bluuebunny/crossref_metadata_2025 huggingface dataset:
A Hierarchy-Aware Geocoding Model Based on Cross-Attention within the Seq2Seq Framework
Authors: Liang Linlin , Chang Yuanfei , Quan Yizhuo , Wang Chengbo
Published: April 2024

Geocoding converts unstructured geographic text into structured spatial data, which is crucial in fields such as urban planning, social media spatial analysis, and emergency response systems. Existing approaches predominantly model geocoding as a geographic grid classification task but struggle with the output space dimensionality explosion as the grid granularity increases. Furthermore, these methods generally overlook the inherent hierarchical structure of geographical texts and grids. In this paper, we propose a hierarchy-aware geocoding model based on cross-attention within the Seq2Seq framework, incorporating S2 geometry to model geocoding as a task for generating grid labels and predicting S2 tokens (labels of S2 grids) character-by-character. By incorporating a cross-attention mechanism into the decoder, the model dynamically perceives the address contexts at the hierarchical level that are most relevant to the current character prediction based on the input address text. Results show that the proposed model significantly outperforms previous approaches across multiple metrics, with a median and mean distance error of 41.46 m and 93.98 m, respectively. Furthermore, our method achieves superior results compared to others in regions with sparse data distribution, reducing the median and mean distance error by 16.27 m and 7.52 m, respectively, suggesting that our model has effectively mitigated the issue of insufficient learning in such regions.
DNA Repair in Nucleosomes: Insights from Histone Modifications and Mutants
Authors: Selvam Kathiresan , Wyrick John J. , Parra Michael A.
Published: April 2024

DNA repair pathways play a critical role in genome stability, but in eukaryotic cells, they must operate to repair DNA lesions in the compact and tangled environment of chromatin. Previous studies have shown that the packaging of DNA into nucleosomes, which form the basic building block of chromatin, has a profound impact on DNA repair. In this review, we discuss the principles and mechanisms governing DNA repair in chromatin. We focus on the role of histone post-translational modifications (PTMs) in repair, as well as the molecular mechanisms by which histone mutants affect cellular sensitivity to DNA damage agents and repair activity in chromatin. Importantly, these mechanisms are thought to significantly impact somatic mutation rates in human cancers and potentially contribute to carcinogenesis and other human diseases. For example, a number of the histone mutants studied primarily in yeast have been identified as candidate oncohistone mutations in different cancers. This review highlights these connections and discusses the potential importance of DNA repair in chromatin to human health.
The Biologic IRL201805 Alters Immune Tolerance Leading to Prolonged Pharmacodynamics and Efficacy in Rheumatoid Arthritis Patients
Authors: Hall Christopher , Pleasance Jill , Hickman Oliver , Kirkham Bruce , Panayi Gabriel S. , Eggleton Paul , Corrigall Valerie M.
Published: April 2024

A homologue of binding immunoglobulin protein/BiP—IRL201805 alters the function of immune cells in pre-clinical in vivo and in vitro studies. The aim of the study was to select biomarkers that clearly delineate between RA patients who respond to IRL201805 and placebo patients and reveal the immunological mode of action of IRL201805 driving the extended pharmacodynamics observed in responding patients. Biomarkers that distinguished between responding patients and placebo patients included downregulation of serum interferon-γ and IL-1β; upregulation of anti-inflammatory mediators, serum soluble CTLA-4, and intracellular monocyte expression of IDO; and sustained increased CD39 expression on CD3+CD4+CD25hi CD127lo regulatory T cells. In the responding patients, selected biomarkers verified that the therapeutic effect could be continuous for at least 12 weeks post-infusion. In secondary co-culture, pre-infusion PBMCs cultured 1:1 with autologous PBMCs, isolated at later time-points during the trial, showed significantly inhibited IL-6 and IL-1β production upon anti-CD3/CD28 stimulation demonstrating IRL201805 alters the function of immune cells leading to prolonged pharmacodynamics confirmed by biomarker differences. IRL201805 may be the first of a new class of biologic drug providing long-term drug-free therapy in RA.
Novel Amidine Derivative K1586 Sensitizes Colorectal Cancer Cells to Ionizing Radiation by Inducing Chk1 Instability
Authors: Kim Hang Soo , Park Ji-Eun , Lee Won Hyung , Kwon Young Bin , Seu Young-Bae , Kim Kwang Seok
Published: April 2024

Checkpoint kinase 1 (Chk1) is a key mediator of the DNA damage response that regulates cell cycle progression, DNA damage repair, and DNA replication. Small-molecule Chk1 inhibitors sensitize cancer cells to genotoxic agents and have shown preclinical activity as single agents in cancers characterized by high levels of replication stress. However, the underlying genetic determinants of Chk1-inhibitor sensitivity remain unclear. Although treatment options for advanced colorectal cancer are limited, radiotherapy is effective. Here, we report that exposure to a novel amidine derivative, K1586, leads to an initial reduction in the proliferative potential of colorectal cancer cells. Cell cycle analysis revealed that the length of the G2/M phase increased with K1586 exposure as a result of Chk1 instability. Exposure to K1586 enhanced the degradation of Chk1 in a time- and dose-dependent manner, increasing replication stress and sensitizing colorectal cancer cells to radiation. Taken together, the results suggest that a novel amidine derivative may have potential as a radiotherapy-sensitization agent that targets Chk1.
An Overview of Frog Skin-Derived Esc Peptides: Promising Multifunctional Weapons against Pseudomonas aeruginosa-Induced Pulmonary and Ocular Surface Infections
Authors: Mangoni Maria Luisa , Loffredo Maria Rosa , Casciaro Bruno , Ferrera Loretta , Cappiello Floriana
Published: April 2024

Antimicrobial resistance is a silent pandemic harming human health, and Pseudomonas aeruginosa is the most common bacterium responsible for chronic pulmonary and eye infections. Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics. In this review, the in vitro/in vivo activities of the frog skin-derived AMP Esc(1-21) are shown. Esc(1-21) rapidly kills both the planktonic and sessile forms of P. aeruginosa and stimulates migration of epithelial cells, likely favoring repair of damaged tissue. However, to undertake preclinical studies, some drawbacks of AMPs (cytotoxicity, poor biostability, and limited delivery to the target site) must be overcome. For this purpose, the stereochemistry of two amino acids of Esc(1-21) was changed to obtain the diastereomer Esc(1-21)-1c, which is more stable, less cytotoxic, and more efficient in treating P. aeruginosa-induced lung and cornea infections in mouse models. Incorporation of these peptides (Esc peptides) into nanoparticles or immobilization to a medical device (contact lens) was revealed to be an effective strategy to ameliorate and/or to prolong the peptides’ antimicrobial efficacy. Overall, these data make Esc peptides encouraging candidates for novel multifunctional drugs to treat lung pathology especially in patients with cystic fibrosis and eye dysfunctions, characterized by both tissue injury and bacterial infection.
Review of Patient Gene Profiles Obtained through a Non-Negative Matrix Factorization-Based Framework to Determine the Role Inflammation Plays in Neuroblastoma Pathogenesis
Authors: Boccarelli Angelina , Del Buono Nicoletta , Esposito Flavia
Published: April 2024

Neuroblastoma is the most common extracranial solid tumor in children. It is a highly heterogeneous tumor consisting of different subcellular types and genetic abnormalities. Literature data confirm the biological and clinical complexity of this cancer, which requires a wider availability of gene targets for the implementation of personalized therapy. This paper presents a study of neuroblastoma samples from primary tumors of untreated patients. The focus of this analysis is to evaluate the impact that the inflammatory process may have on the pathogenesis of neuroblastoma. Eighty-eight gene profiles were selected and analyzed using a non-negative matrix factorization framework to extract a subset of genes relevant to the identification of an inflammatory phenotype, whose targets (PIK3CG, NFATC2, PIK3R2, VAV1, RAC2, COL6A2, COL6A3, COL12A1, COL14A1, ITGAL, ITGB7, FOS, PTGS2, PTPRC, ITPR3) allow further investigation. Based on the genetic signals automatically derived from the data used, neuroblastoma could be classified according to stage rather than as a “cold” or “poorly immunogenic” tumor.
Development of Novel Peptidyl Nitriles Targeting Rhodesain and Falcipain-2 for the Treatment of Sleeping Sickness and Malaria
Authors: Di Chio Carla , Starvaggi Josè , Totaro Noemi , Previti Santo , Natale Benito , Cosconati Sandro , Bogacz Marta , Schirmeister Tanja , Legac Jenny , Rosenthal Philip J. , Zappalà Maria , Ettari Roberta
Published: April 2024

In recent decades, neglected tropical diseases and poverty-related diseases have become a serious health problem worldwide. Among these pathologies, human African trypanosomiasis, and malaria present therapeutic problems due to the onset of resistance, toxicity problems and the limited spectrum of action. In this drug discovery process, rhodesain and falcipain-2, of Trypanosoma brucei rhodesiense and Plasmodium falciparum, are currently considered the most promising targets for the development of novel antitrypanosomal and antiplasmodial agents, respectively. Therefore, in our study we identified a novel lead-like compound, i.e., inhibitor 2b, which we proved to be active against both targets, with a Ki = 5.06 µM towards rhodesain and an IC50 = 40.43 µM against falcipain-2.
Alpha 7 Nicotinic Acetylcholine Receptor Agonist PHA 568487 Reduces Acute Inflammation but Does Not Affect Cardiac Function or Myocardial Infarct Size in the Permanent Occlusion Model
Authors: Mjörnstedt Filip , Miljanovic Azra , Wilhelmsson Rebecka , Levin Malin , Johansson Maria E.
Published: April 2024

Stimulation of the alpha 7 nicotinic acetylcholine receptor (α7nAChR) has shown beneficial effects in several acute inflammatory disease models. This study aims to examine whether treatment with the selective α7nAChR agonist PHA 568487 can dampen inflammation and thereby improve cardiac function after myocardial infarction in mice. The possible anti-inflammatory properties of α7nAChR agonist PHA 568487 were tested in vivo using the air pouch model and in a permanent occlusion model of acute myocardial infarction in mice. Hematologic parameters and cytokine levels were determined. Infarct size and cardiac function were assessed via echocardiography 24 h and one week after the infarction. Treatment with α7nAChR agonist PHA 568487 decreased 12 (CCL27, CXCL5, IL6, CXCL10, CXCL11, CXCL1, CCL2, MIP1a, MIP2, CXCL16, CXCL12 and CCL25) out of 33 cytokines in the air pouch model of acute inflammation. However, α7nAChR agonist PHA 568487 did not alter infarct size, ejection fraction, cardiac output or stroke volume at 24 h or at 7 days after the myocardial infarction compared with control mice. In conclusion, despite promising immunomodulatory effects in the acute inflammatory air pouch model, α7nAChR agonist PHA 568487 did not affect infarct size or cardiac function after a permanent occlusion model of acute myocardial infarction in mice. Consequently, this study does not strengthen the hypothesis that stimulation of the α7nAChR is a future treatment strategy for acute myocardial infarction when reperfusion is lacking. However, whether other agonists of the α7nAChR can have different effects remains to be investigated.
Scandium Ion-Promoted Electron-Transfer Disproportionation of 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-Oxide (PTIO•) in Acetonitrile and Its Regeneration Induced by Water
Authors: Shoji Yoshimi , Terashima Yuri , Ohkubo Kei , Ito Hiromu , Maruyama Kouichi , Fukuzumi Shunichi , Nakanishi Ikuo
Published: April 2024

2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO•), a persistent nitronyl nitroxide radical, has been used for the detection and trapping of nitric oxide, as a redox mediator for batteries, for the activity estimation of antioxidants, and so on. However, there is no report on the reactivity of PTIO• in the presence of redox-inactive metal ions. In this study, it is demonstrated that the addition of scandium triflate, Sc(OTf)3 (OTf = OSO2CF3), to an acetonitrile (MeCN) solution of PTIO• resulted in an electron-transfer disproportionation to generate the corresponding cation (PTIO+) and anion (PTIO−), the latter of which is suggested to be stabilized by Sc3+ to form [(PTIO)Sc]2+. The decay of the absorption band at 361 nm due to PTIO•, monitored using a stopped-flow technique, obeyed second-order kinetics. The second-order rate constant for the disproportionation, thus determined, increased with increasing the Sc(OTf)3 concentration to reach a constant value. A drastic change in the cyclic voltammogram recorded for PTIO• in deaerated MeCN containing 0.10 M Bu4NClO4 was also observed upon addition of Sc(OTf)3, suggesting that the large positive shift of the one-electron reduction potential of PTIO• (equivalent to the one-electron oxidation potential of PTIO−) in the presence of Sc(OTf)3 may result in the disproportionation. When H2O was added to the PTIO•–Sc(OTf)3 system in deaerated MeCN, PTIO• was completely regenerated. It is suggested that the complex formation of Sc3+ with H2O may weaken the interaction between PTIO− and Sc3+, leading to electron-transfer comproportionation to regenerate PTIO•. The reversible disproportionation of PTIO• was also confirmed by electron paramagnetic resonance (EPR) spectroscopy.
SLCO1B1 Exome Sequencing and Statin Treatment Response in 64,000 UK Biobank Patients
Authors: Türkmen Deniz , Bowden Jack , Masoli Jane A. H. , Melzer David , Pilling Luke C.
Published: April 2024

The solute carrier organic anion transporter family member 1B1 (SLCO1B1) encodes the organic anion-transporting polypeptide 1B1 (OATP1B1 protein) that transports statins to liver cells. Common genetic variants in SLCO1B1, such as *5, cause altered systemic exposure to statins and therefore affect statin outcomes, with potential pharmacogenetic applications; yet, evidence is inconclusive. We studied common and rare SLCO1B1 variants in up to 64,000 patients from UK Biobank prescribed simvastatin or atorvastatin, combining whole-exome sequencing data with up to 25-year routine clinical records. We studied 51 predicted gain/loss-of-function variants affecting OATP1B1. Both SLCO1B1*5 alone and the SLCO1B1*15 haplotype increased LDL during treatment (beta*5 = 0.08 mmol/L, p = 6 × 10−8; beta*15 = 0.03 mmol/L, p = 3 × 10−4), as did the likelihood of discontinuing statin prescriptions (hazard ratio*5 = 1.12, p = 0.04; HR*15 = 1.05, p = 0.04). SLCO1B1*15 and SLCO1B1*20 increased the risk of General Practice (GP)-diagnosed muscle symptoms (HR*15 = 1.22, p = 0.003; HR*20 = 1.25, p = 0.01). We estimated that genotype-guided prescribing could potentially prevent 18% and 10% of GP-diagnosed muscle symptoms experienced by statin patients, with *15 and *20, respectively. The remaining common variants were not individually significant. Rare variants in SLCO1B1 increased LDL in statin users by up to 1.05 mmol/L, but replication is needed. We conclude that genotype-guided treatment could reduce GP-diagnosed muscle symptoms in statin patients; incorporating further SLCO1B1 variants into clinical prediction scores could improve LDL control and decrease adverse events, including discontinuation.
The CaMK Family Differentially Promotes Necroptosis and Mouse Cardiac Graft Injury and Rejection
Authors: Lu Haitao , Jiang Jifu , Min Jeffery , Huang Xuyan , McLeod Patrick , Liu Weihua , Haig Aaron , Gunaratnam Lakshman , Jevnikar Anthony M. , Zhang Zhu-Xu
Published: April 2024

Organ transplantation is associated with various forms of programmed cell death which can accelerate transplant injury and rejection. Targeting cell death in donor organs may represent a novel strategy for preventing allograft injury. We have previously demonstrated that necroptosis plays a key role in promoting transplant injury. Recently, we have found that mitochondria function is linked to necroptosis. However, it remains unknown how necroptosis signaling pathways regulate mitochondrial function during necroptosis. In this study, we investigated the receptor-interacting protein kinase 3 (RIPK3) mediated mitochondrial dysfunction and necroptosis. We demonstrate that the calmodulin-dependent protein kinase (CaMK) family members CaMK1, 2, and 4 form a complex with RIPK3 in mouse cardiac endothelial cells, to promote trans-phosphorylation during necroptosis. CaMK1 and 4 directly activated the dynamin-related protein-1 (Drp1), while CaMK2 indirectly activated Drp1 via the phosphoglycerate mutase 5 (PGAM5). The inhibition of CaMKs restored mitochondrial function and effectively prevented endothelial cell death. CaMKs inhibition inhibited activation of CaMKs and Drp1, and cell death and heart tissue injury (n = 6/group, p < 0.01) in a murine model of cardiac transplantation. Importantly, the inhibition of CaMKs greatly prolonged heart graft survival (n = 8/group, p < 0.01). In conclusion, CaMK family members orchestrate cell death in two different pathways and may be potential therapeutic targets in preventing cell death and transplant injury.
Violin Music Emotion Recognition with Fusion of CNN–BiGRU and Attention Mechanism
Authors: Ma Sihan , Zhou Ruohua
Published: April 2024

Music emotion recognition has garnered significant interest in recent years, as the emotions expressed through music can profoundly enhance our understanding of its deeper meanings. The violin, with its distinctive emotional expressiveness, has become a focal point in this field of research. To address the scarcity of specialized data, we developed a dataset specifically for violin music emotion recognition named VioMusic. This dataset offers a precise and comprehensive platform for the analysis of emotional expressions in violin music, featuring specialized samples and evaluations. Moreover, we implemented the CNN–BiGRU–Attention (CBA) model to establish a baseline system for music emotion recognition. Our experimental findings show that the CBA model effectively captures the emotional nuances in violin music, achieving mean absolute errors (MAE) of 0.124 and 0.129. The VioMusic dataset proves to be highly practical for advancing the study of emotion recognition in violin music, providing valuable insights and a robust framework for future research.
Hybrid Siloxane Materials Based on a Mutually Reactive Epoxy–Amine System: Synthesis, Structure, and Thermal Stability Investigations
Authors: Fortună Maria Emiliana , Ignat Maria , Tudorachi Niţă , Ungureanu Elena , Rotaru Răzvan , Harabagiu Valeria
Published: April 2024

Hybrid siloxane materials based on a mutually reactive epoxy–amine system are organic-inorganic hybrid materials synthesized via the sol–gel reaction of siloxane precursors, followed by the polymerization of organo-functionalized oligosiloxanes. Therefore, using a new hybrid system as the reaction product resulting from the reaction between 1,3-bis(3-glycidoxypropyl)-l, 1,3,3-tetramethyldisiloxane—C16H34O5Si2—(gp-DS) and p-phenylenediamine—C6H4(NH2)2—(PPD), an aromatic diamine, was obtained. The chemical structure of the synthesized hybrid siloxane material was confirmed via Fourier Transform Infra-Red (FTIR) spectroscopy, mass spectrometry (MS), and 1H-NMR spectroscopy. The morphology and surface chemical composition was highlighted via scanning electron microscopy (SEM) equipped with an EDX elemental analysis system. Further, the thermal stabilities of the prepared hybrid siloxane and its precursors have been investigated via thermogravimetric analysis (TGA), proving the modification of epoxy-functional disiloxanes with a paraphenylenediamine reagent that made it possible to produce hybrid siloxane materials with very good thermal stabilities and dual weak hydrophilic/hydrophobic surfaces.
Effect of TiC Particles on the Properties of Copper Matrix Composites
Authors: Zhai Zhenjie , Dong Haitao , Li Denghui , Wang Zhe , Sun Changfei , Chen Cong
Published: April 2024

In this study, TiC particle-reinforced Cu-based composites were prepared by powder metallurgy and spark plasma sintering (SPS) techniques. The mechanical and electrical properties of TiC/Cu composites were analyzed in conjunction with micro-morphology. The results showed that: TiC was fully diffused in the Cu matrix at a sintering temperature of 900 °C. The micron-sized TiC particles were most uniformly distributed in the Cu matrix and had the best performance. At this time, the densification of 5 wt.% TiC/Cu composites reached 97.19%, and the conductivity, hardness, and compressive yield strength were 11.47 MS·m−1, 112.9 HV, and 162 MPa, respectively. The effect of TiC content on the overall properties of the composites was investigated at a sintering temperature of 900 °C. The TiC content of the composites was also found to have a significant influence on the overall properties of the composites. The best performance of the composites was obtained when the TiC mass fraction was 10%. The average values of density, hardness, yield strength and conductivity of the 10 wt.% TiC/Cu composites were 90.07%, 128.3 HV, 272 MPa and 9.98 MS·m−1, respectively. The yield strength was 272 MPa, and the compressive strain was 38.8%. With the increase in TiC content, although the yield strength increased, the brittleness increased due to more weak interfaces in the composites.
Decline in Honeybees and Its Consequences for Beekeepers and Crop Pollination in Western Nepal
Authors: Kortsch Susanne , Timberlake Thomas P. , Cirtwill Alyssa R. , Sapkota Sujan , Rokoya Manish , Devkota Kedar , Roslin Tomas , Memmott Jane , Saville Naomi
Published: April 2024

In understudied regions of the world, beekeeper records can provide valuable insights into changes in pollinator population trends. We conducted a questionnaire survey of 116 beekeepers in a mountainous area of Western Nepal, where the native honeybee Apis cerana cerana is kept as a managed bee. We complemented the survey with field data on insect–crop visitation, a household income survey, and an interview with a local lead beekeeper. In total, 76% of beekeepers reported declines in honeybees, while 86% and 78% reported declines in honey yield and number of beehives, respectively. Honey yield per hive fell by 50% between 2012 and 2022, whilst the number of occupied hives decreased by 44%. Beekeepers ranked climate change and declining flower abundance as the most important drivers of the decline. This raises concern for the future food and economic security of this region, where honey sales contribute to 16% of total household income, and where Apis cerana cerana plays a major role in crop pollination, contributing more than 50% of all flower visits to apple, cucumber, and pumpkin. To mitigate further declines, we promote native habitat and wildflower preservation, and using well-insulated log hives to buffer bees against the increasingly extreme temperature fluctuations.
Non-Pharmacological Treatment of Heart Failure—From Physical Activity to Electrical Therapies: A Literature Review
Authors: Scarà Antonio , Palamà Zefferino , Robles Antonio Gianluca , Dei Lorenzo-Lupo , Borrelli Alessio , Zanin Federico , Pignalosa Leonardo , Romano Silvio , Sciarra Luigi
Published: April 2024

Heart failure (HF) represents a significant global health challenge that is still responsible for increasing morbidity and mortality despite advancements in pharmacological treatments. This review investigates the effectiveness of non-pharmacological interventions in the management of HF, examining lifestyle measures, physical activity, and the role of some electrical therapies such as catheter ablation, cardiac resynchronization therapy (CRT), and cardiac contractility modulation (CCM). Structured exercise training is a cornerstone in this field, demonstrating terrific improvements in functional status, quality of life, and mortality risk reduction, particularly in patients with HF with reduced ejection fraction (HFrEF). Catheter ablation for atrial fibrillation, premature ventricular beats, and ventricular tachycardia aids in improving left ventricular function by reducing arrhythmic burden. CRT remains a key intervention for selected HF patients, helping achieve left ventricular reverse remodeling and improving symptoms. Additionally, the emerging therapy of CCM provides a novel opportunity for patients who do not meet CRT criteria or are non-responders. Integrating non-pharmacological interventions such as digital health alongside specific medications is key for optimizing outcomes in HF management. It is imperative to tailor approaches to individual patients in this diverse patient population to maximize benefits. Further research is warranted to improve treatment strategies and enhance patient outcomes in HF management.
Molnupiravir Real-World Utilization in COVID-19 Patients in the Czech Republic
Authors: Dlouhý Pavel , Mucha Cyril , Mokrá Lenka , Kuhn Matyáš , Hrdlickova Lenka , Arnet Urs , Whiteside Yohance
Published: April 2024

Background/Objectives: Molnupiravir (MOV), an oral antiviral COVID-19 treatment, was introduced in the Czech Republic in December 2021 for COVID-19 patients at a high risk of progression to severe disease requiring hospitalization. In this observational, retrospective study, we aimed to describe the characteristics and healthcare resource utilization in non-hospitalized, adult COVID-19 patients prescribed MOV in the Czech Republic between 1 January and 30 April 2022. Methods: A total of 621 patients were included and followed up with for 28 days. Results: The median age was 68.0 (20–99) years, 77.8% were overweight or obese, 14.1% smoked, and 85.7% were vaccinated. The overall cumulative incidence (95% CI) of all-cause hospitalization was 0.71 (0.37; 1.24) per 1000 person years or 1.9%, with similar rates across sexes, age groups, BMI category, multimorbidity category, polypharmacy category, and COVID-19 vaccination status. Among patients reported hospitalized, oxygen-based resources were not observed, and no deaths occurred. Conclusions: These data describe the characteristics and healthcare resource utilization in Czech MOV-treated patients whose clinical characteristics may put them at increased risk of severe disease.
The Potential Role of Presepsin in Predicting Severe Infection in Patients with Diabetic Foot Ulcers
Authors: Ha Eun Yeong , Park Il Rae , Chung Seung Min , Roh Young Nam , Park Chul Hyun , Kim Tae-Gon , Kim Woong , Moon Jun Sung
Published: April 2024

Background/Objectives: Diabetic foot ulcers are one of the complications in patients with diabetes, which can be caused by infection, neuropathy, and blood vessel disorder. Among them, infection is the most common cause, and if it becomes worse, amputation may be necessary. So, it is important to detect and treat infections early, and determining indicators that can confirm infection is also important. Known infection markers include white blood cells (WBCs), the erythrocyte sediment rate (ESR), C-reactive protein (CRP), and procalcitonin, but they are not specific to diabetic foot ulcers. Presepsin, also known as soluble CD14, is known to be an early indicator of sepsis. Recent studies have reported that presepsin can be used as an early indicator of infection. This study investigated whether presepsin could be used as an early marker of severe infection in patients with diabetic foot ulcers. Methods: We retrospectively studied 73 patients who were treated for diabetic foot ulcerations from January 2021 to June 2023 at Yeungnam University Hospital. Results: Out of a total of 73 patients, 46 patients underwent amputations with severe infections, and the WBC level, ESR, and CRP, procalcitonin, and presepsin levels were significantly higher in the group of patients who underwent amputations. The cutoff of presepsin, which can predict serious infections that need amputation, was 675 ng/mL. A regression analysis confirmed that presepsin, HbA1c, and osteomyelitis significantly increased the risk of severe infections requiring amputation. Conclusions: Presepsin will be available as an early predictor of patients with severe infections requiring amputations for diabetic foot ulcerations.
Antiplatelet Therapy and Anticoagulation before, during, and after Acute Coronary Syndrome
Authors: Kaufmann Christoph C. , Muthspiel Marie , Lunzer Laura , Pogran Edita , Zweiker David , Burger Achim Leo , Wojta Johann , Huber Kurt
Published: April 2024

Acute coronary syndrome (ACS) remains a major challenge in clinical practice, requiring rapid and effective antithrombotic treatment to mitigate adverse ischemic events while minimizing the risk of bleeding. In recent years, results from several clinical trials addressing this issue through various approaches have substantially improved the treatment landscape for patients presenting with ACS. The emergence of new, potent P2Y12 inhibitors has significantly enhanced thrombotic risk reduction and different strategies for de-escalating and shortening dual antiplatelet therapy (DAPT) have demonstrated promising outcomes in reducing bleeding rates. Furthermore, data from ongoing trials focusing on novel therapeutic agents and investigating alternative treatment strategies to optimize outcomes for ACS patients are expected in the next few years. In this review, we summarize the current knowledge and emphasize the critical role of individualized treatment approaches tailored to patient-specific risk factors and individual clinical scenarios.
Managing Small Airway Disease in Patients with Severe Asthma: Transitioning from the “Silent Zone” to Achieving “Quiet Asthma”
Authors: Carpagnano Giovanna Elisiana , Portacci Andrea , Dragonieri Silvano , Montagnolo Francesca , Iorillo Ilaria , Lulaj Ernesto , Maselli Leonardo , Buonamico Enrico , Quaranta Vitaliano Nicola
Published: April 2024

Background/Objectives: Several studies have demonstrated the positive clinical and functional impact of adding Long-Acting Muscarinic Antagonist (LAMA) to Inhaled Corticosteroids (ICS) and Long-Acting Beta-Agonists (LABA) therapy in the treatment of severe asthma. Aim and objectives: To demonstrate that treating Small Airways Disease (SAD) in severe asthma patients who are candidates for biologics can improve respiratory symptoms, lung function, and airways inflammation, potentially avoiding or delaying the use of biological therapy. Methods: Thirty-two severe asthma patients with SAD were transitioned from separate inhalers for ICS/LABA and LAMA to extrafine single-inhaler beclomethasone, formoterol, and glycopyrronium. None of these patients underwent biological therapy before the study. Follow-up evaluations were conducted at baseline (T0) and three months after initiation (T3). Assessments included clinical evaluations, spirometry, oscillometry, and inflammation markers. Results: Transitioning to single-inhaler triple therapy from T0 to T3 resulted in significant improvements in Asthma Control Test (ACT) and SAD parameters, including increased Forced Expiratory Volume in the mid-range of lung capacity and improved airway resistance and reactance measurements using impulse oscillometry. A significant reduction in airway inflammation was evidenced by lower levels of Fractional Exhaled Nitric Oxide 350 (FeNO 350) (p < 0.001 for all). Conclusions: Adopting a single-inhaler triple therapy notably enhanced clinical control and small airway function in patients with severe asthma and SAD, supporting the positive impact of target-therapy for the achievement of a stable state termed “Quiet Asthma”.
Impact of Effectiveness of Physical Activity in a Virtual Environment on the Regulation of Sclerostin and Interleukin 6 Levels in Haemodialysis Patients
Authors: Turoń-Skrzypińska Agnieszka , Mińko Alicja , Rył Aleksandra , Mańkowska Katarzyna , Ciechanowski Kazimierz , Bereda Zuzanna , Rotter Iwona , Dutkiewicz Grażyna
Published: April 2024

Background: Chronic kidney disease is a significant public health issue associated with reduced physical activity. This can lead to mineral and bone disorders and increased levels of inflammatory markers. One innovative solution that can significantly contribute to increasing patient motivation is the combination of physical training with virtual reality technology during haemodialysis sessions. The aim of this study is to comprehensively assess the impact of regular virtual reality-based physical activity on plasma sclerostin and interleukin 6 levels, as well as on physical performance and the level of physical activity in patients undergoing renal replacement therapy through haemodialysis. Methods: This study is a prospective cohort study. Patients included in the study were randomly assigned to two groups: the study group and the control group. The study group consisted of patients who were entrusted with the task of conducting training using the prototype of the NefroVR system. The duration of the study period for both the study and control groups was 3 months. Results: One hundred and two (102) patients with stage 5 chronic kidney disease who underwent haemodialysis as a renal replacement therapy participated in the study. Patients from the study group were characterized by higher physical activity compared to the control group. There was a significant difference in the level of IL-6 and SOST between the study and control groups in the second measurement. Conclusions: Regular physical activity, especially using approaches such as virtual reality, contributes to improving physical fitness and overall activity levels in patients undergoing haemodialysis. The study demonstrated that regular exercise may be associated with a reduction in inflammatory parameters and positive effects on bone metabolism in patients undergoing haemodialysis.
Clinical Depression and Anxiety Are Relieved by Microvascular Decompression in Patients with Trigeminal Neuralgia—A Prospective Patient-Reported Outcome Study
Authors: Bauer Marlies , Krigers Aleksandrs , Schoen Victoria , Thomé Claudius , Freyschlag Christian F.
Published: April 2024

Objective: Patients with idiopathic trigeminal neuralgia (TN) live in constant fear of triggering shock-like pain episodes, which may cause symptoms of depression and a reduction in quality of life. Microvascular decompressive surgery has been demonstrated to achieve satisfactory and stable results. With this study, we wanted to investigate prevalence and risk factors for depression and perceived stress in correlation with symptom relief after surgical treatment. Methods: In this prospective study, patients undergoing microvascular decompression (MVD) for TN were included. The Barrow Neurological Institute Pain Score (BNI), Beck Depression Inventory (BDI), Chronic Pain Acceptance Questionnaire (CPAQ), Perceived Stress Questionnaire (PSQ) and McGill questionnaire were used to evaluate depression, stress and anxiety disorders before and 3 months after MVD. Results: A total of 35 patients (16 male (46%)) with a mean age of 55.4 (SD 15) years were included in this study. The BDI revealed that 24 (68.8%) patients harbored mild-to-extreme depression preoperatively (2.4 ± 1.4), which improved to 1.2 (±0.6, p < 0.0001). Pain acceptance also changed from 64 (±11.3) to 67.7 (±9.3, p = 0.006). Perceived stress decreased from 46.9 (±21.9) to 19.6 (±18.6) (p < 0.0001) postoperatively, and pain decreased from 31.0 (±11.7) to 9.4 (±12.9, p < 0.0001). Microvascular decompression reduced the mean BNI pain score significantly from 4.6 to 1.8 postoperatively (p < 0.00001). Conclusions: Depression and perceived stress are prevalent in patients with idiopathic TN. Adequate treatment not only provides a high rate of satisfaction through pain relief, but also leads to immediate and significant improvements in depression and stress. Thus, in patients with TN who do not reach an adequate and timely pain reduction through medical management and develop signs of depression, early treatment with microvascular decompression should be considered.
Genome-Wide Association Screens for Anterior Cruciate Ligament Tears
Authors: Candela Vincenzo , Longo Umile Giuseppe , Berton Alessandra , Salvatore Giuseppe , Forriol Francisco , de Sire Alessandro , Denaro Vincenzo
Published: April 2024

Background: The etiopathogenesis of ACL rupture is not clarified. The aim of this study is to identify genomic regions and genetic variants relevant to anterior cruciate ligament injury susceptibility that could be involved in non-contact anterior cruciate ligament ruptures. Methods: A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines with a PRISMA checklist and algorithm. A search of PubMed, MEDLINE, CINAHL, Cochrane, EMBASE, and Google Scholar databases was conducted using combinations of the terms “anterior cruciate ligament”, “ACL”, “rupture”, “genetics”, “single nucleotide polymorphisms”, and “SNP” since the inception of the databases until 2021. Results: Twenty-three studies were included. A total of 7724 patients were analyzed. In total, 3477 patients had ACL ruptures and 4247 patients were controls. Genetic variants in genes encoding for collagens, elastin, fibrillin, matrix metalloproteinases, proteoglycans, angiogenesis-associated signaling cascade proteins, growth differentiation factors, tissue inhibitors of metalloproteases, interleukins, and fibrinogen were analyzed. Conclusion: Findings regarding the association between genes encoding for collagen (COL3A1, COL1A1, and COL12A1), aggrecan (ACAN), decorin (DCN), matrix metalloproteinase (MMP3), interleukin 6 (IL-6), vascular endothelial growth factor A (VEGFA), biglycan (BGN), fibrinogen (FGB), and ACL injuries were found to be inconclusive. Additional evidence is required in order to establish substantial conclusions regarding the association between genetic variants and ACL rupture.
Post-Process Considerations for Photopolymer 3D-Printed Injection Moulded Insert Tooling Applications
Authors: Keane Gavin , Healy Andrew V. , Devine Declan M.
Published: April 2024

Injection moulding (IM) is a manufacturing technique used to produce intricately detailed plastic components with various surface finishes, enabling the production of high-tolerance functional parts at scale. Conversely, stereolithography (SLA) three-dimensional (3D) printing offers an alternative method for fabricating moulds with shorter lead times and reduced costs compared to conventional manufacturing. However, fabrication in a layer-by-layer fashion results in anisotropic properties and noticeable layer lines, known as the stair-step effect. This study investigates post-processing techniques for plaques with contrasting stair-step effects fabricated from commercially available SLA high-temperature resin, aiming to assess their suitability for IM applications. The results reveal that annealing significantly enhances part hardness and heat deflection temperature (HDT), albeit with a trade-off involving reduced flexural strength. Experimental findings indicate that the optimal stage for abrasive surface treatment is after UV curing and before annealing. Plaques exhibiting contrasting stair-step effects are characterized and evaluated for weight loss, dimensional accuracy, and surface roughness. The results demonstrate that abrasive blasting effectively removes the stair-step effect without compromising geometry while achieving polished surface finishes with roughness average (RA) values of 0.1 μm through sanding. Overall, a combination of abrasive blasting and sanding proves capable of precisely defining surface roughness without significant geometry loss, offering a viable approach to achieving traditional IM finishes suitable for both functional and aesthetic purposes.
Functional Biomaterials and Digital Technologies in Dentistry: From Bench to Bedside
Authors: Li Ping , Wan Guojiang , Xu Shulan , Li An
Published: April 2024

This Special Issue, “Functional Biomaterials and Digital Technologies in Dentistry: From Bench to Bedside”, highlights the integration of advanced materials science and digital technologies in dental and maxillofacial applications [...]
Soft Robot Design, Manufacturing, and Operation Challenges: A Review
Authors: Ambaye Getachew , Boldsaikhan Enkhsaikhan , Krishnan Krishna
Published: April 2024

Advancements in smart manufacturing have embraced the adoption of soft robots for improved productivity, flexibility, and automation as well as safety in smart factories. Hence, soft robotics is seeing a significant surge in popularity by garnering considerable attention from researchers and practitioners. Bionic soft robots, which are composed of compliant materials like silicones, offer compelling solutions to manipulating delicate objects, operating in unstructured environments, and facilitating safe human–robot interactions. However, despite their numerous advantages, there are some fundamental challenges to overcome, which particularly concern motion precision and stiffness compliance in performing physical tasks that involve external forces. In this regard, enhancing the operation performance of soft robots necessitates intricate, complex structural designs, compliant multifunctional materials, and proper manufacturing methods. The objective of this literature review is to chronicle a comprehensive overview of soft robot design, manufacturing, and operation challenges in conjunction with recent advancements and future research directions for addressing these technical challenges.
Design and Optimization of the Teardrop Buoy Driven by Ocean Thermal Energy
Authors: Zhao Danyao , Li Shizhen , Shi Wenzhuo , Zhou Zhengtong , Guo Fen
Published: April 2024

With the inception of the Argo program, the global ocean observation network is undergoing continuous advancement, with profiling buoys emerging as pivotal components of this network, thus garnering increased attention in research. In efforts to enhance the efficiency of profiling buoys and curtail energy consumption, a teardrop-shaped buoy design is proposed in this study. Moreover, an optimization methodology leveraging neural networks and genetic algorithms has been devised to attain an optimal profile curve. This curve seeks to minimize drag and drag coefficient while maximizing drainage, thereby improving hydrodynamic performance. Simulation-based validation and analysis are conducted to assess the efficacy of the optimized buoy design. Results indicate that the drag of the teardrop-shaped buoy with a deflector decreased by 9.2% compared to pre-optimized configurations and by 22% compared to buoys lacking deflectors. The hydrodynamic profile devised in this study effectively enhances buoy performance, laying a solid foundation for ocean thermal energy generation and buoyancy regulation control. Additionally, the optimized scheme serves as a valuable blueprint for the design of ocean exploration devices.
Physical Experimental Study on the Wave Reflection and Run-Up of a New Ecological Hollow Cube
Authors: Zhao Haitao , Ding Feiyue , Ye Junwei , Jiang Huabin , Chen Wei , Gu Weifang , Yu Gengfeng , Li Qiang
Published: April 2024

Implementing quadrangular hollow blocks on breakwaters is a common method for wave mitigation and ocean disaster prevention. In order to improve the wave-damping performance of conventional quadrangular hollow blocks, a new quadrangular hollow block is proposed. In this study, a series of physical modeling experiments were conducted in a two-dimensional wave flume to investigate the wave reflection and wave run-up height of a new quadrilateral hollow block under regular wave action. Test results showed that wave reflection and wave run-up height decreased with the breakwater slope. The wave run-up height increased with wave height, and the reflection coefficient decreased with wave height. Wave reflection and run-up height increased with the wave period. The reflection coefficient of the new quadrangular hollow blocks was lower than that of the conventional quadrangular hollow blocks and decreased with frame height. In addition, this study found that the reflection coefficient and relative run-up height increased with the average wave breaking parameter. The new quadrilateral hollow block has advantages in wave mitigation compared to the conventional quadrilateral hollow block.
Computational Analysis of Deleterious nsSNPs in INS Gene Associated with Permanent Neonatal Diabetes Mellitus
Authors: Ahmed Elsadig Mohamed , Elangeeb Mohamed E. , Adam Khalid Mohamed , Abuagla Hytham Ahmed , MohamedAhmed Abubakr Ali Elamin , Ali Elshazali Widaa , Eltieb Elmoiz Idris , Edris Ali M. , Ali Osman Hiba Mahgoub , Idris Ebtehal Saleh , Khalil Khalil A. A.
Published: April 2024

Insulin gene mutations affect the structure of insulin and are considered a leading cause of neonatal diabetes and permanent neonatal diabetes mellitus PNDM. These mutations can affect the production and secretion of insulin, resulting in inadequate insulin levels and subsequent hyperglycemia. Early discovery or prediction of PNDM can aid in better management and treatment. The current study identified potential deleterious non-synonymous single nucleotide polymorphisms nsSNPs in the INS gene. The analysis of the nsSNPs in the INS gene was conducted using bioinformatics tools by implementing computational algorithms including SIFT, PolyPhen2, SNAP2, SNPs & GO, PhD-SNP, MutPred2, I-Mutant, MuPro, and HOPE tools to investigate the prediction of the potential association between nsSNPs in the INS gene and PNDM. Three mutations, C96Y, P52R, and C96R, were shown to potentially reduce the stability and function of the INS protein. These mutants were subjected to MDSs for structural analysis. Results suggested that these three potential pathogenic mutations may affect the stability and functionality of the insulin protein encoded by the INS gene. Therefore, these changes may influence the development of PNDM. Further researches are required to fully understand the various effects of mutations in the INS gene on insulin synthesis and function. These data can aid in genetic testing for PNDM to evaluate its risk and create treatment and prevention strategies in personalized medicine.