bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-assembled micelles prepared from amphiphilic Dextran-Jeffamine diblock copolymers
Authors: Wang Shuxin , Sun Mengxiao , Zeng Zhaoning , Wang Dandan , Shen Xin , Li Suming , Su Feng
Published: February 2025

The creation of Dextran-Jeffamine (DEX-JEF) amphiphilic block polymers was achieved through the process of reductive amination. This synthesis involved reacting the semi-acetal terminal of the hydrophilic dextran (DEX) with the amine termini of Jeffamine (JEF), which could be in monoamine, diamine, or triamine forms. The result was a collection of block copolymers that included diblock, triblock, and triarm structures, each with distinct hydrophilic ratios and varying block lengths. These polymers were thoroughly analyzed by using nuclear magnetic resonance (NMR) spectroscopy and Fourier-transform infrared (FT-IR) spectroscopy to determine their structural characteristics. After the DEX-JEF polymer was self-assembled into micelles in a water medium, the micellar structure, dimensions, and zeta potential were analyzed by using Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS) techniques. Furthermore, the stability of the micelles was assessed by determining the Critical Micelle Concentration (CMC) through fluorescence spectroscopy measurements. Finally, the drug-carrying properties of the polymer micelles were also evaluated. The results showed that the micelle sizes ranged from 104.6-202.1 nm, CMC ranging from 0.04-0.28 mg/mL, and drug loading ranging from 4.71-7.16%. It is expected to be a potential drug carrier.
Spin distribution and conductance variations in phenoxyl radical single-molecule junctions
Authors: Sun Fanxi , Jiang Shengqing , Zhang Hanjun , Zhu Gaolu , Pan Yangyang , Ji Yu , Li Jiayu , Zheng Yonghao , Wang Dongsheng
Published: February 2025

This study explores the conductance characteristics and spin distributions in single-molecule junctions using phenoxyl radicals linked to bis(methylthio)triphenylene cores. Through a combination of UV-vis spectrophotometry, electron spin resonance (ESR) spectroscopy, and density functional theory (DFT) calculations, we examine how the structural modifications in phenoxyl radicals influence electron delocalization and molecular conductance. Initial tests confirmed the presence of radicals, and subsequent DFT analyses demonstrated significant shifts in electron spin densities affecting the conductive pathways. This study utilized scanning tunneling microscopy-break junction (STM-BJ) techniques to further elucidate the electronic properties of these radical-injected systems, highlighting the critical role of molecular architecture in defining conductive properties. Results indicate that the addition of phenyl rings leads to varying degrees of electron delocalization and corresponding changes in conductance, with a noted decrease in the HOMO-LUMO energy gap across different structures.
Evolution and preparation of graphene oxide and deep learning image characterization
Authors: Zhang Ziyun
Published: February 2025

Graphene-polymer nanocomposites have garnered significant scientific attention because of their excellent electron transport properties, exceptional mechanical strength, large surface area, size-selective ability, and high Young’s modulus. When effectively organized at both the structural and interfacial levels, these graphene-based polymer nanocomposites demonstrate remarkable structural integrity and multifunctional capabilities. Graphene oxide (GO) stands out as one of the most promising materials within the graphene family. This review provides an overview of the synthetic process and characterization of GO and GO-based polymer nanocomposites, including GO-cement and GO-hydrogels. The dispersion of GO in composites is analyzed using techniques such as Raman spectroscopy, atomic force microscopy, scanning electron microscopy, and others. Despite some challenges, GO-based polymer nanocomposites exhibit superior performance in certain aspects and demonstrate wide potential applications.
Properties of acrylate hydrogel nano-oil emulsions with long hydrophobic chain segments
Authors: Bai Lu , Chen Xiaoqi , Zhou Haijun , Zhang Fen , Hu Mingguang , Cheng Hua , Zhao Yating , Li Yantao
Published: February 2025

Hydrogels with rich water content and three-dimensional network structure have broad development prospects in biomedical fields such as drug delivery and cell culture. Polyacrylate (PA) materials can induce innate immunity to play a regulatory role, and polyacrylates with hydrophobic chain segments can enhance the cytocompatibility of polymers. In this study, polyacrylates with different hydrophobic chain segment lengths were prepared, and PA was immersed in pure water to form acrylate hydrogel (AH). The micromorphology of AH was observed, and its rotational viscosity and light transmittance were analyzed. The long-term storage stability of polyacrylate nano-oil emulsion (PNOE) obtained by mixing AH with nano-oil emulsion was examined at 4°C and 37°C, and it was found that 4°C was more favorable for the preservation of the emulsion. In addition, subcutaneous injection of PNOE in BABL/c mice was used to characterize the safety of immunization, and it was found to have a good safety profile, which is an important prerequisite for its use as a vaccine adjuvant.
Carbon dots with recoverable photo-bleaching for reusable UV detectors
Authors: Chen Zhenhui , Zhang Shaofeng , Wu Zefeng , Lin Zhenbo , Yao Xin , Liu Jiong , Huang Zhihao , Zhang Wenfei
Published: February 2025

Carbon dots (CDs) have emerged as a promising category of nanomaterials for sensing applications, primarily due to their cost-effectiveness, thermal stability, low toxicity, and unique luminescence properties. CDs sensors have been widely used in ion detection, but rarely in ultraviolet (UV) light detection. In this paper, we synthesized CDs via one one-step pyrolysis process. The exceptional thermal stability of CDs is exhibited by their ability to maintain 100 % initial photoluminescence (PL) intensity over a temperature range from 300 K to 700 K. The bleached CDs can recover almost 100 % of PL intensity through simple thermal treatment at 800 K. The photoluminescence of CDs retains approximately 80% of their initial intensity following five cycles of photo-bleaching and thermal recovery. Moreover, the fluorescence quenching degree maintains a good linear relationship with the UV photo-bleaching time. These indicate that CDs can be effectively used in reusable UV detectors.
How good is my drought index? Evaluating predictability and ability to estimate impacts across Europe
Authors: Shyrokaya Anastasiya , Pappenberger Florian , Messori Gabriele , Pechlivanidis Ilias , Cloke Hannah Louise , Di Baldassarre Giuliano
Published: February 2025

Identifying drought indices that effectively predict future drought impacts remains a critical challenge in seasonal forecasting, as these indices provide the necessary actionable information that enables stakeholders to better anticipate and respond to drought-related challenges. This study evaluates how drought indices balance forecast skill and relevance for estimating impacts across Europe. Using ECMWF SEAS5 seasonal predictions and ERA5 reanalysis as benchmarks, we assessed the predictability skill of drought indices over various accumulation periods and their relevance in estimating drought impacts across Europe, with the aim of enhancing impact-based forecasting (IbF). To evaluate these relationships, we built upon the findings from a study that utilized drought impact data from the European Drought Impact Report Inventory (EDII) and employed random forest (RF) models to evaluate the significance of various drought indices in predicting sector-specific impacts. Our findings reveal higher predictability in Northern and Southern Europe, particularly during winter and summer, with some regions showing extended predictability up to six months, depending on the season. Focusing on case studies in the UK and Germany, our results highlight regions and seasons where accurate impact predictions are possible. In both countries, high impact predictability was found up to six months ahead, with sectors such as Agriculture, Water Supply, and Tourism in the UK, and Agriculture and Water Transportation in Germany, depending on the region and season. This analysis represents a significant step forward in identifying the most suitable drought indices for predicting impacts across Europe. Our approach not only introduces a new method for evaluating the relationship between drought indices and impacts, but also addresses the challenge of selecting indices for estimating impacts. This framework advances the development of operational impact-based drought forecasting systems for Europe.
Space-time image velocity measurement method based on improved GhostNetV2
Authors: Feng Yifeng , Wang Chao , Pu Xiaolei , He Dianyi , Zhang Guo , wang Jianping
Published: February 2025

The space-time image velocimetry (STIV) method exhibits strong performance in non-contact measurements of river flow velocity and discharge. By identifying the main orientation angles of textures in space-time images and combining it with field data from hydrological stations, surface velocity in rivers can be measured. However, the generated space-time images are often affected by background noise and interfering textures due to video recording conditions or lighting variations, which impact the detection of texture orientation angles. To enhance the accuracy and stability of STIV, this paper proposes preprocessing techniques, including second-order differential frequency domain unsharp enhancement, to address noise and interference issues. Additionally, leveraging the correspondence in texture orientation between space-time images and two-dimensional autocorrelation images, a dataset of two-dimensional autocorrelation images with ninefold central magnification is created. An improved GhostNetV2 network is employed for angular classification of this dataset, resulting in increased classification accuracy that enhances the precision of river surface velocity estimation. Comparative experiments are conducted between existing methods and the proposed approach to validate its effectiveness. The experimental results show that the proposed method achieved relative errors in the average velocity measurements of 3.65% and 2.94% for two rivers, and relative errors in total discharge measurements of 3.73% and 2.08%, indicating greater consistency with the current meter measurements than other methods.
Introduction
Authors: Stump Eleonore
Published: February 2025

There is a kind of knowledge that is non-propositional; one variety of it can be acquired in second-person experience of another person, but it can also be transmitted through narratives. This narratively mediated kind of knowledge can be significant for philosophical and theological reflection. Biblical narratives are specially fruitful in this regard, because they offer profound insights into the nature of the human condition and human flourishing. This book brings together detailed examinations of narratives in the Hebrew Bible and the New Testament to yield one large, emergent story which has something to teach that can be missed when the stories are taken in isolation from one another. These are the stories of Job, Samson, Abraham, Mary of Bethany, the temptations of Christ, the passion of Christ, and the story in the biblical book of Ecclesiastes. Taken together, these stories depict a possible world in which there is a good for suffering human beings that outweighs their suffering and that could not be gotten without the suffering, not even in a world without a Fall. On this emergent larger story, human suffering is defeated; and peace and joy in human life are possible.
The Story of Samson
Authors: Stump Eleonore
Published: February 2025

Samson is an exemplar of a person who suffers greatly but whose suffering stems from his own wrongdoing. This chapter focuses on the problem of suffering as regards not the victims of human evil but as regards the perpetrators of it, whose own lives are wrecked in consequence of the evil they do. The chapter concentrates on the biblical story of Samson and gives a detailed philosophical examination of many parts of the story. In the process, the chapter also explores Milton’s understanding of the story in his Samson Agonistes, as well as Sophocles’s portrayal of an analogous case in his Oedipus at Colonus. The chapter shows that in the story what redeems Samson’s suffering for him is the role of his suffering in bringing him into relationship with God.
Language conflicts
Authors: Coulmas Florian
Published: February 2025

This chapter concentrates on policy questions revolving around conflicts relating to language and their implications for access to power and political participation in democratic and authoritarian regimes. Taking ‘the age of language conflict’, a concept introduced by Max Weber, as point of departure, it explains how language became ever more politically important and often contentious in a world increasingly divided into nation states. The chapter portrays four state-language regimes in characteristically different settings of European and post-colonial nation building processes. Language-related conflicts and tensions in Belgium, Canada, Pakistan, and Yugoslavia and its follower states illustrate the success and failure of specific language policies.
Devils in Petticoats
Authors: Taylor James
Published: February 2025

Chapter 1 surveys evidence for women’s involvement in early financial markets, not only as providers of capital, but also as intermediaries, managing the investments of others, and navigating the nascent financial district. It explores how women’s financial agency was problematized in public discourse, especially in the wake of the South Sea Bubble of 1720, and how financial activity was increasingly understood in gendered and sexualized terms, with male speculators mastering a feminized market. This conceptual exclusion was matched by an institutional exclusion with the enclosure of the market represented by the establishment of the Stock Exchange. The chapter explores the culture of the Stock Exchange as it developed in the nineteenth century, and how this culture depended upon excluding women. It goes on to explore the evolving boundaries between acceptable and unacceptable financial behaviour for women in Victorian Britain. The passive provision of capital for low-risk investments and the passive receipt of male advice were accepted, but the idea that women should speculate, or could become active financial agents in their own right, was scorned.
Being a Female Stockbroker in Late Victorian and Edwardian Britain
Authors: Taylor James
Published: February 2025

Chapter 2 demonstrates how a flourishing market outside the London Stock Exchange made it possible for women to establish stockbroking businesses from the 1880s. It identifies ten women who were active between the 1880s and 1910s, and explores the conditions that made it possible for them to become brokers, including the influence of the pioneering Americans Victoria Woodhull and Tennessee Claflin. It examines the women’s backgrounds, the kinds of businesses they established, and the clients they sought to attract. Some, like Amy Bell, catered to women investors, and saw their purpose in educational as well as commercial terms. Others traded anonymously, not seeking to use their gender as part of their ‘sales pitch’. While some promoted the idea of cautious, low-risk investment, others aimed to capitalize on the late Victorian boom in ‘bucket shops’, which encouraged gambling on stock prices rather than long-term investment. Just as historians have rejected the idea that there was a single ‘type’ of female entrepreneur, so there was no sole way to be a female stockbroker in this period.
The Scattered Torah
Authors: Vidas Moulie
Published: February 2025

Amoraic discussions center on knowledge of rabbinic texts, but this knowledge is presented as fragmentary. Frequently occurring phrases and rhetorical structures highlight the discovery of old-new teachings while at the same time emphasizing that even the greatest scholars do not know pertinent teachings; the recognition that knowledge is subject to the contingencies of individual access and geography is employed in passages that explain that certain teachings resulted from limited access to texts. Rather than presenting these problems as limitations, Amoraic scholarship leveraged them as interpretive and rhetorical resources.
Nine Accounts of Manipulation
Authors: Noggle Robert
Published: February 2025

This chapter surveys several accounts of manipulation, to see how they stack up against the data set of paradigm examples of manipulation from Chapter 2. It argues that while most of them get something right about manipulation, they all face significant challenges. Some fail to identify manipulation in some of the paradigm examples; others imply that manipulation is present when it seems to be clearly absent. The chapter identifies two of the most promising accounts: one that sees manipulation as a form of trickery, akin to lying and deception, and one that sees it as a form of pressure that falls short of coercion. Each of these two accounts fails to identify manipulation in about half of the paradigm examples from Chapter 2. However, each one succeeds precisely where the other fails, so that these two accounts together properly identify manipulation in all the paradigm examples from Chapter 2.
Making Muslims Great Again
Authors: Barylo William
Published: February 2025

The alt-bros are a heterogeneous movement of Muslims openly against women’s rights, vocal against social justice movements, Black people, and, for some, supporting the far-right and embracing white supremacist language. With an allusion to the Red Pill symbol appropriated by men’s right activists and the alt-right, they fear the decline of Islam in Euro-America not because of racism and islamophobia but because of feminism, liberalism, and the LGBTQ. They revendicate an exclusionary form of Muslimness and masculinity, excommunicating anyone who does not abide by their standards. However, what if societal pressures and dominant expectations made these potential community champions turn sour? And what if, reading their story from the perspective of affect, one could see them like bell hooks, as ‘comrades in struggle’?
SCEMENT: Scalable and Memory Efficient Integration of Large-scale Single Cell RNA-sequencing Data
Authors: Chockalingam Sriram P , Aluru Maneesha , Aluru Srinivas
Published: February 2025

Motivation

Integrative analysis of large-scale single cell data collected from diverse cell populations promises an improved understanding of complex biological systems. While several algorithms have been developed for single cell RNA-sequencing data integration, many lack scalability to handle large numbers of datasets and/or millions of cells due to their memory and run time requirements. The few tools which can handle large data do so by reducing the computational burden through strategies such as subsampling of the data or selecting a reference dataset, to improve computational efficiency and scalability. Such shortcuts however hamper accuracy of downstream analyses, especially those requiring quantitative gene expression information.

Results

We present SCEMENT, a SCalablE and Memory-Efficient iNTegration method to overcome these limitations. Our new parallel algorithm builds upon and extends the linear regression model previously applied in ComBat, to an unsupervised sparse matrix setting to enable accurate integration of diverse and large collections of single cell RNA-sequencing data. Using tens to hundreds of real single cell RNA-seq datasets, we show that SCEMENT outperforms ComBat as well as FastIntegration and Scanorama in runtime (upto 214X faster) and memory usage (upto 17.5X less). It not only performs batch correction and integration of millions of cells in under 25 minutes, but also facilitates discovery of new rare cell-types and more robust reconstruction of gene regulatory networks with full quantitative gene expression information.

Availability and implementation

Source code freely available for download at https://github.com/AluruLab/scement, implemented in C ++ and supported on Linux.

Supplementary information

Supplementary data are available at Bioinformatics online.
SimMS: A GPU-Accelerated Cosine Similarity implementation for Tandem Mass Spectrometry
Authors: Onoprishvili Tornike , Yuan Jui-Hung , Petrov Kamen , Ingalalli Vijay , Khederlarian Lila , Leuchtenmuller Niklas , Chandra Sona , Duarte Aurelien , Bender Andreas , Gloaguen Yoann
Published: February 2025

Motivation

Untargeted metabolomics involves a large-scale comparison of the fragmentation pattern of a mass spectrum against a database containing known spectra. Given the number of comparisons involved, this step can be time-consuming.

Results

In this work, we present a GPU-accelerated cosine similarity implementation for Tandem Mass Spectrometry (MS), with an approximately 1000-fold speedup compared to the MatchMS reference implementation, without any loss of accuracy. This improvement enables repository-scale spectral library matching for compound identification without the need for large compute clusters. This impact extends to any spectral comparison-based methods such as molecular networking approaches and analogue search.

Availability

All code, results, and notebooks supporting are freely available under the MIT license at https://github.com/pangeAI/simms/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Formation of biobased-polycarbonates via amorphous solid-state polymerization of isosorbide/isomannide with fluorinated carbonate
Authors: Taniguchi Taihei , Okazoe Takashi , Matsuoka Shin-ichi , Suzuki Masato
Published: February 2025

Polycarbonates (PC) derived from bio-derived diol monomers, isosorbide (ISB) and isomannide (IMN), are attractive alternatives to bisphenol A (BPA) PCs owing to their fused-bicyclic main chain structures. However, conventional solid-state polymerization (SSP) of amorphous polycarbonates requires crystallization of the monomers or oligomeric prepolymers. Previously, we disclosed the amorphous SSP of BPA with bis(1,1,1,3,3,3-hexafluoro-2-propyl) carbonate (BHFC), which efficiently synthesizes high-molecular-weight PCs. Here, we present the first synthesis of biobased PCs via amorphous SSP of a prepolymer prepared from ISB/IMN with BHFC. During the SSP, the reaction temperature was increased stepwise to 170°C, affording moderate- to high-molecular-weight poly(ISB carbonate)s and poly(ISB/IMN carbonate)s. Increasing the feed ratio decreased the molecular weight of the poly(ISB/IMN carbonate) copolymer. We also combined IMN with the bis(hexafluoroisopropyl carbonate) of IMN (IMNBFC) to obtain poly(IMN carbonate). Furthermore, ISB combined with IMNBFC afforded a copolymer consisting of alternating ISB and IMN units. No crystalline structures were observed during any SSP process or the resulting PCs. The PCs achieved satisfactorily high thermal stabilities, high glass transition temperatures, and low discoloration because the SSP was performed at lower temperatures than conventional melt polymerization.
Photocatalytic CO2 reduction in aqueous media using a silver-loaded conjugated polymer and a Ru(II)-Ru(II) supramolecular photocatalyst
Authors: Sakakibara Noritaka , McQueen Ewan , Sprick Reiner Sebastian , Ishitani Osamu
Published: February 2025

Visible-light-driven conversion of CO2 to useful products is a promising process for a more sustainable energy system in a circular economy. Whilst highly efficient, durable and selective systems have been reported in organic media, the photocatalytic process performing efficiently in aqueous media is highly desirable for the purpose of its practical application. However, efficiency and selectivity for CO2 reduction versus proton reduction in aqueous solution has proven challenging to date. Herein, this study demonstrates the enablement of highly efficient and durable visible-light driven photocatalytic CO2 reduction to formate in aqueous media by a hybrid photocatalyst consisting of a silver-loaded conjugated polymer and a binuclear Ru(II) complex. The hybrid photocatalyst exhibited high activity and durability for formate production, with an apparent quantum yield of 4.2% at 460 nm and a turnover number of 38,000 (based on the amount of binuclear complexes adsorbed), both of which are the highest values reported amongst hybrid photocatalysts in aqueous media. Even though the conjugated polymer retains residual amounts of palladium from synthesis (which is an active site for H2 production in aqueous media), the loading of Ag nanoparticles onto the conjugated polymer enhanced the activity and selectivity for photocatalytic CO2 reduction by suppressing H2 production.
TNBC molecular subtypes and potential detection targets for biological therapy indications
Authors: Zhang Yanchuan , Li Qinghua , Lan Jie , Xie Guojing , Zhang Guangjie , Cui Junhao , Leng Ping , Wang Yingshuang
Published: February 2025

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer associated with poor prognosis. While chemotherapy remains the conventional treatment approach, its efficacy is limited and often accompanied by significant toxicity. Advances in precision-targeted therapies have expanded treatment options for TNBC, including immunotherapy, poly (ADP-ribose) polymerase inhibitors, androgen receptor inhibitors, cell cycle-dependent kinase inhibitors, and signaling pathway inhibitors. However, the heterogeneous nature of TNBC contributes to variations in treatment outcomes, underscoring the importance of identifying intrinsic molecular subtypes for personalized therapy. Additionally, due to patient-specific variability, the therapeutic response to targeted treatments is inconsistent. This highlights the need to strategize patients based on potential therapeutic targets for targeted drugs to optimize treatment strategies. This review summarizes the classification strategies and immunohistochemical (IHC) biomarkers for TNBC subtypes, along with potential targets for identifying indications for targeted drug therapy. These insights aim to support the development of personalized treatment approaches for TNBC patients.
Atrophic rash on the trunk
Authors: Kan Siyue , Yang Lianjuan , Cai Qing
Published: February 2025

Atrophying pityriasis versicolor is an unusual presentation of pityriasis versicolor that can be misdiagnosed. Clinicians should be aware of this rare presentation. The clinical presentation, mycological tests and histopathological examinations of the patient were highly indicative of atrophying pityriasis versicolor.
Molecularly imprinted polymer for solid-phase extraction of oleanolic acid from Ligustrum lucidum fruit
Authors: Xu Jianling , Wang Wenna , Chen Yixin , Xu Xiaotian , Duan Ao , Zhu Yongyan , Zhu Quanhong
Published: February 2025

A molecularly imprinted polymer (MIP) was synthesized for the selective extraction of oleanolic acid (OA), employing OA as the template molecule, acrylamide as the functional monomer, ethylene glycol dimethacrylate as the cross-linking agent, azobisisobutyronitrile as the initiator, and chloroform as the porogenic solvent. The characterization of the obtained MIPs was evaluated by scanning electron microscopy, Fourier transform infrared spectroscopy, Brunauer–Emmett–Teller (BET) analysis and X-ray photoelectron spectroscopy. The MIPs reached adsorption equilibrium within 2 hours to OA, with high adsorption capacity of 124.68 mg/g. Subsequently, these MIPs were packed in empty solid-phase extraction (SPE) cartridge to enrichment OA from Ligustrum lucidum fruit extract. The parameters of SPE were optimized as follows: loading 0.5 ml of a 1.0 mg/ml OA reference solution, washing with 0.5 ml of toluene, and eluting with 4 ml of methanol. Under these conditions, the enrichment rate of OA from L. lucidum extract reached 76.0%. Additionally, an high-performance liquid chromatography method for determining OA content was validated. This study provides an effective approach for the separation and enrichment of OA from complex matrices and also provides practical feasibility for the separation and enrichment of other triterpenoids.
The Effectiveness of Newer Beta-Lactams for the Treatment of Antimicrobial-Resistant Gram-Negative Meningitis
Authors: Hsu Alice J , Chiotos Kathleen , Heil Emily L , Shields Ryan K , Tamma Pranita D
Published: February 2025

The treatment of gram-negative bacterial infections exhibiting resistance to all traditional β-lactam and fluoroquinolone agents (i.e., difficult-to-treat resistance [DTR]) poses challenges due to the limited numbers of active antibiotic agents, in addition to limited data on safety and efficacy. Managing DTR gram-negative infections becomes even more complex when present in the central nervous system due to concerns for insufficient concentrations of agents in the cerebrospinal fluid and brain parenchyma. Several newer β-lactam agents with activity against DTR gram-negatives are available including cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-cilastatin-relebactam, meropenem-vaborbactam, and sulbactam-durlobactam. In this article, we review host and drug factors that influence an antibiotic’s likely effectiveness for the treatment of bacterial meningitis. We also review the preclinical and clinical data in support of or against each of the aforementioned agents for the treatment of bacterial meningitis.
Entropic detection of chromatic community structures
Authors: Delaplace Franck
Published: February 2025

The identification of community structure represents a central challenge in the field of complex networks. The objective is to ascertain the internal organization of agents within a network and to provide a representative network partition. Each community is presumed to comprise nodes sharing a common objective or property. The identification of these communities is typically based on the difference in connectivity density between the interior and border of a community. Indeed, nodes sharing a common purpose or property are expected to interact closely. Although this rule appears to be relevant, it nevertheless fails to address fundamental scientific problems such as disease module detection, thereby highlighting the inability to meaningfully determine communities based solely on connectivity for this situation. Consequently, another paradigm is necessary to formalize this problem accurately and detect these communities objectively. In this article, we propose a new framework to study this novel community formation property. Considering that colors represent shared properties, the problem is to maximize groups of nodes of the same color within communities. We propose a novel algorithm for detecting community structure based on a new measurement, chromatic entropy, which quantitatively assesses the community structure based on color constraint.
Sex Steroid Hormones and Subclinical Atherosclerosis Progression in Postmenopausal Women
Authors: Chen Irene J , Stanczyk Frank Z , Sriprasert Intira , Karim Roksana , Shoupe Donna , Kono Naoko , Hodis Howard N , Mack Wendy J
Published: February 2025

Objective

The Early versus Late Intervention Trial with Estradiol demonstrated that hormone therapy (HT) reduces subclinical atherosclerosis progression in healthy postmenopausal women who initiated HT in proximity to menopause (<6 years) but not in those distant from menopause, (≥10 years). This analysis explores the role of serum sex steroid hormones and sex hormone-binding globulin (SHBG) in atherosclerosis progression, examining differences based on time since menopause.

Design

Post-trial analysis.

Methods

The study included 535 healthy postmenopausal women; nearly half received HT. Serum levels of estradiol, estrone, testosterone, and SHBG were measured at baseline, 12 months, and 36 months. Carotid intima-media thickness (CIMT) was assessed every six months. Mixed-effects linear models evaluate the relationship between sex steroid hormones, SHBG, and CIMT progression, with time since menopause included as an interaction term, after adjusting for age, hysterectomy, baseline CIMT, systolic blood pressure, and body mass index.

Results

Late postmenopausal women were older with higher baseline CIMT. Associations between estradiol, estrone, and SHBG levels with CIMT progression differed significantly by time since menopause (interaction p < 0.01). In early postmenopause, CIMT progression was significantly inversely associated with SHBG (p = 0.024) and nonsignificantly inversely with estradiol and estrone. In late postmenopause, CIMT progression was significantly positively associated with estradiol (p = 0.005), estrone (p < 0.001), and SHBG (p = 0.037).

Conclusion

Serum sex steroid hormones and SHBG relate differently to CIMT progression based on time since menopause. Estradiol, estrone, and SHBG levels show opposite associations with CIMT progression in early versus late postmenopause, highlighting the importance of HT timing in cardiovascular disease.
Atrial fibrillation catheter ablation, brain glymphatic function, and cognitive performance
Authors: Guo Jiahuan , Zhang Zhe , Meng Xu , Jing Jing , Hu Yiran , Yao Yan , Ding Ligang , Zheng Lihui , Zhao Xingquan
Published: February 2025

Background and Aims

It remains unknown whether the brain glymphatic system, which is driven by the heartbeat-driven pulsation of arteries and is responsible for cerebral waste clearance, is impaired in atrial fibrillation (AF) and mediates cognitive dysfunction related to AF. The aim of this study was to assess brain glymphatic alterations in AF, their role in cognitive function, and whether catheter ablation can improve glymphatic activity.

Methods

In this case-control and prospective before–and–after study, patients with AF and healthy controls (HCs) were enrolled. Participants underwent brain magnetic resonance imaging and a comprehensive neuropsychological battery. Glymphatic activity was quantified by diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Magnetic resonance imaging was repeated after surgery in patients who underwent ablation.

Results

Overall, 87 patients with AF and 44 HCs were enrolled. Compared with HCs, patients with AF had a lower ALPS index (P = .016). Nonparoxysmal AF patients showed lower ALPS index than both HCs (P = .002) and paroxysmal AF patients (P = .044). A lower ALPS index was associated with worse scores of Trail Making Test, Digit Symbol Substitution Test, Digit Span Test, and Stroop Colour and Word Test (all P < .05). Mediation analyses revealed that glymphatic activity was a mediator between AF and cognitive decline. Among the 50 patients who underwent ablation therapy, DTI-ALPS index was improved after surgery (P = .015).

Conclusions

Brain glymphatic function measured by DTI-ALPS index was impaired in patients with AF, mediates the association between AF and cognitive decline, and was improved after ablation therapy.
SCN10A-short gene therapy to restore conduction and protect against malignant cardiac arrhythmias
Authors: Wang Jianan , Verkerk Arie O , Wilders Ronald , Zhang Yingnan , Zhang Kelly , Prakosa Adityo , Rivaud Mathilde R , Marsman E Madelief J , Boender Arie R , Klerk Mischa , Fokkert Lianne , de Jonge Berend , Neef Klaus , Kirzner Osne F , Bezzina Connie R , Remme Carol Ann , Tan Hanno L , Boukens Bastiaan J , Devalla Harsha D , Trayanova Natalia A , Christoffels Vincent M , Barnett Phil , Boink Gerard J J
Published: February 2025

Background and Aims

Life-threatening arrhythmias are a well-established consequence of reduced cardiac sodium current (INa). Gene therapy approaches to increase INa have demonstrated potential benefits to prevent arrhythmias. However, the development of such therapies is hampered by the large size of sodium channels. In this study, SCN10A-short (S10s), a short transcript encoding the carboxy-terminal domain of the human neuronal sodium channel, was evaluated as a gene therapy target to increase INa and prevent arrhythmias.

Methods

Adeno-associated viral vector overexpressing S10s was injected into wild type and Scn5a-haploinsufficient mice on which patch-clamp studies, optical mapping, electrocardiogram analyses, and ischaemia reperfusion were performed. In vitro and in silico studies were conducted to further explore the effect of S10s gene therapy in the context of human hearts.

Results

Cardiac S10s overexpression increased cellular INa, maximal action potential upstroke velocity, and action potential amplitude in Scn5a-haploinsufficient cardiomyocytes. S10s gene therapy rescues conduction slowing in Scn5a-haploinsufficient mice and prevented ventricular tachycardia induced by ischaemia-reperfusion in wild type mice. S10s overexpression increased maximal action potential upstroke velocity in human inducible pluripotent stem cell-derived cardiomyocytes and prevented inducible arrhythmias in simulated human heart models.

Conclusions

S10s gene therapy may be effective to treat cardiac conduction abnormalities and associated arrhythmias.
Priorities for medical device regulatory approval: a report from the European Society of Cardiology Cardiovascular Round Table
Authors: Windecker Stephan , Fraser Alan G , Szymanski Piotr , Gilard Martine , Lüscher Thomas F , Abid Leila , Brennan John , Byrne Robert , Crotti Lia , Drossart Inga , Franke Jennifer , Cossellu Mario Gabrielli , Kirtane Ajay J , Kurucova Jana , Krucoff Mitchell , McGauran Gearóid , Myers Patrick O , O’Connor Donal B , Parma Radosław , Piscoi Paul , Rao Archana , Rappagliosi Andrea , Stefanini Giulio , Samset Eigil , Vincent Alphons , von Bardeleben Ralph Stephan , Weidinger Franz
Published: February 2025

The European Union (EU) Medical Device Regulation increased regulatory scrutiny to improve the safety and performance of new medical devices. An equally important goal is providing timely access to innovative devices to benefit patient care. The European Society of Cardiology strongly advocates for the evolution of the Medical Device Regulation system to facilitate priority access for innovative devices for unmet needs and orphan cardiovascular (CV) medical devices in EU countries. Although device approval is currently executed by Notified Bodies in the EU, it will be advantageous in the mid-term to consider a single EU regulatory agency for devices. In the short term, steps can be taken to transform the current system into a more efficient, predictable, cost-effective, and user-friendly service. Key strategies include the following: enhancing predictability of the approval process through use of early scientific advice from regulators; establishing unique regulatory pathways for CV orphan, paediatric, and innovative devices; promoting more efficient (re)certification of essential legacy CV devices; improving transparency of sponsor interactions with Notified Bodies; expanding the roles of the Expert Panels to assist in the approval of CV devices; promoting global regulatory harmonization, considering streamlined authorization of CV medical technologies across selected jurisdictions; developing an efficient system to monitor device safety; and ensuring funding for data collection platforms. Some strategies that could help include considering a pilot programme for joint approval processes of selected devices in partnership with other regions (i.e. US Food and Drug Administration); developing priority pathways for accelerated access to innovative or orphan devices; and increasing recognition of the importance of early feasibility studies in the EU.
Frailty trajectories after a cardiovascular event among community-dwelling older people
Authors: Phyo Aung Zaw Zaw , Tonkin Andrew , Espinoza Sara E , Vishwanath Swarna , Murray Anne M , Woods Robyn L , Callahan Kathryn E , Peters Ruth , Ryan Joanne
Published: February 2025

Aims

Individuals with cardiovascular disease (CVD) are more likely to become frail. However, no study has determined whether an incident CVD event alters frailty trajectories in older individuals. This study aims to determine the extent to which an incident CVD event modifies frailty trajectories and to identify factors that influence those changes.

Methods

19,111 individuals (56.4%, women) ≥aged 65 years, who had no prior CVD event or other major health conditions at baseline, were followed for up to 11 years. Frailty was measured annually using the 64-item deficit-accumulation frailty index (FI) and Fried phenotype (Fried). Incident CVD events, including stroke, myocardial infarction and hospitalization for heart failure (HHF), were adjudicated by international experts. Linear mixed models were used to measure frailty changes.

Results

Over a median 8.3-year follow-up, frailty trajectories increased over time and 1934 incident CVD events occurred. Following a CVD event, individuals had a short-term increase in both FI (adjusted-betas: 3.65; 95%CI, 3.34 to 3.96) and Fried (adjusted-beta: 0.32; 95%CI, 0.26 to 0.38). Afterwards, only FI continued to increase over time (adjusted-beta: 0.41, 95%CI, 0.21 to 0.62). Among the CVD events, HHF and stroke were associated with the greatest increase in frailty. Of the factors examined, being >80 years, women, living alone, or residing in regional/remote areas were associated with greater frailty burden.

Conclusion

Our findings provide evidence that incident CVD event increases frailty burden, highlighting the need for targeted intervention to minimise frailty-related clinical complications for those most at risk.
Left Atrial Intramyocardial Fat at Pulmonary Vein Reconnection Sites during Atrial Fibrillation Redo Ablation
Authors: Landra Federico , Saglietto Andrea , Falasconi Giulio , Penela Diego , Soto-Iglesias David , Curti Emanuele , Tonello Bruno , Teresi Lucio , Turturiello Dario , Franco-Ocaña Paula , Gigante Carlo , Valeriano Chiara , Capobianco Claudio , Francia Pietro , Alderete José , Viveros Daniel , Bellido Aldo Francisco , Zaraket Fatima , Martí-Almor Julio , Cameli Matteo , Berruezo Antonio
Published: February 2025

Structured Abstract

Background and Aims

Electrical reconnections between pulmonary veins (PVs) and the left atrium (LA) are frequently responsible for atrial fibrillation (AF) recurrences after pulmonary vein isolation (PVI). Multidetector computed tomography (MDCT)-derived images can be post-processed to detect intramyocardial fat (inFAT) by signal radiodensity thresholding. The role of inFAT on PV-LA reconnections remains unknown. The aim of this study was to analyze the relationship between inFAT localization at pre-procedural MDCT-derived inFAT maps from first AF ablation and PV-LA reconnections in patients with AF recurrence undergoing redo ablation.

Methods

We included 45 consecutive patients who underwent AF redo ablation presenting at least one PV-LA reconnection. First AF ablation preprocedural MDCT-derived data were post-processed with ADAS 3DTM to create 3D LA inFAT maps, that were loaded into CARTO3 navigation system and merged with the electroanatomical map for reconnection site analysis.

Results

In 103 out of 156 (66.0%) PV-LA reconnection points inFAT was identified in the 6mm diameter tag point depicted in the navigation system. When dividing the PVI line into standardized segments, those identified as containing PV-LA reconnection points (i.e. reconnection segments) exhibited significantly higher total inFAT volumes compared with non-reconnection segments (8.05±6.56 vs. 5.40±5.18 μL, p<0.001). Additionally, reconnection segments showed greater volumes of inFAT components, specifically dense inFAT (0.06±0.06 vs. 0.03±0.04 μL, p<0.001) and fat-myocardial admixture (7.98±6.52 vs. 5.37±5.16 μL, p<0.001).

Conclusion

InFAT is co-localized with two thirds of PV-LA reconnection points in patients undergoing AF redo ablation. Reconnection segments exhibit significantly higher inFAT volumes compared to non-reconnection segments. This proof-of-concept study suggests that inFAT may play a role in PV-LA electrical reconnections following PVI.
Relocating seismic events in the North Sea: challenges and insights for earthquake analysis
Authors: Jerkins Annie Elisabeth , Schweitzer Johannes , Kettlety Tom , Martuganova Evgeniia , Kühn Daniela , Oye Volker
Published: February 2025

In this paper, we present a catalogue of relocated seismic events in the North Sea spanning 1961 to 2022. Data from all relevant agencies were combined, incorporating all available seismic phase readings, thereby enhancing station coverage. As a result, our updated locations reveal a more clustered and aligned seismicity pattern compared with the original catalogue. Even with our combined dataset, only 157 of the 7,089 relocated events have azimuthal gaps of less than 90 degrees. Additionally, the distances between onshore stations and offshore events are considerable. Both of these factors lead to relatively poorly constrained hypocentres for most events. We therefore evaluate the performance of 1D velocity models routinely used by different North Sea adjacent monitoring agencies for earthquake location estimations in the North Sea. The variations in assessments due to the seismic velocity model used are significantly larger than the uncertainty ellipses calculated in the relocation, demonstrating that arithmetic uncertainties systematically underestimate location uncertainties in this setting. Obtaining a realistic estimate of location uncertainty is however crucial, particularly for distinguishing between natural and induced seismicity. This is fundamental to safe monitoring of the North Sea offshore industries, including geological CO2 storage. To overcome these discrepancies between the uncertainty ellipses and our multiple relocations, we introduce an alternative method that accounts for variability in the 1D velocity models. This approach enhances the reliability of the earthquake catalogue, and provides a more robust assessment of seismic activity in the North Sea.
Novel Transcriptomic Signatures in Fibrostenotic Crohn’s Disease: Dysregulated Pathways, Promising Biomarkers, and Putative Therapeutic Targets
Authors: Acharjee Animesh , Shivaji Uday , Santacroce Giovanni , Akiror Sarah , Jeffery Louisa , Varnai Csilla , Reynolds Gary , Zardo Davide , Majumder Snehali , Amamou Asma , Gkoutos Georgios V , Iacucci Marietta , Ghosh Subrata
Published: February 2025

Background

Fibrosis is a common complication in Crohn’s disease (CD), often leading to intestinal strictures. This study aims to explore the transcriptomic signature of fibrostenotic ileal CD for a comprehensive characterization of biological and cellular mechanisms underlying intestinal fibrosis.

Methods

Nine CD patients undergoing surgery for fibrotic ileal strictures were prospectively recruited. RNA was extracted from fresh resected samples for bulk transcriptomics. Differentially expressed genes (DEGs) were identified (adj. P value < .05), and machine learning analyses were employed to compare gene expression patterns between strictures and non-strictured margins. Pathway enrichment analysis pinpointed relevant pathways. Furthermore, a random forest model was constructed to evaluate the significance of targeted genes. Relevant genes were subsequently validated through qPCR and further analyzed using a publicly available bulk RNA-seq dataset (GSE192786). Single-cell RNA sequencing (scRNA-seq) analysis was performed using the 10× Chromium Controller platform.

Results

Bulk transcriptomics revealed unique transcriptomes with 81 DEGs, 64 significantly up-regulated, and 17 down-regulated in strictures compared to non-strictured margins. Up-regulated genes were mainly associated with inflammation, matrix and tissue remodeling, adipogenesis and cellular stress, while down-regulated genes were linked to epithelial barrier integrity. LY96, AKAP11, SRM, GREM1, EHD2, SERPINE1, HDAC1, and FGF2 showed high specificity for strictures. scRNA-seq linked up-regulated GREM1 exclusively to fibroblasts, while EHD2 and FGF2 showed upregulation in both fibroblasts and endothelial cells. LY96 and SRM were expressed by immune cells, whereas HDAC1, AKAP11, and SERPINE1 showed low expression across all cellular subsets.

Conclusions

This study comprehensively characterizes resected CD ileal strictures, elucidating main dysregulated pathways and identifying promising biomarkers and putative therapeutic targets.