bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Advances and Mechanisms of Phage-Based Therapies in Cancer Treatment
Authors: Ooi Vivian Y. , Yeh Ting-Yu
Published: September 2024

The increasing interest in bacteriophage technology has prompted its novel applications to treat different medical conditions, most interestingly cancer. Due to their high specificity, manipulability, nontoxicity, and nanosize nature, phages are promising carriers in targeted therapy and cancer immunotherapy. This approach is particularly timely, as current challenges in cancer research include damage to healthy cells, inefficiency in targeting, obstruction by biological barriers, and drug resistance. Some cancers are being kept at the forefront of phage research, such as colorectal cancer and HCC, while others like lymphoma, cervical cancer, and myeloma have not been retouched in a decade. Common mechanisms are immunogenic antigen display on phage coats and the use of phage as transporters to carry drugs, genes, and other molecules. To date, popular phage treatments being tested are gene therapy and phage-based vaccines using M13 and λ phage, with some vaccines having advanced to human clinical trials. The results from most of these studies have been promising, but limitations in phage-based therapies such as reticuloendothelial system clearance or diffusion inefficiency must be addressed. Before phage-based therapies for cancer can be successfully used in oncology practice, more in-depth research and support from local governments are required.
Decursin Induces G1 Cell Cycle Arrest and Apoptosis through Reactive Oxygen Species-Mediated Endoplasmic Reticulum Stress in Human Colorectal Cancer Cells in In Vitro and Xenograft Models
Authors: Kim Danbee , Go Seok-Ho , Song Yeeun , Lee Dong-Keon , Park Jeong-Ran
Published: September 2024

Decursin, a coumarin isolated from Angelica gigas Nakai, possesses anti-inflammatory and anti-cancer properties. However, the molecular mechanisms underlying its anti-cancer effects against human colorectal cancer (CRC) are unclear. Therefore, this study aimed to evaluate the biological activities of decursin in CRC in vitro and in vivo and to determine its underlying mechanism of action. Decursin exhibited anti-tumor activity in vitro, accompanied by an increase in G1 cell cycle arrest and apoptosis in HCT-116 and HCT-8 CRC cells. Decursin also induced the production of reactive oxygen species (ROS), thereby activating the endoplasmic reticulum (ER) stress apoptotic pathway in CRC cells. Furthermore, the role of ROS in decursin-induced apoptosis was investigated using the antioxidant N-acetyl-L-cysteine. Inhibiting ROS production reversed decursin-induced ER stress. Moreover, decursin significantly suppressed tumor growth in a subcutaneous xenograft mouse model of HCT-116 and HCT-8 CRC cells without causing host toxicity. Decursin also decreased cell proliferation, as documented by Ki-67, and partly increased cleaved caspase 3 expression in tumor tissues by activating ER stress apoptotic pathways. These findings suggest that decursin induces cell cycle arrest and apoptosis in human CRC cells via ROS-mediated ER stress, suggesting that decursin could be a therapeutic agent for CRC.
Photo-Crosslinked Pro-Angiogenic Hydrogel Dressing for Wound Healing
Authors: Zhang Wang , Qian Shuyi , Chen Jia , Jian Tianshen , Wang Xuechun , Zhu Xianmin , Dong Yixiao , Fan Guoping
Published: September 2024

Severe burns are one of the most devastating injuries, in which sustained inflammation and ischemia often delay the healing process. Pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF) have been widely studied for promoting wound healing. However, the short half-life and instability of VEGF limit its clinical applications. In this study, we develop a photo-crosslinked hydrogel wound dressing from methacrylate hyaluronic acid (MeHA) bonded with a pro-angiogenic prominin-1-binding peptide (PR1P). The materials were extruded in wound bed and in situ formed a wound dressing via exposure to short-time ultraviolet radiation. The study shows that the PR1P-bonded hydrogel significantly improves VEGF recruitment, tubular formation, and cell migration in vitro. Swelling, Scanning Electron Microscope, and mechanical tests indicate the peptide does not affect the overall mechanical and physical properties of the hydrogels. For in vivo studies, the PR1P-bonded hydrogel dressing enhances neovascularization and accelerates wound closure in both deep second-degree burn and full-thickness excisional wound models. The Western blot assay shows such benefits can be related to the activation of the VEGF–Akt signaling pathway. These results suggest this photo-crosslinked hydrogel dressing efficiently promotes VEGF recruitment and angiogenesis in skin regeneration, indicating its potential for clinical applications in wound healing.
Rhododendron luteum Sweet Flower Supercritical CO2 Extracts: Terpenes Composition, Pro-Inflammatory Enzymes Inhibition and Antioxidant Activity
Authors: Łyko Lena , Olech Marta , Gawlik Urszula , Krajewska Agnieszka , Kalemba Danuta , Tyśkiewicz Katarzyna , Piórecki Narcyz , Prokopiv Andriy , Nowak Renata
Published: September 2024

Terpenes are plant secondary metabolites known for their anti-inflammatory and antioxidant activities. According to ethnobotanical knowledge, Rhododendron luteum Sweet was used in traditional medicine against inflammation. The present study was conducted to determine the triterpene profile and antioxidant and anti-inflammatory activity of supercritical CO2 (SC-CO2) extracts of Rhododendron luteum Sweet flower (RLF). An LC-APCI-MS/MS analysis showed the presence of eight pentacyclic triterpenes and one phytosterol in the extracts obtained with pure CO2 as well as CO2 with the addition of aqueous ethanol as a co-solvent. Among the compounds detected, oleanolic/ursolic acid, β-sitosterol and 3β-taraxerol were the most abundant. The extract obtained with pure SC-CO2 was additionally subjected to HS-SPME-GC-FID-MS, which revealed more than 100 volatiles, mainly eugenol, β-phenylethanol, dodecane, β-caryophyllene, estragole and (Z)- and (E)-cinnamyl alcohol, followed by δ-cadinene. The extracts demonstrated significant hyaluronidase inhibition and exhibited varying modes of lipoxygenase and xanthine oxidase inhibitory activities. The studies of RLF have shown that their SC-CO2 extracts can be a rich source of triterpenes with anti-inflammatory potential.
Does Vitamin B6 Act as an Exercise Mimetic in Skeletal Muscle?
Authors: Kato Norihisa , Yang Yongshou , Bumrungkit Chanikan , Kumrungsee Thanutchaporn
Published: September 2024

Marginal vitamin B6 (B6) deficiency is common in various segments worldwide. In a super-aged society, sarcopenia is a major concern and has gained significant research attention focused on healthy aging. To date, the primary interventions for sarcopenia have been physical exercise therapy. Recent evidence suggests that inadequate B6 status is associated with an increased risk of sarcopenia and mortality among older adults. Our previous study showed that B6 supplementation to a marginal B6-deficient diet up-regulated the expression of various exercise-induced genes in the skeletal muscle of rodents. Notably, a supplemental B6-to-B6-deficient diet stimulates satellite cell-mediated myogenesis in rodents, mirroring the effects of physical exercise. These findings suggest the potential role of B6 as an exercise-mimetic nutrient in skeletal muscle. To test this hypothesis, we reviewed relevant literature and compared the roles of B6 and exercise in muscles. Here, we provide several pieces of evidence supporting this hypothesis and discuss the potential mechanisms behind the similarities between the effects of B6 and exercise on muscle. This research, for the first time, provides insight into the exercise-mimetic roles of B6 in skeletal muscle.
Silver Nanoparticles Improve Fluorophore Photostability: Application to a Hypericin Study
Authors: Wołąkiewicz Grzegorz , Pietrzak Monika , Szabelski Mariusz
Published: September 2024

Protection against the negative effects of solar radiation involves using cosmetics with a UV filter, but visible radiation can also have negative effects. We use dietary supplements and take medications; unfortunately, many of them contain substances that degrade under the influence of visible light, which transform into chemical compounds harmful to health. Manufacturers often include information on the prohibition of exposure to sunlight on the packaging, but consumers often do not read the product leaflet. The solution to this problem may be the addition of silver particles to preparations. In the presented article, we proposed the use of silver nanoparticles to reduce the photobleaching and photoreaction of fluorophore, while increasing the fluorescence intensity. For our research, we used a compound that is particularly sensitive to radiation: hypericin.
Cancer Treatment: New Drugs and Strategies
Authors: Vale Nuno
Published: September 2024

Cancer is a significant global health problem with complex treatment challenges [...]
Interactions of SARS-CoV-2 with Human Target Cells—A Metabolic View
Authors: Eisenreich Wolfgang , Leberfing Julian , Rudel Thomas , Heesemann Jürgen , Goebel Werner
Published: September 2024

Viruses are obligate intracellular parasites, and they exploit the cellular pathways and resources of their respective host cells to survive and successfully multiply. The strategies of viruses concerning how to take advantage of the metabolic capabilities of host cells for their own replication can vary considerably. The most common metabolic alterations triggered by viruses affect the central carbon metabolism of infected host cells, in particular glycolysis, the pentose phosphate pathway, and the tricarboxylic acid cycle. The upregulation of these processes is aimed to increase the supply of nucleotides, amino acids, and lipids since these metabolic products are crucial for efficient viral proliferation. In detail, however, this manipulation may affect multiple sites and regulatory mechanisms of host-cell metabolism, depending not only on the specific viruses but also on the type of infected host cells. In this review, we report metabolic situations and reprogramming in different human host cells, tissues, and organs that are favorable for acute and persistent SARS-CoV-2 infection. This knowledge may be fundamental for the development of host-directed therapies.
Onco-Ontogeny of Squamous Cell Cancer of the First Pharyngeal Arch Derivatives
Authors: Sat-Muñoz Daniel , Balderas-Peña Luz-Ma.-Adriana , Gómez-Sánchez Eduardo , Martínez-Herrera Brenda-Eugenia , Trujillo-Hernández Benjamín , Quiroga-Morales Luis-Aarón , Salazar-Páramo Mario , Dávalos-Rodríguez Ingrid-Patricia , Nuño-Guzmán Carlos M. , Velázquez-Flores Martha-Cecilia , Ochoa-Plascencia Miguel-Ricardo , Muciño-Hernández María-Ivette , Isiordia-Espinoza Mario-Alberto , Mireles-Ramírez Mario-Alberto , Hernández-Salazar Eduardo
Published: September 2024

Head and neck squamous cell carcinoma (H&NSCC) is an anatomic, biological, and genetic complex disease. It involves more than 1000 genes implied in its oncogenesis; for this review, we limit our search and description to the genes implied in the onco-ontogeny of the derivates from the first pharyngeal arch during embryo development. They can be grouped as transcription factors and signaling molecules (that act as growth factors that bind to receptors). Finally, we propose the term embryo-oncogenesis to refer to the activation, reactivation, and use of the genes involved in the embryo’s development during the oncogenesis or malignant tumor invasion and metastasis events as part of an onco-ontogenic inverse process.
The Furin Protease Dependence and Antiviral GBP2 Sensitivity of Murine Leukemia Virus Infection Are Determined by the Amino Acid Sequence at the Envelope Glycoprotein Cleavage Site
Authors: Kubo Yoshinao , Hans Manya Bakatumana , Nakamura Taisuke , Hayashi Hideki
Published: September 2024

Host restriction factor GBP2 suppresses the replication of the ecotropic Moloney murine leukemia virus (E-MLV) by inhibiting furin protease, which cleaves the viral envelope glycoprotein (Env) into surface (SU) and transmembrane (TM) subunits. We analyzed the impacts of GBP2 on the infection efficiency mediated by MLV Envs of different strains of ecotropic Moloney, polytropic Friend, amphotropic, and xenotropic MLV-related (XMRV) viruses. Interestingly, the Envs of ecotropic Moloney and polytropic Friend MLV were sensitive to the antiviral activity of GBP2, while XMRV and amphotropic Envs showed resistance. Consistent with the sensitivity to GBP2, the amino acid sequences of the sensitive Envs at the SU-TM cleavage site were similar, as were the sequences of the resistant Envs. SU-TM cleavage of the GBP2-sensitive Env protein was inhibited by furin silencing, whereas that of GBP2-resistant Env was not. The substitution of the ecotropic Moloney cleavage site sequence with that of XMRV conferred resistance to both GBP2 and furin silencing. Reciprocally, the substitution of the XMRV cleavage site sequence with that of the ecotropic sequence conferred sensitivity to GBP2 and furin silencing. According to the SU-TM cleavage site sequence, there were sensitive and resistant variants among ecotropic, polytropic, and xenotropic MLVs. This study found that the dependence of MLV Env proteins on furin cleavage and GBP2-mediated restriction is determined by the amino acid sequences at the SU-TM cleavage site.
Protein Microarrays for High Throughput Hydrogen/Deuterium Exchange Monitored by FTIR Imaging
Authors: De Meutter Joëlle , Goormaghtigh Erik
Published: September 2024

Proteins form the fastest-growing therapeutic class. Due to their intrinsic instability, loss of native structure is common. Structure alteration must be carefully evaluated as structural changes may jeopardize the efficiency and safety of the protein-based drugs. Hydrogen deuterium exchange (HDX) has long been used to evaluate protein structure and dynamics. The rate of exchange constitutes a sensitive marker of the conformational state of the protein and of its stability. It is often monitored by mass spectrometry. Fourier transform infrared (FTIR) spectroscopy is another method with very promising capabilities. Combining protein microarrays with FTIR imaging resulted in high throughput HDX FTIR measurements. BaF2 slides bearing the protein microarrays were covered by another slide separated by a spacer, allowing us to flush the cell continuously with a flow of N2 gas saturated with 2H2O. Exchange occurred simultaneously for all proteins and single images covering ca. 96 spots of proteins that could be recorded on-line at selected time points. Each protein spot contained ca. 5 ng protein, and the entire array covered 2.5 × 2.5 mm2. Furthermore, HDX could be monitored in real time, and the experiment was therefore not subject to back-exchange problems. Analysis of HDX curves by inverse Laplace transform and by fitting exponential curves indicated that quantitative comparison of the samples is feasible. The paper also demonstrates how the whole process of analysis can be automatized to yield fast analyses.
Pterostilbene, a Dimethyl Derivative of Resveratrol, Exerts Cytotoxic Effects on Melanin-Producing Cells through Metabolic Activation by Tyrosinase
Authors: Tanaka Hitomi , Nishimaki-Mogami Tomoko , Tamehiro Norimasa , Shibata Norihito , Mandai Hiroki , Ito Shosuke , Wakamatsu Kazumasa
Published: September 2024

Pterostilbene (PTS), which is abundant in blueberries, is a dimethyl derivative of the natural polyphenol resveratrol (RES). Several plant species, including peanuts and grapes, also produce PTS. Although RES has a wide range of health benefits, including anti-cancer properties, PTS has a robust pharmacological profile that includes a better intestinal absorption and an increased hepatic stability compared to RES. Indeed, PTS has a higher bioavailability and a lower toxicity compared to other stilbenes, making it an attractive drug candidate for the treatment of various diseases, including diabetes, cancer, cardiovascular disease, neurodegenerative disorders, and aging. We previously reported that RES serves as a substrate for tyrosinase, producing an o-quinone metabolite that is highly cytotoxic to melanocytes. The present study investigated whether PTS may also be metabolized by tyrosinase, similarly to RES. PTS was oxidized as a substrate by tyrosinase to form an o-quinone, which reacted with thiols, such as N-acetyl-L-cysteine, to form di- and tri-adducts. We also confirmed that PTS was taken up and metabolized by human tyrosinase-expressing 293T cells in amounts several times greater than RES. In addition, PTS showed a tyrosinase-dependent cytotoxicity against B16BL6 melanoma cells that was stronger than RES and also inhibited the formation of melanin in B16BL6 melanoma cells and in the culture medium. These results suggest that the two methyl groups of PTS, which are lipophilic, increase its membrane permeability, making it easier to bind to intracellular proteins, and may therefore be more cytotoxic to melanin-producing cells.
Highly Repetitive Genome of Coniella granati (syn. Pilidiella granati), the Causal Agent of Pomegranate Fruit Rot, Encodes a Minimalistic Proteome with a Streamlined Arsenal of Effector Proteins
Authors: Zambounis Antonios , Maniatis Elisseos I. , Mincuzzi Annamaria , Gray Naomi , Hossain Mohitul , Tsitsigiannis Dimitrios I. , Paplomatas Epaminondas , Ippolito Antonio , Schena Leonardo , Hane James K.
Published: September 2024

This study describes the first genome sequence and analysis of Coniella granati, a fungal pathogen with a broad host range, which is responsible for postharvest crown rot, shoot blight, and canker diseases in pomegranates. C. granati is a geographically widespread pathogen which has been reported across Europe, Asia, the Americas, and Africa. Our analysis revealed a 46.8 Mb genome with features characteristic of hemibiotrophic fungi. Approximately one third of its genome was compartmentalised within ‘AT-rich’ regions exhibiting a low GC content (30 to 45%). These regions primarily comprised transposable elements that are repeated at a high frequency and interspersed throughout the genome. Transcriptome-supported gene annotation of the C. granati genome revealed a streamlined proteome, mirroring similar observations in other pathogens with a latent phase. The genome encoded a relatively compact set of 9568 protein-coding genes with a remarkable 95% having assigned functional annotations. Despite this streamlined nature, a set of 40 cysteine-rich candidate secreted effector-like proteins (CSEPs) was predicted as well as a gene cluster involved in the synthesis of a pomegranate-associated toxin. These potential virulence factors were predominantly located near repeat-rich and AT-rich regions, suggesting that the pathogen evades host defences through Repeat-Induced Point mutation (RIP)-mediated pseudogenisation. Furthermore, 23 of these CSEPs exhibited homology to known effector and pathogenicity genes found in other hemibiotrophic pathogens. The study establishes a foundational resource for the study of the genetic makeup of C. granati, paving the way for future research on its pathogenicity mechanisms and the development of targeted control strategies to safeguard pomegranate production.
Immunogenetic Landscape in Pediatric Common Variable Immunodeficiency
Authors: Szczawińska-Popłonyk Aleksandra , Ciesielska Wiktoria , Konarczak Marta , Opanowski Jakub , Orska Aleksandra , Wróblewska Julia , Szczepankiewicz Aleksandra
Published: September 2024

Common variable immunodeficiency (CVID) is the most common symptomatic antibody deficiency, characterized by heterogeneous genetic, immunological, and clinical phenotypes. It is no longer conceived as a sole disease but as an umbrella diagnosis comprising a spectrum of clinical conditions, with defects in antibody biosynthesis as their common denominator and complex pathways determining B and T cell developmental impairments due to genetic defects of many receptors and ligands, activating and co-stimulatory molecules, and intracellular signaling molecules. Consequently, these genetic variants may affect crucial immunological processes of antigen presentation, antibody class switch recombination, antibody affinity maturation, and somatic hypermutation. While infections are the most common features of pediatric CVID, variants in genes linked to antibody production defects play a role in pathomechanisms of immune dysregulation with autoimmunity, allergy, and lymphoproliferation reflecting the diversity of the immunogenetic underpinnings of CVID. Herein, we have reviewed the aspects of genetics in CVID, including the monogenic, digenic, and polygenic models of inheritance exemplified by a spectrum of genes relevant to CVID pathophysiology. We have also briefly discussed the epigenetic mechanisms associated with micro RNA, DNA methylation, chromatin reorganization, and histone protein modification processes as background for CVID development.
The Benefits of Cognitive Therapeutic Exercise in Symptomatic Arnold–Chiari Syndrome Type I: A Case Report on Gait, Balance, and Pain Management
Authors: Tisano Adriana , Alito Angelo , Ragonese de Gregorio Rita , Campo Adele , Santoro Giuseppe , Milardi Demetrio , Cavallaro Filippo , Cucinotta Francesca
Published: September 2024

Background: Chiari malformation is a rare congenital condition in which the cerebellar tonsils herniate through the foramen magnum, causing symptoms related to compression of the surrounding structures. Rehabilitation plays a key role in the pre- and post-operative management of the syndrome, as it can improve strength, range of motion, motor coordination, pain management, and performance of activities of daily living. Methods: This article presents the case of a 43-year-old woman with Chiari malformation 1B who underwent resection of the filum terminale. She presented as an outpatient at the University Hospital “G. Martino” in Messina, complaining of difficulty walking, balance problems, lumbar pain, and heaviness in the lower limbs. Following a multidisciplinary assessment, she underwent an 11-month rehabilitation protocol based on cognitive therapeutic exercise. Results: The patient achieved significant improvements in pain, mental confusion, and quality of life after treatment and at the 12-month follow-up. Conclusions: The results of this study highlight the significant benefits of cognitive therapeutic exercises in Chiari malformation, with improvements in several key areas, including quality of life, pain management, and ability to perform activities of daily living.
In-Hospital Graft Occlusion in Post-Coronary Artery Bypass Grafting Patients in the Early Postoperative Period: A Systematic Review and Meta-Analysis
Authors: Salikhanov Islam , Koechlin Luca , Gahl Brigitta , Zellweger Michael J. , Haaf Philip , Müller Christian , Berdajs Denis
Published: September 2024

Objectives: The objectives of this paper are to evaluate the incidence of early graft occlusion during hospital stays following coronary bypass surgery (CABG) and to assess the factors influencing the odds of in-hospital early graft occlusion. Methods: Reports evaluating the early in-hospital occlusion of coronary bypass grafts were identified through PubMed, Embase, and Cochrane databases. The primary endpoint was to determine the incidence of early graft occlusion following CABG before discharge and to identify and quantify the impact of demographic, clinical, and procedural risk factors on the occurrence of early graft occlusion. The meta-analysis was conducted using a random-effects inverse-variance model with the DerSimonian–Laird estimator, assessing incidence rates, risk factors, and study heterogeneity, with statistical analysis performed using Stata. Results: A total of 22 studies with 35,798 patients were included in the analysis. The overall incidence of in-hospital early graft occlusion was 5% (95% CI: 3% to 7%). In studies using symptom-driven patency assessment, the incidence of occlusion was 2%, whereas in those employing systematic graft patency assessment, it was 6%. Only the presence of a vein graft OR 2.13 (95% CI: 1.19–3.82) was significantly associated with in-hospital graft occlusion. Conclusions: The incidence of in-hospital early graft occlusion seems substantially underestimated if imaging is restricted only to symptomatic patients. Moreover, female gender, increased PI, and the presence of a composite graft could also be potential risk factors for this complication.
Trends in the Use of Weightbearing Computed Tomography
Authors: Bernasconi Alessio , Dechir Yanis , Izzo Antonio , D’Agostino Martina , Magliulo Paolo , Smeraglia Francesco , de Cesar Netto Cesar ,   International Weightbearing CT Society, Lintz François
Published: September 2024

Background: This review aimed to critically appraise the most recent orthopedic literature around cone beam weightbearing computed tomography (WBCT), summarizing what evidence has been provided so far and identifying the main research trends in the area. Methods: This scoping review was performed on studies published between January 2013 and December 2023 on the Pubmed database. All studies (both clinical and nonclinical) in which WBCT had been used were critically analyzed to extract the aim (or aims) of the study, and the main findings related to the role of this imaging modality in the diagnostic pathway. Results: Out of 1759 studies, 129 were selected. One hundred five manuscripts (81%) dealt with elective orthopedic conditions. The majority of the analyses (88 studies; 84%) were performed on foot and ankle conditions, while 13 (12%) studies looked at knee pathologies. There was a progressive increase in the number of studies published over the years. Progressive Collapsing Foot Deformity (22 studies; 25%) and Hallux Valgus (19 studies; 21%) were frequent subjects. Twenty-four (19%) manuscripts dealt with traumatic conditions. A particular interest in syndesmotic injuries was documented (12 studies; 60%). Conclusions: In this review, we documented an increasing interest in clinical applications of weightbearing CT in the orthopedic field between 2013 and 2023. The majority of the analyses focused on conditions related to the foot and the ankle; however, we found several works investigating the value of WBCT on other joints (in particular, the knee).
Myotube Guidance: Shaping up the Musculoskeletal System
Authors: Johnson Aaron N.
Published: September 2024

Myofibers are highly specialized contractile cells of skeletal muscles, and dysregulation of myofiber morphogenesis is emerging as a contributing cause of myopathies and structural birth defects. Myotubes are the myofiber precursors and undergo a dramatic morphological transition into long bipolar myofibers that are attached to tendons on two ends. Similar to axon growth cones, myotube leading edges navigate toward target cells and form cell–cell connections. The process of myotube guidance connects myotubes with the correct tendons, orients myofiber morphology with the overall body plan, and generates a functional musculoskeletal system. Navigational signaling, addition of mass and volume, and identification of target cells are common events in myotube guidance and axon guidance, but surprisingly, the mechanisms regulating these events are not completely overlapping in myotubes and axons. This review summarizes the strategies that have evolved to direct myotube leading edges to predetermined tendon cells and highlights key differences between myotube guidance and axon guidance. The association of myotube guidance pathways with developmental disorders is also discussed.
Investigation of Vessel Manoeuvring Abilities in Shallow Depths by Applying Neural Networks
Authors: Moreira Lúcia , Guedes Soares C.
Published: September 2024

A set of planar motion mechanism experiments of the Duisburg Test Case Post-Panamax container model executed in a towing tank with shallow depth is applied to train a neural network to analyse the ability of the proposed model to learn the effects of different depth conditions on ship’s manoeuvring capabilities. The motivation of the work presented in this paper is to contribute an alternative and effective approach to model non-linear systems through artificial neural networks that address the manoeuvring simulation of ships in shallow water. The system is developed using the Levenberg–Marquardt backpropagation training algorithm and the resilient backpropagation scheme to demonstrate the correlation between the vessel forces and the respective trajectories and velocities. Sensitivity analyses were performed to identify the number of layers necessary for the proposed model to predict the vessel manoeuvring characteristics in two different depths. The outcomes achieved with the proposed system have shown excellent accuracy and ability in predicting ship manoeuvring with varying depths of shallow water.
Effectiveness of Psychological Counseling Intervention in High-Risk Pregnancies in Italy
Authors: Burgio Sofia , Cucinella Gaspare , Perino Antonio , Baglio Giovanni , Crifasi Laura , Krysiak Robert , Kowalcze Karolina , Gullo Giuseppe
Published: September 2024

Background: The longitudinal study examines the effectiveness of a psychological support treatment for high-risk pregnancies using a between-groups design. It assesses the treatment’s impact on depression and fear of COVID-19 at three time points, and on prenatal attachment between the 20th and 24th weeks of gestation (T0), postnatal attachment 15–20 days after birth (T1), and three months after birth (T2). Additionally, the study evaluates the treatment’s effectiveness on PTSD related to childbirth and parental distress at T1 and T2. Methods: The study involved 117 parents experiencing high-risk pregnancies from a Sicilian hospital: 84 mothers (40 in the experimental group, 44 in the control group) and 33 fathers (19 in the experimental group, 14 in the control group). Results: ANOVA results showed that the psychological treatment was effective for maternal variables such as postnatal attachment and parental distress, and for paternal variables such as depression, prenatal attachment, PTSD symptoms, and parental distress (ANOVA, p < 0.05). Conclusions: The study highlights the growing evidence for providing continuous psychological support to couples with high-risk pregnancies, emphasizing that this support should extend beyond childbirth to assist families through this transition.
Cheminformatic Identification of Tyrosyl-DNA Phosphodiesterase 1 (Tdp1) Inhibitors: A Comparative Study of SMILES-Based Supervised Machine Learning Models
Authors: Lai Conan Hong-Lun , Kwok Alex Pak Ki , Wong Kwong-Cheong
Published: September 2024

Background: Tyrosyl-DNA phosphodiesterase 1 (Tdp1) repairs damages in DNA induced by abortive topoisomerase 1 activity; however, maintenance of genetic integrity may sustain cellular division of neoplastic cells. It follows that Tdp1-targeting chemical inhibitors could synergize well with existing chemotherapy drugs to deny cancer growth; therefore, identification of Tdp1 inhibitors may advance precision medicine in oncology. Objective: Current computational research efforts focus primarily on molecular docking simulations, though datasets involving three-dimensional molecular structures are often hard to curate and computationally expensive to store and process. We propose the use of simplified molecular input line entry system (SMILES) chemical representations to train supervised machine learning (ML) models, aiming to predict potential Tdp1 inhibitors. Methods: An open-sourced consensus dataset containing the inhibitory activity of numerous chemicals against Tdp1 was obtained from Kaggle. Various ML algorithms were trained, ranging from simple algorithms to ensemble methods and deep neural networks. For algorithms requiring numerical data, SMILES were converted to chemical descriptors using RDKit, an open-sourced Python cheminformatics library. Results: Out of 13 optimized ML models with rigorously tuned hyperparameters, the random forest model gave the best results, yielding a receiver operating characteristics-area under curve of 0.7421, testing accuracy of 0.6815, sensitivity of 0.6444, specificity of 0.7156, precision of 0.6753, and F1 score of 0.6595. Conclusions: Ensemble methods, especially the bootstrap aggregation mechanism adopted by random forest, outperformed other ML algorithms in classifying Tdp1 inhibitors from non-inhibitors using SMILES. The discovery of Tdp1 inhibitors could unlock more treatment regimens for cancer patients, allowing for therapies tailored to the patient’s condition.
Artificial Intelligence-Driven Diagnostic Processes and Comprehensive Multimodal Models in Pain Medicine
Authors: Cascella Marco , Leoni Matteo L. G. , Shariff Mohammed Naveed , Varrassi Giustino
Published: September 2024

Pain diagnosis remains a challenging task due to its subjective nature, the variability in pain expression among individuals, and the difficult assessment of the underlying biopsychosocial factors. In this complex scenario, artificial intelligence (AI) can offer the potential to enhance diagnostic accuracy, predict treatment outcomes, and personalize pain management strategies. This review aims to dissect the current literature on computer-aided diagnosis methods. It also discusses how AI-driven diagnostic strategies can be integrated into multimodal models that combine various data sources, such as facial expression analysis, neuroimaging, and physiological signals, with advanced AI techniques. Despite the significant advancements in AI technology, its widespread adoption in clinical settings faces crucial challenges. The main issues are ethical considerations related to patient privacy, biases, and the lack of reliability and generalizability. Furthermore, there is a need for high-quality real-world validation and the development of standardized protocols and policies to guide the implementation of these technologies in diverse clinical settings.
Electrochemotherapy Treatment in a Patient with an Extended Basal Cell Carcinoma of the Face: A Case Report
Authors: Russano Francesco , Brugnolo Davide , Bisetto Giovanni , Del Fiore Paolo , Rastrelli Marco , Mocellin Simone , Dall’Olmo Luigi
Published: September 2024

Background. Basal cell carcinomas (BCCs) are common human malignancies with a rising incidence in recent years. While BCCs have a low mortality rate, they are often associated with significant local skin damage characterized by erythema, skin ulceration, and persistent pigmentation. Surgery, radiotherapy, and systemic chemotherapy have traditionally been the principal treatments for these skin injuries. However, electrochemotherapy has recently been proposed as a novel local treatment with promising results for various skin cancers, including BCC, while avoiding the side effects of conventional therapies. ECT involves a local electrical stimulus that enhances cell membrane permeability, thereby enabling the targeted intracellular accumulation of the chemotherapeutic agent. Case Report: We report a case of a 68-year-old man with an ulcerated BCC, following his progress up to 14 months post-ECT treatment, with positive outcomes. Discussion and Conclusions: We achieved a complete clinical response and noted an improvement in the patient’s quality of life. This technique is fast, repeatable, requires minimal hospitalization, and reduces healthcare costs and adverse effects compared to major surgery. Therefore, it can be considered an alternative or complementary approach to traditional surgery for treating BCC of the head and neck.
Housing Market Segmentation as a Driver of Urban Micro-Segregation? An In-Depth Analysis of Two Viennese Districts
Authors: Musil Robert , Kaucic Jiannis
Published: September 2024

The concept of segregation analyses the unequal distribution of social groups between neighbourhoods. It rests on two assumptions: that of homogeneous neighbourhoods and of a market liberal housing system. Both assumptions are applicable the context of American cities, but they display severe limitations when applied to the European context. Vienna’s housing market is particularly highly segmented, not only throughout the city as a whole but also within neighbourhoods. In the densely built-up area, residential buildings of different segments with different underlying rent regulations and entry barriers can be found side by side. Therefore, buildings are expected to show varying tenant and owner structures, which undermines the idea of a homogeneous neighbourhood. Against this background, we analyse at the micro scale small neighbourhoods defined by 100 m grid cells in a case study of two inner-city Viennese districts (districts 6 and 7) characterised by a particularly vivid housing-transformation and commodification dynamic. Using a novel and fine-grained dataset combining building information with the socio-economic data of households, we investigate the patterns and dynamics of income inequality and income segregation, as well as the relationship between housing market segments and socio-economic patterns. As data comprise two cross-sections for the years 2011 and 2020/21, changes in the neighbourhoods during the house-price boom period are also considered. This leads us to ask the question: How do housing market segmentation and its related changes affect income inequality and segregation at the micro scale? Our analysis delivers two main results: Firstly, we show the existence of marked social variation and related dynamics at the micro scale, even within a small urban area. Secondly, we show that the spatial distribution of housing market segments has a strong impact on income inequality in the neighbourhood.
Research on Trajectory Planning and Tracking Algorithm of Crawler Paver
Authors: Zhan Jian , Li Wei , Wang Jiongfan , Xiong Shusheng , Wu Xiaofeng , Shi Wei
Published: September 2024

The implementation of unmanned intelligent construction on the concrete surfaces of an airport effectively improves construction accuracy and reduces personnel investment. On the basis of three known common tracked vehicle dynamics models, reference trajectory planning and trajectory tracking controller algorithms need to be designed. In this paper, based on the driving characteristics of the tracked vehicle and the requirements of the stepping trajectory, a quartic polynomial trajectory planning algorithm was selected with the stability of the curve as a whole and the end point as the optimization goal, combining the tracked vehicle dynamics model, collision constraints, start–stop constraints and other boundary conditions. The objective function of trajectory planning was designed to effectively plan the reference trajectory of the tracked vehicle’s step-by-step travel. In order to realize accurate trajectory tracking control, a nonlinear model predictive controller with transverse-longitudinal integrated control was designed. To improve the real-time performance of the controller, a linear model predictive controller with horizontal and longitudinal decoupling was designed. MATLAB 2023A and CoppeliaSim V4.5.1 were used to co-simulate the two controller models. The experimental results show that the advantages and disadvantages of the tracked vehicle dynamics model and controller design are verified.
Tightness of Harary Graphs
Authors: Javan Abolfazl , Moeini Ali , Shekaramiz Mohammad
Published: September 2024

In the design of real-world networks, researchers evaluate various structural parameters to assess vulnerability, including connectivity, toughness, and tenacity. Recently, the tightness metric has emerged as a potentially superior vulnerability measure, although many related theorems remain unknown due to its novelty. Harary graphs, known for their maximum connectivity, are an important class of graph models for network design. Prior work has evaluated the vulnerability of three types of Harary graphs using different parameters, but the tightness metric has not been thoroughly explored. This article aims to calculate the tightness values for all three types of Harary graphs. First, it will attempt to calculate the lower bound for the value of the tightness parameter in Harary graphs using existing lemmas and theorems. Then, by presenting new lemmas and theorems, we will try to find the exact value or upper bound for this parameter in Harary graphs. For the first type of Harary graph, the tightness is precisely determined, while for the second and third types, upper bounds are provided due to structural complexity. The lemmas, theorems, and proof methods presented in this research may be used to calculate other graph and network parameters. However, the newness of the tightness parameter means that further research is needed to fully characterize its properties.
On the Univariate Vector-Valued Rational Interpolation and Recovery Problems
Authors: Xiao Lixia , Xia Peng , Zhang Shugong
Published: September 2024

In this paper, we consider a novel vector-valued rational interpolation algorithm and its application. Compared to the classic vector-valued rational interpolation algorithm, the proposed algorithm relaxes the constraint that the denominators of components of the interpolation function must be identical. Furthermore, this algorithm can be applied to construct the vector-valued interpolation function component-wise, with the help of the common divisors among the denominators of components. Through experimental comparisons with the classic vector-valued rational interpolation algorithm, it is found that the proposed algorithm exhibits low construction cost, low degree of the interpolation function, and high approximation accuracy.
Quantitative Portfolio Management: Review and Outlook
Authors: Senescall Michael , Low Rand Kwong Yew
Published: September 2024

This survey aims to provide insightful and objective perspectives on the research history of quantitative portfolio management strategies with suggestions for the future of research. The relevant literature can be clustered into four broad themes: portfolio optimization, risk-parity, style integration, and machine learning. Portfolio optimization attempts to find the optimal trade-off of future returns per unit of risk. Risk-parity attempts to match the exposure of various asset classes such that no single asset class dominates portfolio risk. Style integration combines risk factors on a security level such that rebalancing differences cancel out. Finally, machine learning utilizes large arrays of tunable parameters to predict future asset behavior and solve non-convex optimization problems. We conclude that machine learning will likely be the focus of future research.
Understanding the High-Temperature Deformation Behaviors in Additively Manufactured Al6061+TiC Composites via In Situ Neutron Diffraction
Authors: Qu Minglei , Yu Dunji , Chen Lianyi , An Ke , Chen Yan
Published: September 2024

Aluminum matrix composites (AMCs) are designed to enhance the performance of conventional aluminum alloys for engineering applications at both room and elevated temperatures. However, the dynamic phase-specific deformation behavior and load-sharing mechanisms of AMCs at elevated temperatures have not been extensively studied and remain unclear. Here, in situ neutron diffraction experiments are employed to reveal the phase-specific structure evolution of additively manufactured Al6061+TiC composites under compressive loading at 250 °C. It is found that the addition of a small amount of nano-size TiC significantly alters the deformation behavior and increases the strength at 250 °C in comparison to the as-printed Al6061. Unlike the two-stage behavior observed in Al6061, the Al6061+TiC composites exhibit three stages during compression triggered by changes in the interphase stress states. Further analysis of Bragg peak intensity and broadening reveals that the presence of TiC alters the dislocation activity during deformation at 250 °C by influencing dislocation slip planes and promoting dislocation accumulation. These findings provide direct experimental observations of the phase-specific dynamic process in AMCs under deformation at an elevated temperature. The revealed mechanisms provide insights for the future design and optimization of high-performance AMCs.
Gestational Interrelationships among Gut–Metabolism–Transcriptome in Regulating Early Embryo Implantation and Placental Development in Mice
Authors: Lin Shuai , Liang Yuqi , Geng Jingqi , Yan Yunfei , Ding Ruipei , He Maozhang
Published: September 2024

Decidualization of the uterine endometrium is a critical process for embryo implantation in mammals, primarily occurring on gestational day 8 in pregnant mice. However, the interplay between the maternal gut microbiome, metabolism, and the uterus at this specific time point remains poorly understood. This study employed a multi-omics approach to investigate the metabolic, gut microbiome, and transcriptomic changes associated with early pregnancy (gestational day 8 (E8)) in mice. Serum metabolomics revealed a distinct metabolic profile at E8 compared to controls, with the differential metabolites primarily enriched in amino acid metabolism pathways. The gut microbial composition showed that E8 mice exhibited higher alpha-diversity and a significant shift in beta-diversity. Specifically, the E8 group displayed a decrease in pathogenic Proteobacteria and an increase in beneficial Bacteroidetes and S24-7 taxa. Transcriptomics identified myriads of distinct genes between the E8 and control mice. The differentially expressed genes were enriched in pathways involved in alanine, aspartate, and glutamate metabolism, PI3K-Akt signaling, and the PPAR signaling pathway. Integrative analysis of the multi-omics data uncovered potential mechanistic relationships among the differential metabolites, gut microbiota, and uterine gene expression changes. Notably, the gene Asns showed strong correlations with specific gut S24-7 and metabolite L-Aspartatic acid, suggesting its potential role in mediating the crosstalk between the maternal environment and embryo development during early pregnancy. These findings provide valuable insights into the complex interplay between the maternal metabolome, the gut microbiome, and the uterine transcriptome in the context of early pregnancy, which may contribute to our understanding of the underlying mechanisms of embryo implantation and development.
Molecular Dynamics Simulation of Lipid Nanoparticles Encapsulating mRNA
Authors: Zhang Zhigang , Cheng Dazhi , Luo Wenqin , Hu Donling , Yang Tiantian , Hu Kaixuan , Liang Li , Liu Wei , Hu Jianping
Published: September 2024

mRNA vaccines have shown great potential in responding to emerging infectious diseases, with their efficacy and stability largely dependent on the delivery vehicles—lipid nanoparticles (LNPs). This study aims to explore the mechanisms by which LNPs encapsulate mRNA, as well as the effects of different N/P ratios and acid types in nucleic acid solutions on the structure and properties of LNPs, using the ethanol solvent injection method as the encapsulation technique. Six systems were designed, based on the composition and proportions of the existing mRNA vaccine mRNA-1273, and molecular dynamics (MD) simulations were employed to investigate the self-assembly process of LNPs. Ethanol was used as a solvent instead of pure water to better mimic experimental conditions. The results indicate that lipid components self-assemble into nanoparticles under neutral conditions, with the ionizable lipid SM-102 predominantly concentrating in the core of the particles. Upon mixing with nucleic acids in acidic conditions, LNPs undergo disassembly, during which protonated SM-102 encapsulates mRNA through electrostatic interactions, forming stable hydrogen bonds. Cluster structure analysis revealed that the four lipid components of LNPs are distributed sequentially from the outside inwards as DMG-PEG 2000, DSPC, cholesterol, and protonated SM-102. Moreover, LNPs constructed under low pH or low N/P ratios using citric acid exhibited larger volumes and more uniform distribution. These findings provide a scientific basis for further designing and optimizing LNP components to enhance the efficacy of mRNA vaccine encapsulation.