bluuebunny/crossref_metadata_2025 huggingface dataset:
Does the Response to a Stressful Condition in Older Adults with Life Rhythm Dysregulations Provide Evidence of the Existence of the “Dysregulation of Mood, Energy, and Social Rhythms Syndrome”?
Authors: Primavera Diego , Aviles Gonzalez Cesar Ivan , Romano Ferdinando , Kalcev Goce , Pinna Samantha , Minerba Luigi , Scano Alessandra , Orrù Germano , Cossu Giulia
Published: December 2023

Objective: The COVID-19 lockdown periods have given rise to the “Dysregulation of Mood, Energy, and Social Rhythms Syndrome” (DYMERS). This syndrome is characterized by a poor regulation of biological, social, and behavioral rhythms, including sleep, nutrition, and social contacts. The purpose of this cohort study was to examine whether older adults with pre-existing DYMERS had a more negative perception of their health-related quality of life (H-QoL) during the COVID-19 pandemic lockdown, regardless of the presence of concurrent mood disorders. Method: The entire study population (N = 93; age > 65 year) was categorized based on whether they exhibited dysregulated rhythms at the outset of the study. A comparison was made between DYMERS-positive individuals and DYMERS-negative individuals, and we assessed their H-QoL at the conclusion of the study. We also compared the H-QoL of individuals in the cohort who did not have a positive depression score to understand the impact of the rhythm dysregulation alone. Results: The frequency of individuals with a critical health-related quality of life score (SF12 < 25) was higher in the cohort with pre-existing DYMERS during lockdown (33.33% vs. 6.17%). This difference remained significant even when only individuals without depressive symptomatology were considered (27.27% vs. 2.60%). Conclusion: The results of this study indicate that DYMERS can exert a substantial influence on health-related quality of life (H-QoL), even when mood disturbances are not present. Additional research is required to investigate the relationship between DYMERS and other psychiatric conditions as well as its nature as a standalone disorder.
Analysis of Petiole Sap Nutrients Using Rapid and Standard Methods and Its Relation to Leaf Analysis of Fertilized Malus domestica cv. Gala
Authors: Mota Mariana , Martins M. João , Sprey Layanne , Maurício Anabela , Rosa Cristina , Faria João , Martins Miguel B. , de Sousa Miguel L. , Santos Ricardo , de Sousa Rui M. , Ribeiro Henrique , Oliveira Cristina M.
Published: December 2023

Currently, fertilization decisions in apple orchards are based on soil and leaf analyses while the leaf material is sampled after the growing season, usually in June–July (90–110 days after full bloom). This approach is inefficient, as the information becomes available later than the growing season and is therefore only useful in supporting fertilization decisions for the next year, not the current one. To establish a method that provides useful information for fertilization decisions earlier in the growth cycle, our research focused on the assessment of the nutrient content of petiole sap using different methods, the standard method and the rapid method using a reflectometer. For this study, in 2021, four ‘Gala’ orchards were fertilized with different N–P–K levels. Macro and micronutrients were determined in leaves and petiole sap at 45 and 90–110 days after full bloom (DAFB) using standard laboratory methods and the reflectometer. When leaf analysis at 45 and 90–110 DAFB was compared with petiole sap analysis at the same time point, no significant correlations were found between the nutrient contents in leaf material and petiole sap, with the exception of calcium. However, positive results were obtained regarding the correlation between reflectometer determination and standard laboratory analyses. The regression analysis revealed high determination coefficients for N-NO3− (R2 = 0.703), K+ (R2 = 0.705), Ca2+ (R2 = 0.715), and Mg2+ (R2 = 0.780) between standard laboratory methods and the reflectometer. These results suggest that the reflectometer enables a real-time diagnostic tool for monitoring nutrient status throughout the growth cycle, particularly key nutrients related to fruit quality. The N–P–K fertilization strategies had no influence on the nutrient content of leaves or petiole sap. The nutrient content of both sample types varied depending on the orchard.
Identifying Relationship between Regional Centrality and POI Facilities: A Case Study of Seoul Metropolitan Area
Authors: Lee Yose , Seo Ducksu
Published: December 2023

While understanding the dynamic urban network through the concept of regional centrality has provided various implications on the structure and hierarchy of cities, the macroscopic focus of previous studies has largely overlooked the small-scale physical and social urban entities in central places. Meanwhile, recent advances in real-time Point-of-Interest (POI) data have quickly replaced much of traditional urban facility data, emerging as a new representation of urban activities and demands. Therefore, this study proposes a method to identify the relationship between regional centrality and the distribution of POI facilities, particularly focused on the Seoul metropolitan area of South Korea. To this end, this study conducts a correlation analysis between regional centrality results derived from social network analysis and POI indices obtained from POI distribution analysis. The results indicate that a statistically significant relationship exists between regional centrality and the distribution of urban facilities, with a particularly strong correlation exhibited in specific POI categories. The results also demonstrate the effectiveness of the method in capturing disparities in the provision of facilities concerning growing commuting centers. The findings of the study provide pragmatic implications for prioritization and planning of facility development, as well as making informed decisions in real estate and facility investment.
Extracellular Self- and Non-Self DNA Involved in Damage Recognition in the Mistletoe Parasitism of Mesquite Trees
Authors: López-García Claudia Marina , Ávila-Hernández César Alejandro , Quintana-Rodríguez Elizabeth , Aguilar-Hernández Víctor , Lozoya-Pérez Nancy Edith , Rojas-Raya Mariana Atzhiry , Molina-Torres Jorge , Araujo-León Jesús Alfredo , Brito-Argáez Ligia , González-Sánchez Avel Adolfo , Ramírez-Chávez Enrique , Orona-Tamayo Domancar
Published: December 2023

Psittacanthus calyculatus parasitizes mesquite trees through a specialized structure called a haustorium, which, in the intrusive process, can cause cellular damage in the host tree and release DAMPs, such as ATP, sugars, RNA, and DNA. These are highly conserved molecules that primarily function as signals that trigger and activate the defense responses. In the present study, we generate extracellular DNA (exDNA) from mesquite (P. laevigata) tree leaves (self-exDNA) and P. calyculatus (non-self exDNA) mistletoe as DAMP sources to examine mesquite trees’ capacity to identify specific self or non-self exDNA. We determined that mesquite trees perceive self- and non-self exDNA with the synthesis of O2•−, H2O2, flavonoids, ROS-enzymes system, MAPKs activation, spatial concentrations of JA, SA, ABA, and CKs, and auxins. Our data indicate that self and non-self exDNA application differs in oxidative burst, JA signaling, MAPK gene expression, and scavenger systems. This is the first study to examine the molecular biochemistry effects in a host tree using exDNA sources derived from a mistletoe.
The Role of microRNA in Spermatogenesis: Is There a Place for Fertility Preservation Innovation?
Authors: Klees Charlotte , Alexandri Chrysanthi , Demeestere Isabelle , Lybaert Pascale
Published: December 2023

Oncological treatments have dramatically improved over the last decade, and as a result, survival rates for cancer patients have also improved. Quality of life, including concerns about fertility, has become a major focus for both oncologists and patients. While oncologic treatments are often highly effective at suppressing neoplastic growth, they are frequently associated with severe gonadotoxicity, leading to infertility. For male patients, the therapeutic option to preserve fertility is semen cryopreservation. In prepubertal patients, immature testicular tissue can be sampled and stored to allow post-cure transplantation of the tissue, immature germ cells, or in vitro spermatogenesis. However, experimental techniques have not yet been proven effective for restoring sperm production for these patients. MicroRNAs (miRNAs) have emerged as promising molecular markers and therapeutic tools in various diseases. These small regulatory RNAs possess the unique characteristic of having multiple gene targets. MiRNA-based therapeutics can, therefore, be used to modulate the expression of different genes involved in signaling pathways dysregulated by changes in the physiological environment (disease, temperature, ex vivo culture, pharmacological agents). This review discusses the possible role of miRNA as an innovative treatment option in male fertility preservation–restoration strategies and describes the diverse applications where these new therapeutic tools could serve as fertility protection agents.
Statins—From Fungi to Pharmacy
Authors: Sadowska Anna , Osiński Patryk , Roztocka Alicja , Kaczmarz-Chojnacka Karolina , Zapora Ewa , Sawicka Diana , Car Halina
Published: December 2023

Statins have been used in the treatment of hyperlipidemia, both as monotherapy and in combination therapy. Natural fermentation processes of fungi such as Monascus spp., Penicillium spp., Aspergillus terreus, and Pleurotus ostreatus have given rise to natural statins. Compactin (mevastatin), the original naturally occurring statin, is the primary biotransformation substrate in the manufacturing process of marketed drugs. Statins are classified into natural, semi-synthetic derivatives of natural statins, and synthetic ones. Synthetic statins differ from natural statins in their structural composition, with the only common feature being the HMG-CoA-like moiety responsible for suppressing HMG-CoA reductase. Statins do not differ significantly regarding their pleiotropic and adverse effects, but their characteristics depend on their pharmacokinetic parameters and chemical properties. This paper focuses on describing the processes of obtaining natural statins, detailing the pharmacokinetics of available statins, divided into natural and synthetic, and indicating their pleiotropic effects.
Modulation of the Immune Response to Allergies Using Alternative Functional Foods
Authors: López-Enríquez Soledad , Múnera-Rodríguez Ana M. , Leiva-Castro Camila , Sobrino Francisco , Palomares Francisca
Published: December 2023

Modulation of the allergic immune response through alternative therapies is a field of study that aims to address allergic reactions differently from traditional approaches. These therapies encompass the utilization of natural functional foods, which have been observed to exert an influence on the immune response, thus mitigating the severity of allergies. Indeed, some studies suggest that the incorporation of these nutraceuticals can regulate immune function, leading to a reduction in histamine release and subsequent alleviation of allergic symptoms. Moreover, certain herbs and dietary supplements, such as curcumin, are believed to possess anti-inflammatory properties, which may serve to moderate allergic responses. Although the results remain somewhat mixed and require further research, these alternative therapies exhibit the potential to impact the allergic immune response, thereby providing complementary options to conventional treatments. Therefore, in this review, we aim to provide an updated account of functional foods capable of modulating the immune response to allergies. In that sense, the review delves into functional foods sourced from plants (phytochemicals), animals, and marine algae. Emphasis is placed on their potential application in the treatment of allergic disorders. It also provides an overview of how these foods can be effectively utilized as functional foods. Additionally, it explores the molecular mechanisms and scientific validity of various bioactive natural compounds in the management of allergies.
In Vivo and In Silico Studies of the Hepatoprotective Activity of Tert-Butylhydroquinone
Authors: Aldaba-Muruato Liseth Rubi , Sánchez-Barbosa Sandra , Rodríguez-Purata Víctor Hugo , Cabrera-Cruz Georgina , Rosales-Domínguez Estefany , Martínez-Valentín Daniela , Alarcón-López Yoshio Aldo , Aguirre-Vidal Pablo , Hernández-Serda Manuel Alejandro , Cárdenas-Granados Luis Alfonso , Vázquez-Valadez Víctor Hugo , Angeles Enrique , Macías-Pérez José Roberto
Published: December 2023

Tert-butylhydroquinone (TBHQ) is a synthetic food antioxidant with biological activities, but little is known about its pharmacological benefits in liver disease. Therefore, this work aimed to evaluate TBHQ during acute liver damage induced by CCl4 (24 h) or BDL (48 h) in Wistar rats. It was found that pretreatment with TBHQ prevents 50% of mortality induced by a lethal dose of CCl4 (4 g/kg, i.p.), and 80% of BDL+TBHQ rats survived, while only 50% of the BDL group survived. Serum markers of liver damage and macroscopic and microscopic (H&E staining) observations suggest that TBHQ protects from both hepatocellular necrosis caused by the sublethal dose of CCl4 (1.6 g/kg, i.p.), as well as necrosis/ductal proliferation caused by BDL. Additionally, online databases identified 49 potential protein targets for TBHQ. Finally, a biological target candidate (Keap1) was evaluated in a proof-of-concept in silico molecular docking assay, resulting in an interaction energy of −5.5491 kcal/mol, which was higher than RA839 and lower than monoethyl fumarate (compounds known to bind to Keap1). These findings suggest that TBHQ increases the survival of animals subjected to CCl4 intoxication or BDL, presumably by reducing hepatocellular damage, probably due to the interaction of TBHQ with Keap1.
MitoNEET Provides Cardioprotection via Reducing Oxidative Damage and Conserving Mitochondrial Function
Authors: Tam Eddie , Sweeney Gary
Published: December 2023

Cardiometabolic diseases exert a significant health impact, leading to a considerable economic burden globally. The metabolic syndrome, characterized by a well-defined cluster of clinical parameters, is closely linked to an elevated risk of cardiovascular disease. Current treatment strategies often focus on addressing individual aspects of metabolic syndrome. We propose that exploring novel therapeutic approaches that simultaneously target multiple facets may prove more effective in alleviating the burden of cardiometabolic disease. There is a growing body of evidence suggesting that mitochondria can serve as a pivotal target for the development of therapeutics aimed at resolving both metabolic and vascular dysfunction. MitoNEET was identified as a binding target for the thiazolidinedione (TZD) class of antidiabetic drugs and is now recognized for its role in regulating various crucial cellular processes. Indeed, mitoNEET has demonstrated promising potential as a therapeutic target in various chronic diseases, encompassing cardiovascular and metabolic diseases. In this review, we present a thorough overview of the molecular mechanisms of mitoNEET, with an emphasis on their implications for cardiometabolic diseases in more recent years. Furthermore, we explore the potential impact of these findings on the development of novel therapeutic strategies and discuss potential directions for future research.
Unraveling the Multifaceted Roles of Extracellular Vesicles: Insights into Biology, Pharmacology, and Pharmaceutical Applications for Drug Delivery
Authors: Al-Jipouri Ali , Eritja Àuria , Bozic Milica
Published: December 2023

Extracellular vesicles (EVs) are nanoparticles released from various cell types that have emerged as powerful new therapeutic option for a variety of diseases. EVs are involved in the transmission of biological signals between cells and in the regulation of a variety of biological processes, highlighting them as potential novel targets/platforms for therapeutics intervention and/or delivery. Therefore, it is necessary to investigate new aspects of EVs’ biogenesis, biodistribution, metabolism, and excretion as well as safety/compatibility of both unmodified and engineered EVs upon administration in different pharmaceutical dosage forms and delivery systems. In this review, we summarize the current knowledge of essential physiological and pathological roles of EVs in different organs and organ systems. We provide an overview regarding application of EVs as therapeutic targets, therapeutics, and drug delivery platforms. We also explore various approaches implemented over the years to improve the dosage of specific EV products for different administration routes.
GLIS1, Correlated with Immune Infiltrates, Is a Potential Prognostic Biomarker in Prostate Cancer
Authors: Peng Qiang , Xie Tingting , Wang Yuliang , Ho Vincy Wing-Sze , Teoh Jeremy Yuen-Chun , Chiu Peter Ka-Fung , Ng Chi-Fai
Published: December 2023

Prostate cancer (PCa) is a prevalent malignant disease and the primary reason for cancer-related mortality among men globally. GLIS1 (GLIS family zinc finger 1) is a key regulator in various pathologies. However, the expression pattern, clinical relevance, and immunomodulatory function of GLIS1 in PCa remain unclear. In this study, GLIS1 was discovered to serve as a key gene in PCa by integrating mRNA and miRNA expression profiles from GEO database. We systematically explored the expression and prognostic values of GLIS1 in cancers using multiple databases. Additionally, we examined the functions of GLIS1 and the relationship between GLIS1 expression levels and immune infiltration in PCa. Results showed that GLIS1 was differentially expressed between normal and tumor tissues in various cancer types and was significantly low-expressed in PCa. Low GLIS1 expression was associated with poor PCa prognosis. GLIS1 was also involved in the activation, proliferation, differentiation, and migration of immune cells, and its expression showed a positive correlation with the infiltration of various immune cells. Moreover, GLIS1 expression was positively associated with various chemokines/chemokine receptors, indicating the involvement in regulating immune cell migration. In summary, GLIS1 is a potential prognostic biomarker and a therapeutic target to modulate anti-tumor immune response in PCa.
Heating Capacity and Biocompatibility of Hybrid Nanoparticles for Magnetic Hyperthermia Treatment
Authors: Gomes Aline Alexandrina , Valverde Thalita Marcolan , Machado Vagner de Oliveira , do Nascimento da Silva Emanueli , Fagundes Daniele Alves , Oliveira Fernanda de Paula , Freitas Erico Tadeu Fraga , Ardisson José Domingos , Ferreira José Maria da Fonte , Oliveira Junnia Alvarenga de Carvalho , Gomes Eliza Rocha , Rodrigues Caio Fabrini , Goes Alfredo Miranda de , Domingues Rosana Zacarias , Andrade Ângela Leão
Published: December 2023

Cancer is one of the deadliest diseases worldwide and has been responsible for millions of deaths. However, developing a satisfactory smart multifunctional material combining different strategies to kill cancer cells poses a challenge. This work aims at filling this gap by developing a composite material for cancer treatment through hyperthermia and drug release. With this purpose, magnetic nanoparticles were coated with a polymer matrix consisting of poly (L-co-D,L lactic acid-co-trimethylene carbonate) and a poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) triblock copolymer. High-resolution transmission electron microscopy and selected area electron diffraction confirmed magnetite to be the only iron oxide in the sample. Cytotoxicity and heat release assays on the hybrid nanoparticles were performed here for the first time. The heat induction results indicate that these new magnetic hybrid nanoparticles are capable of increasing the temperature by more than 5 °C, the minimal temperature rise required for being effectively used in hyperthermia treatments. The biocompatibility assays conducted under different concentrations, in the presence and in the absence of an external alternating current magnetic field, did not reveal any cytotoxicity. Therefore, the overall results indicate that the investigated hybrid nanoparticles have a great potential to be used as carrier systems for cancer treatment by hyperthermia.
Soluble Forms of Immune Checkpoints and Their Ligands as Potential Biomarkers in the Diagnosis of Recurrent Pregnancy Loss—A Preliminary Study
Authors: Zych Michał , Roszczyk Aleksander , Dąbrowski Filip , Kniotek Monika , Zagożdżon Radosław
Published: December 2023

Immune checkpoints (ICPs) serve as regulatory switches on immune-competent cells. Soluble ICPs consist of fragments derived from ICP molecules typically located on cell membranes. Research has demonstrated that they perform similar functions to their membrane-bound counterparts but are directly present in the bloodstream. Effective control of the maternal immune system is vital for a successful pregnancy due to genetic differences between the mother and fetus. Abnormalities in the immune response are widely acknowledged as the primary cause of spontaneous abortions. In our research, we introduce a novel approach to understanding the immune-mediated mechanisms underlying recurrent miscarriages and explore new possibilities for diagnosing and preventing pregnancy loss. The female participants in the study were divided into three groups: RSA (recurrent spontaneous abortion), pregnant, and non-pregnant women. The analysis of soluble forms of immune checkpoints and their ligands in the serum of the study groups was conducted using the Luminex method Statistically significant differences in the concentrations of (ICPs) were observed between physiological pregnancies and the RSA group. Among patients with RSA, we noted reduced concentrations of sGalectin-9, sTIM-3, and sCD155, along with elevated concentrations of LAG-3, sCD80, and sCD86 ICPs, in comparison to physiological pregnancies. Our study indicates that sGalectin-9, TIM-3, sLAG-3, sCD80, sCD86, sVISTA, sNectin-2, and sCD155 could potentially serve as biological markers of a healthy, physiological pregnancy. These findings suggest that changes in the concentrations of soluble immune checkpoints may have the potential to act as markers for early pregnancy loss.
Concordance between the In Vivo Content of Neurospecific Proteins (BDNF, NSE, VILIP-1, S100B) in the Hippocampus and Blood in Patients with Epilepsy
Authors: Tikhonova Maria A. , Shvaikovskaya Anna A. , Zhanaeva Svetlana Y. , Moysak Galina I. , Akopyan Anna A. , Rzaev Jamil A. , Danilenko Konstantin V. , Aftanas Lyubomir I.
Published: December 2023

The identification of reliable brain-specific biomarkers in periphery contributes to better understanding of normal neurophysiology and neuropsychiatric diseases. The neurospecific proteins BDNF, NSE, VILIP-1, and S100B play an important role in the pathogenesis of neuropsychiatric disorders, including epilepsy. This study aimed to assess the correspondence of the expression of BDNF, NSE, VILIP-1, and S100B in the blood (serum and peripheral blood mononuclear cells (PBMCs)) to the in vivo hippocampal levels of subjects with drug-resistant epilepsy who underwent neurosurgery (N = 44) using multiplex solid-phase analysis, ELISA, and immunohistochemical methods, as well as to analyze the correlations and associations of the blood and hippocampal levels of these proteins with clinical parameters. We first studied the concordance between in vivo brain and blood levels of BDNF, NSE, VILIP-1, and S100B in epileptic patients. A positive correlation for NSE between hippocampal and PBMC levels was revealed. NSE levels in PBMCs were also significantly correlated with average seizure duration. BDNF levels in PBMCs were associated with seizure frequency and hippocampal sclerosis. Thus, NSE and BDNF levels in PBMCs may have potential as clinically significant biomarkers. Significant correlations between the levels of the neurospecific proteins studied herein suggest interactions between BDNF, NSE, VILIP-1, and S100B in the pathophysiology of epilepsy.
Efficacy of Novel Quaternary Ammonium and Phosphonium Salts Differing in Cation Type and Alkyl Chain Length against Antibiotic-Resistant Staphylococcus aureus
Authors: Nunes Bárbara , Cagide Fernando , Fernandes Carlos , Borges Anabela , Borges Fernanda , Simões Manuel
Published: December 2023

Antibacterial resistance poses a critical public health threat, challenging the prevention and treatment of bacterial infections. The search for innovative antibacterial agents has spurred significant interest in quaternary heteronium salts (QHSs), such as quaternary ammonium and phosphonium compounds as potential candidates. In this study, a library of 49 structurally related QHSs was synthesized, varying the cation type and alkyl chain length. Their antibacterial activities against Staphylococcus aureus, including antibiotic-resistant strains, were evaluated by determining minimum inhibitory/bactericidal concentrations (MIC/MBC) ≤ 64 µg/mL. Structure–activity relationship analyses highlighted alkyl-triphenylphosphonium and alkyl-methylimidazolium salts as the most effective against S. aureus CECT 976. The length of the alkyl side chain significantly influenced the antibacterial activity, with optimal chain lengths observed between C10 and C14. Dose–response relationships were assessed for selected QHSs, showing dose-dependent antibacterial activity following a non-linear pattern. Survival curves indicated effective eradication of S. aureus CECT 976 by QHSs at low concentrations, particularly compounds 1e, 3e, and 5e. Moreover, in vitro human cellular data indicated that compounds 2e, 4e, and 5e showed favourable safety profiles at concentrations ≤ 2 µg/mL. These findings highlight the potential of these QHSs as effective agents against susceptible and resistant bacterial strains, providing valuable insights for the rational design of bioactive QHSs.
Specificity Enhancement of Glutenase Bga1903 toward Celiac Disease-Eliciting Pro-Immunogenic Peptides via Active-Site Modification
Authors: Liu Yu-You , Ye Rui-Ling , Meng Menghsiao
Published: December 2023

Celiac disease is an autoimmune disease triggered by oral ingestion of gluten, with certain gluten residues resistant to digestive tract enzymes. Within the duodenum, the remaining peptides incite immunogenic responses, including the generation of autoantibodies and inflammation, leading to irreversible damage. Our previous exploration unveiled a glutenase called Bga1903 derived from the Gram-negative bacterium Burkholderia gladioli. The cleavage pattern of Bga1903 indicates its moderate ability to mitigate the toxicity of pro-immunogenic peptides. The crystal structure of Bga1903, along with the identification of subsites within its active site, was determined. To improve its substrate specificity toward prevalent motifs like QPQ within gluten peptides, the active site of Bga1903 underwent site-directed mutagenesis according to structural insights and enzymatic kinetics. Among the double-site mutants, E380Q/S387L exhibits an approximately 34-fold increase in its specificity constant toward the QPQ sequence, favoring glutamines at the P1 and P3 positions compared to the wild type. The increased specificity of E380Q/S387L not only enhances its ability to break down pro-immunogenic peptides but also positions this enzyme variant as a promising candidate for oral therapy for celiac disease.
Automatic Control and System Theory and Advanced Applications—Volume 2
Authors: Fortuna Luigi , Buscarino Arturo
Published: December 2023

The aim of the Special Issue on Automatic Control and System Theory and Advanced Applications, the second volume of a previous paper selection, is to emphasize the role of new inventions in the area of automatic control applications [...]
Impact of Various Atrial Fibrillation Treatment Strategies on Length of Stay in the Emergency Department and Early Complications—3 Years of a Single-Center Experience
Authors: Kłosiewicz Tomasz , Cholerzyńska Hanna , Zasada Wiktoria , Shadi Amira , Olszewski Jakub , Konieczka Patryk , Podlewski Roland , Puślecki Mateusz
Published: December 2023

Atrial fibrillation (AF) is the most common arrhythmia presenting in emergency departments (EDs), vastly increasing mainly due to society’s lifestyles leading to numerous comorbidities. Its management depends on many factors and is still not unified. Aims: The aim of this study was to compare different AF management strategies in the ED and to evaluate their influence on the length of stay (LOS) in the ED and their safety. We analyzed medical records over 3 years of data collection, including age, primary AF diagnosis, an attempt to restore sinus rhythm, complications, and length of stay. Patients were divided into three groups according to the treatment method received: only pharmacological cardioversion (MED), only electrical cardioversion (EC), and patients who received medications followed by electrical cardioversion (COMB). We included 599 individuals in the analysis with a median age of 71. The restoration of sinus rhythm and LOS were as follows: MED: 64.95%, 173 min; COMB: 87.91%, 295 min; SH: 92.40%, 180 min. The difference between the MED and EC strategies, as well as MED and COMB, was statistically significant (p < 0.001 in both). The total number of complications was 16, with a rate of 32.67%. The majority of them followed a drug administration, and the most common complication was bradycardia. Electrical cardioversion is a safe and effective treatment strategy in stable patients with AF in the ED. It is associated with a shortened LOS. Medication administration preceded the majority of complications.
Stabilization of Traumatic Iliosacral Instability Using Innovative Implants: A Biomechanical Comparison
Authors: Grüneweller Niklas , Leunig Julia , Zderic Ivan , Gueorguiev Boyko , Wähnert Dirk , Vordemvenne Thomas
Published: December 2023

(1) Background: Demographic changes over the past decade have had a significant impact on pelvic ring fractures. They have increased dramatically in the orthogeriatric population. Surgeons are faced with implant fixation issues in the treatment of these fragility fractures. This study compares two innovative implants for stabilizing the iliosacral joint in a biomechanical setting. (2) Methods: An iliosacral screw with a preassembled plate allowing the placement of an additional short, angular stable screw in the ilium and a triangular fixation system consisting of a fenestrated ilium screw and an iliosacral screw quasi-statically inserted through the “fenestra” were instrumented in osteoporotic artificial bone models with a simulated Denis zone 1 fracture. Biomechanical testing was performed on a servo-hydraulic testing machine using increasing, synchronous axial and torsional sinusoidal cyclic loading to failure. (3) Results: The SI-Plate and TriFix showed comparable stiffness values. The values for fracture gap angle and screw tip cutout were significantly lower for the TriFix compared to the SI-Plate. In addition, the number of cycles to failure was significantly higher for the TriFix. (4) Conclusions: Implant anchorage and primary stability can be improved in iliosacral instability using the triangular stabilization system.
Evaluating a Periapical Lesion Detection CNN on a Clinically Representative CBCT Dataset—A Validation Study
Authors: Hadzic Arnela , Urschler Martin , Press Jan-Niclas Aaron , Riedl Regina , Rugani Petra , Štern Darko , Kirnbauer Barbara
Published: December 2023

The aim of this validation study was to comprehensively evaluate the performance and generalization capability of a deep learning-based periapical lesion detection algorithm on a clinically representative cone-beam computed tomography (CBCT) dataset and test for non-inferiority. The evaluation involved 195 CBCT images of adult upper and lower jaws, where sensitivity and specificity metrics were calculated for all teeth, stratified by jaw, and stratified by tooth type. Furthermore, each lesion was assigned a periapical index score based on its size to enable a score-based evaluation. Non-inferiority tests were conducted with proportions of 90% for sensitivity and 82% for specificity. The algorithm achieved an overall sensitivity of 86.7% and a specificity of 84.3%. The non-inferiority test indicated the rejection of the null hypothesis for specificity but not for sensitivity. However, when excluding lesions with a periapical index score of one (i.e., very small lesions), the sensitivity improved to 90.4%. Despite the challenges posed by the dataset, the algorithm demonstrated promising results. Nevertheless, further improvements are needed to enhance the algorithm’s robustness, particularly in detecting very small lesions and the handling of artifacts and outliers commonly encountered in real-world clinical scenarios.
Factors Contributing to the Development of Choroidal Microvasculature Dropout in Glaucoma Suspects and Patients with Glaucoma
Authors: Shin Hee Jong , Oh Si Eun , Kim Seong Ah , Park Chan Kee , Park Hae-Young Lopilly
Published: December 2023

We aimed to characterize and compare the occurrence of peripapillary microvasculature dropout (MvD) between glaucoma suspects and patients with glaucoma. In addition, the factors related to the development of parapapillary MvD in glaucoma suspects and patients with glaucoma were investigated. Of a total 150 eyes, 68 eyes of glaucoma suspects and 82 eyes of glaucoma patients were analyzed in this study. Univariate and multivariate logistic regression analyses were used to identify factors associated with MvD development. The classification of glaucoma patients or glaucoma suspects was not significantly associated with MvD development (beta 1.368, 95% CI, 0.718–2.608, p = 0.341). In the regression analysis of the glaucoma suspect group, greater axial length (beta 1.520, 95% CI, 1.008–2.291, p = 0.046) and baseline cup volume (beta 3.993, 95% CI, 1.292–12.345, p = 0.035) among the baseline factors and the slope of ganglion cell–inner plexiform layer (GCIPL) thickness (beta 0.027, 95% CI, 0.072–0.851, p = 0.027) and central visual field (VF) progression (beta 7.040, 95% CI, 1.781–16.306, p = 0.014) among follow-up factors were significantly associated with MvD development. In the glaucoma group, central VF progression (beta 5.985, 95% CI, 1.474–24.083, p = 0.012) and ONH depression (beta 3.765, 95% CI, 1.301–10.895, p = 0.014) among follow-up elements were observed as significant factors and the baseline factor had little relationship. MvD appears not only as a result of the progression of axonal loss of RGC in glaucoma but may also be developed due to structural changes and mechanical susceptibility of the ONH associated with baseline characteristics. Analyzing the structural susceptibility of the ONH can predict the occurrence of MvD, which can be helpful in predicting the progression of glaucoma.
Longitudinal Changes of Ocular Surface Microbiome in Patients Undergoing Hemopoietic Stem Cell Transplant (HSCT)
Authors: Clougher Suzanne , Severgnini Marco , Marangoni Antonella , Consolandi Clarissa , Camboni Tania , Morselli Sara , Arpinati Mario , Bonifazi Francesca , Dicataldo Michele , Lazzarotto Tiziana , Fontana Luigi , Versura Piera
Published: December 2023

Purpose: To evaluate changes in the ocular surface microbiome (OSM) between pre- and post-haemopoietic stem cell transplant (HSCT) in the same patient, and to assess the potential impact of these changes in ocular graft-versus-host disease (o)GVHD development. Methods: Lower fornix conjunctival swabs of 24 patients were obtained before and after HSCT and subjected to DNA extraction for amplification and sequencing of the V3-V4 regions of the bacterial 16S rRNA gene. The obtained reads were reconstructed, filtered, and clustered into zero-radius operational taxonomic units (zOTUs) at 97% identity level before taxonomic assignment, and biodiversity indexes were calculated. Transplant characteristics were recorded, and dry eye was diagnosed and staged 1–4 according to the Dry Eye WorkShop (DEWS) score. Results: No significant difference in OSM alpha diversity between pre- and post-transplant was found. A significant difference in beta diversity was observed between patients with a DEWS score of 1 versus 3 (p = 0.035). Increased corneal damage between pre- and post-HSCT was significantly associated with a decrease in alpha diversity. The changes in OSM were not associated with oGVHD, nor with any transplant parameter. Conclusions: This preliminary study is the first study to analyse changes in the OSM before and after HSCT longitudinally. No trend in OSM biodiversity, microbial profile, or overall composition changes before and after HSCT was significant or associated with oGVHD onset. The great variability in the observed OSM profiles seems to suggest the absence of a patient-specific OSM “signature”.
Transcultural Adaptation and Validation of the Spanish Version of the Visual Analogue Scale for the Foot and Ankle (VASFA)
Authors: Cervera-Garvi Pablo , Galan-Hurtado Maria Hermas , Marchena-Rodriguez Ana , Chicharro-Luna Esther , Guerra-Marmolejo Cristina , Diaz-Miguel Salvador , Ortega-Avila Ana Belen
Published: December 2023

Background: The main aim of this study is to perform a cross-cultural adaptation and validation of the Visual Analogue Scale for the Foot and Ankle (VASFA) questionnaire, creating a Spanish-language version (VASFA-Sp), and to determine the measurement properties of this instrument. Methods: VASFA was cross-culturally translated into Spanish following the guidelines of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). The study sample was composed of 228 participants who were recruited from February to May 2022. All were at least 18 years old, gave signed informed consent to take part and properly completed the Foot and Ankle Ability Measures-Sp and VASFA-Sp questionnaires. Cronbach’s alpha and test/re-test reliability values were calculated. Structural validity was assessed via exploratory factor analysis. Results: The 228 patients included in the final analysis presented the following characteristics: 35.53% were male and 64.47% were female; the mean age was 35.95 (18–81) years; and the mean body mass index was 23.79. Internal consistency was excellent. The Cronbach’s alpha for VASFA-Sp was 0.96 and the intraclass correlation coefficient was 0.932 (95% CI; 0.84 to 0.97). Exploratory factor analysis identified one main factor. Conclusions: VASFA-Sp is a reliable, valid and sensitive questionnaire that is suitable for measuring perceived foot and ankle function impairment in a Spanish-speaking population.
Title Expression of FOXO3 and MAPK1 Genes in Patients with Benign Salivary Gland Tumors
Authors: Kolary-Siekierska Katarzyna , Niewiadomski Piotr , Namieciński Wojciech , Miłoński Jarosław
Published: December 2023

Pleomorphic adenomas (PAs) and Warthin tumors (WTs) are the most common benign tumors that occur in the salivary gland. PA has a tendency towards malignant transformation. Thus, searching for new methods to diagnose salivary gland tumors and treatment is important. The members of the class O forehead box transcription factor (FOXO3) and mitogen-activated protein kinase 1 (MAPK1) genes participate in the cellular processes, including in cell proliferation. The aim of this study was to analyze these genes’ expression in the salivary gland tissues and in salivary gland tumors. The study group consisted of 50 patients treated for salivary gland tumors. For genetic tests, fresh samples of tissue collected during the surgery were used. The expression levels of the FOXO3 and MAPK1 genes were statistically significantly lower in PA tissue than in normal salivary gland tissue and WT tissue. This research revealed that the FOXO3 and MAPK1 genes are present in benign salivary gland tumors and also indicated a role of these genes in the development of benign salivary gland tumors. The cause of the development of pleomorphic adenomas may be apoptotic disorder and the activation of the inflammatory process. The examined genes may have potential to be new therapeutic targets for the treatment of pleomorphic adenomas.
Direct Oral Anticoagulants in Special Patient Populations
Authors: Kessler Asa , Kolben Yotam , Puris Gal , Ellis Martin , Alperin Mordechai , Simovich Vered , Lerman Shivek Hila , Muszkat Mordechai , Maaravi Yoram , Biton Yitschak
Published: December 2023

Anticoagulants are a cornerstone of treatment in atrial fibrillation. Nowadays, direct oral anticoagulants (DOACs) are extensively used for this condition in developed countries. However, DOAC treatment may be inappropriate in certain patient populations, such as: patients with chronic kidney disease in whom DOAC concentrations may be dangerously elevated; frail elderly patients with an increased risk of falls; patients with significant drug–drug interactions (DDI) affecting either DOAC concentration or effect; patients at the extremes of body mass in whom an “abnormal” volume of distribution may result in inappropriate drug concentrations; patients with recurrent stroke reflecting an unusually high thromboembolic tendency; and, lastly, patients who experience major hemorrhage on an anticoagulant and in whom continued anticoagulation is deemed necessary. Herein we provide a fictional case-based approach to review the recommendations for the use of DOACs in these special patient populations.
Increased Soluble Interleukin 6 Receptors in Fabry Disease
Authors: Lenzini Livia , Iori Elisabetta , Vettore Monica , Gugelmo Giorgia , Radu Claudia , Padoan Andrea , Carraro Gianni , Simioni Paolo , Calò Lorenzo , Avogaro Angelo , Rossi Gian Paolo , Vitturi Nicola
Published: December 2023

Fabry disease (FD) is an X-linked lysosome storage disease that results in the accumulation of globotriaosylceramide (Gb3) throughout the body leading to irreversible target organ damage. As the role of secondary mediators (inflammatory molecules) and their mechanisms has not been fully elucidated, we focused on the interleukin (IL)-6 system in adult FD patients and in matched healthy subjects. To obtain insights into the complex regulation of IL-6 actions, we used a novel approach that integrates information from plasma and exosomes of FD patients (n = 20) and of healthy controls (n = 15). Soluble IL-6 receptor (sIL-6R) levels were measured in plasma with the ELISA method, and membrane-bound IL-6R was quantified in plasma and urinary exosomes using flow cytometry. In FD patients, the levels of soluble IL-6R in plasma were higher than in control subjects (28.0 ± 5.4 ng/mL vs. 18.9 ± 5.4 ng/mL, p < 0.0001); they were also higher in FD subjects with the classical form as compared to those with the late-onset form of the disease (36.0 ± 11.4 ng/mL vs. 26.1 ± 4.5 ng/mL, p < 0.0001). The percentage of urinary exosomes positive for IL-6R was slightly lower in FD (97 ± 1 vs. 100 ± 0% of events positive for IL-6R, p < 0.05); plasma IL-6 levels were not increased. These results suggest a potential role of IL-6 in triggering the inflammatory response in FD. As in FD patients only the levels of sIL-6Rs are consistently higher than in healthy controls, the IL-6 pathogenic signal seems to prevail over the homeostatic one, suggesting a potential mechanism causing multi-systemic damage in FD.
Fatigue Analysis of Printed Composites of Onyx and Kevlar
Authors: Jimenez-Martinez Moises , Varela-Soriano Julio , De La Trinidad-Rendon Julio S. , Torres-Cedillo Sergio G. , Cortés-Pérez Jacinto , Coca-Gonzalez Manuel
Published: December 2023

The transformation of powertrains, powered by internal combustion engines, into electrical systems generates new challenges in developing lightweight materials because electric vehicles are typically heavy. It is therefore important to develop new vehicles and seek more aesthetic and environmentally friendly designs whilst integrating manufacturing processes that contribute to reducing the carbon footprint. At the same time, this research explores the development of new prototypes and custom components using printed composite materials. In this framework, it is essential to formulate new approaches to estimate fatigue life, specifically for components tailored and fabricated with these kinds of advanced materials. This study introduces a novel fatigue life prediction approach based on an artificial neural network. When presented with given inputs, this neural network is trained to predict the accumulation of fatigue damage and the temperature generated during cyclic loading, along with the mechanical properties of the compound. Its validation involves comparing the network’s response with the load ratio result, which can be calculated using the fatigue damage parameter. Comparing both results, the network can successfully predict the fatigue damage accumulation; this implies an ability to directly employ data on the mechanical behavior of the component, eliminating the necessity for experimental testing. Then, the current study introduces a neural network designed to predict the accumulated fatigue damage in printed composite materials with an Onyx matrix and Kevlar reinforcement.
Experimental Ultrasound Approach for Studying Knee Intra-Articular Femur–Tibia Movements under Different Loads
Authors: Ivanov Ivan , Ranchev Sergey , Stoychev Stoyan
Published: December 2023

The purpose of the present study was to develop an experimental model for the study of intra-articular knee movements depending on the function of the knee joint and involved muscle groups under isometric stretching conditions with different loads. The experimental procedure included an ultrasound examination of a knee joint after isometric stretching in healthy men (n = 32). The changes (in millimeters) in the distances between the femur and tibia were measured using an ultrasound sonographer at three stages. The first stage was performed on ten (n = 10) healthy men in five different sitting and upright positions. In the second and third experimental model stages, lower limbs loading was applied to 22 participants. Our hypothesis, which was confirmed, was that as a result of increased loads on the participant’s back, an intra-articular decrease in the femur–tibia cartilage surface distance would be observed. The accuracy of the created experimental model was improved over its three stages from 30% to 9%. Quantitative model data can help to create a mathematical model of the mechanical effects during the deformation of knee joint bone cartilage and it can also help outline some future tasks: increasing loading weights, enlarging participant groups, performing comparisons of men and women, and performing comparisons of healthy and pathological individuals.
Optimizing Resistance Training Technique to Maximize Muscle Hypertrophy: A Narrative Review
Authors: Androulakis Korakakis Patroklos , Wolf Milo , Coleman Max , Burke Ryan , Piñero Alec , Nippard Jeff , Schoenfeld Brad J.
Published: December 2023

Regimented resistance training (RT) has been shown to promote increases in muscle size. When engaging in RT, practitioners often emphasize the importance of appropriate exercise technique, especially when trying to maximize training adaptations (e.g., hypertrophy). This narrative review aims to synthesize existing evidence on what constitutes proper RT exercise technique for maximizing muscle hypertrophy, focusing on variables such as exercise-specific kinematics, contraction type, repetition tempo, and range of motion (ROM). We recommend that when trying to maximize hypertrophy, one should employ a ROM that emphasizes training at long muscle lengths while also employing a repetition tempo between 2 and 8 s. More research is needed to determine whether manipulating the duration of either the eccentric or concentric phase further enhances hypertrophy. Guidelines for body positioning and movement patterns are generally based on implied theory from applied anatomy and biomechanics. However, existing research on the impact of manipulating these aspects of exercise technique and their effect on hypertrophy is limited; it is therefore suggested that universal exercise-specific kinematic guidelines are followed and adopted in accordance with the above recommendations. Future research should investigate the impact of stricter versus more lenient exercise technique variations on hypertrophy.