of the 12 competences for sustainability of the GreenComp framework in higher-education curricula. The authors showcase its potential through application of the GreenComp framework as an evaluation tool to a science, technology, engineering and mathematics-based bachelor program taught at the University of Aruba.

Findings

The GreenComp Evaluation Roadmap not only allows for an evaluation of the curriculum and identification of competence gaps. It also supports educators to conduct a self-reflection on individual course(s) and the program as a whole. The paper shows promising results that the roadmap developed could be a reproducible approach. Moreover, it provides guidance to other higher education institutes for self-evaluation and self-reflection on how the competences for sustainability are integrated in their curricula and how this can be enhanced in the future.

Originality/value

The need to integrate sustainability throughout higher-education curricula is broadly recognized. The GreenComp Evaluation Roadmap contributes to the literature by offering a methodological approach to evaluate the integration of the 12 competences for sustainability throughout a curriculum.
Predicting the churn patterns of monetizers and non-monetizers: exploring the influence of behavioral variability in churn prediction
Authors: Wu Ruei-Yan , Hu Ya-Han , Chou En-Yi
Published: January 2025

Purpose

Although prior research has employed various variables to predict player churn, the dynamic evolution of the behavioral patterns of players has received limited attention. In this study, churn prediction models are developed by incorporating the progress level, in-game purchase, social interaction, behavioral pattern and behavioral variability (BV) of players in social casino games (SCGs). The study distinguishes churn prediction between two player groups: monetizers and non-monetizers.

Design/methodology/approach

This study employs three machine learning techniques—logistic regression, decision trees and random forests—using real-world player data from an SCG company to construct churn prediction models. Two experiments were conducted. In Experiment 1, BV was combined with four other variable categories to effectively predict churn behaviors across all players (n = 52,246). In Experiment 2, churn prediction models were developed separately for monetizers (n = 16,628) and non-monetizers (n = 35,618).

Findings

The findings from Experiment 1 indicate that incorporating BV significantly improves the overall performance of churn prediction models. Experiment 2 demonstrates that churn prediction models achieve better performance and predictive accuracy for monetizers and non-monetizers when BV is calculated over the 3-day to 7-day and 7-day to 14-day windows, respectively.

Originality/value

This study introduces BV as a novel variable category for churn prediction, emphasizing within-person variability and demonstrating its effectiveness in enhancing model performance. Churn prediction models were independently constructed for monetizers and non-monetizers, utilizing different time windows for variable extraction. This approach improves predictive performance and highlights key differences in critical variables influencing churn across the two player groups. The findings provide valuable insights into churn management strategies tailored for monetizers and non-monetizers.