bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-Fermentative Addition of Grape Seed Protein Hydrolysates and Their Impact on Wine Colour-Related Polyphenols
Authors: Mora-Garrido Ana Belén , Escudero-Gilete M. Luisa , González-Miret M. Lourdes , Heredia Francisco J. , Cejudo-Bastante María Jesús
Published: December 2024

This study evaluates the effect of protein hydrolysates, obtained from grape seed meal (industrial waste), as colour stabilisers in red wines from warm climates. Protein hydrolysates were added to the wine after fermentation and maceration. Assays were performed using different types and doses of protein hydrolysates. Two grapevine-growing seasons were monitored over 8 months. Attention was focused on different families of polyphenolic compounds, copigmentation, and polymerisation, and colour changes were assessed by differential tristimulus colourimetry. Regardless of doses and typology, wines with protein hydrolysates suffered a decrease in the amount of phenolics and an increase in % polymerisation. Only wines treated with 3 g/L of hydrolysates showed lower colour intensity and greater clarity and hue after 8 months, while treatment with 0.5 g/L produced brownish wines. The addition of hydrolysates from a low hydrolysis time did not affect the copigmentation balances or produced negative visually perceptible colour differences over time. These results indicate that the post-fermentation addition of protein hydrolysates does not seem to significantly improve the stabilisation of the wine colour, in contrast to the addition at other stages. This information is of great interest to wineries to consider the application of this novel technique at the optimal time.
Impact of Soybean Bioactive Peptides on Growth, Lipid Metabolism, Antioxidant Ability, Molecular Responses, and Gut Microbiota of Oriental River Prawn (Macrobrachium nipponense) Fed with a Low-Fishmeal Diet
Authors: Yang Chang , Liu Bo , Pan Liangkun , Xia Dong , Sun Cunxin , Zheng Xiaochuan , Chen Peng , Hu He , Zhou Qunlan
Published: December 2024

The substitution of fishmeal with high-level soybean meal in the diet of crustaceans usually induces lipid accumulation and oxidative stress in the hepatopancreas. Therefore, it is essential to alleviate these adverse effects. In the present study, SBPs were used to alleviate the negative effects of a fishmeal decrease on the growth performance, lipid metabolism, antioxidant capacity, and gut microbiota of oriental river prawn (Macrobrachium nipponense) in an 8-week feeding trial. Three isonitrogenic and isolipidic diets were prepared as follows: R (reference diet with 32% fishmeal), CT (control diet with 22% fishmeal), and SBP (22% fishmeal with 1.25 g/kg soybean bioactive peptides). The prawns (initial biomass per tank 17 g) were randomly divided into three groups with four replicates. The results showed that the low-fishmeal diet induced the following: (1) the inhibition of growth performance and survival of prawns; (2) an increase in triglyceride content in the hepatopancreas and hemolymph and downregulation of carnitine palmitoyl transferase 1 (cpt1) gene expression; (3) a reduction in antioxidant enzymes’ activities and their genes expression levels and an increase malondialdehyde (MDA) content; and (4) an increase in the abundance of the conditional pathogen Pseudomonas in the gut. SBPs supplementation in the CT diet effectively alleviated most of the above adverse effects. SBPs enhanced inducible nitric oxide synthase (iNOS) activity to synthesize nitric oxide (NO) by activating the imd-relish pathway. Most importantly, SBPs increased the potential probiotic Rikenellaceae_RC9_gut_group abundance and decreased the abundance of the conditional pathogen Pseudomonas in the gut. In conclusion, SBPs supplementation can improve low-fishmeal-diet-induced growth inhibition by regulating the gut microbiota composition to ameliorate lipid deposition and oxidative stress and strengthen immune status in oriental river prawn.
Populations of the Invasive Mussel Mytella strigata in China Showed Lower Genetic Diversity in Autumn than in Spring
Authors: Ma Peizhen , Zuo Chenxia , Yan Shaojing , Wu Xiangyu , Ma Xiaojie , Zhu Yi , Zhang Zhen
Published: December 2024

Native to tropical America, the charru mussel, Mytella strigata, has been spreading rapidly in the West Pacific Ocean, including the South China Sea. In order to study the adaptive evolution of M. strigata and examine the present status of invasion in China, the mitochondrial nad2 gene fragment was employed to analyze the genetic variations of seven populations sampled in both spring and autumn 2023. Results showed that all the populations had high haplotype diversity (>0.5) and low nucleotide diversity (<0.005), suggesting the ongoing rapid expansion following a genetic bottleneck. The Zhanjiang population had the highest genetic diversity in spring with 22 haplotypes, 37 polymorphic sites, and haplotype diversity, nucleotide diversity, and the average number of nucleotide differences being 0.911, 0.00623, and 4.341, respectively. However, in autumn, the Shanwei population had the most haplotypes (11) and polymorphic sites (19), with the highest haplotype diversity value of 0.891, while the Qunjian population had the highest nucleotide diversity (0.00392) and average number of nucleotide differences (2.809). Combining geographic populations by seasons confirmed lower genetic diversity in autumn compared to spring, evidenced by fewer haplotypes and polymorphic sites, reduced haplotype diversity and nucleotide diversity, and lower genetic distance within populations. These findings provided evidence for understanding the molecular characteristics of M. strigata population expansion in China.
Atypical Metastases from Prostate Cancer: Alpha-Methylacyl-Coenzyme A Racemase (AMACR) as a Potential Molecular Target in Prostate-Specific Membrane Antigen-Negative Prostate Adenocarcinoma
Authors: Badrane Ilham , Castello Angelo , Brunelli Matteo , Cittanti Corrado , Adamantiadis Sara , Bagni Ilaria , Mindicini Noemi , Lancia Federica , Castellani Massimo , Uccelli Licia , Bartolomei Mirco , Urso Luca
Published: December 2024

Prostate cancer (PCa) is a high-prevalence disease usually characterized by metastatic spread to the pelvic lymph nodes and bones and the development of visceral metastases only in the late stages of disease. Positron Emission Tomography (PET) plays a key role in the detection of PCa metastases. Several PET radiotracers are used in PCa patients according to the stage and pathological features of the disease, in particular 68Ga/18F-prostate-specific membrane antigen (PSMA) ligands. Moreover, 2-deoxy-2-[18F]fluoro-D-glucose 18F-FDG PET usually shows metastases in the late stages of disease, when dedifferentiated neoplastic clones lose PSMA expression. In some cases, PCa patients may present atypical sites of metastases, with uncommon appearance at PET imaging with different radiotracers. We present the case of a patient with biochemical recurrence of PCa (ISUP Grade Group IV; PSA 4.7 ng/mL) showing atypical sites of metastases (the testis and multiple lung nodules) with absent PSMA expression and high [18F]FDG avidity. The patient showed diffuse positivity to alpha-methylacyl-coenzyme A racemase (AMACR). Moreover, a literature review was performed by collecting cases of PCa patients with atypical metastatic spread detected via PET imaging, with the aim of highlighting the relationship between atypical sites of metastases, imaging presentation, and pathology findings.
The Intersection of Epigenetics and Senolytics in Mechanisms of Aging and Therapeutic Approaches
Authors: Burdusel Daiana , Doeppner Thorsten R. , Surugiu Roxana , Hermann Dirk M. , Olaru Denissa Greta , Popa-Wagner Aurel
Published: December 2024

The biological process of aging is influenced by a complex interplay of genetic, environmental, and epigenetic factors. Recent advancements in the fields of epigenetics and senolytics offer promising avenues for understanding and addressing age-related diseases. Epigenetics refers to heritable changes in gene expression without altering the DNA sequence, with mechanisms like DNA methylation, histone modification, and non-coding RNA regulation playing critical roles in aging. Senolytics, a class of drugs targeting and eliminating senescent cells, address the accumulation of dysfunctional cells that contribute to tissue degradation and chronic inflammation through the senescence-associated secretory phenotype. This scoping review examines the intersection of epigenetic mechanisms and senolytic therapies in aging, focusing on their combined potential for therapeutic interventions. Senescent cells display distinct epigenetic signatures, such as DNA hypermethylation and histone modifications, which can be targeted to enhance senolytic efficacy. Epigenetic reprogramming strategies, such as induced pluripotent stem cells, may further complement senolytics by rejuvenating aged cells. Integrating epigenetic modulation with senolytic therapy offers a dual approach to improving healthspan and mitigating age-related pathologies. This narrative review underscores the need for continued research into the molecular mechanisms underlying these interactions and suggests future directions for therapeutic development, including clinical trials, biomarker discovery, and combination therapies that synergistically target aging processes.
Visceral Adipose Tissue Inflammation and Vascular Complications in a Rat Model with Severe Dyslipidemia: Sex Differences and PAI-1 Tissue Involvement
Authors: Markova Irena , Hüttl Martina , Gayova Natalie , Miklankova Denisa , Cerna Kristyna , Kavanova Martina , Skaroupkova Petra , Cacanyiova Sona , Malinska Hana
Published: December 2024

We investigated the sex-dependent effects of inflammatory responses in visceral adipose tissue (VAT) and perivascular adipose tissue (PVAT), as well as hematological status, in relation to cardiovascular disorders associated with prediabetes. Using male and female hereditary hypertriglyceridemic (HHTg) rats—a nonobese prediabetic model featuring dyslipidemia, hepatic steatosis, and insulin resistance—we found that HHTg females exhibited more pronounced hypertriglyceridemia than males, while HHTg males had higher non-fasting glucose levels. Additionally, HHTg females had higher platelet counts, larger platelet volumes, and lower antithrombin inhibitory activity. Regarding low-grade chronic inflammation, HHTg males exhibited increased serum leptin and leukocyte levels, while females had increased serum interleukin-6 (IL-6). Both sexes had increased circulating plasminogen activator inhibitor-1 (PAI-1), higher PAI-1 gene expression in VAT and PVAT, and elevated intercellular adhesion molecule-1 (ICAM-1) gene expression in the aorta, contributing to endothelial dysfunction in the HHTg strain. However, HHTg females had lower tumor necrosis factor alpha (TNFα) gene expression in the aorta. Severe dyslipidemia in this prediabetic model was associated with hypercoagulation and low-grade chronic inflammation. The increase in PAI-1 expression in both VAT and PVAT seems to indicate a link between inflammation and vascular dysfunction. Despite the more pronounced dyslipidemia and procoagulation status in females, their milder inflammatory response may reflect an association between reduced cardiovascular damage and prediabetes.
The Change of Skeletal Muscle Caused by Inflammation in Obesity as the Key Path to Fibrosis: Thoughts on Mechanisms and Intervention Strategies
Authors: Li Yixuan , Guo Wenwen , Li Han , Wang Yuhao , Liu Xinwei , Kong Wen
Published: December 2024

Obesity leads to a chronic inflammatory state throughout the body, with increased infiltration of immune cells and inflammatory factors in skeletal muscle tissue, and, at the same time, the level of intracellular mitochondrial oxidative stress rises. Meanwhile, obesity is closely related to the development of skeletal muscle fibrosis and can affect the metabolic function of skeletal muscle, triggering metabolic disorders such as insulin resistance (IR) and type 2 diabetes (T2D). However, whether there is a mutual regulatory effect between the two pathological states of inflammation and fibrosis in obese skeletal muscle and the specific molecular mechanisms have not been fully clarified. This review focuses on the pathological changes of skeletal muscle inflammation and fibrosis induced by obesity, covering the metabolic changes it causes, such as lipid deposition, mitochondrial dysfunction, and dysregulation of inflammatory factors, aiming to reveal the intricate connections between the two. In terms of intervention strategies, aerobic exercise, dietary modification, and pharmacotherapy can improve skeletal muscle inflammation and fibrosis. This article provides insight into the important roles of inflammation and fibrosis in the treatment of obesity and the management of skeletal muscle diseases, aiming to provide new ideas for the diagnosis and treatment of metabolic diseases such as obesity and IR.
Evaluation of Plasma E-Selectin Concentration as a Risk Marker for Atherosclerotic Vascular Damage in Patients with Early CAD
Authors: Rac Monika , Rac Michal , Krzystolik Andrzej , Safranow Krzysztof , Chlubek Dariusz , Dziedziejko Violetta
Published: December 2024

Background: Inflammation markers in the blood may indicate a higher risk of unstable atherosclerosis. Selectins, a group of transmembrane glycoproteins, contribute to inflammation by helping certain blood cells bind to the endothelium. Methods: The study included 100 patients with stable early-onset coronary artery disease (CAD), 75 men (aged 50–54) and 25 women (aged 55–64). Tests performed included biochemical analysis, ultrasound, and Doppler imaging of arteries and peripheral vessels. A biochemical control group of 50 cases without CAD (74% men, average age 48 ± 3.20 years) was also studied. Results: Higher triglyceride levels were strongly linked to elevated plasma E-selectin levels. However, no significant relationship was found between plasma E-selectin levels and biochemical, clinical, radiographic, or echographic measures. Conclusion: Plasma E-selectin levels are not a reliable marker for detecting atherosclerotic plaques or related problems in individuals with stable, well-managed CAD. While E-selectin levels can be measured in clinical labs using immunoassays, they cannot replace standard cardiological and vascular imaging tests for diagnosing cardiac or vascular conditions.
Extracellular Vesicles and Tunnelling Nanotubes as Mediators of Prostate Cancer Intercellular Communication
Authors: Heatlie Jessica K. , Lazniewska Joanna , Moore Courtney R. , Johnson Ian R. D. , Nturubika Bukuru D. , Williams Ruth , Ward Mark P. , O’Leary John J. , Butler Lisa M. , Brooks Doug A.
Published: December 2024

Prostate cancer (PCa) pathogenesis relies on intercellular communication, which can involve tunnelling nanotubes (TNTs) and extracellular vesicles (EVs). TNTs and EVs have been reported to transfer critical cargo involved in cellular functions and signalling, prompting us to investigate the extent of organelle and protein transfer in PCa cells and the potential involvement of the androgen receptor. Using live cell imaging microscopy, we observed extensive formation of TNTs and EVs operating between PCa, non-malignant, and immune cells. PCa cells were capable of transferring lysosomes, mitochondria, lipids, and endoplasmic reticulum, as well as syndecan-1, sortilin, Glut1, and Glut4. In mechanistic studies, androgen-sensitive PCa cells exhibited changes in cell morphology when stimulated by R1881 treatment. Overexpression assays of a newly designed androgen receptor (AR) plasmid revealed its novel localization in PCa cellular vesicles, which were also transferred to neighbouring cells. Selected molecular machinery, thought to be involved in intercellular communication, was investigated by knockdown studies and Western blotting/immunofluorescence/scanning electron microscopy (SEM). PCa TNTs and EVs transported proteins and organelles, which may contain specialist signalling, programming, and energy requirements that support cancer growth and progression. This makes these important intercellular communication systems ideal potential targets for therapeutic intervention.
Cardiometabolic Risk Factors Among African University Students: A Systematic Review
Authors: Enoh Jude Eteneneng , Akah Roland Tiagha , Nkeh-Chungag Benedicta
Published: December 2024

Background: Cardiometabolic risk factors such as hypertension, overweight, and obesity have become increasingly common among African students who tend to become more sedentary in urban environments. This systematic review aimed to determine and identify major risk factors of cardiometabolic disease prevalence reported among African university students. Methods: The protocol was registered with PROSPERO (registration no.CRD42024553280). A comprehensive literature search was performed using scientific databases from Google Scholar, PubMed, Web of Science, Scopus, ProQuest, and African Journals Online (AJOL). The search was limited to articles published between 2000 and 2024, which reported cardiometabolic diseases/risk factors among African university students. Data were extracted using a standardised form, capturing details on study characteristics (author, year, location, study design), participant demographics (age, sex), prevalence of cardiometabolic diseases, and associated risk factors. Results: A total of thirty-seven studies that met the inclusion criteria, thirty-six cross-sectional and one longitudinal, were included in the study. The prevalence range of the various risk factors identified was 0.6–21.7% (obesity) and 0.28–26.4% (hypertension), 1.7–18.8% (diabetes), 0.5–18.2% (pre-diabetes), 1.9–48.6% (metabolic syndrome), and 1.1% to 57.3% (dyslipidemia). Some common sedentary lifestyles and unhealthy behaviours identified among the students were fast foods (21.3–85.73%), alcohol (3.7–63%), and smoking (1.02–13%). Conclusions: The review’s findings suggest that rapid urbanisation and changes in lifestyle and behaviours are responsible for an increased prevalence of cardiometabolic risk factors in African university students. Targeted health promotion programmes, regular screening, and policy interventions might all go a long way in preventing the predicted increase in the prevalence of cardiovascular and metabolic diseases among this group of young adults in Africa.
A Cost-Effective and Robust Cell-Based Bioassay Method for Evaluating the Bioactivity of Trastuzumab-like Antibodies
Authors: Bharali Pooja , Chand Subhash , Chander Harish
Published: December 2024

Background/Objectives: Trastuzumab is an effective therapeutic intervention for treating HER2-positive breast cancers. The cost-effectiveness, global demand, and patent expiration of trastuzumab have led to the inflow of its biosimilars in the global market. With the rise of biosimilars in the biopharmaceutical market, it has become crucial to ensure that the biosimilar is at par with the original monoclonal antibody (mAb)in terms of efficacy, safety, and quality. Bioassay is one of the critical quality attributes (CQAs), hence developing a reliable and robust bioassay is essential for the evaluation of their biological activity and the harmonization of the quality of these biologics, supporting their safe and effective use in clinical practice. Methods: The present study aimed to develop a robust cell-based bioassay to assess the bioactivity of trastuzumab and its biosimilars for quality control testing. For this purpose, molecular characterization of different HER2-positive breast cancer cell lines of SKBR3, BT474, MDA-MD-453, MDA-MB-175, MCF-7, and MDA-MB-231 was performed to select a suitable cell line for the cell-based bioassay. Results: The SKBR3 cell line was found to express the HER2 receptors significantly higher in comparison to the other cell lines, and it was thereby selected for further bioassay optimization. The biological activity of trastuzumab was determined using the inhibition of proliferation (IOP) assay on the SKBR3, which was optimized based on the parameters of cell seeding density, drug dilution range, and incubation time, and it was further validated as per the compendial guidelines and found valid for the parameters of specificity, accuracy (% relative bias = 0.0067%), precision (repeatability: % GCV = 1.21%), linearity (R2 = 0.99), and range (50% to 200%). Additionally, the biological activity of different trastuzumab biosimilars was assessed using the validated IOP assay and compared to the HER2 binding assay performed by flow cytometry. The biological activity of different trastuzumab biosimilars was found to be comparable to the WHO primary reference standard of trastuzumab in terms of its relative potency using the IOP assay and binding assay by flow cytometry. Conclusions: Thus, an economic and robust cell-based bioassay method was successfully developed to assess the bioactivity of trastuzumab and its biosimilars.
Unveiling DENND2D as a Novel Prognostic Biomarker for Prostate Cancer Recurrence: From Gene to Prognosis
Authors: Chang Chi-Fen , Chen Lih-Chyang , Chen Yei-Tsung , Huang Chao-Yuan , Yu Chia-Cheng , Lin Victor C. , Lu Te-Ling , Huang Shu-Pin , Bao Bo-Ying
Published: December 2024

Background: Prostate cancer is a major global health burden, with biochemical recurrence (BCR) following radical prostatectomy affecting 20–40% of patients and posing significant challenges to prognosis and treatment. Emerging evidence suggests a critical role for differentially expressed in normal and neoplastic cell (DENN) domain-containing genes in oncogenesis; however, their implications in prostate cancer and BCR risk remain underexplored. Methods: This study systematically evaluated 151 single-nucleotide polymorphisms in DENN domain-containing genes in 458 patients with prostate cancer and BCR, followed by validation in an independent cohort of 185 patients. Results: Multivariate Cox regression analyses identified DENND2D rs610261 G>A as significantly associated with improved BCR-free survival in both cohorts (adjusted hazard ratio = 0.39, 95% confidence interval = 0.23–0.66, p = 0.001). Functional analysis revealed rs610261’s regulatory potential, with the protective A allele correlating with increased DENND2D expression in various human tissues. Compared to normal prostate tissues, DENND2D expression was reduced in prostate cancer, with higher expression being linked to favorable patient prognosis (p = 0.03). Gene set enrichment analysis revealed an association between DENND2D expression and the negative regulation of MYC target genes, including MAD2L1, ERH, and CLNS1A, which are overexpressed in prostate cancer and associated with poor survival. Furthermore, the elevated DENND2D expression promotes immune infiltration in prostate cancer, supporting its role in immune modulation. Conclusions: DENND2D is a prognostic biomarker for BCR in prostate cancer and offers new avenues for personalized treatment strategies.
The Pathogenic Role of Expanded CD8⁺CD28null Angiogenic T Cells in ANCA-Associated Vasculitis
Authors: Shen Haomiao , Miao Jinlin , Sun Haoyang , Zhang Kui , Liu Renli , Li Zichao , Zhang Leyang , Zhang Peiyan , Wang Jiawei , Zhang Bei , Chen Longyu , Zheng Zhaohui , Zhu Ping
Published: December 2024

Objectives: Angiogenic T cells (Tang) are crucial in promoting angiogenesis, with the loss of CD28 serving as a marker for highly differentiated and senescent T cells. This study aims to investigate the characteristics and potential roles of CD8+CD28null Tang in patients with ANCA-associated vasculitis (AAV). Methods: A cohort of AAV patients and matched healthy controls (HCs) were analyzed. Flow cytometry was used to assess the profiles of circulating CD8+CD28null Tang. In vitro functional assays were performed to evaluate the pathogenic properties of CD8+CD28null Tang. Results: CD8+CD28null Tang levels were significantly higher in the peripheral blood of AAV patients compared to HCs, and their levels were further increased in AAV patients with MPO⁺, p-ANCA⁺, or interstitial lung disease compared to their respective control groups. Additionally, there was a positive correlation between both the percentage and absolute count of CD8+CD28null Tang and the Birmingham Vasculitis Activity Score (BVAS). In patients with a good treatment response, both the percentage and absolute count of CD8+CD28null Tang were significantly reduced, and this reduction was positively correlated with the decrease in BVAS scores. In vitro studies revealed that CD8+CD28null Tang displayed enhanced chemotactic properties, induced apoptosis in human umbilical vein endothelial cells (HUVECs), and inhibited their proliferation, migration, and tube formation. Conclusions: AAV patients exhibit increased levels of circulating CD8+CD28null Tang, which can be reduced following effective treatment. Furthermore, CD8+CD28null Tang may contribute to the pathogenesis of AAV by promoting apoptosis and inhibiting the proliferation, migration, and tube formation of HUVECs.
Epicardial Ablation for Arrhythmogenic Disorders in Patients with Brugada Syndrome
Authors: Matteucci Andrea , Mariani Marco Valerio , Sgarra Luca , Bonanni Michela , Frazzetto Marco , La Fazia Vincenzo Mirco , Pierucci Nicola , Lavalle Carlo , Pandozi Claudio , Nardi Federico , Colivicchi Furio
Published: December 2024

Brugada syndrome (BrS) is an inherited arrhythmogenic disorder characterized by distinct electrocardiographic patterns and an increased risk of sudden cardiac death due to ventricular arrhythmias. Effective management of BrS is essential, particularly for high-risk patients with recurrent arrhythmias. While implantable cardioverter–defibrillator (ICD) is effective in terminating life-threatening arrhythmias, it does not prevent arrhythmia onset and can lead to complications such as inappropriate shocks. Epicardial ablation has emerged as a promising treatment option for patients with recurrent ventricular arrhythmias and frequent ICD interventions. This review examines the latest advancements in the management of Brugada syndrome, focusing on the role and rationale of epicardial ablation for the treatment of patients at risk of sudden cardiac death.
Association of Low-Attenuation Plaque with Impaired Glucose Tolerance and Type 2 Diabetes Mellitus in Patients with Suspected Coronary Artery Disease
Authors: Andersen Thomas R. , Overgaard Katrine S. , Heinsen Laurits Juhl , Mohamed Roda Abdulkadir , Precht Helle , Lambrechtsen Jess , Auscher Søren , Egstrup Kenneth
Published: December 2024

Aim: The aim of this study was to evaluate the differences in plaque composition and burden between normal glycemic status (NGS) and dysglycemia expressed as impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). Methods: Clinically indicated coronary computed tomography angiography was used to evaluate patients with suspected coronary artery disease (CAD). An oral glucose tolerance test was performed to assess glycemic status. Patients were stratified as NGS, IGT, and T2DM. Plaque volumes were quantified using validated software, with further compositional measurements of low-attenuation, non-calcified, and calcified plaque burden. Results: Of 355 patients with suspected CAD, 220 had NGS, 92 were diagnosed with IGT, and 43 with known T2DM. Low-attenuation plaque volume was significantly higher in IGT (209 mm3, p < 0.02) and T2DM (243 mm3, p = 0.005) compared with NGS (166 mm3). Total plaque burden was similar between all groups, but a significantly greater low-attenuation plaque burden was seen in IGT (p = 0.03) and T2DM (p = 0.02) compared with NGS. The multivariate linear regression model adjusted for clinical risk factors showed that patients with IGT had a greater low-attenuation plaque burden compared with those with NGS (p = 0.03). Interestingly, no significant differences in plaque burdens were observed between those with IGT and T2DM in both univariate and multivariate analyses. Conclusions: Dysglycemia, including impaired glucose tolerance and type 2 diabetes mellitus, was associated with increased low-attenuation plaque burden compared with normal glycemic status. Patients with IGT demonstrated plaque burden similar to patients with known T2DM, underscoring the need for early metabolic intervention.
Novel Role of Pin1-Cis P-Tau-ApoE Axis in the Pathogenesis of Preeclampsia and Its Connection with Dementia
Authors: Amabebe Emmanuel , Huang Zheping , Jash Sukanta , Krishnan Balaji , Cheng Shibin , Nakashima Akitoshi , Li Yitong , Li Zhixong , Wang Ruizhi , Menon Ramkumar , Zhou Xiao Zhen , Lu Kun Ping , Sharma Surendra
Published: December 2024

Preeclampsia (preE) is a severe multisystem hypertensive syndrome of pregnancy associated with ischemia/hypoxia, angiogenic imbalance, apolipoprotein E (ApoE)-mediated dyslipidemia, placental insufficiency, and inflammation at the maternal–fetal interface. Our recent data further suggest that preE is associated with impaired autophagy, vascular dysfunction, and proteinopathy/tauopathy disorder, similar to neurodegenerative diseases such as Alzheimer’s disease (AD), including the presence of the cis stereo-isoform of phosphorylated tau (cis P-tau), amyloid-β, and transthyretin in the placenta and circulation. This review provides an overview of the factors that may lead to the induction and accumulation of cis P-tau-like proteins by focusing on the inactivation of peptidyl-prolyl cis–trans isomerase (Pin1) that catalyzes the cis to trans isomerization of P-tau. We also highlighted the novel role of the Pin1-cis P-tau-ApoE axis in the development of preE, and propagation of cis P-tau-mediated abnormal protein aggregation (tauopathy) from the placenta to cerebral tissues later in life, leading to neurodegenerative conditions. In the case of preE, proteinopathy/tauopathy may interrupt trophoblast differentiation and induce cell death, similar to the events occurring in neurons. These events may eventually damage the endothelium and cause systemic features of disorders such as preE. Despite impressive research and therapeutic advances in both fields of preE and neurodegenerative diseases, further investigation of Pin1-cis P-tau and ApoE-related mechanistic underpinnings may unravel novel therapeutic options, and new transcriptional and proteomic markers. This review will also cover genetic polymorphisms in the ApoE alleles leading to dyslipidemia induction that may regulate the pathways causing preE or dementia-like features in the reproductive age or later in life, respectively.
Prolonged Cardiopulmonary Bypass Time-Induced Endothelial Dysfunction via Glypican-1 Shedding, Inflammation, and Matrix Metalloproteinase 9 in Patients Undergoing Cardiac Surgery
Authors: Li Shiyi , Nordick Katherine V. , Murrieta-Álvarez Iván , Kirby Randall P. , Bhattacharya Rishav , Garcia Ismael , Hochman-Mendez Camila , Rosengart Todd K. , Liao Kenneth K. , Mondal Nandan K.
Published: December 2024

Objectives: A prolonged cardiopulmonary bypass (CPB) time of over 180 min is linked to poorer outcomes and higher mortality in cardiac surgery. This study examines how glypican-1 shedding, matrix metallopeptidase 9 (MMP9), and the pro-inflammatory cytokine IL-1β may contribute to endothelial dysfunction in patients undergoing on-pump surgery with an extended CPB. Methods: Fifty-one patients undergoing cardiac surgical procedures were divided into two groups based on the intraoperative CPB duration: (i) normal CPB (<180 min, n = 23) and (ii) prolonged CPB (>180 min, n = 28). The preoperative, intraoperative, and postoperative plasma levels of glypican-1, MMP9, and IL-1β were measured. Results: Before surgery, the plasma levels of glypican-1, MMP9, and IL-1β were comparable between the normal CPB and the prolonged CPB groups. However, after the end of the CPB, all three markers showed significant elevation in the prolonged CPB group compared to the normal CPB group. Significant correlations were observed between the intraoperative and postoperative levels of MMP9, IL-1β, and glypican-1. A strong positive correlation was also observed between the intraoperative and postoperative levels of glypican-1 and the duration of the CPB. Conclusions: A prolonged CPB triggers a systemic inflammatory response and activates MMP9, leading to glypican-1 shedding and endothelial dysfunction.
Outcomes of Idecabtagene Vicleucel Therapy in Patients with Relapsed/Refractory Multiple Myeloma: A Single-Institution Experience
Authors: Trando Aaron , Ghamsari Farid , Yeung Philip , Costello Caitlin , Saunders Ila , Jeong Ah-Reum
Published: December 2024

Background/Objectives: Idecabtagene vicleucel (ide-cel), an anti-B-cell maturation chimeric antigen receptor T-cell therapy, represents an unprecedented treatment option for relapsed/refractory multiple myeloma (R/R MM). Nevertheless, given its limitations, including the risk of adverse effects and unclear durability of efficacy, there remains a need to report the real-world clinical outcomes of ide-cel therapy in patients with R/R MM, as well as explore host predictive factors for therapy. Methods: We performed a single-center retrospective analysis of 25 adult patients with R/R MM who received ide-cel between 2021 and 2023 at the University of California San Diego Health. Data on baseline characteristics, efficacy, safety, and post-relapse outcomes were collected. Treatment responses were assessed using the International Myeloma Working Group criteria while survival analyses were conducted using the Kaplan–Meier and Cox proportional hazards methods. Results: The median age was 65. Twelve patients (48%) were male. Patients received a median of six lines of prior therapy with four patients (16%) receiving prior BCMA-targeted therapy. Six patients (24%) had high-risk cytogenetics while ten patients (40%) had extramedullary disease. The incidence of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome incidence was 92% and 12%, respectively. All grade infection occurred in 11 patients (44%). Cytomegalovirus (CMV) reactivation occurred in 9 of 19 patients (47%) who were CMV IgG positive prior to CAR T-cell therapy. The objective response rate (ORR) was 84%; stringent complete response was seen in 14 patients (56%). After a median follow-up of 13 months, median progression-free survival (PFS) was 13.9 months (95% CI: 9.21 months—not reached [NR]); median overall survival (OS) was not reached (95% CI: 19.5 months—NR). Among the 11 patients (44%) who progressed after ide-cel therapy, median OS2 was 13.7 months; especially poor outcomes (median OS2 of 1.74 months) were observed in four patients who did not respond to ide-cel. Six of these eleven patients remained alive at time of data cutoff. Univariate and multivariate analysis revealed no significant predictors of ORR, PFS, or OS. Conclusions: Overall, ide-cel had comparable efficacy and safety to the KarMMa-1 trial and other reported real-world experiences.
Prognostic Value of CXCL13, CCL11, and CCL20 Chemokines in Multiple Sclerosis
Authors: Peker Işıl , İçli Hacer Eroğlu , Mutluay Belgin , Yüksel Burcu , Özdemir Zeynep , Köseoğlu Mesrure , Şen Aysu , Ataklı Dilek , Soysal Aysun , Öztürk Musa
Published: December 2024

Objective: The course of relapsing–remitting multiple sclerosis (RRMS) is highly variable and there is a lack of effective prognostic biomarkers. This study aimed to assess the potential prognostic value of the chemokines B lymphocyte chemoattractant molecule (CXCL13), eotaxin-1 (CCL11), and macrophage inflammatory protein 3-alpha (CCL20) in RRMS. Methods: Forty-two patients with MS were enrolled, along with 22 controls, 12 of the controls were idiopathic intracranial hypertension (IIH) patients, and 10 of the controls were other neurologic diseases (OND). Chemokine levels were measured using enzyme-linked immunosorbent assay (ELISA) in serum and cerebrospinal fluid (CSF) samples. Results: No significant differences were observed among the groups in serum levels of CXCL13, CCL11, and CCL20 (p = 0.509, p = 0.979, p = 0.169, respectively). CSF CXCL13 levels were significantly higher in the OND group (p = 0.016). A PATH analysis showed CSF CXCL13 was significantly associated with new T2 hyperintense lesions on brain magnetic resonance imaging (p < 0.001), and baseline serum CCL11 levels were associated with EDSS (p = 0.030), implying its potential role in indicating neurodegenerative processes and possible progression risk. Serum CCL20 correlated with EDSS (p = 0.002) and lesion burden (p < 0.001), reflecting disease severity. Conclusions: These findings suggest that CSF CXCL13 could serve as a useful biomarker for predicting active disease in RRMS, while follow-up serum CCL11 may assist in identifying progression. Although these chemokines are not specific to MS, higher levels may signal disease activity, severity, and transition to more progressive stages.
Enhancing CO2 Adsorption on MgO: Insights into Dopant Selection and Mechanistic Pathways
Authors: Wu Shunnian , Lee W. P. Cathie , Thenuwara Hashan N. , Li Xu , Wu Ping
Published: December 2024

Inspired by our recent success in designing CO2-phobic and CO2-philic domains on nano-MgO for effective CO2 adsorption, our ongoing efforts focus on incorporating dopants into pristine MgO to further enhance its CO2 adsorption capabilities. However, a clear set of guidelines for dopant selection and a holistic understanding of the underlying mechanisms is still lacking. In our investigation, we combined first-principles calculations with experimental approaches to explore the crystal and electronic structural changes in MgO doped with high-valence elements (Al, C, Si, and Ti) and their interactions with CO2. Our findings unveiled two distinct mechanisms for CO2 capture: Ti-driven catalytic CO2 decomposition and CO2 polarization induced by Al, C, and Si. Ti doping induced outward Ti atom displacement and structural distortion, facilitating CO2 dissociation, whereas C doping substantially bolstered the electron donation capacity and CO2 adsorption energy. Pristine and C-doped MgO engaged CO2 through surface O atoms, while Al-, Si-, and Ti-doped MgO predominantly relied on dopant–O atom interactions. Our comprehensive research, integrating computational modeling and experimental work supported by scanning electron microscopy and thermal gravimetric analysis, confirmed the superior CO2 adsorption capabilities of C-doped MgO. This yielded profound insights into the mechanisms and principles that govern dopant selection and design.
A Mechanical–Electrochemical Dual-Model E-Skin for the Monitoring of Cardiovascular Healthcare
Authors: Fang Jianxiao , Jia Yunting , Liao Zelong , Qi Bairui , Huang Tao
Published: December 2024

The early monitoring of cardiovascular biomarkers is essential for the prevention and management of some cardiovascular diseases. Here, we present a novel, compact, and highly integrated skin electrode as a mechanical–electrochemical dual-model E-skin, designed for the real-time monitoring of heart rate and sweat ion concentration, two critical parameters for assessing cardiovascular health. As a pressure sensor, this E-skin is suitable for accurate heart rate monitoring, as it exhibits high sensitivity (25.2 pF·kPa−1), a low detection limit of 6 Pa, and a rapid response time of ~20 ms, which is attributed to the iontronic sensing interface between the skin and the electrode. Additionally, the electrode functions as a potassium ion-selective electrode based on chemical doping, achieving an enhanced response of 11 mV·mM−1. A test based on the real-time monitoring of a subject riding an indoor bike demonstrated the device’s capability to monitor heart rate and sweat potassium ion levels reliably and accurately. This advancement in wearable technology offers significant potential for enhancing patient care based on the early detection and proactive management of cardiovascular conditions.
The Association Between Periodontitis, Gingivitis, Tooth Loss and Stroke: An Umbrella Study with Meta-Analysis
Authors: El Masri Jad , Al Malak Ahmad , El Masri Diala , Ghazi Maya , Al Boussi Silva , El Masri Yasmina , Hassoun Mohammad , Tlayss Maryam , Salameh Pascale , Hosseini Hassan
Published: December 2024

Background: Cerebrovascular diseases (CVAs) have several risk factors that are categorized as modifiable and nonmodifiable. Periodontal diseases (PD) have a modifiable role in causing CVA, where several studies suggested direct or indirect correlations with systemic diseases. This study aims to summarize, evaluate and analyze all the evidence available in literature, to reach a better understanding of the relation between periodontitis, gingivitis, tooth loss and CVA. Methods: PubMed, Cochrane, Scopus and Web of Science databases were searched for all meta-analyses assessing the effect of PD on CVA in accordance with Joanna Briggs Institute guidance for umbrella reviews in March 2024. Assessment of Multiple Systematic Reviews (AMSTAR) was used for quality assessment. Pooled analysis was performed to assess the effect of periodontitis, gingivitis and tooth loss on CVA, depending on the availability of data using Review Manager Version 5.2.11. Results: Seven of the identified meta-analyses were of high quality, and they were distributed in different countries. Periodontitis was generally associated with a significant increase in CVA risk (OR = 2.32, 95% CI: 1.70, 3.17, p < 0.00001 and RR = 1.22, 95% CI: 1.15–1.29, p < 0.00001), same as tooth loss, but to a lower degree (0.78). However, the effect of gingivitis was insignificant in terms of CVA (RR = 1.32, 95% CI: 1.12–1.56, p = 0.0008). Conclusions: This study confirms the effect of periodontitis and tooth loss on CVA, disregarding any significant role for gingivitis. The relation reached favors the suggested role of some inflammatory changes in the pathogenic pathway leading to atherosclerotic changes.
The Role of Immersive Experience in Anxiety Reduction: Evidence from Virtual Reality Sessions
Authors: Wilczyńska Dominika , Walczak-Kozłowska Tamara , Alarcón David , Arenilla María José , Jaenes Jose Carlos , Hejła Marcelina , Lipowski Mariusz , Nestorowicz Joanna , Olszewski Henryk
Published: December 2024

Background/Objectives: Virtual reality (VR) is an innovative technology with the potential to transform digital experiences, particularly in relation to mental health concerns such as anxiety. Therefore, this study investigates the potential of a newly designed VR experience to alleviate anxiety by focusing on the mediating role of VR-induced immersion. Methods: The study included 419 individuals aged 10 to 80 years, with 29 aged 10–15 years and 390 above 15 years, who were randomly assigned to experimental and control groups on the basis of project-defined criteria, including a random allocation to the wheelchair-using group. Both groups used goggles for virtual space navigation, with the experimental group employing a multijoint arm mounted on an aluminum frame and special algorithms to navigate without controllers. We assessed immersion in VR using the Polish adaptation of the Immersion Questionnaire and anxiety using the Polish adaptations of the State–Trait Anxiety Inventory (STAI-X1) and its early adolescent version, the State–Trait Anxiety Inventory–Children (STAI-C1). Results and Conclusions: The results indicate that individuals using the new VR device demonstrated increased immersion and reduced post-test anxiety levels, highlighting the significance of immersion in enhancing positive affect, mitigating the negative effects of VR technology, and offering insights for future development and refinement of VR solutions.
Dutch Validation of the Self-Evaluation of Negative Symptoms Scale (SNS)
Authors: van Brouwershaven Tim , Poppe Anika , Pijnenborg Gerdina Hendrika Maria , Aleman André , Boonstra Nynke , Gangadin Shiral , Dollfus Sonia , Veling Wim , Castelein Stynke , de Vos Jan Alexander , Liemburg Edith ,   PHAMOUS-researchers, van der Meer Lisette
Published: December 2024

Background/objectives: Negative symptoms in schizophrenia spectrum disorders are related to impaired social functioning and lower quality of life, making accurate assessment important. To date, most tools for assessing negative symptoms are observational, which can be influenced by the raters’ experience and opinion. Self-rating scales, like the Self-Evaluation of Negative Symptoms (SNS), could complement observer ratings by adding information from the patient’s perspective. Here, we aim to evaluate the psychometric properties of the Dutch translation of the SNS and the relationship between the SNS and functional outcomes. Methods: The SNS was added to the Pharmacotherapy Monitoring Outcome Survey (PHAMOUS)-protocol for adults with a DSM-5 classification of a disorder in the psychosis spectrum. Internal consistency was assessed by Cronbach’s alpha. Confirmatory factor analysis (CFA) was used to evaluate the construct validity of the five subscales of the SNS. Correlational analyses were performed between the SNS and the Positive and Negative Syndrome Scale (PANSS), the Health of Nation Outcomes Scales (HoNOS), the Global Assessment of Functioning (GAF), Functional Remission tool (FR) and the Manchester Short Assessment of Quality of Life (ManSA). Results: A total of 247 patients participated in this study. Internal consistency was good (α = 0.87). CFA confirmed the five-factor structure of the SNS. The SNS was significantly correlated (all p < 0.001) with the PANSS positive (r = 0.31), PANSS negative (r = 0.33), HoNOS (r = 0.37), FR (r = 0.27) and the ManSA (r = −0.40). Conclusions: The Dutch SNS shows good psychometric properties and is related to functional outcomes and quality of life. The SNS can be valuable in complementing current observational-based instruments, and future research may investigate whether the SNS can be used as a standalone measurement tool for the assessment of negative symptoms.
Non-Linear Effects of Acute Sleep Deprivation on Spatial Working Memory: Cognitive Depletion and Neural Compensation
Authors: Shao Yongcong , Xu Lin , Peng Ziyi , An Xin , Gong Jingjing , Han Mengfei
Published: December 2024

Background: Spatial working memory is crucial for processing visual and spatial information, serving as a foundation for complex cognitive tasks. However, the effects of prolonged sleep deprivation on its dynamics and underlying neural mechanisms remain unclear. This study aims to investigate the specific trends and neural mechanisms underlying spatial working memory alterations during 36 h of acute sleep deprivation. Methods: Twenty participants underwent a 36 h protocol of acute sleep deprivation. Utilizing the spatial 2-back task for assessing spatial working memory, combined with event-related potential (ERP) technology, we compared behavioral and neural responses at four critical time points—before deprivation, and after 12, 24, and 36 h of sleep deprivation—to uncover dynamic cognitive changes. Results: The findings indicate that the impact of sleep deprivation on spatial working memory exhibits significant temporal dependence. After 24 h of deprivation, both behavioral performance and ERP component amplitudes showed significant declines. During the period from 24 to 36 h, the amplitudes of the P2, N2, and P3 components exhibited a recovery trend, potentially reflecting neural compensatory mechanisms. Conclusions: The impact of 36 h acute sleep deprivation on spatial working memory is characterized by time-dependent and phase-specific effects. Initially, sleep deprivation leads to severe cognitive depletion, followed by an adaptive compensatory phase where neural mechanisms may partially restore function. These findings highlight the non-linear nature of cognitive impairment due to sleep deprivation, involving complex self-regulatory and compensatory mechanisms, with implications for understanding cognitive resilience and adaptive processes.