bluuebunny/crossref_metadata_2025 huggingface dataset:
Activity of Potassium Channels in CD8+ T Lymphocytes: Diagnostic and Prognostic Biomarker in Ovarian Cancer?
Authors: Jusztus Vivien , Medyouni Ghofrane , Bagosi Adrienn , Lampé Rudolf , Panyi György , Matolay Orsolya , Maka Eszter , Krasznai Zoárd Tibor , Vörös Orsolya , Hajdu Péter
Published: February 2024

CD8+ T cells play a role in the suppression of tumor growth and immunotherapy. Ion channels control the Ca2+-dependent function of CD8+ lymphocytes such as cytokine/granzyme production and tumor killing. Kv1.3 and KCa3.1 K+ channels stabilize the negative membrane potential of T cells to maintain Ca2+ influx through CRAC channels. We assessed the expression of Kv1.3, KCa3.1 and CRAC in CD8+ cells from ovarian cancer (OC) patients (n = 7). We found that the expression level of Kv1.3 was higher in patients with malignant tumors than in control or benign tumor groups while the KCa3.1 activity was lower in the malignant tumor group as compared to the others. We demonstrated that the Ca2+ response in malignant tumor patients is higher compared to control groups. We propose that altered Kv1.3 and KCa3.1 expression in CD8+ cells in OC could be a reporter and may serve as a biomarker in diagnostics and that increased Ca2+ response through CRAC may contribute to the impaired CD8+ function.
Carnosic Acid against Lung Cancer: Induction of Autophagy and Activation of Sestrin-2/LKB1/AMPK Signalling
Authors: O’Neill Eric J. , Sze Newman Siu Kwan , MacPherson Rebecca E. K. , Tsiani Evangelia
Published: February 2024

Non-small cell lung cancer (NSCLC) represents 80% of all lung cancer cases and is characterized by low survival rates due to chemotherapy and radiation resistance. Novel treatment strategies for NSCLC are urgently needed. Liver kinase B1 (LKB1), a tumor suppressor prevalently mutated in NSCLC, activates AMP-activated protein kinase (AMPK) which in turn inhibits mammalian target of rapamycin complex 1 (mTORC1) and activates unc-51 like autophagy activating kinase 1 (ULK1) to promote autophagy. Sestrin-2 is a stress-induced protein that enhances LKB1-dependent activation of AMPK, functioning as a tumor suppressor in NSCLC. In previous studies, rosemary (Rosmarinus officinalis) extract (RE) activated the AMPK pathway while inhibiting mTORC1 to suppress proliferation, survival, and migration, leading to the apoptosis of NSCLC cells. In the present study, we investigated the anticancer potential of carnosic acid (CA), a bioactive polyphenolic diterpene compound found in RE. The treatment of H1299 and H460 NSCLC cells with CA resulted in concentration and time-dependent inhibition of cell proliferation assessed with crystal violet staining and 3H-thymidine incorporation, and concentration-dependent inhibition of survival, assessed using a colony formation assay. Additionally, CA induced apoptosis of H1299 cells as indicated by decreased B-cell lymphoma 2 (Bcl-2) levels, increased cleaved caspase-3, -7, poly (ADP-ribose) polymerase (PARP), Bcl-2-associated X protein (BAX) levels, and increased nuclear condensation. These antiproliferative and proapoptotic effects coincided with the upregulation of sestrin-2 and the phosphorylation/activation of LKB1 and AMPK. Downstream of AMPK signaling, CA increased levels of autophagy marker light chain 3 (LC3), an established marker of autophagy; inhibiting autophagy with 3-methyladenine (3MA) blocked the antiproliferative effect of CA. Overall, these data indicate that CA can inhibit NSCLC cell viability and that the underlying mechanism of action of CA involves the induction of autophagy through a Sestrin-2/LKB1/AMPK signaling cascade. Future experiments will use siRNA and small molecule inhibitors to better elucidate the role of these signaling molecules in the mechanism of action of CA as well as tumor xenograft models to assess the anticancer properties of CA in vivo.
Observing Dynamic Conformational Changes within the Coiled-Coil Domain of Different Laminin Isoforms Using High-Speed Atomic Force Microscopy
Authors: Akter Lucky , Flechsig Holger , Marchesi Arin , Franz Clemens M.
Published: February 2024

Laminins are trimeric glycoproteins with important roles in cell-matrix adhesion and tissue organization. The laminin α, ß, and γ-chains have short N-terminal arms, while their C-termini are connected via a triple coiled-coil domain, giving the laminin molecule a well-characterized cross-shaped morphology as a result. The C-terminus of laminin alpha chains contains additional globular laminin G-like (LG) domains with important roles in mediating cell adhesion. Dynamic conformational changes of different laminin domains have been implicated in regulating laminin function, but so far have not been analyzed at the single-molecule level. High-speed atomic force microscopy (HS-AFM) is a unique tool for visualizing such dynamic conformational changes under physiological conditions at sub-second temporal resolution. After optimizing surface immobilization and imaging conditions, we characterized the ultrastructure of laminin-111 and laminin-332 using HS-AFM timelapse imaging. While laminin-111 features a stable S-shaped coiled-coil domain displaying little conformational rearrangement, laminin-332 coiled-coil domains undergo rapid switching between straight and bent conformations around a defined central molecular hinge. Complementing the experimental AFM data with AlphaFold-based coiled-coil structure prediction enabled us to pinpoint the position of the hinge region, as well as to identify potential molecular rearrangement processes permitting hinge flexibility. Coarse-grained molecular dynamics simulations provide further support for a spatially defined kinking mechanism in the laminin-332 coiled-coil domain. Finally, we observed the dynamic rearrangement of the C-terminal LG domains of laminin-111 and laminin-332, switching them between compact and open conformations. Thus, HS-AFM can directly visualize molecular rearrangement processes within different laminin isoforms and provide dynamic structural insight not available from other microscopy techniques.
Metabonomics and Transcriptomics Analyses Reveal the Development Process of the Auditory System in the Embryonic Development Period of the Small Yellow Croaker under Background Noise
Authors: Jiang Qinghua , Liang Xiao , Ye Ting , Zhang Yu , Lou Bao
Published: February 2024

Underwater noise pollution has become a potential threat to aquatic animals in the natural environment. The main causes of such pollution are frequent human activities creating underwater environmental noise, including commercial shipping, offshore energy platforms, scientific exploration activities, etc. However, in aquaculture environments, underwater noise pollution has also become an unavoidable problem due to background noise created by aquaculture equipment. Some research has shown that certain fish show adaptability to noise over a period of time. This could be due to fish’s special auditory organ, i.e., their “inner ear”; meanwhile, otoliths and sensory hair cells are the important components of the inner ear and are also essential for the function of the auditory system. Recently, research in respect of underwater noise pollution has mainly focused on adult fish, and there is a lack of the research on the effects of underwater noise pollution on the development process of the auditory system in the embryonic development period. Thus, in this study, we collected embryo–larval samples of the small yellow croaker (Larimichthys polyactis) in four important stages of otic vesicle development through artificial breeding. Then, we used metabonomics and transcriptomics analyses to reveal the development process of the auditory system in the embryonic development period under background noise (indoor and underwater environment sound). Finally, we identified 4026 differentially expressed genes (DEGs) and 672 differential metabolites (DMs), including 37 DEGs associated with the auditory system, and many differences mainly existed in the neurula stage (20 h of post-fertilization/20 HPF). We also inferred the regulatory mode and process of some important DEGs (Dnmt1, CPS1, and endothelin-1) in the early development of the auditory system. In conclusion, we suggest that the auditory system development of L. polyactis begins at least in the neurula stage or earlier; the other three stages (tail bud stage, caudal fin fold stage, and heart pulsation stage, 28–35 HPF) mark the rapid development period. We speculate that the effect of underwater noise pollution on the embryo–larval stage probably begins even earlier.
Photodynamic Therapy for Atherosclerosis
Authors: Mytych Wiktoria , Bartusik-Aebisher Dorota , Łoś Aleksandra , Dynarowicz Klaudia , Myśliwiec Angelika , Aebisher David
Published: February 2024

Atherosclerosis, which currently contributes to 31% of deaths globally, is of critical cardiovascular concern. Current diagnostic tools and biomarkers are limited, emphasizing the need for early detection. Lifestyle modifications and medications form the basis of treatment, and emerging therapies such as photodynamic therapy are being developed. Photodynamic therapy involves a photosensitizer selectively targeting components of atherosclerotic plaques. When activated by specific light wavelengths, it induces localized oxidative stress aiming to stabilize plaques and reduce inflammation. The key advantage lies in its selective targeting, sparing healthy tissues. While preclinical studies are encouraging, ongoing research and clinical trials are crucial for optimizing protocols and ensuring long-term safety and efficacy. The potential combination with other therapies makes photodynamic therapy a versatile and promising avenue for addressing atherosclerosis and associated cardiovascular disease. The investigations underscore the possibility of utilizing photodynamic therapy as a valuable treatment choice for atherosclerosis. As advancements in research continue, photodynamic therapy might become more seamlessly incorporated into clinical approaches for managing atherosclerosis, providing a blend of efficacy and limited invasiveness.
Development of Antioxidant and Antimicrobial Membranes Based on Functionalized and Crosslinked Chitosan for Tissue Regeneration
Authors: Ciarlantini Clarissa , Lacolla Elisabetta , Francolini Iolanda , Fernández-García Marta , Muñoz-Núñez Carolina , Muñoz-Bonilla Alexandra , Piozzi Antonella
Published: February 2024

Tissue engineering is an interdisciplinary field that develops new methods to enhance the regeneration of damaged tissues, including those of wounds. Polymer systems containing bioactive molecules can play an important role in accelerating tissue regeneration, mitigating inflammation process, and fighting bacterial infection. Chitosan (CS) has attracted much attention regarding its use in wound healing system fabrication thanks to its biocompatibility, biodegradability, and the presence of functional groups in its structure. In this work, bioactive chitosan-based membranes were obtained by both chemical and physical modifications of the polymer with glycidyl methacrylate and glycerol (GLY), respectively. The most suitable GLY concentration to obtain wound healing systems with good elongation at break, a good water vapor transmission rate (WVTR), and good wettability values was 20% (w/w). Afterwards, the membranes were crosslinked with different concentrations of ethylene glycol dimethacrylate (EGDMA). By using a concentration of 0.05 mM EGDMA, membranes with a contact angle and WVTR values suitable for the application were obtained. To make the system bioactive, 3,4-dihydrocinnamic acid (HCAF) was introduced into the membranes, either by imbibition or chemical reaction, using laccase as a catalyst. Thermal and mechanical analyses confirmed the formation of a cohesive network, which limited the plasticizing effect of GLY, particularly when HCAF was chemically bound. The HCAF-imbibed membrane showed a good antioxidant and antimicrobial activity, highlighting the potential of this system for the treatment of wound healing.
Unveiling Novel Urease Inhibitors for Helicobacter pylori: A Multi-Methodological Approach from Virtual Screening and ADME to Molecular Dynamics Simulations
Authors: Valenzuela-Hormazabal Paulina , Sepúlveda Romina V. , Alegría-Arcos Melissa , Valdés-Muñoz Elizabeth , Rojas-Pérez Víctor , González-Bonet Ileana , Suardíaz Reynier , Galarza Christian , Morales Natalia , Leddermann Verónica , Castro Ricardo I. , Benso Bruna , Urra Gabriela , Hernández-Rodríguez Erix W. , Bustos Daniel
Published: February 2024

Helicobacter pylori (Hp) infections pose a global health challenge demanding innovative therapeutic strategies by which to eradicate them. Urease, a key Hp virulence factor hydrolyzes urea, facilitating bacterial survival in the acidic gastric environment. In this study, a multi-methodological approach combining pharmacophore- and structure-based virtual screening, molecular dynamics simulations, and MM-GBSA calculations was employed to identify novel inhibitors for Hp urease (HpU). A refined dataset of 8,271,505 small molecules from the ZINC15 database underwent pharmacokinetic and physicochemical filtering, resulting in 16% of compounds for pharmacophore-based virtual screening. Molecular docking simulations were performed in successive stages, utilizing HTVS, SP, and XP algorithms. Subsequent energetic re-scoring with MM-GBSA identified promising candidates interacting with distinct urease variants. Lys219, a residue critical for urea catalysis at the urease binding site, can manifest in two forms, neutral (LYN) or carbamylated (KCX). Notably, the evaluated molecules demonstrated different interaction and energetic patterns in both protein variants. Further evaluation through ADMET predictions highlighted compounds with favorable pharmacological profiles, leading to the identification of 15 candidates. Molecular dynamics simulations revealed comparable structural stability to the control DJM, with candidates 5, 8 and 12 (CA5, CA8, and CA12, respectively) exhibiting the lowest binding free energies. These inhibitors suggest a chelating capacity that is crucial for urease inhibition. The analysis underscores the potential of CA5, CA8, and CA12 as novel HpU inhibitors. Finally, we compare our candidates with the chemical space of urease inhibitors finding physicochemical similarities with potent agents such as thiourea.
Current Insights in Prolactin Signaling and Ovulatory Function
Authors: Szukiewicz Dariusz
Published: February 2024

Prolactin (PRL) is a pleiotropic hormone released from lactotrophic cells of the anterior pituitary gland that also originates from extrapituitary sources and plays an important role in regulating lactation in mammals, as well as other actions. Acting in an endocrine and paracrine/autocrine manner, PRL regulates the hypothalamic–pituitary–ovarian axis, thus influencing the maturation of ovarian follicles and ovulation. This review provides a detailed discussion of the current knowledge on the role of PRL in the context of ovulation and ovulatory disorders, particularly with regard to hyperprolactinemia, which is one of the most common causes of infertility in women. Much attention has been given to the PRL structure and the PRL receptor (PRLR), as well as the diverse functions of PRLR signaling under normal and pathological conditions. The hormonal regulation of the menstrual cycle in connection with folliculogenesis and ovulation, as well as the current classifications of ovulation disorders, are also described. Finally, the state of knowledge regarding the importance of TIDA (tuberoinfundibular dopamine), KNDγ (kisspeptin/neurokinin B/dynorphin), and GnRH (gonadotropin-releasing hormone) neurons in PRL- and kisspeptin (KP)-dependent regulation of the hypothalamic–pituitary–gonadal (HPG) axis in women is reviewed. Based on this review, a rationale for influencing PRL signaling pathways in therapeutic activities accompanying ovulation disorders is presented.
Hydrogel-Based Skin Regeneration
Authors: Arabpour Zohreh , Abedi Farshad , Salehi Majid , Baharnoori Seyed Mahbod , Soleimani Mohammad , Djalilian Ali R.
Published: February 2024

The skin is subject to damage from the surrounding environment. The repair of skin wounds can be very challenging due to several factors such as severe injuries, concomitant infections, or comorbidities such as diabetes. Different drugs and wound dressings have been used to treat skin wounds. Tissue engineering, a novel therapeutic approach, revolutionized the treatment and regeneration of challenging tissue damage. This field includes the use of synthetic and natural biomaterials that support the growth of tissues or organs outside the body. Accordingly, the demand for polymer-based therapeutic strategies for skin tissue defects is significantly increasing. Among the various 3D scaffolds used in tissue engineering, hydrogel scaffolds have gained special significance due to their unique properties such as natural mimicry of the extracellular matrix (ECM), moisture retention, porosity, biocompatibility, biodegradability, and biocompatibility properties. First, this article delineates the process of wound healing and conventional methods of treating wounds. It then presents an examination of the structure and manufacturing methods of hydrogels, followed by an analysis of their crucial characteristics in healing skin wounds and the most recent advancements in using hydrogel dressings for this purpose. Finally, it discusses the potential future advancements in hydrogel materials within the realm of wound healing.
Gut Microbiota and Biomarkers of Endothelial Dysfunction in Cirrhosis
Authors: Efremova Irina , Maslennikov Roman , Poluektova Elena , Medvedev Oleg , Kudryavtseva Anna , Krasnov George , Fedorova Maria , Romanikhin Filipp , Bakhitov Vyacheslav , Aliev Salekh , Sedova Natalia , Kuropatkina Tatiana , Ivanova Anastasia , Zharkova Maria , Pervushova Ekaterina , Ivashkin Vladimir
Published: February 2024

Our aim was to study the association of endothelial dysfunction biomarkers with cirrhosis manifestations, bacterial translocation, and gut microbiota taxa. The fecal microbiome was assessed using 16S rRNA gene sequencing. Plasma levels of nitrite, big endothelin-1, asymmetric dimethylarginine (ADMA), presepsin, and claudin were measured as biomarkers of endothelial dysfunction, bacterial translocation, and intestinal barrier dysfunction. An echocardiography with simultaneous determination of blood pressure and heart rate was performed to evaluate hemodynamic parameters. Presepsin, claudin 3, nitrite, and ADMA levels were higher in cirrhosis patients than in controls. Elevated nitrite levels were associated with high levels of presepsin and claudin 3, the development of hemodynamic circulation, hypoalbuminemia, grade 2–3 ascites, overt hepatic encephalopathy, high mean pulmonary artery pressure, increased abundance of Proteobacteria and Erysipelatoclostridium, and decreased abundance of Oscillospiraceae, Subdoligranulum, Rikenellaceae, Acidaminococcaceae, Christensenellaceae, and Anaerovoracaceae. Elevated ADMA levels were associated with higher Child–Pugh scores, lower serum sodium levels, hypoalbuminemia, grade 2–3 ascites, milder esophageal varices, overt hepatic encephalopathy, lower mean pulmonary artery pressure, and low abundance of Erysipelotrichia and Erysipelatoclostridiaceae. High big endothelin-1 levels were associated with high levels of presepsin and sodium, low levels of fibrinogen and cholesterol, hypocoagulation, increased Bilophila and Coprobacillus abundances, and decreased Alloprevotella abundance.
Chinese Cyberbullying Detection Using XLNet and Deep Bi-LSTM Hybrid Model
Authors: Chen Shifeng , Wang Jialin , He Ketai
Published: February 2024

The popularization of the internet and the widespread use of smartphones have led to a rapid growth in the number of social media users. While information technology has brought convenience to people, it has also given rise to cyberbullying, which has a serious negative impact. The identity of online users is hidden, and due to the lack of supervision and the imperfections of relevant laws and policies, cyberbullying occurs from time to time, bringing serious mental harm and psychological trauma to the victims. The pre-trained language model BERT (Bidirectional Encoder Representations from Transformers) has achieved good results in the field of natural language processing, which can be used for cyberbullying detection. In this research, we construct a variety of traditional machine learning, deep learning and Chinese pre-trained language models as a baseline, and propose a hybrid model based on a variant of BERT: XLNet, and deep Bi-LSTM for Chinese cyberbullying detection. In addition, real cyber bullying remarks are collected to expand the Chinese offensive language dataset COLDATASET. The performance of the proposed model outperforms all baseline models on this dataset, improving 4.29% compared to SVM—the best performing method in traditional machine learning, 1.49% compared to GRU—the best performing method in deep learning, and 1.13% compared to BERT.
Fine-Scale Genetic Structure of Curculio chinensis (Coleoptera: Curculionidae) Based on Mitochondrial COI: The Role of Host Specificity and Spatial Distance
Authors: Zhang Li , Wang Fuping , Wu Jiaxi , Ye Sicheng , Xu Ye , Liu Yanan
Published: February 2024

The Camellia weevil, Curculio chinensis (Chevrolat, 1978), is a dominant oligophagous pest that bores into the fruit of oil-tea Camellia. Genetic differentiation among populations in various hosts can easily occur, which hinders research on pest management. In this study, the genetic structure, genetic diversity, and phylogenetic structure of local C. chinensis populations were examined using 147 individuals (from 6 localities in Jiangxi), based on 2 mitochondrial COI markers. Results indicated that the C. chinensis population in Jiangxi exhibits a high haplotype diversity, especially for the populations from Cam. meiocarpa plantations. Structural differentiation was observed between Haplogroup 1 (73 individuals from Ganzhou, Jian, and Pingxiang) in the monoculture plantations of Cam. meiocarpa and Haplogroup 2 (75 individuals from Pingxiang and Jiujiang) in Cam. oleifera. Two haplogroups have recently undergone a demographic expansion, and Haplogroup 1 has shown a higher number of effective migrants than Haplogroup 2. This suggests that C. chinensis has been spreading from Cam. meiocarpa plantations to other oil-tea Camellia, such as Cam. oleifera. The increased cultivation of oil-tea Camellia in Jiangxi has contributed to a unique genetic structure within the C. chinensis population. This has, in turn, expanded the distribution of C. chinensis and increased migration between populations.
Measurement of Fitness and Predatory Ability of Four Predatory Mite Species in Tibetan Plateau under Laboratory Conditions
Authors: Xiang Dong , Wang Zhen , Xu Long , Wang Yunchao , Zhang Huanhuan , Yang Kun
Published: February 2024

Predatory mites are biological control agents used in many countries against various vegetable pests, particularly spider mites. Despite the significant presence of predatory mites in the Tibetan plateau, there is limited research on their potential against spider mites in the area. This study investigated the fitness parameters and performance against TSSM of four predatory, including Amblyseius swirskii (Athias-Henriot) and three species from the genus Neoseiulus (Neoseiulus californicus (McGregor), Neoseiulus barkeri (Hughes), and Neoseiulus cucumeris (Oudemans)), originally collected from fields in the Tibetan Plateau. Compared to the other three predatory species, A. swirskii exhibited the highest fecundity (11.60 ± 0.34) and the highest pre-adult survival rate (83.33 ± 3.33%). Since their juvenile survival rate (SR) was extremely low (13.33% ± 5.77%), most N. barkeri nymphs died before emergence. Compared to the other three predatory mites, A. swirskii showed the highest predation capacity against adult TSSMs at 15 d post-release (14.28 ± 2.24). Based on the results, A. swirskii was the most effective, and N. barkeri was the least effective in controlling two-spotted mites in the Tibetan Plateau among the four species tested in this study. Collectively, these findings imply notable advantages in employing A. swirskii for controlling two-spotted mites in the Tibetan Plateau. This study informs the development of a feasible biological control method based on suitable predatory mite species to manage TSSMs in the Tibetan Plateau.
The Diagnostic Value of CEUS in Assessing Non-Ossified Thyroid Cartilage Invasion in Patients with Laryngeal Squamous Cell Carcinoma
Authors: Pucėtaitė Milda , Farina Davide , Ryškienė Silvija , Mitraitė Dalia , Tarasevičius Rytis , Lukoševičius Saulius , Padervinskis Evaldas , Vaitkus Saulius
Published: February 2024

Background: Accurate assessment of thyroid cartilage invasion in squamous cell carcinoma (SCC) of the larynx remains a challenge in clinical practice. The aim of this study was to assess the diagnostic performance of contrast-enhanced ultrasound (CEUS), contrast-enhanced computed tomography (CECT), and magnetic resonance imaging (MRI) in the detection of non-ossified thyroid cartilage invasion in patients with SCC. Methods: CEUS, CECT, and MRI scans of 27 male patients with histologically proven SCC were evaluated and compared. A total of 31 cases were assessed via CEUS and CECT. The MR images of five patients and six cases were excluded (one patient had two suspected sites), leaving twenty-five cases for analysis via MRI. Results: CEUS showed the highest accuracy and specificity compared with CECT and MRI (87.1% vs. 64.5% and 76.0% as well as 84.0% vs. 64.0% and 72.7%, respectively). The sensitivity and negative predictive value of CEUS and MRI were the same (100%). CEUS yielded four false-positive findings. However, there were no statistically significant differences among the imaging modalities (p > 0.05). Conclusions: CEUS showed better diagnostic performance than CECT and MRI. Therefore, CEUS has the potential to accurately assess non-ossified thyroid cartilage invasion and guide appropriate treatment decisions, hopefully leading to improved patient outcomes.
One Anastomosis Gastric Bypass vs. Sleeve Gastrectomy in the Remission of Type 2 Diabetes Mellitus: A Retrospective Analysis on 3 Years of Follow-Up
Authors: Gambardella Claudio , Mongardini Federico Maria , Paolicelli Maddalena , Lucido Francesco Saverio , Tolone Salvatore , Brusciano Luigi , Parisi Simona , Esposito Rosetta , Iovino Francesco , Nazzaro Luca , Pizza Francesco , Docimo Ludovico
Published: February 2024

Background. Obesity is a prevalent condition associated with various comorbidities, impacting mortality, fertility, and quality of life. Its relationship with type 2 diabetes mellitus (DMII) is well established, with nearly 44% prevalence. Bariatric surgery has proven crucial for treating both obesity and DMII. The comparison between surgical techniques, such as sleeve gastrectomy (SG) and one anastomosis gastric bypass (OAGB), remains controversial in terms of glycemic control efficacy. This retrospective study aimed to assess DMII remission efficacy between SG and OAGB after 36 months. Methods. From January 2016 to September 2020, 201 patients who underwent SG and OAGB for morbid obesity associated with DMII were accurately followed-up with for 36 months, focusing on %HbA1c, DMII remission, anthropometric results, and nutrient deficiency. Results. Although DMII remission did not exhibit statistical significance between the groups (82% vs. 93%, SG vs. OAGB, p = 0.051), OAGB demonstrated a more robust association with glycemic control (Odds Ratio 0.51) throughout the entire follow-up and yielded superior anthropometric outcomes. Notably, nutrient deficiencies, excluding cholecalciferol, iron, and riboflavin, did not show significant intergroup differences. Conclusions. This study contributes valuable insights into the extended-term efficacy of SG and OAGB in DMII remission. The nuanced findings underscore the multifaceted nature of metabolic outcomes, suggesting that factors beyond weight loss influence diabetes resolution. Larger comparative studies are warranted to comprehensively address this issue.
Malondialdehyde Serum Levels in a Full Characterized Series of 430 Rheumatoid Arthritis Patients
Authors: Merino de Paz Nayra , Quevedo-Abeledo Juan Carlos , Gómez-Bernal Fuensanta , de Vera-González Antonia , Abreu-González Pedro , Martín-González Candelaria , González-Gay Miguel Ángel , Ferraz-Amaro Iván
Published: February 2024

Background. Oxidative stress has been involved in the pathogenesis of rheumatoid arthritis (RA). The serum malondialdehyde (MDA) level is a reliable biomarker of oxidative stress status. In the present work, we aimed to analyze how a comprehensive characterization of the disease characteristics in RA, including a lipid profile, insulin resistance, and subclinical atherosclerosis, relates to serum MDA levels. Methods. In a cross-sectional study that included 430 RA patients, serum MDA levels were evaluated. Multivariable analysis was performed to examine the relationship of MDA with disease activity scores and disease characteristics, including subclinical carotid atherosclerosis, a comprehensive lipid molecule profile, and indices of insulin resistance and beta cell function indices. Results. The erythrocyte sedimentation rate (ESR) showed a significant and positive relationship with MDA. However, this did not occur for other acute phase reactants such as C-reactive protein or interleukin-6. Although the DAS28-ESR score (Disease Activity Score in 28 joints) had a positive and significant association with MDA serum levels, other disease activity scores that do not use the erythrocyte sedimentation rate in their formula did not show a significant relationship with MDA. Other disease characteristics, such as disease duration and the existence of rheumatoid factor and antibodies against citrullinated protein, were not related to serum MDA levels. This also occurred for lipid profiles, insulin resistance indices, and subclinical carotid atherosclerosis, for which no associations with circulating MDA were found. Conclusions. The disease characteristics are not related to circulating MDA levels in patients with RA.
Two-Stage Exchange Arthroplasty for Periprosthetic Reverse Shoulder Arthroplasty Infection Provides Comparable Functional Outcomes to Primary Reverse Shoulder Arthroplasty
Authors: Saccomanno Maristella Francesca , Lädermann Alexandre , Collin Philippe
Published: February 2024

This study aimed to compare functional outcomes after two-stage revision reverse shoulder arthroplasty (RSA) for periprosthetic joint infection (PJI) with the results of primary RSA. Patients affected by PJI and treated by means of two-stage revision RSA were 1:1 matched with a group of patients who were treated electively with RSA without developing any complications. Out of 1477 RSAs performed between 2009 and 2021, 16 patients developed a PJI. Each matched cohort comprised 16 patients (3 females, 13 males). The mean age was 69.13 ± 5.43 years old in the PJI group and 70.28 ± 5.04 (p = 0.543) in the matched cohort. The mean follow-up was 41.23 ± 26.9 months in the PJI group and 28.5 ± 20.2 (p = 0.142) in the matched group. Only one patient showed recurrent PJI five years after revision RSA. Comparison between the PJI patients and matched patients did not show any significant differences at the latest follow-up, nor for subjective shoulder value (SSV) (p = 0.101) or Constant score (p = 0.134). Two-stage exchange RSA for PJI allows for appropriate control of the disease and good functional outcomes. Comparison with an age- and sex-matched cohort of uninfected patients showed no significant differences, thus confirming the idea that revision surgeries may lead to satisfactory functional outcomes, as expected after primary surgery.
Safety and Efficacy of PCSK9 Inhibitors in Patients with Acute Coronary Syndrome Who Underwent Coronary Artery Bypass Grafts: A Comparative Retrospective Analysis
Authors: Nasso Giuseppe , Larosa Claudio , Bartolomucci Francesco , Brigiani Mario Siro , Contegiacomo Gaetano , Demola Maria Antonietta , Vignaroli Walter , Tripoli Alessandra , Girasoli Cataldo , Lisco Rosanna , Trivigno Marialisa , Tunzi Roberto Michele , Loizzo Tommaso , Hila Dritan , Franchino Rosalba , Amodeo Vincenzo , Ventra Simone , Diaferia Giuseppe , Schinco Giacomo , Agrò Felice Eugenio , Zingaro Maddalena , Rosa Isabella , Lorusso Roberto , Del Prete Armando , Santarpino Giuseppe , Speziale Giuseppe
Published: February 2024

Background. The in-hospital reduction in low-density lipoprotein cholesterol (LDL-C) levels following acute coronary syndrome (ACS) is recommended in the current clinical guidelines. However, the efficacy of proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors in those patients undergoing coronary artery bypass graft (CABG) has never been demonstrated. Methods. From January 2022 to July 2023, we retrospectively analyzed 74 ACS patients characterized by higher LDL-C levels than guideline targets and who underwent coronary bypass surgery. In the first period (January 2022–January 2023), the patients increased their statin dosage and/or added Ezetimibe (Group STEZE, 43 patients). At a later time (February 2023–July 2023), the patients received not only statins and Ezetimibe but also Evolocumab 140 mg every 2 weeks starting as early as possible (Group STEVO, 31 patients). After one and three months post-discharge, the patients underwent clinical and laboratory controls with an evaluation of the efficacy lipid measurements and every adverse event. Results. The two groups did not differ in terms of preoperative risk factors and Euroscore II (STEVO: 2.14 ± 0.75 vs. STEZE: 2.05 ± 0.6, p = 0.29). Also, there was no difference between the groups in terms of ACS (ST-, Instable angina, or NSTE) and time of symptoms onset regarding total cholesterol, LDL-C, and HDL-C trends from the preprocedural period to 3-month follow-up, but there was a more significant reduction in LDL-C and total cholesterol in the STEVO group (p = 0.01 and p = 0.04, respectively) and no difference in HDL-C rise (p = 0.12). No deaths were reported. In three STEZE group patients, angina recurrence posed the need for percutaneous re-revascularization. No STEVO patients developed significant adverse events. The statistical difference in these serious events, 7% in STEZE vs. 0% in STEVO, was not significant (p = 0.26). Conclusions. Evolocumab initiated “as soon as possible” in ACS patients submitted to CABG with high-intensity statin therapy and Ezetimibe was well tolerated and resulted in a substantial and significant reduction in LDL-C levels at discharge, 1 month, and 3 months. This result is associated with a reduction but without a statistical difference between groups.
Comparison of Incidence or Recurrence of Anterior Uveitis in Patients with Ankylosing Spondylitis Treated with Tumor Necrosis Factor Inhibitors
Authors: Kwon Hyeon Yoon , Kim Yu Jeong , Kim Tae-Hwan , Ahn Seong Joon
Published: February 2024

Background: Anterior uveitis (AU) is a significant concern in patients with ankylosing spondylitis (AS), and the choice of tumor necrosis factor inhibitors (TNFi) as a treatment modality raises questions regarding its effects on AU. We compared the effects of TNFi on AU in patients with AS. Methods: Patients diagnosed with AS and treated with at least one TNFi, including anti-TNFα antibodies (adalimumab and infliximab) or a soluble TNF receptor molecule (etanercept), between January 2010 and December 2022, were retrospectively reviewed. We compared the recurrence rate of AU in patients with a history of uveitis and the incidence of new-onset AU in those without a history of uveitis among the three TNFi groups. We also compared the effects of two different TNFi agents in patients who underwent TNFi switching. Results: Within two years of treatment initiation, there was no significant difference in AU recurrence among the three TNFi groups. However, the incidence of new-onset AU was significantly higher in the etanercept group than in the adalimumab group (26.4% vs. 6.3%; p = 0.024). After two years, the AU recurrence rate was significantly lower in the adalimumab group than in the other groups (p < 0.001). Among patients who underwent anti-TNFi switching, adalimumab treatment was associated with a significantly lower incidence of uveitis than etanercept (p = 0.023). Conclusion: In the short-term period following TNFi therapy, etanercept induced new-onset AU more frequently than adalimumab in patients with AS. Adalimumab recipients experienced fewer AU recurrences during the subsequent long-term period compared to other TNFi recipients.
Impact of the Order of Movement on the Median Nerve Root Function: A Neurophysiological Study with Implications for Neurodynamic Exercise Sequencing
Authors: Ibrahim Dalia , Ahbouch Amal , Qadah Raneen Mohammed , Kim Meeyoung , Alrawaili Saud M. , Moustafa Ibrahim M.
Published: February 2024

Background: Neurodynamic exercise is a common clinical practice used to restore neural dynamic balance. The order in which movements are performed during these exercises is believed to play a crucial role in their effectiveness. This study aimed to investigate the impact of different sequences of neurodynamic exercise on nerve root function, with a specific focus on the median nerve. Methods: Participants were assigned randomly to three experimental groups, each undergoing a different test sequence: standard, proximal-to-distal, and distal-to-proximal. Dermatomal somatosensory evoked potentials (DSSEPs) were recorded at key levels (C6, C7, C8, and T1). Results: The findings revealed a significant influence of the movement sequence on DSSEP amplitudes. The execution of neurodynamic exercise in the proximal-to-distal sequence was associated with a notable reduction in amplitudes (p < 0.05). Conversely, the distal-to-proximal sequence resulted in increased amplitudes compared to the standard sequence (p < 0.05). Conclusions: This study underscores the importance of carefully considering the order of movements during neurodynamic exercising, particularly when evaluating nerve roots that lack the protective perineurium. The choice of sequence appears to have a substantial impact on nerve function, with implications for optimizing clinical neurodynamic exercise techniques.
The Impact of Extracorporeal Magnetic Stimulation as Addition to Mirabegron in Overactive Bladder Treatment in Women: A Single-Centre Randomized Sham-Controlled Study
Authors: Bele Uros , Serdinšek Tamara , Homšak Evgenija , But Igor
Published: February 2024

(1) Background: The purpose of our prospective, single-blinded, randomized, sham-controlled study was to investigate the effect of the additional extracorporeal magnetic stimulation (ExMI) to pharmacological treatment in overactive bladder syndrome (OAB) in women. (2) Methods: We recruited 56 women with OAB, who were allocated into two study groups: the active group received mirabegron 50 mg daily and a total of 16 sessions of ExMI in 8 weeks, whereas the sham group received mirabegron 50 mg daily and sham stimulation following the same treatment protocol. Treatment success was evaluated after 4 and 8 weeks. (3) Results: Both groups experienced significant reduction in daytime urinary frequency, nocturia, and number of weekly incontinence episodes after 8 weeks. There were no statistically significant differences in end-point daytime urinary frequency and nocturia between groups. However, the overall average reduction rate in weekly number of incontinence episodes was 43.7% in treatment group and 24.2% in the control group. The number of urinary incontinence episodes in the treatment and control group was reduced for 3.8 ± 11.8 vs. 2.5 ± 4.3 episodes at week 4 and additional 3.3 ± 6 vs. 0.4 ± 3.2 episodes at week 8, respectively (p = 0.013). Moreover, IIQ-7 score showed a significantly greater score reduction and patients’ evaluated improvement of symptoms was higher in the active group. (4) Conclusions: The addition of ExMI to mirabegron in OAB treatment further improves the weekly incontinence episode reduction rate and also leads to grater improvement in symptoms.
Quality Indicators and Clinical Outcomes of Acute Stroke: Results from a Prospective Multicenter Registry in Greece (SUN4P)
Authors: Korompoki Eleni , Ntaios George , Tountopoulou Argyro , Mavraganis Georgios , Tsampalas Evangelos , Kalliontzakis Ioannis , Vassilopoulou Sofia , Manios Efstathios , Savopoulos Christos , Milionis Haralampos , Protogerou Athanasios , Kakaletsis Nikolaos , Galanis Petros , Kaitelidou Daphne , Siskou Olga , Vemmos Konstantinos ,   on behalf of the SUN4P Project Collaborators
Published: February 2024

Aim: The Stroke Units Necessity for Patients (SUN4P) project aims to provide essential data on stroke healthcare in Greece. Herein, we present results on established quality indicators and outcomes after first-ever stroke occurrences. Methods: This prospective multicenter study included consecutive patients admitted to nine hospitals across Greece in 2019–2021. Descriptive statistics were used to present patients’ characteristics, key performance measures and stroke outcomes. Results: Among 892 patients, 755 had ischemic stroke (IS) (mean age 75.6 ± 13.6, 48.7% males) and 137 had hemorrhagic stroke (HS) (mean age 75.8 ± 13.2, 57.7% males). Of those, 15.4% of IS and 8% of HS patients were treated in the acute stroke unit (ASU) and 20.7% and 33.8% were admitted to the intensive care unit (ICU) or high-dependency unit (HDU), respectively. A total of 35 (4.6%) out of 125 eligible patients received intravenous alteplase with a door-to needle time of 60 min (21–90). The time to first scan for IS patients was 60 min (31–105) with 53.2% undergoing a CT scan within 60 min post presentation. Furthermore, 94.4% were discharged on antiplatelets, 69.8% on lipid-lowering therapy and 61.6% on antihypertensives. Oral anticoagulants (OAC) were initiated in 73.2% of the 153 IS patients with atrial fibrillation (AF). Among the 687 IS patients who survived, 85.4% were discharged home, 12% were transferred to rehabilitation centers, 1.2% to nursing homes and 1.3% to another hospital. Conclusions: The SUN4P Registry is the first study to provide data from a prospectively collected cohort of consecutive patients from nine representative national hospitals. It represents an important step in the evaluation and improvement of the quality of acute stroke care in Greece.
No Harmful Effect of Endovascular Treatment before Decompressive Surgery—Implications for Handling Patients with Space-Occupying Brain Infarction
Authors: Pelz Johann Otto , Engelmann Simone , Scherlach Cordula , Bungert-Kahl Peggy , Dabbagh Alhuda , Lindner Dirk , Michalski Dominik
Published: February 2024

This study explored short- and mid-term functional outcomes in patients undergoing decompressive hemicraniectomy (DHC) due to space-occupying cerebral infarction and asked whether there is a potentially harmful effect of a priorly performed endovascular treatment (EVT). Medical records were screened for patients requiring DHC due to space-occupying cerebral infarction between January 2016 and July 2021. Functional outcomes at hospital discharge and at 3 months were assessed by the modified Rankin Scale (mRS). Out of 65 patients with DHC, 39 underwent EVT before DHC. Both groups, i.e., EVT + DHC and DHC alone, had similar volumes (280 ± 90 mL vs. 269 ± 73 mL, t-test, p = 0.633) and proportions of edema and infarction (22.1 ± 6.5% vs. 22.1 ± 6.1%, t-test, p = 0.989) before the surgical intervention. Patients undergoing EVT + DHC tended to have a better functional outcome at hospital discharge compared to DHC alone (mRS 4.8 ± 0.8 vs. 5.2 ± 0.7, Mann–Whitney-U, p = 0.061), while the functional outcome after 3 months was similar (mRS 4.6 ± 1.1 vs. 4.8 ± 0.9, Mann–Whitney-U, p = 0.352). In patients initially presenting with a relevant infarct demarcation (Alberta Stroke Program Early CT Score ≤ 5), the outcome was similar at hospital discharge and after 3 months between patients with EVT + DHC and DHC alone. This study provided no evidence for a harmful effect of EVT before DHC in patients with space-occupying brain infarction.
Use of the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) in Spinal Muscular Atrophy
Authors: Brown Laurey , Hoffman Katie , Corbo-Galli Chiara , Dong Siyuan , Zumpf Katelyn , Weigel Christa , Blomgren Colleen , Munson Hannah , Bidwell Jessa , Rao Vamshi , Kuntz Nancy L. , Schwaede Abigail , Krosschell Kristin J.
Published: February 2024

Background: Spinal muscular atrophy (SMA) has a remarkable impact on function and participation. Subsequently, the caregivers of individuals with SMA are impacted as well. Providers and the SMA community should be aware of the presence of and likely expectations for the existence of caregiver burden. Methods: The Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) quantifies caregivers’ perceptions of function and quality of life pertaining to time, finance and emotion. Analyses were conducted among SMA types and ambulatory and ventilatory status. Participants with SMA had varying ranges of function and were on pharmaceutical treatment. Total ACEND score, longitudinal change in total ACEND score, total quality of life (QOL) score, change in total QOL score and subdomains for QOL, including time, emotion and finance, were all explored. Results: Overall, the ACEND demonstrated discriminant validity and some observed trends. Total ACEND scores improved for caregivers of those with SMA 2, remained stable longitudinally for caregivers of those with SMA 1 and 3 and were not influenced by ventilation status. The caregivers of individuals with SMA 1 had the lowest total quality of life (QOL) score, as did the caregivers of non-ambulatory individuals and those requiring assisted ventilation. Longitudinally, there were no changes in total QOL between caregivers of individuals with different SMA types or ambulatory or ventilation status. There were some differences in emotional needs, but no differences in financial impact between the caregivers of individuals with different types of SMA or ambulatory and ventilatory status. Conclusions: With this information enlightening the presence of caregiver burden and expected changes in burden with pharmaceutical treatment, providers, third party payors and the SMA community at large can better assist, equip and empower those providing the necessary assistance to enable the lives of those with SMA.
Reduction of Post-Surgical Facial Edema Following Bromelain and Coumarin Intake in Traumatology: A Prospective Study with 100 Patients
Authors: Consorti Giuseppe , Monarchi Gabriele , Paglianiti Mariagrazia , Betti Enrico , Balercia Paolo
Published: February 2024

Background: Bromelain and coumarins are recognized as safe and effective therapeutic agents, used by individuals to treat ailments such as postoperative edema, inflammation and other diseases. Bromelain has been proven to be well absorbed by the body after oral administration, and it has no major side effects even after prolonged use. The purpose of this study is to evaluate the effectiveness of bromelain and other nutraceuticals in reducing post-surgical swelling, pain and the need of anti-inflammatory drugs in maxillofacial post-traumatic surgery. Methods: This prospective open-label study was conducted on patients undergoing surgery for trauma of the maxillofacial area. One hundred patients were selected and divided into two groups: one group who underwent therapy with bromelain, Aesculus hippocastanum and Melilotus officinalis and a control group that was not given the drug in postoperative therapy. Results: Patients in the experimental group showed a reduction of edema in the first and second postoperative weeks, a faster complete reduction of facial edema and a lower reduction in maximum mouth opening and needed less anti-inflammatory therapy to control pain. Conclusions: These findings seem to provide evidence that Brovas® may be effective in improving postoperative edema outcomes in patients undergoing surgical treatment of facial fractures.