bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling the Binding of Anticancer Peptides and Mcl-1
Authors: Alhammadi Shamsa Husain Ahmed , Baby Bincy , Antony Priya , Jobe Amie , Humaid Raghad Salman Mohammed , Alhammadi Fatema Jumaa Ahmed , Vijayan Ranjit
Published: June 2024

Mcl-1 (myeloid cell leukemia 1), a member of the Bcl-2 family, is upregulated in various types of cancer. Peptides representing the BH3 (Bcl-2 homology 3) region of pro-apoptotic proteins have been demonstrated to bind the hydrophobic groove of anti-apoptotic Mcl-1, and this interaction is responsible for regulating apoptosis. Structural studies have shown that, while there is high overall structural conservation among the anti-apoptotic Bcl-2 (B-cell lymphoma 2) proteins, differences in the surface groove of these proteins facilitates binding specificity. This binding specificity is crucial for the mechanism of action of the Bcl-2 family in regulating apoptosis. Bim-based peptides bind specifically to the hydrophobic groove of Mcl-1, emphasizing the importance of these interactions in the regulation of cell death. Molecular docking was performed with BH3-like peptides derived from Bim to identify high affinity peptides that bind to Mcl-1 and to understand the molecular mechanism of their interactions. The interactions of three identified peptides, E2gY, E2gI, and XXA1_F3dI, were further evaluated using 250 ns molecular dynamics simulations. Conserved hydrophobic residues of the peptides play an important role in their binding and the structural stability of the complexes. Understanding the molecular basis of interaction of these peptides will assist in the development of more effective Mcl-1 specific inhibitors.
Hair Thickness Growth Effect of Adenosine Complex in Male-/Female-Patterned Hair Loss via Inhibition of Androgen Receptor Signaling
Authors: Kim Jaeyoon , Shin Jae young , Choi Yun-Ho , Joo Jang Ho , Kwack Mi Hee , Sung Young Kwan , Kang Nae Gyu
Published: June 2024

Aging (senescence) is an unavoidable biological process that results in visible manifestations in all cutaneous tissues, including scalp skin and hair follicles. Previously, we evaluated the molecular function of adenosine in promoting alopecia treatment in vitro. To elucidate the differences in the molecular mechanisms between minoxidil (MNX) and adenosine, gene expression changes in dermal papilla cells were examined. The androgen receptor (AR) pathway was identified as a candidate target of adenosine for hair growth, and the anti-androgenic activity of adenosine was examined in vitro. In addition, ex vivo examination of human hair follicle organ cultures revealed that adenosine potently elongated the anagen stage. According to the severity of alopecia, the ratio of the two peaks (terminal hair area/vellus hair area) decreased continuously. We further investigated the adenosine hair growth promoting effect in vivo to examine the hair thickness growth effects of topical 5% MNX and the adenosine complex (0.75% adenosine, 1% penthenol, and 2% niacinamide; APN) in vivo. After 4 months of administration, both the MNX and APN group showed significant increases in hair density (MNX + 5.01% (p < 0.01), APN + 6.20% (p < 0.001)) and thickness (MNX + 5.14% (p < 0.001), APN + 10.32% (p < 0.001)). The inhibition of AR signaling via adenosine could have contributed to hair thickness growth. We suggest that the anti-androgenic effect of adenosine, along with the evaluation of hair thickness distribution, could help us to understand hair physiology and to investigate new approaches for drug development.
A Machine Learning Approach to Identify Key Residues Involved in Protein–Protein Interactions Exemplified with SARS-CoV-2 Variants
Authors: Quitté Léopold , Leclercq Mickael , Prunier Julien , Scott-Boyer Marie-Pier , Moroy Gautier , Droit Arnaud
Published: June 2024

Human infection with the coronavirus disease 2019 (COVID-19) is mediated by the binding of the spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the human angiotensin-converting enzyme 2 (ACE2). The frequent mutations in the receptor-binding domain (RBD) of the spike protein induced the emergence of variants with increased contagion and can hinder vaccine efficiency. Hence, it is crucial to better understand the binding mechanisms of variant RBDs to human ACE2 and develop efficient methods to characterize this interaction. In this work, we present an approach that uses machine learning to analyze the molecular dynamics simulations of RBD variant trajectories bound to ACE2. Along with the binding free energy calculation, this method was used to characterize the major differences in ACE2-binding capacity of three SARS-CoV-2 RBD variants—namely the original Wuhan strain, Omicron BA.1, and the more recent Omicron BA.5 sublineages. Our analyses assessed the differences in binding free energy and shed light on how it affects the infectious rates of different variants. Furthermore, this approach successfully characterized key binding interactions and could be deployed as an efficient tool to predict different binding inhibitors to pave the way for new preventive and therapeutic strategies.
Biological Activity of Complexes Involving Nitro-Containing Ligands and Crystallographic-Theoretical Description of 3,5-DNB Complexes
Authors: Fonseca-López Daniela , Lozano Johan D. , Macías Mario A. , Muñoz-Castro Álvaro , MacLeod-Carey Desmond , Nagles Edgar , Hurtado John
Published: June 2024

Drug resistance in infectious diseases developed by bacteria and fungi is an important issue since it is necessary to further develop novel compounds with biological activity that counteract this problem. In addition, new pharmaceutical compounds with lower secondary effects to treat cancer are needed. Coordination compounds appear to be accessible and promising alternatives aiming to overcome these problems. In this review, we summarize the recent literature on coordination compounds based on nitrobenzoic acid (NBA) as a ligand, its derivatives, and other nitro-containing ligands, which are widely employed owing to their versatility. Additionally, an analysis of crystallographic data is presented, unraveling the coordination preferences and the most effective crystallization methods to grow crystals of good quality. This underscores the significance of elucidating crystalline structures and utilizing computational calculations to deepen the comprehension of the electronic properties of coordination complexes.
Lysophosphatidylcholines Promote Influenza Virus Reproduction through the MAPK/JNK Pathway in PMA-Differentiated THP-1 Macrophages
Authors: Cha Min-Ho , Choi Hee-Jeong , Ma Jin-Yeul
Published: June 2024

Obesity and metabolic syndrome alter serum lipid profiles. They also increase vulnerability to viral infections and worsen the survival rate and symptoms after infection. How serum lipids affect influenza virus proliferation is unclear. Here, we investigated the effects of lysophosphatidylcholines on influenza A virus (IAV) proliferation. IAV particles in the culture medium were titrated using extraction-free quantitative PCR, and viral RNA and protein levels were assessed using real-time PCR and Western blot, respectively. RNA sequencing data were analyzed using PCA and heatmap analysis, and pathway analysis was performed using the KEGG mapper and PathIN tools. Statistical analysis was conducted using SPSS21.0. LPC treatment of THP-1 cells significantly increased IAV proliferation and IAV RNA and protein levels, and saturated LPC was more active in IAV RNA expression than unsaturated LPC was. The functional analysis of genes affected by LPCs showed that the expression of genes involved in IAV signaling, such as suppressor of cytokine signaling 3 (SOCS3), phosphoinositide-3-kinase regulatory subunit 3 (PI3K) and AKT serine/threonine kinase 3 (AKT3), Toll-like receptor 7 (TKR7), and interferon gamma receptor 1 (IFNGR1), was changed by LPC. Altered influenza A pathways were linked with MAPK and PI3K/AKT signaling. Treatment with inhibitors of MAPK or PI3K attenuated viral gene expression changes induced by LPCs. The present study shows that LPCs stimulated virus reproduction by modifying the cellular environment to one in which viruses proliferated better. This was mediated by the MAPK, JNK, and PI3K/AKT pathways. Further animal studies are needed to confirm the link between LPCs from serum or the respiratory system and IAV proliferation.
Limited Added Diagnostic Value of Whole Genome Sequencing in Genetic Testing of Inherited Retinal Diseases in a Swiss Patient Cohort
Authors: Maggi Jordi , Koller Samuel , Feil Silke , Bachmann-Gagescu Ruxandra , Gerth-Kahlert Christina , Berger Wolfgang
Published: June 2024

The purpose of this study was to assess the added diagnostic value of whole genome sequencing (WGS) for patients with inherited retinal diseases (IRDs) who remained undiagnosed after whole exome sequencing (WES). WGS was performed for index patients in 66 families. The datasets were analyzed according to GATK’s guidelines. Additionally, DeepVariant was complemented by GATK’s workflow, and a novel structural variant pipeline was developed. Overall, a molecular diagnosis was established in 19/66 (28.8%) index patients. Pathogenic deletions and one deep-intronic variant contributed to the diagnostic yield in 4/19 and 1/19 index patients, respectively. The remaining diagnoses (14/19) were attributed to exonic variants that were missed during WES analysis due to bioinformatic limitations, newly described loci, or unclear pathogenicity. The added diagnostic value of WGS equals 5/66 (9.6%) for our cohort, which is comparable to previous studies. This figure would decrease further to 1/66 (1.5%) with a standardized and reliable copy number variant workflow during WES analysis. Given the higher costs and limited added value, the implementation of WGS as a first-tier assay for inherited eye disorders in a diagnostic laboratory remains untimely. Instead, progress in bioinformatic tools and communication between diagnostic and clinical teams have the potential to ameliorate diagnostic yields.
Inhibition of Protein Synthesis Attenuates Formation of Traumatic Memory and Normalizes Fear-Induced c-Fos Expression in a Mouse Model of Posttraumatic Stress Disorder
Authors: Zamorina Tatyana A. , Ivashkina Olga I. , Toropova Ksenia A. , Anokhin Konstantin V.
Published: June 2024

Posttraumatic stress disorder (PTSD) is a debilitating psychosomatic condition characterized by impairment of brain fear circuits and persistence of exceptionally strong associative memories resistant to extinction. In this study, we investigated the neural and behavioral consequences of inhibiting protein synthesis, a process known to suppress the formation of conventional aversive memories, in an established PTSD animal model based on contextual fear conditioning in mice. Control animals were subjected to the conventional fear conditioning task. Utilizing c-Fos neural activity mapping, we found that the retrieval of PTSD and normal aversive memories produced activation of an overlapping set of brain structures. However, several specific areas, such as the infralimbic cortex and the paraventricular thalamic nucleus, showed an increase in the PTSD group compared to the normal aversive memory group. Administration of protein synthesis inhibitor before PTSD induction disrupted the formation of traumatic memories, resulting in behavior that matched the behavior of mice with usual aversive memory. Concomitant with this behavioral shift was a normalization of brain c-Fos activation pattern matching the one observed in usual fear memory. Our findings demonstrate that inhibiting protein synthesis during traumatic experiences significantly impairs the development of PTSD in a mouse model. These data provide insights into the neural underpinnings of protein synthesis-dependent traumatic memory formation and open prospects for the development of new therapeutic strategies for PTSD prevention.
Versatile Self-Assembly of Triblock Peptides into Stable Collagen Mimetic Heterotrimers
Authors: Yao Linyan , Ling Biyang , Zhao Sha , Yu Fansen , Liu Huanxiang , Wang Shenlin , Xiao Jianxi
Published: June 2024

The construction of peptides to mimic heterogeneous proteins such as type I collagen plays a pivotal role in deciphering their function and pathogenesis. However, progress in the field has been severely hampered by the lack of capability to create stable heterotrimers with desired functional sequences and without the effect of homotrimers. We have herein developed a set of triblock peptides that can assemble into collagen mimetic heterotrimers with desired amino acids and are free from the interference of homotrimers. The triblock peptides comprise a central collagen-like block and two oppositely charged N-/C-terminal blocks, which display inherent incompetency of homotrimer formation. The favorable electrostatic attraction between two paired triblock peptides with complementary terminal charged sequences promptly leads to stable heterotrimers with controlled chain composition. The independence of the collagen-like block from the two terminal blocks endows this system with the adaptability to incorporate desired amino acid sequences while maintaining the heterotrimer structure. The triblock peptides provide a versatile and robust tool to mimic the composition and function of heterotrimer collagen and may have great potential in the design of innovative peptides mimicking heterogeneous proteins.
Polymer Microspheres and Their Application in Cancer Diagnosis and Treatment
Authors: Zhai Mingyue , Wu Pan , Liao Yuan , Wu Liangliang , Zhao Yongxiang
Published: June 2024

Cancer is a significant global public health issue with increasing morbidity and mortality rates. To address this challenge, novel drug carriers such as nano-materials, liposomes, hydrogels, fibers, and microspheres have been extensively researched and utilized in oncology. Among them, polymer microspheres are gaining popularity due to their ease of preparation, excellent performance, biocompatibility, and drug-release capabilities. This paper categorizes commonly used materials for polymer microsphere preparation, summarizes various preparation methods (emulsification, phase separation, spray drying, electrospray, microfluidics, and membrane emulsification), and reviews the applications of polymer microspheres in cancer diagnosis, therapy, and postoperative care. The current status and future development directions of polymer microspheres in cancer treatment are analyzed, highlighting their importance and potential for improving patient outcomes.
Wheat MIXTA-like Transcriptional Activators Positively Regulate Cuticular Wax Accumulation
Authors: Wang Xiaoyu , Fu Yixian , Liu Xiaofeng , Chang Cheng
Published: June 2024

MIXTA-like transcription factors AtMYB16 and AtMYB106 play important roles in the regulation of cuticular wax accumulation in dicot model plant Arabidopsis thaliana, but there are very few studies on the MIXTA-like transcription factors in monocot plants. Herein, wheat MIXTA-like transcription factors TaMIXTA1 and TaMIXTA2 were characterized as positive regulators of cuticular wax accumulation. The virus-induced gene silencing experiments showed that knock-down of wheat TaMIXTA1 and TaMIXTA2 expressions resulted in the decreased accumulation of leaf cuticular wax, increased leaf water loss rate, and potentiated chlorophyll leaching. Furthermore, three wheat orthologous genes of ECERIFERUM 5 (TaCER5-1A, 1B, and 1D) and their function in cuticular wax deposition were reported. The silencing of TaCER5 by BSMV-VIGS led to reduced loads of leaf cuticular wax and enhanced rates of leaf water loss and chlorophyll leaching, indicating the essential role of the TaCER5 gene in the deposition of wheat cuticular wax. In addition, we demonstrated that TaMIXTA1 and TaMIXTA2 function as transcriptional activators and could directly stimulate the transcription of wax biosynthesis gene TaKCS1 and wax deposition gene TaCER5. The above results strongly support that wheat MIXTA-Like transcriptional activators TaMIXTA1 and TaMIXTA2 positively regulate cuticular wax accumulation via activating TaKCS1 and TaCER5 gene transcription.
The Waxy Gene Has Pleiotropic Effects on Hot Water-Soluble and -Insoluble Amylose Contents in Rice (Oryza sativa) Grains
Authors: Wu Hongkai , Wang Siyuan , Wu Min
Published: June 2024

Rice (Oryza sativa) is a cereal crop with a starchy endosperm. Starch is composed of amylose and amylopectin. Amylose content (AC) is the principal determinant of rice quality, but varieties with similar ACs can still vary substantially in their quality. In this study, we analyzed the total AC (TAC) and its constituent fractions, the hot water-soluble amylose content (SAC) and hot water-insoluble amylose content (IAC), in two sets of related chromosome segment substitution lines of rice with a common genetic background grown in two years. We searched for quantitative trait loci (QTLs) associated with SAC, IAC, and TAC and identified one common QTL (qSAC–6, qIAC–6, and qTAC–6) on chromosome 6. Map-based cloning revealed that the gene underlying the trait associated with this common QTL is Waxy (Wx). An analysis of the colors of soluble and insoluble starch–iodine complexes and their λmax values (wavelengths at the positions of their peak absorbance values) as well as gel permeation chromatography revealed that Wx is responsible for the biosynthesis of amylose, comprising a large proportion of the soluble fractions of the SAC. Wx is also involved in the biosynthesis of long chains of amylopectin, comprising the hot water-insoluble fractions of the IAC. These findings highlight the pleiotropic effects of Wx on the SAC and IAC. This pleiotropy indicates that these traits have a positive genetic correlation. Therefore, further studies of rice quality should use rice varieties with the same Wx genotype to eliminate the pleiotropic effects of this gene, allowing the independent relationship between the SAC or IAC and rice quality to be elucidated through a multiple correlation analysis. These findings are applicable to other valuable cereal crops as well.
Association Study of Serotonin 1A Receptor Gene, Personality, and Anxiety in Women with Alcohol Use Disorder
Authors: Boroń Agnieszka , Suchanecka Aleksandra , Chmielowiec Krzysztof , Chmielowiec Jolanta , Lachowicz Milena , Strońska-Pluta Aleksandra , Trybek Grzegorz , Wach Tomasz , González Domenech Pablo José , Grzywacz Anna
Published: June 2024

Alcohol use disorder is considered a chronic and relapsing disorder affecting the central nervous system. The serotonergic system, mainly through its influence on the mesolimbic dopaminergic reward system, has been postulated to play a pivotal role in the underlying mechanism of alcohol dependence. The study aims to analyse the association of the rs6295 polymorphism of the 5HTR1A gene in women with alcohol use disorder and the association of personality traits with the development of alcohol dependence, as well as the interaction of the rs6295, personality traits, and anxiety with alcohol dependence in women. The study group consisted of 213 female volunteers: 101 with alcohol use disorder and 112 controls. NEO Five-Factor and State-Trait Anxiety Inventories were applied for psychometric testing. Genotyping of rs6295 was performed by real-time PCR. We did not observe significant differences in 5HTR1A rs6295 genotypes (p = 0.2709) or allele distribution (p = 0.4513). The AUD subjects scored higher on the anxiety trait (p < 0.0001) and anxiety state (p < 0.0001) scales, as well as on the neuroticism (p < 0.0001) and openness (p = 0134) scales. Significantly lower scores were obtained by the AUD subjects on the extraversion (p < 0.0001), agreeability (p < 0.0001), and conscientiousness (p < 0.0001) scales. Additionally, we observed a significant effect of 5HTR1A rs6295 genotype interaction and alcohol dependency, or lack thereof, on the openness scale (p = 0.0016). In summary, this study offers a comprehensive overview of alcohol dependence among women. It offers valuable insights into this complex topic, contributing to a more nuanced understanding of substance use among this specific demographic. Additionally, these findings may have implications for developing prevention and intervention strategies tailored to individual genetic and, most importantly, personality and anxiety differences.
Folding and Binding Kinetics of the Tandem of SH2 Domains from SHP2
Authors: Pagano Livia , Pennacchietti Valeria , Malagrinò Francesca , Di Felice Mariana , Toso Julian , Puglisi Elena , Gianni Stefano , Toto Angelo
Published: June 2024

The SH2 domains of SHP2 play a crucial role in determining the function of the SHP2 protein. While the folding and binding properties of the isolated NSH2 and CSH2 domains have been extensively studied, there is limited information about the tandem SH2 domains. This study aims to elucidate the folding and binding kinetics of the NSH2-CSH2 tandem domains of SHP2 through rapid kinetic experiments, complementing existing data on the isolated domains. The results indicate that while the domains generally fold and unfold independently, acidic pH conditions induce complex scenarios involving the formation of a misfolded intermediate. Furthermore, a comparison of the binding kinetics of isolated NSH2 and CSH2 domains with the NSH2-CSH2 tandem domains, using peptides that mimic specific portions of Gab2, suggests a dynamic interplay between NSH2 and CSH2 in binding Gab2 that modulate the microscopic association rate constant of the binding reaction. These findings, discussed in the context of previous research on the NSH2 and CSH2 domains, enhance our understanding of the function of the SH2 domain tandem of SHP2.
Immunogenetic and Environmental Factors in Age-Related Macular Disease
Authors: Brodzka Sylwia , Baszyński Jędrzej , Rektor Katarzyna , Hołderna-Bona Karolina , Stanek Emilia , Kurhaluk Natalia , Tkaczenko Halina , Malukiewicz Grażyna , Woźniak Alina , Kamiński Piotr
Published: June 2024

Age-related macular degeneration (AMD) is a chronic disease, which often develops in older people, but this is not the rule. AMD pathogenesis changes include the anatomical and functional complex. As a result of damage, it occurs, in the retina and macula, among other areas. These changes may lead to partial or total loss of vision. This disease can occur in two clinical forms, i.e., dry (progression is slowly and gradually) and exudative (wet, progression is acute and severe), which usually started as dry form. A coexistence of both forms is possible. AMD etiology is not fully understood. Extensive genetic studies have shown that this disease is multifactorial and that genetic determinants, along with environmental and metabolic-functional factors, are important risk factors. This article reviews the impact of heavy metals, macro- and microelements, and genetic factors on the development of AMD. We present the current state of knowledge about the influence of environmental factors and genetic determinants on the progression of AMD in the confrontation with our own research conducted on the Polish population from Kuyavian-Pomeranian and Lubusz Regions. Our research is concentrated on showing how polluted environments of large agglomerations affects the development of AMD. In addition to confirming heavy metal accumulation, the growth of risk of acute phase factors and polymorphism in the genetic material in AMD development, it will also help in the detection of new markers of this disease. This will lead to a better understanding of the etiology of AMD and will help to establish prevention and early treatment.
The Effect of Targeted Hyperoxemia on Brain Immunohistochemistry after Long-Term, Resuscitated Porcine Acute Subdural Hematoma and Hemorrhagic Shock
Authors: Münz Franziska , Datzmann Thomas , Hoffmann Andrea , Gröger Michael , Mathieu René , Mayer Simon , Zink Fabian , Gässler Holger , Wolfschmitt Eva-Maria , Hogg Melanie , Calzia Enrico , Asfar Pierre , Radermacher Peter , Kapapa Thomas , Merz Tamara
Published: June 2024

Epidemiological data suggest that moderate hyperoxemia may be associated with an improved outcome after traumatic brain injury. In a prospective, randomized investigation of long-term, resuscitated acute subdural hematoma plus hemorrhagic shock (ASDH + HS) in 14 adult, human-sized pigs, targeted hyperoxemia (200 < PaO2 < 250 mmHg vs. normoxemia 80 < PaO2 < 120 mmHg) coincided with improved neurological function. Since brain perfusion, oxygenation and metabolism did not differ, this post hoc study analyzed the available material for the effects of targeted hyperoxemia on cerebral tissue markers of oxidative/nitrosative stress (nitrotyrosine expression), blood–brain barrier integrity (extravascular albumin accumulation) and fluid homeostasis (oxytocin, its receptor and the H2S-producing enzymes cystathionine-β-synthase and cystathionine-γ-lyase). After 2 h of ASDH + HS (0.1 mL/kgBW autologous blood injected into the subdural space and passive removal of 30% of the blood volume), animals were resuscitated for up to 53 h by re-transfusion of shed blood, noradrenaline infusion to maintain cerebral perfusion pressure at baseline levels and hyper-/normoxemia during the first 24 h. Immediate postmortem, bi-hemispheric (i.e., blood-injected and contra-lateral) prefrontal cortex specimens from the base of the sulci underwent immunohistochemistry (% positive tissue staining) analysis of oxidative/nitrosative stress, blood–brain barrier integrity and fluid homeostasis. None of these tissue markers explained any differences in hyperoxemia-related neurological function. Likewise, hyperoxemia exerted no deleterious effects.
Recent Advances in Endometriosis Pathophysiology and Pharmacological Treatment
Authors: Perricos Alexandra , Wenzl René
Published: June 2024

Endometriosis, affecting an estimated 10% of women of reproductive age [...]
The P2X7 Hypothesis of Central Post-Stroke Pain
Authors: Huang Andrew Chih Wei , Shih Hsi-Chien , Shyu Bai Chuang
Published: June 2024

The present study examined how P2X7 receptor knockout (KO) modulates central post-stroke pain (CPSP) induced by lesions of the ventrobasal complex (VBC) of the thalamus in behaviors, molecular levels, and electrical recording tests. Following the experimental procedure, the wild-type and P2X7 receptor KO mice were injected with 10 mU/0.2 μL type IV collagenase in the VBC of the thalamus to induce an animal model of stroke-like thalamic hemorrhage. Behavioral data showed that the CPSP group induced thermal and mechanical pain. The P2X7 receptor KO group showed reduced thermal and mechanical pain responses compared to the CPSP group. Molecular assessments revealed that the CPSP group had lower expression of NeuN and KCC2 and higher expression of GFAP, IBA1, and BDNF. The P2X7 KO group showed lower expression of GFAP, IBA1, and BDNF but nonsignificant differences in KCC2 expression than the CPSP group. The expression of NKCC1, GABAa receptor, and TrkB did not differ significantly between the control, CPSP, and P2X7 receptor KO groups. Muscimol, a GABAa agonist, application increased multiunit numbers for monitoring many neurons and [Cl−] outflux in the cytosol in the CPSP group, while P2X7 receptor KO reduced multiunit activity and increased [Cl−] influx compared to the CPSP group. P2X4 receptor expression was significantly decreased in the 100 kDa but not the 50 kDa site in the P2X7 receptor KO group. Altogether, the P2X7 hypothesis of CPSP was proposed, wherein P2X7 receptor KO altered the CPSP pain responses, numbers of astrocytes and microglia, CSD amplitude of the anterior cingulate cortex and the medial dorsal thalamus, BDNF expression, [Cl−] influx, and P2X4 expression in 100 kDa with P2X7 receptors. The present findings have implications for the clinical treatment of CPSP symptoms.
Identifying Long COVID Definitions, Predictors, and Risk Factors in the United States: A Scoping Review of Data Sources Utilizing Electronic Health Records
Authors: Luke Rayanne A. , Shaw George , Saarunya Geetha , Mollalo Abolfazl
Published: June 2024

This scoping review explores the potential of electronic health records (EHR)-based studies to characterize long COVID. We screened all peer-reviewed publications in the English language from PubMed/MEDLINE, Scopus, and Web of Science databases until 14 September 2023, to identify the studies that defined or characterized long COVID based on data sources that utilized EHR in the United States, regardless of study design. We identified only 17 articles meeting the inclusion criteria. Respiratory conditions were consistently significant in all studies, followed by poor well-being features (n = 14, 82%) and cardiovascular conditions (n = 12, 71%). Some articles (n = 7, 41%) used a long COVID-specific marker to define the study population, relying mainly on ICD-10 codes and clinical visits for post-COVID-19 conditions. Among studies exploring plausible long COVID (n = 10, 59%), the most common methods were RT-PCR and antigen tests. The time delay for EHR data extraction post-test varied, ranging from four weeks to more than three months; however, most studies considering plausible long COVID used a waiting period of 28 to 31 days. Our findings suggest a limited utilization of EHR-derived data sources in defining long COVID, with only 59% of these studies incorporating a validation step.
Microrobots Based on Smart Materials with Their Manufacturing Methods and Applications
Authors: Sun Jiawei , Cai Shuxiang , Yang Wenguang , Leng Huiwen , Ge Zhixing , Liu Tangying
Published: June 2024

In recent years, the field of microrobots has exploded, yielding many exciting new functions and applications, from object grasping and release to in vivo drug transport. Smart responsive materials have had a profound impact on the field of microrobots and have given them unique functions and structures. We analyze three aspects of microrobots, in which the future development of microrobots requires more efforts to be invested, and in which smart materials play a significant role in the development of microrobots. These three aspects are smart materials for building microrobots, manufacturing methods, and the functions and applications they achieve. In this review, we discuss the deformation mechanism of materials in response to external stimuli, starting from smart materials, and discuss fabrication methods to realize microrobots, laying the theoretical foundation for future smart material-based microrobots to realize their intelligence and programmability.
An e-Health Psychoeducation Program for Managing the Mental Health of People with Bipolar Disorder during the COVID-19 Pandemic: A Randomized Controlled Study
Authors: Perra Alessandra , Sancassiani Federica , Cantone Elisa , Pintus Elisa , D’Oca Silvia , Casula Alessio , Littarru Sara , Zucca Sara , Tumolillo Davide , Pinna Irene , Primavera Diego , Cossu Giulia , Nardi Antonio Egidio , Kalcev Goce , Carta Mauro Giovanni
Published: June 2024

Background: Social rhythm dysregulation has been identified as a determining factor in bipolar disorder (BD) relapses. It directly impacts individuals’ quality of life (QoL). This study aims to present preliminary data on the efficacy of an e-health psychoeducational intervention for BD for improving clinical outcomes. Methods: This study used an open-label, crossover, randomized controlled trial design. The inclusion criteria consisted of a BD diagnosis, affiliation with the Consultation Psychiatry and Psychosomatic Center at the University Hospital in Cagliari, Italy, age over 18, and the obtaining of informed consent. Anxiety and depressive symptoms, QoL, and social and biological rhythms were measured using standardized instruments validated in Italian. Results: A total of 36 individuals were included in the experimental group (EG) and 18 in the control group (CG). The final sample consisted of 25 in the EG and 14 in the CG. A statistically significant improvement in QoL was found in the EG post-treatment (p = 0.011). Significant correlations were found between QoL and the dysregulation of biorhythms in the EG at T0 (p = 0.0048) and T1 (p = 0.0014). Conclusions: This study shows that, during extreme distress, an e-health group psychoeducation intervention for people with BD could significantly improve the perception of QoL. The results must be confirmed by studies conducted with larger-sized samples.
ZH-ECochG Bode Plot: A Novel Approach to Visualize Electrocochleographic Data in Cochlear Implant Users
Authors: Geys Marlies , Sijgers Leanne , Dobrev Ivo , Dalbert Adrian , Röösli Christof , Pfiffner Flurin , Huber Alexander
Published: June 2024

Background: Various representations exist in the literature to visualize electrocochleography (ECochG) recordings along the basilar membrane (BM). This lack of generalization complicates comparisons within and between cochlear implant (CI) users, as well as between publications. This study synthesized the visual representations available in the literature via a systematic review and provides a novel approach to visualize ECochG data in CI users. Methods: A systematic review was conducted within PubMed and EMBASE to evaluate studies investigating ECochG and CI. Figures that visualized ECochG responses were selected and analyzed. A novel visualization of individual ECochG data, the ZH-ECochG Bode plot (ZH = Zurich), was devised, and the recordings from three CI recipients were used to demonstrate and assess the new framework. Results: Within the database search, 74 articles with a total of 115 figures met the inclusion criteria. Analysis revealed various types of representations using different axes; their advantages were incorporated into the novel visualization framework. The ZH-ECochG Bode plot visualizes the amplitude and phase of the ECochG recordings along the different tonotopic regions and angular insertion depths of the recording sites. The graph includes the pre- and postoperative audiograms to enable a comparison of ECochG responses with the audiometric profile, and allows different measurements to be shown in the same graph. Conclusions: The ZH-ECochG Bode plot provides a generalized visual representation of ECochG data, using well-defined axes. This will facilitate the investigation of the complex ECochG potentials generated along the BM and allows for better comparisons of ECochG recordings within and among CI users and publications. The scripts used to construct the ZH-ECochG Bode plot are provided by the authors.
Association between Epicardial Adipose Tissue and Atrial Fibrillation in Patients with Transfusion-Dependent β-Thalassemia
Authors: Malagù Michele , Tonet Elisabetta , Orazio Giovanni , Longo Filomena , De Raffele Martina , Sirugo Paolo , Capanni Andrea , Clò Stefano , Berloni Maria Letizia , Marchini Federico , Manfrini Marco , Mari Elisa , Soffritti Olga , Culcasi Martina , Balla Cristina , Vitali Francesco , Cossu Alberto , Bertini Matteo
Published: June 2024

Background: Modern treatments for transfusion-dependent β-thalassemia (TDβT) have allowed patients to reach high life expectancy with no iron overload. Despite survival improvement, atrial fibrillation (AF) has emerged as a relevant issue. AF pathophysiology and characteristics in TDβT are different than in the general population. Epicardial adipose tissue (EAT) may play a role but its relationship with AF in patients with TDβT has not been explored. Methods: A monocentric, cross-sectional study, enrolling consecutive patients with TDβT. Epicardial adipose tissue (EAT) was evaluated at magnetic resonance. Characteristics of patients with and without history of AF were investigated. Factors independently associated with AF prevalence were analyzed. Results: A total of 116 patients were enrolled. All patients were treated with regular chelation therapy. The prevalence of AF was 29.3% (34/116). Cardiac T2* and liver iron concentration were no different between patients with and without AF. EAT thickness was significantly higher in patients with AF at left atrium, right atrium and right ventricle (5.0 vs. 4.0 mm, p < 0.01, 4.4 vs. 4.0, p = 0.02 and 5.0 vs. 4.3, p = 0.04). Patients with AF presented with older age, (53 vs. 49 years, p < 0.01), more hypothyroidism (44.1 vs. 20.7%, p = 0.01), pulmonary hypertension (23.5 vs. 2.4% p < 0.01), splenectomy (88.2 vs. 64.6%, p = 0.01), higher right and left atrial volume (61 vs. 40 and 74 vs. 43 mL, both p < 0.01). At multivariable analysis, hypothyroidism, left atrial volume and left atrial EAT were independently associated with AF (odds ratio 9.95, 1.09 and 1.91, respectively). Conclusions: In a contemporary cohort of patients with TDβT, treated with regular chelation therapy, prevalence of AF was unrelated to iron overload. EAT was independently associated with AF.
Platelet-Rich Fibrin Treatment Evaluation in Patients with Medication-Related Osteonecrosis of the Jaw and Osteoradionecrosis
Authors: Roman Rareș Călin , Moldovan Mădălina Anca , Pop Loredana Sabrina , Megieșan Sergiu , Faur Cosmin Ioan
Published: June 2024

Background. Medication-related osteonecrosis of the jaw (MRONJ) and osteoradionecrosis (ORN) are associated with severe disability and continuous pain, both of which are very difficult to control. This study aims to evaluate the outcome of platelet-rich fibrin (PRF) treatment compared to iodoform gauze packing and the primary suture of oral mucosa in patients with both MRONJ and ORN. Methods. Patients suffering from MRONJ and ORN who were treated in the Oral and Maxillofacial Surgery Clinic of Cluj-Napoca in the last 10 years were selected for this study from the hospital database. Results. PRF treatment proved to be a reliable method to help heal the necrotic bone sites. High-ASA risk patients and immunosuppressed patients are more prone to recurrence and persistent signs and symptoms. Intravenous bisphosphonates produce more intense symptomatology compared to oral administration. The posterior mandible is more difficult to treat compared to other sites. Conclusions. The quality of life of MRONJ and ORN patients may be improved by a protocol that reduces pain and hospitalization.
A Comparison between 2-Octyl Cyanoacrylate and Conventional Suturing for the Closure of Epiblepharon Incision Wounds in Children: A Retrospective Case–Control Study
Authors: Hsu Chia-Chen , Lee Lung-Chi , Chang Hsu-Chieh , Chen Yi-Hao , Hsieh Meng-Wei , Chien Ke-Hung
Published: June 2024

Background: Tissue adhesive has been widely used in ophthalmic surgery for various procedures, proving both effective and safe. However, no studies have compared the surgical efficacy of the tissue adhesive 2-octyl cyanoacrylate (SurgiSeal®) to that of traditional suture closure in Asian children undergoing surgery for lower lid epiblepharon. Methods: This is a single-center retrospective case-control study. Surgical correction for epiblepharon was performed on 22 patients from November 2019 to May 2023. A total of 20 patients who were followed up for at least 1 month were included for analysis. After standardized epiblepharon surgery, group A underwent wound closure with a subcuticular suture and 2-octyl cyanoacrylate, and group B underwent closure with a 6-O fast-absorbing surgical gut suture. Patients were followed up at 1, 4, and 12 weeks post-surgery. Results: A total of 10 patients (20 eyes) underwent skin closure with tissue adhesives (group A), and 10 patients (18 eyes) underwent wound closure using conventional suture material (group B). No significant differences in the sex ratio, mean age at operation, pre- and postoperative best-corrected visual acuity (BCVA), or average surgical time were observed between groups. Both groups exhibited improved postoperative BCVA, with symptom relief and a significant decrease in the severity of keratopathy after surgery. Neither recurrence nor complications were reported during follow-up. The aesthetic results were similar between groups, while caregivers of children in the tissue adhesive group expressed high satisfaction regarding the ease of postoperative care. Conclusions: Successful closure of lower lid epiblepharon surgery wounds in children can be performed using 2-octyl cyanoacrylate (SurgiSeal®). This method is simple, safe, and effective when compared to conventional sutures.
Complexity and Diversity of the Neurological Spectrum of SARS-CoV-2 over Three Waves of COVID-19
Authors: Jachman-Kapułka Justyna , Zińczuk Aleksander , Szymański Wojciech , Simon Krzysztof , Rorat Marta
Published: June 2024

Background/Objectives: SARS-CoV-2 continually mutates, with five identified variants. Many neurological manifestations were observed during the COVID-19 pandemic, with differences between virus variants. The aim of this study is to assess the frequency and characteristics of neurological manifestations during COVID-19 in hospitalized patients over three waves in Poland with comparison and analysis correlation with the course of infection. Methods: This retrospective single-center study included 600 consecutive adults with confirmed COVID-19, hospitalized during 3 waves (pre-Delta, Delta and Omicron) in Poland. Demographic and clinical information and neurological manifestations were collected and compared across three periods. Results: The median age of the study group was 68, lower during the Delta wave. In the Omicron period, the disease severity at admission and inflammatory markers concentration were the lowest. Neurological manifestations were observed in 49%. The most common were altered mentation, headache, myalgia, mood disorder, ischemic stroke and encephalopathy. Smell and taste disturbances (STDs) were less frequent in the Omicron period. Neurological complications were predominant in the pre-Delta and Omicron periods. Ischemic stroke was observed more often in pre-Delta period. Altered mentation was related to higher severity at admission, worse lab test results, higher admission to ICU and mortality, while headache reduced mortality. Pre-existing dementia was related to higher mortality. Conclusions: Neurological manifestations of COVID-19 are frequent, with a lower rate of STDs in the Omicron period and more often cerebrovascular diseases in the pre-Delta period. Headache improves the course of COVID-19, while altered mentation, stroke and neurological comorbidities increase severity and mortality.
Tissue Iron Distribution in Anemic Patients with End-Stage Kidney Disease: Results of a Pilot Study
Authors: Lanser Lukas , Plaikner Michaela , Fauser Josia , Petzer Verena , Denicolò Sara , Haschka David , Neuwirt Hannes , Stefanow Kiril , Rudnicki Michael , Kremser Christian , Henninger Benjamin , Weiss Guenter
Published: June 2024

Background/Objectives: Anemia is a frequent multifactorial co-morbidity in end-stage kidney disease (ESKD) associated with morbidity and poor QoL. Apart from insufficient erythropoietin formation, iron deficiency (ID) contributes to anemia development. Identifying patients in need of iron supplementation with current ID definitions is difficult since no good biomarker is available to detect actual iron needs. Therefore, new diagnostic tools to guide therapy are needed. Methods: We performed a prospective cohort study analyzing tissue iron content with MRI-based R2*-relaxometry in 20 anemic ESKD patients and linked it with iron biomarkers in comparison to 20 otherwise healthy individuals. Results: ESKD patients had significantly higher liver (90.1 s−1 vs. 36.1 s−1, p < 0.001) and spleen R2* values (119.8 s−1 vs. 19.3 s−1, p < 0.001) compared to otherwise healthy individuals, while their pancreas and heart R2* values did not significantly differ. Out of the 20 ESKD patients, 17 had elevated spleen and 12 had elevated liver R2* values. KDIGO guidelines (focusing on serum iron parameters) would recommend iron supplementation in seven patients with elevated spleen and four patients with elevated liver R2* values. Conclusions: These findings highlight that liver and especially spleen iron concentrations are significantly higher in ESKD patients compared to controls. Tissue iron overload diverged from classical iron parameters suggesting need of iron supplementation. Measurement of MRI-guided tissue iron distribution might help guide treatment of anemic ESKD patients.
Comparison of Nefopam-Based Patient-Controlled Analgesia with Opioid-Based Patient-Controlled Analgesia for Postoperative Pain Management in Immediate Breast Reconstruction Surgery: A Randomized Controlled Trial
Authors: Huh Jaewon , Lee Noori , Kim Minju , Choi Hoon , Oh Deuk Young , Choi Jangyoun , Hwang Wonjung
Published: June 2024

Background/Objectives: Immediate breast reconstruction surgery (BRS) often leads to significant postoperative pain, necessitating effective analgesia. This study aimed to compare the analgesic efficacy of patient-controlled analgesia (PCA) containing nefopam with that of PCA containing opioids alone in patients undergoing BRS. Methods: A prospective, double-blind, randomized controlled trial was conducted on 120 patients undergoing immediate BRS after mastectomy. Patients were randomly allocated to receive PCA with fentanyl alone (Group F: fentanyl 10 mcg/kg), fentanyl and nefopam (Group FN: fentanyl 5 mcg/kg + nefopam 1 mg/kg), or nefopam alone (Group N: nefopam 2 mg/kg). Pain intensity (expressed in VASr and VASm), opioid consumption, and opioid-related complications were assessed. Results: PCA with nefopam, either alone or in combination with opioids, demonstrated non-inferior analgesic efficacy compared to PCA with fentanyl alone. At 24 h postoperatively, the VASr scores were 2.9 ± 1.0 in Group F, 3.1 ± 1.2 in Group FN, and 2.8 ± 0.9 in Group N (p = 0.501). At the same timepoint, the VASm scores were 4.1 ± 1.2 in Group F, 4.5 ± 1.5 in Group FN, and 3.8 ± 1.4 in Group N (p = 0.129). Significant differences among the three groups were observed at all timepoints except for PACU in terms of the total opioid consumption (p < 0.0001). However, there were no significant differences in opioid-related complications among the three groups. Conclusions: PCA with nefopam, whether alone or in combination with opioids, offers non-inferior analgesic efficacy compared to PCA with fentanyl alone in patients undergoing immediate BRS.
Is Oral Microflora Related to Development of Malfunction in Patients Using Voice Prosthesis?
Authors: Immordino Angelo , Dispenza Francesco , Sireci Federico , Anzalone Riccardo , Immordino Palmira , Calà Cinzia , Gallina Salvatore , Lorusso Francesco
Published: June 2024

Background: this prospective study investigated the correlation between the oral bacterial microflora and the microflora found in voice prostheses (VPs) among 20 patients who had undergone laryngectomy. The aim was to explore the associations between the microflora’s presence and the malfunction of VPs, along with the association between the predominant microorganism and the longevity of VPs. Methods: the research process included gathering medical histories, conducting ENT examinations, replacing VPs, and performing check-ups every four months for a period of 15.5 months. Additionally, microbiological examinations, blood tests, and voice change surveys were conducted. Results: a correlation between the microflora isolated from VPs and that from oral rinses was demonstrated in a large percentage of patients who experienced a loss of prosthetic functional efficiency. The correlation analysis between the type of microorganism and the lifespan of VPs showed a non-significant Pearson correlation coefficient (r = 0.043, p = 0.678). Conclusions: there is no significant linear correlation between the predominant microorganism and the average lifespan of VPs.
Maritime Security and Risk Assessments
Authors: Perkovič Marko , Gucma Lucjan , Feuerstack Sebastian
Published: June 2024

The main topics of the presented papers focus on various aspects of maritime operations and security, including anomaly detection in maritime traffic, collision risk assessment, and the use of Automatic Identification System (AIS) data for enhancing maritime safety and surveillance. These papers cover a wide range of subjects within the maritime domain, such as trajectory clustering, kinematic behaviour analysis, Bayesian networks for risk assessment, resilience analysis of shipping networks, and the development of novel methods for detecting abnormal maritime behaviour. The emphasis is on using data-driven approaches, statistical methodologies, and advanced technologies to improve maritime operations and security.