bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum Levels of IFABP2 and Differences in Lactobacillus and Porphyromonas gingivalis Abundance on Gut Microbiota Are Associated with Poor Therapeutic Response in Rheumatoid Arthritis: A Pilot Study
Authors: Zaragoza-García Oscar , Castro-Alarcón Natividad , Pérez-Rubio Gloria , Falfán-Valencia Ramcés , Briceño Olivia , Navarro-Zarza José Eduardo , Parra-Rojas Isela , Tello Mario , Guzmán-Guzmán Iris Paola
Published: January 2023

Intestinal dysbiosis is related to the physiopathology and clinical manifestation of rheumatoid arthritis (RA) and the response to pharmacologic treatment. The objectives of this study were (1) to analyze the effect of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) on the abundance of gut microbiota’s bacteria; (2) to evaluate the relationship between the differences in microbial abundance with the serum levels of intestinal fatty-acid binding protein 2 (IFABP2), cytokines, and the response phenotype to csDMARDs therapy in RA. A cross-sectional study was conducted on 23 women diagnosed with RA. The abundance of bacteria in gut microbiota was determined with qPCR. The ELISA technique determined serum levels of IFABP2, TNF-α, IL-10, and IL-17A. We found that the accumulated dose of methotrexate or prednisone is negatively associated with the abundance of Lactobacillus but positively associated with the abundance of Bacteroides fragilis. The Lactobacillus/Porphyromonas gingivalis ratio was associated with the Disease Activity Score-28 for RA with Erythrocyte Sedimentation Rate (DAS28-ESR) (r = 0.778, p = 0.030) and with the levels of IL-17A (r = 0.785, p = 0.027) in the group treated with csDMARD. Moreover, a relation between the serum levels of IFABP2 and TNF-α (r = 0.593, p = 0.035) was observed in the group treated with csDMARD. The serum levels of IFABP2 were higher in patients with secondary non-response to csDMARDs therapy. In conclusion, our results suggest that the ratios of gut microbiota’s bacteria and intestinal permeability seems to establish the preamble for therapeutic secondary non-response in RA.
Resistance to BRAF Inhibitors: EZH2 and Its Downstream Targets as Potential Therapeutic Options in Melanoma
Authors: Uebel Anne , Kewitz-Hempel Stefanie , Willscher Edith , Gebhardt Kathleen , Sunderkötter Cord , Gerloff Dennis
Published: January 2023

Activating BRAF mutations occurs in 50–60% of malignant melanomas. Although initially treatable, the development of resistance to BRAF-targeted therapies (BRAFi) is a major challenge and limits their efficacy. We have previously shown that the BRAFV600E signaling pathway mediates the expression of EZH2, an epigenetic regulator related to melanoma progression and worse overall survival. Therefore, we wondered whether inhibition of EZH2 would be a way to overcome resistance to vemurafenib. We found that the addition of an EZH2 inhibitor to vemurafenib improved the response of melanoma cells resistant to BRAFi with regard to decreased viability, cell-cycle arrest and increased apoptosis. By next-generation sequencing, we revealed that the combined inhibition of BRAF and EZH2 dramatically suppresses pathways of mitosis and cell cycle. This effect was linked to the downregulation of Polo-kinase 1 (PLK1), a key regulator of cell cycle and proliferation. Subsequently, when we inhibited PLK1, we found decreased cell viability of melanoma cells resistant to BRAFi. When we inhibited both BRAF and PLK1, we achieved an improved response of BRAFi-resistant melanoma cells, which was comparable to the combined inhibition of BRAF and EZH2. These results thus reveal that targeting EZH2 or its downstream targets, such as PLK1, in combination with BRAF inhibitors are potential novel therapeutic options in melanomas with BRAF mutations.
Epigenetic Regulation of MAP3K8 in EBV-Associated Gastric Carcinoma
Authors: Roy Gaurab , Yang Ting , Liu Shangxin , Luo Yi-Ling , Liu Yuantao , Zhong Qian
Published: January 2023

Super-enhancers (SEs) regulate gene expressions, which are critical for cell type-identity and tumorigenesis. Although genome wide H3K27ac profiling have revealed the presence of SE-associated genes in gastric cancer (GC), their roles remain unclear. In this study, ChIP-seq and HiChIP-seq experiments revealed mitogen-activated protein kinase 8 (MAP3K8) to be an SE-associated gene with chromosome interactions in Epstein–Barr virus-associated gastric carcinoma (EBVaGC) cells. CRISPRi mediated repression of the MAP3K8 SEs attenuated MAP3K8 expression and EBVaGC cell proliferation. The results were validated by treating EBVaGC cells with bromodomain and the extra-terminal motif (BET) inhibitor, OTX015. Further, functional analysis of MAP3K8 in EBVaGC revealed that silencing MAP3K8 could inhibit the cell proliferation, colony formation, and migration of EBVaGC cells. RNA-seq and pathway analysis indicated that knocking down MAP3K8 obstructed the notch signaling pathway and epithelial-mesenchymal transition (EMT) in EBVaGC cells. Further, analysis of the cancer genome atlas (TCGA) and GSE51575 databases exhibited augmented MAP3K8 expression in gastric cancer and it was found to be inversely correlated with the disease-free progression of GC. Moreover, Spearman’s correlation revealed that MAP3K8 expression was positively correlated with the expressions of notch pathway and EMT related genes, such as, Notch1, Notch2, C-terminal binding protein 2 (CTBP2), alpha smooth muscle actin isotype 2 (ACTA2), transforming growth factor beta receptor 1 (TGFβR1), and snail family transcriptional repressors 1/2 (SNAI1/SNAI2) in GC. Taken together, we are the first to functionally interrogate the mechanism of SE-mediated regulation of MAP3K8 in EBVaGC cell lines.
The Impact of Non-Pathogenic Bacteria on the Spread of Virulence and Resistance Genes
Authors: Dionisio Francisco , Domingues Célia P. F. , Rebelo João S. , Monteiro Francisca , Nogueira Teresa
Published: January 2023

This review discusses the fate of antimicrobial resistance and virulence genes frequently present among microbiomes. A central concept in epidemiology is the mean number of hosts colonized by one infected host in a population of susceptible hosts: R0. It characterizes the disease’s epidemic potential because the pathogen continues its propagation through susceptible hosts if it is above one. R0 is proportional to the average duration of infections, but non-pathogenic microorganisms do not cause host death, and hosts do not need to be rid of them. Therefore, commensal bacteria may colonize hosts for prolonged periods, including those harboring drug resistance or even a few virulence genes. Thus, their R0 is likely to be (much) greater than one, with peculiar consequences for the spread of virulence and resistance genes. For example, computer models that simulate the spread of these genes have shown that their diversities should correlate positively throughout microbiomes. Bioinformatics analysis with real data corroborates this expectation. Those simulations also anticipate that, contrary to the common wisdom, human’s microbiomes with a higher diversity of both gene types are the ones that took antibiotics longer ago rather than recently. Here, we discuss the mechanisms and robustness behind these predictions and other public health consequences.
Mitochondrial Transplantation in Mitochondrial Medicine: Current Challenges and Future Perspectives
Authors: D’Amato Marco , Morra Francesca , Di Meo Ivano , Tiranti Valeria
Published: January 2023

Mitochondrial diseases (MDs) are inherited genetic conditions characterized by pathogenic mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA). Current therapies are still far from being fully effective and from covering the broad spectrum of mutations in mtDNA. For example, unlike heteroplasmic conditions, MDs caused by homoplasmic mtDNA mutations do not yet benefit from advances in molecular approaches. An attractive method of providing dysfunctional cells and/or tissues with healthy mitochondria is mitochondrial transplantation. In this review, we discuss what is known about intercellular transfer of mitochondria and the methods used to transfer mitochondria both in vitro and in vivo, and we provide an outlook on future therapeutic applications. Overall, the transfer of healthy mitochondria containing wild-type mtDNA copies could induce a heteroplasmic shift even when homoplasmic mtDNA variants are present, with the aim of attenuating or preventing the progression of pathological clinical phenotypes. In summary, mitochondrial transplantation is a challenging but potentially ground-breaking option for the treatment of various mitochondrial pathologies, although several questions remain to be addressed before its application in mitochondrial medicine.
Localization of Pyranose 2-Oxidase from Kitasatospora aureofaciens: A Step Closer to Elucidate a Biological Role
Authors: Virginia Ludovika Jessica , Peterbauer Clemens
Published: January 2023

Lignin degradation in fungal systems is well characterized. Recently, a potential for lignin depolymerization and modification employing similar enzymatic activities by bacteria is increasingly recognized. The presence of genes annotated as peroxidases in Actinobacteria genomes suggests that these bacteria should contain auxiliary enzymes such as flavin-dependent carbohydrate oxidoreductases. The only auxiliary activity subfamily with significantly similar representatives in bacteria is pyranose oxidase (POx). A biological role of providing H2O2 for peroxidase activation and reduction of radical degradation products suggests an extracellular localization, which has not been established. Analysis of the genomic locus of POX from Kitasatospora aureofaciens (KaPOx), which is similar to fungal POx, revealed a start codon upstream of the originally annotated one, and the additional sequence was considered a putative Tat-signal peptide by computational analysis. We expressed KaPOx including this additional upstream sequence as well as fusion constructs consisting of the additional sequence, the KaPOx mature domain and the fluorescent protein mRFP1 in Streptomyces lividans. The putative signal peptide facilitated secretion of KaPOx and the fusion protein, suggesting a natural extracellular localization and supporting a potential role in providing H2O2 and reducing radical compounds derived from lignin degradation.
Cembrane Diterpenes Possessing Nonaromatic Oxacycles from the Hainan Soft Coral Sarcophyton mililatensis
Authors: Zhang Ling , Yang Min , Chen Zi-Hui , Ge Zeng-Yue , Li Song-Wei , Yan Xian-Yun , Yao Li-Gong , Liang Lin-Fu , Guo Yue-Wei
Published: January 2023

Documents on the chemical composition of the soft coral Sarcophyton mililatensis are sparse. The present investigation of the Hainan soft coral S. mililatensis resulted in the discovery of six new cembrane diterpenes, sarcoxacyclols A–F (1–6) and four known analogs (7–10). Their structures were elucidated by extensive spectroscopic analysis along with a comparison with the data in current literature. The nonaromatic oxacycles in their structures were the rarely found tetrahydrofuran ether across C-1 and C-12 and tetrahydropyran ether across C-1 and C-11, respectively. Moreover, the absolute configuration of compound 4 was established unambiguously by X-ray diffraction analysis using Ga Kα radiation (λ = 1.34139 Å). Based on the biogenetical consideration, the absolute configurations of other five new compounds were tentatively assumed. Assessment of the bioactivity for these secondary metabolites revealed that compound 1 exhibited significant tumor necrosis factor (TNF)-α inhibitory activity (IC50 = 9.5 μmol/L), similar to the positive control dexamethasone (IC50 = 8.7 μmol/L), but no obvious cytotoxicity towards RAW264.7 cells (CC50 > 50 μmol/L). The preliminary molecular docking suggested the crucial roles of the hydroxyl and acetoxyl groups in the computational prediction of the binding mode between the diterpene and the protein.
Design and Synthesis of New Quinazolin-4-one Derivatives with Negative mGlu7 Receptor Modulation Activity and Antipsychotic-Like Properties
Authors: Kaczorowska Katarzyna , Stankiewicz Anna , Bugno Ryszard , Paluchowska Maria H. , Burnat Grzegorz , Brański Piotr , Cieślik Paulina , Wierońska Joanna M. , Milik Mariusz , Nowak Mateusz , Przybyłowicz Agnieszka , Kozioł Aneta , Hogendorf Agata , Hogendorf Adam S. , Kalinowska-Tłuścik Justyna , Duszyńska Beata , Pilc Andrzej , Bojarski Andrzej J.
Published: January 2023

Following the glutamatergic theory of schizophrenia and based on our previous study regarding the antipsychotic-like activity of mGlu7 NAMs, we synthesized a new compound library containing 103 members, which were examined for NAM mGlu7 activity in the T-REx 293 cell line expressing a recombinant human mGlu7 receptor. Out of the twenty-two scaffolds examined, active compounds were found only within the quinazolinone chemotype. 2-(2-Chlorophenyl)-6-(2,3-dimethoxyphenyl)-3-methylquinazolin-4(3H)-one (A9-7, ALX-171, mGlu7 IC50 = 6.14 µM) was selective over other group III mGlu receptors (mGlu4 and mGlu8), exhibited satisfactory drug-like properties in preliminary DMPK profiling, and was further tested in animal models of antipsychotic-like activity, assessing the positive, negative, and cognitive symptoms. ALX-171 reversed DOI-induced head twitches and MK-801-induced disruptions of social interactions or cognition in the novel object recognition test and spatial delayed alternation test. On the other hand, the efficacy of the compound was not observed in the MK-801-induced hyperactivity test or prepulse inhibition. In summary, the observed antipsychotic activity profile of ALX-171 justifies the further development of the group of quinazolin-4-one derivatives in the search for a new drug candidate for schizophrenia treatment.
Male Stressed Mice Having Behavioral Control Exhibit Escalations in Dorsal Dentate Adult-Born Neurons and Spatial Memory
Authors: Sun Li-Han , Liao Yi-Han , Chan Ya-Hsuan , Yu Anna E. , Wu Chun-Hsien , Kuo Ing-Tiau , Yu Lung
Published: January 2023

An escapable (ES)/inescapable stress (IS) paradigm was used to study whether behavioral control and repeated footshock stressors may affect adult neurogenesis and related cognitive function. Male stressed mice having behavioral control (ES) had a short-term escalation in dorsal dentate gyrus (DG) neurogenesis, while similarly stressed mice having no such control had unaltered neurogenesis as compared to control mice receiving no stressors. Paradoxically, ES and IS mice had comparable stress-induced corticosterone elevations throughout the stress regimen. Appetitive operant conditioning and forced running procedures were used to model learning and exercise effects in this escapable/inescapable paradigm. Further, conditioning and running procedures did not seem to affect the mice’s corticosterone or short-term neurogenesis. ES and IS mice did not show noticeable long-term changes in their dorsal DG neurogenesis, gliogenesis, local neuronal density, apoptosis, autophagic flux, or heterotypic stress responses. ES mice were found to have a greater number of previously labeled and functionally integrated DG neurons as compared to IS and control mice 6 weeks after the conclusion of the stressor regimen. Likewise, ES mice outperformed IS and non-stressed control mice for the first two, but not the remaining two, trials in the object location task. Compared to non-stressed controls, temozolomide-treated ES and IS mice having a lower number of dorsal DG 6-week-old neurons display poor performance in their object location working memory. These results, taken together, prompt us to conclude that repeated stressors, albeit their corticosterone secretion-stimulating effect, do not necessary affect adult dorsal DG neurogenesis. Moreover, stressed animals having behavioral control may display adult neurogenesis escalation in the dorsal DG. Furthermore, the number of 6-week-old and functionally-integrated neurons in the dorsal DG seems to confer the quality of spatial location working memory. Finally, these 6-week-old, adult-born neurons seem to contribute spatial location memory in a use-dependent manner.
Sigma-1 Receptor Signaling: In Search of New Therapeutic Alternatives for Cardiovascular and Renal Diseases
Authors: Munguia-Galaviz Francisco Javier , Miranda-Diaz Alejandra Guillermina , Cardenas-Sosa Miguel Alejandro , Echavarria Raquel
Published: January 2023

Cardiovascular and renal diseases are among the leading causes of death worldwide, and regardless of current efforts, there is a demanding need for therapeutic alternatives to reduce their progression to advanced stages. The stress caused by diseases leads to the activation of protective mechanisms in the cell, including chaperone proteins. The Sigma-1 receptor (Sig-1R) is a ligand-operated chaperone protein that modulates signal transduction during cellular stress processes. Sig-1R interacts with various ligands and proteins to elicit distinct cellular responses, thus, making it a potential target for pharmacological modulation. Furthermore, Sig-1R ligands activate signaling pathways that promote cardioprotection, ameliorate ischemic injury, and drive myofibroblast activation and fibrosis. The role of Sig-1R in diseases has also made it a point of interest in developing clinical trials for pain, neurodegeneration, ischemic stroke, depression in patients with heart failure, and COVID-19. Sig-1R ligands in preclinical models have significantly beneficial effects associated with improved cardiac function, ventricular remodeling, hypertrophy reduction, and, in the kidney, reduced ischemic damage. These basic discoveries could inform clinical trials for heart failure (HF), myocardial hypertrophy, acute kidney injury (AKI), and chronic kidney disease (CKD). Here, we review Sig-1R signaling pathways and the evidence of Sig-1R modulation in preclinical cardiac and renal injury models to support the potential therapeutic use of Sig-1R agonists and antagonists in these diseases.
Dissecting Platelet’s Role in Viral Infection: A Double-Edged Effector of the Immune System
Authors: El Filaly Hajar , Mabrouk Meryem , Atifi Farah , Guessous Fadila , Akarid Khadija , Merhi Yahye , Zaid Younes
Published: January 2023

Platelets play a major role in the processes of primary hemostasis and pathological inflammation-induced thrombosis. In the mid-2000s, several studies expanded the role of these particular cells, placing them in the “immune continuum” and thus changing the understanding of their function in both innate and adaptive immune responses. Among the many receptors they express on their surface, platelets express Toll-Like Receptors (TLRs), key receptors in the inflammatory cell–cell reaction and in the interaction between innate and adaptive immunity. In response to an infectious stimulus, platelets will become differentially activated. Platelet activation is variable depending on whether platelets are activated by a hemostatic or pathogen stimulus. This review highlights the role that platelets play in platelet modulation count and adaptative immune response during viral infection.
Transmembrane Protein 68 Functions as an MGAT and DGAT Enzyme for Triacylglycerol Biosynthesis
Authors: Wang Yu , Zeng Fansi , Zhao Zheng , He Lin , He Xiaohong , Pang Huimin , Huang Feifei , Chang Pingan
Published: January 2023

Triacylglycerol (TG) biosynthesis is an important metabolic process for intracellular storage of surplus energy, intestinal dietary fat absorption, attenuation of lipotoxicity, lipid transportation, lactation and signal transduction in mammals. Transmembrane protein 68 (TMEM68) is an endoplasmic reticulum (ER)-anchored acyltransferase family member of unknown function. In the current study we show that overexpression of TMEM68 promotes TG accumulation and lipid droplet (LD) formation in a conserved active sites-dependent manner. Quantitative targeted lipidomic analysis showed that diacylglycerol (DG), free fatty acid (FFA) and TG levels were increased by TMEM68 expression. In addition, TMEM68 overexpression affected the levels of several glycerophospholipids, such as phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol, as well as sterol ester contents. TMEM68 exhibited monoacylglycerol acyltransferase (MGAT) and diacylglycerol acyltransferase (DGAT) activities dependent on the conserved active sites in an in vitro assay. The expression of lipogenesis genes, including DGATs, fatty acid synthesis-related genes and peroxisome proliferator-activated receptor γ was upregulated in TMEM68-overexpressing cells. These results together demonstrate for the first time that TMEM68 functions as an acyltransferase and affects lipogenic gene expression, glycerolipid metabolism and TG storage in mammalian cells.
Synergistic Effect of Medical Information Systems Integration: To What Extent Will It Affect the Accuracy Level in the Reports and Decision-Making Systems?
Authors: Azadi Ali , García-Peñalvo Francisco José
Published: January 2023

Nowadays, according to the intention of many hospitals and medical centers to computerize their processes and medical treatments, including data forms and medical images, which are generating a considerable amount of data, IT specialists and data scientists who are oriented to eHealth and related issues know the importance of data integration and its benefits. This study indicates the significance of data integration, especially in medical information systems. It means that the medical subsystems in the HIS (hospital information system) must be integrated, and it is also necessary to unify with the MIS (management information system). In this paper, the accuracy level of the extracted reports from the information system (to evaluate the staff’s performance) will be measured in two ways: (1) At first, the performance of the clinic reception staff will be evaluated. In this way, the personnel attendance system is an independent and separate software, and the mentioned evaluation has been performed by its report. (2) The following year, in the same location, the same evaluation has been performed based on the data extracted from the personnel attendance subsystem, which has been added to the medical information system as an integrated information system. After comparing the accuracy level of both ways, this paper concludes that when the personnel attendance subsystem as a part of the MIS has been unified with the HIS, the reports and, consequently, management decisions will be more accurate; therefore, the managers and decision-makers will perceive the importance of data integration more than in the past.
Oxo-Stabilised Phosphonium Ylides as Hydrogen Bond Acceptors
Authors: Aitken R. Alan , Cleghorn Lee P. , Dawson Graham , Gray Ian P. , Lashtabeg Anna , Slawin Alexandra M. Z.
Published: January 2023

Oxo-stabilised phosphonium ylides are found to form crystalline hydrogen-bonded adducts with aromatic carboxylic acids, as confirmed by X-ray diffraction. There is also strong hydrogen bonding in solution as indicated by 13C NMR spectroscopy and this confirmed adduct formation with acetic acid, benzamide, thiobenzamide, benzyl alcohol, benzenesulfinic acid and diphenylphosphinic acid. The X-ray structure of the benzamide adduct was also determined, showing a hydrogen-bonded dimeric structure. A bis(stabilised ylide) was also prepared and is found to form a complex hydrogen-bonded adduct with benzoic acid, ethanol and water.
BaTiO3/NixZn1−xFe2O4 (x = 0, 0.5, 1) Composites Synthesized by Thermal Decomposition: Magnetic, Dielectric and Ferroelectric Properties
Authors: Šuljagić Marija , Petronijević Ivan , Mirković Miljana M. , Kremenović Aleksandar , Džunuzović Adis , Pavlović Vladimir B. , Kalezić-Glišović Aleksandra , Andjelković Ljubica
Published: January 2023

To investigate the influence of spinel structure and sintering temperature on the functional properties of BaTiO3/NixZn1−xFe2O4 (x = 0, 0.5, 1), NiFe2O4, ZnFe2O4, and Ni0.5Zn0.5Fe2O4 were in situ prepared by thermal decomposition onto BaTiO3 surface from acetylacetonate precursors. As-prepared powders were additionally sintered at 1150 °C and 1300 °C. X-ray powder diffraction (XRPD) and scanning electron microscopy (SEM) coupled with electron dispersive spectroscopy (EDS) were used for the detailed examination of phase composition and morphology. The magnetic, dielectric, and ferroelectric properties were investigated. The optimal phase composition in the BaTiO3/NiFe2O4 composite, sintered at 1150 °C, resulted in a wide frequency range stability. Additionally, particular phase composition indicates favorable properties such as low conductivity and ideal-like hysteresis loop behavior. The favorable properties of BaTiO3/NiFe2O4 make this particular composite an ideal material choice for further studies on applications of multi-ferroic devices.
Analysis of Mathematical Methods of Integral Expert Evaluation for Predictive Diagnostics of Technical Systems Based on the Kemeny Median
Authors: Manusov Vadim , Kalanakova Aysulu , Ahyoev Javod , Zicmane Inga , Praveenkumar Seepana , Safaraliev Murodbek
Published: January 2023

At present, diagnostics of the current technical condition of high-voltage power equipment in power systems have become more important. This allows the estimation of the real technical condition of power equipment more accurately with its removal into repair based on the results of the diagnostics. This paper presents the comparative analysis of expert evaluations with the use of the arithmetical mean and median values of expert evaluations. In this case, individual expert opinions, influenced by a level of competence, correspond to each other in a different manner, depending on the applied approach. As the comparison of the consistency of expert opinions is the basis for decision-making, it is recommended to make a decision on the technical condition using median estimations because these estimations are less subjected to distortions from single outliers of judgments. This provides more reliable information for making key decisions. Three approaches are considered in this paper: the method of arithmetical mean estimations, the method of median estimations based on the Kemeny median method, and the analytic hierarchy process of Saaty. The considered methods allow decisions on power equipment operation to be made very quickly; namely, if the power equipment is in an operable state and may remain operated, or it has considerable defects and should be removed from operation for routine maintenance, or it has reached the final technical state and needs to be removed from operation.
Patient-Specific Numerical Simulations of Endovascular Procedures in Complex Aortic Pathologies: Review and Clinical Perspectives
Authors: Derycke Lucie , Avril Stephane , Millon Antoine
Published: January 2023

The endovascular technique is used in the first line treatment in many complex aortic pathologies. Its clinical outcome is mostly determined by the appropriate selection of a stent-graft for a specific patient and the operator’s experience. New tools are still needed to assist practitioners with decision making before and during procedures. For this purpose, numerical simulation enables the digital reproduction of an endovascular intervention with various degrees of accuracy. In this review, we introduce the basic principles and discuss the current literature regarding the use of numerical simulation for endovascular management of complex aortic diseases. Further, we give the future direction of everyday clinical applications, showing that numerical simulation is about to revolutionize how we plan and carry out endovascular interventions.
Factors Associated with Progression of Atrial Fibrillation and Impact on All-Cause Mortality in a Cohort of European Patients
Authors: Vitolo Marco , Proietti Marco , Imberti Jacopo F. , Bonini Niccolò , Romiti Giulio Francesco , Mei Davide A. , Malavasi Vincenzo L. , Diemberger Igor , Fauchier Laurent , Marin Francisco , Nabauer Michael , Potpara Tatjana S. , Dan Gheorghe-Andrei , Lip Gregory Y. H. , Boriani Giuseppe
Published: January 2023

Background: Paroxysmal atrial fibrillation (AF) may often progress towards more sustained forms of the arrhythmia, but further research is needed on the factors associated with this clinical course. Methods: We analyzed patients enrolled in a prospective cohort study of AF patients. Patients with paroxysmal AF at baseline or first-detected AF (with successful cardioversion) were included. According to rhythm status at 1 year, patients were stratified into: (i) No AF progression and (ii) AF progression. All-cause death was the primary outcome. Results: A total of 2688 patients were included (median age 67 years, interquartile range 60–75, females 44.7%). At 1-year of follow-up, 2094 (77.9%) patients showed no AF progression, while 594 (22.1%) developed persistent or permanent AF. On multivariable logistic regression analysis, no physical activity (odds ratio [OR] 1.35, 95% CI 1.02–1.78), valvular heart disease (OR 1.63, 95% CI 1.23–2.15), left atrial diameter (OR 1.03, 95% CI 1.01–1.05), or left ventricular ejection fraction (OR 0.98, 95% CI 0.97–1.00) were independently associated with AF progression at 1 year. After the assessment at 1 year, the patients were followed for an extended follow-up of 371 days, and those with AF progression were independently associated with a higher risk for all-cause death (adjusted hazard ratio 1.77, 95% CI 1.09–2.89) compared to no-AF-progression patients. Conclusions: In a contemporary cohort of AF patients, a substantial proportion of patients presenting with paroxysmal or first-detected AF showed progression of the AF pattern within 1 year, and clinical factors related to cardiac remodeling were associated with progression. AF progression was associated with an increased risk of all-cause mortality.
Post-Stroke Status Epilepticus: Time of Occurrence May Be the Difference?
Authors: Nilo Annacarmen , Pauletto Giada , Lorenzut Simone , Merlino Giovanni , Verriello Lorenzo , Janes Francesco , Bax Francesco , Gigli Gian Luigi , Valente Mariarosaria
Published: January 2023

(1) Background: Stroke is one of the most frequent causes of status epilepticus (SE) in adults. Patients with stroke and SE have poorer prognosis than those with stroke alone. We described characteristics and prognosis of early- and late-onset post-stroke SE (PSSE). (2) Methods: We retrospectively analyzed consecutive stroke patients who experienced a first SE between August 2012 and April 2021, comparing clinical characteristics, stroke, and SE features between early- versus late-onset SE in relation to patients’ outcome. (3) Results: Forty stroke patients experienced PSSE. Fourteen developed an early-onset SE (35%) and twenty-six a late-onset SE (65%). Early-onset SE patients had a slightly higher NIHSS score at admission (6.9 vs. 6.0; p = 0.05). Early-onset SE was more severe than late-onset, according to STESS (Status Epilepticus Severity Score) (3.5 vs. 2.8; p = 0.05) and EMSE (Epidemiology-based Mortality score in Status Epilepticus) score (97.0 vs. 69.5; p = 0.04); furthermore, it had a significant impact on disability at 3-month and 1-year follow-up (p = 0.03 and p = 0.02). SE recurrence and seizures relapse were observed mainly in cases of late-onset SE. (4) Conclusions: Early-onset SE seems to be associated with higher disability in short- and long-term follow-up as possible expression of severe acute brain damage.
The Effect of Semaglutide on Blood Pressure in Patients without Diabetes: A Systematic Review and Meta-Analysis
Authors: Kennedy Cormac , Hayes Peter , Salama Sulafa , Hennessy Martina , Fogacci Federica
Published: January 2023

(1) Background: Recent advances in the pharmacological treatment of obesity with glucagon-like peptide-1 receptor agonists (GLP-1 RA) highlight the potential to target excess body weight to improve blood pressure (BP). This review aimed to determine the BP reduction in trials of semaglutide for weight reduction in patients without diabetes. (2) Methods: Relevant studies were identified via a search of research databases. Studies were screened to include randomized controlled trials (RCTs) of semaglutide versus a placebo in adults. Pooled and sensitivity analyses were performed, and risk of bias was assessed. (3) Results: six RCTs, with 4744 participants, were included in the final analysis. At baseline, the cohorts in these studies had a mean BP in the normotensive range. The mean difference in systolic BP was −4.83 mmHg (95% CI: −5.65 to −4.02), while that for diastolic BP was −2.45 mmHg (95% CI: −3.65 to −1.24). All included studies were of a high methodological quality. (4) Conclusions: A clinically significant reduction in BP was evident following semaglutide treatment in normotensive populations without diabetes. The effect of semaglutide in those with obesity and hypertension is as yet undetermined. Targeting excess body weight may be a novel therapeutic strategy for these patients.
Prognostic Role of Sonographic Decongestion in Patients with Acute Heart Failure with Reduced and Preserved Ejection Fraction: A Multicentre Study
Authors: Pugliese Nicola R. , Mazzola Matteo , Bandini Giulia , Barbieri Greta , Spinelli Stefano , De Biase Nicolò , Masi Stefano , Moggi-Pignone Alberto , Ghiadoni Lorenzo , Taddei Stefano , Sicari Rosa , Pang Peter S. , De Carlo Marco , Gargani Luna
Published: January 2023

Background: We investigated the role of the dynamic changes of pulmonary congestion, as assessed by sonographic B-lines, as a tool to stratify prognosis in patients admitted for acute heart failure with reduced and preserved ejection fraction (HFrEF, HFpEF). Methods: In this multicenter, prospective study, lung ultrasound was performed at admission and before discharge by trained investigators, blinded to clinical findings. Results: We enrolled 208 consecutive patients (mean age 76 [95% confidence interval, 70–84] years), 125 with HFrEF, 83 with HFpEF (mean ejection fraction 32% and 57%, respectively). The primary composite endpoint of cardiovascular death or HF re-hospitalization occurred in 18% of patients within 6 months. In the overall population, independent predictors of the occurrence of the primary endpoint were the number of B-lines at discharge, NT-proBNP levels, moderate-to-severe mitral regurgitation, and inferior vena cava diameter on admission. B-lines at discharge were the only independent predictor in both HFrEF and HFpEF subgroups. A cut-off of B-lines > 15 at discharge displayed the highest accuracy in predicting the primary endpoint (AUC = 0.80, p < 0.0001). Halving B-lines during hospitalization further improved event classification (continuous net reclassification improvement = 22.8%, p = 0.04). Conclusions: The presence of residual subclinical sonographic pulmonary congestion at discharge predicts 6-month clinical outcomes across the whole spectrum of acute HF patients, independent of conventional biohumoral and echocardiographic parameters. Achieving effective pulmonary decongestion during hospitalization is associated with better outcomes.
A 14-Day Therapeutic Exercise Telerehabilitation Protocol of Physiotherapy Is Effective in Non-Hospitalized Post-COVID-19 Conditions: A Randomized Controlled Trial
Authors: Rodriguez-Blanco Cleofas , Bernal-Utrera Carlos , Anarte-Lazo Ernesto , Gonzalez-Gerez Juan Jose , Saavedra-Hernandez Manuel
Published: January 2023

The emergence of COVID-19 has led to serious public health problems. Now that the acute phase of the pandemic has passed, new challenges have arisen in relation to this disease. The post-COVID-19 conditions are a priority for intervention, as months after the onset of the disease, they continue to present symptoms, especially physical and respiratory symptoms. Our aim is to test the efficacy of a fourteen-day telerehabilitation program of respiratory and strength exercises in people with post-COVID-19 conditions. For this purpose, a randomized controlled trial was generated in which data from 48 patients were analyzed using the BS, 30STSTST, MD12, VAFS, and 6MWT tests. The obtained results showed the benefit of the intervention in generating great results with respect to the control group.
Gender Differences in the Association between Physical Activity and Mortality in Chronic Kidney Disease: Results from the National Health and Nutrition Examination Survey (2011–2018)
Authors: Peng Wei , Han Min , Xu Gang
Published: January 2023

Background: Physical activity is indispensable in the management of chronic kidney disease (CKD). The aim of this study was to investigate gender difference in the association of physical activity with mortality among the CKD population. Methods: In total, 3701 participants with CKD from the 2011 to 2018 NHANES with linked mortality data were classified into different groups based on the intensity of self-reported physical activity. Multivariable-adjusted Cox proportional hazards models were used to examine the associations between physical activity and mortality. Results: During the median follow-up of 53.7 months, 694 all-cause deaths and 226 cardiovascular deaths were recorded. Patients were categorized into extremely highly active (>1500 MET-min/week), highly active (>600, ≤1500 MET-min/week), low-active (>0, ≤600 MET-min/week), or inactive (0 MET-min/week) groups. Among males, the multivariable Cox regression showed that the low-active group (HR, 0.67; 95% CI, 0.48–0.93) and highly active group (HR, 0.60; 95% CI, 0.41–0.88) were independently associated with lower risks for all-cause mortality, compared to the inactive group. The risks of all-cause mortality did not further decrease once physical activity surpassed 1500 MET-min/week, indicating a U-shaped association in males. In females, only the extremely highly active group (>1500 MET-min/week) was significantly associated with a mortality risk compared to inactivity (HR, 0.59; 95% CI, 0.39–0.89). Conclusions: Any amount of physical activity is associated with reduced all-cause mortality in male CKD participants, while in female patients, only the extremely highly active group shows the significant association.
Immunohistochemical Markers of Temporomandibular Disorders: A Review of the Literature
Authors: Almeida Luis Eduardo , Doetzer Andrea , Beck Matthew L.
Published: January 2023

Temporomandibular disorders (TMD) are a group of internal derangements encompassing dysfunction, displacement, degeneration of the temporomandibular joints and surroundings muscles of mastication, often accompanied by pain. Relationships between TMD and various chemical biomarkers have been examined throughout the years. This paper aims to gather evidence from the literature regarding other biomarkers and presenting them as one systematic review to investigate the potential links between TMD and different biochemical activity. To identify relevant papers, a comprehensive literature search was carried out in MEDLINE/PubMED, EMBASE, Web of Science and a manual search was performed in the International Journal of Oral and Maxillofacial Surgery, Journal of Oral and Maxillofacial surgery, and Journal of Cranio-Maxillo-Facial Surgery. The literature review produced extensive results relating to the biochemical and immunohistochemical markers of TMD. Many enzymes, inflammatory markers, proteoglycans, and hormones were identified and organized in tables, along with a brief description, study design, and conclusion of each study. Through this review, recurring evidence provides confidence in suggesting involvement of certain biomarkers that may be involved in this complex pathogenesis, in addition to pointing to differences in gender prevalence of TMD. However, more organized research on large human samples needs to be conducted to delve deeper into the understanding of how this disease develops and progresses.
Analysis of Patients with NET G1/G2 Neuroendocrine Tumors of the Small Intestine in the Course of Carcinoid Heart Disease—A Retrospective Study
Authors: Konsek-Komorowska Sonia J. , Pęczkowska Mariola , Kolasińska-Ćwikła Agnieszka D. , Cichocki Andrzej , Konka Marek , Roszkowska-Purska Katarzyna , Ćwikła Jarosław B.
Published: January 2023

Neuroendocrine neoplasms of the small intestine (SI-NENs) are one of the most commonly recognized gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Carcinoid heart disease (CHD) is the primary cause of death in patients with the carcinoid syndrome (CS). The aim of this retrospective study was to evaluate possible factors impacting upon overall survival (OS) in subjects with both neuroendocrine tumors (NETs) G1/G2 of the small intestine (SI-NET) and CHD. Enrolled in our study of 275 patients with confirmed G1/G2 SI-NET, were 28 (10%) individuals with CHD. Overall survival was assessed using the Kaplan–Meier method. The Cox–Mantel test was used to determine how OS varied between groups. A Cox proportional hazards model was used to conduct univariate analyses of predictive factors for OS and estimate hazard ratios (HRs). Of the 28 individuals with confirmed carcinoid heart disease, 12 (43%) were found to have NET G1 and 16 (57%) were found to have NET G2. Univariate analysis revealed that subjects with CHD and without resection of the primary tumor had a lower OS. Our retrospective study observed that patients who presented with CHD and without resection of primary tumor had worse prognosis of survival. These results suggest that primary tumors may need to be removed when feasible, but further research is needed. However, no solid recommendations can be issued on the basis of our single retrospective study.
Transperineal Laser Ablation of the Prostate (TPLA) for Lower Urinary Tract Symptoms Due to Benign Prostatic Obstruction
Authors: Sessa Francesco , Polverino Paolo , Siena Giampaolo , Bisegna Claudio , Lo Re Mattia , Spatafora Pietro , Pecoraro Alessio , Rivetti Anna , Moscardi Luisa , Saladino Marco , Cocci Andrea , Gacci Mauro , Li Marzi Vincenzo , Carini Marco , Minervini Andrea , Campi Riccardo , Serni Sergio
Published: January 2023

We aimed to review the current evidence on surgical and functional outcomes of Transperineal Laser Ablation for LUTS due to BPH. A comprehensive review of the English-language literature was performed using the MEDLINE and Web of Science databases until 1 August 2022, aiming to select studies evaluating TPLA for the treatment of LUTS due to BPH. Additional records were found from Google Scholar. Data were extracted and summarized in Tables. An appropriate form was used for qualitative data synthesis. Seven studies were included in the review, with all being single arm, non-comparative studies. In all studies, functional outcomes were evaluated with uroflowmetry parameters and validated questionnaires, showing a promising effectiveness at short- and mid-term follow-up. There is a lack of standardized pathways for preoperative assessment of patients suitable for TPLA, and even the technique itself has been reported with a few nuances. A good safety profile has been reported by all the authors. Although promising results have been reported by different groups, selection criteria for TPLA and few technical nuances regarding the procedure were found to be heterogeneous across the published series that should be standardized in the future. Further research is needed to confirm these findings.
Validation of Noninvasive Assessment of Pulmonary Gas Exchange in Patients with Chronic Obstructive Pulmonary Disease during Initial Exposure to High Altitude
Authors: Champigneulle Benoit , Reinhard Lukas , Mademilov Maamed , Marillier Mathieu , Ulrich Tanja , Carta Arcangelo , Scheiwiller Philipp , Shabykeeva Saltanat , Sheraliev Ulan , Abdraeva Ainura , Magdieva Kamila , Mirzalieva Gulzada , Taalaibekova Aijan , Ozonova Aigul , Erkinbaeva Aidai , Shakiev Nurdin , Azizbekov Syimyk , Ainslie Philip , Sooronbaev Talant , Ulrich Silvia , Bloch Konrad , Verges Samuel , Furian Michael
Published: January 2023

Investigation of pulmonary gas exchange efficacy usually requires arterial blood gas analysis (aBGA) to determine arterial partial pressure of oxygen (mPaO2) and compute the Riley alveolar-to-arterial oxygen difference (A-aDO2); that is a demanding and invasive procedure. A noninvasive approach (AGM100), allowing the calculation of PaO2 (cPaO2) derived from pulse oximetry (SpO2), has been developed, but this has not been validated in a large cohort of chronic obstructive pulmonary disease (COPD) patients. Our aim was to conduct a validation study of the AG100 in hypoxemic moderate-to-severe COPD. Concurrent measurements of cPaO2 (AGM100) and mPaO2 (EPOC, portable aBGA device) were performed in 131 moderate-to-severe COPD patients (mean ±SD FEV1: 60 ± 10% of predicted value) and low-altitude residents, becoming hypoxemic (i.e., SpO2 < 94%) during a short stay at 3100 m (Too-Ashu, Kyrgyzstan). Agreements between cPaO2 (AGM100) and mPaO2 (EPOC) and between the O2-deficit (calculated as the difference between end-tidal pressure of O2 and cPaO2 by the AGM100) and Riley A-aDO2 were assessed. Mean bias (±SD) between cPaO2 and mPaO2 was 2.0 ± 4.6 mmHg (95% Confidence Interval (CI): 1.2 to 2.8 mmHg) with 95% limits of agreement (LoA): −7.1 to 11.1 mmHg. In multivariable analysis, larger body mass index (p = 0.046), an increase in SpO2 (p < 0.001), and an increase in PaCO2-PETCO2 difference (p < 0.001) were associated with imprecision (i.e., the discrepancy between cPaO2 and mPaO2). The positive predictive value of cPaO2 to detect severe hypoxemia (i.e., PaO2 ≤ 55 mmHg) was 0.94 (95% CI: 0.87 to 0.98) with a positive likelihood ratio of 3.77 (95% CI: 1.71 to 8.33). The mean bias between O2-deficit and A-aDO2 was 6.2 ± 5.5 mmHg (95% CI: 5.3 to 7.2 mmHg; 95%LoA: −4.5 to 17.0 mmHg). AGM100 provided an accurate estimate of PaO2 in hypoxemic patients with COPD, but the precision for individual values was modest. This device is promising for noninvasive assessment of pulmonary gas exchange efficacy in COPD patients.
Multimodality Cardiac Imaging in Young and Veteran Athletes: Updates on Atrial Function Assessment, Arrhythmia Predisposition and Pathology Discrimination
Authors: Androulakis Emmanuel , Perone Francesco
Published: January 2023

Sports physicians and physiologists have aimed to assess exercise in young and master athletes so as to work out their conditioning levels and design training programs accordingly [...]
Development and Assessment of a Novel Predictive Nomogram to Predict the Risk of Secondary CR-GNB Bloodstream Infections among CR-GNB Carriers in the Gastroenterology Department: A Retrospective Case–Control Study
Authors: Zhang Hongchen , Hu Shanshan , Li Lingyun , Jin Hangbin , Yang Jianfeng , Shen Hongzhang , Zhang Xiaofeng
Published: January 2023

Background: With the number of critically ill patients increasing in gastroenterology departments (GEDs), infections associated with Carbapenem-resistant Gram-negative bacteria (CR-GNB) are of great concern in GED. However, no CR-GNB bloodstream infection (BSI) risk prediction model has been established for GED patients. Almost universally, CR-GNB colonization precedes or occurs concurrently with CR-GNB BSI. The objective of this study was to develop a nomogram that could predict the risk of acquiring secondary CR-GNB BSI in GED patients who are carriers of CR-GNB. Methods: We conducted a single-center retrospective case–control study from January 2020 to March 2022. Univariate and multivariable logistic regression analysis was used to identify independent risk factors of secondary CR-GNB bloodstream infections among CR-GNB carriers in the gastroenterology department. A nomogram was constructed according to a multivariable regression model. Various aspects of the established predicting nomogram were evaluated, including discrimination, calibration, and clinical utility. We assessed internal validation using bootstrapping. Results: The prediction nomogram includes the following predictors: high ECOG PS, severe acute pancreatitis, diabetes mellitus, neutropenia, a long stay in hospital, and parenteral nutrition. The model demonstrated good discrimination and good calibration. Conclusions: With an estimate of individual risk using the nomogram developed in this study, clinicians and nurses can identify patients with a high risk of secondary CR-GNB BSI early.
The Conundrum of Systemic Arterial Pressure Management on Cardiopulmonary Bypass
Authors: Ranucci Marco , Cotza Mauro , Di Dedda Umberto
Published: January 2023

The recently released EACTS/EACTA/EBCP guidelines on cardiopulmonary bypass (CPB) in adult cardiac surgery [...]