bluuebunny/crossref_metadata_2025 huggingface dataset:
Individualized Alpha-tACS for Modulating Pain Perception and Neural Oscillations: A Sham-Controlled Study in Healthy Participants
Authors: Fathi Yaser , Dissassuca Françoise , Ricci Gloria , Liberati Giulia
Published: January 2025

Pain encompasses sensory, affective, and cognitive dimensions, with neural oscillations increasingly recognized as key mechanisms in their integration. However, the underlying processes remain inadequately understood. Transcranial alternating current stimulation (tACS) offers a promising tool for modulating these oscillations, yet the widespread reliance on ‘one-size-fits-all’ tACS protocols with fixed frequencies has led to limited and contradictory findings on its efficacy in pain treatment. In this study, we employed individualized tACS at individual peak alpha frequency (IAF) over the primary motor cortex (M1) contralateral to the dominant arm of 38 healthy participants, in a within-subject, sham-controlled design, to investigate its effects on pain perception and neural oscillations. Sustained and periodic 0.2 Hz thermonociceptive stimuli were applied to the dominant forearm before and after tACS. We measured participants pain perception and heat pain thresholds (HPT) before and after tACS stimulation. Scalp electroencephalography (EEG) measurements were used to measure neural activity during thermonociceptive stimuli. To calculate IAF, we used a discriminative approach based on independent component analysis (ICA) to separate sensorimotor related IAF (SM-IAF). The results revealed an overall increase in pain perception and a decrease in HPT in both sham and active conditions, with no significant interactions between conditions. However, a trend toward reduced sensitization post-tACS was observed. Exploratory analyses indicated a significant tACS effect on HPT in women. Furthermore, a significant correlation was found between SM-IAF and HPT. These findings provide a novel perspective on advancing individualized neuromodulation approaches for pain and neurobiological disorders.
Classifying Mild Cognitive Impairment from Normal Cognition: fMRI Complexity Matches Tau PET Performance
Authors: Jann Kay , Park Gilsoon , Kim Hosung ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: January 2025

Background

Tau protein accumulation is closely linked to synaptic and neuronal loss in Alzheimer’s disease (AD), resulting in progressive cognitive decline. Although tau-PET imaging is a direct biomarker of tau pathology, it is costly, carries radiation risks, and is not widely accessible. Resting-state functional MRI (rs-fMRI) complexity—an entropy-based measure of BOLD signal variation—has been proposed as a non-invasive surrogate biomarker of early neuronal dysfunction associated with tau pathology.

Objectives

To determine whether fMRI-based brain complexity (sample entropy and multiscale entropy) can match or exceed tau-PET in classifying cognitively normal (CN) versus cognitively impaired (MCI/AD) individuals. And to investigate and compare the most influential network regions-of-interest (ROIs) for classification between fMRI complexity and tau-PET, thereby identifying key neuroanatomical correlates of AD-related changes.

Design

A cross-sectional study employing 3D convolutional neural network (CNN) classification with five-fold cross-validation and leave-one-network-out analysis.

Setting

Data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database.

Participants

One hundred forty-seven older adults (age 72.5 ± 7.5 years), including 95 CN, 45 MCI, and 7 AD.

Measurements

We created whole-brain complexity maps from rs-fMRI and standardized uptake value ratio (SUVR) maps from tau-PET. Each modality was separately fed into CNN classifiers. Region-based analyses (leave-one-network-out) were performed to identify critical ROIs for classification.

Results

fMRI complexity showed classification accuracy comparable to tau-PET yet surpassed it in F1-score (0.64 vs. 0.61) and area under the curve (AUC; 0.73 vs. 0.67). Salience and dorsal attention networks contributed most to fMRI-based classification, and a dorsal attention network contributed most to tau-PET-based classification.

Conclusions

fMRI complexity performs similarly to tau-PET in detecting cognitive impairment related to AD and identifies partially distinct critical ROIs, suggesting an alternative, radiation- free imaging biomarker for earlier detection and broader clinical application.
Effects of age in the strategic control of recollected content as reflected by modulation of scene reinstatement
Authors: de Chastelaine Marianne , Srokova Sabina , Monier Sarah , Olivier Joshua M. , Rugg Michael D.
Published: January 2025

A previous study employing fMRI measures of retrieval-related cortical reinstatement reported that young, but not older, adults employ ‘retrieval gating’ to attenuate aspects of an episodic memory that are irrelevant to the retrieval goal. We examined whether the weak memories of the older adults in that study rendered goal-irrelevant memories insufficiently intrusive to motivate retrieval gating. Young and older participants studied words superimposed on rural or urban scenes, or on pixelated backgrounds. To strengthen memory for background information, word-image pairs were studied twice, initially centrally, and then in one of three locations. During scanning, one retrieval test probed memory for the test words’ studied backgrounds and another test assessed memory for their location. Background memory performance was markedly higher than in the prior study. Retrieval gating was examined in two scene-selective regions of interest, the parahippocampal place area (PPA) and the medial place area (MPA). In the background task, robust retrieval-related scene reinstatement effects were identified in both age groups. These effects were attenuated (‘gated’) in the location task in the young age group only, replicating the prior finding. The results did not differ when the two groups were sub-sampled to match strength of scene reinstatement when scene information was goal relevant. The findings indicate that older adults’ failure to gate goal-irrelevant scene information does not reflect age differences in memory strength and may instead reflect an age-related decline in top-down inhibitory control.
Compromised 2-start zigzag chromatin folding in immature mouse retina cells driven by irregularly spaced nucleosomes with short DNA linkers
Authors: Kable Brianna , Portillo-Ledesma Stephanie , Popova Evgenya Y. , Jentink Nathan , Swulius Matthew , Li Zilong , Schlick Tamar , Grigoryev Sergei A.
Published: January 2025

The formation of condensed heterochromatin is critical for establishing cell-specific transcriptional programs. To reveal structural transitions underlying heterochromatin formation in maturing mouse rod photoreceptors, we apply cryo-EM tomography, AI-assisted deep denoising, and molecular modeling. We find that chromatin isolated from immature retina cells contains many closely apposed nucleosomes with extremely short or absent nucleosome linkers, which are inconsistent with the typical two-start zigzag chromatin folding. In mature retina cells, the fraction of short-linker nucleosomes is much lower, supporting stronger chromatin compaction. By Cryo-EM-assisted nucleosome interaction capture we observe that chromatin in immature retina is enriched with i±1 interactions while chromatin in mature retina contains predominantly i±2 interactions typical of the two-start zigzag. By mesoscale modeling and computational simulation, we clarify that the unusually short linkers typical of immature retina are sufficient to inhibit the two-start zigzag and chromatin compaction by the interference of very short linkers with linker DNA stems. We propose that this short linker composition renders nucleosome arrays more open in immature retina and that, as the linker DNA length increases in mature retina, chromatin fibers become globally condensed via tight zigzag folding. This mechanism may be broadly utilized to introduce higher chromatin folding entropy for epigenomic plasticity.
Development of conditional-siRNA programmable riboswitch for targeting adverse cardiac remodeling
Authors: Gokulnath Priyanka , Salvador Ane M. , Graham Caleb , Han Si-ping , Li Guoping , Kannappan Ramaswamy , Azzam Christopher , Spanos Michail , Scherer Lisa , Sethu Palaniappan , Rossi John , Goddard William A. , Das Saumya
Published: January 2025

Heart Failure (HF) remains a global epidemic and a significant healthcare burden, with an unmet need for novel therapies to target the preceding pathological hypertrophy in vulnerable patients. Here we report the development of novel conditional-siRNA (Cond-siRNA) constructs that are selectively activated by disease-specific RNA biomarkers to enable cell-specific inhibition of a target disease-causing RNA. We designed aCond-siRNA that can be activated bynppamRNA, upregulated specifically in CMs under pathological stress, to silence the key pro-hypertrophic gene calcineurin by the effector siRNA. In cellular models including neonatal rat ventricular myocyte (NRVM) and rat cardiomyocyte cell-line (H9C2),Cond-siRNA exhibited low baseline activity in the absence of the disease biomarker but achieved targeted calcineurin silencing uponnppamRNA induction by phenylephrine (PE)-induced stress in a two-dimensional (2D) cell culture system and pressure overload in three-dimensional (3D) heart-on a chip system. NRVM transfection with theCond-siRNA resulted in a decreased expression of calcineurin mRNA specifically after PE or pressure-overload treatment, but not after vehicle treatment, provingnppamRNA-specific activation of the effector siRNA against calcineurin. Specificity was confirmed asCond-siRNA did not significantly silence calcineurin in cardiac fibroblasts and T cells, lackingnppaexpression. Reduced calcineurin protein levels and NFATc1 nuclear translocation correlated with decreased NRVM hypertrophy after PE treatment, confirmingCond-siRNA’s efficacy. This study offers proof-of-concept forCond-siRNA as a targeted therapy to mitigate hypertrophic progression, paving the way for novel HF treatments.

One sentence summary

Conditional-siRNA targeting adverse cardiac remodeling

GRAPHICAL ABSTRACT
Reciprocal roles of crowding and serial dependence on visual perception
Authors: Cass John , Jertberg Robert , Van der Burg Erik
Published: January 2025

Visual perception arises from the interplay between current and prior sensory inputs. Two perceptual phenomena-serial dependence and visual crowding-result from the mandatory integration of retinal information across time and space, respectively. This study investigated, for the first time, their functional relationship for orientation and brightness discrimination tasks. Participants performed orientation and brightness discrimination tasks (blocked) on peripheral targets surrounded by distractors of varying color, orientation, and proximity. Both serial dependence (the influence of prior stimuli on current judgments) and visual crowding (impaired peripheral recognition caused by nearby distractors) were observed. Similar double dissociations in task and stimulus specificity emerged for both phenomena, suggesting functional links mediated by distinct processing mechanisms for brightness and orientation judgments. Additionally, the two effects interacted: crowding reduced serial dependence on subsequent trials, indicating that spatial information is prioritized over temporal information when spatial redundancy is high. Conversely, serial dependence increased crowding for orientation judgments, while for brightness judgments, serial dependence operated additively without affecting crowding. These interactions were spatially specific, occurring only when targets appeared in the same location across consecutive trials. Notably, a positive correlation between crowding and serial dependence was found exclusively for orientation judgments and only when targets appeared at the same location across trials. The reciprocal interaction and positive correlation between serial dependence and crowding observed for orientation judgments indicate that that these processes are intrinsically linked, possibly via a common neural mechanism. In contrast, for brightness judgments, the unilateral effect of crowding on serial dependence—along with the absence of correlation-indicates distinct neural mechanisms. Here, brightness crowding likely precedes serial dependence, reflecting a prioritization of spatial redundancy minimization over temporal stabilization. These findings suggest that the brain strategically integrates spatial and temporal information through distinct yet overlapping mechanisms, balancing spatial precision with temporal stability based on task demands and stimulus characteristics.
Determining the variability associated with measuring visual acuity and refractive error measurements: a systematic review
Authors: Van der Zee C , Muijzer MB , Claessens JLJ , Wisse RPL
Published: January 2025

Topic

This systematic review examines variability regarding measuring visual acuity (VA) and refractive error (RE).

Clinical Relevance

VA and RE are key factors that determine visual function, and although accurately measuring VA and RE is fundamental to clinical practice, no scientific consensus has been reached with respect to variability. This lack of consensus affects our ability to establish a limit of agreement (LoA) for clinically accepted variability and may subsequently affect the clinical decision-making process, regulations, and research in the field of ophthalmology.

Methods

This systematic review was performed in accordance with PRISMA guidelines and was registered at PROSPERO (ID: CRD42024554663). We searched the Medline, PubMed, and Embase databases. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was then used to assess the risk of bias (RoB). We included studies that directly compared the accuracy of VA or RE and reported the LoA and mean difference expressed in logarithm of the minimum angle of resolution (LogMAR) for VA and diopters (D) for refraction. We then report the summarized mean LoA values with 95% confidence intervals (CIs).

Results

After applying the inclusion and exclusion criteria, our analysis included 13 and 6 studies that reported VA and RE measurements, respectively. From these 19 studies, only 6 (32%) scored a low RoB in at least three out of four QUADAS-2 domains. In 27 out of 38 subgroups (71%), LoA exceeded the generally accepted ranges for VA or RE (namely, ±0.15 LogMAR and ±0.5D, respectively). Based on our analysis, the summarized mean LoA values were ±0.20 LogMAR (95% CI: 0.17, 0.23) and ±0.70D (95% CI: 0.50, 0.89) for VA and RE measurements, respectively.

Conclusions

We found that both VA and RE measurements have relatively high variability, exceeding currently accepted limits. Thus, the currently accepted limits of this variability are either unrealistic or reflect studies with methodological weaknesses. Rigorous studies are therefore needed in order to more accurately estimate the acceptable limits of variability for both VA and RE measurements. For now, we propose using the mean LoA values obtained in our study as a provisional frame of reference. In addition, we discuss several aspects of understanding the variability that exists when measuring VA and RE, particularly with respect to comparing studies.
Cost-effectiveness of alternative cascade screening strategies for familial hypercholesterolemia with realistic cascade screening acceptance rates and use of high-cost drugs
Authors: Lou Jing , Chong Kok Joon , Ting Pek Sharon Li , Bylstra Yasmin , Drum Chester Lee , Lim Weng Khong , Wang Yi , Yeo Khung Keong , Tavintharan Subramaniam , Wee Hwee-Lin
Published: January 2025

Background

Cascade screening (CS) for familial hypercholesterolemia (FH) is cost-effective in many countries. However, most existing economic evaluation studies (i) ignored or overstated first-degree relative (FDR) participation rate (as 60-100%), (ii) did not consider novel and expensive therapies, e.g. PCSK9 inhibitors (PCSK9i), (iii) were conducted outside of Asia. In Singapore, FDR participation rate is about 25% among probands who have known pathogenic variants.

Aims

To evaluate and identify drivers of cost-effectiveness of CS protocols for FH

Methods

Four CS protocols, which vary in the application of genetic testing, were examined using a hybrid decision tree-Markov model. Sensitivity analysis and scenario analyses were conducted to identify drivers of cost-effectiveness.

Results

All CS protocols are likely to be cost-effective (probabilities of being cost-effective: 85%-95% when no access to PCSK9i; 73%-99% when PCSK9i are provided). The most cost-effective protocol differs depending on whether PCSK9i are provided. Cascade acceptance rates are key drivers of cost-effectiveness. Other drivers include timeliness of starting treatment post-screening, age of proband, health-related quality of life loss with cardiovascular disease, prevalence of FH mutation among probands, conventional treatment effect and cost of PCSK9i.

Conclusion

CS for FH is cost-effective across most scenarios and assumptions. For better cost-effectiveness, health systems need to look for ways to improve proband’s willingness to share contact of their relatives and relatives’ willingness to be screened. Other ways to improve cost-effectiveness include to select age groups for proband screening, improve screening detection rate among probands, and start timely treatment post-screening.
Magnetic properties of a staggered
S=1
chain with an alternating single-ion anisotropy direction
Authors: Vaidya S. , Curley S. P. M. , Manuel P. , Stewart J. Ross , Le M. Duc , Balz C. , Shiroka T. , Blundell S. J. , Wheeler K. A. , Calderon-Lin I. , Manson Z. E. , Manson J. L. , Singleton J. , Lancaster T. , Johnson R. D. , Goddard P. A.
Published: January 2025

Materials composed of spin-1 antiferromagnetic (AFM) chains are known to adopt complex ground states that are sensitive to the single-ion-anisotropy (SIA) energy (D), and intrachain (J0) and interchain (J1,2′) exchange energy scales. While theoretical and experimental studies have extended this model to include various other energy scales, the effect of the lack of a common SIA axis is not well explored. Here we investigate the magnetic properties of Ni(pyrimidine)(H2O)2(NO3)2, a chain compound where the tilting of Ni octahedra leads to a twofold alternation of the easy-axis directions along the chain. Muon-spin relaxation measurements indicate a transition to long-range order at TN=2.3K and the magnetic structure is initially determined to be antiferromagnetic and collinear using elastic neutron diffraction experiments. Inelastic neutron scattering measurements were used to find J0=5.107(7)K, D=2.79(1)K,J1′=0.00(5)K, J2′=0.18(3)K, and a rhombic anisotropy energy E=0.19(9)K. Mean-field modeling reveals that the ground state structure hosts spin canting of ϕ≈6.5∘, which is not detectable above the noise floor of the elastic neutron diffraction data. Monte Carlo simulation of the powder-averaged magnetization, M(H), is then used to confirm these Hamiltonian parameters, while single-crystal M(H) simulations provide insight into features observed in the data.

Published by the American Physical Society
2025
Electromagnetic nucleon form factors in the extended vector meson dominance model
Authors: Kuzmin K. S. , Levashko N. M. , Krivoruchenko M. I.
Published: January 2025

An extended vector meson dominance model is developed to describe electromagnetic nucleon form factors. The model includes families of the ρ- and ω-mesons with the associated radial excitations. The free parameters of the model are determined using a global statistical analysis of experimental data on the electromagnetic nucleon form factors in space- and timelike regions of transferred momenta. The vector meson masses and widths are equal to their empirical values, while the residues of form factors at the poles corresponding to the ground states of the ρ- and ω-mesons are consistent with the findings of both the Frazer-Fulco unitarity relations and the Bonn potential for coupling constants of the ρ- and ω-mesons with nucleons. Theoretical constraints imposed on the model include the quark counting rules, the Okubo-Zweig-Iizuka rule, the scaling law of Sachs form factors at moderate momentum transfers, and the suppression of Sachs form factors near the nucleon–antinucleon threshold. A reasonable description of the nucleon form factors in the experimentally accessible range of transferred momenta, as well as the electric and magnetic nucleon radii and Zemach radii, is obtained.

Published by the American Physical Society
2025
Modular family symmetry in fluxed GUTs
Authors: Basiouris Vasileios , Crispim Romão Miguel , King Stephen F. , Leontaris George K.
Published: January 2025

We discuss modular family symmetry in effective theories based on generic properties of bottom-up local F-theory inspired grand unified theories (GUTs) broken by fluxes, which we refer to as fluxed GUTs. We argue that the Yukawa couplings will depend on the complex structure moduli of the matter curves in such a way that they can be modular forms associated with these symmetries. To illustrate the approach, we analyze in detail a concrete local fluxed SU(5) GUT with modular S4 family symmetry.

Published by the American Physical Society
2025
Fundamental Limit on the Power of Entanglement Assistance in Quantum Communication
Authors: Wolff Lasse H. , Belzig Paula , Christandl Matthias , Durhuus Bergfinnur , Tomamichel Marco
Published: January 2025

The optimal rate of reliable communication over a quantum channel can be enhanced by preshared entanglement. Whereas the enhancement may be unbounded in infinite-dimensional settings even when the input power is constrained, a long-standing conjecture asserts that the ratio between the entanglement-assisted and unassisted classical capacities is bounded in finite-dimensional settings [Bennett , ]. In this Letter, we prove this conjecture by showing that their ratio is upper bounded by o(d2), where d is the input dimension of the channel. An application to quantum communication with noisy encoders and decoders is given.

Published by the American Physical Society
2025
Load balancing for high performance computing using quantum annealing
Authors: Rathore Omer , Basden Alastair , Chancellor Nicholas , Kusumaatmaja Halim
Published: January 2025

With the advent of exascale computing, effective load balancing in massively parallel software applications is critically important for leveraging the full potential of high-performance computing systems. Load balancing is the distribution of computational work between available processors. Here, we investigate the application of quantum annealing to load balance two paradigmatic algorithms in high-performance computing. Namely, adaptive mesh refinement and smoothed particle hydrodynamics are chosen as representative grid and off-grid target applications. While the methodology for obtaining real simulation data to partition is application specific, the proposed balancing protocol itself remains completely general. In a grid based context, quantum annealing is found to outperform classical methods such as the round robin protocol but lacks a decisive advantage over more advanced methods such as steepest descent or simulated annealing despite remaining competitive. The primary obstacle to scalability is found to be limited coupling on current quantum annealing hardware. However, for the more complex particle formulation, approached as a multiobjective optimization, quantum annealing solutions are demonstrably Pareto dominant to state of the art classical methods across both objectives. This signals a noteworthy advancement in solution quality which can have a large impact on effective CPU usage.

Published by the American Physical Society
2025
Design and implementation of a user office system for the Canadian Light Source
Authors: Janzen Kathryn , Fodje Michel
Published: January 2025

To streamline the management of thousands of users and proposals for synchrotron experiments at the Canadian Light Source (CLS), we developed a modern, web-based user services software system that enables the facility to transition away from manual paper-based processes. This user-friendly system offers comprehensive features for managing users, proposals, reviews, sample safety and publications. It has been in active use at the CLS for six years and has simplified and significantly transformed user operations. The system is designed for integration into other large-scale facilities with minimal effort, and the source code is publicly available.
Sustainability development in vocational education: a case study in Indonesia
Authors: Suharno Suharno , Ihsan Fatihul , Himawanto Dwi Aris , Pambudi Nugroho Agung , Rizkiana Reza
Published: January 2025

Purpose

The study aimed to measure the perception of prospective vocational education (VE) students in Indonesia toward the sustainable development of VE. Additionally, it sought to evaluate the implications of these perceptions for improving the quality of VE and preparing superior human resources to meet future demands.

Design/methodology/approach

This research employed a quantitative approach, utilizing descriptive statistical analysis, Top Two Boxes (T2B) and independent sample t-tests. Data were collected via an online questionnaire distributed through Google Forms to 394 prospective VE students from 23 provinces across Indonesia. The gender distribution of the respondents was 61% male and 39% female.

Findings

The analysis revealed that prospective VE students had a high perception of the sustainable development of VE, with a T2B value of 92.2%. This perception was significantly influenced by the presence of appropriate government regulations. Furthermore, the study noted an increase in the community’s trust in VE, as reflected in the growing ratio of vocational to general education, which shifted from 30%:70% in 2008 to 52%:48% in 2023.

Practical implications

Despite the positive perceptions, challenges persist in recruiting vocational teachers proportionally. Currently, only 5% of vocational teachers are appointed as government employees, which may affect the quality and relevance of vocational school graduates. To address this issue, the government must allocate adequate budgetary resources for recruiting and appointing vocational teachers. This step is essential to ensure sustainable growth and further enhance public trust in VE.

Originality/value

This research provides valuable insights into the perceptions of prospective VE students in Indonesia regarding the sustainable development of VE. By identifying key factors influencing these perceptions, such as government regulations, and highlighting existing challenges, the study contributes to the ongoing discourse on improving VE quality and aligning it with future demands.
The longitudinal interplay between father–child and mother–child home literacy activities and Children's learning English as a second language in Hong Kong
Authors: Liu Catrina Cuina , Chung Kevin Kien Hoa
Published: January 2025

Background

The associations between the characteristics of the home literacy environment (HLE) and children's language and literacy skills have been established in first languages. This study investigated the longitudinal interplay between the father–child and mother–child HLE and children's English language skills as L2.

Methods

In this study, 176 second‐year kindergarten children (Mean = 55.06 months, SD = 4.30; 96 boys, 54.5%) were followed into their third year and were assessed on their English vocabulary and word reading. The child's father and mother completed a questionnaire on their independent HLE with their child.

Results

The cross‐lagged panel analysis showed that previous father–child formal HLE predicted subsequent activity levels of mother–child and father–child informal HLE. The mother–child formal HLE positively predicted the development of English word reading. A child's prior English vocabulary was positively associated with subsequent father–child informal HLE.

Conclusions

The crossover effects between the father–child and mother–child HLE emphasize that the behaviours of one parent's HLE could influence one another. Family‐based interventions could consider promoting both fathers' and mothers' roles in fostering children's language learning and reading development in a positive home learning environment. The implications for the effectiveness of the HLE in supporting children's English language learning as L2 are discussed.
Direct Evidence of Microbial Sunscreen Production by Scum‐Forming Cyanobacteria in the Baltic Sea
Authors: Vuori Inkeri , Gaiani Greta , Arsın Sıla , Delbaje Endrews , Järn Julia , Snårbacka Robert , Couëdelo Annaël , Murukesan Gayathri , Wahlsten Matti , Jokela Jouni , Shishido Tânia Keiko , Fewer David P.
Published: January 2025

Mycosporine‐like amino acids are water‐soluble secondary metabolites that protect photosynthetic microorganisms from ultraviolet radiation. Here, we present direct evidence for the production of these compounds in surface scums of cyanobacteria along the Baltic Sea coast. We collected 59 environmental samples from the southern coast of Finland during the summers of 2021 and 2022 and analysed them using high‐resolution liquid chromatography‐mass spectrometry. Our results revealed the presence of microbial sunscreens in nearly all surface scum samples. Mycosporine‐like amino acids are synthesised through the coordinated action of four biosynthetic enzymes encoded in a compact biosynthetic pathway. Bioinformatics analysis of the mysB biosynthetic gene from a surface scum indicated that the cyanobacteria responsible for production belonged to the Anabaena/Dolichospermum/Aphanizomenon species complex. We mapped the distribution of biosynthetic enzymes onto a phylogenomic tree, utilising 120 bacterial single‐copy conserved genes from 101 draft or complete genomes within the species complex. This analysis showed that 48% of identified species possess the ability to produce these compounds, with biosynthetic pathways being most common in Dolichospermum and Aphanizomenon strains. We detected the production of porphyra‐334 and shinorine, two widely reported family members, in Dolichospermum strains isolated from the Gulf of Finland's surface layer. The estimated content of porphyra‐334 in Dolichospermum sp. UHCC 0684 was 7.4 mg per gram dry weight. Our results suggest that bloom‐forming cyanobacteria could be a potential source of these compounds for cosmetic and biotechnological applications and may play a significant role in cyanobacterial bloom formation.
Second‐Trimester Inflammatory Markers in Predicting Fetal Growth Restriction: A Retrospective Analysis
Authors: Aktemur Gizem , Çakır Betül Tokgöz , Karabay Gülşan , Filiz Ahmet Arif , Seyhanlı Zeynep , Sucu Serap Topkara , Tonyalı Nazan Vanlı , Çelen Şevki
Published: January 2025

Problem:

Fetal growth restriction (FGR) is a critical pregnancy complication linked to increased perinatal morbidity and mortality. Inflammation plays a key role in FGR's pathophysiology, and systemic inflammation markers may serve as predictors. This study evaluates the role of various inflammation indices; systemic immune‐inflammation index (SII), systemic inflammatory response index (SIRI), pan‐immune‐inflammation value (PIV), neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), monocyte‐to‐lymphocyte ratio (MLR), lymphocyte‐to‐platelet ratio (LMR), monocyte‐to‐platelet ratio (MPR), aggregate systemic inflammation index (AISI), systemic coagulation inflammation index (SCII), and immature granulocyte percentage (IG%) in predicting FGR.

Methods of Study

This retrospective study included 403 pregnant women treated at Ankara Etlik City Hospital between August 2022 and May 2024. The study population comprised 202 women with uncomplicated pregnancies (control group) and 201 women diagnosed with FGR per the Delphi Consensus Criteria. Second‐trimester blood samples were used to calculate the inflammatory indices.

Results

SII and NLR levels were significantly higher in the FGR group compared to controls (p = 0.020, p = 0.028, respectively). However, no significant associations were found between these indices and adverse neonatal outcomes. Cut‐off values for SII and NLR were 896 and 3.91, respectively, with moderate sensitivity and specificity.

Conclusions

SII and NLR, measured in the second trimester, may be useful in predicting FGR. Although these indices did not correlate with adverse neonatal outcomes, further prospective studies with larger populations are needed to validate their clinical utility.
Is germline genome‐editing person‐affecting or identity‐affecting, and does it matter?
Authors: McGee Andrew , Prince Sinead
Published: January 2025

Writers have debated whether germline genome‐editing is person‐affecting or identity‐affecting. The difference is thought to be ethically relevant to whether we should choose genome‐editing or choose preimplantation genetic diagnosis and embryo selection, when seeking to prevent or produce bad conditions (e.g., cystic fibrosis, or deafness) in the individuals who will grow from the embryo edited or selected. We consider the very recent views of three prominent bioethicists and philosophers who have grappled with this issue. We claim that both sides are right, but that the sense in which genome‐editing is person‐affecting is less important, morally, when the aim is to have healthy children. Since this is the predominant objective of engaging in embryo selection and genome‐editing, and since there are certain risks, at least for now, with genome‐editing, it remains better, morally, to engage in embryo selection than genome‐editing.
Evolving interdependencies between two waves of gentrifiers in the wax and wane of a ‘Utopian Village’: A case study of Cenbu Village, Shanghai
Authors: Hao Jinwei , Zhu Jin , He Shenjing , Lu Junhua
Published: January 2025

Amid the escalating rural gentrification, a diverse array of gentrifiers is precipitating the path from coexistence and cooperation to conflict and eventual displacement. Existing literature has primarily addressed gentrifiers as a homogeneous group and focuses on the displacement of indigenous villagers, while the staged interdependencies and the displacement of gentrifiers have remained largely understudied. Drawing on a longitudinal study of a Shanghai village on a path to rural super‐gentrification, this article investigates the complex interdependencies of two waves of gentrifiers, from commensal relations to exclusion, culminating in the eventual displacement of the first‐wave gentrifiers. The study further analyses the construction and deconstruction of a ‘Utopian Village’ and the role of the gentrifiers' divergent perceptions of rurality in this evolving process. First‐wave gentrifiers tend to value the authenticity of villages, and seek to construct a ‘Utopian Village’ through commensal socio‐economic relations and the maintenance of a sustainable ecosystem, while preserving the authenticity and openness of the landscape. Their efforts, however, attract a second wave of gentrifiers who hold differing views of rurality, and this misalignment results in the over‐consumption and alienation of rurality, characterised by introverted social networks and over‐decorative landscapes. The originally envisaged ‘Utopian Village’ is thus undermined, leading to the exclusion and displacement of the first‐wave gentrifiers. This research contributes to a deeper understanding of the evolving dynamics of rural gentrification, the super‐gentrification trend, the complex interdependencies of the different types of gentrifiers and the effects on the communities in question.
Effective Reduction of Transgene‐Specific Immune Response With rAAV Vectors Co‐Expressing miRNA‐UL112‐5p or ERAP1 shRNA
Authors: Huang Xiaoping , Wang Xiao , Sun Yaqi , Xie Xinrui , Xiao Luming , Xu Yihang , Yan Qiongshi , Xu Xianxiang , Li Ling , Xu Wentao , Weng Wenting , Wu Wenlin , Xie Xiaolan , Dai Congjie , Diao Yong
Published: January 2025

Recombinant adeno‐associated virus (rAAV) has emerged as one of the best gene delivery vectors for human gene therapy in vivo. However, the clinical efficacy of rAAV gene therapy is often hindered by the host immune response against its transgene products. Endoplasmic reticulum aminopeptidase 1 (ERAP1) is specialised to process peptides presented by class I molecules of major histocompatibility complex. Therefore, we hypothesise that modulation of the ERAP1 activity in rAAV transduced cells may be favoured to evade immune response against transgene products. In this study, we incorporated either miRNA‐UL112‐5p or ERAP1 shRNA into rAAV vectors expressing full‐length ovalbumin (OVA) as a model antigen, and evaluated their effects for antigen presentation, cellular and humour immune response induced by OVA expression. The results indicated that silencing ERAP1 using miR‐UL112‐5p or ERAP1 shRNA did not affect the expression of OVA in cells, but inhibited the processing and presentation of OVA antigen peptide SIINFEKL in antigen presenting cells (APCs). Moreover, the rAAV vector co‐expressing ERAP1 shRNA maintains stable and high expression of OVA in vivo, while simultaneously suppressing the humoral immunity of OVA. In addition, experimental results demonstrated that rAAV vectors incorporated ERAP1 shRNA efficiently repress costimulatory signals in dendritic cells (DCs), significantly attenuated the cytotoxic T‐cell response, allowed for sustained transgene expression and reduced clearance of transduced muscle cells in mice. Moreover, our study suggested that the incorporation of miRNA‐UL112‐5p or ERAP1 shRNA into rAAV vectors effectively reduced transgene products induced immune response. The proposed method may potentially be applied in clinics to deliver therapeutic proteins safely and efficiently.
Anticancer Effects of MAPK6 siRNA‐Loaded PLGA Nanoparticles in the Treatment of Breast Cancer
Authors: Toruntay Ceyhun , Poyraz Fatma Sayan , Susgun Seda , Yucesan Emrah , Mansuroglu Banu
Published: January 2025

siRNA‐loaded nanoparticles open new perspectives for cancer treatment. MAPK6 is upregulated in breast cancer and is involved in cell growth, differentiation and cell cycle regulation. Herein, we aimed to investigate the anticancer effects of MAPK6 knockdown by using MAPK6 siRNA‐loaded PLGA nanoparticles (siMAPK6‐PLGA‐NPs) in MCF‐7 breast cancer cells. After the synthesis and characterisation of nanoparticles, treatment concentrations were determined with cytotoxicity assay. Subsequently, MAPK6 knockdown and anticancer effects of siMAPK6‐PLGA‐NPs were evaluated by in vitro assays. siMAPK6‐PLGA‐NPs have been determined to suppress MAPK6 expression efficiently. In vitro studies revealed that siMAPK6‐PLGA‐NPs significantly reduced the migration, proliferation and colony‐forming ability and enhanced the apoptosis in MCF‐7 cells. Taken together, siMAPK6‐PLGA‐NPs exhibited robust and promising anticancer effects against MCF‐7 cells. Our findings demonstrated that siRNA‐loaded PLGA nanoparticles have great potential for breast cancer treatment and MAPK6 gene may be the therapeutic target in breast cancer.
In‐Depth Examination of TPBG as a New Predictive Indicator for Gastric Cancer
Authors: Yang Lianlei , Weng Chunyan , Zhang Yaping , Zhao Yu , Chen Kexin , Li Guodong , Zhong Xueqing , He Chenghai
Published: January 2025

Trophoblast glycoprotein (TPBG) plays a significant part in the growth of specific cancers, yet its connection to gastric cancer (GC) remains uncertain. This research seeks to analyse the fluctuation in TPBG levels in GC and evaluate how TPBG expression relates to the prognosis of GC patients. TPBG expression in GC and normal gastric tissues was investigated in The Cancer Genome Atlas (TCGA) and Genotype‐Tissue Expression (GTEx) database, further extracting the immunohistochemistry images from HPA database and validating by Western blot. The connection between TPBG and GC patients' survival rates was investigated by Kaplan–Meier and COX regression analysis. Genes related to TPBG were enriched using GO and KEGG data. In vitro and in vivo tumour models were utilised to evaluate the function of TPBG in GC. Western blot analysis was performed to detect the expression of PI3K/AKT signalling pathway proteins following TPBG knockdown. Immune infiltration was analysed using the CIBERSOFT and ssGSEA methods. The association between TPBG and immune cells that infiltrate tumours was evaluated through the utilisation of GSVA. TPBG expression increased in several tumour tissues (including GC) more than in adjacent noncancerous tissues. Elevated TPBG level predicted worse outcomes, such as poorer overall survival, pathological stage, and therapy response in GC. Enrichment analysis primarily focused on biological processes like the organisation of external encapsulating structures, extracellular structure, and collagen metabolism. Biological experiments further demonstrated that TPBG knockdown successfully inhibits the progression, migration, and invasion of GC cells. Western blot analysis revealed that TPBG knockdown inhibits the PI3K/AKT signalling pathway. Furthermore, TPBG is associated with the infiltration of immune cells in GC, which correlates with the expression of macrophage cells. There is a positive relationship between TPBG and malignant behaviour of GC tissues and cells, suggesting that TPBG can be useful for diagnosing and prognosing GC.
Diagnostic Power of MicroRNAs in Melanoma: Integrating Machine Learning for Enhanced Accuracy and Pathway Analysis
Authors: Rafiepoor Haniyeh , Ghorbankhanloo Alireza , Soleimani Dorcheh Soroush , Angouraj Taghavi Elham , Ghanadan Alireza , Shirkoohi Reza , Aryanian Zeinab , Amanpour Saeid
Published: January 2025

This study identifies microRNAs (miRNAs) with significant discriminatory power in distinguishing melanoma from nevus, notably hsa‐miR‐26a and hsa‐miR‐211, which have exhibited diagnostic potential with accuracy of 81% and 78% respectively. To enhance diagnostic accuracy, we integrated miRNAs into various machine‐learning (ML) models. Incorporating miRNAs with AUC scores above 0.70 significantly improved diagnostic accuracy to 94%, with a sensitivity of 91%. These findings underscore the potential of ML models to leverage miRNA data for enhanced melanoma diagnosis. Additionally, using the miRNet tool, we constructed a network of miRNA–miRNA interactions, revealing 170 key genes in melanoma pathophysiology. Protein–protein interaction network analysis via Cytoscape identified hub genes including MYC, BRCA1, JUN, AURKB, CDKN2A, DDX5, MAPK14, DDX3X, DDX6, FOXM1 and GSK3B. The identification of hub genes and their interactions with miRNAs enhances our understanding of the molecular mechanisms driving melanoma. Pathway enrichment analyses highlighted key pathways associated with differentially expressed miRNAs, including the PI3K/AKT, TGF‐beta signalling pathway and cell cycle regulation. These pathways are implicated in melanoma development and progression, reinforcing the significance of our findings. The functional enrichment of miRNAs suggests their critical role in modulating essential pathways in melanoma, suggesting their potential as therapeutic targets.
ALBA3 maintains male fertility under heat stress in plants
Authors: Ci Dong , Liu Yi , Wang Lishuan , Zhu Ruixian , Chen Yong , Bai Ge , Xu Ziyan , Zhou Huanbin , Zhou Xueping , Fan Liu‐Min , Qian Weiqiang
Published: January 2025

Heat stress (HS) at the reproductive stage detrimentally affects crop yields and seed quality. However, the molecular mechanisms that protect reproductive processes in plants under HS remain largely unknown. Here, we report that Acetylation Lowers Binding Affinity 3 (ALBA3) is crucial for safeguarding male fertility against HS in Arabidopsis. ALBA3 is highly expressed in pollen, and ALBA3 is localized in the cytoplasm of both sperm and vegetative cells. Mutants lacking functional ALBA3 exhibit hypersensitivity to HS, with reduced silique length and fertility due to defects in pollen germination, pollination, pollen tube growth, and fertilization under HS. ALBA3 binds and stabilizes a subset of messenger RNAs (mRNAs) essential for pollen function, thereby protecting male fertility. Two residues in the Alba domain, K46 and L90, are critical for ALBA3's ability to bind and stabilize mRNAs and are necessary for its proper function. Interestingly, the loss of rice ALBA3 also leads to severe pollen abortion and male sterility under HS, highlighting the conserved role of ALBA3 in protecting male fertility across plant species. This study uncovers a conserved mechanism by which ALBA3 safeguards male fertility during HS by stabilizing specific mRNAs crucial for pollen function.
Angiostrongylus cantonensis Meningo‐Encephalitis in Children—Heightened Awareness Needed During Prolonged Wet Weather Conditions
Authors: Hasan Nadia , Nourse Clare , Heney Claire , Lee Rogan , Kapoor Vishal , Berkhout Angela
Published: January 2025

Aim

Angiostrongylus cantonensis, the leading cause of eosinophilic meningoencephalitis, is well established in eastern Australia. Prolonged wet weather in Queensland during 2021–2022 coincided with anecdotal reports of increased neuroangiostrongyliasis cases, prompting an evaluation of paediatric cases from 2013 to 2022.

Methods

This retrospective observational study reviewed children (0–16 years) with cerebrospinal fluid (CSF) eosinophilia (≥ 10% of the total CSF leukocyte count) and/or A. cantonensis testing (serology or polymerase chain reaction) between 01/01/2013 and 31/12/2022, using statewide laboratory data and patient records.

Results

Eighty children were identified: 59 (74%) had CSF eosinophilia without A. cantonensis testing, 9 (11%) had CSF eosinophilia with A. cantonensis testing, and 12 (15%) had A. cantonensis testing without CSF eosinophilia. Neuroangiostrongyliasis was either proven or probable in seven children: five (71%) during 2021–2022, coinciding with prolonged wet weather. A significant positive correlation was observed between rainfall and case numbers (r = 0.88, p < 0.01). Median age of diagnosed children was 4 years (IQR 1.8–8.5, range 1.5–13 years) and five (71%) were male. Snail or slug exposure was reported in four (57%) children. All children presented with vomiting, and six also had a headache and focal neurology (86%). Abnormal neuroimaging was noted in six (86%) cases. Five children received corticosteroid therapy alone (71%), while two (29%) were managed conservatively. There were no deaths, but one child had persistent focal neurological abnormalities at discharge.

Conclusion

Awareness of A. cantonensis and exposure risks is crucial, especially during prolonged wet weather conditions. While most children in this study had good outcomes, this is not always the case.