bluuebunny/crossref_metadata_2025 huggingface dataset:
Macrophages Orchestrate Airway Inflammation, Remodeling, and Resolution in Asthma
Authors: Britt Rodney D. , Ruwanpathirana Anushka , Ford Maria L. , Lewis Brandon W.
Published: June 2023

Asthma is a heterogenous chronic inflammatory lung disease with endotypes that manifest different immune system profiles, severity, and responses to current therapies. Regardless of endotype, asthma features increased immune cell infiltration, inflammatory cytokine release, and airway remodeling. Lung macrophages are also heterogenous in that there are separate subsets and, depending on the environment, different effector functions. Lung macrophages are important in recruitment of immune cells such as eosinophils, neutrophils, and monocytes that enhance allergic inflammation and initiate T helper cell responses. Persistent lung remodeling including mucus hypersecretion, increased airway smooth muscle mass, and airway fibrosis contributes to progressive lung function decline that is insensitive to current asthma treatments. Macrophages secrete inflammatory mediators that induce airway inflammation and remodeling. Additionally, lung macrophages are instrumental in protecting against pathogens and play a critical role in resolution of inflammation and return to homeostasis. This review summarizes current literature detailing the roles and existing knowledge gaps for macrophages as key inflammatory orchestrators in asthma pathogenesis. We also raise the idea that modulating inflammatory responses in lung macrophages is important for alleviating asthma.
Comparative Proteomic Analysis of Toxoplasma gondii RH Wild-Type and Four SRS29B (SAG1) Knock-Out Clones Reveals Significant Differences between Individual Strains
Authors: Hänggeli Kai Pascal Alexander , Hemphill Andrew , Müller Norbert , Heller Manfred , Uldry Anne-Christine , Braga-Lagache Sophie , Müller Joachim , Boubaker Ghalia
Published: June 2023

In T. gondii, as well as in other model organisms, gene knock-out using CRISPR-Cas9 is a suitable tool to identify the role of specific genes. The general consensus implies that only the gene of interest is affected by the knock-out. Is this really the case? In a previous study, we generated knock-out (KO) clones of TgRH88_077450 (SRS29B; SAG1) which differed in the numbers of the integrated dihydrofolate-reductase-thymidylate-synthase (MDHFR-TS) drug-selectable marker. Clones 18 and 33 had a single insertion of MDHFR-TS within SRS29B. Clone 6 was disrupted by the insertion of a short unrelated DNA-sequence, but the marker was integrated elsewhere. In clone 30, the marker was inserted into SRS29B, and several other MDHFR-TS copies were found in the genome. KO and wild-type (WT) tachyzoites had similar shapes, dimensions, and vitality. This prompted us to investigate the impact of genetic engineering on the overall proteome patterns of the four clones as compared to the respective WT. Comparative shotgun proteomics of the five strains was performed. Overall, 3236 proteins were identified. Principal component analysis of the proteomes revealed five distinct clusters corresponding to the five strains by both iTop3 and iLFQ algorithms. Detailed analysis of the differentially expressed proteins revealed that the target of the KO, srs29B, was lacking in all KO clones. In addition to this protein, 20 other proteins were differentially expressed between KO clones and WT or between different KO clones. The protein exhibiting the highest variation between the five strains was srs36D encoded by TgRH_016110. The deregulated expression of SRS36D was further validated by quantitative PCR. Moreover, the transcript levels of three other selected SRS genes, namely SRS36B, SRS46, and SRS57, exhibited significant differences between individual strains. These results indicate that knocking out a given gene may affect the expression of other genes. Therefore, care must be taken when specific phenotypes are regarded as a direct consequence of the KO of a given gene.
Laboratory Findings and Biomarkers in Long COVID: What Do We Know So Far? Insights into Epidemiology, Pathogenesis, Therapeutic Perspectives and Challenges
Authors: Tsilingiris Dimitrios , Vallianou Natalia G. , Karampela Irene , Christodoulatos Gerasimos Socrates , Papavasileiou Georgios , Petropoulou Dimitra , Magkos Faidon , Dalamaga Maria
Published: June 2023

Long COVID (LC) encompasses a constellation of long-term symptoms experienced by at least 10% of people after the initial SARS-CoV-2 infection, and so far it has affected about 65 million people. The etiology of LC remains unclear; however, many pathophysiological pathways may be involved, including viral persistence; a chronic, low-grade inflammatory response; immune dysregulation and a defective immune response; the reactivation of latent viruses; autoimmunity; persistent endothelial dysfunction and coagulopathy; gut dysbiosis; hormonal and metabolic dysregulation; mitochondrial dysfunction; and autonomic nervous system dysfunction. There are no specific tests for the diagnosis of LC, and clinical features including laboratory findings and biomarkers may not specifically relate to LC. Therefore, it is of paramount importance to develop and validate biomarkers that can be employed for the prediction, diagnosis and prognosis of LC and its therapeutic response, although this effort may be hampered by challenges pertaining to the non-specific nature of the majority of clinical manifestations in the LC spectrum, small sample sizes of relevant studies and other methodological issues. Promising candidate biomarkers that are found in some patients are markers of systemic inflammation, including acute phase proteins, cytokines and chemokines; biomarkers reflecting SARS-CoV-2 persistence, the reactivation of herpesviruses and immune dysregulation; biomarkers of endotheliopathy, coagulation and fibrinolysis; microbiota alterations; diverse proteins and metabolites; hormonal and metabolic biomarkers; and cerebrospinal fluid biomarkers. At present, there are only two reviews summarizing relevant biomarkers; however, they do not cover the entire umbrella of current biomarkers, their link to etiopathogenetic mechanisms or the diagnostic work-up in a comprehensive manner. Herein, we aim to appraise and synopsize the available evidence on the typical laboratory manifestations and candidate biomarkers of LC, their classification based on pathogenetic mechanisms and the main LC symptomatology in the frame of the epidemiological and clinical aspects of the syndrome and furthermore assess limitations and challenges as well as potential implications in candidate therapeutic interventions.
LC-MS/MS-Based Serum Metabolomics and Transcriptome Analyses for the Mechanism of Augmented Renal Clearance
Authors: Wang Yidan , Luo Yifan , Yang Shu , Jiang Mingyan , Chu Yang
Published: June 2023

Augmented Renal Clearance (ARC) refers to the increased renal clearance of circulating solute in critically ill patients. In this study, the analytical research method of transcriptomics combined with metabolomics was used to study the pathogenesis of ARC at the transcriptional and metabolic levels. In transcriptomics, 534 samples from 5 datasets in the Gene Expression Omnibus database were analyzed and 834 differential genes associated with ARC were obtained. In metabolomics, we used Ultra-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry to determine the non-targeted metabolites of 102 samples after matching propensity scores, and obtained 45 differential metabolites associated with ARC. The results of the combined analysis showed that purine metabolism, arginine biosynthesis, and arachidonic acid metabolism were changed in patients with ARC. We speculate that the occurrence of ARC may be related to the alteration of renal blood perfusion by LTB4R, ARG1, ALOX5, arginine and prostaglandins E2 through inflammatory response, as well as the effects of CA4, PFKFB2, PFKFB3, PRKACB, NMDAR, glutamate and cAMP on renal capillary wall permeability.
Editorial: Chronic Inflammation and Related Diseases: From Mechanisms to Therapies
Authors: Kang Suk-Yun , Ryu Yeonhee
Published: June 2023

The purpose of this Special Issue is to identify the exact mechanism underlying inflammation to direct more effective strategies for inflammation management and to provide basic data for the development of anti-inflammatory and analgesic treatment methods for patients with inflammatory pain [...]
Analysis of the Mutational Landscape of Osteosarcomas Identifies Genes Related to Metastasis and Prognosis and Disrupted Biological Pathways of Immune Response and Bone Development
Authors: Pires Sara Ferreira , Barros Juliana Sobral de , Costa Silvia Souza da , Carmo Gabriel Bandeira do , Scliar Marília de Oliveira , Lengert André van Helvoort , Boldrini Érica , Silva Sandra Regini Morini da , Vidal Daniel Onofre , Maschietto Mariana , Krepischi Ana Cristina Victorino
Published: June 2023

Osteosarcoma (OS) is the most prevalent type of bone tumor, but slow progress has been achieved in disentangling the full set of genomic events involved in its initiation and progression. We assessed by NGS the mutational spectrum of 28 primary OSs from Brazilian patients, and identified 445 potentially deleterious SNVs/indels and 1176 copy number alterations (CNAs). TP53 was the most recurrently mutated gene, with an overall rate of ~60%, considering SNVs/indels and CNAs. The most frequent CNAs (~60%) were gains at 1q21.2q21.3, 6p21.1, and 8q13.3q24.22, and losses at 10q26 and 13q14.3q21.1. Seven cases presented CNA patterns reminiscent of complex events (chromothripsis and chromoanasynthesis). Putative RB1 and TP53 germline variants were found in five samples associated with metastasis at diagnosis along with complex genomic patterns of CNAs. PTPRQ, KNL1, ZFHX4, and DMD alterations were prevalent in metastatic or deceased patients, being potentially indicative of poor prognosis. TNFRSF11B, involved in skeletal system development and maintenance, emerged as a candidate for osteosarcomagenesis due to its biological function and a high frequency of copy number gains. A protein–protein network enrichment highlighted biological pathways involved in immunity and bone development. Our findings reinforced the high genomic OS instability and heterogeneity, and led to the identification of novel disrupted genes deserving further evaluation as biomarkers due to their association with poor outcomes.
Protonation-State Dependence of Hydration and Interactions in the Two Proton-Conducting Channels of Cytochrome c Oxidase
Authors: Gorriz Rene F. , Volkenandt Senta , Imhof Petra
Published: June 2023

Cytochrome c Oxidase (CcO), a membrane protein of the respiratory chain, pumps protons against an electrochemical gradient by using the energy of oxygen reduction to water. The (“chemical”) protons required for this reaction and those pumped are taken up via two distinct channels, named D-channel and K-channel, in a step-wise and highly regulated fashion. In the reductive phase of the catalytic cycle, both channels transport protons so that the pumped proton passes the D-channel before the “chemical” proton has crossed the K-channel. By performing molecular dynamics simulations of CcO in the O→E redox state (after the arrival of the first reducing electron) with various combinations of protonation states of the D- and K-channels, we analysed the effect of protonation on the two channels. In agreement with previous work, the amount of water observed in the D-channel was significantly higher when the terminal residue E286 was not (yet) protonated than when the proton arrived at this end of the D-channel and E286 was neutral. Since a sufficient number of water molecules in the channel is necessary for proton transport, this can be understood as E286 facilitating its own protonation. K-channel hydration shows an even higher dependence on the location of the excess proton in the K-channel. Also in agreement with previous work, the K-channel exhibits a very low hydration level that likely hinders proton transfer when the excess proton is located in the lower part of the K-channel, that is, on the N-side of S365. Once the proton has passed S365 (towards the reaction site, the bi-nuclear centre (BNC)), the amount of water in the K-channel provides hydrogen-bond connectivity that renders proton transfer up to Y288 at the BNC feasible. No significant direct effect of the protonation state of one channel on the hydration level, hydrogen-bond connectivity, or interactions between protein residues in the other channel could be observed, rendering proton conductivity in the two channels independent of each other. Regulation of the order of proton uptake and proton passage in the two channels such that the “chemical” proton leaves its channel last must, therefore, be achieved by other means of communication, such as the location of the reducing electron.
Extracellular Vesicles in Phylogeny
Authors: Lange Sigrun
Published: June 2023

Extracellular vesicles (EVs) are cell-derived lipid vesicles in a size range of 20–1000 nm; often, these are classified as smaller and larger EVs in the literature or also commonly called small EVs (“exosomes”) and medium/large EVs (“microvesicles”) [...]
The Review of Current Knowledge on Neutrophil Gelatinase-Associated Lipocalin (NGAL)
Authors: Romejko Katarzyna , Markowska Magdalena , Niemczyk Stanisław
Published: June 2023

Neutrophil gelatinase-associated lipocalin (NGAL) is a 25-kDa protein that is secreted mostly by immune cells such as neutrophils, macrophages, and dendritic cells. Its production is stimulated in response to inflammation. The concentrations of NGAL can be measured in plasma, urine, and biological fluids such as peritoneal effluent. NGAL is known mainly as a biomarker of acute kidney injury and is released after tubular damage and during renal regeneration processes. NGAL is also elevated in chronic kidney disease and dialysis patients. It may play a role as a predictor of the progression of renal function decreases with complications and mortality due to kidney failure. NGAL is also useful in the diagnostic processes of cardiovascular diseases. It is highly expressed in injured heart tissue and atherosclerostic plaque; its serum concentrations correlate with the severity of heart failure and coronary artery disease. NGAL increases inflammatory states and its levels rise in arterial hypertension, obesity, diabetes, and metabolic complications such as insulin resistance, and is also involved in carcinogenesis. In this review, we present the current knowledge on NGAL and its involvement in different pathologies, especially its role in renal and cardiovascular diseases.
Clearance and Utilization of Dicarbonyl-Modified LDL in Monkeys and Humans
Authors: Lankin Vadim Z. , Konovalova Galina G. , Domogatsky Sergey P. , Tikhaze Alla K. , Klots Igor N. , Ezhov Marat V.
Published: June 2023

The kinetics of elimination of various dicarbonyl-modified low-density lipoproteins from the bloodstream of Macaca mulatta monkeys were investigated. The low-density lipoproteins (LDL) in the monkey blood plasma were isolated by density gradient ultracentrifugation and labeled in vitro with the fluorescent dye FITC; thereupon, they were modified with different natural low molecular-weight dicarbonyls: malondialdehyde (MDA), glyoxal, or methylglyoxal. The control native FITC-labeled LDL and dicarbonyl-modified FITC-labeled LDL were injected into the monkey’s ulnar vein; thereafter, blood samples were taken at fixed time intervals during 24 h. The plasma level of FITC-labeled LDL was determined with spectrofluorimetry. The study established that glyoxal- and monkeysglyoxal-labeled LDL circulated in monkey virtually at the same time as native (non-modified) LDL. In contrast, MDA-modified LDL disappeared from the blood extremely rapidly. Administration of the PCSK9 inhibitor involocumab (which increases LDL utilization) to patients with coronary heart disease (CHD) was found to significantly reduce levels of MDA-modified LDL.
Important Lessons on Long-Term Stability of Amino Acids in Stored Dried Blood Spots
Authors: Dijkstra Allysa M. , de Blaauw Pim , van Rijt Willemijn J. , Renting Hanneke , Maatman Ronald G. H. J. , van Spronsen Francjan J. , Maase Rose E. , Schielen Peter C. J. I. , Derks Terry G. J. , Heiner-Fokkema M. Rebecca
Published: June 2023

Residual heel prick Dried Blood Spots (DBS) are valuable samples for retrospective investigation of inborn metabolic diseases (IMD) and biomarker analyses. Because many metabolites suffer time-dependent decay, we investigated the five-year stability of amino acids (AA) in residual heel prick DBS. In 2019/2020, we analyzed 23 AAs in 2170 residual heel prick DBS from the Dutch neonatal screening program, stored from 2013–2017 (one year at +4 °C and four years at room temperature), using liquid chromatography mass-spectrometry. Stability was assessed by AA changes over the five years. Hydroxyproline could not be measured accurately and was not further assessed. Concentrations of 19 out of the remaining 22 AAs degraded significantly, ranked from most to least stable: aspartate, isoleucine, proline, valine, leucine, tyrosine, alanine, phenylalanine, threonine, citrulline, glutamate, serine, ornithine, glycine, asparagine, lysine, taurine, tryptophan and glutamine. Arginine, histidine and methionine concentrations were below the limit of detection and were likely to have been degraded within the first year of storage. AAs in residual heel prick DBS stored at room temperature are subject to substantial degradation, which may cause incorrect interpretation of test results for retrospective biomarker studies and IMD diagnostics. Therefore, retrospective analysis of heel prick blood should be done in comparison to similarly stored heel prick blood from controls.
“Who Should I Trust with My Data?” Ethical and Legal Challenges for Innovation in New Decentralized Data Management Technologies
Authors: Asgarinia Haleh , Chomczyk Penedo Andres , Esteves Beatriz , Lewis Dave
Published: June 2023

News about personal data breaches or data abusive practices, such as Cambridge Analytica, has questioned the trustworthiness of certain actors in the control of personal data. Innovations in the field of personal information management systems to address this issue have regained traction in recent years, also coinciding with the emergence of new decentralized technologies. However, only with ethically and legally responsible developments will the mistakes of the past be avoided. This contribution explores how current data management schemes are insufficient to adequately safeguard data subjects, and in particular, it focuses on making these data flows transparent to provide an adequate level of accountability. To showcase this, and with the goal of enhancing transparency to foster trust, this paper investigates solutions for standardizing machine-readable policies to express personal data processing activities and their application to decentralized personal data stores as an example of ethical, legal, and technical responsible innovation in this field.
Ensemble System of Deep Neural Networks for Single-Channel Audio Separation
Authors: Al-Kaltakchi Musab T. S. , Mohammad Ahmad Saeed , Woo Wai Lok
Published: June 2023

Speech separation is a well-known problem, especially when there is only one sound mixture available. Estimating the Ideal Binary Mask (IBM) is one solution to this problem. Recent research has focused on the supervised classification approach. The challenge of extracting features from the sources is critical for this method. Speech separation has been accomplished by using a variety of feature extraction models. The majority of them, however, are concentrated on a single feature. The complementary nature of various features have not been thoroughly investigated. In this paper, we propose a deep neural network (DNN) ensemble architecture to completely explore the complimentary nature of the diverse features obtained from raw acoustic features. We examined the penultimate discriminative representations instead of employing the features acquired from the output layer. The learned representations were also fused to produce a new features vector, which was then classified by using the Extreme Learning Machine (ELM). In addition, a genetic algorithm (GA) was created to optimize the parameters globally. The results of the experiments showed that our proposed system completely considered various features and produced a high-quality IBM under different conditions.
Spatial Knowledge Acquisition for Pedestrian Navigation: A Comparative Study between Smartphones and AR Glasses
Authors: Lakehal Aymen , Lepreux Sophie , Efstratiou Christos , Kolski Christophe , Nicolaou Pavlos
Published: June 2023

Smartphone map-based pedestrian navigation is known to have a negative effect on the long-term acquisition of spatial knowledge and memorisation of landmarks. Landmark-based navigation has been proposed as an approach that can overcome such limitations. In this work, we investigate how different interaction technologies, namely smartphones and augmented reality (AR) glasses, can affect the acquisition of spatial knowledge when used to support landmark-based pedestrian navigation. We conducted a study involving 20 participants, using smartphones or augmented reality glasses for pedestrian navigation. We studied the effects of these systems on landmark memorisation and spatial knowledge acquisition over a period of time. Our results show statistically significant differences in spatial knowledge acquisition between the two technologies, with the augmented reality glasses enabling better memorisation of landmarks and paths.
Miticidal Tools for Management of Southern Red Mites Infesting Southern Highbush Blueberries
Authors: Lopez Lorena , Liburd Oscar E.
Published: June 2023

Tetranychid outbreaks have been detected since 2016 in southern highbush blueberries (SHB); however, it was not until 2019 that the southern red mite (SRM), Oligonychus ilicis (Acari: Tetranychidae) was confirmed as the pest causing severe bronzing and stunting, in multiple Florida and Georgia commercial blueberry plantings. To date, only three miticides (fenazaquin, fenpyroximate, and acequinocyl) have been registered for use in SHB and there are no clear guidelines on how to manage SRM in SHB. Similarly, there is no knowledge regarding the existence of natural enemies of SRM in SHB. This is the first report of naturally occurring predatory mites (Amblyseius sp. and Neoseiulus ilicis) associated with SRM in SHB. Predatory mites were recorded in blueberry bushes after treatment with seven miticides used to suppress SRM populations including spiromesifen, acequinocyl, sulfur, sulfur + molasses, bifenazate, fenpyroximate, and fenazaquin. The number of SRM recorded per leaf and averaged plant damage ratings (0 = no bronzing–4 = 100% bronzing) were used to evaluate miticide efficacy. Additionally, the presence or absence of predatory mites per sample was recorded. Fenpyroximate used as the standard miticide, significantly reduced mite numbers seven days after application, as well as acequinocyl and fenazaquin. Fenpyroximate and fenazaquin demonstrated the best performance for managing O. ilicis on SHB and treated bushes demonstrated significantly less bronzing compared with the control plants. These miticides were also safe to naturally occurring predatory mites. Lastly, the level of growers’ awareness regarding SRM was assessed using surveys in 2020 to design adequate educational materials available to the grower community.
Percutaneous Vertebral Reconstruction (PVR) Technique of Pathological Compression Fractures: An Innovative Combined Treatment of Microwave Ablation, Bilateral Expandable Titanium SpineJack Implants Followed by Vertebroplasty
Authors: Pusceddu Claudio , Marsico Salvatore , Derudas Daniele , Ballicu Nicola , Melis Luca , Zedda Stefano , de Felice Carlo , Calabrese Alessandro , De Francesco Davide , Venturini Massimo , Santucci Domiziana , Faiella Eliodoro
Published: June 2023

(1) Background: to retrospectively evaluate safety and efficacy of combined microwave ablation (MWA) and bilateral expandable titanium SpineJack (SJ) implants followed by vertebroplasty (VP) for the treatment of painful thoracolumbar pathological vertebral compression fracture. (2) Methods: from July 2017 to October 2022, twenty-eight patients (13 women and 15 men; mean age 68 ± 11 years) with a history of primary neoplasm and thirty-six painful vertebral metastases with vertebral compression fracture underwent combined MWA and bilateral expandable titanium SpineJack implants with vertebroplasty. We analyzed safety through complications rate, and efficacy through vertebral height restoration and pain decrease, evaluated using a visual analogue scale (VAS), and Functional Mobility Scale (FMS), and local tumor control. Contrast-enhanced CT scans were performed at 1, 3, and 6 months and a contrast-enhanced spine MRI at 6 months after the procedure. (3) Results: Technical success rate was 100%. No procedure-related major complications or death occurred. Vertebral height restoration was observed in 22 levels (58%), with a mean anterior height restoration of 2.6 mm ± 0.6 and a mean middle height restoration of 4.4 mm ± 0.6 (p < 0.001). Mean VAS score of pain evaluation on the day before treatment was 6.3 ± 1.5 (range 4–9). At the 6-month evaluation, the median VAS score for pain was 0.4 ± 0.6 (range 0–2) with a mean reduction of 93.65% (6.8 ± 0.7 vs. 0.4 ± 0.6; p < 0.000) compared with baseline evaluation. Contrast-enhanced CT scans were performed at 1, 3, and 6 months and a contrast-enhanced spine MRI was performed at 6 months after the procedure, showing no local recurrence, implant displacement, or new fractures in the treated site. (4) Conclusions: combined microwave ablation and bilateral expandable titanium SpineJack implants with vertebroplasty is a safe and effective procedure for the treatment of pathological compressive vertebral fractures. The vertebral stabilization achieved early and persistent pain relief, increasing patient mobility, improving recovery of walking capacity, and providing local tumor control.
Outcomes of Social Egg Freezing: A Cohort Study and a Comprehensive Literature Review
Authors: Kakkar Pragati , Geary Joanna , Stockburger Tania , Kaffel Aida , Kopeika Julia , El-Toukhy Tarek
Published: June 2023

The purpose of this study is to evaluate the live birth outcome following oocyte thaw in women who underwent social egg freezing at Guy’s Hospital, alongside a detailed published literature review to compare published results with the current study. A retrospective cohort study was conducted between January 2016 and March 2022 for all women who underwent egg freezing during this period. Overall, 167 women had 184 social egg freezing cycles. The mean age at freeze was 37.1 years and an average of 9.5 eggs were frozen per retrieval. In total, 16% of the women returned to use their frozen eggs. The mean egg thaw survival rate post egg thaw was 74%. The mean egg fertilisation rate was 67%. The pregnancy rate achieved per embryo transfer was 48% and the live birth rate per embryo transfer was 35%. We also noted that irrespective of age at freezing, a significantly high live birth rate was achieved when the number of eggs frozen per patient was 15 or more. Despite the rapid increase in social egg freezing cycles, the utilisation rate remains low. Pregnancy and live birth rate post thaw are encouraging if eggs are frozen at a younger age and if 15 eggs or more were frozen per patient.
Caregivers’ Expectations on Possible Functional Changes following Disease-Modifying Treatment in Type II and III Spinal Muscular Atrophy: A Comparative Study
Authors: Pera Maria , Coratti Giorgia , Casiraghi Jacopo , Bravetti Chiara , Fedeli Alessandro , Strika Milija , Albamonte Emilio , Antonaci Laura , Rossi Diletta , Pane Marika , Sansone Valeria , Mercuri Eugenio
Published: June 2023

Background: The primary aim of this study was to explore current caregivers’ expectations on possible functional changes following treatment in comparison to data obtained in the pre-pharmacological era. Methods: A questionnaire, previously used in 2016, was administered to caregivers of type II and III SMA patients of age between 3 and 71 years, and to patients over the age of 13 years. The questionnaire focuses on (1) caregivers and patients expectations, (2) meaningfulness of the changes observed on the functional motor scales, and (3) their willingness to be enrolled in a clinical trial. A comparative study was performed with data obtained using the same questionnaire soon before the advent of disease-modifying therapies. Results: We administered the questionnaire to 150 caregivers. When comparing current caregiver data to those obtained in 2016, the most obvious differences were related to disease perception over the last year (stability: 16.5% in 2016 vs. 43.6% in 2022; deterioration 70.5% vs. 12.8%, and improvement: 12.9% vs. 43.6%) and expectations from clinical trials with higher expectations in 2022 compared to 2016 (p < 0.001). Forty-five of the 150 in the current study were caregivers of patients above the age of 13. In these 45 the questionnaire was also administered to the patient. No difference was found in responses between patients and their caregivers. Conclusions: Both carers and patients reported that even small changes on functional scales, similar to those reported by clinical studies and real-world data, are perceived as meaningful. Comparing the recent responses to those obtained in 2016, before pharmacological treatment was available, we found significant changes in caregivers’ perception with increased expectations. These findings will provide a better understanding of the patients’ expectations and facilitate discussion with regulators.
The EUPEMEN (EUropean PErioperative MEdical Networking) Protocol for Bowel Obstruction: Recommendations for Perioperative Care
Authors: Ioannidis Orestis , Ramirez Jose M. , Ubieto Javier Martínez , Feo Carlo V. , Arroyo Antonio , Kocián Petr , Sánchez-Guillén Luis , Bellosta Ana Pascual , Whitley Adam , Enguita Alejandro Bona , Teresa Marta , Anestiadou Elissavet
Published: June 2023

Mechanical bowel obstruction is a common symptom for admission to emergency services, diagnosed annually in more than 300,000 patients in the States, from whom 51% will undergo emergency laparotomy. This condition is associated with serious morbidity and mortality, but it also causes a high financial burden due to long hospital stay. The EUPEMEN project aims to incorporate the expertise and clinical experience of national clinical specialists into development of perioperative rehabilitation protocols. Providing special recommendations for all aspects of patient perioperative care and the participation of diverse specialists, the EUPEMEN protocol for bowel obstruction, as presented in the current paper, aims to provide faster postoperative recovery and reduce length of hospital stay, postoperative morbidity and mortality rate.
Endometriosis, Oocyte, and Embryo Quality
Authors: Latif Sania , Saridogan Ertan
Published: June 2023

Endometriosis is a common finding among women with infertility, and women who are diagnosed with endometriosis are almost twice as likely to experience infertility. Mechanisms by which endometriosis causes infertility remain poorly understood. In this review, we evaluate the current literature on the impact of endometriosis on oocyte and embryo quality. The presence of endometriosis evidently reduces ovarian reserve, oocyte quality, and embryo quality; however, this does not appear to translate to a clear clinical impact. Analysis of data from large assisted reproduction technology registries has shown that women with endometriosis have a lower oocyte yield but no reduction in reproductive outcomes. There is a need for future studies in the form of well-designed randomized controlled trials to further evaluate the role of surgical and medical treatment options in women with endometriosis undergoing assisted conception.
Vaginal Cuff Dehiscence: Two Case Reports and a Review of the Literature
Authors: Jaime Moens Babette , Buonomo Antonino , De Sutter Philippe
Published: June 2023

Vaginal cuff dehiscence (VCD) is a rare but serious condition associated with high morbidity, especially in the presence of an evisceration. It usually occurs as a complication of hysterectomy, but has also been reported after other pelvic surgeries. In this article, we will present two cases of vaginal cuff dehiscence with evisceration in post-menopausal patients. Both cases occurred post-operatively, the first after a laparoscopic radical hysterectomy and the other after a trachelectomy performed by robotic-assisted laparoscopy (with a prior history of subtotal hysterectomy). Both cases were treated surgically, the first by a combined laparoscopic and vaginal approach, and the second case only by laparoscopic approach. The main risk and protective factors are discussed in a narrative literature review which summarizes the available evidence on this rare condition, discussed by type of study designs and thus evidence level. A laparoscopic vaginal cuff closure is the most protective factor in preventing VCD, compared to a vaginal closure. Clinicians should be aware of this condition and of its risk factors and precipitating events in order to identify high-risk patients. Knowledge of these allows prompt recognition, which is crucial for adequate management, for which multiple approaches have been described.
Investigation of the Influence of Roughness and Dental Implant Design on Primary Stability via Analysis of Insertion Torque and Implant Stability Quotient: An In Vitro Study
Authors: Romero Marta , Herrero-Climent Mariano , Ríos-Carrasco Blanca , Brizuela Aritza , Romero Manuel María , Gil Javier
Published: June 2023

In the placement of dental implants, the primary fixation between the dental implant and the bone is of great importance and corresponds to compressive mechanical fixation that aims to prevent micromovement of the implant. The aim of this research was to determine the role of roughness and the type of dental implant (tissue-level or bone-level) in implant stability, measured using resonance frequency analysis (RFA) and insertion torque (IT). We analyzed 234 titanium dental implants, placed in fresh calf ribs, at the half-tissue level and half-bone level. The implant surface was subjected to grit-blasting treatments with alumina particles of 120, 300, and 600 μm at a projection pressure of 2.5 bar, resulting in three types of roughness. Roughness was determined via optical interferometry. The wettability of the surfaces was also determined. Implant stability was measured using a high-precision torquemeter to obtain IT, and RFA was used to determine the implant stability quotient (ISQ). The results show that rough surfaces with Sa values of 0.5 to 4 μm do not affect the primary stability. However, the type of implant is important; bone-level implants obtained the highest primary stability values. A good correlation between the primary stability values obtained via IT and ISQ was demonstrated. New in vivo studies are necessary to know whether these results can be maintained in the long term.
Serum Malondialdehyde-Oxidized Low-Density Lipoprotein Level Is Associated with Arterial Stiffness by Cardio-Ankle Vascular Index in Coronary Artery Bypass Graft Patients
Authors: Hung Ting , Jhan Jin-You , Lin Jian-Hong , Yang Kun-Ta , Hsu Bang-Gee , Chang Jui-Chih
Published: June 2023

A high malondialdehyde-oxidized low-density lipoprotein (MDA-oxLDL) level is associated with atherosclerotic cardiovascular diseases and major adverse cardiovascular events. A higher cardio-ankle vascular index (CAVI) is independently associated with an increased risk of cardiovascular events, cardiovascular mortality, myocardial infarction, and stroke in patients with cardiovascular risk. Thus, this study aimed to evaluate the relationship between serum MDA-oxLDL levels and CAVI in patients with triple-vessel coronary artery disease who underwent coronary artery bypass graft (CABG) surgery. Fasting blood samples and baseline characteristics were obtained from 88 patients who had undergone CABG. A commercialized enzyme-linked immunosorbent assay was used to measure MDA-oxLDL levels. An automatic pulse wave analyzer was used to measure CAVI values, and each side of CAVI values of ≥9 was designated as arterial stiffness. In total, 47 participants were assigned to the arterial stiffness group. More patients had diabetes mellitus, were older, and had higher serum MDA-oxLDL levels in the arterial stiffness group than in the control group. A multivariate logistic regression analysis disclosed that MDA-oxLDL and diabetes mellitus were independent predictors of arterial stiffness. Moreover, according to the Spearman’s correlation analysis, the serum MDA-oxLDL level was positively associated with both left and right CAVI. Serum MDA-oxLDL levels were positively associated with arterial stiffness in patients who had undergone CABG.
Phenomenological Considerations of the World of the Obsessive Patient
Authors: Demaria Francesco , Pontillo Maria , Bellantoni Domenica , Di Vincenzo Cristina , Vicari Stefano
Published: June 2023

Despite significant scientific advances in research on obsessive-compulsive disorder (OCD), the psychological and behavioral symptoms of this pathological condition remain hard to understand, until they seem paradoxical. The present work seeks to consider the significance and potential contribution of a phenomenological reading of OCD and how phenomenalism has influenced some cognitive models of this disorder. Transcendental phenomenology is a philosophical approach that attaches primary importance to intuitive experience and considers all phenomena intrinsically associated with the subject’s inner world. Thus, the subject’s intuition is considered the starting point for understanding their essential experience. This approach has had a profound influence on modern cognitive sciences. Among current cognitive models, post-rationalist cognitivism and cognitive neuropsychological psychotherapy seem most effective in capturing the world experiences of OCD patients. Both apply a phenomenological approach to identify these experiences, which are typically characterized by hyper-reflexivity, at the expense of ‘natural evidence.’ The models have found that OCD patients experience the world emotionally as a sterile set of rules, and this experience determines their suffering.
Assessment of Frontal Hemispherical Lateralization in Plaque Psoriasis and Atopic Dermatitis
Authors: Bozsányi Szabolcs , Czurkó Natália , Becske Melinda , Kasek Roland , Lázár Botond Keve , Boostani Mehdi , Meznerics Fanni Adél , Farkas Klára , Varga Noémi Nóra , Gulyás Lili , Bánvölgyi András , Fehér Bence Ágoston , Fejes Emese , Lőrincz Kende , Kovács Anikó , Gergely Hunor , Takács Szabolcs , Holló Péter , Kiss Norbert , Wikonkál Norbert , Lázár Imre
Published: June 2023

Background: Each brain hemisphere plays a specialized role in cognitive and behavioral processes, known as hemispheric lateralization. In chronic skin diseases, such as plaque psoriasis (Pso) and atopic dermatitis (AD), the degree of lateralization between the frontal hemispheres may provide insight into specific connections between skin diseases and the psyche. This study aims to analyze the hemispherical lateralization, neurovegetative responses, and psychometric characteristics of patients with Pso and AD. Methods: The study included 46 patients with Pso, 56 patients with AD, and 29 healthy control (Ctrl) subjects. The participants underwent frontal electroencephalogram (EEG) measurement, heart rate variability (HRV) assessment, and psychological tests. Statistical analyses were performed using ANOVA, with Bonferroni correction applied for multiple comparisons. Results: This study shows a significant right-lateralized prefrontal activity in both AD patients (p < 0.001) and Pso patients (p = 0.045) compared with Ctrl, with no significant difference between the AD and Pso groups (p = 0.633). AD patients with right-hemispheric dominant prefrontal activation exhibited increased inhibition and avoidance markers, while Pso patients showed elevated sympathetic nervous system activity. Conclusion: Psychophysiological and psychometric data suggest a shared prevalence of right-hemispheric dominance in both AD and Pso patient groups. However, the findings indicate distinct psychodermatological mechanisms in AD and Pso.
The Biology of Chronic Pain and Its Implications for Pain Neuroscience Education: State of the Art
Authors: Zimney Kory , Van Bogaert Wouter , Louw Adriaan
Published: June 2023

Pain is an individualized experience for the person suffering from chronic pain. Significant strides have been made in the last few decades in understanding various biological changes that coincide with chronic pain. This state-of-the-art overview looks at the current evidence related to the biology of chronic pain and the implications these findings have on the delivery of pain neuroscience education (PNE). The paper summarizes the various (epi)genetic, neural, endocrine, and immune factors discovered and explored in the scientific literature concerning chronic pain. Each of these biological factors has various implications for the content and delivery of PNE. We discuss the future directions these biological factors have for the clinical implementation of PNE by linking the importance of behavior change, optimizing the learning environment, and using an individualized multimodal treatment approach with PNE. In addition, future directions for research of PNE based on these biological factors are provided with importance placed on individualized patient-centered care and how PNE can be used with traditional modes of care and growing trends with other care methods. PNE was originally and continues to be rooted in understanding chronic pain biology and how that understanding can improve patient care and outcomes.
Cu-Doped Porous ZnO-ZnAl2O4 Nanocomposites Synthesized by Polymer-Salt Method for Photocatalytic Water Purification
Authors: Shelemanov Andrey , Tincu Artem , Evstropiev Sergey , Nikonorov Nikolay , Vasilyev Vladimir
Published: June 2023

In this work, the adsorption and photocatalytic properties of ZnO-ZnAl2O4-CuO nanosized porous composites synthesized by the polymer-salt method have been studied. To evaluate the efficiency of adsorption, experiments were carried out on the decolorization of aqueous solutions of the Chicago Sky Blue diazo dye. The adsorption process is divided into two stages, at the first stage, the dye is rapidly adsorbed on the outer surface of the composite particles (kf = 0.0073 min−1), at the second stage, the dye diffuses into the pores of the material (kf = 0.0007 min−1). It was noted that the rate of photocatalytic decomposition of the dye (kf = 0.021 min−1) is higher than the rate of the adsorption process, which indicates the occurrence of photocatalytic decomposition of dye molecules both on the surface of the composites and in the liquid phase. With an increase in the light intensity, the photocatalytic process is significantly accelerated, linearly at low intensities, and at high intensities (I > 100 mW/cm2) the dependence becomes a power law.
Plant Gel-Mediated Synthesis of Gold-Coated Nanoceria Using Ferula gummosa: Characterization and Estimation of Its Cellular Toxicity toward Breast Cancer Cell Lines
Authors: Mousavi-Kouhi Seyed Mousa , Beyk-Khormizi Abdollah , Amiri Mohammad Sadegh , Mashreghi Mohammad , Hashemzadeh Alireza , Mohammadzadeh Vahideh , Alavi Fariba , Mottaghipisheh Javad , Sarafraz Ardakani Mohammad Reza , Taghavizadeh Yazdi Mohammad Ehsan
Published: June 2023

In this study, a novel method using Ferula gummosa gums as a capping agent was used to synthesize the nanoceria for the first time. The method was economical and performed at room temperature. Furthermore, it was coated with gold (Au/nanoceria) and fully characterized using X-ray powder diffraction (XRD), field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy (FESEM-EDX), Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and zeta potential (ζ potential). The crystallite size obtained from the results was 28.09 nm for Au/nanoceria. The energy-dispersive X-ray spectroscopy (EDX) analysis of Au/nanoceria revealed the compositional constituents of the product, which display the purity of the Au/nanoceria. The cell toxicity properties of the non-doped and Au-coated nanoceria were identified by a MTT analysis on a breast cancer cell line (MCF7). Additionally, human foreskin fibroblast cells (HFF) were used as a normal cell line. The cytotoxicity results indicated that the toxicological effect of Au/nanoceria on cancer cells was significant while having little toxic effect on normal cells. The toxicity effect of nanoceria clearly shows the dependence on dose and time, so, with increasing the dose of Au/nanoceria, the death of cancer cells also increases.
Quantifying the Displacement of Data Matrix Code Modules: A Comparative Study of Different Approximation Approaches for Predictive Maintenance of Drop-on-Demand Printing Systems
Authors: Bischoff Peter , Carreiro André V. , Schuster Christiane , Härtling Thomas
Published: June 2023

Drop-on-demand printing using colloidal or pigmented inks is prone to the clogging of printing nozzles, which can lead to positional deviations and inconsistently printed patterns (e.g., data matrix codes, DMCs). However, if such deviations are detected early, they can be useful for determining the state of the print head and planning maintenance operations prior to reaching a printing state where the printed DMCs are unreadable. To realize this predictive maintenance approach, it is necessary to accurately quantify the positional deviation of individually printed dots from the actual target position. Here, we present a comparison of different methods based on affinity transformations and clustering algorithms for calculating the target position from the printed positions and, subsequently, the deviation of both for complete DMCs. Hence, our method focuses on the evaluation of the print quality, not on the decoding of DMCs. We compare our results to a state-of-the-art decoding algorithm, adopted to return the target grid positions, and find that we can determine the occurring deviations with significantly higher accuracy, especially when the printed DMCs are of low quality. The results enable the development of decision systems for predictive maintenance and subsequently the optimization of printing systems.
Effect of the Added Acyl Homoserine Lactones on Separated Free-Living Marine Bacteria as a Model of Quorum Sensing
Authors: Schultz Gary E. , Santschi Peter H.
Published: June 2023

Quorum sensing is a communication system by which bacteria use signal molecules to induce a physiological response. In natural marine environments, quorum sensing is suspected to occur in regions with high cell densities. Free-living bacteria, however, are largely believed to exist at concentrations too low to make use of a density-dependent quorum-sensing system. Due to so-called ‘free-living’ bacteria inhabiting marine gels composed of exopolymeric substances occurring in an operationally defined colloidal fraction, it is possible that quorum-sensing molecules would also occur in this fraction. In this study, possible signaling molecules were collected from marine water, separated, and concentrated as some organic matter. Their identification with an Agrobacterium tumefaciens assay indicated the presence of AHLs. In fall 2002 and spring 2003, free-living (single cells) fraction of marine bacterioplankton was sampled and separated. Various AHLs were added to these disperse populations (109 cells/L). The studied bacterial communities responded with change in the thymidine incorporation. The results are discussed as existence of active reaction of marine free-living bacteria to signaling molecules even in sparse inhabiting marine gels. That there is a bacterial response to signaling molecules in so sparse populations is of great significance for marine and environmental sciences.