bluuebunny/crossref_metadata_2025 huggingface dataset:
How Do Classical Subtypes Correspond to Endotypes in Atopic Dermatitis?
Authors: Suzuki Tsuyoshi , Kondo Shumpei , Ogura Yasuaki , Otsuka Masaki , Tokura Yoshiki
Published: December 2023

Since atopic dermatitis (AD) is a heterogeneous condition, the subtyping of AD is a crucial issue. The classical subtypes of AD are represented by extrinsic and intrinsic subtypes, European–American and Asian subtypes, and adult and pediatric subtypes. While the subtyping of AD was historically conducted based on the phenotype, recent findings on the mechanisms of AD have revealed the importance of the endotype, which can characterize individual patients more accurately. Considering the current development of AD therapies, AD endotyping is a prerequisite for a personalized therapeutic choice. Endotypes of AD can be stratified from different viewpoints, including cytokine expression patterns, allergen properties, epidermal barrier conditions, ceramide variation, the involvement of innate immunity, and serum biomarkers. Among them, the cytokine-based endotype seems to be the most useful one and is categorized into type 2 cytokine (IL-4, IL-13 and IL-31)-high, type 1 cytokine (IFN-γ)-high, and/or type 3 cytokine (IL-22 and IL-17)-high, or mixed subtypes. Recently proposed biomarker endotyping aims at individualized treatment options, although the daily clinical use of endotypes is a future issue. To better understand the endotypes for clinicians, attempts to adjust each of the classical subtypes to endotypes are required. This review will discuss the correspondence of the classical subtypes to the various endotypes that have recently been proposed.
Phylogeny and Evolution of Cocconeiopsis (Cocconeidaceae) as Revealed by Complete Chloroplast and Mitochondrial Genomes
Authors: Du Feichao , Li Yuhang , Xu Kuidong
Published: December 2023

The genus Cocconeiopsis was separated from Navicula, but its systematic position is in debate. We sequenced the complete chloroplast and mitochondrial genome of Cocconeidaceae for the first time with Cocconeiopsis kantsiensis and investigated its phylogeny and evolutionary history. Results showed that the plastid genome was 140,415 bp long with 167 genes. The mitochondrial genome was 43,732 bp long with 66 genes. Comparative analysis showed that the plastid genome structure of C. kantsiensis was most similar to those of three Navicula species and Halamphora americana, and its size was significantly smaller than that of a monoraphid species. Its mitochondrial genome was similar to that of related species except for Phaeodactylum tricornutum. The multigene phylogeny reconstruction showed that Cocconeiopsis was sister to Didymosphenia but distant from Naviculaceae. The two-gene phylogenetic analysis containing 255 species showed Cocconeiopsis was sister to Cocconeis, and distant from Naviculaceae as well. Divergence time estimation indicates the common ancestor of cocconeid species occurred about 62.8 Ma and Cocconeiopsis diverged with monoraphid Cocconeis about 58.9 Ma. Our results support the assignment of Cocconeiopsis to Cocconeidaceae and that monoraphid cocconeids were likely evolved from the lineage of Cocconeiopsis.
TET Enzymes and 5hmC Levels in Carcinogenesis and Progression of Breast Cancer: Potential Therapeutic Targets
Authors: Salmerón-Bárcenas Eric Genaro , Zacapala-Gómez Ana Elvira , Torres-Rojas Francisco Israel , Antonio-Véjar Verónica , Ávila-López Pedro Antonio , Baños-Hernández Christian Johana , Núñez-Martínez Hober Nelson , Dircio-Maldonado Roberto , Martínez-Carrillo Dinorah Nashely , Ortiz-Ortiz Julio , Jiménez-Wences Hilda
Published: December 2023

Breast Cancer (BC) was the most common female cancer in incidence and mortality worldwide in 2020. Similarly, BC was the top female cancer in the USA in 2022. Risk factors include earlier age at menarche, oral contraceptive use, hormone replacement therapy, high body mass index, and mutations in BRCA1/2 genes, among others. BC is classified into Luminal A, Luminal B, HER2-like, and Basal-like subtypes. These BC subtypes present differences in gene expression signatures, which can impact clinical behavior, treatment response, aggressiveness, metastasis, and survival of patients. Therefore, it is necessary to understand the epigenetic molecular mechanism of transcriptional regulation in BC, such as DNA demethylation. Ten-Eleven Translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) on DNA, which in turn inhibits or promotes the gene expression. Interestingly, the expression of TET enzymes as well as the levels of the 5hmC epigenetic mark are altered in several types of human cancers, including BC. Several studies have demonstrated that TET enzymes and 5hmC play a key role in the regulation of gene expression in BC, directly (dependent or independent of DNA de-methylation) or indirectly (via interaction with other proteins such as transcription factors). In this review, we describe our recent understanding of the regulatory and physiological function of the TET enzymes, as well as their potential role as biomarkers in BC biology.
New Chalcone Derivatives Containing 2,4-Dichlorobenzenesulfonamide Moiety with Anticancer and Antioxidant Properties
Authors: Bułakowska Anita , Sławiński Jarosław , Hering Anna , Gucwa Magdalena , Ochocka J. Renata , Hałasa Rafał , Balewski Łukasz , Stefanowicz-Hajduk Justyna
Published: December 2023

Chalcones and their derivatives, both natural and synthetic, exhibit diverse biological activities. In this study, we focused on designing and synthesizing (E)-2,4-dichloro-N-(4-cinnamoylphenyl)-5-methylbenzenesulfonamides 4–8 with the following two pharmacophore groups: 2,4-dichlorobenzenesulfonamide and chalcone. The obtained compounds displayed notable anticancer effects on various human cancer cells, such as cervical HeLa, acute promyelocytic leukemia HL-60, and gastric adenocarcinoma AGS, when assessed with the MTT test. The activity of all compounds against cancer cells was significant, and the obtained IC50 values were in the range of 0.89–9.63 µg/mL. Among all the tested compounds, derivative 5 showed the highest activity on the AGS cell line. Therefore, it was tested for cell cycle inhibition, induction of mitochondrial membrane depolarization, and activation of caspase-8 and -9. These results showed that this compound strongly arrested the cell cycle in the subG0 phase, depolarized the mitochondrial membrane, and activated caspase-8 and -9. Similar to the anticancer effects, all the obtained compounds 4–8 were also assessed for their antioxidant activity. The highest antiradical effect was demonstrated for derivative 5, which was able to inhibit DPPH and ABTS radicals. All examined compounds showed dose-dependent activity against neutrophil elastase. Notably, derivatives 7 and 8 demonstrated inhibitory properties similar to oleanolic acid, with IC50 values of 25.61 ± 0.58 and 25.73 ± 0.39 µg/mL, respectively. To determine the antibacterial activity of derivatives 4–8, the minimum bacteriostatic concentration (MIC) values were estimated (>500 µg/mL for all the tested bacterial strains). The findings demonstrate the substantial potential of sulfonamide-based chalcone 5 as a promising drug in anticancer therapy.
Resistance and Aerobic Training Were Effective in Activating Different Markers of the Browning Process in Obesity
Authors: Pontes Lidia Passinho Paz , Alves Nakakura Fernanda Cristina , Neto Nelson Inácio Pinto , Boldarine Valter Tadeu , Maza Paloma Korehisa , Santos Paloma Freire , Avila Felipe , Silva-Neto Artur Francisco , Antunes Hanna Karen Moreira , Dâmaso Ana Raimunda , Oyama Lila Missae
Published: December 2023

Lifestyle changes regarding diet composition and exercise training have been widely used as a non-pharmacological clinical strategy in the treatment of obesity, a complex and difficult-to-control disease. Taking the potential of exercise in the browning process and in increasing thermogenesis into account, the aim of this paper was to evaluate the effect of resistance, aerobic, and combination training on markers of browning of white adipose tissue from rats with obesity who were switched to a balanced diet with normal calorie intake. Different types of training groups promote a reduction in the adipose tissue and delta mass compared to the sedentary high-fat diet group (HS). Interestingly, irisin in adipose tissues was higher in the resistance exercise (RE) and aerobic exercise (AE) groups compared to control groups. Moreover, in adipose tissue, the fibroblast growth factor 21 (FGF21), coactivator 1 α (PGC1α), and peroxisome proliferator-activated receptor gamma (PPARγ) were higher in response to resistance training RE compared with the control groups, respectively. Additionally, uncoupling protein 1 (UCP1) showed higher levels in response to group AE compared to the HS group. In conclusion, the browning process in white adipose tissue responds differently toward different training exercise protocols, with resistance and aerobic training efficient in activating different biomarkers of the browning process, upregulating irisin, FGF21, PGC1α, PPARγ, and UCP1 in WAT, which together may suggest an improvement in the thermogenic process in the adipose tissue. Considering the experimental conditions of the present investigation, we suggest future research to pave new avenues to be applied in clinical practices to combat obesity.
Bioactive Properties of Tagetes erecta Edible Flowers: Polyphenol and Antioxidant Characterization and Therapeutic Activity against Ovarian Tumoral Cells and Caenorhabditis elegans Tauopathy
Authors: Rivas-García Lorenzo , Crespo-Antolín Lara , Forbes-Hernández Tamara Y. , Romero-Márquez Jose M. , Navarro-Hortal María D. , Arredondo Miguel , Llopis Juan , Quiles José L. , Sánchez-González Cristina
Published: December 2023

Tagetes erecta is an edible flower deeply rooted in traditional Mexican culture. It holds a central role in the most popular and iconic Mexican celebration, “the Day of the Dead”. Furthermore, it is currently receiving interest as a potential therapeutic agent, motivated mainly by its polyphenol content. The present study aims to evaluate the biological activity of an extract synthesized from the petals of the edible flower T. erecta. This extract showed significant antioxidant scores measured by the most common in vitro methodologies (FRAP, ABTS, and DPPH), with values of 1475.3 μM trolox/g extr, 1950.3 μM trolox/g extr, and 977.7 μM trolox/g extr, respectively. In addition, up to 36 individual polyphenols were identified by chromatography. Regarding the biomedical aspects of the petal extract, it exhibited antitumoral activity against ovarian carcinoma cells evaluated by the MTS assay, revealing a lower value of IC50 compared to other flower extracts. For example, the extract from T. erecta reported an IC50 value half as low as an extract from Rosa × hybrida and six times lower than another extract from Tulbaghia violacea. This antitumoral effect of T. erecta arises from the induction of the apoptotic process; thus, incubating ovarian carcinoma cells with the petal extract increased the rate of apoptotic cells measured by flow cytometry. Moreover, the extract also demonstrated efficacy as a therapeutic agent against tauopathy, a feature of Alzheimer’s disease (AD) in the Caenorhabditis elegans experimental model. Treating worms with the experimental extract prevented disfunction in several motility parameters such as wavelength and swimming speed. Furthermore, the T. erecta petal extract prevented the release of Reactive Oxygen Species (ROS), which are associated with the progression of AD. Thus, treatment with the extract resulted in an approximate 20% reduction in ROS production. These findings suggest that these petals could serve as a suitable source of polyphenols for biomedical applications.
Structure and Neuroprotector Properties of a Complex Compound of Lithium with Comenic Acid
Authors: Kozin Stanislav , Kravtsov Alexandr , Ivashchenko Lev , Dotsenko Victor , Dzhimak Stepan , Aksenov Nicolai , Vashurin Arthur , Ivlev Vasily , Baryshev Mikhail , Bespalov Alexandr , Fedulova Lilia , Dorohova Anna , Anashkina Anastasia
Published: December 2023

The structure, antioxidant and neuroprotective properties of lithium comenate (lithium 5-hydroxy-4-oxo-4H-pyran-2-carboxylate) were studied. Lithium comenate was obtained by reacting comenic acid (H2Com) with lithium hydroxide in an aqueous solution. The structure of lithium comenate was confirmed via thermal analysis, mass spectrometry, IR, NMR and UV spectroscopy. The crystal structure was studied in detail via X-ray diffraction. The compound crystallized in a non-centrosymmetric space group of symmetry of the orthorhombic system Pna21 in the form of a hydrate, with three water molecules entering the first coordination sphere of the cation Li+ and one molecule forming a second environment through non-valent contacts. The gross formula of the complex compound was established [Li(HCom)(H2O)3]·H2O. It has been established that lithium comenate has a pronounced neuroprotective activity under the excitotoxic effect of glutamate, increasing the survival rate of cultured rat cerebellar neurons more than two-fold. It has also been found that the pre-stress use of lithium comenate at doses of 1 and 2 mg/kg has an antioxidant effect, which is manifested in a decrease in oxidative damage to the brain tissues of mice subjected to immobilization stress. Based on the data available in the literature, we believe that the high neuroprotective and antioxidant efficacy of lithium comenate is a consequence of the mutual potentiation of the pharmacological effects of lithium and comenic acid.
Preclinical and Clinical Observations Implying Combination Therapy to Enhance the Efficacy of the Her-2/neu B-Cell Peptide-Based Vaccine HER-Vaxx and to Prevent Immune Evasion
Authors: Tobias Joshua , Högler Sandra , Raigel Martin , Lin Diego Shih-Chieh , Chao Yee , Kenner Lukas , Garner-Spitzer Erika , Yavrom Sharon , Ede Nicholas J. , Zielinski Christoph C. , Kundi Michael , Wiedermann Ursula
Published: December 2023

Her-2/neu-targeting therapy by passive application with trastuzumab is associated with acquired resistance and subsequent metastasis development, which is attributed to the upregulation of tumoral PD-L1 expression and the downregulation of Her-2/neu. We aimed to investigate this association, following active immunization with our recently constructed B-cell peptide-based Her-2/neu vaccines in both preclinical and clinical settings. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and combined positive score (CPS) were applied to evaluate Her-2/neu and PD-L1 expression using a murine syngeneic tumor model for Her-2/neu lung metastases and tumor biopsies from a gastric cancer patient with disease progression. A significant and concomitant reduction in Her-2/neu and the upregulation of PD-L1 expression was observed in vaccinated mice after 45 days, but not after 30 days, of metastases development. A significant increase in tumor-infiltrating B lymphocytes was observed at both time points. The downregulation of Her-2/neu and the upregulation of PD-L1 were observed in a patient’s primary tumor at the disease progression time point but not prior to vaccination (Her-2/neu IHC: 3 to 0, FISH: 4.98 to 1.63; PD-L1 CPS: 0% to 5%). Our results further underline the need for combination therapy by targeting PD-L1 to prevent metastasis formation and immune evasion of Her-2/neu-positive and PD-L1-negative tumor cells.
G Protein-Coupled Receptors in Cell Signaling Transduction
Authors: Beer-Hammer Sandra , Liebscher Ines
Published: December 2023

G protein-coupled receptors (GPCRs) and their downstream signaling pathways are critical targets for current pharmacotherapy [...]
Dynamic Structures of Bioactive Proteins as Determined by Nuclear Magnetic Resonance
Authors: Toke Orsolya , Batta Gyula
Published: December 2023

According to “Panta rhei”, a phrase by the ancient Greeks, you cannot enter the same river two times [...]
Catastrophic Antiphospholipid Syndrome: A Review
Authors: Siniscalchi Carmine , Basaglia Manuela , Riva Michele , Meschi Michele , Meschi Tiziana , Castaldo Giampiero , Di Micco Pierpaolo
Published: December 2023

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic or obstetric events occurring in individuals who have persistent antiphospholipid antibodies. Catastrophic antiphospholipid syndrome (CAPS) is a rare and potentially fatal form of APS characterized by severe thrombotic complications occurring in multiple organs over a short period of time or simultaneously. CAPS is associated with a high (50%) death rate. Infections, multi-organ failure, and cerebral and heart thrombosis represent the main complications of this syndrome. Generally, anticoagulants, glucocorticoids, therapeutic plasmapheresis (TPE), and intravenous immunoglobulin (IVIG) are used in combination for treatment. Multidisciplinary care involving different specialists from hematology, rheumatology, nephrology, infectious disease, critical care, and obstetrics is often required due to the complexity of the disease. Recent data emphasize the effectiveness of biologics such as anti-TNF-a monoclonal antibodies (adalimumab, certolizumab), anti-CD38 monoclonal antibody (daratumumab), BAFF/Blys inhibitor (belimumab), and BTK inhibitor (zanubrutinib) against CAPS. In order to understand the underlying causes of CAPS, one future possibility involves investigating and characterizing the hereditary and acquired risk factors associated with CAPS.
Li-Rich Mn-Based Cathode Materials for Li-Ion Batteries: Progress and Perspective
Authors: Guo Weibin , Weng Zhangzhao , Zhou Chongyang , Han Min , Shi Naien , Xie Qingshui , Peng Dong-Liang
Published: December 2023

The development of cathode materials with high specific capacity is the key to obtaining high-performance lithium-ion batteries, which are crucial for the efficient utilization of clean energy and the realization of carbon neutralization goals. Li-rich Mn-based cathode materials (LRM) exhibit high specific capacity because of both cationic and anionic redox activity and are expected to be developed and applied as cathode materials for a new generation of high-energy density lithium-ion batteries. Nevertheless, the difficulty of regulating anionic redox reactions poses significant challenges to LRM, such as low initial Coulombic efficiency, poor rate capability, and fast cycling capacity and voltage decay. To address the existing challenges of LRM, this review introduces their basic physicochemical characteristics in detail, analyzes the original causes of these challenges, focuses on the recent progress of the modification strategies, and then especially discusses the development prospects of LRM from different aspects.
Intraoperative Iridectomy in Femto-Laser Assisted Smaller-Incision New Generation Implantable Miniature Telescope
Authors: Mastropasqua Rodolfo , Gironi Matteo , D’Aloisio Rossella , Pastore Valentina , Boscia Giacomo , Vecchiarino Luca , Perna Fabiana , Clemente Katia , Palladinetti Ilaria , Calandra Michela , Piepoli Marina , Porreca Annamaria , Di Nicola Marta , Boscia Francesco
Published: December 2023

Background: In this study, we aimed to report the short-term (6 months) effects on visual functionality and safety of femto-laser assisted smaller-incision new-generation implantable miniature telescope (SING-IMT™) implanting, particularly related to postsurgical intraocular pressure increase, in patients suffering from end-stage age-related macular degeneration (AMD) and cataract. This device, designed for monocular use, aims to minimise the impact of the central scotoma by projecting the images onto a larger area of the photoreceptors surrounding the macula. Methods: In this prospective multicentric observational case series study, 6 eyes of 6 patients who underwent SING-IMT™ implantations were enrolled. At baseline and 6 months follow-up, best corrected distance visual acuity (BCDV) and best corrected near visual acuity (BCNVA), intraocular pressure (IOP), anterior chamber depth, endothelial cells count were assessed. In addition, IOP was also measured at 7, 15, 30, 45 days, and at 3 months follow-up. Finally, the incidence of complications was evaluated. Results: At final follow-up, in the study eyes, mean BCDVA improved by +10.0 letters (6.25; 13.8) letters and mean BCNVA improved by −0.30 logMAR (−0.55; −0.20). At postoperative month 6, we reported a mean IOP decrease of 4.50 mmHg (−5.75; −0.25). Interestingly, 83.3% of patients had an increased IOP value in at least one of the first two postoperative follow-ups (7 days and 15 days). In patients in whom intraoperative mechanical iridotomy was not performed, it was necessary to perform a postoperative YAG laser iridotomy to improve IOP management. Compared to the baseline, ECD loss at 6 months follow-up was 12.6%. Conclusions: The SING IMT™ device was found to be effective in the distance and near vision improvement, without serious postoperative complications. We recommend intraoperative mechanical iridectomy in order to easily manage post-operative IOP and to avoid sudden IOP rise with its possible consequences. These good results can be a hope to partially improve the quality of life of patients suffering from severe end stage macular atrophy.
Opioid Therapy and Implications for Oxidative Balance: A Clinical Study of Total Oxidative Capacity (TOC) and Total Antioxidative Capacity (TAC)
Authors: Kosciuczuk Urszula , Jakubow Piotr , Tarnowska Katarzyna , Rynkiewicz-Szczepanska Ewa
Published: December 2023

Background: Opioids are used in pharmacotherapy for chronic pain. The phenomenon of their influence on the oxidative–antioxidant balance is poorly understood. Additionally, little is known about the oxidative status in patients receiving chronic opioid noncancer pain therapy. Methods: The primary goal was to explore oxidative status using the total oxidative capacity (TOC) and total antioxidative capacity (TAC) in patients with chronic lower back pain (LBP) treated with opioids. The secondary task was to present the risk factors connected with the duration of therapy or anthropometric parameters. Plasma TOC and TAC were analyzed in the study group (n = 28), i.e., patients with chronic LBP treated with opioids, and in the control group (n = 11), i.e., healthy volunteers. Results: The TAC was significantly lower in the study group compared to the control group (p < 0.05), while the TOC did not differ significantly. A statistically lower TOC for buprenorphine compared to oxycodone (p = 0.019) and tramadol (p = 0.036) was observed. The TOC did not differ between tramadol and oxycodone. The highest TAC was described for oxycodone, while the TAC for buprenorphine and tramadol was significantly lower in comparison with oxycodone (p = 0.007 and p = 0.016). The TOC/TAC ratio was higher in patients with nicotinism in both groups.Conclusions: Patients receiving chronic opioid therapy presented a lower antioxidative capacity. There were differences in opioid-induced oxidative imbalance, which is very important clinically. Nicotinism increases the oxidative–antioxidative imbalance. The least oxidative capacity was associated with buprenorphine, while oxycodone showed the greatest antioxidant activity. The most favorable TOC/TAC ratio was observed for buprenorphine. It is suggested that buprenorphine or oxycodone has the best profile, and there is no correlation with the duration of opioid therapy or the opioid dose. However, all opioid substances can potentially enhance the oxidative–antioxidative status.
The Use of End-Tidal CO2 and Integrated Pulmonary Index to Predict Postspinal Hypotension in Cesarean Section
Authors: Aslanlar Emine , Alharach Camille Kamel , Kara İnci , Onal Ozkan , Aslanlar Durmuş Ali
Published: December 2023

Early diagnosis and treatment of postspinal hypotension (PSH) in obstetric anaesthesia reduces the risk of maternofetal complications. In this study, the effect of EtCO2 and the integrated pulmonary index (IPI) in predicting PSH was investigated. Patients scheduled for cesarean section under spinal anaesthesia were included. The Capnostream 35 respiratory monitor (Medtronic, Inc., Dublin, Ireland) was used for EtCO2 and IPI. PSH developed in 52 (63.4%) of the 82 patients. EtCO2 and IPI values decreased significantly compared with baseline values in patients who developed PSH. There were statistically significant differences in EtCO2 (p = 0.001) and the IPI change (p = 0.045) in patients who developed PSH compared with those who did not. It was found that the EtCO2 difference had an independent effect on predicting PSH (p < 0.05), whereas the IPI difference did not (p > 0.05). One unit decrease in EtCO2 from the baseline increased the risk of PSH by 3.3 times. ROC curve analysis showed that the magnitude of change in EtCO2 was diagnostic for predicting PSH (AUC: 0.90 (0.83–0.97; p < 0.001)). IPI showed no predictive value for postspinal hypotension in cesarean section. However, EtCO2 monitoring, which is non-invasive and real-time monitoring, can be used to predict postspinal hypotension.
Decreased Risk of Knee Osteoarthritis with Taller Height in an East Asian Population: A Nationwide Cohort Study
Authors: Lee Dong Hwan , Lee Hwa Sung , Jang Soo Hyun , Heu Jun-Young , Han Kyungdo , Lee Se-Won
Published: December 2023

Background: Numerous studies have explored factors impacting osteoarthritis (OA), but its relationship with height remains uncertain. This study investigates the relationship between height and osteoarthritis risk in South Korea. Methods: Participants aged 50 or older who underwent health screenings in 2009 were selected from the National Health Insurance System database. A total of 1,138,904 subjects were divided into height quartiles (Q1–Q4) based on age and gender. Cox proportional hazard models were used to assess knee osteoarthritis incidence risk, with the shortest quartile (Q1) as the reference. Results: After adjusting for age, sex, income, smoking, drinking, exercise, hypertension, diabetes mellitus, dyslipidemia, and body mass index (BMI), no significant difference in OA incidence risk based on height was observed. However, when adjusted for weight instead of BMI, we observed a gradual decrease in hazard ratio with increasing height. The hazard ratio for the tallest group was 0.787 (95% CI, 0.781~0.795). Similar results were obtained in all subgroups. Conclusions: Compared to previous studies, our findings present a clear distinction. Therefore, there may be racial differences in the association between height and knee OA risk, and our study provides evidence that, in East Asian populations, taller individuals have a reduced risk of knee OA.
Exploring the Prognostic Performance of MECKI Score in Heart Failure Patients with Non-Valvular Atrial Fibrillation Treated with Edoxaban
Authors: Mapelli Massimo , Mattavelli Irene , Salvioni Elisabetta , Capra Nicolò , Bonomi Alice , Cattadori Gaia , Pezzuto Beatrice , Campodonico Jeness , Piotti Arianna , Nava Alessandro , Piepoli Massimo , Magrì Damiano , Paolillo Stefania , Corrà Ugo , Raimondo Rosa , Lagioia Rocco , Vignati Carlo , Badagliacca Roberto , Perrone Filardi Pasquale , Senni Michele , Correale Michele , Cicoira Mariantonietta , Metra Marco , Guazzi Marco , Limongelli Giuseppe , Parati Gianfranco , De Martino Fabiana , Bandera Francesco , Bussotti Maurizio , Re Federica , Lombardi Carlo M. , Scardovi Angela B. , Sciomer Susanna , Passantino Andrea , Emdin Michele , Santolamazza Caterina , Perna Enrico , Passino Claudio , Sinagra Gianfranco , Agostoni Piergiuseppe
Published: December 2023

Introduction: Risk stratification in heart failure (HF) is essential for clinical and therapeutic management. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score is a validated prognostic model for assessing cardiovascular risk in HF patients with reduced ejection fraction (HFrEF). From the validation of the score, the prevalence of HF patients treated with direct oral anticoagulants (DOACs), such as edoxaban, for non-valvular atrial fibrillation (NVAF) has been increasing in recent years. This study aims to evaluate the reliability of the MECKI score in HFrEF patients treated with edoxaban for NVAF. Materials and Methods: This study included consecutive outpatients with HF and NVAF treated with edoxaban (n = 83) who underwent a cardiopulmonary exercise test (CPET). They were matched by propensity score with a retrospective group of HFrEF patients with NVAF treated with vitamin K antagonists (VKAs) from the MECKI score registry (n = 844). The study endpoint was the risk of cardiovascular mortality, urgent heart transplantation, or Left Ventricle Assist Device (LVAD) implantation. Results: Edoxaban patients were treated with a more optimized HF therapy and had different clinical characteristics, with a similar MECKI score. After propensity score, 77 patients treated with edoxaban were successfully matched with the MECKI-VKA control cohort. In both groups, MECKI accurately predicted the composite endpoint with similar area under the curves (AUC = 0.757 vs. 0.829 in the MECKI-VKA vs. edoxaban-treated group, respectively, p = 0.452). The two populations’ survival appeared non-significantly different at the 2-year follow-up. Conclusions: this study confirms the prognostic accuracy of the MECKI score in HFrEF patients with NVAF treated with edoxaban, showing improved predictive power compared to VKA-treated patients.
An Overview of Growth Factors as the Potential Link between Psoriasis and Metabolic Syndrome
Authors: Matwiejuk Mateusz , Myśliwiec Hanna , Chabowski Adrian , Flisiak Iwona
Published: December 2023

Psoriasis is a chronic, complex, and immunologically mediated systemic disease that not only affects the skin, but also the joints and nails. It may coexist with various other disorders, such as depression, psoriatic arthritis, cardiovascular diseases, diabetes mellitus, and metabolic syndrome. In particular, the potential link between psoriasis and metabolic syndrome is an issue worthy of attention. The dysregulation of growth factors could potentially contribute to the disturbances of keratinocyte proliferation, inflammation, and itch severity. However, the pathophysiology of psoriasis and its comorbidities, such as metabolic syndrome, remains incompletely elucidated. Growth factors and their abnormal metabolism may be a potential link connecting these conditions. Overall, the objective of this review is to analyze the role of growth factor disturbances in both psoriasis and metabolic syndrome.
BRAF Inhibitors in BRAF-Mutated Colorectal Cancer: A Systematic Review
Authors: Aiman Wajeeha , Ali Muhammad Ashar , Jumean Samer , Asfeen Ummul , Garcia Jose , Quirem Murad , Ahmad Amaar , Rayad Mohammad Nabil , Alkhlaifat Osama , Al Omour Bader , Chemarthi Venkata S. , Maroules Michael , Guron Gunwant , Shaaban Hamid
Published: December 2023

Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths globally. BRAF mutation is present in about 10% of CRC patients and is associated with a poor response to chemotherapy. These patients have a relatively poor prognosis. This review aims to assess the efficacy and safety of BRAF inhibitors in BRAF-mutated CRC patients. A literature search was performed on PubMed and Embase, and clinical trials relevant to BRAF inhibitors in CRC were included. Data were extracted for efficacy and safety variables. Two randomized clinical trials (n = 765) and eight non-randomized trials (n = 281) were included based on inclusion criteria. In RCTs, an overall response was reported in 23% of the patients treated with BRAF inhibitor-based regimens compared to 2.5% with control regimens. The hazard ratio of overall survival was also significantly better with triplet encorafenib therapy at 0.52 (95% CI = 0.39–0.70). In single-arm trials, ORR was 17% and 34% in two-drug and three-drug regimens, respectively. BRAF inhibitor-based regimens were safe and effective in the treatment of BRAF-mutated CRC. Large-scale randomized trials are needed to find a suitable population for each regimen. PROSPERO registration No. CRD42023471627.
The Influence of Aggressive Environmental Conditions on the Adhesion of Applied Crystalline Materials
Authors: Mottl Martin , Reiterman Pavel , Pazderka Jiří
Published: December 2023

Crystalline coatings are waterproofing systems used for additional protection against increased moisture and subsurface water ingress. Even though these crystalline materials are commonly used in moisture-protective systems, they have not yet been sufficiently scientifically described. The weakest link in the chain of interaction between crystalline coatings and underlying concrete is the transition zone. To increase knowledge of the interaction between these materials, a series of experiments was prepared using a specially formulated protective mortar as the final surface layer, with the function of additionally waterproofing the structure. An experimental study of the adhesion of surface layers based on secondary crystallization to provide additional protection to concrete structures loaded with moisture or ground water exposure is presented in this paper. The series of experiments carried out consisted of an analysis of protective crystalline mortar adhesion to concrete samples of identical composition. A set of experimental measurements under the influence of various boundary conditions was carried out to determine the bond strength between two different materials. For the experimental measurements, the materials were exposed to aggressive environments for which durability verification had not yet been performed. A modified protective mortar with crystalline admixture was used as an overlayed material. This mortar worked similarly to a crystalline coating after application. Over time, there was penetration of the underlaying concrete and a secondary hydration of the cement matrix which resulted in the waterproofing of the structure. The test samples were exposed to aggressive environmental conditions in the form of freezing–thawing cycles and a carbonation process. Pull-off tests were carried out on every test sample to determine the strength of the surface layers. The penetration of the crystalline agent into the base concrete was confirmed with an SEM observation. The results of the experimental program showed that exposure to the aggressive environment further reduced the strength of the modified mortar containing the crystalline admixture. However, the bond strength between the concrete and the modified mortar exceeded the tensile strength of the concrete.
An In Vivo Investigation of Non-Metallic vs. Metallic Hand Scalers on Zirconia Implant-Supported Crowns: A Year-Long Analysis of Peri-Implant Maintenance
Authors: Roemermann Dayna L. , Atout Reem , Pesun Igor , Kelekis-Cholakis Anastasia , Stavropoulou Chrysi , Renvert Stefan N. , França Rodrigo
Published: December 2023

This study examined whether the degree of abutment surface modification that may occur with regular periodontal instrumentation has a clinical impact in terms of increased plaque accumulation and increased peri-implant tissue inflammation on zirconia implant abutments. Thirteen patients who had zirconia implant crowns were recruited in this randomized clinical trial. Each patient acted as their control and had either the buccal or lingual surface of their screw-retained implant restoration scaled with a metallic scaler and the other surface with a non-metallic scaler at 3, 6, 9, and 12 months. Cytokine testing of the peri-implant crevicular fluid was completed at 0, 3, and 12 months for IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, or IFNγ. Implant crowns were removed at 12 months and evaluated under an atomic force microscope for the average roughness (Ra). The implant crowns were polished and re-inserted. The results were analyzed using the Kruskal–Wallis test, and post hoc tests were conducted with a significance level of α = 0.05. Significant differences in surface roughness (Ra) were observed between the metallic and non-metallic scalers. The median Ra values were 274.0 nm for metallic scalers and 147.1 nm for non-metallic scalers. However, there were no significant differences between the type of scaler used and the amount of clinical inflammation or cytokine production. Metallic scalers produced deeper, more aggressive surface alterations to the abutment/crown zirconia surface, but there was no statistically significant difference between the degree of surface alterations, amount of BOP, and the amplitude of cytokine inflammation produced.
A Level Set-Based Model for Image Segmentation under Geometric Constraints and Data Approximation
Authors: Khayretdinova Guzel , Apprato Dominique , Gout Christian
Published: December 2023

In this paper, we propose a new model for image segmentation under geometric constraints. We define the geometric constraints and we give a minimization problem leading to a variational equation. This new model based on a minimal surface makes it possible to consider many different applications from image segmentation to data approximation.
Aging Makes the Heart Grow Fonder: Age Influences Hearing Ability and Interactions between Psychological Phenomena in Patients with Chronic Tinnitus
Authors: Fresemann Maren , Boecking Benjamin , Steinmetzger Kurt , Brueggemann Petra , Rose Matthias , Mazurek Birgit
Published: December 2023

(1) Background: Risk factors for chronic tinnitus comprise interactions of individuals’ hearing difficulties and psychological distress—including anxiety, depression, and perceived stress levels. Both groups of factors likely become more pronounced with age, although mixed literature has also suggested increases in psychological resilience over time. To this end, only a few studies have delineated direct and indirect effects of age on audiological and psychological variables that might influence tinnitus-related distress in patients with chronic tinnitus. (2) Methods: N = 678 patients with chronic tinnitus completed audiological assessments alongside self-report measures of psychological and tinnitus-related distress. Path analyses investigated the effect of age on patients’ tinnitus-related distress via both audiological and psychological variables. (3) Results: Age was significantly associated with both hearing ability and psychological distress indices, with perceived stress and anxiety decreasing with aging. Different mediation models revealed that the association between age and tinnitus-related distress was mediated completely by hearing ability and partly by perceived stress and anxiety. (4) Conclusions: Whilst interactions of individuals’ hearing ability and psychological distress levels maintain tinnitus-related distress across the age span, the weighting of these factors may shift with age. Treatment approaches should consider hearing ability across the lifespan. Psychological factors should be individually conceptualized, considering both distress-related and potential resilience factors in old age.
An Update on Hypomagnesemia and Hypermagnesemia
Authors: Van Laecke Steven
Published: December 2023

Magnesium is an essential element with a pleiotropic role in human biology. Despite tight intestinal and renal regulation of its balance, insufficient intake can finally result in hypomagnesemia, which is a proxy of intracellular deficiency. Conditions such as diabetes, cancer, and infections are often associated with hypomagnesemia, which mostly predicts an unfavorable outcome. The effects of hypomagnesemia can either be direct and include neurological and cardiovascular symptoms or indirect, taking a mechanistic role in inflammation, endothelial dysfunction, and oxidative stress. The indication for intravenous magnesium as a treatment of torsades de pointes and pre-eclampsia is unrefuted, but new indications of peroral or intravenous supplementation, albeit with less supporting evidence, have emerged suggesting, respectively, an attenuation of vascular calcification in chronic kidney disease and improved rate control in atrial fibrillation. Other potential beneficial properties of magnesium, which were claimed by observational data, such as lipid lowering and renal protection, were not, or only partially, investigated in randomized controlled trials. Thus, the role of peroral supplementation of mild chronic asymptomatic hypomagnesemia should be separated from the more targeted prescription of magnesium in specific study populations. (Severe) hypermagnesemia is potentially life-threatening and occurs almost uniformly in subjects with severe renal failure exposed to either supplements or to magnesium-containing cathartics or antacids. Moderate hypermagnesemia is very common in pre-eclamptic women treated with intravenous magnesium. For most (but not all) studied endpoints, mild hypermagnesemia yields a survival benefit. Long-lasting concerns about the potential negative effects of mild hypermagnesemia on bone physiology and structure have so far not been unequivocally demonstrated to be troublesome.
Existential Constructions, Definiteness Effects, and Linguistic Contact: At the Crossroads between Spanish and Catalan
Authors: Agulló Jorge
Published: December 2023

Existential sentences in Spanish are sensitive to the definiteness or quantification restriction or effect, which prevents personal pronouns, proper nouns, and definite constituents from occupying the pivot position. Contact varieties between Spanish, a robust language as regards the effect, and Catalan, which has a weaker version, remain largely unexplored. This paper fills this void. A large corpus was gathered to quantitatively study the variation between definite and indefinite pivots. Examples involving definite, specific pivots and even proper names, hitherto unnoticed, are brought to the fore. The pivot of the existential in Spanish is argued to bear Partitive case, as shown by (i) pronominal existential pivots in other Romance languages, (ii) the phi-feature defectiveness of the clitic out of the pivot position, (iii) and partitive pronouns with unaccusatives in Spanish. The hypothesis is put forth that varieties of Spanish in contact with Catalan no longer relate Partitive case to the non-definiteness of the pivot.
The Devil’s Marriage: Folk Horror and the Merveilleux Louisianais
Authors: Doherty Ryan Atticus
Published: December 2023

At the beginning of his Creole opus The Grandissimes, George Washington Cable refers to Louisiana as “A land hung in mourning, darkened by gigantic cypresses, submerged; a land of reptiles, silence, shadow, decay”. This anti-pastoral view of Louisiana as an ecosystem of horrific nature and the very human melancholy it breeds is one that has persisted in popular American culture to the present day. However, the literature of Louisiana itself is marked by its creativity in blending elements of folktales, fairy tales, and local color. This paper proposes to examine the transhuman, or the transcendence of the natural by means of supernatural transformation, in folk horror tales of Louisiana. As the locus where the fairy tale meets the burgeoning Southern Gothic, these tales revolve around a reworking of what Vladimir Propp refers to as transfiguration, the physical and metaphysical alteration of the human into something beyond the human. The focus of this paper will be on three recurring figures in Louisiana folk horror: yellow fever, voodoo, and the Devil. Drawing upon works including Alcée Fortier’s collection of Creole folktales Louisiana Folktales (1895), Dr. Alfred Mercier’s “1878”, and various newspaper tales of voodoo ceremonies from the ante- and post-bellum periods, this article brings together theorizations about the fairy tale from Vladimir Propp and Jack Zipes and historiological approaches to the Southern Gothic genre to demonstrate that Louisiana, in its multilingual literary traditions, serves as a nexus where both genres blend uncannily together to create tales that are both geographically specific and yet exist outside of the historical time of non-fantastic fiction. Each of these figures, yellow fever, voodoo, and the Devil, challenges the expectations of what limits the human. Thus, this paper seeks to examine what will be termed the “Louisiana gothic”, a particular blend of fairy-tale timelessness, local color, and the transfiguration of the human. Ultimately, the Louisiana gothic, as expressed in French, English, and Creole, tends toward a view of society in decay, mobilizing these elements of horror and of fairy tales to comment on a society that, after the revolution in Saint-Domingue, the Louisiana Purchase, and the Civil War, was seen as falling into inevitable decline. This commentary on societal decay, expressed through elements of folk horror, sets apart Louisiana gothic as a distinct subgenre that challenges conventions about the structures and functions of the fairy tale.
N-Doped Carbon Nanowire-Modified Macroporous Carbon Foam Microbial Fuel Cell Anode: Enrichment of Exoelectrogens and Enhancement of Extracellular Electron Transfer
Authors: Liu Ke , Ma Zhuo , Li Xinyi , Qiu Yunfeng , Liu Danqing , Liu Shaoqin
Published: December 2023

Microbial fuel cell (MFC) performance is affected by the metabolic activity of bacteria and the extracellular electron transfer (EET) process. The deficiency of nanostructures on macroporous anode obstructs the enrichment of exoelectrogens and the EET. Herein, a N-doped carbon nanowire-modified macroporous carbon foam was prepared and served as an anode in MFCs. The anode has a hierarchical porous structure, which can solve the problem of biofilm blockage, ensure mass transport, favor exoelectrogen enrichment, and enhance the metabolic activity of bacteria. The microscopic morphology, spectroscopy, and electrochemical characterization of the anode confirm that carbon nanowires can penetrate biofilm, decrease charge resistance, and enhance long-distance electron transfer efficiency. In addition, pyrrolic N can effectively reduce the binding energy and electron transfer distance of bacterial outer membrane hemin. With this hierarchical anode, a maximum power density of 5.32 W/m3 was obtained, about 2.5-fold that of bare carbon cloth. The one-dimensional nanomaterial-modified macroporous anodes in this study are a promising strategy to improve the exoelectrogen enrichment and EET for MFCs.
Microstructure and Wear Behavior of Heat-Treated Mg-1Zn-1Ca Alloy for Biomedical Applications
Authors: Pulido-González Nuria , García-Rodríguez Sonia , Torres Belén , Rams Joaquin
Published: December 2023

The microstructure and wear properties of a Mg-1wt.% Zn-1wt.% Ca (ZX11) alloy with different heat treatments have been investigated. The ZX11 alloy was tested in the as-cast state and after different heat treatment conditions: solution-treated (at 450 °C for 24 h), peak-aged (solution-treated + aged at 180 °C for 3 h), and over-aged (solution-treated + aged at 180 °C for 24 h). The microstructure of the as-cast sample showed a continuous intermetallic phase at the grain boundaries, while the heat-treated samples exhibited discrete precipitated particles within the grains. To evaluate the wear behavior, the samples were tested using a pin-on-disc configuration, where the wear rates and friction coefficients were measured at different loads and sliding speeds. An AZ31 magnesium alloy was used as the counterbody. The worn surfaces and the wear debris were studied to identify the main wear mechanisms corresponding to each test condition. The results indicated the presence of abrasion, oxidation, and adhesive wear mechanisms in all testing conditions. In the as-cast state, delamination and plastic deformation were the dominant wear mechanisms, while they were less relevant in the heat-treated conditions. The peak-aged samples exhibited the lowest wear rates, suggesting that modifying the distribution of intermetallic precipitates contributed to enhancing the wear resistance of the alloy.