bluuebunny/crossref_metadata_2025 huggingface dataset:
Future Therapeutic Strategies for Alzheimer’s Disease: Focus on Behavioral and Psychological Symptoms
Authors: Kwon Kyoung Ja , Kim Hahn Young , Han Seol-Heui , Shin Chan Young
Published: October 2024

Alzheimer’s disease (AD) is a progressive, degenerative brain disorder that impairs memory and thinking skills, leading to significant economic and humanistic burdens. It is associated with various neuropsychiatric symptoms (NPS) such as anxiety, agitation, depression, aggression, apathy, and psychosis. NPSs are common in patients with AD, affecting up to 97% of individuals diagnosed with AD. The severity of NPS is linked to disease progression and cognitive decline. NPS in Alzheimer’s disease leads to increased morbidity, mortality, caregiver burden, earlier nursing home placement, and higher healthcare costs. Despite their significant impact, clinical research on NPS in AD is limited. In clinical settings, accurately distinguishing and diagnosing NPS related to AD remains a challenge. Additionally, conventional treatments for NPS in AD are often ineffective, highlighting the need for new therapies that target these specific symptoms. Understanding these comorbidities can aid in early diagnosis and better management of AD. In this review, we provide a summary of the various neurological and psychiatric symptoms (NPS) associated with AD and new candidates under development for the treatment of NPS based on their therapeutic targets and mechanisms. On top of the conventional NPS studied so far, this review adds recent advancements in the understanding of social functional impairment in AD. This review also provides information that can contribute to the advancement of studies and translational research in this field by emphasizing therapeutic targets and mechanisms of action focused on AD-related NPS rather than conventional mechanisms targeted in AD drug development. Above all, considering the relative lack of research in this new field despite the importance of clinical, medical, and translational research, it may increase interest in NPS in AD, its pathophysiological mechanisms, and potential therapeutic candidates such as molecules with antioxidant potential.
The Role of Retinoic-Acid-Related Orphan Receptor (RORs) in Cellular Homeostasis
Authors: Nematisouldaragh Darya , Kirshenbaum Eryn , Uzonna Michael , Kirshenbaum Lorrie , Rabinovich-Nikitin Inna
Published: October 2024

Retinoic-acid-related orphan receptors (RORs) are transcription factors belonging to the nuclear receptor subfamily consisting of RORα, RORβ, and RORγ. By binding to the ROR response elements (ROREs) on target gene promoters, RORs regulate a wide variety of cellular processes, including autophagy, mitophagy, oxidative stress, and inflammation. The regulatory roles of RORs are observed in cardiac cells, hepatocytes, pulmonary epithelial cells, renal cells, immune cells, and cancer cells. A growing body of clinical and experimental evidence suggests that ROR expression levels are markedly reduced under different pathological and stress conditions, suggesting that RORs may play a critical role in the pathogenesis of a variety of disease states, including myocardial infarction, immune disorders, cancer, and metabolic syndrome. Reductions in RORs are also associated with inhibition of autophagy, increased reactive oxygen species (ROS), and increased cell death, underscoring the importance of RORs in the regulation of these processes. Herein, we highlight the relationship between RORs and homeostatic processes that influence cell viability. Understanding how these intricate processes are governed at the cellular level is of high scientific and clinical importance to develop new therapeutic strategies that modulate ROR expression and disease progression.
Regulation Mechanisms of the Glutamate Transporter in the Response of Pacific Oyster upon High-Temperature Stress
Authors: Zhang Xueshu , Wen Xue , Si Yiran , Li Deliang , Yang Chuanyan , Wang Lingling , Song Linsheng
Published: October 2024

Glutamate transporters (GLTs) are integral to the glutamatergic system, modulating glutamate homeostasis to enhance resilience and resistance against environmental stress. There are six GLTs identified in the Pacific oyster (Crassostrea gigas), which were categorized into two subfamilies: excitatory amino acid transporters (CgEAATs) and vesicular glutamate transporters (CgVGLUTs). The CgEAATs harbor a GltP domain, while CgVGLUTs feature an MFS domain, both with conserved sequence and structural characteristics. The expression of CgGLTs is elevated during the planktonic larval stage compared to the fertilized egg stage and is constitutively expressed in various tissues of adult oysters, suggesting its critical role in both larval development and the physiological processes of adult oysters. Transcriptomic analysis revealed diverse expression patterns of GLTs in oyster gills after 7 days of high-temperature stress, with CgEAAT3 showing a significant upregulation. A KEGG pathway enrichment analysis identified glutathione metabolism and ferroptosis as prominently enriched pathways. At 48 h after high-temperature stress, the expression levels of Glutathione Peroxidase 4 (CgGPX4) and CgEAAT3, along with elevated Fe content in the gills, significantly increased. Moreover, the RNAi-mediated the inhibition of CgEAAT3 expression under high-temperature stress, resulting in a significant reduction in CgGPX4 expression and a further increase in Fe accumulation in oyster gills. These results indicate that CgEAAT3 contributes to the regulation of ferroptosis and redox homeostasis by modulating CgGPX4 expression. This study provides new insights into the adaptive mechanisms of bivalves to environmental stress.
A BPTF Inhibitor That Interferes with the Multidrug Resistance Pump to Sensitize Murine Triple-Negative Breast Cancer Cells to Chemotherapy
Authors: Sinanian Melanie M. , Rahman Afshan , Elshazly Ahmed M. , Neely Victoria , Nagarajan Balaji , Kellogg Glen E. , Risinger April L. , Gewirtz David A.
Published: October 2024

Triple-negative breast cancer (TNBC) is associated with a generally poor prognosis due to its highly aggressive and metastatic nature, lack of targetable receptors, as well as the frequent development of resistance to chemotherapy. We previously reported that AU1, a small molecule developed as an inhibitor of BPTF (bromodomain PHD finger-containing transcription factor), was capable of sensitizing preclinical models of TNBC to chemotherapy in part via the promotion of autophagy. In studies reported here, we identify an additional property of this compound, specifically that sensitization is associated with the inhibition of the P-glycoprotein (P-gp) efflux pump. In silico molecular docking studies indicate that AU1 binds to active regions of the efflux pump in a manner consistent with the inhibition of the pump function. This work identifies a novel chemical structure that can influence multidrug efflux, an established mechanism of drug resistance in TNBC, that has not yet been successfully addressed by clinical efforts.
Wound Healing, Anti-Inflammatory and Anti-Oxidant Activities, and Chemical Composition of Korean Propolis from Different Sources
Authors: Dekebo Aman , Geba Chalshisa , Bisrat Daniel , Jeong Jin Boo , Jung Chuleui
Published: October 2024

Propolis, such as is used as bio-cosmetics and in functional materials, is increasing because of its antioxidant medicinal benefits. However, its pharmacological and chemical composition is highly variable, relative to its geography and botanical origins. Comparative studies on three propolis samples collected from different regions in Korea have been essential for linking its provenance, chemical composition, and biological activity, thereby ensuring the efficient utilization of its beneficial properties. Here, we report the chemical composition and biological activities such as the antioxidant, wound healing, and anti-inflammatory effects of the ethanolic extract of Korean propolis collected from two regions. We compared the chemical constituents of three 70% ethanol-extracted (EE) samples, including the Andong, Gongju field (GF), and Gongju mountain (GM)-sourced propolis using Gas chromatography–mass spectrometry (GC–MS). The major and common components of these EE Korean propolis were flavonoids such as pinocembrin (12.0–17.7%), chrysin (5.2–6.8%), and apigenin (5.30–5.84%). The antioxidant property using a 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity assay of EEP showed substantial differences among samples with the highest from Andong. The sample 10% GM levigated in simple ointment was found to be the most active in wound healing activity based on the excision, incision, and dead space wound models. The potential of propolis for wound healing is mainly due to its evidenced properties, such as its antimicrobial, anti-inflammatory, analgesic, and angiogenesis promoter effects, which need further study. The anti-inflammatory activity and NO production inhibitory effect were highest in GM samples. However, GM and GF samples demonstrated similar inhibitory effects on the expression of inflammatory mediators such as iNOS, IL-1β, and IL-6. The presence of a higher concentration of flavonoids in Korean EE propolis might be responsible for their promising wound healing, anti-inflammatory, and antioxidant properties.
The Role of miR-155 in Modulating Gene Expression in CD4+ T Cells: Insights into Alternative Immune Pathways in Autoimmune Encephalomyelitis
Authors: Cichalewska-Studzinska Maria , Szymanski Jacek , Stec-Martyna Emilia , Perdas Ewelina , Studzinska Miroslawa , Jerczynska Hanna , Kulczycka-Wojdala Dominika , Stawski Robert , Mycko Marcin P.
Published: October 2024

CD4+ T cells are considered the main orchestrators of autoimmune diseases. Their disruptive effect on CD4+ T cell differentiation and the imbalance between T helper cell populations can be most accurately determined using experimental autoimmune encephalomyelitis (EAE) as an animal model of multiple sclerosis (MS). One epigenetic factor known to promote autoimmune inflammation is miRNA-155 (miR-155), which is significantly upregulated in inflammatory T cells. The aim of the present study was to profile the transcriptome of immunized mice and determine their gene expression levels based on mRNA and miRNA sequencing. No statistically significant differences in miRNA profile were observed; however, substantial changes in gene expression between miRNA-155 knockout (KO) mice and WT were noted. In miR-155 KO mice, mRNA expression in CD4+ T cells changed in response to immunization with the myeloid antigen MOG35-55. After restimulation with MOG35-55, increased Ffar1 (free fatty acid receptor 1) and Scg2 (secretogranin-2) expression were noted in the CD4+ T cells of miR-155-deficient mice; this is an example of an alternative response to antigen stimulation.
Identification of SNP and SilicoDArT Markers and Characterization of Their Linked Candidate Genes Associated with Maize Smut Resistance
Authors: Tomkowiak Agnieszka
Published: October 2024

The implementation of biological advancements in agricultural production is the response to the needs of the agricultural sector in the 21st century, enabling increased production and improved food quality. Biological progress in the maize breeding and seed industries is unique in terms of their social and ecological innovation aspects. It affects agricultural productivity and the adaptation of cultivated maize varieties to market demands and changing climate conditions without compromising the environment. Modern maize resistance breeding relies on a wide range of molecular genetic research techniques. These technologies enable the identification of genomic regions associated with maize smut resistance, which is crucial for characterizing and manipulating these regions. Therefore, the aim of this study was to identify molecular markers (SilicoDArT and SNP) linked to candidate genes responsible for maize smut resistance, utilizing next-generation sequencing, as well as association and physical mapping. By using next-generation sequencing (NGS) and statistical tools, the analyzed maize genotypes were divided into heterotic groups, which enabled the prediction of the hybrid formula in heterosis crosses. In addition, Illumina sequencing identified 60,436 SilicoDArT markers and 32,178 SNP markers (92,614 in total). For association mapping, 32,900 markers (26,234 SilicoDArT and 6666 SNP) meeting the criteria (MAF > 0.25 and the number of missing observations < 10%) were used. Among the selected markers, 61 were highly statistically significant (LOD > 2.3). Among the selected 61 highly statistically significant markers (LOD > 2.3), 10 were significantly associated with plant resistance to maize smut in two locations (Smolice and Kobierzyce). Of the 10 selected markers, 3 SilicoDArT (24016548, 2504588, 4578578) and 3 SNP (4779579, 2467511, 4584208) markers were located within genes. According to literature reports, of these six genes, three (ATAD3, EDM2, and CYP97A3) are characterized proteins that may play a role in the immune response that develops in response to corn smut infection. In the case of genotypes belonging to the same origin groups, markers linked to these genes can be used to select varieties resistant to corn smut. These markers will also be tested on genotypes belonging to other maize origin groups to demonstrate their universality.
Short Peptides Protect Fibroblast-Derived Induced Neurons from Age-Related Changes
Authors: Kraskovskaya Nina , Linkova Natalia , Sakhenberg Elena , Krieger Daria , Polyakova Victoria , Medvedev Dmitrii , Krasichkov Alexander , Khotin Mikhail , Ryzhak Galina
Published: October 2024

Neurons become more vulnerable to stress factors with age, which leads to increased oxidative DNA damage, decreased activity of mitochondria and lysosomes, increased levels of p16, decreased LaminB1 proteins, and the depletion of the dendritic tree. These changes are exacerbated in vulnerable neuronal populations during the development of neurodegenerative diseases. Glu-Asp-Arg (EDR) and Lys-Glu-Asp (KED), and Ala-Glu-Asp-Gly (AEDG) peptides have previously demonstrated neuroprotective effects in various models of Alzheimer’s disease. In this study, we investigated the influence of EDR, KED, and AEDG peptides on the aging of fibroblast-derived induced neurons. We used a new in vitro cellular model of human neuronal aging based on the transdifferentiation of aged dermal fibroblasts from elderly donors into induced cortical neurons. All peptides promote the arborization of the dendritic tree, increasing both the number of primary processes and the total length of dendrites. Tripeptides have no effect on the activity of mitochondria and lysosomes and the level of p16 protein in induced neurons. EDR peptide reduces oxidative DNA damage in induced neurons derived from elderly donor fibroblasts. Short peptides partially protect induced neurons from age-related changes and stimulate dendritogenesis in neurons. They can be recommended for use as neuroprotective agents.
Comparative Validation of Scintillator Materials for X-Ray-Mediated Neuronal Control in the Deep Brain
Authors: Hildebrandt Mercedes , Koshimizu Masanori , Asada Yasuki , Fukumitsu Kansai , Ohkuma Mahito , Sang Na , Nakano Takashi , Kunikata Toshiaki , Okazaki Kai , Kawaguchi Noriaki , Yanagida Takayuki , Lian Linyuan , Zhang Jianbing , Yamashita Takayuki
Published: October 2024

When exposed to X-rays, scintillators emit visible luminescence. X-ray-mediated optogenetics employs scintillators for remotely activating light-sensitive proteins in biological tissue through X-ray irradiation. This approach offers advantages over traditional optogenetics, allowing for deeper tissue penetration and wireless control. Here, we assessed the short-term safety and efficacy of candidate scintillator materials for neuronal control. Our analyses revealed that lead-free halide scintillators, such as Cs3Cu2I5, exhibited significant cytotoxicity within 24 h and induced neuroinflammatory effects when injected into the mouse brain. In contrast, cerium-doped gadolinium aluminum gallium garnet (Ce:GAGG) nanoparticles showed no detectable cytotoxicity within the same period, and injection into the mouse brain did not lead to observable neuroinflammation over four weeks. Electrophysiological recordings in the cerebral cortex of awake mice showed that X-ray-induced radioluminescence from Ce:GAGG nanoparticles reliably activated 45% of the neuronal population surrounding the implanted particles, a significantly higher activation rate than europium-doped GAGG (Eu:GAGG) microparticles, which activated only 10% of neurons. Furthermore, we established the cell-type specificity of this technique by using Ce:GAGG nanoparticles to selectively stimulate midbrain dopamine neurons. This technique was applied to freely behaving mice, allowing for wireless modulation of place preference behavior mediated by midbrain dopamine neurons. These findings highlight the unique suitability of Ce:GAGG nanoparticles for X-ray-mediated optogenetics. The deep tissue penetration, short-term safety, wireless neuronal control, and cell-type specificity of this system offer exciting possibilities for diverse neuroscience applications and therapeutic interventions.
Microbiomes-Plant Interactions and K-Humate Application for Salinity Stress Mitigation and Yield Enhancement in Wheat and Faba Bean in Egypt’s Northeastern Delta
Authors: Mostafa Soha S. M. , Fares Clair N. , Bishara Mounira M. , Azzam Clara R. , Awad Adel A. , Elgaml Naayem M. M. , Mostafa Mohamed S. M.
Published: October 2024

Salinity, resulting from climate change and excessive mineral fertilization, burdens farmers and negatively impacts soil and water ecosystems in the Northeastern Nile Delta. Organic and biological approaches are crucial for addressing these issues. This study examined the effects of individual and combined inoculations with cyanobacteria, yeast, and Arbuscular Mycorrhizal Fungi (AMF), with or without K-Humate and reducing Nitrogen, phosphorus and potassium (NPK) mineral fertilizers application rates to crop quality of wheat and faba bean. In preliminary laboratory experiments, the interactive effects of these microbiomes on plant antioxidant and soil enzyme production were examined under salinity stress. Results showed that co-inoculation, especially with K-Humate, yielded superior outcomes compared to individual inoculations. These findings were validated by a field trial conducted in saline-alkaline soil in the Northeastern Nile Delta region. All biological treatments 25% of recommended doses, and enhancing salinity tolerance, increasing yield, and improving enhanced rhizosphere microbial activity, including soil enzyme activity, AMF colonization, spore density, and the total numbers of bacteria, cyanobacteria, and yeast. These effects were further amplified by K-Humate and were more pronounced with combined inoculations than with individual ones, leading to improved soil fertility and significant increases in both crop quantity and quality compared to control treatments. The triple treatment, combining cyanobacteria, yeast, and mycorrhizae in the presence of K-Humate while reducing the mineral NPK rate by 75%, achieved superior increases in the productivity of wheat grains and faba bean seeds, reaching 54.72% and 128.92%, respectively, compared to the 100% NPK mineral control. This treatment also significantly improved crop quality, with notable increases in nitrogen, potassium, phosphorus, and protein percentages in wheat grains and faba bean seeds. Microbiomes-interaction increased potassium uptake over sodium, enhancing the plant’s potassium/sodium ratio and improving salt stress tolerance. This approach reduces reliance on costly mineral fertilizers, enabling bio-organic farming in marginal lands, optimizing resource utilization, and preserving natural resources.
Timing of Plant Extracts Application in the Management of Meloidogyne incognita on Tomato Plants
Authors: Mnyambo Nicholus M. , Rantho Lebogang P. , Dube Zakheleni P. , Timana Moses
Published: October 2024

Meloidogyne incognita, a widespread and damaging plant parasite, reduces crop yields. Chemical treatments are common but pose health and environmental risks, leading to a search for safer alternatives. Plant extracts with secondary metabolites, like those from Maerua angolensis and Tabernaemontana elegans, show promise for nematode control, though their efficacies vary. This study aimed to investigate how the timing of applying T. elegans and M. angolensis extracts influenced the population densities of M. incognita and the growth of tomato (Solanum lycopersicon L.) plants. The experiment was a factorial design with two plant extracts applied at 5 g per plant and three different timings of application relative to nematode inoculation. Additionally, the experiment included positive (chemical standard (Nemacur® 10 GR)) and negative (plants inoculated with nematodes only) controls, alongside naturally grown plants. The results indicate that applying plant extracts before the nematode inoculation or simultaneously with the inoculation reduced the total nematode populations as effectively as the Nemacur positive control. Plants treated with extracts showed improved growth variables compared with those treated with Nemacur® and the natural growing conditions. In conclusion, applying plant extracts before or simultaneously with nematode inoculation effectively suppressed the nematodes and enhanced the plant growth variables. These findings suggest that such plant extracts could be adopted as part of integrated nematode management strategies in agricultural settings.
A Context-Based Perspective on Frost Analysis in Reuse-Oriented Big Data-System Developments
Authors: Buccella Agustina , Cechich Alejandra , Saurin Federico , Montenegro Ayelén , Rodríguez Andrea , Muñoz Angel
Published: October 2024

The large amount of available data, generated every second via sensors, social networks, organizations, and so on, has generated new lines of research that involve novel methods, techniques, resources, and/or technologies. The development of big data systems (BDSs) can be approached from different perspectives, all of them useful, depending on the objectives pursued. In particular, in this work, we address BDSs in the area of software engineering, contributing to the generation of novel methodologies and techniques for software reuse. In this article, we propose a methodology to develop reusable BDSs by mirroring activities from software product line engineering. This means that the process of building BDSs is approached by analyzing the variety of domain features and modeling them as a family of related assets. The contextual perspective of the proposal, along with its supporting tool, is introduced through a case study in the agrometeorology domain. The characterization of variables for frost analysis exemplifies the importance of identifying variety, as well as the possibility of reusing previous analyses adjusted to the profile of each case. In addition to showing interesting findings from the case, we also exemplify our concept of context variety, which is a core element in modeling reusable BDSs.
Early Postoperative Outcomes of the Direct Superior Approach versus the Posterior Approach in Total Hip Arthroplasty: A Systematic Review and Meta-Analysis
Authors: Shin Kyun-Ho , Kim Jin-Uk , Jang Il-Tae
Published: October 2024

Background/Objectives: The direct superior approach (DSA) is a tissue-sparing alternative to the traditional posterior approach (PA) in total hip arthroplasty (THA), potentially offering improved recovery and fewer complications. This study compares perioperative parameters, radiological and functional outcomes, and complications between the DSA and the PA in primary THA. Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. Databases searched included MEDLINE/PubMed, Cochrane Library, Embase, and Scopus. Studies comparing the DSA and the PA in primary THA were included based on predefined criteria. Data extraction and quality assessment were performed independently by two authors. Statistical analyses included calculating standardized mean differences (SMD), odds ratios (OR), and 95% confidence intervals (CI). Heterogeneity was assessed using the χ2 test, I2 statistics, and sensitivity analyses. Results: Out of 126 identified articles, 10 studies were included, which encompassed 28,063 patients (DSA: 1464; PA: 26,599). Significant advantages of the DSA over the PA were observed in blood loss (SMD −0.26, p < 0.01), transfusion rate (OR 0.59, p = 0.03), length of stay (SMD −0.59, p < 0.01), discharge to home rates (OR 2.32, p < 0.01), and incision length (SMD −2.75, p < 0.01). No significant differences were found in radiological outcomes or most functional scores, although the DSA showed higher Harris Hip Scores at 1 month (SMD 0.77, p < 0.01). Conclusions: The DSA offers significant perioperative advantages over the PA, including reduced blood loss, transfusion rates, LOS, incision length, and improved early functional recovery with higher discharge to home rates. Comparable complication rates and radiological outcomes support the DSA’s safety and efficacy for quicker recovery in THA.
The Therapeutic Potential of GLP-1 Receptor Agonists in the Management of Hidradenitis Suppurativa: A Systematic Review of Anti-Inflammatory and Metabolic Effects
Authors: Krajewski Piotr K. , Złotowska Aleksandra , Szepietowski Jacek C.
Published: October 2024

Background: Glucagon-like peptide-1 receptor agonists (GLP1-RAs) are synthetic peptides that mimic the natural activity of GLP-1, widely known for lowering blood glucose levels and promoting weight reduction. These characteristics make them a valuable tool in managing type 2 diabetes and obesity-related conditions. Recent findings indicate that GLP1-RAs may also offer therapeutic benefits in managing hidradenitis suppurativa (HS), a chronic inflammatory skin disorder closely associated with metabolic abnormalities, including obesity, diabetes, and dyslipidemia. This review explores the potential role of GLP1-RAs in managing HS. Methods: A systematic review was conducted by searching electronic databases, including MEDLINE and Google Scholar, without date limitations. Key search terms included “GLP-1” or “GLP-1 agonists” combined with “hidradenitis suppurativa” or “acne inversa”. Inclusion criteria were set for studies reporting on the use of GLP1-RAs as a treatment for HS, with articles discussing theoretical applications excluded. Data synthesis included findings from 25 relevant studies. Results: The analysis revealed that GLP1-RAs, specifically liraglutide and semaglutide, led to significant reductions in weight and systemic inflammation in HS patients. Notably, improvements in lesion severity and quality of life were reported. The anti-inflammatory effects of GLP1-RAs were attributed to the suppression of key inflammatory pathways involving TNF-α, IL-17, and NF-κB. Conclusions: GLP1-RAs demonstrate significant potential as an adjunct therapy for HS, addressing both the metabolic and inflammatory aspects of the condition. While early results are promising, further research is necessary to determine their long-term efficacy in managing HS.
Echocardiographic Assessment of Left Atrial Mechanics in Patients with Atrial Fibrillation Undergoing Electrical Cardioversion: A Systematic Review
Authors: Sonaglioni Andrea , Nicolosi Gian Luigi , Bruno Antonino , Lombardo Michele , Muti Paola
Published: October 2024

Background: To date, only a few studies have evaluated left atrial (LA) mechanics in patients with atrial fibrillation (AF) scheduled for electrical cardioversion (ECV). The present systematic review has been primarily designed to summarize the main findings of these studies and to examine the overall effect of AF on left atrial reservoir strain (LASr) in patients undergoing ECV. Methods: All the echocardiographic studies evaluating the effect of AF on LA mechanics in patients scheduled for ECV, selected from the PubMed and EMBASE databases, were included. There was no limitation of time period. The risk of bias was assessed by using the National Institutes of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: The full texts of 12 studies with 880 AF patients were analyzed. The pooled ECV success rate was 91.5% (range 65.8–100%). Over a median follow-up of 5.4 months (range 0.3–12 months), 35.2% of the patients (range 5–68.8%) experienced AF recurrence. At baseline, the average LASr was 11.4% (range 6.2–17.7%). A reduced LASr before ECV was strongly correlated with reduced left atrial appendage (LAA) flow velocities and/or thrombosis. The main independent predictors of cardioversion failure were impaired LASr and previous AF history. A severe LASr deterioration was independently correlated with AF recurrence after ECV. The other independent predictors of AR relapses were LA asynchrony, reduced difference between post- and pre-ECV LASr, and reduced right atrial reservoir strain. Conclusions: LASr assessment before ECV may provide useful prognostic information about AF relapses and improve the refinement of the thromboembolic risk of AF patients scheduled for ECV.
Impact of Tumor Volume and Other Factors on Renal Function After Partial Nephrectomy
Authors: González-Ginel Ignacio , Hernández-Arroyo Mario , García-Rayo Clara , Gómez-del-Cañizo Carmen , Rodríguez-Antolín Alfredo , Guerrero-Ramos Félix
Published: October 2024

Background and Objectives: One of the main objectives of partial nephrectomy is to preserve as much renal function as possible. However, the removal of functioning nephrons and ischemic damage secondary to the clamping of the renal pedicle can be associated with a certain degree of renal function loss. We aim to evaluate the relationship between tumor volume and other factors on renal function in the short term (1–3 months) and long term (6–12 months) in our series of partial nephrectomies. Methods: A retrospective study was conducted on 147 patients who underwent open or laparoscopic partial nephrectomy between 2018 and 2022. Tumor volume was estimated through reconstructions from the computed tomography images. Univariate and multivariate analyses of the data were performed. Results: The mean age was 58.2 years, with an average glomerular filtration rate (GFR) of 79 mL/min/m2. Of all partial nephrectomies, 76.2% were laparoscopic, 57.1% were T1a tumors, and the mean volume was 17 cc. The average ischemia time during surgery was 14.3 min, with a mean hemoglobin loss of 2.8 g/dL in the immediate postoperative period. No significant differences were found either in the short or long term regarding ischemia time (p = 0.57, p = 0.32) or tumor volume (p = 0.57, p = 0.33). However, in the multivariate analysis, it was observed that the variable with the greatest influence on short-term renal function was perioperative glomerular filtration, while in the long term, ischemia time, age, and tumor volume also had an influence. Conclusions: Tumor volume is not an independent factor for renal function deterioration in the short or long term. Short-term renal function is primarily determined by perioperative glomerular filtration. Perioperative glomerular filtration, ischemia time, age, and tumor volume can jointly predict long-term renal function.
Beyond Boundaries of a Trial: Post-Market Clinical Follow-Up of SOYA Patients
Authors: Gavín Carlos , Sebastián Victoria , Gimeno Mercedes , Coronel Pilar
Published: October 2024

Background/Objectives: osteoarthritis (OA) is a leading cause of disability. With an aging population and rising obesity rates, OA presents a growing challenge to health systems worldwide. Current OA treatments involve a mix of pharmacological and nonpharmacological interventions. Viscosupplementation with hyaluronic acid (HA) has proven effective, especially in knee OA, leading to its recommendation in international guidelines. This study investigates the sustained benefits of a single intra-articular HA injection beyond one year in patients coming from the SOYA trial, considering the EU MDR 2017/745 emphasis on post-market follow-up. Methods: A prospective, observational, open, post-marketing study in a cohort of patients that participated in the SOYA trial. Follow-up was carried out by means of a telephone survey, and the data were anonymized and coded so that patients could not be identified. The study was approved by the Alcorcón Hospital Institutional Review Board (Alcorcón, Madrid, Spain). Results: In the follow-up of the SOYA trial, 81.5% of patients sustained positive effects for over 6 months after the trial ended. This correlated with improved daily functioning, enhanced mood, and high patient satisfaction. Younger age and milder OA grades were associated with prolonged treatment effects. Notably, 82% of patients with >6 months of improvement did not require additional medication. Conclusions: the results of this study support the safety and performance of Adant® Plus as a treatment for patients with mild and moderate knee OA, with results lasting more than one year. Post-marketing studies are particularly relevant to examine the experience gained with the use of the device in routine clinical practice.
Clinical Remission Predictors in Non-Colonized Bronchiectasis and Severe Asthma with Type 2-Targeted Biologic Therapy: A Retrospective Real-Life Pilot Study
Authors: Quaranta Vitaliano Nicola , Portacci Andrea , Montagnolo Francesca , Dragonieri Silvano , Iorillo Ilaria , Lulaj Ernesto , Maselli Leonardo , Buonamico Enrico , Carpagnano Giovanna Elisiana
Published: October 2024

Background/Objective: Patients with severe asthma (SA) and non-cystic fibrosis bronchiectasis (BE) without microbiological colonization represent a unique and understudied population. Type 2-targeted biologic therapies have emerged as a promising treatment for these patients. However, predictive factors for achieving clinical remission remain unclear. This study aims to identify the predictive factors for achieving clinical remission in patients with severe asthma and non-colonized bronchiectasis undergoing type 2-targeted biologic therapies. Methods: A retrospective longitudinal analysis was conducted on 14 patients with severe asthma and non-cystic fibrosis bronchiectasis without microbiological colonization. Clinical remission was assessed at baseline (T0) and after 12 months (T1) of biologic therapy. Clinical remission was defined according to the Severe Asthma Network Italy (SANI) criteria, including the absence of oral corticosteroid use, no asthma-related symptoms, stable lung function, and no exacerbations. Logistic regression was performed to identify predictors of remission. ROC curves were constructed to evaluate the predictive accuracy of lung function parameters, specifically FEV1 and FVC. Results: After 12 months of biologic therapy, 28.6% of patients (n = 4) achieved clinical remission. The mean FEV1 percentage at baseline was significantly higher in the remission group (92.25 ± 15.64%) compared to the non-remission group (65.10 ± 23.36%, p = 0.034). Logistic regression analysis identified baseline FEV1 as a significant predictor of remission (OR = 1.008, p = 0.050). ROC curve analysis revealed that an FEV1 cutoff of 72.5% had a sensitivity of 100% and a specificity of 70% (AUC = 0.900, p = 0.024) for predicting clinical remission. Conclusions: FEV1 is a crucial predictor of clinical remission in patients with severe asthma and non-colonized bronchiectasis treated with type 2-targeted biologic therapies. An FEV1 threshold of 72.5% can guide clinicians in identifying patients most likely to achieve remission. These findings underline the importance of preserving lung function to optimize therapeutic outcomes in this complex population.
Cost-Effectiveness Analysis of Topical Treatments for Actinic Keratosis in Italian National Health System
Authors: Hyeraci Mariafrancesca , Pistore Gianluca , Ricci Francesco , Moro Francesco , Lella Giovanni Di , Dellambra Elena , Abeni Damiano , Fania Luca
Published: October 2024

Introduction: Actinic keratosis (AK) is a widespread pre-cancerous skin condition that may evolve to squamous cell carcinoma, a non-melanoma skin cancer, which is able to become locally invasive and metastatic. Thus, it is important to treat AK. Methods: We conducted a cost-effectiveness analysis for the field-directed therapeutic approaches: local application of drugs containing 5-fluorouracil, both alone at a 4% concentration and associated to 10% salicylic acid at a 0.5% concentration (0.5% 5-FU + 10% SA cut. sol.); diclofenac-hyaluronic acid gel; imiquimod, both at 3.75% and 5% (5% IMQ cream) concentrations; and tirbanibulin ointment. The effectiveness data were abstracted from the literature. The cost-effectiveness analysis was performed by considering the prices reported by Agenzia Italiana del Farmaco (AIFA) for each medicine. Results: We obtained the total cost for each treatment by computing the cost of a single treatment for its duration. Application of 0.5% 5-FU + 10% SA cut. sol. appeared as the most convenient approach, as it was more effective and less expensive than all treatments except for 5% IMQ cream. For this last option, the incremental cost/effectiveness ratio analysis showed that a modest gain in effectiveness has a cost of EUR 7.94, therefore making it less cost effective.
Sex Differences in Outcomes After Elective and Acute Aortic Surgery—A Single-Centre Experience over the Last Two Decades
Authors: Strypet Magnus , Bozic Caitlin , Mansvelder Floor J. , Breel Jennifer S. , Jansen Evert K. , de Klerk Eline S. , López González Desiré E. , Hermanns Henning , Eberl Susanne
Published: October 2024

Background/Objectives: Recent studies show conflicting results regarding sex-related differences in outcomes following aortic surgery. This study primarily evaluated 20-year mortality rates, along with 30-day and one- and five-year rates, and postoperative complications in female and male patients who underwent elective and acute ascending aortic surgery at a tertiary care centre. Methods: This retrospective observational study analysed data from 676 adult patients who underwent ascending aortic surgery in Amsterdam UMC, between January 2001 and December 2020. Descriptive statistics, Fisher’s Exact test, Kaplan–Meier survival analysis, and logistic regression were used to assess differences in mortality rates. Results: Patient characteristics for elective and acute procedures were different. Females were generally older (elective: 69 vs. 62 years, p < 0.001, acute: 70 vs. 62 years, p = 0.002), with smaller body surface area (elective/acute: 1.8 vs. 2.1 m2, p < 0.001), lower preoperative haemoglobin (elective: 8.3 vs. 8.9 mmol/L, p < 0.001, acute: 7.8 vs. 8.4 mmol/L, p < 0.001) and estimated glomerular filtration rate (elective: 64 vs. 91 mL/min, p < 0.001; acute: 67 vs. 83 mL/min, p = 0.004). Females undergoing elective procedures had a lower body mass index (25.0 vs. 26.6 kg/m2, p = 0.006), better left ventricle function (p = 0.048) and higher incidence of chronic obstructive pulmonary disease (15 vs. 8%, p = 0.032). In elective procedures, the 20-year mortality rate (49% vs. 30%, p < 0.001) was significantly higher in females, especially those under 60 years (OR of 3.158 [1.2–8.6], p = 0.024). Mortality rates up to one year were comparable. Five-year mortality rate (26% vs. 16%, p = 0.027) was higher. Females had longer ventilation times (32% vs. 15%, p < 0.001) and intensive care unit stays (2 vs. 1 days, p = 0.005). For acute procedures, morbidity and mortality rates were comparable between sexes. Conclusions: Females under 60, undergoing elective ascending aortic surgery showed higher long-term all-cause mortality rates. Implementing sex-specific management strategies and extended follow-up could be essential for improving outcomes in this group.
Psoas Muscle Index and Density as Prognostic Predictors in Patients Hospitalized with Acute Pancreatitis
Authors: Kirzhner Alena , Rossels Anton , Sapojnik Danielle , Zaharoni Hilla , Cohen Ramon , Lin Guy , Schiller Tal
Published: October 2024

Background: Early prognostication of acute pancreatitis (AP) patients for those at high risk of complications during hospitalization can facilitate clinical decision-making. Sarcopenia has been proven to be a risk factor for poor prognosis in patients with AP. We aimed to evaluate the association between the muscle parameters measured in computed tomography (CT) and the clinical outcomes of hospitalized patients with AP. Methods: A total of 132 consecutive patients hospitalized between 1 January 2015 and 31 December 2021 for AP with a valid CT scan were analyzed. The first CT conducted during hospitalization was analyzed for psoas muscle area (PMA), index (PMI), and density (PMD) at the L3 vertebral level. The main adverse outcomes indicating a worse prognosis were the development of extrapancreatic complications, infections, ICU transfer, in-hospital mortality, and hospitalization length. Results: The lowest tertile of PMI, as a surrogate for sarcopenia, was significantly correlated with increased rates of extrapancreatic complications, infections, and longer hospitalizations. It was additionally correlated with a worse CT severity index. The results for PMA and PMD also showed worse outcomes, largely mirroring the results for PMI. Although in-hospital mortality was relatively low, none of the patients died in the highest tertile of PMI. A clear cutoff with sufficient predictive capability could not be found. Conclusions: A low psoas muscle index can serve as an additional potential predictive marker for more severe disease and worse outcomes in hospitalized acute pancreatitis patients. More studies are needed to determine its combination with existing prediction tools.
Effect of Graft Choice for ACL Reconstruction on Clinical Outcomes in Combined ACL and MCL Injuries: Comparison Between Bone-Patellar Tendon-Bone and Hamstring Autografts
Authors: Chung Kwangho , Ham Hyeongwon , Kim Sung-Hwan , Seo Young-Jin
Published: October 2024

Background/Objectives: The optimal graft, particularly in combined anterior cruciate ligament (ACL) and medial collateral ligament (MCL) injuries, remains controversial. We evaluated the influence of graft choice between bone-patellar tendon-bone (BPTB) and hamstring autografts on clinical outcomes in combined ACL and MCL injuries. Methods: This retrospective analysis included patients with concurrent ACL and MCL injuries who underwent single-bundle ACL reconstruction with BPTB (group B) or hamstring (group H) grafts, between 2010 and 2019, with a ≥2-year follow-up. Patients were classified based on the MCL injury grade (I, II, or III). Clinical outcomes were assessed through knee stability evaluations using valgus stress radiographs and the KT-2000 arthrometer, patient-reported outcomes using the International Knee Documentation Committee (IKDC) subjective score and Lysholm score, and radiologic outcomes using the IKDC radiographic grade. Results: The study included 169 patients (group B, 92; group H, 77). No significant between-group differences in knee stability or functional outcomes were found after follow-up. Within the same MCL injury grade, particularly in high-grade MCL injuries, BPTB grafts resulted in significantly better medial stability (side-to-side difference in medial joint opening on valgus stress radiographs: grade II, p = 0.006; grade III, p = 0.039) and functional outcomes (IKDC subjective score: grade II, p = 0.045; grade III, p = 0.038) than hamstring grafts. In the hamstring group, higher-grade MCL injuries were associated with worse outcomes (Lysholm knee score, p = 0.009; IKDC subjective score, p = 0.015). Conclusions: Graft choice in ACL reconstruction with concomitant MCL injuries may affect clinical outcomes, particularly in high-grade MCL injuries. Although both graft types performed similarly overall, BPTB grafts provided superior medial stability and functional results in higher-grade MCL injuries. However, caution is needed when interpreting these results due to limitations such as the small sample size and the lack of randomization in graft selection.
Focal Versus Combined Focal Plus Radial Extracorporeal Shockwave Therapy in Lateral Elbow Tendinopathy: A Retrospective Study
Authors: Delia Caterina , Santilli Gabriele , Colonna Vincenzo , Di Stasi Valerio , Latini Eleonora , Ciccarelli Antonello , Taurone Samanta , Franchitto Antonio , Santoboni Flavia , Trischitta Donatella , Nusca Sveva Maria , Vetrano Mario , Vulpiani Maria Chiara
Published: October 2024

Background: Lateral epicondylitis of the elbow, commonly known as tennis elbow, is a musculoskeletal disorder characterized by pain and degeneration of the common extensor tendon. Despite various treatments, optimal management remains debated. Objective: This study aimed to compare the effectiveness of focal extracorporeal shockwave therapy (F-ESWT) alone versus a combination of focal and radial pressure waves (F-ESWT+R-PW) in treating chronic lateral epicondylitis. Methods: This retrospective observational study included 45 patients diagnosed with chronic lateral epicondylitis divided into two groups based on the treatment received: group A (F-ESWT, n = 23) and group B (F-ESWT+R-PW, n = 22). Both groups underwent three weekly sessions of their respective treatments. Patients were also given a home exercise protocol. Primary outcomes were assessed using the Visual Analog Scale (VAS) for pain and the Patient-Rated Tennis Elbow Evaluation (PRTEE) for pain and functional impairment at baseline (T0), 4 weeks (T1), 12 weeks (T2), and 24 weeks (T3) post-treatment. Secondary outcomes included grip strength and ultrasonographic measurements of common extensor tendon (CET) thickness and vascularization. Results: Significant improvements in VAS and PRTEE scores were observed in both groups at all follow-up points. Group B showed greater pain reduction at T1 (VAS: 3.0 ± 1.6 vs. 4.43 ± 1.47; p < 0.005) and T2 (VAS: p < 0.030) compared to group A. Functional outcomes (PRTEE) also favored group B at T1 (p < 0.030) and in the pain section at T2 (p < 0.020). Grip strength improved similarly in both groups. CET thickness showed no significant differences at T3. Vascularization decreased significantly in both groups, with a non-significant trend favoring group B. Conclusions: The combined F-ESWT+R-PW therapy proved more effective than F-ESWT alone in the short- to mid-term management of chronic lateral epicondylitis, significantly enhancing pain reduction and functional outcomes. The combination of focal and radial pressure waves offers a superior therapeutic approach, leveraging the distinct mechanisms of each modality for better clinical results. Further research is needed to confirm these findings and establish long-term efficacy.