bluuebunny/crossref_metadata_2025 huggingface dataset:
Co‐Design of Watermarking and Controller for Reducing Detection Delay of Replay Attacks
Authors: Xia Chenggang , Liu Kun , Wang Haojun , Liu Tao , Li Juntao , Xia Yuanqing
Published: February 2025

This paper investigates the problem of reducing the detection delay of the replay attacks by co‐designing the watermarking signal and the controller parameters. Based on the dynamic encryption‐decryption scheme, we propose a cumulative sum test, which utilizes the sensor measurements and watermarking signals to detect the replay attacks, and derive the relationship between the detection delay and the watermarking signal covariance. Then, we analyze the control performance loss caused by the watermarking signal added to the sensor measurements to expose the replay attacks. Furthermore, to reduce the detection delay, an optimization problem is formulated to design the optimal covariance of the watermarking signal with a tolerable control performance loss. Finally, we reformulate another optimization problem of co‐designing the watermarking signal and the controller parameters to simultaneously reduce the detection delay and the control performance loss. A numerical example is provided to verify the effectiveness of theoretical results.
Carbon Quantum Dots with Tunable Size and Fluorescence Intensity for Development of a Nano‐biosensor
Authors: Park So Yeon , Tan Justin Kok Soon , Mo Xuancheng , Song Yujin , Lim Jiaqi , Liew Xuan Ru , Chung Hyunsoo , Kim Sangho
Published: February 2025

Carbon quantum dots (CQDs) are a class of nanomaterials known for their remarkable photostability, chemical inertness and biocompatibility. Changing their size, structure, and surface chemistry enable the tuning of their luminescence property, which gives them tremendous potential for various applications. CQDs synthesis typically involves long tedious processes, requiring multiple steps and harsh reaction conditions. Here, a new reliable, economical, and ultra‐rapid one‐step fabrication method is introduced to obtain CQDs with well‐defined and reproducible photoluminescence properties via a simple heat treatment. These solid‐state CQDs are homogenous in size and are ready to use without the need for further purification. The size of the fabricated CQDs and their corresponding peak fluorescence intensity are confirmed to be tunable by simple adjustment of the heat treatment conditions. Coupled with their selective fluorescence quenching by metal ions, the clinical potential of CQDs is demonstrated for biosensing applications by designing a new nano‐biosensor to assess the quality of stored blood units through hemolysis quantification without disrupting storage conditions. This may pave the way for a new standard in blood bank inventory management.
Interaction Between Strain and Phase Formation in HfxZr1‐xO2 Thin Films
Authors: Wunderwald Florian , Xu Bohan , Kersch Alfred , Holsgrove Kristina M. , Kao Yu‐Cheng , Richter Claudia , Enghardt Stefan , Mikolajick Thomas , Schroeder Uwe
Published: February 2025

HfxZr1‐xO2 thin films have excellent complementary metal–oxide semiconductor compatibility and scalability compared to other ferroelectric materials. This makes them a promising candidate for non‐volatile memory applications. However, the polymorphism of the materials presents a challenge in stabilizing the ferroelectric properties. Since the wake‐up free non‐volatile memory applications require the presence of ferroelectric properties in the pristine state of the films without additional electric field cycling, it is necessary to understand how to promote the ferroelectric orthorhombic phase formation. In this work, the interaction between in‐plane tensile strain and phase formation of atomic layer deposition grown HfxZr1‐xO2 thin films with different thicknesses and different compositions is demonstrated. By combining the biaxial in‐plane tensile strain with the electric switching field and remanent polarization, it is observed that the best ferroelectric properties correlated with an in‐plane tensile strain range of 0.4–0.6%. Moreover, the observed correlation between strain and phase formation indicates that strain exerts an influence on phase formation in the pristine state, and that phase formation, in turn, affects strain during electrical field cycling. This work is expected to be helpful to improve the ferroelectric properties in HfxZr1‐xO2 films, which can be processed for different memory devices with specialized requirements.
A Novel Multicompartment Barrier‐Free Microfluidic Device Reveals the Impact of Extracellular Matrix Stiffening and Temozolomide on Immune‐Tumor Interactions in Glioblastoma
Authors: Bayona Clara , Olaizola‐Rodrigo Claudia , Sharko Vira , Ashrafi Mehran , Barrio Jesús del , Doblaré Manuel , Monge Rosa , Ochoa Ignacio , Oliván Sara
Published: February 2025

The immune system plays a crucial role in shaping the glioblastoma tumor microenvironment, characterized by its complexity and dynamic interactions. Understanding the tumor‐immune crosstalk is essential for advancing cancer research and therapeutic development. Here, a novel multicompartment, barrier‐free microfluidic device is presented that overcomes the limitations of existing models by enabling direct tumor‐immune interactions without physical barriers, preserving natural immune cell infiltration. This platform supports the independent and simultaneous culture of tumor and immune cells, replicating the healthy‐tumoral stroma interface, and allows investigating the effect of matrix stiffness and chemotherapy on both populations. The findings reveal that increased collagen concentration promotes tumor invasiveness while impairing immune cell infiltration. Additionally, temozolomide treatment reduces immune cell motility but enhances anti‐tumor immune responses. These insights highlight the critical roles of extracellular matrix mechanics and chemotherapy in tumor progression and immune modulation, establishing this device as a powerful tool for studying glioblastoma‐immune dynamics and evaluating therapeutic strategies.
Advanced Adaptive Protein Membrane with Super‐High Flux and Precise Molecular Sieving of Dyes from Salts
Authors: Zhang Zhaoqian , Sun Hao , Xin Shaopeng , Hu Qiaoxia , Wang Jian , Hu Yunxia
Published: February 2025

Precise separation of small organic molecules and electrolyte salts is critical for various industrial processes, necessitating advanced membranes with uniform pores. Proteins, as one typical nature polymer having the exactly same structure and molecular weight, offer a promising material for making such membranes. Here, hemoglobin (BHb) and lysozyme (Lyz) are utilized to fabricate precise nanofiltration membranes through amyloid‐like co‐assembly, triggered by Tris(2‐carboxyethyl) phosphine. Molecular dynamics simulations reveal that BHb intercalates between Lyz molecules, enhancing tight assembly and reducing defects. The Lyz/BHb membrane exhibits a high void volume of 27.2% and achieves an exceptional permeance of 335 L m−2 h−1 bar−1. Amazingly, the Lyz/BHb membrane achieves ultra‐selective molecular sieving of dyes and salts with an unparalleled high separation factor of 1.25 × 103 for the NaCl/Brilliant blue. The unique adaptive separation layer is formed by anchoring dye molecules into the larger pores and thus narrowing down the pore size distribution and enhancing electrostatic repulsion, endowing the membrane with a distinctive molecular sieving of dyes and salts. This study offers valuable insights to finely tailor the pore structure of the membrane by co‐assembly of proteins and to significantly enhance the membrane perm‐selectivity by creating an adaptive protein separation layer with a unique molecular sieving property.
Controllable Syntheses, Structure Identifications, and Property Explorations of Self‐Intercalated 2D Transition Metal Chalcogenides
Authors: Cheng Yujin , Quan Wenzhi , Wang Jialong , Peng You , Zhou Tong , Ding Haoxuan , Zhang Yanfeng
Published: February 2025

2D transition metal dichalcogenides (2D TMDCs) have attracted intensive interest in physics and materials science‐related fields, due to their exotic properties (e.g., superconductivity, charge density wave (CDW) phase transition, magnetism, electrocatalytic property). Intercalation of native metal atoms in the layered 2D TMDCs (e.g., from VS2 to V5S8 by V intercalation) can afford new stoichiometric ratios, phase states, and thus rich properties. This review hereby summarizes the recent progress in the controllable syntheses, structure characterizations, and property explorations of self‐intercalated 2D transition metal chalcogenides (TMCs), with the metal elements focusing on group‐V, VI, and VIII metals. The self‐intercalation‐related synthetic strategies will be introduced via chemical vapor deposition (CVD) and molecule beam epitaxy (MBE), especially by tuning the chemical potentials of intercalated metal elements, growth promoters, substrates, etc. Additionally, the structure/phase identifications of the self‐intercalated 2D TMCs through various characterization techniques will be overviewed. More significantly, the intriguing properties in such 2D TMCs will be thoroughly discussed, such as the thickness‐ or composition‐dependent magnetism, CDW phase transition, electrocatalytic property, etc. Finally, challenges and prospects are proposed for developing new self‐intercalated 2D materials and their heterostructures and exploring their unique properties and applications.
Effects of Various Physical Field–Assisted Techniques and Combination Methods on Extraction of Flavonoids and Polyphenols From Angelica keiskei
Authors: Sun Guoxiu , Wang Jiaqi , Wang Ningning , Zhao Shengnan , Zhao Yuting , Yan Yunqing , Tang Shuwei , Li Zichao
Published: February 2025

Angelica keiskei has been well documented as a promising resource rich in bioactive chemicals, especially flavonoids. Field‐assisted extraction and their hybrids have been proved to be advanced approaches for the efficient utilization of flavonoids compared to conventional extraction methods. The current study aims to optimize the extraction conditions of the flavonoids from A. keiskei through high‐pressure processing, ultrasound‐assisted extraction, and microwave‐assisted extraction. Furthermore, taking total flavonoid content, total phenolic content, and antioxidant activity as indexes, three combination methods, high‐pressure processing combined with ultrasound‐assisted extraction, high‐pressure processing combined with microwave‐assisted extraction, and ultrasound‐assisted extraction combined with microwave‐assisted extraction, were further investigated and compared to enhance the extraction efficiency. The results indicate that the A. keiskei extracts obtained by ultrasound‐assisted extraction combined with microwave‐assisted extraction have the optimal total flavonoid content (41.671 mg/g) and total phenolic content (12.071 mg/g), as well as the strongest antioxidant activity. Scanning electron microscopy analyses reflect that the ultrasound‐assisted extraction combined with microwave‐assisted extraction treatment imposed the most pronounced damage to A. keiskei, in which the particles were changed into the smaller size. In vitro experiments for A. keiskei extracts demonstrate that it can effectively inhibit α‐amylase and tyrosinase, suggesting its potential hypoglycemic and whitening activity. This study demonstrates that A. keiskei extracts may serve as a possible source of antioxidants, whereas ultrasound‐assisted extraction combined with microwave‐assisted extraction might represent an innovative and advantageous method for flavonoid extraction from A. keiskei.
Isolation, LC–MS/MS, NMR Characterization, In Silico Toxicity, and ADME Evaluation of Stress‐Degradation Products of Sunitinib With Optimized Stability‐Indicating HPLC Method for Quantification of Sunitinib and its Impurities
Authors: Shaik Rasheed Babu , Devi Dharmasoth Rama , Basavaiah K. , Rao B. M.
Published: February 2025

Sunitinib belongs to the tyrosine kinase inhibitors class of medical drugs prescribed to treat various types of cancers, including renal cell carcinoma, gastrointestinal stromal tumors, and pancreatic neuroendocrine tumors by blocking the action of enzymes that promote cancer cell growth. Forced degradation studies are crucial for assessing drug stability and will be helpful in drug discovery and development. In this study, sunitinib underwent different stress testing according to ICH guidelines to identify and analyze its degradation products (DPs). The stress study findings proved that sunitinib is highly sensitive to acid (2DPs), base (1 DP), and oxidation (1 DP) degradation but remains stable in other stress conditions with significantly less degradation. The separation of sunitinib and its impurities and four DPs was achieved using a Waters XBridge C18 column (250 mm × 4.6 mm, 5 µm) with 0.7 mL/min gradient flow of ammonium formate buffer (pH 4.8) and acetonitrile with a detection wavelength of 258 nm. These conditions produce well‐retained and resolved peaks corresponding to sunitinib at 8.4 min, whereas 4.8, 3.5, and 1.9 min are noticed for impurities 1, 2, and 3, respectively. These study findings provide a comprehensive analysis of sunitinib, its impurities, and DPs, offering crucial insights into its stability and toxicity that can enhance drug development and safety profiling. The study also detailed the degradation pathway of sunitinib, its impurities, and the fragmentation patterns of DPs, which had not been previously reported in any other studies. All these four DPs belong to Class 4 (moderate) toxicity with distinct pharmacokinetic profiles. Hence, it can be concluded that these study findings provide a comprehensive analysis of sunitinib, its impurities, and DPs, offering crucial insights into its stability and toxicity that can enhance drug development and safety profiling.
Colloidal Magnetoelectric Shape Recognition Based on Machine Learning
Authors: Hu Xichen , Liu Xianhu , Ikkala Olli , Peng Bo
Published: February 2025

Functionalized particles ranging from nanoscale to microscale and their assemblies have facilitated a wide variety of sensing concepts, from molecular‐scale chemical and biological detection to large‐scale engineering defect testing. Related to macroscopic object shape sensing, visual recognition is generally the most versatile approach whenever possible. However, under certain conditions where visual perception is hindered, for example, dark space or underwater, electrosensing can serve as an alternative sensation manner. Inspired by this concept, the sensing of rudimentary object shapes using electrically conductive, soft ferromagnetic Ni particles is demonstrated, herein denoted as colloidal magnetoelectric shape recognition. By confining the target and sensory particles between two planar electrodes and using a magnetic field to drive the particles toward object edges, changes in electrical conductivity are monitored. Machine learning is then used to resolve the exact object shapes with high fidelity. This study introduces a colloidal magnetoelectric shape recognition strategy for short‐range shape sensing, with potential applications suggested for the fields such as soft robotics, drug delivery, and biomedical diagnostics.
Minimal Damage and Tunable Fabrication of Atomic‐Scale Ultrathin YBa2Cu3O7‐δ Nanowires with High Uniformity
Authors: Ma Huiqin , Wang Hanbin , Wang Yang , Luo Zhengyang , Li Zongpei , Wang Yong , Du Xinchuan , Yang Chao , Huang Jianwen , Wu Chunyang , Li Nannan , Wang Xianfu , Liu Yuqing , Li Peng
Published: February 2025

The growing demand for deep‐space optical communication and remote sensing has highlighted the need for high‐temperature superconducting nanowire single photon detectors (SNSPDs). However, fabricating ultrathin and ultranarrow high‐temperature superconducting nanowires remains significant challenges due to the extreme instability of their films. Herein, an effective approach is presented for fabricating high‐quality YBa2Cu3O7−δ (YBCO) nanowires by utilizing in situ protective layers that shield ultrathin films from environmental and processing‐induced degradation, coupled with low‐temperature etching techniques to achieve precise, and tunable etching while minimizing damage. Thus, YBCO nanowires are successfully fabricated with a minimum width of 68 nm, an atomic‐scale thickness of 5 nm, and lateral damage limited to ≈15 nm. These nanowires exhibit robust I–V hysteresis and a minimum switching current (Is) of about 120 μA. The coefficient of variation for the Is less than 6% and for the critical temperature (Tc0) is below 1%, confirming the exceptional uniformity of the nanowires. Electrical transport measurements reveal that voltage switching in these nanowires is governed by phase slip and hotspot effects. These advancements open new avenues for YBCO‐based high‐temperature SNSPDs, addressing a key challenge in the broader deployment of high‐temperature superconducting devices, including SNSPDs, superconducting quantum interference devices, and superconducting diodes.
Mapping the Foreign Investments (OFDI) From Emerging Economies Toward Developed Nations: A Consequential Convergence of Investment Outflows and the OLI Paradigm
Authors: Nomani Abuzar , Rithi S. R. , Negi Raghuveer
Published: February 2025

A fascinating insight we present in this research is what instigated the flow of outward FDI from emerging economies (EE) to developed nations by employing the O‐L‐I framework. Here, we offer the novelty of our research through earlier studies that only used the O‐L‐I framework to understand the genesis of FDI outflow from developed nations (DN) to developing/emerging economies. The mapping of investment patterns from EE materialized in 3‐D (EE to DN, EE to EE, and DN to EE) by incorporating country‐specific ownership, location, and internalization advantages. Twenty years of panel data have been used from nine countries. We used pooled OLS, random‐effects, and fixed‐effect models to understand the cause–effect relationship. Our findings exhibit that technological advancement, infrastructure, and economic stability are the major drivers for outward investment flow from one nation to another. In addition, patents and infrastructure can initiate the outward flow of FDI from emerging countries to developed countries.
Copper‐doped ZnO‐chitin‐cellulose mesoporous nanostructures for enhanced structural, optoelectronic, and antimicrobial efficacy
Authors: El Nahrawy Amany M. , Seddeek M. K.
Published: February 2025

This study shows the development and characterization of innovative mesoporous Cu‐doped ZnO‐chitin‐cellulose nanostructures, leveraging a semi‐dissolved chitin templating approach to reinforce their structural and functional properties. This innovative approach enhances the structural and functional properties of the composites, demonstrating significant advancements in optoelectronic and antimicrobial performance. FTIR peaks at 971, 787, 621, and 482 cm−1 suggest metal‐oxygen vibrations and interactions between Zn, Cu ions, and functional groups in the chitin‐cellulose matrix. The chitin‐cellulose and ZnO‐chitin‐cellulose composite were influenced by the presence of Cu ions, by the appearance of absorption peaks at 240 and 303 nm. Incorporating Zn and ZnCu ions altered the composite's bandgap, reducing it from 3.6 to 2.75 eV, thereby enhancing its optical properties. Band gap analysis manifests a decrease in energy gap attributed to Cu doping and the interaction between Cu‐3d and O‐2p states. The antimicrobial efficacy of chitin‐cellulose composites loaded with Zn and ZnCu was significantly enhanced compared to the unloaded samples, with the loaded composites achieving nanoparticle sizes ranging from 26 to 32 nm, respectively. Significant antibacterial activity was observed, with zones of inhibition measured at 26–29 ± 1 mm for E. coli, 29–30 ± 1 mm for B. subtilis, 26–24 ± 1 mm for C. albicans, and 30–32 mm ± 1 for A. fumigatus. The addition of Cu‐doped ZnO into the chitin‐cellulose matrix significantly enhances the composite's surface area, band gap, photonic activity, and antimicrobial activity, further amplifying its functionality. These advanced properties position the materials as highly suitable for diverse critical applications, including active packaging, drug delivery systems, optoelectronic, and UV shielding solutions.

Highlights

Innovative mesopores Copper@ ZnO‐Chitin‐Cellulose nanostructures.

Nanoparticle ratios influence the properties of chitin‐cellulose nanostructures.

Cu@ ZnO enhances absorption and decreases the band gap, providing strong UV protection.

Bioactive mesoporous structures display strong antimicrobial efficacy for biomedical use.
Theological Journals Between Professionalisation and Cooperation: Navigating the High-Low Distinction Between Editorial Boards and Non-academic Contributors in Germany, 1828–1870
Authors: Smits Johan C.
Published: February 2025

Theological journals were an important stage for negotiating the high–low distinction between academic and non-academic scholars. This chapter examines three German theological journals (1828–1870), focussing on the interactions between their editorial boards and non-academic scholars. The fates of these journals, the Theologische Studien und Kritiken, the Deutsche Zeitschrift für christliche Wissenschaft und christliches Leben and the Jahrbücher für deutsche Theologie, give valuable insight into both the attempted professionalisation of academic theology and the impossibility of fully disentangling it from non-academic scholarship. The chapter argues that the involvement of non-academic contributors was integral to the journals’ inception plans. Over the years, some non-academic contributors, primarily those from the clergy or involved in education, developed an impressive activity in the journals’ content. This chapter seeks to assess the motivations of these authors through an analysis of their publications. It concludes with case studies from the editorial correspondence of the Theologische Studien und Kritiken to illustrate the tensions between maintaining academic standards and incorporating contributions from scholars outside academia.
“He teaches me so I can teach”: Revivalism and Protestant Laywomen in 19th-Century Italy
Authors: Popa Laura
Published: February 2025

In the 19th century, religious awakenings transformed popular culture in both the Protestant United Kingdom and the United States, as well as in Catholic Italy. Yet very little is known about Protestant laywomen’s experiences in Catholic countries. This archival-research-based chapter first frames the revival in the Waldensian Church following the Italian Unification, then the roles Italian women played in the 19th-century revivals. It then focuses on the conversion story and life of a schoolteacher and Bible Woman, Giuseppina Pusterla (1827–1913). By focusing on this case study, the chapter proposes that laywomen experienced religious self-empowerment through the act of conversion, which was ignited by a personal Bible reading in vernacular Italian. According to Giuseppina Pusterla, a converted Waldensian, appropriating the Bible for herself enabled her to break free from institutionalised Catholicism and resist subsequent persecution. The chapter also suggests that laywomen manifested emancipatory impulses, yet without directly addressing emancipation. Drawing inspiration from the Bible, Giuseppina Pusterla broke with stereotypical gender roles by teaching children and adults, evangelising both men and women and engaging in debates with male clergy.
WD Detector: deep learning-based hybrid sensor design for wood defect detection
Authors: Kılıç Kenan , Kılıç Kazım , Doğru İbrahim Alper , Özcan Uğur
Published: February 2025

The fast-growing human demands in the world are leading to the expansion of industrialization. As wooden materials are increasingly used in industrial settings, detecting defects in wood has become crucial. Wood defects adversely affect the quality and durability of materials. A wood defect detection method, named WD Detector, is proposed in this study to identify wood defects. There are 18,284 defective wood surface images and 1,992 undefect wood images in a dataset of 20,276 wood images used for wood defect detection. 12 different classical machine learning algorithms are used to classify wood defects after extracting features from images with various CNNs and transfer learning approaches. In this study, feature extraction is performed by training the Xception CNN model. Once the features are extracted, classical machine learning algorithms are used to classify the wood defects. For the first time, a deep learning-based hybrid sensor design has been implemented on this dataset for wood defect detection. WD Detector achieved 99.32% accuracy in detecting wood surface defects using the new method. The success of this study’s method in detecting wood defects is believed to pave the way for future studies.
The impact of circadian rhythm disruption on oxaliplatin tolerability and pharmacokinetics in Cry1−/−Cry2−/− mice under constant darkness
Authors: Akyel Yasemin Kubra , Seyhan Narin Ozturk , Gül Şeref , Çelik Melis , Taşkın Ali Cihan , Selby Christopher P. , Sancar Aziz , Kavakli Ibrahim Halil , Okyar Alper
Published: February 2025

Circadian rhythms, the 24-h oscillations of biological activities guided by the molecular clock, play a pivotal role in regulating various physiological processes in organisms. The intricate relationship between the loss of circadian rhythm and its influence on the tolerability and pharmacokinetic properties of anticancer drugs is poorly understood. In our study, we investigated the effects of oxaliplatin, a commonly used anticancer drug, on Cry1

−/−
and Cry2

−/−
mice (Cry DKO mice) under darkness conditions, where they exhibit free-running phenotype. We administered oxaliplatin at a dosage of 12 mg/kg/day at two distinct circadian times, CT8 and CT16, under constant darkness conditions to Cry DKO mice and their wild type littermates. Our results revealed a striking disparity in oxaliplatin tolerance between Cry DKO mice and their wild-type counterparts. Oxaliplatin exhibited severe toxicity in Cry DKO mice at both CT8 and CT16, in contrast to the wild type mice. Pharmacokinetic analyses suggested that such toxicity was a result of high concentrations of oxaliplatin in the serum and liver of Cry DKO mice after repeated dose injections. To understand the molecular basis of such intolerance, we performed RNA-seq studies using mouse livers. Our findings from the RNA-seq analysis highlighted the substantial impact of circadian rhythm disruption on gene expression, particularly affecting genes involved in detoxification and xenobiotic metabolism, such as the Gstm gene family. This dysregulation in detoxification pathways in Cry DKO mice likely contributes to the increased toxicity of oxaliplatin. In conclusion, our study highlights the crucial role of an intact molecular clock in dictating the tolerability of oxaliplatin. These findings emphasize the necessity of considering circadian rhythms in the administration of anticancer drugs, providing valuable insights into optimizing treatment strategies for cancer patients.
Exploring the effects of adolescent social isolation stress on the serotonin system and ethanol-motivated behaviors
Authors: McElroy Bryan D. , Li Chen , McCloskey Nicholas S. , Alberici Amber R. , Kirby Lynn G.
Published: February 2025

Rationale

Alcohol is one of the most frequently used drugs of abuse and has a major impact on human health worldwide. People assigned female at birth and those with adverse childhood experiences are stress-vulnerable and more likely to report drinking as a means of “self-medication.” Prior studies in our laboratory showed that adolescent social isolation stress (SIS) increases vulnerability to ethanol (EtOH) intake and consumption despite negative consequences in female rats.

Objectives

Here, we explored modulation of the dorsal raphe nucleus (DRN)-serotonin (5-HT) system, a sexually dimorphic neurotransmitter system involved in stress-reward interactions, to determine its contribution to EtOH-motivated behaviors in rats that have undergone SIS.

Results

We employed electrophysiological and functional neuroanatomy strategies to show that both SIS and EtOH exposure induce persistent hypofunction of the DRN 5-HT system, particularly in females. Chemogenetic activation of DRN 5-HT neurons attenuated reward value for both EtOH and sucrose and elevated punished responding for EtOH in a stress-dependent manner.

Conclusions

Our results highlight an inverse relationship between EtOH consumption and the 5-HT system, the sex- and stress-dependent nature of this relationship, and a connection between DRN 5-HT signaling and acute responding to rewards and punishment. These data support the DRN 5-HT system as a potential target to treat aberrant alcohol consumption and drinking despite negative consequences in stress-vulnerable populations.
An in-depth comparison of vascular inflammation on ultrasound, FDG-PET/CT and MRI in patients with suspected giant cell arteritis
Authors: van Nieuwland Marieke , Nienhuis Pieter H. , Haagsma Cees , van der Geest Kornelis S. M. , Wagenaar Nils R. L. , Appelman Auke P. A. , Vijlbrief Onno D. , van Bon Lenny , Colin Edgar M. , Brouwer Elisabeth , Slart Riemer H. J. A. , Alves Celina
Published: February 2025

Background

Giant cell arteritis (GCA) is a difficult to diagnose large vessel vasculitis. CDUS, FDG-PET/CT and MRI are increasingly used for GCA diagnosis. This study aims to assess vascular wall lesions in GCA suspected patients, directly comparing CDUS, FDG-PET/CT and MRI with each other.

Methods

In a nested-case control study, consecutive GCA suspected patients were included. Scans were retrospectively assessed by two experts per imaging modality. Inter- and intraobserver agreement using Cohen’s or Fleiss Kappa were calculated to assess agreement between experts, a few duplicated scans and between imaging modalities. Sensitivity and specificity of the imaging modalities for overall diagnostic performance and for individual arteries were calculated.

Results

In total, 42 patients were included. Overall diagnostic performance of imaging modalities was comparable. Sensitivity and specificity were highest in the temporal artery for CDUS (76% and 93%; Kappa > 0.7) and MRI (60% and 100%; Kappa > 0.7), and in the vertebral (61% and 100%; Kappa 0.56) and maxillary artery (52% and 100%; Kappa 0.75) for FDG-PET/CT. Agreement between all modalities for a positive temporal artery was 0.76, but only 0.28 between CDUS and FDG-PET/CT. Agreement for the axillary artery was 0.7 between CDUS and FDG-PET/CT.

Conclusion

The temporal artery can be assessed by CDUS and MRI with good sensitivity and high specificity, and the axillary artery by CDUS and FDG-PET/CT with high agreement between the two modalities. In addition, the vertebral and maxillary artery can be assessed by FDG-PET/CT with good sensitivity and specificity, however the vertebral artery had moderate interobserver agreement.
Beta-tricalcium phosphate combined with native bone proteins (β-TCP - NBP): a novel bone graft substitute for ankle and hindfoot arthrodesis
Authors: Leppilahti Juhana , Kuoppala Mari , Sirola Timo , Kolodziej Lukasz , Ahonen Katri , Aulamo Mikko , Niinimäki Jaakko , Jalovaara Pekka
Published: February 2025

Purpose

The purpose of this prospective, multi-centre study was to assess the performance and safety of a combination of osteoconductive β-tricalcium phosphate and osteoinductive native bone proteins (β-TCP - NBP) used as alternative for autograft in ankle and hindfoot arthrodesis.

Methods

Thirty-four patients enrolled underwent ankle or hindfoot arthrodesis with β-TCP - NBP and were evaluated radiographically, clinically, and functionally up to fifty-two weeks. The primary performance endpoint was fusion rate evaluated with CT at six months. Safety was assessed based on the severity and incidence of adverse events. Functional evaluation was performed using the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score and pain was recorded using the Visual Analogue Scale (VAS).

Results

CT at 6 months showed that 85.3% had osseous bridging of the joint of ≥ 25%, 52.9% ≥50%, 8.8% <25% and 5.9% showed no bridging. The AOFAS score increased significantly from 60.4 ± 17.6 points at operation to 68.6 ± 17.2 points at six months and to 73.5 ± 17.7 points at 12 months. The group with fusion rate ≥25% showed significantly higher AOFAS score than that with fusion rate < 25% at 12 months. The mean VAS pain score at rest and during weight bearing decreased significantly (p < 0.0001) from operation to six and 12 months.

Conclusion

This study demonstrated that β-TCP - NBP is a valuable bone graft substitute for fusion of ankle and hindfoot due to debilitating osteoarthritis and offers an alternative for autograft.

Level of evidence

Level II.
Enhancing endurance performance predictions: the role of movement velocity in metabolic simulations demonstrated by cycling cadence
Authors: Dunst Anna Katharina , Hesse Clemens , Ueberschär Olaf
Published: February 2025

Background

Mader’s mathematical model, widely employed for endurance performance prediction, aims to accurately represent metabolic response to exercise. However, it traditionally overlooks dynamic changes in metabolic processes at varying movement velocities.

Methods

This narrative review examined the effect of cycling cadence on its key input parameters, including oxygen demand per Watt (

$$\text{CE}_{{\dot{\text{V}}}\text{O2}}$$

CE

V
˙

O2

), resting oxygen uptake (

$${{\dot{\text{V}}}\text{O}_{\text{2Base}}}$$

V
˙

O
2Base

), maximal oxygen uptake (

$${{\dot{\text{V}}}\text{O}_{\text{2max}}}$$

V
˙

O
2max

), and maximal blood lactate accumulation rate (vLamax). These findings were integrated into the model to assess cadence-induced variations in predicted power output at maximal aerobic power (MAP), maximal lactate steady state (MLSS), and peak fat oxidation (FATmax).

Results

A U-shaped relationship was found between cadence and both

$$\text{CE}_{{\dot{\text{V}}}\text{O2}}$$

CE

V
˙

O2

and

$${{\dot{\text{V}}}\text{O}_{\text{2Base}}}$$

V
˙

O
2Base

, while

$${{\dot{\text{V}}}\text{O}_{\text{2max}}}$$

V
˙

O
2max

remained largely cadence-independent within typical cadences. vLamax exhibited a polynomial increase with cadence, attributed to changes in lactate elimination, suggesting cadence-independent maximal glycolytic flux. Incorporating these findings into Mader’s model considering various scenarios revealed significant cadence-induced variations, with power output differences of up to > 100 W. Using cadence-dependent

$$\text{CE}_{{\dot{\text{V}}}\text{O2}}$$

CE

V
˙

O2

and

$${{\dot{\text{V}}}\text{O}_{\text{2Base}}}$$

V
˙

O
2Base

while maintaining constant

$${{\dot{\text{V}}}\text{O}_{\text{2max}}}$$

V
˙

O
2max

and vLamax yielded polynomial power output-cadence relationships, with optimal cadences of 84 rpm at MAP, 80 rpm at MLSS, and 70 rpm at FATmax. Incorporating cadence-dependent vLamax produced implausible results, supporting cadence-independent maximal glycolytic flux. A hypothesized cadence-dependent

$${{\dot{\text{V}}}\text{O}_{\text{2max}}}$$

V
˙

O
2max

improved alignment between model predictions and empirical data.

Conclusion

Neglecting dynamic changes in metabolic processes across different movement velocities can lead to inaccurate modelling results. Incorporating cadence alongside established parameters enhances the precision of Mader’s metabolic model for cycling performance prediction.

Graphical abstract
The impact of PD-L1 polymorphisms on the efficacy of immune checkpoint inhibitors depends on the tumor proportion score: a retrospective study
Authors: Suminaga Keiichiro , Nomizo Takashi , Yoshida Hironori , Ozasa Hiroaki
Published: February 2025

Purpose

This study aims to clarify the relationship between rs2282055, a single-nucleotide polymorphism (SNP) in programmed death-ligand 1 (PD-L1), and TPS. Polcaro et al. (2024) showed that rs822336, a SNP in PD-L1, predicts the effect of immune checkpoint inhibitors (ICIs). However, the study did not show a relationship between rs822336 and the tumor proportion score (TPS), which is currently used as a primary marker. Therefore, we examined this relationship.

Method

Patients treated with immune checkpoint inhibitor monotherapy for non-small cell lung cancer at Kyoto University Hospital until January 2023, with TPS data and biological specimens available for SNP measurement, were eligible for this study. Genomic DNA was extracted from peripheral blood leukocytes. We used rs2282055, which is in linkage disequilibrium with rs822336, instead of rs822336, because of its distribution in the Asian patient population. We retrospectively extracted data on age, sex, smoking history, driver mutations, TPS, progression-free survival (PFS), and best response to ICI from medical records.

Result

The rs2282055 T/T genotype was associated with significantly better PFS in the TPS-negative population than in the other genotypes. In contrast, no differences were observed in TPS-positive patients.

Conclusion

The rs2282055 genotype may help in selecting cases from the TPS-negative patient population that may benefit from ICI therapy.
Impact of indocyanine green fluorescence angiography on surgeon action and anastomotic leak in colorectal resections. A systematic review and meta-analysis
Authors: Mc Entee Philip D. , Singaravelu Ashokkumar , Boland Patrick A. , Moynihan Alice , Creavin Ben , Cahill Ronan A.
Published: February 2025

Background

Indocyanine green fluorescence angiography (ICGFA) during colorectal surgery either reassures surgeons regarding intestinal perfusion sufficiency or prompts changed surgical strategy by indicating unsuspected insufficiency. This study describes existing evidence supporting ICGFA use in colorectal surgery, particularly regarding impact on intraoperative decisions.

Methods

Searches were performed on PubMed, ScienceDirect, Scopus, Web of Science, Cochrane Collaboration databases on 5th December 2023, updated to 19th August 2024. Full English language publications of clinical studies in human patients undergoing colorectal resection with primary anastomosis with the use of ICGFA to assess bowel perfusion intraoperatively, with a control group, were included. Pooling of anastomotic leak (AL) rates was performed for primary outcome analysis with odds ratio (OR) and number-needed-to-treat (NNT) calculated regarding leak reduction.

Results

45 studies comprising 14,333 patients were included, with 7 randomised controlled trials (2911 patients). Overall, AL rate was 6.8%, 4.5% with ICGFA and 8.5% without (OR:0.47, p < 0.001, NNT 23), increasing to 9.5%, 7.5% and 11.6%, respectively, in randomised controlled trials (OR:0.62, p < 0.01, NNT 25). In rectal resections, AL rate was 4.7% with ICGFA vs 11.5% without (OR: 0.38, p < 0.0001). 26 studies performed ICGFA before and after anastomosis formation and 19 used ICGFA only prior to bowel transection, with no significant difference of AL rate reduction on subgroup testing. ICGFA prompted a change in surgical plan in 8.4% of thirty-four studies reporting this. Interestingly, in these studies, leak rates overall were 3.7% when ICGFA matched surgeon judgement versus 5.7% when it prompted change (OR 0.51, p < 0.0025), versus 7.7% without (OR 0.45, p < 0.0001). In rectal resections, these figures were 5%, 8.8% (OR 0.42, p = 0.01) and 12.0% (OR0.39, p < 0.0001), respectively.

Conclusions

ICGFA colorectal perfusion assessment is associated with lower anastomotic leak rates, especially when confirming surgeons’ judgement, and may so stratify patients post-operatively regarding subsequent anastomotic leak rate.
Urinary Dickkopf-related protein 3 as a novel biomarker for kidney function decline in children with Alport syndrome
Authors: Boeckhaus Jan , Tönshoff Burkhard , Weber Lutz T. , Pape Lars , Latta Kay , Fehrenbach Henry , Lange-Sperandio Baerbel , Kettwig Matthias , König Sabine , John-Kroegel Ulrike , Gellermann Jutta , Galiano Matthias , Jami Sima , Pieper Dennis , Dihazi Gry Helene , Hafke Angelika , Kohl Stefan , Liebau Max C. , König Jens , Haffner Dieter , Gross Oliver , Wallbach Manuel
Published: February 2025

Background

Chronic kidney disease (CKD) seriously affects the well-being and shortens the life expectancy of children and adolescents, but its progression is challenging to predict. Therefore, there is an urgent need for biomarkers that can identify children at risk of faster CKD progression. Alport syndrome (AS) is the most common monogenetic glomerular kidney disease. Urinary Dickkopf-related protein 3 (DKK3) is associated with a decline in estimated glomerular filtration rate (eGFR) in adults and children with advanced CKD. However, its potential for early detection of CKD and its prognostic value in children with AS remain unknown.

Methods

Urine samples from 49 children enrolled in the EARLY PRO-TECT Alport trial were analyzed to evaluate whether DKK3 could identify children with AS to be at risk for faster CKD progression.

Results

DKK3 levels in patients with AS were higher than those of healthy individuals reported in the literature. DKK3 levels were more elevated in patients with later stages of AS. Furthermore, children who were not treated with renin angiotensin system inhibitors (RASi) had higher DKK3 levels than treated children. Children with above-average DKK3 levels were more likely to have increased albuminuria after 2 years of follow-up than children with below-average DKK3 levels.

Conclusion

Urinary DKK3 is significantly elevated in children at early stages of AS. There was a potential association between higher DKK3 levels, worsening albuminuria, and a decline in kidney function. These findings suggest that DKK3 may be a prognostic marker for predicting the risk of kidney damage in children with AS.

Graphical Abstract
Association between chemotherapy and the risk of developing breast cancer-related lymphedema: a nationwide retrospective cohort study
Authors: Jeong Sung Hoon , Chun Seong Min , Lee Hyunji , Kim Miji , Choi Mira , Leigh Ja-Ho
Published: February 2025

Purpose

Breast cancer-related lymphedema (BCRL) is a well-known complication of breast cancer treatment, which often includes chemotherapy. This study aimed to investigate the association between chemotherapy and the risk of developing BCRL in patients with new-onset breast cancer.

Methods

This nationwide retrospective cohort study utilized data from the Korean National Health Insurance database and the Korea National Cancer Incidence Database (2006–2017). Using 1:1 propensity score matching, 37,202 participants who received chemotherapy and 37,202 who did not receive chemotherapy were included in the analysis. Cox proportional hazard regression models were employed to examine the association between chemotherapy and the risk of developing BCRL.

Results

Among the 74,404 participants, 11,508 (15.5%) were diagnosed with BCRL during the follow-up period. Compared with patients who did not receive chemotherapy, the risk of BCRL was higher in patients undergoing chemotherapy (hazard ratio [95% confidence interval]: 1.95 [1.87–2.04]). Furthermore, compared to patients who did not receive chemotherapy, the risk of BCRL was confirmed in the taxane (3.38 [3.19–3.58]), antimetabolite (1.79 [1.67–1.91]), and anthracycline (1.49 [1.41–1.56]) chemotherapy groups.

Conclusion

Chemotherapy administration following a diagnosis of breast cancer increases the risk of BCRL. Therefore, vigilant monitoring for BCRL, particularly in patients undergoing chemotherapy with taxanes, antimetabolites, or anthracyclines, is warranted during follow-up.
Machine learning algorithms for predicting future curve using first and second visit data in female adolescent idiopathic scoliosis patients
Authors: Ohyama Shuhei , Maki Satoshi , Kotani Toshiaki , Ogata Yosuke , Sakuma Tsuyoshi , Iijima Yasushi , Akazawa Tsutomu , Inage Kazuhide , Shiga Yasuhiro , Inoue Masahiro , Arai Takahito , Toshi Noriyasu , Tokeshi Soichiro , Okuyama Kohei , Tashiro Susumu , Suzuki Noritaka , Eguchi Yawara , Orita Sumihisa , Minami Shohei , Ohtori Seiji
Published: February 2025

Purpose

This study was designed to develop a machine learning (ML) model that predicts future Cobb angle in patients with adolescent idiopathic scoliosis (AIS) using minimal radiographs and simple questionnaires during the first and second visits.

Methods

Our study focused on 887 female patients with AIS who were initially consulted at a specialized scoliosis center from July 2011 to February 2023. Patient data, including demographic and radiographic data based on anterior-posterior and lateral whole-spine radiographs, were collected at the first, second, and final visits. ML algorithms were employed to develop individual regression models for future Cobb angles of each curve type (proximal thoracic: PT, main thoracic: MT, and thoracolumbar/lumbar: TLL) using PyCaret in Python. Multiple models were explored and analyzed, with the selection of optimal models based on the coefficient of determination (R2) and median absolute error (MAE).

Results

For the future curve of PT, MT, and TLL, the top-performing models exhibit R2 of 0.73, 0.63, and 0.61 and achieve MAE of 2.3°, 4.0°, and 4.2°.

Conclusions

The ML-based model using items commonly evaluated at the first and second visits accurately predicted future Cobb angles in female patients with AIS.
Parametric model order reduction for a wildland fire model via the shifted POD-based deep learning method
Authors: Burela Shubhaditya , Krah Philipp , Reiss Julius
Published: February 2025

Parametric model order reduction techniques often struggle to accurately represent transport-dominated phenomena due to a slowly decaying Kolmogorov n-width. To address this challenge, we propose a non-intrusive, data-driven methodology that combines the shifted proper orthogonal decomposition (POD) with deep learning. Specifically, the shifted POD technique is utilized to derive a high-fidelity, low-dimensional model of the flow, which is subsequently utilized as input to a deep learning framework to forecast the flow dynamics under various temporal and parameter conditions. The efficacy of the proposed approach is demonstrated through the analysis of one- and two-dimensional wildland fire models with varying reaction rates, and its error is compared with the error of other similar methods. The results indicate that the proposed approach yields reliable results within the percent range, while also enabling rapid prediction of system states within seconds.
A comprehensive review of optic disc segmentation methods in adult and pediatric retinal images: from conventional methods to artificial intelligence (CR-ODSeg-AP-CM2AI)
Authors: Bansal Avinash , Kubíček Jan , Penhaker Marek , Augustynek Martin
Published: February 2025

This review, titled CR-ODSeg-AP-CM2AI (Comprehensive Review of Optic Disc Segmentation in Adult and Pediatric Retinal Images: From Conventional Methods to Artificial Intelligence), explores optic disc segmentation techniques for adult and pediatric retinal images. It emphasizes the clinical implications of these techniques in diagnosing and monitoring retinal diseases across diverse populations. We systematically categorize each segmentation method, comparing traditional approaches with advancements in artificial intelligence (AI) to highlight innovative hybrid techniques that enhance segmentation accuracy and efficiency. This review also discusses evaluation metrics and the use of larger datasets to provide insights into the effectiveness and robustness of these methods.