bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-Path Routing Algorithm Based on Deep Reinforcement Learning for SDN
Authors: Zhang Yi , Qiu Lanxin , Xu Yangzhou , Wang Xinjia , Wang Shengjie , Paul Agyemang , Wu Zhefu
Published: November 2023

Software-Defined Networking (SDN) enhances network control but faces Distributed Denial of Service (DDoS) attacks due to centralized control and flow-table constraints in network devices. To overcome this limitation, we introduce a multi-path routing algorithm for SDN called Trust-Based Proximal Policy Optimization (TBPPO). TBPPO incorporates a Kullback–Leibler divergence (KL divergence) trust value and a node diversity mechanism as the security assessment criterion, aiming to mitigate issues such as network fluctuations, low robustness, and congestion, with a particular emphasis on countering DDoS attacks. To avoid routing loops, differently from conventional ‘Next Hop’ routing decision methodology, we implemented an enhanced Depth-First Search (DFS) approach involving the pre-computation of path sets, from which we select the best path. To optimize the routing efficiency, we introduced an improved Proximal Policy Optimization (PPO) algorithm based on deep reinforcement learning. This enhanced PPO algorithm focuses on optimizing multi-path routing, considering security, network delay, and variations in multi-path delays. The TBPPO outperforms traditional methods in the Germany-50 evaluation, reducing average delay by 20%, cutting delay variation by 50%, and leading in trust value by 0.5, improving security and routing efficiency in SDN. TBPPO provides a practical and effective solution to enhance SDN security and routing efficiency.
Castanea spp. Nut Traceability: A Multivariate Strategy Based on Phytochemical Data
Authors: Prezzi Elisabetta , Donno Dario , Mellano Maria Gabriella , Beccaro Gabriele Loris , Gamba Giovanni
Published: November 2023

The phytochemical characterization of Castanea spp. fruits is very important for the development of effective strategies for the biodiversity conservation and traceability of chestnuts, as the chestnut is one of the most important Italian and European nut and forest species. In this study, several cultivars of C. sativa (sweet chestnuts and “marrone-type”), C. crenata, and hybrids of C. sativa × C. crenata were characterized by spectrophotometric (Folin–Ciocalteu assay for the total polyphenolic content and ferric reducing antioxidant power test for the antioxidant capacity) and chromatographic (high-performance liquid chromatography coupled to a diode array UV-Vis detector) protocols to define their phytochemical composition and nutraceutical properties. The phytochemical results were then used to build a multivariate statistical model (by principal component analysis) and obtain an effective and rapid tool to discriminate unknown cultivars (i.e., no information about their origin) belonging to different species. The multivariate approach showed that the genotype was a significantly discriminating variable (p < 0.05) for the phytochemical composition. Polyphenols (in particular, phenolic acids and tannins) have been identified as the main bioactive classes with the highest discriminating power among the different genotypes. The total polyphenol content (TPC) and antioxidant capacity (AOC) showed a rich presence of bioactive compounds (74.09 ± 15.10 mgGAE 100 g−1 DW and 11.05 ± 1.35 mmol Fe2+ kg−1 DW, respectively), underlining the potential health benefits and functional traits of chestnuts. The principal component analysis applied to phytochemical variables has proved to be an excellent and effective tool for genotype differentiation to be used as a preliminary method for identifying the species of Castanea spp. fruits with an unknown origin. The present study showed that a multivariate approach, based on phytochemical data and preliminary to genetic analysis, may represent a rapid, effective, and low-cost tool for the traceability and quality evaluation of chestnuts from different species and hybrids with no information on their origin.
Design of Flexible Bearing with Larger Inner Diameter
Authors: Hu Feng , Xin Hongbing
Published: November 2023

The flexible bearing is the kernel component of the cam wave generator. In precision transmission applications such as miniature robot joints, flexible bearings are required to have a smaller mass, lower moment of inertia, and larger inner diameter. Based on the theory of conventional rolling bearing, and by considering the working characteristics of flexible bearing for harmonic drive, this paper studies the influence law of structural parameters on the fatigue life of the flexible bearing; achieves a technical approach for expanding the bore size of the standard flexible bearing; and deduces the theoretical formulas applicable to the design of the flexible bearing. The new formula is utilized to improve the design parameters of the flexible bearing. The novel design with smaller diameter and more numbers of rolling elements can meet the above performance requirements compared to the conventional flexible bearing. Under the same conditions of radial deformation and materials used, finite element analysis results show that the maximum equivalent stress in the improved flexible bearing is smaller and that the novel design can meet the strength requirements of the harmonic drive.
Asphalt Pavement Transverse Cracking Detection Based on Vehicle Dynamic Response
Authors: Ye Wenya , Yuan Wenzhi , Yang Qun
Published: November 2023

Transverse cracking is thought of as the typical distress of asphalt pavements. A faster detection technique can provide pavement performance information for maintenance administrations. This paper proposes a novel vehicle-vibration-based method for transverse cracking detection. A theoretical model of a vehicle-cracked pavement vibration system was constructed using the d’Alembert principle. A testing system installed with a vibration sensor was put in and applied to a testing road. Then, parameter optimization of the Short-time Fourier transform (STFT) was conducted. Transverse cracking and normal sections were processed by the optimized STFT algorithm, generating two ideal indicators. The maximum power spectral density and the relative power spectral density, which were extracted from 3D time–frequency maps, performed well. It was found that the power spectral density caused by transverse cracks was above 100 dB/Hz. The power spectral density at normal sections was below 80 dB/Hz. The distribution of the power spectral density for the cracked sections is more discrete than for normal sections. The classification model based on the above two indicators had an accuracy, true positive rate, and false positive rate of 94.96%, 92.86%, and 4.80%, respectively. The proposed vehicle-vibration-based method is capable of accurately detecting pavement transverse cracking.
The Rainwater Interception Process and Capacity of Urban Tree Organs in Shanghai
Authors: Wang Benyao , Zhang Yanting , Guo Jiankang
Published: November 2023

The process of rainwater interception by tree organs is crucial in mitigating the impact of intense rainfall on urban drainage systems, particularly in the context of climate change. For this study, we selected ten commonly found tree species in Shanghai, and the main parts of trees, including their leaves, branches, and bark, were collected to analyze their ability to intercept rainwater. The optimized Artificial Rainfall Simulation System (ARSS) was applied to simulate rainfall. The time-changing process of rainwater interception in three organs was measured during a 180 min rainfall event under four different rainfall intensities (4, 8, 12, and 16 mm/h, respectively). Process models of rainwater interception in different organs were fitted with adsorption kinetic equations. The rainwater interception process of tree organs complied with the quasi second-order adsorption kinetic equation. The rainwater interception capacity values of the leaves, branches, and bark of the ten urban tree species ranged from 0.05 to 0.34 mm, 0.13 to 0.24 mm, and 0.29 to 1.22 mm, respectively. The rainwater interception capacity values of the three organs significantly differ (p < 0.05). The results of this study reveal that bark exhibits the greatest rainwater interception ability. Coniferous tree species have a greater ability to intercept rainwater than broad-leaved tree species. There are also differences in the rainwater interception ability of trees in urban and natural areas.
Algebrodynamics: Shear-Free Null Congruences and New Types of Electromagnetic Fields
Authors: Kassandrov Vladimir V. , Rizcallah Joseph A. , Matveev Ivan A.
Published: November 2023

We briefly present our version of noncommutative analysis over matrix algebras, the algebra of biquaternions (B) in particular. We demonstrate that any B-differentiable function gives rise to a null shear-free congruence (NSFC) on the B-vector space CM and on its Minkowski subspace M. Making use of the Kerr–Penrose correspondence between NSFC and twistor functions, we obtain the general solution to the equations of B-differentiability and demonstrate that the source of an NSFC is, generically, a world sheet of a string in CM. Any singular point, caustic of an NSFC, is located on the complex null cone of a point on the generating string. Further we describe symmetries and associated gauge and spinor fields, with two electromagnetic types among them. A number of familiar and novel examples of NSFC and their singular loci are described. Finally, we describe a conservative algebraic dynamics of a set of identical particles on the “Unique Worldline” and discuss the connections of the theory with the Feynman–Wheeler concept of “One-Electron Universe”.
The Weighted, Relaxed Gradient-Based Iterative Algorithm for the Generalized Coupled Conjugate and Transpose Sylvester Matrix Equations
Authors: Wu Xiaowen , Huang Zhengge , Cui Jingjing , Long Yanping
Published: November 2023

By applying the weighted relaxation technique to the gradient-based iterative (GI) algorithm and taking proper weighted combinations of the solutions, this paper proposes the weighted, relaxed gradient-based iterative (WRGI) algorithm to solve the generalized coupled conjugate and transpose Sylvester matrix equations. With the real representation of a complex matrix as a tool, the necessary and sufficient conditions for the convergence of the WRGI algorithm are determined. Also, some sufficient convergence conditions of the WRGI algorithm are presented. Moreover, the optimal step size and the corresponding optimal convergence factor of the WRGI algorithm are given. Lastly, some numerical examples are provided to demonstrate the effectiveness, feasibility and superiority of the proposed algorithm.
Existence and Uniqueness Results of Fractional Differential Inclusions and Equations in Sobolev Fractional Spaces
Authors: Meftah Safia , Hadjadj Elhabib , Biomy Mohamad , Yazid Fares
Published: November 2023

In this work, by using the iterative method, we discuss the existence and uniqueness of solutions for multiterm fractional boundary value problems. Next, we examine some existence and uniqueness returns for semilinear fractional differential inclusions and equations for multiterm problems by using some notions and properties on set-valued maps and give some examples to explain our main results. We explore and use in this paper the fundamental properties of set-valued maps, which are needed for the study of differential inclusions. It began only in the mid-1900s, when mathematicians realized that their uses go far beyond a mere generalization of single-valued maps.
Assemblage Structure of Ichthyoplankton Communities in the Southern Adriatic Sea (Eastern Mediterranean)
Authors: Bergamasco Alessandro , Minutoli Roberta , Belmonte Genuario , Giordano Daniela , Guglielmo Letterio , Perdichizzi Anna , Rinelli Paola , Spinelli Andrea , Granata Antonia
Published: November 2023

Studies based on fish early life stages can provide information on spawning grounds and nursery areas, helping to determine the implications for stock biomass fluctuations of recruitment variability. This study describes the composition, abundance, spatial distribution and differences in day/night vertical distribution of ichthyoplankton in the southern Adriatic Sea. Samples were collected within the framework of the COCONET project (Towards COast to COast NETworks of marine protected areas) from 9 to 18 May 2013 by the R/V Urania, using the electronic multinet EZ-NET BIONESS (Bedford Institute of Oceanography Net Environmental Sampling System). A total of 20 species, belonging to 20 genera and 13 families, were identified. Of the collected larvae, 74.3% were meso- or bathypelagic species, 24.7% were epipelagic and 0.9% were demersal. The community was dominated by Gonostomatidae, followed by Engraulidae, Myctophidae and Photychthaidae. The most abundant species was Cyclothone braueri (45.6%), followed by Engraulis encrasicolus, Ceratoscopelus maderensis, Cyclothone pygmaea, Vinciguerria attenuata and Myctophum punctatum. An inshore/offshore increasing gradient in biodiversity and abundance was observed. Different weighted mean depths (WMDs) were observed for larvae and juveniles. No diel vertical migrations were observed. The high abundance of meso- or bathypelagic species in the upper 100 m confirms the epipelagic zone as an important environment for the development of the larval stages of these fish.
Characterization of Rickets Type II Model Rats to Reveal Functions of Vitamin D and Vitamin D Receptor
Authors: Iwai Yuichiro , Iijima Ayano , Kise Satoko , Nagao Chika , Senda Yuto , Yabu Kana , Mano Hiroki , Nishikawa Miyu , Ikushiro Shinichi , Yasuda Kaori , Sakaki Toshiyuki
Published: November 2023

Vitamin D has been known to exert a wide range of physiological effects, including calcemic, osteogenic, anticancer, and immune responses. We previously generated genetically modified (GM) rats and performed a comparative analysis of their physiological properties to elucidate the roles of vitamin D and vitamin D receptor (VDR). In this study, our primary goal was to investigate the manifestations of type II rickets in rats with the VDR(H301Q) mutation, analogous to the human VDR(H305Q). Additionally, we created a double-mutant rat with the VDR(R270L/H301Q) mutation, resulting in almost no affinity for 1,25-dihydroxy-vitamin D3 (1,25D3) or 25-hydroxy-vitamin D3 (25D3). Notably, the plasma calcium concentration in Vdr(R270L/H301Q) rats was significantly lower than in wild-type (WT) rats. Meanwhile, Vdr(H301Q) rats had calcium concentrations falling between those of Vdr(R270L/H301Q) and WT rats. GM rats exhibited markedly elevated plasma parathyroid hormone and 1,25D3 levels compared to those of WT rats. An analysis of bone mineral density in the cortical bone of the femur in both GM rats revealed significantly lower values than in WT rats. Conversely, the bone mineral density in the trabecular bone was notably higher, indicating abnormal bone formation. This abnormal bone formation was more pronounced in Vdr(R270L/H301Q) rats than in Vdr(H301Q) rats, highlighting the critical role of the VDR-dependent function of 1,25D3 in bone formation. In contrast, neither Vdr(H301Q) nor Vdr(R270L/H301Q) rats exhibited symptoms of alopecia or cyst formation in the skin, which were observed in the Vdr-KO rats. These findings strongly suggest that unliganded VDR is crucial for maintaining the hair cycle and normal skin. Our GM rats hold significant promise for comprehensive analyses of vitamin D and VDR functions in future research.
The Role of Long Noncoding RNAs in Intestinal Health and Diseases: A Focus on the Intestinal Barrier
Authors: Lu Qianying , Liang Yangfan , Meng Xiangyan , Zhao Yanmei , Fan Haojun , Hou Shike
Published: November 2023

The gut is the body’s largest immune organ, and the intestinal barrier prevents harmful substances such as bacteria and toxins from passing through the gastrointestinal mucosa. Intestinal barrier dysfunction is closely associated with various diseases. However, there are currently no FDA-approved therapies targeting the intestinal epithelial barriers. Long noncoding RNAs (lncRNAs), a class of RNA transcripts with a length of more than 200 nucleotides and no coding capacity, are essential for the development and regulation of a variety of biological processes and diseases. lncRNAs are involved in the intestinal barrier function and homeostasis maintenance. This article reviews the emerging role of lncRNAs in the intestinal barrier and highlights the potential applications of lncRNAs in the treatment of various intestinal diseases by reviewing the literature on cells, animal models, and clinical patients. The aim is to explore potential lncRNAs involved in the intestinal barrier and provide new ideas for the diagnosis and treatment of intestinal barrier damage-associated diseases in the clinical setting.
Apiaceae Family an Important Source of Petroselinic Fatty Acid: Abundance, Biosynthesis, Chemistry, and Biological Proprieties
Authors: Hajib Ahmed , El Harkaoui Said , Choukri Hasnae , Khouchlaa Aya , Aourabi Sarra , El Menyiy Naoual , Bouyahya Abdelhakim , Matthaeus Bertrand
Published: November 2023

Petroselinic fatty acid (PeFA) is considered a rare fatty acid and one of the most important fatty acids in the Apiaceae family. Its content varies depending on plant species, geographical origin, extraction method, ripeness, etc. Indeed, reported levels of petroselinic fatty acid range from 10.4 to 75.6% (in anise seed oil), 1 to 81.9% (in coriander seed oil), 28.5 to 57.6% (in caraway seed oil), 49.4 to 75.6% (in celery seed oil), 41.3 to 61.8% (in caraway seed oil), 79.9 to 87.2% (in dill seed oil), 43.1 to 81.9% (in fennel seed oil), and 35 to 75.1% (parsley seed oil). In this review, we also show current knowledge about genes encoding biosynthesis, from the desaturation of 16:0-ACP to petroselinic acid stored in triacylglycerol in the seeds. Furthermore, petroselinic acid is not related to the synthesis of ABA. PeFA was successfully isolated from Apiaceae family plant seeds in order to study their reactivity and biological activities. Several investigations showed that this fatty acid has a wide range of biological potentials, including antidiabetic, antibacterial, and antifungal activities. In cosmetics, PeFA alone or in association with other active compounds has interesting applications as an anti-inflammatory agent for the treatment of skin, hair, and nail disorders.
Visible Light-Induced Templated Metathesis of Peptide–Nucleic Acid Conjugates with a Diselenide Bridge
Authors: Waliczek Mateusz , Gancarz Wiktoria , Pochwała Paulina , Pehlivan Özge , Stefanowicz Piotr
Published: November 2023

The use of template molecules as chemical scaffolds that significantly influence the course of the reaction has recently been intensively studied. Peptide nucleic acids (PNA) are molecules that mimic natural nucleic acids. They are a promising matrix in such reactions because they possess high affinity and specificity in their interactions. The manner of PNA interaction is predictable based on sequence complementarity. Recently, we report the visible light-induced metathesis reaction in peptides containing a diselenide bond. Herein, we present an efficient and straightforward method of the visible light-driven diselenide-based metathesis of peptide–nucleic acid conjugates. Compared to a similar photochemical transformation in peptides, a significant increase in the metathesis efficiency was obtained due to the template effect.
A Computer-Assisted Diagnostic Method for Accurate Detection of Early Nondisplaced Fractures of the Femoral Neck
Authors: Hsieh S. L. , Chiang J. L. , Chuang C. H. , Chen Y. Y. , Hsu C. J.
Published: November 2023

Nondisplaced femoral neck fractures are sometimes misdiagnosed by radiographs, which may deteriorate into displaced fractures. However, few efficient artificial intelligent methods have been reported. We developed an automatic detection method using deep learning networks to pinpoint femoral neck fractures on radiographs to assist physicians in making an accurate diagnosis in the first place. Our proposed accurate automatic detection method, called the direction-aware fracture-detection network (DAFDNet), consists of two steps, namely region-of-interest (ROI) segmentation and fracture detection. The first step removes the noise region and pinpoints the femoral neck region. The fracture-detection step uses a direction-aware deep learning algorithm to mark the exact femoral neck fracture location in the region detected in the first step. A total of 3840 femoral neck parts in anterior–posterior (AP) pelvis radiographs collected from the China Medical University Hospital database were used to test our method. The simulation results showed that DAFDNet outperformed the U-Net and DenseNet methods in terms of the IOU value, Dice value, and Jaccard value. Our proposed DAFDNet demonstrated over 94.8% accuracy in differentiating non-displaced Garden type I and type II femoral neck fracture cases. Our DAFDNet method outperformed the diagnostic accuracy of general practitioners and orthopedic surgeons in accurately locating Garden type I and type II fracture locations. This study can determine the feasibility of applying artificial intelligence in a clinical setting and how the use of deep learning networks assists physicians in improving correct diagnoses compared to the current traditional orthopedic manual assessments.
The Design and Experimental Validation of a Biomimetic Stubble-Cutting Device Inspired by a Leaf-Cutting Ant’s Mandibles
Authors: Qi Hongyan , Ma Zichao , Xu Zihe , Wang Shuo , Ma Yunhai , Wu Siyang , Guo Mingzhuo
Published: November 2023

Under the conditions of conservation tillage, the existence of the root–soil complex greatly increases the resistance and energy consumption of stubble-cutting blades, especially in Northeast China. In this research, the corn root–soil complex in Northeast China was selected as the research object. Based on the multi-toothed structure of the leaf-cutting ant’s mandibles and the unique bite mode of its mandibles on leaves, a gear-tooth, double-disk, bionic stubble-cutting device (BSCD) was developed by using a combination of power cutting and passive cutting. The effects of rotary speed, tillage depth, and forward speed on the torque and power of the BSCD were analyzed using orthogonal tests, and the results showed that all of the factors had a large influence on the torque and power, in the order of tillage depth > rotary speed > forward speed. The performance of the BSCD and the traditional power straight blade (TPSB) was explored using comparative tests. It was found that the optimal stubble-cutting rate of the BSCD was 97.4%. Compared with the TPSB, the torque of the BSCD was reduced by 15.2–16.4%, and the power was reduced by 9.2–11.3%. The excellent performance of the BSCD was due to the multi-toothed structure of the cutting edge and the cutting mode.
A Review of Electroactive Nanomaterials in the Detection of Nitrogen-Containing Organic Compounds and Future Applications
Authors: Jagannathan Mohanraj , Dhinasekaran Durgalakshmi , Rajendran Ajay Rakkesh , Cho Sungbo
Published: November 2023

Electrochemical and impedimetric detection of nitrogen-containing organic compounds (NOCs) in blood, urine, sweat, and saliva is widely used in clinical diagnosis. NOC detection is used to identify illnesses such as chronic kidney disease (CKD), end-stage renal disease (ESRD), cardiovascular complications, diabetes, cancer, and others. In recent years, nanomaterials have shown significant potential in the detection of NOCs using electrochemical and impedimetric sensors. This potential is due to the higher surface area, porous nature, and functional groups of nanomaterials, which can aid in improving the sensing performance with inexpensive, direct, and quick-time processing methods. In this review, we discuss nanomaterials, such as metal oxides, graphene nanostructures, and their nanocomposites, for the detection of NOCs. Notably, researchers have considered nanocomposite-based devices, such as a field effect transistor (FET) and printed electrodes, for the detection of NOCs. In this review, we emphasize the significant importance of electrochemical and impedimetric methods in the detection of NOCs, which typically show higher sensitivity and selectivity. So, these methods will open a new way to make embeddable electrodes for point-of-detection (POD) devices. These devices could be used in the next generation of non-invasive analysis for biomedical and clinical applications. This review also summarizes recent state-of-the-art technology for the development of sensors for on-site monitoring and disease diagnosis at an earlier stage.
Can We Predict Skeletal Lesion on Bone Scan Based on Quantitative PSMA PET/CT Features?
Authors: Laudicella Riccardo , Bauckneht Matteo , Maurer Alexander , Heimer Jakob , Gennari Antonio G. , Di Raimondo Tania , Paone Gaetano , Cuzzocrea Marco , Messerli Michael , Eberli Daniel , Burger Irene A.
Published: November 2023

Objective: The increasing use of PSMA-PET/CT for restaging prostate cancer (PCa) leads to a patient shift from a non-metastatic situation based on conventional imaging (CI) to a metastatic situation. Since established therapeutic pathways have been designed according to CI, it is unclear how this should be translated to the PSMA-PET/CT results. This study aimed to investigate whether PSMA-PET/CT and clinical parameters could predict the visibility of PSMA-positive lesions on a bone scan (BS). Methods: In four different centers, all PCa patients with BS and PSMA-PET/CT within 6 months without any change in therapy or significant disease progression were retrospectively selected. Up to 10 non-confluent clear bone metastases were selected per PSMA-PET/CT and SUVmax, SUVmean, PSMAtot, PSMAvol, density, diameter on CT, and presence of cortical erosion were collected. Clinical variables (age, PSA, Gleason Score) were also considered. Two experienced double-board physicians decided whether a bone metastasis was visible on the BS, with a consensus readout for discordant findings. For predictive performance, a random forest was fit on all available predictors, and its accuracy was assessed using 10-fold cross-validation performed 10 times. Results: A total of 43 patients were identified with 222 bone lesions on PSMA-PET/CT. A total of 129 (58.1%) lesions were visible on the BS. In the univariate analysis, all PSMA-PET/CT parameters were significantly associated with the visibility on the BS (p < 0.001). The random forest reached a mean accuracy of 77.6% in a 10-fold cross-validation. Conclusions: These preliminary results indicate that there might be a way to predict the BS results based on PSMA-PET/CT, potentially improving the comparability between both examinations and supporting decisions for therapy selection.
CX3CR1-Expressing Immune Cells Infiltrate the Tumor Microenvironment and Promote Radiation Resistance in a Mouse Model of Lung Cancer
Authors: Ben-Mordechai Tamar , Lawrence Yaacov R. , Symon Zvi , Shimoni-Sebag Ariel , Amit Uri
Published: November 2023

Introduction: Chemokine (C-X3-C Motif) Receptor 1 (CX3CR1) is present in a subset of the immune cells in the tumor microenvironment (TME) and plays an essential and diverse role in cancer progression. However, its potential function in the irradiated TME remains unknown. Materials and Methods: A mouse lung cancer model was performed by subcutaneously inoculating Lewis Lung Carcinoma (LLC) cells expressing luciferase (Luc-2) and mCherry cells in CX3CR1GFP/GFP, CX3CR1DTR/+, and wild–type (WT) mice. Bioluminescence imaging, clonogenic assay, and flow cytometry were used to assess tumor progression, proliferation, and cell composition after radiation. Results: Radiation provoked a significant influx of CX3CR1-expressing immune cells, notably monocytes and macrophages, into the TME. Co-culturing irradiated LLC cells with CX3CR1-deficient monocytes, and macrophages resulted in reduced clonogenic survival and increased apoptosis of the cancer cells. Interestingly, deficiency of CX3CR1 in macrophages led to a redistribution of the irradiated LLC cells in the S-phase, parallel to increased expression of cyclin E1, required for cell cycle G1/S transition. In addition, the deficiency of CX3CR1 expression in macrophages altered the cytokine secretion with a decrease in interleukin 6, a crucial mediator of cancer cell survival and proliferation. Next, LLC cells were injected subcutaneously into CX3CR1DTR/+ mice, sensitive to diphtheria toxin (DT), and WT mice. After injection, tumors were irradiated with 8 Gy, and mice were treated with DT, leading to conditional ablation of CX3CR1-expressing cells. After three weeks, CX3CR1-depleted mice displayed reduced tumor progression. Furthermore, combining the S-phase-specific chemotherapeutic gemcitabine with CX3CR1 cell ablation resulted in additional attenuation of tumor progression. Conclusions: CX3CR1-expressing mononuclear cells invade the TME after radiation therapy in a mouse lung cancer model. CX3CR1 cell depletion attenuates tumor progression following radiation and sensitizes the tumor to S–phase-specific chemotherapy. Thus, we propose a novel strategy to improve radiation sensitivity by targeting the CX3CR1-expressing immune cells.
CBCT-to-CT Synthesis for Cervical Cancer Adaptive Radiotherapy via U-Net-Based Model Hierarchically Trained with Hybrid Dataset
Authors: Liu Xi , Yang Ruijie , Xiong Tianyu , Yang Xueying , Li Wen , Song Liming , Zhu Jiarui , Wang Mingqing , Cai Jing , Geng Lisheng
Published: November 2023

Purpose: To develop a deep learning framework based on a hybrid dataset to enhance the quality of CBCT images and obtain accurate HU values. Materials and Methods: A total of 228 cervical cancer patients treated in different LINACs were enrolled. We developed an encoder–decoder architecture with residual learning and skip connections. The model was hierarchically trained and validated on 5279 paired CBCT/planning CT images and tested on 1302 paired images. The mean absolute error (MAE), peak signal to noise ratio (PSNR), and structural similarity index (SSIM) were utilized to access the quality of the synthetic CT images generated by our model. Results: The MAE between synthetic CT images generated by our model and planning CT was 10.93 HU, compared to 50.02 HU for the CBCT images. The PSNR increased from 27.79 dB to 33.91 dB, and the SSIM increased from 0.76 to 0.90. Compared with synthetic CT images generated by the convolution neural networks with residual blocks, our model had superior performance both in qualitative and quantitative aspects. Conclusions: Our model could synthesize CT images with enhanced image quality and accurate HU values. The synthetic CT images preserved the edges of tissues well, which is important for downstream tasks in adaptive radiotherapy.
K-RAS Is…Complicated
Authors: Clark Geoffrey J.
Published: November 2023

There is little argument that the K-RAS onco-protein is the most important single oncoprotein in human cancer [...]
Mobilization of Circulating Tumor Cells after Short- and Long-Term FOLFIRINOX and GEM/nab-PTX Chemotherapy in Xenograft Mouse Models of Human Pancreatic Cancer
Authors: Ito Yukako , Kobuchi Shinji , Kawakita Amiri , Tosaka Kazuki , Matsunaga Yume , Yoshioka Shoma , Jonan Shizuka , Amagase Kikuko , Hashimoto Katsunori , Kanda Mitsuro , Saito Takuya , Nakanishi Hayao
Published: November 2023

Mobilization of CTCs after various types of therapy, such as radiation therapy, has been reported, but systematic study of CTCs after chemotherapy remained quite limited. In this study, we sequentially examined CTC numbers after single-dose and repetitive-dose chemotherapy, including FORFIRINOX (FFX) and Gemcitabine and nab-Paclitaxel (GnP) using two pancreatic cancer xenograft models. CTC was detected by the immunocytology-based microfluidic platform. We further examined the dynamic change in the histology of primary tumor tissues during chemotherapy. We confirmed a transient increase in CTCs 1–2 weeks after single-dose and repetitive-dose of FFX/GnP chemotherapy. Histological examination of the primary tumors revealed that the peak period of CTC at 1–2 weeks after chemotherapy corresponded to the maximal destructive phase consisting of cell cycle arrest, apoptosis of tumor cells, and blood vessel destruction without secondary reparative tissue reactions and regeneration of tumor cells. These findings indicate that mobilization of CTCs early after chemotherapy is mediated by the shedding of degenerated tumor cells into the disrupted blood vessels driven by the pure destructive histological changes in primary tumor tissues. These results suggest that sequential CTC monitoring during chemotherapy can be a useful liquid biopsy diagnostic tool to predict tumor chemosensitivity and resistance in preclinical and clinical settings.
Targeting Myeloid-Derived Suppressor Cell Trafficking as a Novel Immunotherapeutic Approach in Microsatellite Stable Colorectal Cancer
Authors: Johnson Benny
Published: November 2023

Myeloid-derived suppressor cells (MDSCs) are a unique subset of immune cells that promote an immunosuppressive phenotype due to their impacts on CD8 and regulatory T cell function. The inhibition of MDSC trafficking to the tumor microenvironment (TME) may represent a novel target in microsatellite stable (MSS) colorectal cancer with the potential to reprogram the immune system. Here, we review the rationale of inhibiting myeloid suppressor cell trafficking in treatment-refractory MSS colorectal cancer and circulating tumor DNA (ctDNA) positive settings to determine whether this approach can serve as a backbone for promoting immunotherapy response in this difficult-to-treat disease.
Setup Uncertainty of Pediatric Brain Tumor Patients Receiving Proton Therapy: A Prospective Study
Authors: Becksfort Jared , Uh Jinsoo , Saunders Andrew , Byrd Julia A. , Worrall Hannah M. , Marker Matt , Melendez-Suchi Christian , Li Yimei , Chang Jenghwa , Raghavan Kavitha , Merchant Thomas E. , Hua Chia-ho
Published: November 2023

This study quantifies setup uncertainty in brain tumor patients who received image-guided proton therapy. Patients analyzed include 165 children, adolescents, and young adults (median age at radiotherapy: 9 years (range: 10 months to 24 years); 80 anesthetized and 85 awake) enrolled in a single-institution prospective study from 2020 to 2023. Cone-beam computed tomography (CBCT) was performed daily to calculate and correct manual setup errors, once per course after setup correction to measure residual errors, and weekly after treatments to assess intrafractional motion. Orthogonal radiographs were acquired consecutively with CBCT for paired comparisons of 40 patients. Translational and rotational errors were converted from 6 degrees of freedom to a scalar by a statistical approach that considers the distance from the target to the isocenter. The 95th percentile of setup uncertainty was reduced by daily CBCT from 10 mm (manual positioning) to 1–1.5 mm (after correction) and increased to 2 mm by the end of fractional treatment. A larger variation existed between the roll corrections reported by radiographs vs. CBCT than for pitch and yaw, while there was no statistically significant difference in translational variation. A quantile mixed regression model showed that the 95th percentile of intrafractional motion was 0.40 mm lower for anesthetized patients (p=0.0016). Considering additional uncertainty in radiation-imaging isocentricity, the commonly used total plan robustness of 3 mm against positional uncertainty would be appropriate for our study cohort.
Regucalcin Is a Potential Regulator in Human Cancer: Aiming to Expand into Cancer Therapy
Authors: Yamaguchi Masayoshi
Published: November 2023

Regucalcin, a calcium-binding protein lacking the EF-hand motif, was initially discovered in 1978. Its name is indicative of its function in calcium signaling regulation. The rgn gene encodes for regucalcin and is situated on the X chromosome in both humans and vertebrates. Regucalcin regulates pivotal enzymes involved in signal transduction and has an inhibitory function, which includes protein kinases, protein phosphatases, cysteinyl protease, nitric oxide dynthetase, aminoacyl-transfer ribonucleic acid (tRNA) synthetase, and protein synthesis. This cytoplasmic protein is transported to the nucleus where it regulates deoxyribonucleic acid and RNA synthesis as well as gene expression. Overexpression of regucalcin inhibits proliferation in both normal and cancer cells in vitro, independent of apoptosis. During liver regeneration in vivo, endogenous regucalcin suppresses cell growth when overexpressed. Regucalcin mRNA and protein expressions are significantly downregulated in tumor tissues of patients with various types of cancers. Patients exhibiting upregulated regucalcin in tumor tissue have shown prolonged survival. The decrease of regucalcin expression is linked to the advancement of cancer. Overexpression of regucalcin carries the potential for preventing and treating carcinogenesis. Additionally, extracellular regucalcin has displayed control over various types of human cancer cells. Regucalcin may hold a prominent role as a regulatory factor in cancer development. Supplying the regucalcin gene could prove to be a valuable asset in cancer treatment. The therapeutic value of regucalcin suggests its potential significance in treating cancer patients. This review delves into the most recent research on the regulatory role of regucalcin in human cancer development, providing a novel approach for treatment.
A Clinical Viewpoint on the Use of Targeted Therapy in Advanced Gastric Cancer
Authors: Skórzewska Magdalena , Gęca Katarzyna , Polkowski Wojciech P.
Published: November 2023

The development of therapies for advanced gastric cancer (GC) has made significant progress over the past few years. The identification of new molecules and molecular targets is expanding our understanding of the disease’s intricate nature. The end of the classical oncology era, which relied on well-studied chemotherapeutic agents, is giving rise to novel and unexplored challenges, which will cause a significant transformation of the current oncological knowledge in the next few years. The integration of established clinically effective regimens in additional studies will be crucial in managing these innovative aspects of GC. This study aims to present an in-depth and comprehensive review of the clinical advancements in targeted therapy and immunotherapy for advanced GC.
The Role of the Tumor Microenvironment in Triple-Positive Breast Cancer Progression and Therapeutic Resistance
Authors: Pu Qian , Gao Haidong
Published: November 2023

Breast cancer (BRCA) is a highly heterogeneous systemic disease. It is ranked first globally in the incidence of new cancer cases and has emerged as the primary cause of cancer-related death among females. Among the distinct subtypes of BRCA, triple-positive breast cancer (TPBC) has been associated with increased metastasis and invasiveness, exhibiting greater resistance to endocrine therapy involving trastuzumab. It is now understood that invasion, metastasis, and treatment resistance associated with BRCA progression are not exclusively due to breast tumor cells but are from the intricate interplay between BRCA and its tumor microenvironment (TME). Accordingly, understanding the pathogenesis and evolution of the TPBC microenvironment demands a comprehensive approach. Moreover, addressing BRCA treatment necessitates a holistic consideration of the TME, bearing significant implications for identifying novel targets for anticancer interventions. This review expounds on the relationship between critical cellular components and factors in the TPBC microenvironment and the inception, advancement, and therapeutic resistance of breast cancer to provide perspectives on the latest research on TPBC.
Ni-BaMnO3 Perovskite Catalysts for NOx-Assisted Soot Oxidation: Analyzing the Effect of the Nickel Addition Method
Authors: Montilla-Verdú Salvador , Díaz-Verde Álvaro , Torregrosa-Rivero Verónica , Illán-Gómez María José
Published: November 2023

In this study, we analyzed the role of a series of BaMn1−xNixO3 (x = 0, 0.2, and 0.4) mixed oxide catalysts, synthesized using the sol–gel method, in NOx-assisted diesel soot oxidation. ICP-OES, XRD, XPS, and H2-TPR techniques were used for characterization and Temperature-Programmed Reaction experiments (NOx-TPR and Soot-NOx-TPR), and isothermal reactions at 450 °C (for the most active sample) were carried out to determine the catalytic activity. All samples catalyzed NO and soot oxidation at temperatures below 400 °C, presenting nickel-containing catalysts with the highest soot conversion and selectivity to CO2. However, the nickel content did not significantly modify the catalytic performance, and in order to improve it, two catalysts (5 wt % in Ni) were synthesized via the hydrothermal method (BMN2H) and the impregnation of nickel on a BaMnO3 perovskite as support (M5). The two samples presented higher activity for NO and soot oxidation than BMN2E (obtained via the sol–gel method) as they presented more nickel on the surface (as determined via XPS). BMN2H was more active than M5 as it presented (i) more surface oxygen vacancies, which are active sites for oxidation reactions; (ii) improved redox properties; and (iii) a lower average crystal size for nickel (as NiO). As a consequence of these properties, BMN2H featured a high soot oxidation rate at 450 °C, which hindered the accumulation of soot during the reaction and, thus, the deactivation of the catalyst.
Gut Microbiota, Inflammatory Bowel Disease, and Cancer: The Role of Guardians of Innate Immunity
Authors: Giambra Vincenzo , Pagliari Danilo , Rio Pierluigi , Totti Beatrice , Di Nunzio Chiara , Bosi Annalisa , Giaroni Cristina , Gasbarrini Antonio , Gambassi Giovanni , Cianci Rossella
Published: November 2023

Inflammatory bowel diseases (IBDs) are characterized by a persistent low-grade inflammation that leads to an increased risk of colorectal cancer (CRC) development. Several factors are implicated in this pathogenetic pathway, such as innate and adaptive immunity, gut microbiota, environment, and xenobiotics. At the gut mucosa level, a complex interplay between the immune system and gut microbiota occurs; a disequilibrium between these two factors leads to an alteration in the gut permeability, called ‘leaky gut’. Subsequently, an activation of several inflammatory pathways and an alteration of gut microbiota composition with a proliferation of pro-inflammatory bacteria, known as ‘pathobionts’, take place, leading to a further increase in inflammation. This narrative review provides an overview on the principal Pattern Recognition Receptors (PRRs), including Toll-like receptors (TLRs) and NOD-like receptors (NLRs), focusing on their recognition mechanisms, signaling pathways, and contributions to immune responses. We also report the genetic polymorphisms of TLRs and dysregulation of NLR signaling pathways that can influence immune regulation and contribute to the development and progression of inflammatory disease and cancer.
Exploration of the Noncoding Genome for Human-Specific Therapeutic Targets—Recent Insights at Molecular and Cellular Level
Authors: Poller Wolfgang , Sahoo Susmita , Hajjar Roger , Landmesser Ulf , Krichevsky Anna M.
Published: November 2023

While it is well known that 98–99% of the human genome does not encode proteins, but are nevertheless transcriptionally active and give rise to a broad spectrum of noncoding RNAs [ncRNAs] with complex regulatory and structural functions, specific functions have so far been assigned to only a tiny fraction of all known transcripts. On the other hand, the striking observation of an overwhelmingly growing fraction of ncRNAs, in contrast to an only modest increase in the number of protein-coding genes, during evolution from simple organisms to humans, strongly suggests critical but so far essentially unexplored roles of the noncoding genome for human health and disease pathogenesis. Research into the vast realm of the noncoding genome during the past decades thus lead to a profoundly enhanced appreciation of the multi-level complexity of the human genome. Here, we address a few of the many huge remaining knowledge gaps and consider some newly emerging questions and concepts of research. We attempt to provide an up-to-date assessment of recent insights obtained by molecular and cell biological methods, and by the application of systems biology approaches. Specifically, we discuss current data regarding two topics of high current interest: (1) By which mechanisms could evolutionary recent ncRNAs with critical regulatory functions in a broad spectrum of cell types (neural, immune, cardiovascular) constitute novel therapeutic targets in human diseases? (2) Since noncoding genome evolution is causally linked to brain evolution, and given the profound interactions between brain and immune system, could human-specific brain-expressed ncRNAs play a direct or indirect (immune-mediated) role in human diseases? Synergistic with remarkable recent progress regarding delivery, efficacy, and safety of nucleic acid-based therapies, the ongoing large-scale exploration of the noncoding genome for human-specific therapeutic targets is encouraging to proceed with the development and clinical evaluation of novel therapeutic pathways suggested by these research fields.
Role of Stress on Driving the Intestinal Paracellular Permeability
Authors: Molotla-Torres Daniel Efrain , Guzmán-Mejía Fabiola , Godínez-Victoria Marycarmen , Drago-Serrano Maria Elisa
Published: November 2023

The gut epithelium is a polarized monolayer that exhibits apical and basolateral membrane surfaces. Monolayer cell components are joined side by side via protein complexes known as tight junction proteins (TJPs), expressed at the most apical extreme of the basolateral membrane. The gut epithelium is a physical barrier that determinates intestinal permeability, referred to as the measurement of the transit of molecules from the intestinal lumen to the bloodstream or, conversely, from the blood to the gut lumen. TJPs play a role in the control of intestinal permeability that can be disrupted by stress through signal pathways triggered by the ligation of receptors with stress hormones like glucocorticoids. Preclinical studies conducted under in vitro and/or in vivo conditions have addressed underlying mechanisms that account for the impact of stress on gut permeability. These mechanisms may provide insights for novel therapeutic interventions in diseases in which stress is a risk factor, like irritable bowel syndrome. The focus of this study was to review, in an integrative context, the neuroendocrine effects of stress, with special emphasis on TJPs along with intestinal permeability.
Investigation of the Change in Roughness and Microhardness during Laser Surface Texturing of Copper Samples by Changing the Process Parameters
Authors: Ghalot Risham Singh , Lazov Lyubomir , Yankov Emil , Angelov Nikolay
Published: November 2023

The aim of this research is to achieve a high-quality and long-lasting laser marking of ammunition, which is of interest to the defense industry. The study is about the effects of speed, raster pitch and power on the roughness and microhardness of the marked areas of copper samples. The experiments were carried out with a fiber laser and a copper bromide laser—modern lasers widely used in industrial production. Laser power, scan speed and raster step were varied to determine their effects on the resulting microhardness and surface roughness. The lasers operate in different wavelength ranges, with the optical laser operating at 1064 nm in the near-infrared region and the copper bromide laser at 511 nm and 578 nm in the visible region, allowing the influence of wavelengths on the process to be investigated. The roughness and microhardness velocity dependence for three powers and two pulse durations for the fiber laser were obtained from the experimental data. The dependence of roughness and microhardness on the raster step for both types of lasers was also demonstrated.