bluuebunny/crossref_metadata_2025 huggingface dataset:
Bilateral Iliosacral and Transsacral Screws Are Biomechanically Favorable and Reduce the Risk for Fracture Progression in Fragility Fractures of the Pelvis—A Finite Element Analysis
Authors: Lodde Moritz F. , Klimek Matthias , Herbst Elmar , Peez Christian , Riesenbeck Oliver , Raschke Michael J. , Roßlenbroich Steffen
Published: January 2025

(1) Background: The incidence of fragility fractures of the pelvis (FFP) has increased significantly over the past decades. Unilateral non-displaced fractures, defined as FFP II, are the most common type of fracture. When conservative treatment fails, surgical treatment is indicated. We hypothesize that the use of bilateral SI screws (BSIs) or a transsacral screw (TSI) is superior compared to a unilateral screw (USI) because of a significant reduction in the risk of adjacent fractures and a reduction in fracture progression. (2) Methods: A finite element model of a female pelvic ring was constructed. The ligaments were simulated as tension springs. The load was applied through the sacrum with the pelvis fixed to both acetabula. An FFP IIc was simulated and fixed with either a USI or BSI or TSI. The models were analyzed for a quantitative statement of stress and fracture dislocation. (3) Results: The BSI and TSI resulted in less dislocation compared to the USI. The stress distribution on both sides of the sacrum was favorable in the BSI and TSI groups. The BSI resulted in a higher rotational stability compared to the TSI. (4) Conclusions: The use of either a BSI or TSI for fixation of unilateral FFP is biomechanically favorable compared to the use of a USI. In addition, the use of a BSI or TSI reduces the stress on the contralateral uninjured side of the sacrum. This may reduce the risk of an adjacent fracture or fracture progression.
Ex Vivo Regional Gene Therapy Compared to Recombinant BMP-2 for the Treatment of Critical-Size Bone Defects: An In Vivo Single-Cell RNA-Sequencing Study
Authors: Sarkar Arijita , Gallo Matthew C. , Bell Jennifer A. , Mayfield Cory K. , Ball Jacob R. , Ayad Mina , Lechtholz-Zey Elizabeth , Chang Stephanie W. , Sugiyama Osamu , Evseenko Denis , Lieberman Jay R.
Published: January 2025

Ex vivo regional gene therapy is a promising tissue-engineering strategy for bone regeneration: osteogenic mesenchymal stem cells (MSCs) can be genetically modified to express an osteoinductive stimulus (e.g., bone morphogenetic protein-2), seeded onto an osteoconductive scaffold, and then implanted into a bone defect to exert a therapeutic effect. Compared to recombinant human BMP-2 (rhBMP-2), which is approved for clinical use, regional gene therapy may have unique benefits related to the addition of MSCs and the sustained release of BMP-2. However, the cellular and transcriptional mechanisms regulating the response to these two strategies for BMP-2 mediated bone regeneration are largely unknown. Here, for the first time, we performed single-cell RNA sequencing (10x Genomics) of hematoma tissue in six rats with critical-sized femoral defects that were treated with either regional gene therapy or rhBMP-2. Our unbiased bioinformatic analysis of 2393 filtered cells in each group revealed treatment-specific differences in their cellular composition, transcriptional profiles, and cellular communication patterns. Gene therapy treatment induced a more robust chondrogenic response, as well as a decrease in the proportion of fibroblasts and the expression of profibrotic pathways. Additionally, gene therapy was associated with an anti-inflammatory microenvironment; macrophages expressing canonical anti-inflammatory markers were more common in the gene therapy group. In contrast, pro-inflammatory markers were more highly expressed in the rhBMP-2 group. Collectively, the results of our study may offer insights into the unique pathways through which ex vivo regional gene therapy can augment bone regeneration compared to rhBMP-2. Furthermore, an improved understanding of the cellular pathways involved in segmental bone defect healing may allow for the further optimization of regional gene therapy or other bone repair strategies.
The Role of Exosomes in Cancer Progression and Therapy
Authors: Sergazy Shynggys , Seydahmetova Roza , Gulyayev Alexandr , Shulgau Zarina , Aljofan Mohamad
Published: January 2025

Exosomes are small extracellular vesicles and are crucial in intercellular communication. Interestingly, tumor-derived exosomes carry oncogenic molecules, such as proteins and microRNAs, which can reprogram recipient cells, promote angiogenesis, and stimulate cancer pre-metastatic niche, supporting cancer growth and metastasis. On the other hand, their biocompatibility, stability, and ability to cross biological barriers make them attractive candidates for drug delivery. Recent advances have shown the potential for exosomes to be used in early disease detection and in targeted drug therapy by delivering therapeutic agents specifically to tumor sites. Despite the promising applications, a number of challenges remain, including exosome isolation and characterization, as well as their inherent heterogeneity. Thus, the current review aims to describe the roles of exosomes in health and disease, and discuss the challenges that hinder their development into becoming useful medical tools.
Dominance of Sulfur-Oxidizing Bacteria, Thiomicrorhabdus, in the Waters Affected by a Shallow-Sea Hydrothermal Plume
Authors: Chung Chih-Ching , Gong Gwo-Ching , Tseng Hsiao-Chun , Chou Wen-Chen , Ho Chuan-Hsin
Published: January 2025

The shallow-sea hydrothermal vent at Guishan Islet, located off the coast of Taiwan, serves as a remarkable natural site for studying microbial ecology in extreme environments. In April 2019, we investigated the composition of prokaryotic picoplankton communities, their gene expression profiles, and the dissolved inorganic carbon uptake efficiency. Our results revealed that the chemolithotrophs Thiomicrorhabdus spp. contributed to the majority of primary production in the waters affected by the hydrothermal vent plume. The metatranscriptomic analysis aligned with the primary productivity measurements, indicating the significant gene upregulations associated with carboxysome-mediated carbon fixation in Thiomicrorhabdus. Synechococcus and Prochlorococcus served as the prokaryotic photoautotrophs for primary productivity in the waters with lower influence from hydrothermal vent emissions. Thiomicrorhabdus and picocyanobacteria jointly provided organic carbon for sustaining the shallow-sea hydrothermal vent ecosystem. In addition to the carbon fixation, the upregulation of genes involved in the SOX (sulfur-oxidizing) pathway, and the dissimilatory sulfate reduction indicated that energy generation and detoxification co-occurred in Thiomicrorhabdus. This study improved our understanding of the impacts of shallow-sea hydrothermal vents on the operation of marine ecosystems and biogeochemical cycles.
Effect of Electric Fields on the Mechanical Mechanism of Regorafenib–VEGFR2 Interaction to Enhance Inhibition of Hepatocellular Carcinoma
Authors: Tian Yichen , Liao Fenghui , Sun Heng , Lei Yongrong , Fu Yuna , Xia Feng , Wang Jianhua
Published: January 2025

The interaction between molecular targeted therapy drugs and target proteins is crucial with regard to the drugs’ anti-tumor effects. Electric fields can change the structure of proteins, which determines the interaction between drugs and proteins. However, the regulation of the interaction between drugs and target proteins and the anti-tumor effects of electric fields have not been studied thoroughly. Here, we explored how electric fields enhance the inhibition of regorafenib with regard to the activity, invasion, and metastasis of hepatocellular carcinoma cells. We found that electric fields lead to an increase in the normal (adhesion) and transverse (friction) interaction forces between regorafenib and VEGFR2. In single molecule pair interactions, there are changes in specific and nonspecific forces. Hydrogen bonds, hydrophobic interactions, and van der Waals forces are the main influencing factors. Importantly, the increase in the adhesion force and friction force between regorafenib and VEGFR2 caused by electric fields is related to the activity and migration ability of hepatocellular carcinoma cells. The morphological changes in VEGFR2 prove that electric fields regulate protein conformation. Overall, our work proves the drug–protein mechanical mechanism by which electric fields enhance the anti-tumor effect of regorafenib and provides insights into the application of electric fields in clinical tumor treatment.
The Inhibitory Effects of Alpha 1 Antitrypsin on Endosomal TLR Signaling Pathways
Authors: Elshikha Ahmed S. , Abboud Georges , Avdiaj Rigena , Morel Laurence , Song Sihong
Published: January 2025

Endosomal toll-like receptors (TLRs) TLR7, TLR8, and TLR9 play an important role in systemic lupus erythematosus (SLE) pathogenesis. The proteolytic processing of these receptors in the endolysosome is required for signaling in response to DNA and single-stranded RNA, respectively. Targeting this proteolytic processing may represent a novel strategy to inhibit TLR-mediated pathogenesis. Human alpha 1 antitrypsin (hAAT) is a protease inhibitor with anti-inflammatory and immunoregulatory properties. However, the effect of hAAT on endosomal TLRs remains elusive. In this study, we first tested the effect of hAAT on TLR9 signaling in dendritic cells (DCs). We showed that hAAT inhibited TLR9-mediated DC activation and cytokine production. Human AAT also lowered the expressions of interferon signature genes. Western blot analysis showed that hAAT reduced the expression of the active form (cleaved) of TLR9 in DCs, indicating a novel mechanism of hAAT function in the immune system. We next tested the effect of hAAT on TLR7/8 signaling. Similar to the effect on TLR9 signaling, hAAT also inhibited R848 (TLR7 and 8 agonist)-induced DC activation and functions and lowered the expressions of interferon signature genes. Our in vivo studies using hAAT transgenic mice also showed that hAAT attenuated R848-induced pathogenesis. Specifically, hAAT completely blocked the R848 induction of germinal center T cells (GC T), B cells (GC B), and plasma cells (GC PCs), as well as T follicular T helper cells (TFH), which are all critical in lupus development. These data demonstrated that hAAT inhibited TLR7/8 and TLR9 signaling pathways, which are critical for lupus development. These findings not only advanced the current knowledge of hAAT biology, but also implied an insight into the clinical application of hAAT.
Effects of Semaglutide Treatment on Psoriatic Lesions in Obese Patients with Type 2 Diabetes Mellitus: An Open-Label, Randomized Clinical Trial
Authors: Petković-Dabić Jelena , Binić Ivana , Carić Bojana , Božić Ljiljana , Umičević-Šipka Sanja , Bednarčuk Nataša , Dabić Saša , Šitum Mirna , Popović-Pejičić Snježana , Stojiljković Miloš P. , Škrbić Ranko
Published: January 2025

Psoriasis is a chronic inflammatory skin disease with relapsing nature. Estimates are that approximately 2–3% of the world’s population suffers from this disease. More severe forms of psoriasis are conditions of high inflammation, which is confirmed by the clinical picture and numerous inflammatory parameters such as C-reactive protein (CRP), cytokines and homocysteine, which vary with disease activity. The objective of this clinical study was to investigate the effect of GLP-1 receptor agonist semaglutide therapy on pro-inflammatory factors in the serum and the severity of the clinical picture of psoriasis in obese patients with type 2 diabetes mellitus (T2DM) on chronic metformin therapy. This randomized clinical study was conducted on 31 psoriatic patients with T2DM that were randomized into two groups: one that received semaglutide during the 12-week trial (n = 15), while the second was control (n = 16). The results demonstrated that the severity of the clinical picture of psoriasis, determined by the Psoriasis Area and Severity Index (PASI) score, was significantly better after the administration of semaglutide (the median baseline PASI score in patients treated with semaglutide was 21 (IQR = 19.8), while after 12 weeks of therapy the score was 10 (IQR = 6; p = 0.002). Also, the quality of life in the group of patients who received the drug, measured by the Dermatology Life Quality Index (DLQI), improved significantly after 3 months (a median baseline DLQI score in the semaglutide group was 14 (IQR = 5) at the beginning of the study, and after 12 weeks of treatment the median DLQI score was 4 (IQR = 4; p = 0.002)). The use of semaglutide led to a significant decrease in pro-inflammatory cytokines in the serum (IL6), as well as a significant decrease in CRP values (p < 0.05). A significant decrease in the body mass index (BMI) value in the semaglutide-treated group was also identified, as well as a significant decrease in the level of low-density cholesterol (LDL) (p < 0.05). In conclusion, semaglutide, based on its systemic anti-inflammatory characteristics, could contribute to the treatment of psoriatic obese patients with T2DM.
Tryptophan Kynurenine Pathway-Based Imaging Agents for Brain Disorders and Oncology—From Bench to Bedside
Authors: Stauff Erik , Xu Wenqi , Kecskemethy Heidi H. , Langhans Sigrid A. , Kandula Vinay V. R. , Averill Lauren W. , Yue Xuyi
Published: January 2025

Tryptophan (Trp)-based radiotracers have excellent potential for imaging many different types of brain pathology because of their involvement with both the serotonergic and kynurenine (KYN) pathways. However, radiotracers specific to the kynurenine metabolism pathway are limited. In addition, historically Trp-based radiopharmaceuticals were synthesized with the short-lived isotope carbon-11. A newer generation of Trp-based imaging agents using the longer half-lived and commercially available isotopes, such as fluorine-18 and iodine-124, are being developed. The newly developed amino acid-based tracers have been demonstrated to have favorable radiochemical and imaging characteristics in pre-clinical studies. However, many barriers still exist in the clinical translation of KYN pathway-specific radiotracers.
The Interplay of Dual Tasks, Sleep Quality and Load Carriage on Postural Stability in Young, Healthy Adults
Authors: Martin Joel , Sax van der Weyden Megan , Estep Amanda
Published: January 2025

Background/Objectives: To examine the combined effects of sleep quality, dual tasks, and load carriage on postural stability. Methods: Twenty-three university student participants (12 males, ages: 24.6 ± 6.1 year) completed the Pittsburgh Sleep Quality Index (PSQI), then performed quiet standing and a dual task while standing on force plates with and without load carriage. Correlations and repeated measures analysis of variances were used to assess relationships, main effects, and interaction effects of tasks on center of pressure (COP) to assess postural stability. Both a traditional PSQI global score and a sensitivity analysis of the PSQI cut-off were conducted. Results: With the traditional PSQI criteria, a main effect of sleep quality on 95% ellipse area was observed, with good sleepers outperforming bad sleepers (p = 0.016). Additionally, a significant interaction between sleep quality and task (p = 0.049) indicated that COP anterior–posterior velocity was lower during the dual task for good sleepers. No effects on sleep quality or interaction were found for other COP measures. The sensitivity analysis yielded no effect on sleep quality or interaction effects on any COP measure. There were no significant correlations between the PSQI global scores and COP variables. Conclusions: Overall, the results indicate that sleep quality alone had a limited effect and did not significantly interact with dual tasks or load carriage during quiet standing. Practitioners working with individuals who commonly experience poor sleep quality and perform load carriage and dual tasks should consider that common COP screens to assess postural stability may not detect differences due to self-reported sleep quality in healthy, young adults.
The Influence of Gastric Microbiota and Probiotics in Helicobacter pylori Infection and Associated Diseases
Authors: Verma Jagriti , Anwar Md Tanveer , Linz Bodo , Backert Steffen , Pachathundikandi Suneesh Kumar
Published: January 2025

The role of microbiota in human health and disease is becoming increasingly clear as a result of modern microbiome studies in recent decades. The gastrointestinal tract is the major habitat for microbiota in the human body. This microbiota comprises several trillion microorganisms, which is equivalent to almost ten times the total number of cells of the human host. Helicobacter pylori is a known pathogen that colonizes the gastric mucosa of almost half of the world population. H. pylori is associated with several gastric diseases, including gastric cancer (GC) development. However, the impact of the gastric microbiota in the colonization, chronic infection, and pathogenesis is still not fully understood. Several studies have documented qualitative and quantitative changes in the microbiota’s composition in the presence or absence of this pathogen. Among the diverse microflora in the stomach, the Firmicutes represent the most notable. Bacteria such as Prevotella sp., Clostridium sp., Lactobacillus sp., and Veillonella sp. were frequently found in the healthy human stomach. In contrast, H.pylori is very dominant during chronic gastritis, increasing the proportion of Proteobacteria in the total microbiota to almost 80%, with decreasing relative proportions of Firmicutes. Likewise, H. pylori and Streptococcus are the most abundant bacteria during peptic ulcer disease. While the development of H. pylori-associated intestinal metaplasia is accompanied by an increase in Bacteroides, the stomachs of GC patients are dominated by Firmicutes such as Lactobacillus and Veillonella, constituting up to 40% of the total microbiota, and by Bacteroidetes such as Prevotella, whereas the numbers of H. pylori are decreasing. This review focuses on some of the consequences of changes in the gastric microbiota and the function of probiotics to modulate H. pylori infection and dysbiosis in general.
Novel Predictive Strategy Using CA19-9 and Fecal Elastase Levels to Make Treatment Decisions for Resectable Pancreatic Cancer: A Retrospective Study
Authors: Kim Hyung Sun , Kim Woojin , Yun Won-Gun , Jung Hye-Sol , Han Youngmin , Lee Mirang , Kwon Wooil , Jang Jin-Young , Park Joon Seong
Published: January 2025

Background: Carbohydrate antigen 19-9 (CA19-9) is used as a marker to predict recurrence and survival of patients with pancreatic ductal adenocarcinoma (PDAC). Recently, fecal elastase-1 (FE-1) has been shown to correlate with prognosis in patients with PDAC. Method: A total of 536 patients who underwent curative intent surgery between 2010 and 2019 were included in the study. The cutoff points of preoperative CA19-9 and FE-1 levels were extracted from the Youden index and previous studies. Cox proportional hazard models were used to investigate the association between preoperative tumor marker levels and survival after surgery. Results: Patients with CA19-9 ≥ 385 had more advanced T-/N-stages and lower survival rates compared to those with CA19-9 < 385. Multivariate Cox analyses demonstrated that combining preoperative tumor markers was associated with worse 3-year overall survival (both CA19-9 and FE-1 low, HR = 1.41, p = 0.044; both high, HR = 1.44, p = 0.047; CA19-9 high and FE-1 low, HR = 2.00, p < 0.001; and p for trend < 0.001). The same trend was confirmed in the analysis with recurrence-free survival. Conclusions: This study presents a new predictive strategy using combined CA19-9 and FE-1 levels to determine the treatment for resectable pancreatic cancer.
The Effect of Anesthetic Depth on the Occurrence of Emergence Delirium in Children Undergoing Strabismus Surgery: A Prospective Observational Study
Authors: Lee Yea-Ji , Hwang Jung-Won , Do Sang-Hwan , Na Hyo-Seok
Published: January 2025

Background/Objectives: Emergence delirium (ED) is one of the most frequent postoperative complications in pediatric patients after general anesthesia. In adults, a deeper intraoperative level of anesthesia has been reported as an independent predictor of postoperative delirium. However, the effect of anesthetic depth on ED has rarely been demonstrated in the pediatric population. We evaluated whether the depth of general anesthesia could affect the occurrence of emergence delirium (ED). Methods: Patients aged 3–5 years, scheduled for strabismus surgery were enrolled in this prospective observational study. Intraoperative bispectral index (BIS) was monitored, and the pediatric anesthesia emergence delirium (PAED) scale was evaluated. When the PAED scale was 10 or more, it was designated as an ED case. Results: According to the intraoperative mean BIS range, enrolled patients were divided into two groups: the low BIS (BIS < 40; n = 28) and the normal BIS (BIS 40–60; n = 34) group. The incidence of ED was comparable between the two groups (67.6% vs. 67.9%, odds ratio = 0.99, 95% CI = 0.34–2.89, p = 0.986). Conclusions: The intraoperative anesthetic depth did not seem to affect the occurrence of ED in pediatric patients undergoing strabismus surgery under general anesthesia. Future studies with a larger sample size are necessary for more authentic results.
Nitrate–Nitrite–Nitric Oxide Pathway, Oxidative Stress, and Fertility Outcomes in Morbidly Obese Women Following Bariatric Surgery: A Systematic Review
Authors: Voros Charalampos , Mavrogianni Despoina , Minaoglou Aspasia , Karakasis Alexios , Papahliou Anthi-Maria , Topalis Vasileios , Varthaliti Antonia , Mantzioros Raphail , Kondili Panagiota , Darlas Menelaos , Sotiropoulou Regina , Athanasiou Diamantis , Loutradis Dimitrios , Daskalakis Georgios
Published: January 2025

Obesity reduces nitric oxide (NO) production due to endothelial nitric oxide synthase (eNOS) dysfunction, resulting in oxidative stress, mitochondrial dysfunction, and chronic inflammation. These factors have a negative impact on reproductive health, including oocyte quality, endometrial receptivity, and embryo implantation. When oxidative stress affects eNOS function, the nitrate–nitrite–nitric oxide (NO3-NO2-NO) pathway provides an alternate route for NO production. Bariatric surgery has been found to restore NO production, reduce oxidative stress, and improve fertility in morbidly obese women. This review investigates the molecular mechanisms by which bariatric surgery affects eNOS activity, the NO3-NO2-NO pathway, and oxidative stress reduction, with an emphasis on intracellular activities including mitochondrial biogenesis and NO production. A systematic review employing PRISMA criteria included articles published between 2000 and 2024 from PubMed, Scopus, and Embase that investigated NO3-NO2 pathways, oxidative stress markers, hormonal alterations, and reproductive outcomes in morbidly obese women following bariatric surgery. After evaluating 1542 studies, 11 were selected for the final analysis. Results showed a 45% increase in NO3-NO2 levels (p < 0.001), a 35% reduction in oxidative stress indicators (p < 0.01), a 60% increase in pregnancy rates, and a 50% increase in spontaneous ovulation rates following surgery. These benefits were connected to improved mitochondrial function and endometrial receptivity as a result of reduced oxidative stress and inflammation. The NO3-NO2-NO route is critical in compensating for lower NO generation under oxidative stress and hypoxia, and bariatric surgery significantly improves this pathway to optimize blood flow, mitochondrial function, and reproductive results.
Efficacy of Photobiomodulation Therapy Utilizing 808 nm and 660 nm Alone and in Combination for Treatment of Paresthesia in Rats
Authors: Hajesmaelzade Ehsan , Mohammadi Mohammad , Kakooei Sina , Solimei Luca , Benedicenti Stefano , Chiniforush Nasim
Published: January 2025

Background/Objectives: This study assessed the efficacy of photobiomodulation therapy (PBM) by 808 nm and 660 nm alone and in combination for the treatment of paresthesia in rats. Methods: This animal study was conducted on 36 adult male Wistar rats. After general anesthesia, the facial nerve of the right side of the face of rats was surgically exposed and pinched, returned in place, and sutured. The rats were randomly assigned to six groups (n = 6) of (I) no-intervention (control), (II) no-laser, (III) 808 nm laser (250 mW, 4 W/cm2, 20 s, 8 J/cm2, (IV) 660 nm laser (150 mW, 0.25 W/cm2, 32 s, 8 J/cm2, (V) 808 nm plus 660 nm laser with the original settings, and (VI) 808 nm plus 660 nm laser with half of the time and energy density. After 16 days, a biopsy sample was taken from the nerve injury site and underwent histological, histometric, and immunohistochemical assessments. Results: Significantly lower edema and congestion were seen in the combined laser group with original settings (p < 0.05); this group had no significant difference with the control group regarding degenerative changes of the nerve fibers and Schwann cells (p > 0.05). The 660 nm, and combined laser groups, had a significantly lower accumulation of inflammatory cells (p < 0.05). The number of blood vessels in combined laser groups was significantly lower than that in the no-laser group (p < 0.05). Conclusions: The results showed the positive efficacy of PBM by 808 nm and 660 nm lasers in resolution of inflammation and reduction of degenerative changes of Schwann cells and nerve fibers.
Angiotensin IV Receptors in the Rat Prefrontal Cortex: Neuronal Expression and NMDA Inhibition
Authors: Papp Zsolt Tamás , Ribiczey Polett , Kató Erzsébet , Tóth Zsuzsanna E. , Varga Zoltán V. , Giricz Zoltán , Hanuska Adrienn , Al-Khrasani Mahmoud , Zsembery Ákos , Zelles Tibor , Harsing Laszlo G. , Köles László
Published: January 2025

Background: N-methyl-D-aspartate type glutamate receptors (NMDARs) are fundamental to neuronal physiology and pathophysiology. The prefrontal cortex (PFC), a key region for cognitive function, is heavily implicated in neuropsychiatric disorders, positioning the modulation of its glutamatergic neurotransmission as a promising therapeutic target. Our recently published findings indicate that AT1 receptor activation enhances NMDAR activity in layer V pyramidal neurons of the rat PFC. At the same time, it suggests that alternative angiotensin pathways, presumably involving AT4 receptors (AT4Rs), might exert inhibitory effects. Angiotensin IV (Ang IV) and its analogs have demonstrated cognitive benefits in animal models of learning and memory deficits. Methods: Immunohistochemistry and whole-cell patch-clamp techniques were used to map the cell-type-specific localization of AT4R, identical to insulin-regulated aminopeptidase (IRAP), and to investigate the modulatory effects of Ang IV on NMDAR function in layer V pyramidal cells of the rat PFC. Results: AT4R/IRAP expression was detected in pyramidal cells and GABAergic interneurons, but not in microglia or astrocytes, in layer V of the PFC in 9–12-day-old and 6-month-old rats. NMDA (30 μM) induced stable inward cation currents, significantly inhibited by Ang IV (1 nM–1 µM) in a subset of pyramidal neurons. This inhibition was reproduced by the IRAP inhibitor LVVYP-H7 (10–100 nM). Synaptic isolation of pyramidal neurons did not affect the Ang IV-mediated inhibition of NMDA currents. Conclusions: Ang IV/IRAP-mediated inhibition of NMDA currents in layer V pyramidal neurons of the PFC may represent a way of regulating cognitive functions and thus a potential pharmacological target for cognitive impairments and related neuropsychiatric disorders.
Modeling of Blood Flow Dynamics in Rat Somatosensory Cortex
Authors: Battini Stéphanie , Cantarutti Nicola , Kotsalos Christos , Roussel Yann , Cattabiani Alessandro , Arnaudon Alexis , Favreau Cyrille , Antonel Stefano , Markram Henry , Keller Daniel
Published: January 2025

Background: The cerebral microvasculature forms a dense network of interconnected blood vessels where flow is modulated partly by astrocytes. Increased neuronal activity stimulates astrocytes to release vasoactive substances at the endfeet, altering the diameters of connected vessels. Methods: Our study simulated the coupling between blood flow variations and vessel diameter changes driven by astrocytic activity in the rat somatosensory cortex. We developed a framework with three key components: coupling between the vasculature and synthesized astrocytic morphologies, a fluid dynamics model to compute flow in each vascular segment, and a stochastic process replicating the effect of astrocytic endfeet on vessel radii. Results: The model was validated against experimental flow values from the literature across cortical depths. We found that local vasodilation from astrocyte activity increased blood flow, especially in capillaries, exhibiting a layer-specific response in deeper cortical layers. Additionally, the highest blood flow variability occurred in capillaries, emphasizing their role in cerebral perfusion regulation. We discovered that astrocytic activity impacted blood flow dynamics in a localized, clustered manner, with most vascular segments influenced by two to three neighboring endfeet. Conclusions: These insights enhance our understanding of neurovascular coupling and guide future research on blood flow-related diseases.
Gut Microbiota as Emerging Players in the Development of Alcohol-Related Liver Disease
Authors: Li Wei , Gao Wenkang , Yan Shengqi , Yang Ling , Zhu Qingjing , Chu Huikuan
Published: January 2025

The global incidence and mortality rates of alcohol-related liver disease are on the rise, reflecting a growing health concern worldwide. Alcohol-related liver disease develops due to a complex interplay of multiple reasons, including oxidative stress generated during the metabolism of ethanol, immune response activated by immunogenic substances, and subsequent inflammatory processes. Recent research highlights the gut microbiota’s significant role in the progression of alcohol-related liver disease. In patients with alcohol-related liver disease, the relative abundance of pathogenic bacteria, including Enterococcus faecalis, increases and is positively correlated with the level of severity exhibited by alcohol-related liver disease. Supplement probiotics like Lactobacillus, as well as Bifidobacterium, have been found to alleviate alcohol-related liver disease. The gut microbiota is speculated to trigger specific signaling pathways, influence metabolite profiles, and modulate immune responses in the gut and liver. This research aimed to investigate the role of gut microorganisms in the onset and advancement of alcohol-related liver disease, as well as to uncover the underlying mechanisms by which the gut microbiota may contribute to its development. This review outlines current treatments for reversing gut dysbiosis, including probiotics, fecal microbiota transplantation, and targeted phage therapy. Particularly, targeted therapy will be a vital aspect of future alcohol-related liver disease treatment. It is to be hoped that this article will prove beneficial for the treatment of alcohol-related liver disease.
Targeted Plasma Bile Acid Metabolomic Analysis in Metabolic Dysfunction-Associated Steatohepatitis and Alcoholic Hepatitis
Authors: Hirata Yuta , Sakuma Yasunaru , Ogiso Hideo , Nagai Ryozo , Aizawa Kenichi
Published: January 2025

Background: Even though many metabolic liver diseases can now be diagnosed using blood tests and diagnostic imaging, early diagnosis remains difficult. Understanding mechanisms contributing to the progression from Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Alcoholic Hepatitis (AH) to cirrhosis is critical to reduce the burden of end-stage liver disease. Monitoring individual bile acids has been proposed as a way to distinguish various liver disorders. Methods: This study explored bile acid profiles in patients with MASH and AH. Plasma samples from patients with MASH, AH, and a control group were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify bile acid concentrations. Targeted metabolomic analysis was performed to compare bile acid levels between the hepatitis and control groups. Results: Concentrations of ursodeoxycholic acid (UDCA), chenodeoxycholic acid (CDCA), taurocholic acid (TCA), tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA), glycoursodeoxycholic acid (GUDCA), glycochenodeoxycholic acid (GCDCA), and glycocholic acid (GCA) were significantly elevated in the hepatitis group. Correlation analysis revealed strong positive relationships between the total and direct bilirubin levels and TUDCA and GCDCA. Aspartate aminotransferase (AST) showed strong positive correlations with TCDCA and GCDCA. Child–Pugh score, Fibrosis-4 index, and non-alcoholic fatty liver disease fibrosis score were positively correlated with GCA, whereas the aspartate aminotransferase-to-platelet ratio correlated with TCA, TCDCA, and GCA. The model for end-stage liver disease (MELD) score showed a strong positive correlation with GCDCA. Implications: GCDCA may serve as a predictive biomarker for liver damage, potentially enabling early diagnosis and targeted intervention in patients with MASH and AH.
Advancements in Cardiac Amyloidosis Treatment
Authors: Arabi Tarek Ziad , Shaik Abdullah , El-Shaer Ahmed , Al Tamimi Omar , Ahmed Eman Nayaz , Alabdaljabar Mohamad S. , Safdar Ahmad , Mushtaq Ali
Published: January 2025

Cardiac amyloidosis (CA) is a progressive condition resulting from the deposition of amyloid fibrils in the heart, which leads to severe diastolic dysfunction and restrictive cardiomyopathy. The disease has two main subtypes: light-chain and transthyretin (TTR) CA, with the latter subdivided into wild-type and hereditary forms. Despite advances in diagnostic imaging, early detection remains a challenge due to non-specific symptoms that mimic other cardiac conditions. Treatment has evolved significantly with targeted therapies like TTR stabilizers, gene silencers, and RNA interference, showing promise in altering disease progression. However, barriers such as high costs, limited availability of genetic testing, and inadequate multidisciplinary care continue to impede comprehensive management. Future strategies should focus on integrating novel gene-editing therapies, expanding access to diagnostics, and enhancing multidisciplinary care models to improve outcomes. Overall, early diagnosis, equitable access to therapies, and personalized management plans are crucial to advancing care for CA patients.
Visual System Inspired Algorithm for Enhanced Visibility in Coronary Angiograms (VIAEVCA)
Authors: Spitzer Hedva , Kashi Yosef Shai , Mosseri Morris , Erel Jacob
Published: January 2025

Numerous efforts have been invested in previous algorithms to expose and enhance blood vessel (BV) visibility derived from clinical coronary angiography (CAG) procedures, such as noise reduction, segmentation, and background subtraction. Yet, the visibility of the BVs and their luminal content, particularly the small ones, is still limited. We propose a novel visibility enhancement algorithm, whose main body is inspired by a line completion mechanism of the visual system, i.e., lateral interactions. It facilitates the enhancement of the BVs along with simultaneous noise reduction. In addition, we developed a specific algorithm component that allows better visibility of small BVs and the various CAG tools utilized during the procedure. It is accomplished by enhancing the BVs’ fine resolutions, located in the coarse resolutions at the BV zone. The visibility of the most significant clinical features during the CAG procedure was evaluated and qualitatively compared by the consensus of two cardiologists (MM and JE) to the algorithm’s results. These included the visibility of the whole frame, the coronary BVs as well as the small ones, the main obstructive lesions within the BVs, and the various angiography interventional tools utilized during the procedure. The algorithm succeeded in producing better visibility of all these features, even under low-contrast or low-radiation conditions. Despite its major advantages, the algorithm also caused the appearance of disturbing vertebral and bony artifacts, which could somewhat lower diagnostic accuracy. Yet, viewing the processed images from multiple angles and not just from a single one and evaluating the cine mode usually overcomes this drawback. Thus, our novel algorithm potentially leads to a better clinical diagnosis, improved procedural capabilities, and a successful outcome.
Examining Insula–Default Mode Network Functional Connectivity and Its Relationship with Heart Rate Variability
Authors: Nogueira Marlene , Magalhães Juliana da Silva , Sampaio Adriana , Sousa Sónia , Coutinho Joana F.
Published: January 2025

Background: The Default Mode Network (DMN) is involved in self-referential and emotional processes, while the insula integrates emotional and interoceptive signals. Functional connectivity between the insula and the DMN is proposed to enhance these processes by linking internal bodily states with self-referential thoughts and emotional regulation. Heart Rate Variability (HRV), a measure of parasympathetic regulation of cardiac activity, has been associated with the capacity to regulate autonomic arousal. This study explored the relationship between insula–DMN functional connectivity and HRV. We hypothesized that (1) insula’s functional activity and volume would be related to HRV; (2) insula activation would be functionally connected with the DMN; and (3) stronger insula–DMN connectivity would correlate with higher HRV. Methods: Forty-three healthy adults underwent a structural and functional MRI acquisition to assess insula–DMN connectivity during resting state. HRV was measured also at rest using the BIOPAC system. Results: A significant positive correlation was found between insula–DMN connectivity, but no correlation was observed between insula–DMN connectivity and HRV. We also found a positive significant association between left insula volume and HRV. Conclusions: These findings suggest that while the AI and DMN are functionally interconnected, this connectivity may not be directly related to HRV. The results highlight the complexity of the relationship between brain connectivity and autonomic function, suggesting that other factors may influence HRV.
Trauma, Justice, and Equity: Using Critical Theories and Concepts to Address Systemic Harm Among Youth Punishment System-Involved Black Girls
Authors: Quinn Camille R.
Published: January 2025

This review critically evaluates the existing literature on youth punishment system (YPS)-involved Black girls and their intersections of with trauma and post-traumatic stress disorder (PTSD). It synthesizes findings from previous studies, identifying key research trends, gaps, and controversies, while also highlighting areas in need of further investigation. Black girls, particularly those involved in systems such as juvenile justice, child welfare, and education, often face disproportionate exposure to violence, abuse and neglect, trauma, and systemic racism. For Black girls with histories of trauma and PTSD, these intersecting challenges are compounded by the added vulnerabilities of race, gender, and YPS involvement. This article argues that addressing the complex needs of this population requires recognition that Black girls’ harm is criminalized and, therefore, inextricably linked to their YPS-involvement, so a comprehensive, culturally responsive approach that includes trauma-informed care, healing-centered engagement, and holistic support systems are needed. Equitable access to tailored mental health services, educational resources, and culturally relevant interventions is essential to mitigate the long-term effects of trauma, promote resilience, and foster healing. Additionally, advocacy efforts to dismantle systemic harm and address racial and gender disparities are critical for creating inclusive environments that empower and support Black girls in these systems. By centering their lived experiences, this review emphasizes the importance of fostering environments of healing, justice, and equity for this vulnerable population.
Cognitive and Neural Differences in Exact and Approximate Arithmetic Using the Production Paradigm: An fNIRS Study
Authors: Yue Tianqi , Guan Buxuan , Wu Yan
Published: January 2025

This study investigated the cognitive and neural mechanisms of exact and approximate arithmetic using fNIRS technology during natural calculation processes (i.e., the production paradigm). Behavioral results showed (1) a significantly longer reaction time for exact arithmetic compared to approximate arithmetic, and (2) both exact and approximate arithmetic exhibited a problem size effect, with larger operands requiring more time. The fNIRS results further revealed differences in the neural bases underlying these two arithmetic processes, with exact arithmetic showing greater activation in the L-SFG (left superior frontal gyrus, CH16), while approximate arithmetic exhibited problem size effect in the right hemisphere. Additionally, larger operands registered more brain activities in the R-DLPFC (right dorsolateral prefrontal cortex, CH4), R-SFG (right superior frontal gyrus, CH2), and PMC and SMA (pre- and supplementary motor cortexes, CH3) compared to smaller operands in approximate arithmetic. Moreover, correlation analysis found a significant correlation between approximate arithmetic and semantic processing in the R-PMC and R-SMA (right pre- and supplementary motor cortexes). These findings suggest a neural dissociation between exact and approximate arithmetic, with exact arithmetic processing showing a dominant role in the left hemisphere, while approximate arithmetic processing was more sensitive in the right hemisphere.
Exploring the Relation: Does Forgiveness Enhance Interpersonal Problem Solving?
Authors: Girgin Büyükbayraktar Çağla , Barbaros Yalçın Süleyman , Yavuz Öztürk İsmail , Say Serkan
Published: January 2025

This study explores the relationship between forgiveness and interpersonal problem-solving skills among university students using a correlational design. The sample includes 443 students aged 18–26 from Mersin and Selçuk Universities, selected through convenience sampling. Data were collected using the Heartland Forgiveness Scale, the Interpersonal Problem-Solving Inventory, and a personal information form. Pearson correlation and multiple regression analyses were conducted. Results indicate significant relationships between forgiveness and problem-solving skills. Forgiveness positively predicts constructive problem-solving (r = 0.45, p < 0.01) and negatively correlates with negative approaches to problems (r = −0.37, p < 0.01), lack of self-confidence (r = −0.29, p < 0.01), and unwillingness to take responsibility (r = −0.31, p < 0.01). Forgiveness explains 25.2% of the variance in negative approaches, 8% in constructive problem-solving, 13.4% in self-confidence, and 10.3% in responsibility avoidance. Self-forgiveness, forgiveness of others, and situational forgiveness are significant predictors across these dimensions. Findings suggest that forgiving students manage interpersonal conflicts more positively, with reduced negative emotions and avoidance behaviors. Promoting forgiveness and problem-solving skills through educational programs may enhance students’ social harmony, adjustment, and life satisfaction, benefiting both individuals and society. This aligns with existing literature highlighting the emotional and relational benefits of forgiveness.
Effective School Leadership for Supporting Students’ Mental Health: Findings from a Narrative Literature Review
Authors: Daly Brian P. , Resnikoff Annie , Litke Shannon
Published: January 2025

There is a compelling literature base in the field of education that highlights how school leaders are crucial to improving academic processes and outcomes, including instruction and raising student achievement. Research has also demonstrated that effective school leaders exhibit behaviors aligned with promoting the core issues of teaching, learning, and school improvement. Less well-known is what science says about the effectiveness of professional development and leadership preparation programs for developing the competencies needed for addressing the diverse mental health needs of students. Better understanding the science is important as school leaders are increasingly tasked with connecting leadership behaviors to students’ social and emotional outcomes, and these leaders play a large role in whether, and to what extent, mental health promotion and prevention are effectively implemented in school settings. Drawing from diverse literature bases of education and psychology, the primary objective of this narrative literature review is to determine and define effective leadership behaviors, skills, and competencies in the context of implementing school mental health programs and strategies. The secondary objective is to summarize the existing research examining leadership preparation and professional development programs that promote effective leadership practices and highlight examples of leadership programs focused on enhancing school mental health.
Course Evaluation of Advanced Structural Dynamics Based on Improved SAPSO and FAHP
Authors: Huang Minshui , He Zhongao , Zhang Jianwei , Deng Zhihang , Tang Dina
Published: January 2025

Talent cultivation is the fundamental mission of higher education institutions, and the key to improving the quality of talent cultivation lies in enhancing the quality of teaching. In this regard, the Joint Committee recommends that the United Nations Educational, Scientific and Cultural Organization (UNESCO) should be invited to participate in this conference, in accordance with their respective mandates. However, in China, research on course evaluation systems and mechanisms in application-oriented universities is relatively scarce, and the evaluation dimensions are often limited; therefore, the evaluation of graduate courses in universities faces challenges such as a lack of specialized assessment systems, limitation of evaluation methods, and an imbalance between emphasis on outcomes and neglect of the teaching process. In this study, a comprehensive evaluation system for the Advanced Structural Dynamics (ASD) course is constructed based on the context-input-process-product (CIPP) evaluation model. The evaluation was conducted from four perspectives: teaching objectives, teaching inputs, teaching processes, and teaching outcomes. The fuzzy analytic hierarchy process (AHP) and simulated annealing particle swarm algorithm (SAPSO) are employed to study evaluation indicators and weights at various levels for the ASD course, and the proposed method is validated through practical examples. This study combines qualitative and quantitative evaluation indicators to achieve comprehensive assessment and adopts more scientifically rational algorithms for weight calculation, aiming to improve the accuracy and efficiency of weight calculation. The research findings of this study can further enhance the evaluation level of teaching quality and talent cultivation in graduate courses at application-oriented universities.