bluuebunny/crossref_metadata_2025 huggingface dataset:
Next Point-of-Interest Recommendation Based on Joint Mining of Spatial–Temporal and Semantic Sequential Patterns
Authors: Tian Jing , Zhao Zilin , Ding Zhiming
Published: July 2023

With the widespread use of the location-based social networks (LBSNs), the next point-of-interest (POI) recommendation has become an essential service, which aims to understand the user’s check-in behavior at the current moment by analyzing and mining the correlations between the user’s check-in behaviors within his/her historical trajectory and then recommending the POI that the user is most likely to visit at the next time step. However, the user’s check-in trajectory presents extremely irregular sequential patterns, such as spatial–temporal patterns, semantic patterns, etc. Intuitively, the user’s visiting behavior is often accompanied by a certain purpose, which makes the check-in data in LBSNs often have rich semantic activity characteristics. However, existing research mainly focuses on exploring the spatial–temporal sequential patterns and lacks the mining of semantic information within the trajectory, so it is difficult to capture the user’s visiting intention. In this paper, we propose a self-attention- and multi-task-based method, called MSAN, to explore spatial–temporal and semantic sequential patterns simultaneously. Specifically, the MSAN proposes to mine the user’s visiting intention from his/her semantic sequence and uses the user’s visiting intention prediction task as the auxiliary task of the next POI recommendation task. The user’s visiting intention prediction uses hierarchical POI category attributes to describe the user’s visiting intention and designs a hierarchical semantic encoder (HSE) to encode the hierarchical intention features. Moreover, a self-attention-based hierarchical intention-aware module (HIAM) is proposed to mine temporal and hierarchical intention features. The next POI recommendation uses the self-attention-based spatial–temporal-aware module (STAM) to mine the spatial–temporal sequential patterns within the user’s check-in trajectory and fuses this with the hierarchical intention patterns to generate the next POI list. Experiments based on two real datasets verified the effectiveness of the model.
Increased Drop in Activity of Alkaline Phosphatase in Plasma from Patients with Endocarditis
Authors: Kahrovic Amila , Poschner Thomas , Schober Anna , Angleitner Philipp , Alajbegovic Leila , Andreas Martin , Hutschala Doris , Brands Ruud , Laufer Günther , Wiedemann Dominik
Published: July 2023

(1) Infective endocarditis is a severe inflammatory disease associated with substantial mortality and morbidity. Alkaline phosphatase (AP) levels have been shown to change significantly during sepsis. Additionally, we previously found that a higher initial AP drop after cardiac surgery is associated with unfavorable outcomes. Therefore, the course of AP after surgery for endocarditis is of special interest. (2) A total of 314 patients with active isolated left-sided infective endocarditis at the Department of Cardiac Surgery (Medical University of Vienna, Vienna, Austria) between 2009 and 2018 were enrolled in this retrospective analysis. Blood samples were analyzed at different time points (baseline, postoperative days 1–7, postoperative days 14 and 30). Patients were categorized according to relative alkaline phosphatase drop (≥30% vs. <30%). (3) A higher rate of postoperative renal replacement therapy with or without prior renal replacement therapy (7.4 vs. 21.8%; p = 0.001 and 6.7 vs. 15.6%; p = 0.015, respectively) and extracorporeal membrane oxygenation (2.2 vs. 19.0%; p = 0.000) was observed after a higher initial alkaline phosphatase drop. Short-term (30-day mortality 3.0 vs. 10.6%; p = 0.010) and long-term mortality (p = 0.008) were significantly impaired after a higher initial alkaline phosphatase drop. (4) The higher initial alkaline phosphatase drop was accompanied by impaired short- and long-term outcomes after cardiac surgery for endocarditis. Future risk assessment scores for cardiac surgery should consider alkaline phosphatase.
HIV and SIV Envelope Glycoproteins Interact with Glycolipids and Lipids
Authors: Planes Rémi , Bahraoui Elmostafa
Published: July 2023

The present study demonstrates that, in addition to interacting with galactosylceramide (GalCer), HIV-1, HIV-2, and SIV envelope glycoproteins are able to interact with glucosylceramide (GlcCer), lactosylceramide (LacCer), and ceramide. These interactions were characterized by using three complementary approaches based on molecular binding and physicochemical assays. The binding assays showed that iodinated radiolabeled HIV-1 and HIV-2 glycoproteins (125I-gp) interact physically with GalCer, GlcCer, LacCer, and ceramide previously separated by thin layer chromatography (TLC) or directly coated on a flexible 96-well plate. These interactions are specific as demonstrated, on the one hand, by the dose-dependent inhibition in the presence of various dilutions of immune, but not non-immune, sera, and, on the other hand, by the absence of interaction of these glycolipids/lipids with 125I-IgG used as an unrelated control protein. These interactions were further confirmed in a physicochemical assay, based on the capacity of these glycolipids for insertion in a pre-established monomolecular film, as a model of the cell membrane, with each glycolipid/lipid. The addition of HIV envelope glycoproteins, but not ovomucoid protein used as a negative control, resulted in a rapid increase in surface pressure of the glycolipid/lipid films, thus indirectly confirming their interactions with GalCer, GlcCer, LacCer, and ceramide. In summary, we show that HIV and SIV envelope glycoproteins bind to GalCer, GlcCer, LacCer, and ceramide in a dose-dependent, saturable, and specific manner. These interactions may function as receptors of attachment in order to facilitate infection of CD4 low or negative cells or promote interactions with other receptors leading to the activation of signaling pathways or pathogenesis.
Understanding the Molecular Basis of the Multiple Mitochondrial Dysfunctions Syndrome 2: The Disease-Causing His96Arg Mutation of BOLA3
Authors: Bargagna Beatrice , Banci Lucia , Camponeschi Francesca
Published: July 2023

Multiple mitochondrial dysfunctions syndrome type 2 with hyperglycinemia (MMDS2) is a severe disorder of mitochondrial energy metabolism, associated with biallelic mutations in the gene encoding for BOLA3, a protein with a not yet completely understood role in iron-sulfur (Fe-S) cluster biogenesis, but essential for the maturation of mitochondrial [4Fe-4S] proteins. To better understand the role of BOLA3 in MMDS2, we have investigated the impact of the p.His96Arg (c.287A > G) point mutation, which involves a highly conserved residue, previously identified as a [2Fe-2S] cluster ligand in the BOLA3-[2Fe-2S]-GLRX5 heterocomplex, on the structural and functional properties of BOLA3 protein. The His96Arg mutation has been associated with a severe MMDS2 phenotype, characterized by defects in the activity of mitochondrial respiratory complexes and lipoic acid-dependent enzymes. Size exclusion chromatography, NMR, UV-visible, circular dichroism, and EPR spectroscopy characterization have shown that the His96Arg mutation does not impair the interaction of BOLA3 with its protein partner GLRX5, but leads to the formation of an aberrant BOLA3-[2Fe-2S]-GLRX5 heterocomplex, that is not functional anymore in the assembly of a [4Fe-4S] cluster on NFU1. These results allowed us to rationalize the severe phenotype observed in MMDS2 caused by His96Arg mutation.
Neuromodulation for Brain Tumors: Myth or Reality? A Narrative Review
Authors: D’Alessandris Quintino Giorgio , Menna Grazia , Izzo Alessandro , D’Ercole Manuela , Della Pepa Giuseppe Maria , Lauretti Liverana , Pallini Roberto , Olivi Alessandro , Montano Nicola
Published: July 2023

In recent years, research on brain cancers has turned towards the study of the interplay between the tumor and its host, the normal brain. Starting from the establishment of a parallelism between neurogenesis and gliomagenesis, the influence of neuronal activity on the development of brain tumors, particularly gliomas, has been partially unveiled. Notably, direct electrochemical synapses between neurons and glioma cells have been identified, paving the way for new approaches for the cure of brain cancers. Since this novel field of study has been defined “cancer neuroscience”, anticancer therapeutic approaches exploiting these discoveries can be referred to as “cancer neuromodulation”. In the present review, we provide an up-to-date description of the novel findings and of the therapeutic neuromodulation perspectives in cancer neuroscience. We focus both on more traditional oncologic approaches, aimed at modulating the major pathways involved in cancer neuroscience through drugs or genetic engineering techniques, and on electric stimulation proposals; the latter is at the cutting-edge of neuro-oncology.
The Effects of Statins, Ezetimibe, PCSK9-Inhibitors, Inclisiran, and Icosapent Ethyl on Platelet Function
Authors: Di Costanzo Assunta , Indolfi Ciro , Sorrentino Sabato , Esposito Giovanni , Spaccarotella Carmen Anna Maria
Published: July 2023

This review aims to examine the complex interaction between dyslipidemia, platelet function, and related drug treatments. In particular, the manuscript provides an overview of the effects of major hypolipidemic drugs on platelet function. Indeed, growing evidence supports the view that statins, ezetimibe, PCSK9 inhibitors, inclisiran, and icosapent ethyl also act as antithrombotics. It is known that platelets play a key role not only in the acute phase of coronary syndromes but also in the early phase of atherosclerotic plaque formation. The goal of cholesterol-lowering therapy is to reduce cardiovascular events. The direct effects of cholesterol-lowering drugs are widely described in the literature. Lowering LDL-c (low-density lipoprotein cholesterol) by 1 mmol/L results in a 22–23% reduction in cardiovascular risk. Numerous studies have examined the direct antithrombotic effects of these drugs on platelets, endothelium, monocytes, and smooth muscle cells, and thus, potentially independent of blood LDL-cholesterol reduction. We reviewed in vitro and in vivo studies evaluating the complex interaction between hypercholesterolemia, hypertriglyceridemia, platelet function, and related drug treatments. First, we discussed the role of statins in modulating platelet activation. Discontinuation of statin therapy was associated with increased cardiovascular events with increased ox-LDL, P-selectin, and platelet aggregation. The effect of PCSK9-I (inhibitors of proprotein convertase subtilisin/kexin type 9, PCSK9 involved in the degradation of LDL receptors in the liver) was associated with a statistically significant reduction in platelet reactivity, calculated in P2Y12 reaction units (PRU), in the first 14 days and no difference at 30 days compared to placebo. Finally, in patients with hypertriglyceridemia, the REDUCE-IT study showed that icosapent ethyl (an ethyl ester of eicosapentaenoic acid that reduces triglyceride synthesis and improves triglyceride clearance) resulted in a 25% reduction in ischemic events and cardiovascular death. However, to date, there is not yet clear clinical evidence that the direct antithrombotic effects of the drugs may have a beneficial impact on outcomes independently from the reduction in LDL-C or triglycerides.
Multiple Roles of LOXL2 in the Progression of Hepatocellular Carcinoma and Its Potential for Therapeutic Targeting
Authors: Radić Jelena , Kožik Bojana , Nikolić Ivan , Kolarov-Bjelobrk Ivana , Vasiljević Tijana , Vranjković Bojana , Despotović Sanja
Published: July 2023

LOXL2, a copper-dependent amine oxidase, has emerged as a promising therapeutic target in hepatocellular carcinoma (HCC). Increased LOXL2 expression in HCC has been linked with an aggressive phenotype and represents a poor prognostic factor. Here, we focus on the mechanisms through which LOXL2 orchestrates multiple oncogenic functions in HCC development. We performed a review of the current knowledge on the roles LOXL2 performs in the modulation of the HCC tumor microenvironment, formation of premetastatic niches, and epithelial–mesenchymal transition. We also highlighted the complex interplay between LOXL2 and hypoxia, angiogenesis, and vasculogenic mimicry in HCC. At the end of the review, we summarize the current LOXL2 inhibitors and discuss their potential in HCC precision treatment.
Development of Hydrophobic Cell-Penetrating Stapled Peptides as Drug Carriers
Authors: Tsuchiya Keisuke , Horikoshi Kanako , Fujita Minami , Hirano Motoharu , Miyamoto Maho , Yokoo Hidetomo , Demizu Yosuke
Published: July 2023

Cell-penetrating peptides (CPPs) are widely used for the intracellular delivery of a variety of cargo molecules, including small molecules, peptides, nucleic acids, and proteins. Many cationic and amphiphilic CPPs have been developed; however, there have been few reports regarding hydrophobic CPPs. Herein, we have developed stapled hydrophobic CPPs based on the hydrophobic CPP, TP10, by introducing an aliphatic carbon side chain on the hydrophobic face of TP10. This side chain maintained the hydrophobicity of TP10 and enhanced the helicity and cell penetrating efficiency. We evaluated the preferred secondary structures, and the ability to deliver 5(6)-carboxyfluorescein (CF) as a model small molecule and plasmid DNA (pDNA) as a model nucleotide. The stapled peptide F-3 with CF, in which the stapling structure was introduced at Gly residues, formed a stable α-helical structure and the highest cell-membrane permeability via an endocytosis process. Meanwhile, peptide F-4 demonstrated remarkable stability when forming a complex with pDNA, making it the optimal choice for the efficient intracellular delivery of pDNA. The results showed that stapled hydrophobic CPPs were able to deliver small molecules and pDNA into cells, and that different stapling positions in hydrophobic CPPs can control the efficiency of the cargo delivery.
Let-7a Downregulation Accompanied by KRAS Mutation Is Predictive of Lung Cancer Onset in Cigarette Smoke–Exposed Mice
Authors: Pulliero Alessandra , Mastracci Luca , Tarantini Letizia , Khalid Zumama , Bollati Valentina , Izzotti Alberto
Published: July 2023

Background: Let-7 is a tumor suppressor microRNA targeting the KRAS lung oncogene. Let-7a downregulation is reversible during the early stages of lung carcinogenesis but is irreversible in cancer cells. The aim of this study is to shed light on the relationship between oncogene (KRAS) mutation and let-7a downregulation in cigarette smoke (CS)-induced lung carcinogenesis. Methods: A total of 184 strain H Swiss albino mice were either unexposed (control) or exposed to CS for 2 weeks (short CS) or 8 months (long CS). After 8 months, the lungs were individually collected. The following end points have been evaluated: (a) DNA methylation of the let-7a gene promoter by bisulphite-PCR and pyrosequencing; (b) let-7a expression by qPCR; (c) KRAS mutation by DNA pyrosequencing; (d) cancer incidence by histopathological examination. Results: let-7a expression decreased by 8.3% in the mice exposed to CS for two weeks (CS short) and by 33.4% (p ≤ 0.01) in the mice exposed to CS for 8 months (CS long). No significant difference was detected in the rate of let-7a-promoter methylation between the Sham-exposed mice (55.1%) and the CS short-(53%) or CS long (51%)-exposed mice. The percentage of G/T transversions in KRAS codons 12 and 13 increased from 2.3% (Sham) to 6.4% in CS short– and to 11.5% in CS long–exposed mice. Cancer incidence increased significantly in the CS long–exposed mice (11%) as compared to both the Sham (4%) and the CS short–exposed (2%) mice. In the CS long–exposed mice, the correlation between let-7a expression and the number of KRAS mutations was positive (R = +0.5506) in the cancer-free mice and negative (R = −0.5568) in the cancer-bearing mice. Conclusions: The effects of CS-induced mutations in KRAS are neutralized by the high expression of let-7a in cancer-free mice (positive correlation) but not in cancer-bearing mice where an irreversible let-7a downregulation occurs (negative correlation). This result provides evidence that both genetic (high load of KRAS mutation) and epigenetic alterations (let-7a irreversible downregulation) are required to produce lung cancer in CS-exposed organisms.
Photo-Methionine, Azidohomoalanine and Homopropargylglycine Are Incorporated into Newly Synthesized Proteins at Different Rates and Differentially Affect the Growth and Protein Expression Levels of Auxotrophic and Prototrophic E. coli in Minimal Medium
Authors: Jecmen Tomas , Tuzhilkin Roman , Sulc Miroslav
Published: July 2023

Residue-specific incorporation of non-canonical amino acids (ncAAs) introduces bio-orthogonal functionalities into proteins. As such, this technique is applied in protein characterization and quantification. Here, we studied protein expression with three methionine analogs, namely photo-methionine (pMet), azidohomoalanine (Aha) and homopropargylglycine (Hpg), in prototrophic E. coli BL-21 and auxotrophic E. coli B834 to maximize ncAA content, thereby assessing the effect of ncAAs on bacterial growth and the expression of cytochrome b5 (b5M46), green fluorescence protein (MBP-GFP) and phage shock protein A. In auxotrophic E. coli, ncAA incorporation ranged from 50 to 70% for pMet and reached approximately 50% for Aha, after 26 h expression, with medium and low expression levels of MBP-GFP and b5M46, respectively. In the prototrophic strain, by contrast, the protein expression levels were higher, albeit with a sharp decrease in the ncAA content after the first hours of expression. Similar expression levels and 70–80% incorporation rates were achieved in both bacterial strains with Hpg. Our findings provide guidance for expressing proteins with a high content of ncAAs, highlight pitfalls in determining the levels of methionine replacement by ncAAs by MALDI-TOF mass spectrometry and indicate a possible systematic bias in metabolic labeling techniques using Aha or Hpg.
Influence of Extracellular Vesicles on Lung Stromal Cells during Breast Cancer Metastasis
Authors: Patel Urvi , Susman David , Allan Alison L.
Published: July 2023

Breast cancer is a prominent cause of cancer diagnosis and death in women globally, with over 90% of deaths being attributed to complications that arise from metastasis. One of the common locations for breast cancer metastasis is the lung, which is associated with significant morbidity and mortality. Curative treatments for metastatic breast cancer patients are not available and the molecular mechanisms that underlie lung metastasis are not fully understood. In order to better treat these patients, identifying events that occur both prior to and during metastatic spread to the lung is essential. Several studies have demonstrated that breast cancer-derived extracellular vesicles secreted from the primary breast tumor play a key role in establishing the lung pre-metastatic niche to support colonization of metastatic tumor cells. In this review, we summarize recent work supporting the influence of extracellular vesicles on stromal components of the lung to construct the pre-metastatic niche and support metastasis. Furthermore, we discuss the potential clinical applications of utilizing extracellular vesicles for diagnosis and treatment. Together, this review highlights the dynamic nature of extracellular vesicles, their roles in breast cancer metastasis to the lung, and their value as potential biomarkers and therapeutics for cancer prevention.
Impact of Continuous Estroprogestin Treatment on Circulating Microparticle Levels in Deep Endometriosis Patients
Authors: Carrillo Torres Pilar , Martínez-Zamora María Ángeles , Tàssies Dolors , Castillo Helena , Gracia Meritxell , Feixas Georgina , Reverter Joan Carles , Carmona Francisco
Published: July 2023

There has been increasing interest in the study of new pathogenic mechanisms in endometriosis (END), including the coagulation/fibrinolysis system and its link with inflammation and tissue remodeling. It has been suggested that END patients, especially with deep-infiltrating (DE) forms, could present a hypercoagulable state revealing higher levels of proinflammatory and procoagulant markers, such as total circulating microparticles (cMPs) and cMP-TF (tissue factor), released by cells in response to damage, activation, or apoptosis. However, no previous study has assessed the effect of END hormonal treatments on cMP and cMP-TF levels. Therefore, the aim of this study was to evaluate the impact of these treatments on cMP and cMP-TF levels in DE patients. Three groups were compared: DE patients receiving a continuous combined oral contraceptive regimen (CCOCR) (n = 41), DE patients without CCOCR (n = 45), and a control group (n = 43). cMP and cMP-TF levels were evaluated in platelet-free plasma. A significant decrease in the total cMP levels was found in the DE group with CCOCR versus the group without CCOCR, reflecting a higher chronic inflammatory status in DE patients that decreased with the treatment. cMP-TF levels were higher in DE patients receiving CCOCR versus those not receiving CCOCR, suggesting that treatments containing estrogens play a predominant role in suppressing the inhibitory pathway of TF.
Assessing the Link between Diabetic Metabolic Dysregulation and Breast Cancer Progression
Authors: Ahmed Samrein B. M. , Radwan Nada , Amer Sara , Saheb Sharif-Askari Narjes , Mahdami Amena , Samara Kamel A. , Halwani Rabih , Jelinek Herbert F.
Published: July 2023

Diabetes mellitus is a burdensome disease that affects various cellular functions through altered glucose metabolism. Several reports have linked diabetes to cancer development; however, the exact molecular mechanism of how diabetes-related traits contribute to cancer progression is not fully understood. The current study aimed to explore the molecular mechanism underlying the potential effect of hyperglycemia combined with hyperinsulinemia on the progression of breast cancer cells. To this end, gene dysregulation induced by the exposure of MCF7 breast cancer cells to hyperglycemia (HG), or a combination of hyperglycemia and hyperinsulinemia (HGI), was analyzed using a microarray gene expression assay. Hyperglycemia combined with hyperinsulinemia induced differential expression of 45 genes (greater than or equal to two-fold), which were not shared by other treatments. On the other hand, in silico analysis performed using a publicly available dataset (GEO: GSE150586) revealed differential upregulation of 15 genes in the breast tumor tissues of diabetic patients with breast cancer when compared with breast cancer patients with no diabetes. SLC26A11, ALDH1A3, MED20, PABPC4 and SCP2 were among the top upregulated genes in both microarray data and the in silico analysis. In conclusion, hyperglycemia combined with hyperinsulinemia caused a likely unique signature that contributes to acquiring more carcinogenic traits. Indeed, these findings might potentially add emphasis on how monitoring diabetes-related metabolic alteration as an adjunct to diabetes therapy is important in improving breast cancer outcomes. However, further detailed studies are required to decipher the role of the highlighted genes, in this study, in the pathogenesis of breast cancer in patients with a different glycemic index.
Kinase Suppressor of RAS 1 (KSR1) Maintains the Transformed Phenotype of BRAFV600E Mutant Human Melanoma Cells
Authors: Liu Zhi , Krstic Aleksandar , Neve Ashish , Casalou Cristina , Rauch Nora , Wynne Kieran , Cassidy Hilary , McCann Amanda , Kavanagh Emma , McCann Brendan , Blanco Alfonso , Rauch Jens , Kolch Walter
Published: July 2023

Kinase Suppressor of RAS 1 (KSR1) is a scaffolding protein for the RAS-RAF-MEK-ERK pathway, which is one of the most frequently altered pathways in human cancers. Previous results have shown that KSR1 has a critical role in mutant RAS-mediated transformation. Here, we examined the role of KSR1 in mutant BRAF transformation. We used CRISPR/Cas9 to knock out KSR1 in a BRAFV600E-transformed melanoma cell line. KSR1 loss produced a complex phenotype characterised by impaired proliferation, cell cycle defects, decreased transformation, decreased invasive migration, increased cellular senescence, and increased apoptosis. To decipher this phenotype, we used a combination of proteomic ERK substrate profiling, global protein expression profiling, and biochemical validation assays. The results suggest that KSR1 directs ERK to phosphorylate substrates that have a critical role in ensuring cell survival. The results further indicate that KSR1 loss induces the activation of p38 Mitogen-Activated Protein Kinase (MAPK) and subsequent cell cycle aberrations and senescence. In summary, KSR1 function plays a key role in oncogenic BRAF transformation.
I Feel! Therefore, I Am from Pain to Consciousness in DOC Patients
Authors: Riganello Francesco , Tonin Paolo , Soddu Andrea
Published: July 2023

Pain assessment and management in patients with disorders of consciousness (DOC) is a challenging and important aspect of care, with implications for detecting consciousness and promoting recovery. This narrative review explores the role of pain in consciousness, the challenges of pain assessment, pharmacological treatment in DOC, and the implications of pain assessment when detecting changes in consciousness. The review discusses the Nociception Coma Scale and its revised version, which are behavioral scales used to assess pain in DOC patients, and the challenges and controversies surrounding the appropriate pharmacological treatment of pain in these patients. Moreover, we highlight recent evidence suggesting that an accurate pain assessment may predict changes in the level of consciousness in unresponsive wakefulness syndrome/vegetative state patients, underscoring the importance of ongoing pain management in these patients.
Anti-Inflammatory and Histological Analysis of Skin Wound Healing through Topical Application of Mexican Propolis
Authors: Balderas-Cordero Daniela , Canales-Alvarez Octavio , Sánchez-Sánchez Roberto , Cabrera-Wrooman Alejandro , Canales-Martinez Maria Margarita , Rodriguez-Monroy Marco Aurelio
Published: July 2023

Skin wound healing is a complex biochemical process of tissue repair and remodeling in response to injury. Currently, the drugs used to improve the healing process are inaccessible to the population, are costly, and have side effects, making the search for new treatment alternatives necessary. Propolis is a natural product produced by bees that is widely recognized and used in folk medicine for its multiple biomedical activities. However, therapeutic information regarding Mexican propolis is limited. This study aimed to evaluate the wound-healing effect of the Chihuahua ethanolic extract of propolis (ChEEP). Macroscopic and histological analyses were performed using a mouse wound-healing model. The topic acute toxicity assay showed that propolis at 10% w/v had no toxic effects. ChEEP has antibacterial activity against the Gram-positive bacteria Staphylococcus aureus and Staphylococcus epidermidis. Moreover, it exhibited good anti-inflammatory activity evaluated through mouse ear edema induced by 12-O-tetradeca-noylphorbol-13-acetate (TPA). A full-thickness incision lesion was created in mice and treated topically with 10% ChEEP. At Day 14 post-treatment, it was observed that propolis increased wound contraction and reduced healing time and wound length; furthermore, propolis increased the tensile strength of the wound, as determined with the tensiometric method, and promoted the formation of type I collagen at the site of injury, as evaluated with Herovici stain. These findings suggest that the topical administration of ChEEP can improve skin wound healing, probably due to the synergistic effect of its components, mainly polyphenols, in different steps of the wound-healing process. It should be noted this is the first time that the wound-healing activity of a Mexican propolis has been evaluated.
Investigation of Clinically Significant Molecular Aberrations in Patients with Prostate Cancer: Implications for Personalized Treatment, Prognosis and Genetic Testing
Authors: Fountzilas Elena , Kouspou Maria , Eliades Alexia , Papadopoulou Kyriaki , Bournakis Evangelos , Goussia Anna , Tsiatas Marinos , Achilleos Achilleas , Tsangaras Kyriakos , Billioud Gaetan , Loizides Charalambos , Lemesios Christos , Kypri Elena , Ioannides Marios , Koumbaris George , Levva Sofia , Vakalopoulos Ioannis , Paliouras Athanasios , Pervana Stavroula , Koinis Filippos , Bumci Redi , Christopoulou Athina , Meditskou Soultana , Psyrri Amanda , Boukovinas Ioannis , Visvikis Anastasios , Karavasilis Vasilios , Koukoulis George K. , Kotsakis Athanasios , Giannakis Dimitrios , Fountzilas George , Patsalis Philippos C.
Published: July 2023

The data on tumor molecular profiling of European patients with prostate cancer is limited. Our aim was to evaluate the prevalence and prognostic and predictive values of gene alterations in unselected patients with prostate cancer. The presence of gene alterations was assessed in patients with histologically confirmed prostate cancer using the ForeSENTIA® Prostate panel (Medicover Genetics), targeting 36 clinically relevant genes and microsatellite instability testing. The primary endpoint was the prevalence of gene alterations in homologous recombination repair (HRR) genes. Overall, 196 patients with prostate cancer were evaluated (median age 72.2 years, metastatic disease in 141 (71.9%) patients). Gene alterations were identified in 120 (61%) patients, while alteration in HRR genes were identified in 34 (17.3%) patients. The most commonly mutated HRR genes were ATM (17, 8.7%), BRCA2 (9, 4.6%) and BRCA1 (4, 2%). The presence of HRR gene alterations was not associated with advanced stage (p = 0.21), age at diagnosis (p = 0.28), Gleason score (p = 0.17) or overall survival (HR 0.72; 95% CI: 0.41–1.26; p = 0.251). We identified clinically relevant somatic gene alterations in European patients with prostate cancer. These molecular alterations have prognostic significance and therapeutic implications and/or may trigger genetic testing in selected patients. In the era of precision medicine, prospective research on the predictive role of these alterations for innovative treatments or their combinations is warranted.
Inducing Magnetic Properties with Ferrite Nanoparticles in Resins for Additive Manufacturing
Authors: Redón Rocío , Aviles-Avila Miriam D. , Ruiz-Huerta Leopoldo , Montiel Herlinda , Elías-Zúñiga Alex , Daza-Gómez Lucy-Caterine , Martínez-Romero Oscar
Published: July 2023

Additive manufacturing and nanotechnology have been used as fundamental tools for the production of nanostructured parts with magnetic properties, expanding the range of applications in additive processes through tank photopolymerization. Magnetic cobalt ferrite (CoFe2O4) and barium ferrite (BaFe12O19) nanoparticles (NPs) with an average size distribution value (DTEM) of 12 ± 2.95 nm and 37 ± 12.78 nm, respectively, were generated by the hydroxide precipitation method. The dispersion of the NPs in commercial resins (Anycubic Green and IRIX White resin) was achieved through mechanochemical reactions carried out in an agate mortar for 20 min at room temperature, with limited exposure to light. The resulting product of each reaction was placed in amber vials and stored in a box to avoid light exposure. The photopolymerization process was carried out only at low concentrations (% w/w NPs/resin) since high concentrations did not result in the formation of pieces, due to the high refractive index of ferrites. The Raman spectroscopy of the final pieces showed the presence of magnetic NPs without any apparent chemical changes. The electron paramagnetic resonance (EPR) results of the pieces demonstrated that their magnetic properties were maintained and not altered during the photopolymerization. Although significant differences were observed in the dispersion process of the NPs in each piece, we determined that the photopolymerization did not affect the structure and superparamagnetic behavior of ferrite NPs during processing, successfully transferring the magnetic properties to the final 3D-printed piece.
Correction of Threshold Determination in Rapid-Guessing Behaviour Detection
Authors: Alfian Muhammad , Yuhana Umi Laili , Pardede Eric , Bimantoro Akbar Noto Ponco
Published: July 2023

Assessment is one benchmark in measuring students’ abilities. However, assessment results cannot necessarily be trusted, because students sometimes cheat or even guess in answering the questions. Therefore, to obtain valid results, it is necessary to separate valid and invalid answers by considering rapid-guessing behaviour. We conducted a test to record exam log data from undergraduate and postgraduate students to model rapid-guessing behaviour by determining the threshold response time. Rapid-guessing behaviour detection is inspired by the common k-second method. However, the method flattens the application of the threshold, thus allowing misclassification. The modified method considers item difficulty in determining the threshold. The evaluation results show that the system can identify students’ rapid-guessing behaviour with a success rate of 71%, which is superior to the previous method. We also analysed various aggregation techniques of response time and compared them to see the effect of selecting the aggregation technique.
Pheromone and Host Plant Odor Detection in Eastern Spruce Budworm, Choristoneura fumiferana Clemens (Lepidoptera: Tortricidae)
Authors: Suresh Thanusha , Roscoe Lucas E. , Hillier N. Kirk
Published: July 2023

Spruce budworm, Choristoneura fumiferana Clemens, is an ecologically significant defoliator of spruce and balsam fir in North America. Optimization of semiochemical-mediated control is needed to improve the existing integrated pest management systems such as mating disruption and population estimation. This study used single sensillum recordings (SSR) to identify the responses of olfactory receptor neurons (ORNs) in the antennal sensilla of adult male and female C. fumiferana to host plant volatiles, and female sex pheromones. There have been few SSR studies done on spruce budworm, and to our knowledge, the present study represents the first attempt to examine the responses of ORNs from antennal sensilla in response to a range of host and conspecific stimuli. A total of 86 sensilla were characterized and sorted into 15 possible sensillum categories based on odor responses. We observed that specialist sensilla responding to few ligands were more abundant in both male and female than sensilla exhibiting more generalized odorant responses. (E/Z)-11-tetradecenal elicited responses from ORNs from any sensilla which were sensitive to pheromones in both males and females. Female C. fumiferana ORNs were able to detect and physiologically respond to female-produced sex pheromones with the same degree of sensitivity as their male counterparts. Together, these data improve our knowledge of mechanisms by which adult budworms respond to pheromone and host plant volatiles and provide insights that may be complementary to existing integrated pest management (IPM) strategies based on the chemical ecology of spruce budworm.
Comparison of Nailfold Videocapillaroscopy with Retinal and Choroidal Vascular Parameters in Patients with Central Serous Chorioretinopathy
Authors: Latalska Małgorzata , Bartosińska Joanna , Dresler Sławomir , Toro Mario Damiano , Krasowska Dorota , Rejdak Robert
Published: July 2023

Aim: This study seeks to evaluate the results of nailfold videocapillaroscopies (NVCs) among patients with central serous chorioretinopathy (CSC) and their correlation with the choroid and retinal parameters. Material and Methods: The examined group included 152 patients with acute, recurrent, chronic and neovascular CSC (34 F, 118 M, mean age 45.9 ± 8.9) and 41 healthy controls (12 F, 29 M, mean age 47 ± 11.5). The NVC examination, ophthalmoscopy, angio-OCT and OCT were performed. In addition, the medical history regarding chronic general disorders and known risk factors were recorded. Results: Abnormal NVC patterns and the dilated apical part of capillaries were found only in CSC patients (p = 0.000). Neoangiogenesis was observed in 25 acute (58.14%), 22 recurrent (42.31%), 16 chronic (36.36%) and 5 neovascular patients (45.45%) and 2 control subjects (4.88%) (p = 0.000). Glomerular capillaries were found in 8 acute (18.6%), 17 recurrent (31.48%), 25 chronic (56.82%) and 8 neovascular patients (72.73%) (p = 0.000). Meandering capillaries were more common in acute and recurrent CSC and glomerular capillaries were more common in chronic and aneurysmal dilations in neovascular CSC. Conclusions: The observed digital microcirculation abnormalities in patients with CSC, such as dilation, meandering, tortuosity and glomerular, may confirm systemic micro-vasculopathy. The potential role of the NVC examination in assessing the CSC prognosis requires further evaluation.
The Impact of the COVID-19 Pandemic on the Prevalence of Head Lice Infestation among Children Attending Schools and Kindergartens in Poland
Authors: Padzik Marcin , Olędzka Gabriela , Gromala-Milaniuk Anita , Kopeć Ewa , Hendiger Edyta Beata
Published: July 2023

Pediculosis capitis predominantly affects child populations. During the COVID-19 pandemic, various types of social limitations such as social isolation and limitations on educational facilities’ functionalities were introduced worldwide, including in Poland. The impact of these pandemic restrictions on the prevalence of pediculosis capitis has not been extensively investigated so far. Existing data on this topic are limited mainly to indirect evaluation methods, such as online surveys or Internet analysis. In this study, we directly examined a cohort of over five thousand children to assess the influence of COVID-19 pandemic restrictions on the prevalence of head lice infestation among school and kindergarten attendees in Poland. Our findings demonstrate that the restrictions imposed during the COVID-19 pandemic led to a decrease in the number of children infested with head lice compared to pre-pandemic data. These results confirm that head lice infestations remain an ongoing epidemiological concern and warrant continued monitoring.
COVID-19 and Oral Lichen Planus: Between an “Intriguing Plot” and the “Fata Morgana Effect”
Authors: Scotto Gaetano , Fazio Vincenzina , Massa Salvatore , Lo Muzio Lorenzo , Spirito Francesca
Published: July 2023

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to significant morbidity and mortality worldwide since its declaration as a global pandemic in March 2020. Alongside the typical respiratory symptoms, unusual clinical manifestations such as oral lichen planus (OLP) have been observed. OLP is a chronic inflammatory mucocutaneous dermatosis that results from a cell-mediated reaction, and its pathogenesis involves the loss of immunological tolerance. OLP has been associated with several triggering factors, such as certain drugs, stress, smoking, and even some viruses. Exposure to the spike protein antigen of SARS-CoV-2 during an infection can trigger autoimmune reactions and lead to the onset or flare of OLP. The E3 protein ligase TRIM21, which is identified in the lamina propria of OLP lesions, is overexpressed in COVID-19 patients and plays a critical role in autoimmune pathologies. Furthermore, the psychological stress of the lockdown and quarantine can be a trigger for the onset or exacerbation of OLP. However, the diagnosis of OLP is complex and requires a biopsy in order to confirm a clinical diagnosis, rule out other pathologies, and establish the most appropriate therapeutic procedure. Further research is needed to understand the potential link between Co-19 and OLP.
Predictors of Conduction Disturbances Requiring New Permanent Pacemaker Implantation following Transcatheter Aortic Valve Implantation Using the Evolut Series
Authors: Abdelshafy Mahmoud , Elkoumy Ahmed , Elzomor Hesham , Abdelghani Mohammad , Campbell Ruth , Kennedy Ciara , Kenny Gibson William , Fezzi Simone , Nolan Philip , Wagener Max , Arsang-Jang Shahram , Mohamed Sameh K. , Mostafa Mansour , Shawky Islam , MacNeill Briain , McInerney Angela , Mylotte Darren , Soliman Osama
Published: July 2023

(1) Background: Conduction disturbance requiring a new permanent pacemaker (PPM) after transcatheter aortic valve implantation (TAVI) has traditionally been a common complication. New implantation techniques with self-expanding platforms have reportedly reduced the incidence of PPM. We sought to investigate the predictors of PPM at 30 days after TAVI using Evolut R/PRO/PRO+; (2) Methods: Consecutive patients who underwent TAVI with the Evolut platform between October 2019 and August 2022 at University Hospital Galway, Ireland, were included. Patients who had a prior PPM (n = 10), valve-in-valve procedures (n = 8) or received >1 valve during the index procedure (n = 3) were excluded. Baseline clinical, electrocardiographic (ECG), echocardiographic and multislice computed tomography (MSCT) parameters were analyzed. Pre-TAVI MSCT analysis included membranous septum (MS) length, a semi-quantitative calcification analysis of the aortic valve leaflets, left ventricular outflow tract, and mitral annulus. Furthermore, the implantation depth (ID) was measured from the final aortography. Multivariate binary logistic analysis and receiver operating characteristic (ROC) curve analysis were used to identify independent predictors and the optimal MS and ID cutoff values to predict new PPM requirements, respectively; (3) Results: A total of 129 TAVI patients were included (age = 81.3 ± 5.3 years; 36% female; median EuroSCORE II 3.2 [2.0, 5.4]). Fifteen patients (11.6%) required PPM after 30 days. The patients requiring new PPM at 30 days were more likely to have a lower European System for Cardiac Operative Risk Evaluation II, increased prevalence of right bundle branch block (RBBB) at baseline ECG, have a higher mitral annular calcification severity and have a shorter MS on preprocedural MSCT analysis, and have a ID, as shown on the final aortogram. From the multivariate analysis, pre-TAVI RBBB, MS length, and ID were shown to be predictors of new PPM. An MS length of <2.85 mm (AUC = 0.85, 95%CI: (0.77, 0.93)) and ID of >3.99 mm (area under the curve (AUC) = 0.79, (95% confidence interval (CI): (0.68, 0.90)) were found to be the optimal cut-offs for predicting new PPM requirements; (4) Conclusions: Membranous septum length and implantation depth were found to be independent predictors of new PPM post-TAVI with the Evolut platform. Patient-specific implantation depth could be used to mitigate the requirement for new PPM.
Evaluation of the Michigan Clinical Consultation and Care Program: An Evidence-Based Approach to Perinatal Mental Healthcare
Authors: Muzik Maria , Menke Rena A. , Issa Meriam , Fisk Chelsea , Charles Jordan , Jester Jennifer M.
Published: July 2023

Mood and anxiety disorders affect pregnant individuals and their families at increased rates throughout the perinatal period. Geographic, financial, and social barriers often preclude adequate diagnosis and treatment. The aim of this manuscript is to describe the consultation and care arms of the Michigan Clinical Consultation and Care (MC3) program, a statewide program designed to facilitate access to perinatal mental healthcare for OB/Gyn patients, and to describe the participants engaged in the program, examine the predictors of participant retention, and provide preliminary data regarding participants’ mental health outcomes. We enrolled 209 participants to the clinical care arm, of which 48 were lost to follow-up, while 107 remained enrolled at the time of data analysis. A total of 54 participants met their treatment goals. A total of 97% of participants asserted they were satisfied with the services they received. Black race and public insurance predicted faster attrition from the care arm treatment; risks for interpersonal violence exposure and substance use were unrelated to attrition. Preliminary mental health outcomes showed significant decreases in anxiety and depression, with the most dramatic decreases in the first month of treatment. Overall, the MC3 clinical care arm shows promising rates of adherence, excellent program satisfaction, and a positive impact on perinatal mental health, supporting continued program implementation and ongoing evaluation.
The Efficacy and Safety of Single-Strain Probiotic Formulations Containing Bifidobacterium lactis or Bacillus coagulans in Adult Patients with Irritable Bowel Syndrome—A Randomized Double-Blind Placebo-Controlled Three-Arm Interventional Trial
Authors: Skrzydło-Radomańska Barbara , Prozorow-Król Beata , Kurzeja-Mirosław Anetta , Cichoż-Lach Halina , Laskowska Katarzyna , Majsiak Emilia , Bierła Joanna B. , Agnieszka Sowińska , Cukrowska Bożena
Published: July 2023

Probiotics offer a potential new therapeutic approach for irritable bowel syndrome (IBS), but current results are still controversial. The aim of this study was to assess the efficacy and safety of single-strain probiotic formulations in adult IBS patients and to compare the effects of Bifidobacterium lactis NORDBIOTIC™ BI040 (DSM 33812/34614) and Bacillus coagulans NORDBIOTIC™ BC300 (DSM 33836) in a prospective three-arm interventional randomized double-blind placebo-controlled clinical trial. The study included 123 IBS subjects diagnosed according to the Rome IV criteria. The primary outcomes were changes in symptom severity and symptom improvement as assessed using the IBS Severity Scoring System (IBS-SSS) after 4, 8, and 12 weeks of intervention and after 4 weeks of follow-up. Secondary outcomes included the assessment of individual IBS symptoms and the occurrence of adverse events. During the 12-week intervention, IBS-SSS scores significantly decreased (p-values < 0.001) in the study groups but differences between the interventional and placebo groups did not reach statistical significance. However, at the 16th week of follow-up, a significant improvement in the total IBS-SSS score in comparison to the placebo group (20.5%) was found in 43.8% and 52.9% of the Bifidobacterium lactis (p = 0.038, OR 3.0, [95% CI 1.1–8.6]) and the Bacillus coagulans (p = 0.005, OR 4.6 [95% CI 1.5–12.2]) groups, respectively. Bifidobacterium lactis had a beneficial effect on the intensity and frequency of pain, whereas Bacillus coagulans decreased the bowel dissatisfaction. Both strains increased the percentage of patients with normal stool consistency, but only Bifidobacterium lactis induced a decrease in the number of patients with constipation after 6 weeks of supplementation. Both probiotic strains were well tolerated, without differences in the occurrence of adverse events between groups. In conclusion, single-strain supplementation was safe and efficient in IBS patients but showed a different range of effects. Bifidobacterium lactis BI040 primarily reduced the frequency and intensity of pain, while Bacillus coagulans BC300 increased bowel satisfaction [ClinicalTrials.gov NCT05064930].