bluuebunny/crossref_metadata_2025 huggingface dataset:
Decelerated Epigenetic Aging in Long Livers
Authors: Guvatova Zulfiya G. , Kobelyatskaya Anastasiya A. , Pudova Elena A. , Tarasova Irina V. , Kudryavtseva Anna V. , Tkacheva Olga N. , Strazhesko Irina D. , Moskalev Alexey A.
Published: November 2023

Epigenetic aging is a hot topic in the field of aging research. The present study estimated epigenetic age in long-lived individuals, who are currently actively being studied worldwide as an example of successful aging due to their longevity. We used Bekaert’s blood-based age prediction model to estimate the epigenetic age of 50 conditionally “healthy” and 45 frail long-livers over 90 years old. Frailty assessment in long-livers was conducted using the Frailty Index. The control group was composed of 32 healthy individuals aged 20–60 years. The DNA methylation status of 4 CpG sites (ASPA CpG1, PDE4C CpG1, ELOVL2 CpG6, and EDARADD CpG1) included in the epigenetic clock was assessed through pyrosequencing. According to the model calculations, the epigenetic age of long-livers was significantly lower than their chronological age (on average by 21 years) compared with data from the group of people aged 20 to 60 years. This suggests a slowing of epigenetic and potentially biological aging in long livers. At the same time, the obtained results showed no statistically significant differences in delta age (difference between the predicted and chronological age) between “healthy” long livers and long livers with frailty. We also failed to detect sex differences in epigenetic age either in the group of long livers or in the control group. It is possible that the predictive power of epigenetic clocks based on a small number of CpG sites is insufficient to detect such differences. Nevertheless, this study underscores the need for further research on the epigenetic status of centenarians to gain a deeper understanding of the factors contributing to delayed aging in this population.
The Role H-Bonding and Supramolecular Structures in Homogeneous and Enzymatic Catalysis
Authors: Matienko Ludmila I. , Mil Elena M. , Albantova Anastasia A. , Goloshchapov Alexander N.
Published: November 2023

The article analyzes the role of hydrogen bonds and supramolecular structures in enzyme catalysis and model systems. Hydrogen bonds play a crucial role in many enzymatic reactions. However, scientists have only recently attempted to harness the power of hydrogen bonds in homogeneous catalytic systems. One of the newest directions is associated with attempts to control the properties of catalysts by influencing the “second coordination sphere” of metal complexes. The role H-bonding, and the building of stable supramolecular nanostructures due to intermolecular H-bonds, based on catalytic active heteroligand iron (Fe) or nickel (Ni) complexes formed during hydrocarbon oxidations were assessed via the AFM (Atomic-force microscopy) method, which was proposed and applied by authors of this manuscript. Th is article also discusses the roles of hydrogen bonds and supramolecular structures in oxidation reactions catalyzed by heteroligand Ni and Fe complexes, which are not only effective homogeneous catalysts but also structural and functional models of Oxygenases.
Alterations in Rat Hippocampal Glutamatergic System Properties after Prolonged Febrile Seizures
Authors: Griflyuk Alexandra V. , Postnikova Tatyana Y. , Malkin Sergey L. , Zaitsev Aleksey V.
Published: November 2023

Febrile seizures during early childhood may result in central nervous system developmental disorders. However, the specific mechanisms behind the impact of febrile seizures on the developing brain are not well understood. To address this gap in knowledge, we employed a hyperthermic model of febrile seizures in 10-day-old rats and tracked their development over two months. Our objective was to determine the degree to which the properties of the hippocampal glutamatergic system are modified. We analyzed whether pyramidal glutamatergic neurons in the hippocampus die after febrile seizures. Our findings indicate that there is a reduction in the number of neurons in various regions of the hippocampus in the first two days after seizures. The CA1 field showed the greatest susceptibility, and the reduction in the number of neurons in post-FS rats in this area appeared to be long-lasting. Electrophysiological studies indicate that febrile seizures cause a reduction in glutamatergic transmission, leading to decreased local field potential amplitude. This impairment could be attributable to diminished glutamate release probability as evidenced by decreases in the frequency of miniature excitatory postsynaptic currents and increases in the paired-pulse ratio of synaptic responses. We also found higher threshold current causing hind limb extension in the maximal electroshock seizure threshold test of rats 2 months after febrile seizures compared to the control animals. Our research suggests that febrile seizures can impair glutamatergic transmission, which may protect against future seizures.
Connexins Control Glial Inflammation in Various Neurological Diseases
Authors: Yamasaki Ryo
Published: November 2023

Connexins (Cxs) form gap junctions through homotypic/heterotypic oligomerization. Cxs are initially synthesized in the endoplasmic reticulum, then assembled as hexamers in the Golgi apparatus before being integrated into the cell membrane as hemichannels. These hemichannels remain closed until they combine to create gap junctions, directly connecting neighboring cells. Changes in the intracellular or extracellular environment are believed to trigger the opening of hemichannels, creating a passage between the inside and outside of the cell. The size of the channel pore depends on the Cx isoform and cellular context-specific effects such as posttranslational modifications. Hemichannels allow various bioactive molecules, under ~1 kDa, to move in and out of the host cell in the direction of the electrochemical gradient. In this review, we explore the fundamental roles of Cxs and their clinical implications in various neurological dysfunctions, including hereditary diseases, ischemic brain disorders, degenerative conditions, demyelinating disorders, and psychiatric illnesses. The influence of Cxs on the pathomechanisms of different neurological disorders varies depending on the circumstances. Hemichannels are hypothesized to contribute to proinflammatory effects by releasing ATP, adenosine, glutamate, and other bioactive molecules, leading to neuroglial inflammation. Modulating Cxs’ hemichannels has emerged as a promising therapeutic approach.
Towards a Long-Read Sequencing Approach for the Molecular Diagnosis of RPGRORF15 Genetic Variants
Authors: Bonetti Gabriele , Cozza William , Bernini Andrea , Kaftalli Jurgen , Mareso Chiara , Cristofoli Francesca , Medori Maria Chiara , Colombo Leonardo , Martella Salvatore , Staurenghi Giovanni , Salvetti Anna Paola , Falsini Benedetto , Placidi Giorgio , Attanasio Marcella , Pertile Grazia , Bengala Mario , Bosello Francesca , Petracca Antonio , D’Esposito Fabiana , Toschi Benedetta , Lanzetta Paolo , Ricci Federico , Viola Francesco , Marceddu Giuseppe , Bertelli Matteo
Published: November 2023

Sequencing of the low-complexity ORF15 exon of RPGR, a gene correlated with retinitis pigmentosa and cone dystrophy, is difficult to achieve with NGS and Sanger sequencing. False results could lead to the inaccurate annotation of genetic variants in dbSNP and ClinVar databases, tools on which HGMD and Ensembl rely, finally resulting in incorrect genetic variants interpretation. This paper aims to propose PacBio sequencing as a feasible method to correctly detect genetic variants in low-complexity regions, such as the ORF15 exon of RPGR, and interpret their pathogenicity by structural studies. Biological samples from 75 patients affected by retinitis pigmentosa or cone dystrophy were analyzed with NGS and repeated with PacBio. The results showed that NGS has a low coverage of the ORF15 region, while PacBio was able to sequence the region of interest and detect eight genetic variants, of which four are likely pathogenic. Furthermore, molecular modeling and dynamics of the RPGR Glu-Gly repeats binding to TTLL5 allowed for the structural evaluation of the variants, providing a way to predict their pathogenicity. Therefore, we propose PacBio sequencing as a standard procedure in diagnostic research for sequencing low-complexity regions such as RPGRORF15, aiding in the correct annotation of genetic variants in online databases.
AhR and CYP1B1 Control Oxygen Effects on Bone Marrow Progenitor Cells: The Enrichment of Multiple Olfactory Receptors as Potential Microbiome Sensors
Authors: Larsen Michele C. , Rondelli Catherine M. , Almeldin Ahmed , Song Yong-Seok , N’Jai Alhaji , Alexander David L. , Forsberg E. Camilla , Sheibani Nader , Jefcoate Colin R.
Published: November 2023

Polycyclic aromatic hydrocarbon (PAH) pollutants and microbiome products converge on the aryl hydrocarbon receptor (AhR) to redirect selective rapid adherence of isolated bone marrow (BM) cells. In young adult mice, Cyp1b1-deficiency and AhR activation by PAH, particularly when prolonged by Cyp1a1 deletion, produce matching gene stimulations in these BM cells. Vascular expression of Cyp1b1 lowers reactive oxygen species (ROS), suppressing NF-κB/RelA signaling. PAH and allelic selectivity support a non-canonical AhR participation, possibly through RelA. Genes stimulated by Cyp1b1 deficiency were further resolved according to the effects of Cyp1b1 and Cyp1a1 dual deletions (DKO). The adherent BM cells show a cluster of novel stimulations, including select developmental markers; multiple re-purposed olfactory receptors (OLFR); and α-Defensin, a microbial disruptor. Each one connects to an enhanced specific expression of the catalytic RNA Pol2 A subunit, among 12 different subunits. Mesenchymal progenitor BMS2 cells retain these features. Cyp1b1-deficiency removes lymphocytes from adherent assemblies as BM-derived mesenchymal stromal cells (BM-MSC) expand. Cyp1b1 effects were cell-type specific. In vivo, BM-MSC Cyp1b1 expression mediated PAH suppression of lymphocyte progenitors. In vitro, OP9-MSC sustained these progenitors, while Csf1 induced monocyte progenitor expansion to macrophages. Targeted Cyp1b1 deletion (Cdh5-Cre; Cyp1b1fl/fl) established endothelium control of ROS that directs AhR-mediated suppression of B cell progenitors. Monocyte Cyp1b1 deletion (Lyz2-Cre; Cyp1b1fl/fl) selectively attenuated M1 polarization of expanded macrophages, but did not enhance effects on basal M2 polarization. Thus, specific sources of Cyp1b1 link to AhR and to an OLFR network to provide BM inflammatory modulation via diverse microbiome products.
Mediating Effect of Stress Recognition on the Effect of Generalized Anxiety Disorder on Smartphone Dependence
Authors: Lee Se Ryeon , Kim Eun-Yeob , Ha Seunghan , Kim Jaeyoung
Published: November 2023

The widespread adoption of the smartphone has led to both positive and negative consequences for adolescents’ mental health. This study examines the interplay between smartphone dependence (SPD), generalized anxiety disorder (GAD), and various mental health outcomes among Korean adolescents. Data from the 16th Adolescence Health Behavior Survey (2020), including 54,948 middle and high school students, were analyzed. Adolescents were categorized into three groups based on SPD severity. The GAD-7 scale assessed anxiety, and other factors such as subjective health recognition, happiness, weight control efforts, and body mass index (BMI) were considered. Adolescents with higher SPD exhibited lower academic performance, decreased happiness, and increased perception of stress. GAD levels were positively correlated with SPD, with higher SPD linked to more severe GAD symptoms. Additionally, higher SPD was associated with increased loneliness, sadness, and suicidal thoughts, plans, and attempts as well as a greater likelihood of habitual drug use. Gender differences revealed that females were more prone to sadness, hopelessness, and suicidal thoughts, while males exhibited higher rates of drug use. This study highlights the complex relationship between SPD, GAD, and mental health outcomes among Korean adolescents. Stress recognition was found to mediate the association between GAD and SPD. The process-macro result of the total effect between SPD on GAD and the direct effect of the SPD pathway on GAD was significant; thus, the stress recognition was mediated. Effective interventions should target stress management, especially among adolescents with high smartphone dependence, to mitigate the risk of mental health issues. These findings underscore the importance of addressing smartphone dependence and its impact on the mental well-being of adolescents.
Multivisceral Resection for Locally Advanced Gastric Cancer: A Systematic Review and Evidence Quality Assessment
Authors: Schizas Dimitrios , Giannakodimos Ilias , Mylonas Konstantinos S. , Kapetanakis Emmanouil I. , Papavgeri Alexandra , Lianos Georgios D. , Dellaportas Dionysios , Mastoraki Aikaterini , Alexandrou Andreas
Published: November 2023

Patients with locally advanced gastric cancer (LAGC) often require multivisceral resection (MVR) of the involved organs to achieve R0 resection and local disease control. The aim of the present study was to systematically review all available literature on the postoperative and long-term outcomes of MVR for gastric cancer. The PubMed database was systematically searched by two independent investigators for studies concerning MVR for LAGC. In total, 30 original studies with 3362 patients met our inclusion criteria. R0 resection was achieved in 67.77% (95% CI, 65.75–69.73%) of patients. The spleen, colon and pancreas comprised the most frequently resected organs in the context of MVR. Pancreatic fistulae (10.08%, 95% CI, 7.99–12.63%), intraabdominal abscesses (9.92%, 95% CI, 7.85–12.46%) and anastomotic leaks (8.09%, 95% CI, 6.23–10.45%) constituted the most common postoperative complications. Using the available data, we estimated the mean 1-year survival at 62.2%, 3-year survival at 33.05%, and 5-year survival at 30.21% for the entire cohort. The survival rates were mainly correlated with lymphatic invasion, tumor size and patient age. Therefore, gastrectomy, together with MVR, is feasible and may offer a survival advantage compared to gastrectomy alone or no other surgical treatment in a selected group of patients. Consequently, both patient and tumor characteristics should be carefully assessed to optimize candidate selection.
Splanchnic Vein Thrombosis in Inflammatory Bowel Disease: An Observational Study from the ENEIDA Registry and Systematic Review
Authors: Puig Maria , Masnou Helena , Mesonero Francisco , Menchén Luís , Bujanda Luís , Castro Jesús , González-Partida Irene , Vicente Raquel , González-Muñoza Carlos , Iborra Marisa , Sierra Mónica , Huguet José María , García María José , De Francisco Ruth , García-Alonso Francisco Javier , Mañosa Míriam , Domènech Eugeni ,   on behalf of ENEIDA-GETECCU Registry
Published: November 2023

Background: Thromboembolic events are frequent among patients with inflammatory bowel disease (IBD). However, there is little information on the prevalence, features and outcomes of splanchnic vein thrombosis (SVT) in patients with IBD. Aims: To describe the clinical features and outcomes of SVT in patients with IBD and to perform a systematic review of these data with published cases and series. Methods: A retrospective observational study from the Spanish nationwide ENEIDA registry was performed. A systematic search of the literature was performed to identify studies with at least one case of SVT in IBD patients. Results: A new cohort of 49 episodes of SVT from the Eneida registry and 318 IBD patients with IBD identified from the literature review (sixty studies: two multicentre, six single-centre and fifty-two case reports or case series) were analysed. There was a mild predominance of Crohn’s disease and the most frequent clinical presentation was abdominal pain with or without fever followed by the incidental finding in cross-sectional imaging techniques. The most frequent SVT location was the main portal trunk in two-thirds of the cases, followed by the superior mesenteric vein. Anticoagulation therapy was prescribed in almost 90% of the cases, with a high rate of radiologic resolution of SVT. Thrombophilic conditions other than IBD itself were found in at least one-fifth of patients. Conclusions: SVT seems to be a rare (or underdiagnosed) complication in IBD patients. SVT is mostly associated with disease activity and evolves suitably when anticoagulation therapy is started.
The Incidence, Impact, and Techniques of Commissural Alignment in Transcatheter Aortic Valve Implantation: A Review
Authors: Paredes-Vazquez Jose G. , Tirado-Conte Gabriela , Shabbir Asad , Mon-Noboa Matias , Chavez Jorge F. , Nuñez-Gil Ivan , Jimenez-Quevedo Pilar , Pozo-Osinalde Eduardo , Gomez de Diego Jose Juan , Salinas Pablo , Mejia-Renteria Hernan , Macaya Fernando , de Agustin-Loeches Jose Alberto , Gonzalo Nieves , Escaned Javier , Fernandez-Ortiz Antonio , Nombela-Franco Luis
Published: November 2023

In current clinical practice, commissural alignment of the transcatheter heart valve (THV) during transcatheter aortic valve implantation (TAVI) is seldom achieved. Orientation of the THV within the aortic root and the subsequent influence upon leaflet haemodynamic function, coronary blood flow, and ease of access to the coronary ostia are gaining significant interest. Herein, we review the incidence and clinical implications of commissural misalignment in TAVI and offer thorough descriptions of how optimal alignment can be achieved with several different contemporary THV devices.
Developing New Strategies for Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Authors: Gonzalez Barca Eva
Published: November 2023

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and biologically heterogeneous disease. Approximately 40% of patients with DLBCL will experience disease relapse or will be refractory to first-line chemo immunotherapy. In recent years, there have been several new therapeutic agents approved for the treatment of relapsed/refractory (R/R) DLBCL. These agents include anti-CD19 chimeric antigen receptor T-cell (CAR T-cell) and monoclonal antibody therapies such as polatuzumab and tafasitamab. Nevertheless, despite the high efficacy of all these new therapies, there are still patients who do not respond or relapse, representing an unmet clinical need. This review describes new promising therapies that are in clinical development to treat R/R DLBCL.
The Dose Optimization and Evaluation of Image Quality in the Adult Brain Protocols of Multi-Slice Computed Tomography: A Phantom Study
Authors: Prabsattroo Thawatchai , Wachirasirikul Kanokpat , Tansangworn Prasit , Punikhom Puengjai , Sudchai Waraporn
Published: November 2023

Computed tomography examinations have caused high radiation doses for patients, especially for CT scans of the brain. This study aimed to optimize the radiation dose and image quality in adult brain CT protocols. Images were acquired using a Catphan 700 phantom. Radiation doses were recorded as CTDIvol and dose length product (DLP). CT brain protocols were optimized by varying parameters such as kVp, mAs, signal-to-noise ratio (SNR) level, and Clearview iterative reconstruction (IR). The image quality was also evaluated using AutoQA Plus v.1.8.7.0 software. CT number accuracy and linearity had a robust positive correlation with the linear attenuation coefficient (µ) and showed more inaccurate CT numbers when using 80 kVp. The modulation transfer function (MTF) showed a higher value in 100 and 120 kVp protocols (p < 0.001), while high-contrast spatial resolution showed a higher value in 80 and 100 kVp protocols (p < 0.001). Low-contrast detectability and the contrast-to-noise ratio (CNR) tended to increase when using high mAs, SNR, and the Clearview IR protocol. Noise decreased when using a high radiation dose and a high percentage of Clearview IR. CTDIvol and DLP were increased with increasing kVp, mAs, and SNR levels, while the increasing percentage of Clearview did not affect the radiation dose. Optimized protocols, including radiation dose and image quality, should be evaluated to preserve diagnostic capability. The recommended parameter settings include kVp set between 100 and 120 kVp, mAs ranging from 200 to 300 mAs, SNR level within the range of 0.7–1.0, and an iterative reconstruction value of 30% Clearview to 60% or higher.
Recognizing Instantaneous Group Patterns in Vessel Trajectory Data: A Snapshot Perspective
Authors: Zhang Xiang , Zhou Yuchuan , Li Lianying
Published: November 2023

Recognizing vessel navigation patterns plays a vital role in understanding maritime traffic behaviors, managing and planning vessel activities, spotting outliers, and predicting traffic. However, the growth in trajectory data and the complexity of maritime traffic in recent years presents formidable challenges to this endeavor. Existing approaches predominantly adopt a ‘trajectory perspective’, where the instantaneous behaviors of vessel groups (e.g., the homing of fishing vessels) that occurred at certain times are concealed in the massive trajectories. To bridge this gap and to reveal collective patterns and behaviors, we look at vessel patterns and their dynamics at only individual points in time (snapshots). In particular, we propose a recognition framework from the snapshot perspective, mixing ingredients from group dynamics, computational geometry, graph theory, and visual perception theory. This framework encompasses algorithms for detecting basic types of patterns (e.g., collinear, curvilinear, and flow) and strategies to combine the results. Case studies were carried out using vessel trajectory (AIS) data around the Suez Canal and other areas. We show that the proposed methodology outperformed DBSCAN and clustering by measuring local direction centrality (CDC) in recognizing fine-grained vessel groups that exhibit more cohesive behaviors. Our results find interesting collective behaviors such as convoy, turning, avoidance, mooring (in open water), and berthing (in the dock), and also reveal abnormal behaviors. Such results can be used to better monitor, manage, understand, and predict maritime traffic and/or conditions.
A Pre-Procession Module for Point-Based Deep Learning in Dense Point Clouds in the Ship Engineering Field
Authors: Huo Shilin , Liu Yujun , Wang Ji , Li Rui , Liu Xiao , Shi Jiawei
Published: November 2023

Recently, point cloud technology has been applied in the ship engineering field. However, the dense point cloud acquired by terrestrial laser scanning (TLS) technology in ship engineering applications brings an obstacle to some powerful and advanced point-based deep learning point cloud processing methods. This paper presents a deep learning pre-procession module to ensure the feasibility of processing dense point clouds on commonly available computer devices. The pre-procession module is designed according to the traditional point cloud processing methods and the PointNet++ paradigm, and is evaluated on two ship structure datasets and two popular point cloud datasets. Experimental results illustrate that (i) the proposed module improves the performance of point-based deep learning semantic segmentation networks, and (ii) the proposed module empowers the existing point-based deep learning networks with the capability to process dense input point clouds. The proposed module may provide a useful semantic segmentation tool for realistic dense point clouds in various industrial applications.
The Role of Adjuvant Systemic and Intravitreal Corticosteroids in Fungal Endophthalmitis Treatment
Authors: Azhari Jamal , Tetelbom Pedro S. , Sallam Ahmed B.
Published: November 2023

Endophthalmitis refers to inflammation involving internal ocular structures, including the anterior and posterior eye segments, associated with infectious agents, most commonly bacteria and fungi. This review focuses on endophthalmitis caused by fungi. Medical and surgical management are the two main treatment modalities for fungal endophthalmitis, with medical management utilizing systemic or intravitreal antifungals. The use of systemic or intravitreal corticosteroids as an adjuvant treatment to dampen the severity of inflammation is controversial. Based on the pathobiology of fungal endophthalmitis as well as the mechanism of action of corticosteroids, it was hypothesized that corticosteroids affected the immune response against fungal infection. In vitro studies mostly carried out during the 1980s showed that dexamethasone plays a role in the suppression of phagocytosis of yeasts and demonstrated the facilitation of yeast proliferation by dexamethasone. In vivo studies analysis was compromised entirely of retrospective studies describing steroid use in fungal endophthalmitis, with the outcomes of the patients in these studies varying greatly and often being anecdotally noted, thus difficult to discern any definitive results. Given the limited clinical data and the heterogeneity of the existing studies, additional experimentation human studies with clinical trials or observations over more extended periods analyzing the effect of systemic and intravitreal corticosteroids in fungal endophthalmitis are needed before definitive conclusions can be drawn.
Additions to Diatrypaceae (Xylariales): Novel Taxa and New Host Associations
Authors: Afshari Naghmeh , Karimi Omid , Gomes de Farias Antonio R. , Suwannarach Nakarin , Bhunjun Chitrabhanu S. , Zeng Xiang-Yu , Lumyong Saisamorn
Published: November 2023

Diatrypaceae members have a broad distribution and are commonly found on decaying wood. Despite taxonomic and morphological challenges within this group, there has been a growing interest in Diatrypaceae in recent years. The dead branches of several plant hosts with fungal fruiting bodies were collected from Doi Tung National Park, Chiang Rai, and the Narathiwat Provinces in Thailand. Their morphological characteristics, coupled with a molecular phylogeny of combined ITS and tub2 sequence data, were used to introduce two novel Allodiatrype species (A. dalbergiae and A. eleiodoxae) and one new Melanostictus species (M. chiangraiensis). Moreover, four new host records, Diatrypella heveae, D. major, Melanostictus thailandicus, and Paraeutypella citricola on Microcos paniculata, Nayariophyton zizyphifolium, Dalbergia cultrata, and M. paniculata, respectively, as well as a new geographical record of D. major are reported. This research provides detailed descriptions of macro- and microcharacteristics, coupled with a phylogenetic tree for the newly introduced species and host records. The morphological features of Allodiatrype and Melanostictus are listed in the synoptic table.
Do Tumor SURVIVIN and MDM2 Expression Levels Correlate with Treatment Response and Clinical Outcome in Isolated Limb Perfusion for In-Transit Cutaneous Melanoma Metastases?
Authors: Russano Francesco , Del Fiore Paolo , Cassalia Fortunato , Benna Clara , Dall’Olmo Luigi , Rastrelli Marco , Mocellin Simone
Published: November 2023

Isolated limb perfusion (ILP) involves the local administration of high doses of anticancer drugs into a limb affected by unresectable locally advanced tumors (with special regard to in-transit melanoma metastases), minimizing systemic side effects. Tumor response to anticancer drugs may depend on the expression of apoptosis-related genes, such as SURVIVIN and MDM2. This retrospective cohort study investigated the association between tumor SURVIVIN and MDM2 expression levels and treatment response or clinical outcomes in patients undergoing ILP for in-transit melanoma metastases. The study cohort consisted of 62 patients with in-transit metastases who underwent ILP with tumor necrosis factor (TNF) and melphalan. Tissue samples were taken from the in-transit metastases, and RNA was extracted for gene expression analysis. Patients’ response to treatment was assessed using clinical and radiological criteria two months after ILP, and disease response was classified as complete, partial, or stable/progressive disease. Disease-free survival (DFS) and overall survival (OS) were also analyzed. Expression of SURVIVIN and/or MDM2 was observed in 48% of patients; in these cases, complete response to ILP occurred in 40% of cases, with the overall response rate (complete + partial) being 85%. Patients with expression of MDM2 alone had a lower complete response rate (28%), while patients with expression of SURVIVIN alone had a higher complete response rate (50%). The combined expression of MDM2 and SURVIVIN resulted in a complete response rate of 30%. Patients without expression (of SURVIVIN or MDM2) had the highest complete response rate (58%). Survival analysis showed that high MDM2 expression was independently associated with a lower probability of a complete response to ILP. In addition, patients with MDM2 expression were three times more likely to have an incomplete response to ILP. This study highlights the importance of considering SURVIVIN and MDM2 expression in patients undergoing ILP for in-transit cutaneous melanoma metastases. High MDM2 expression was found to be an independent factor associated with a reduced likelihood of achieving a complete response to ILP, suggesting potential mechanisms of chemoresistance. These data support further research to explore the role of already available targeted therapies (i.e., MDM2 inhibitors) in improving tumor response to ILP in patients with in-transit melanoma metastases.
Virtual Surgical Planning and Patient-Specific Instruments for Correcting Lower Limb Deformities in Pediatric Patients: Preliminary Results from the In-Office 3D Printing Point of Care
Authors: Trisolino Giovanni , Depaoli Alessandro , Menozzi Grazia Chiara , Lerma Luca , Di Gennaro Michele , Quinto Carmelo , Vivarelli Leonardo , Dallari Dante , Rocca Gino
Published: November 2023

(1) Background: Virtual reality and 3D printing are transforming orthopedic surgery by enabling personalized three-dimensional (3D) models for surgical planning and Patient-Specific Instruments (PSIs). Hospitals are establishing in-house 3D printing centers to reduce costs and improve patient care. Pediatric orthopedic surgery also benefits from these technologies, enhancing the precision and personalization of treatments. This study presents preliminary results of an In-Office 3D Printing Point of Care (PoC), outlining considerations and challenges in using this program for treating lower limb deformities in pediatric patients through Virtual Surgical Planning (VSP) and 3D-printed Patient-Specific Instruments (PSIs). (2) Materials and Methods: Pediatric patients with congenital or acquired lower limb deformities undergoing surgical correction based on VSP, incorporating 3D-printed PSIs when required, were included in this study. The entire process of VSP and 3D printing at the In-Office PoC was illustrated. Data about deformity characteristics, surgical procedures, and outcomes, including the accuracy of angular correction, surgical times, and complications, were reported. (3) Results: In total, 39 bone correction procedures in 29 patients with a mean age of 11.6 ± 4.7 years (range 3.1–18.5 years) were performed according to VSP. Among them, 23 procedures were accomplished with PSIs. Surgeries with PSIs were 45 min shorter, with fewer fluoroscopy shots. Optimal correction was achieved in 37% of procedures, while the remaining cases showed under-corrections (41%) or over-corrections (22%). Major complications were observed in four patients (13.8%). (4) Conclusions: The In-Office 3D Printing Point of Care is becoming an essential tool for planning and executing complex corrections of lower limb deformities, but additional research is needed for optimizing the prediction and accuracy of the achieved corrections.
Effect of the Duration of Restrictive Fluid Therapy on Acute Kidney Injury in Robot-Assisted Laparoscopic Prostatectomy
Authors: Aktas Yildirim Serap , Sarikaya Zeynep Tugce , Dogan Lerzan , Gucyetmez Bulent , Turkeri Levent , Toraman Fevzi
Published: November 2023

Background: In robot-assisted laparoscopic prostatectomy (RALP), restrictive fluid therapy (RFT) is often utilized until the vesicourethral anastomosis (console period) is completed. RFT can cause acute kidney injury (AKI). Thus, RFT prolongation in surgeries that utilize the Trendelenburg position and pneumoperitoneum may increase the risk of postoperative AKI. We aimed to evaluate the effect of RFT duration on postoperative AKI. Methods: Forty-four patients who underwent RALP were included in this prospective observational study. Patients were divided into two groups according to the RFT duration (Group I, RFT duration ≤ 3 h, and Group II, RFT duration >3 h). AKI was diagnosed and staged according to the Kidney Disease Improving Global Outcomes criteria (KDIGO) using patients’ serum creatinine levels after the first 24 h postoperatively. Hemodynamic parameters were monitored using the pressure recording analytical method. Results: The AKI incidence was significantly higher in Group II than in Group I (45.5% vs. 9.1%; p = 0.016). In both groups, all patients who developed AKI were KDIGO stage 1 and all recovered on the second postoperative day. At the end of the console period, the heart rate and arterial elastance were significantly higher, whereas the stroke volume index was significantly lower in Group II than in Group I (p = 0.041, p = 0.016, and p < 0.001, respectively). Although the amounts of fluid administered before and after the anastomosis were similar between the groups, the total amount of fluid administered was significantly different (p < 0.001). There was a significant negative correlation between RFT duration and the total amount of fluid administered (r2 = 0.43, p < 0.001). RFT duration of >3 h, total fluid administration of ≤3.3 mL/kg/h, and stroke volume index (SVI) at the end of the console period of ≤32 mL/m2 increased the risk of AKI by 12.0 times (1.7–85.2) (p = 0.013). Conclusion: RFT prolongation in RALP may increase the risk of developing AKI.
Sperm DNA Fragmentation after Cryopreservation and Sperm Selection Has No Implications for Clinical Pregnancies and Live Births after Intrauterine Insemination with Donor Sperm
Authors: Sugihara Alessa , Punjabi Usha , Chimienti Tiziana , Goovaerts Ilse , Peeters Kris , Bouziotis Jason , De Neubourg Diane
Published: November 2023

Intrauterine insemination with donor sperm (IUI-D) requires multiple in vitro manipulations such as sperm selection and cryopreservation during which spermatozoa may be exposed to oxidative stress (OS) and other insults that may produce potential damage including sperm DNA fragmentation (SDF). High levels of SDF, referring to damage or breaks in the genetic material of sperm cells, are linked to an increased risk of reproductive failure. This retrospective, observational study set out to evaluate whether SDF assessment could predict clinical outcome in an IUI-D program, where sperm donors are selected on strict conventional semen parameters. A total of 18 donors and 106 recipients were matched for IUI-D. Out of 429 cycles, 100 (23.3%) resulted in clinical pregnancy. We counted 78 live births (18.2% of cycles), while 20 pregnancies ended in miscarriage (4.7% of cycles), 1 in extra-uterine pregnancy and 1 in stillbirth. Female age significantly influenced clinical pregnancy and miscarriage rates. SDF increased after cryopreservation (26.3 ± 14.5%; p < 0.001) and more so after post-thaw density gradient (34.9 ± 22.1%; p = 0.04) without affecting clinical pregnancy (OR [95% CI] 1.01 [0.99; 1.02]; p = 0.27), live birth (1.00 [0.99; 1.02]; p = 0.72) and miscarriage rates (1.02 [1.00; 1.05]; p = 0.08). The implications of our findings extend to a better selection of sperm donors and a better sperm preparation technique tailored to the donor semen’s properties in order to maximize the chances of a favorable treatment outcome.
Can L2 Pronunciation Be Evaluated without Reference to a Native Model? Pillai Scores for the Intrinsic Evaluation of L2 Vowels
Authors: Mairano Paolo , Santiago Fabián , Roa Leonardo Contreras
Published: November 2023

In this article, we explore the possibility of evaluating L2 pronunciation, and, more specifically, L2 vowels, without referring to a native model, i.e., intrinsically. Instead of comparing L2 vowel productions to native speakers’ productions, we use Pillai scores to measure the overlap between target vowel categories in L2 English (/iː/ — /ɪ/, /ɑː/ — /æ/, /ɜː/ — /ʌ/, /uː/ — /ʊ/) for L1 French, L1 Spanish, and L1 Italian learners (n = 40); and in L2 French (/y/ — /u/, /ø/ — /o/, /ø/ — /e/, /ɛ˜/ — /e /, /ɑ˜/ — /a/, /ɔ˜/ — /o/) for L1 English, L1 Spanish, and L1 Italian learners (n = 48). We assume that a greater amount of overlap within a contrast indicates assimilated categories in a learner’s production, whereas a smaller amount of overlap indicates the establishment of phonological categories and distinct realisations for members of the contrast. Pillai scores were significant predictors of native ratings of comprehensibility and/or nativelikeness for many of the contrasts considered. Despite some limitations and caveats, we argue that Pillai scores and similar methods for the intrinsic evaluation of L2 pronunciation can be used, (i) to avoid direct comparisons of L2 users’ performance with native monolinguals, following recent trends in SLA research; (ii) when comparable L1 data are not available; (iii) within longitudinal studies to track the progressive development of new phonological categories.
Why Does Your Uterus Become Malignant? The Impact of the Microbiome on Endometrial Carcinogenesis
Authors: Morańska Katarzyna , Englert-Golon Monika , Durda-Masny Magdalena , Sajdak Stefan , Grabowska Marlena , Szwed Anita
Published: November 2023

The aim of this review was to describe the uterine microbiome composition that has been analyzed so far and describe potential pathways in the carcinogenesis of the endometrium. The microbiome in the uterine environment is involved in apoptosis and proliferation during the menstruation cycle, pregnancy maintenance, and immune system support. However, bacteria in the uterus could stimulate inflammation, which when chronic results in malignancy. An altered gut microbiota initiates an inflammatory response through microorganism-associated molecular patterns, which leads to intensified steroidogenesis in the ovaries and cancers. Moreover, intestinal bacteria secreting the enzyme β-glucuronidase may increase the level of circulating estrogen and, as a result, be influential in gynecological cancers. Both the uterine and the gut microbiota play a pivotal role in immune modulation, which is why there is a demand for further investigation from both the diagnostic and the therapeutic perspectives.
Current State of Application of Machine Learning for Investigation of MgO-C Refractories: A Review
Authors: Sado Sebastian , Jastrzębska Ilona , Zelik Wiesław , Szczerba Jacek
Published: November 2023

Nowadays, digitalization and automation in both industrial and research activities are driving forces of innovations. In recent years, machine learning (ML) techniques have been widely applied in these areas. A paramount direction in the application of ML models is the prediction of the material service time in heating devices. The results of ML algorithms are easy to interpret and can significantly shorten the time required for research and decision-making, substituting the trial-and-error approach and allowing for more sustainable processes. This work presents the state of the art in the application of machine learning for the investigation of MgO-C refractories, which are materials mainly consumed by the steel industry. Firstly, ML algorithms are presented, with an emphasis on the most commonly used ones in refractories engineering. Then, we reveal the application of ML in laboratory and industrial-scale investigations of MgO-C refractories. The first group reveals the implementation of ML techniques in the prediction of the most critical properties of MgO-C, including oxidation resistance, optimization of the C content, corrosion resistance, and thermomechanical properties. For the second group, ML was shown to be mostly utilized for the prediction of the service time of refractories. The work is summarized by indicating the opportunities and limitations of ML in the refractories engineering field. Above all, reliable models require an appropriate amount of high-quality data, which is the greatest current challenge and a call to the industry for data sharing, which will be reimbursed over the longer lifetimes of devices.
Green Synthesis of ZnO/SnO2 Hybrid Nanocomposite for Degradation of Cationic and Anionic Dyes under Sunlight Radiation
Authors: Abduh Naaser A. Y. , Al-Odayni Abdel-Basit
Published: November 2023

The aim of this work was to biosynthesize SnO2-decorated ZnO (ZT) nanocomposites (NCs) of different Sn content (10, 20, and 30 mol%), namely, ZT10, ZT20, and ZT30, using Olea europaea leaf aqueous extract-based phytocompounds as nanoparticle facilitating agents for application as effective photocatalyst in the removal of dyes from polluted water. The obtained ZT NCs were characterized using various techniques, including FTIR, XRD, TGA, TEM, EDS, UV–Vis, PL, and BET surface area. X-ray diffraction patterns show that rutile SnO2 and hexagonal ZnO coexist in the composites, and their crystallite size (D) is affected by the SnO2 ratio; the obtained D-values were 17.24, 19.07, 13.99, 6.45, and 12.30 nm for ZnO, SnO2, ZT10, ZT20, and ZT30, respectively. The direct band gaps of the ZT heterostructure increase with increasing SnO2 ratio (band gap = 3.10, 3.45, 3.14, 3.17, and 3.21 eV, respectively). TEM spectroscopy revealed nanorod and spherical grain morphologies of the composites, while EDS confirmed the elemental composition, the element ratio, and the composite’s purity. All catalysts exhibit type III isotherm with macropore structure. The photocatalytic efficiency against cationic (methylene blue (MB), rhodamine B (RB)), and anionic (methyl orange (MO)) dyes, under sunlight, was optimal with ZT20. The results revealed almost complete degradation at 55, 65, and 55 min, respectively. Hence, it is evident that incorporating SnO2 improves the photocatalyst’s performance, with an apparent optimal enhancement at 20 mol% Sn decorating ZT NCs. More interestingly, the catalyst stability and activity remained unaffected even after four activating cycles.
Preparation of Steel-Slag-Based Hydrotalcite and Its Adsorption Properties on Cl− and SO42−
Authors: Dong Zebo , Huang Bei , Zhang Tao , Liu Na , Mao Zhongyang
Published: November 2023

Large amounts of chloride ions (Cl−) and sulfate ions (SO42−) are present in salt-washing wastewater, making it unsuitable for direct release. Adsorption can be used to eliminate Cl− and SO42− from salt-washing wastewater, and hydrotalcite is an excellent adsorbent with high adsorption properties for these ions because of a layered bimetallic hydroxide structure. The selective extraction of various metals, such as calcium, magnesium, aluminum, and iron, from steel slag via acid leaching facilitates the utilization of steel slag in the preparation of hydrotalcite. In this study, the leaching mechanism of metal in steel slag was investigated using steel slag as a raw material and acetic acid as the reaction medium. The study obtained the optimal leaching mechanism for preparing hydrotalcite. Hydrotalcite was synthesized from the steel slag leaching solution by hydrothermal synthesis, and its structure was characterized. The adsorption performance of Cl− and SO42− in salt-washing wastewater was investigated by solution adsorption experiments. The removal rates of Cl− and SO42− in salt-washing wastewater reached 12.8% and 38.0%, respectively. After multiple adsorption cycles, the removal rates increased to 98.0% for Cl− and 96.4% for SO42−.
Reinforcement Learning-Based Dynamic Zone Positions for Mixed Traffic Flow Variable Speed Limit Control with Congestion Detection
Authors: Vrbanić Filip , Gregurić Martin , Miletić Mladen , Ivanjko Edouard
Published: November 2023

Existing transportation infrastructure and traffic control systems face increasing strain as a result of rising demand, resulting in frequent congestion. Expanding infrastructure is not a feasible solution for enhancing the capacity of the road. Hence, Intelligent Transportation Systems are often employed to enhance the Level of Service (LoS). One such approach is Variable Speed Limit (VSL) control. VSL increases the LoS and safety on motorways by optimizing the speed limit according to the traffic conditions. The proliferation of Connected and Autonomous Vehicles (CAVs) presents fresh prospects for improving the operation and measurement of traffic states for the operation of the VSL control system. This paper introduces a method for the detection of multiple congested areas that is used for state estimation for a dynamically positioned VSL control system for urban motorways. The method utilizes Q-Learning (QL) and CAVs as mobile sensors and actuators. The proposed control approach, named Congestion Detection QL Dynamic Position VSL (CD-QL-DPVSL), dynamically detects all of the congested areas and applies two sets of actions, involving the dynamic positioning of speed limit zones and imposed speed limits for all detected congested areas simultaneously. The proposed CD-QL-DPVSL control approach underwent an evaluation across six distinct traffic scenarios, encompassing CAV penetration rates spanning from 10% to 100% and demonstrated a significantly better performance compared to other control approaches, including no control, rule-based VSL, two Speed-Transition-Matrices-based QL-VSL configurations with fixed speed limit zone positions, and a Speed-Transition-Matrices-based QL-DVSL with a dynamic speed limit zone position. It achieved enhancements in macroscopic traffic parameters such as the Mean Travel Time and Total Time Spent by adapting its control policy to every simulated scenario.
A Non-Linear Trend Function for Kriging with External Drift Using Least Squares Support Vector Regression
Authors: Baisad Kanokrat , Chutsagulprom Nawinda , Moonchai Sompop
Published: November 2023

Spatial interpolation of meteorological data can have immense implications on risk management and climate change planning. Kriging with external drift (KED) is a spatial interpolation variant that uses auxiliary information in the estimation of target variables at unobserved locations. However, traditional KED methods with linear trend functions may not be able to capture the complex and non-linear interdependence between target and auxiliary variables, which can lead to an inaccurate estimation. In this work, a novel KED method using least squares support vector regression (LSSVR) is proposed. This machine learning algorithm is employed to construct trend functions regardless of the type of variable interrelations being considered. To evaluate the efficiency of the proposed method (KED with LSSVR) relative to the traditional method (KED with a linear trend function), a systematic simulation study for estimating the monthly mean temperature and pressure in Thailand in 2017 was conducted. The KED with LSSVR is shown to have superior performance over the KED with the linear trend function.