bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review of serious games as tools for STEM education
Authors: Tene Talia , Vique López Diego Fabián , Valverde Aguirre Paulina Elizabeth , Cabezas Oviedo Nilo Israel , Vacacela Gomez Cristian , Bellucci Stefano
Published: February 2025

Objective

Serious games are increasingly recognized as innovative tools in STEM (Science, Technology, Engineering, and Mathematics) education, providing engaging and interactive learning environments that can enhance student performance, engagement, and learning outcomes. This systematic review aims to synthesize current research on serious games in STEM education, evaluating their impact and identifying implications for educators, policymakers, and future research.

Methods

A comprehensive literature search was conducted across Scopus, Web of Science, PubMed, and IEEE Xplore databases, yielding 584 articles. A total of 37 peer-reviewed journal articles met the inclusion criteria, guided by the PICOS framework, which focused on studies reporting the use of serious games in STEM education contexts. Data extraction included study characteristics, game types, participant demographics, educational contexts, and reported outcomes.

Analysis

The selected studies were analyzed to assess the effectiveness of serious games in enhancing learning outcomes, engagement, and performance in STEM education. The analysis also explored challenges related to the implementation of serious games, including technological limitations, the need for comprehensive educator training, and ethical considerations around data privacy, all of which may impact adoption in educational settings.

Results

Serious games demonstrated a positive impact on learning outcomes, such as knowledge acquisition, skill retention, and the application of STEM concepts, along with increased student engagement and motivation. These findings suggest that serious games can serve as valuable tools for educators seeking to foster active learning environments. For policymakers, the results indicate a need for strategic investments in technology infrastructure, teacher training, and curriculum integration to maximize the benefits of serious games in STEM education. However, significant limitations were identified, including technological barriers, variability in study quality, and the need for sustained educator support, which may impact generalizability and implementation.

Conclusion

This review highlights the transformative potential of serious games as tools for STEM education but emphasizes the importance of addressing key challenges to realize their full benefits. For educators, implementing serious games requires alignment with curriculum goals and access to adequate training and resources. Policymakers are encouraged to support these efforts by providing financial resources and promoting frameworks for ethical, data-secure use of serious games in education. Future research should focus on establishing a globally recognized framework for serious games in STEM, conducting longitudinal studies to evaluate long-term impacts, and exploring diverse educational contexts to ensure inclusive and effective integration.
Pre-diabetes and cardiovascular risk factors in NAFLD patients: a retrospective comparative analysis
Authors: Teimouri Azam , Ebrahimpour Zahra , Feizi Awat , Iraj Bijan , Saffari Elahe , Akbari Mojtaba , Karimifar Mozhgan
Published: February 2025

Objectives

Insulin resistance plays a critical role in the pathophysiology of diabetes mellitus and non-alcoholic fatty liver disease (NAFLD). Moreover, insulin resistance has a central role in atherogensis as the major leading cause of cardiovascular disease (CVD). The aim of the present study was to assess the frequency of pre-diabetes and evaluate the cardiometabolic risk factors among NAFLD patients, comparing those with pre-diabetes to those with normal glucose tolerance.

Methods

In the current retrospective case-control study, the data of 1031 NAFLD patients was retrieved. Based on blood glucose levels, 337 diabetics, 340 pre-diabetes, and, 354 normal glucose patients were diagnosed. After excluding diabetic NAFLD patients, 694 individuals were divided into two groups: normal glucose and pre-diabetes. Various variables, such as age, anthropometric measurements, hypertension, systolic and diastolic blood pressure, and lipid profiles, were extracted from patient files. Statistical analysis was conducted to assess cardiovascular risk factors in NAFLD patients.

Results

Higher age, female gender, higher BMI, triglyceride, waist and hip circumference and waist-to-hip ratio were found in pre-diabetic NAFLD individuals compared with normoglycemic ones (P-value<0.05). Multivariable age-, sex-, BMI- and smoking- adjusted logistic regression showed a predicting role of pre-diabetes and NAFLD concurrence with metabolic syndrome (P-value<0.001, OR:4.31, 95% CI: 2.95- 6.29), but not CVD (P-value=0.353, OR:1.37, 95% CI: 0.71- 2.61).

Conclusion

In this study, nearly one-third of NAFLD patients had pre-diabetes. The mean value of age, BMI, TG, waist and Hip circumference was significantly higher in pre-diabetic patients. The concurrence of pre-diabetes and NAFLD was a predicting factor for metabolic syndrome, but not CVD events.
Efficacy in Japanese adults with growth hormone deficiency receiving weekly somapacitan or daily growth hormone: results from phase 3 REAL 1 trial
Authors: Otsuka Fumio , Rasmussen Michael Højby , Endo Takaaki , Sværke Claus , Tahara Shigeyuki , Johannsson Gudmundur
Published: February 2025

Introduction

Somapacitan is a long-acting growth hormone (GH) derivative approved for once-weekly treatment of adult GH deficiency (AGHD). This study aimed to evaluate the efficacy and safety of somapacitan and daily GH in Japanese individuals with AGHD.

Methods

This subgroup study included the 34-week main period of the multinational, randomized, parallel-group, phase 3 trial, REAL 1 (NCT02229851). Participants received once-weekly somapacitan or daily GH (Norditropin®), both administered subcutaneously. Investigators and trial sites were blinded. A total of 36 Japanese GH-naïve individuals with AGHD were allocated to somapacitan or daily GH (excluding the placebo group of the global trial). Endpoints included change in truncal fat percentage to week 34 measured using dual-energy x-ray absorptiometry, as well as other body composition measures. Insulin-like growth factor I standard deviation score values were used for dose titration.

Results

In total, 36 Japanese individuals were included (18 and 18 in the somapacitan and daily GH group, respectively). 35 completed the main period (34 weeks). Mean (SD) change from baseline to week 34 in truncal fat percentage was -2.23 (2.50) %-points in the somapacitan group and -2.12 (4.21) %-points in the daily GH group. Other body composition measures also improved in both groups, including reduced visceral fat and increased lean body mass. Somapacitan was well tolerated, with a safety profile similar to daily GH.

Conclusions

In Japanese treatment-naïve individuals with AGHD, once-weekly somapacitan demonstrated similar efficacy and safety to daily GH after 34 weeks of treatment. Somapacitan provides an effective alternative to daily GH in AGHD.

Clinical trial registration

http://www.clinicaltrials.gov, identifier NCT02229851.
Immune-endocrine crossroads: the impact of nuclear receptors in Tuberculosis and Chagas disease
Authors: Pérez Ana R. , Bottasso Oscar A. , Santucci Natalia E.
Published: February 2025

Nuclear Receptors (NRs) comprise a superfamily of proteins with essential roles in cell signaling, survival, proliferation, and metabolism. They act as transcription factors and are subclassified into families based on their ligands, DNA-binding sequences, tissue specificity, and functions. Evidence indicates that in infectious diseases, cancer, and autoimmunity, NRs modulate immune and endocrine responses, altering the transcriptional profile of cells and organs and influencing disease progression. Chronic infectious diseases, characterized by pathogen persistence, are particularly notable for an exaggerated inflammatory process. Unlike acute inflammation, which helps the host respond to pathogens, chronic inflammation leads to metabolic disorders and a dysregulated neuro-immuno-endocrine response. Over time, disturbances in cytokine, hormone, and other compound production foster an unbalanced, detrimental defensive response. This complexity underscores the significant role of ligand-dependent NRs. Tuberculosis and Chagas Disease are two critical chronic infections. The causative agents, Mycobacterium tuberculosis and Trypanosoma cruzi, have developed evasion strategies to establish chronic infections. Their clinical manifestations are associated with disrupted immuno-endocrine responses, pointing to a potential involvement of NRs. This review explores the current understanding of NRs in regulating immune-endocrine interactions within the context Tuberculosis and Chagas Disease. These diseases remain significant global health concerns, particularly in developing countries, highlighting the importance of understanding the molecular mechanisms underlying host-pathogen interactions mediated by NRs.
Between financial, environmental and health concerns: the role of risk perceptions in modeling efuel acceptance
Authors: Arning Katrin , Offermann Julia , Engelmann Linda , Gimpel Regina , Ziefle Martina
Published: February 2025

The transition towards sustainable and defossilized mobility systems relies on public perception and acceptance of innovations like efuels. Understanding the role of risk perceptions and their different dimensions in shaping public acceptance is therefore critical for facilitating the introduction of efuels into mobility systems. A quantitative survey was conducted among a representative sample of 517 German participants to assess their risk perceptions and acceptance of efuels. A Structural Equation Modeling (SEM) approach was employed to analyze the relationships between cognitive, affective, and domain-specific risk perceptions (health, environmental, and financial) and public acceptance of efuels. The analysis revealed low levels of both cognitive and affective risk perceptions as well as positive acceptance levels for efuels. Financial risk perception was more pronounced than health or environmental risk perceptions. Affective and cognitive risk perceptions were found to negatively impact acceptance, with cognitive risk perception showing a stronger influence. Environmental risk perception was negatively associated with acceptance, while health and financial risks showed no significant association. The findings suggest that while efuels are generally accepted, financial and environmental concerns might hinder widespread adoption. Addressing these concerns through targeted communication strategies that combine cognitive (economic, environmental) and affective (health) dimensions is essential for a socially accepted design of sustainable mobility systems.
Green tides: the Suez Canal as key hub and green corridor for a hydrogen future between the Middle East and Europe
Authors: Zumbraegel Tobias , Kegel Alisa
Published: February 2025

The shipping industry faces the dual challenge of reducing emissions to meet net-zero targets by 2050 and transporting green energy sources like hydrogen and its derivatives. Green shipping corridors provide experimental routes for low-carbon solutions, with the Suez Canal uniquely positioned to lead. This paper examines the canal’s evolving role as a dynamic energy space, where diverse actors and networks intersect, shaping spatial power relations and aligning with green capitalism interests. It explores the Suez Canal’s potential to serve as a model for hydrogen initiatives and its capacity to influence global energy governance and geopolitical dynamics in the transition to a sustainable shipping future. The canal also represents a microcosm of broader global shifts toward a future hydrogen economy, where numerous stakeholders vie for power and influence.
Geochemistry and mineralogy of Cobalt in mine wastes: examples from Cobalt, Canada and Cornwall, England
Authors: Ziwa Gabriel , Crane Rich , Hudson-Edwards Karen A.
Published: February 2025

Mine wastes can pose environmental and human health risks, especially when they contain high concentrations of potentially toxic metal(loid)s. In this study, the geochemistry (bulk and sequential extraction analysis, paste pH) and mineralogy (X-ray diffraction, scanning electron microscopy, electron microprobe analysis) of Co in mine wastes from Cobalt (Canada) and Cornwall (UK) were characterised to assess potential Co and other metal(loid) mobility in the aquatic environment. Cobalt concentrations in Nipissing high- and low-grade tailings at Cobalt were high (up to 5,630 mg kg−1 and 1,230 mg kg−1, respectively), and were several orders of magnitude higher than those at Poldice, Wheal Unity, and Dolcoath in Cornwall (average 40 mg kg−1, 76 mg kg−1, and 59 mg kg−1, respectively). Community Bureau of Reference (BCR)-sequential extraction analysis suggested that Co was equally mobile within the samples from Cobalt and Cornwall, with averages of 46% extracted in the exchangeable fraction. Erythrite was the most important secondary Co-bearing mineral that occurred widely in the Nipissing tailings. Other Co-bearing secondary minerals included arseniosiderite, scorodite, and Fe oxyhydroxides. Primary Co-bearing minerals identified included cobaltite and safflorite-skutterudite, and Co was also taken up in primary arsenopyrite, loellingite, pyrite and chalcopyrite. At the sites in Cornwall, however, Co-bearing primary and secondary minerals were not identified. Instead, Co was observed as a trace component in primary arsenopyrite, pyrite, and chalcopyrite and in secondary scorodite and Fe-Mn oxyhydroxides. Despite these mineralogical and other geological and processing differences, Co showed consistently high potential for mobilization from the wastes. In addition, risk assessment codes for Co fell in the medium to very high risk category in the aquatic and non-aquatic environments. This classification suggests that the mine waste-hosted Co is likely to affect humans via the food chain. Further research is required to determine if Co shows similar behaviour in mine wastes globally.
Manipulating the cGAS-STING Axis: advancing innovative strategies for osteosarcoma therapeutics
Authors: Li BingBing , Zhang Cheng , Xu XiaoJuan , Shen QiQin , Luo ShuNan , Hu JunFeng
Published: February 2025

This paper explored the novel approach of targeting the cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator of interferon genes (cGAS-STING) pathway for the treatment of osteosarcoma (OS). Osteosarcoma is a common malignancy in adolescents. Most patients die from lung metastasis. It reviewed the epidemiology and pathological characteristics of OS, highlighting its highly malignant nature and tendency for pulmonary metastasis, underscoring the importance of identifying new therapeutic targets. The cGAS-STING pathway was closely associated with the malignant biological behaviors of OS cells, suggesting that targeting this pathway could be a promising therapeutic strategy. Currently, research on the role of the cGAS-STING pathway in OS treatment has been limited, and the underlying mechanisms remain unclear. Therefore, further investigation into the mechanisms of the cGAS-STING pathway in OS and the exploration of therapeutic strategies based on this pathway are of great significance for developing more effective treatments for OS. This paper offered a fresh perspective on the treatment of OS, providing hope for new therapeutic options for OS patients by targeting the cGAS-STING pathway.
Descriptive ecology of abyssal decapods from Chapopote Knoll (southwestern Gulf of Mexico)
Authors: Gaytán-Caballero Adriana , Schubotz Florence , MacDonald Ian R. , Escobar-Briones Elva G.
Published: February 2025

The Chapopote Knoll at 3200 m depth, in the southern Gulf of Mexico harbors highly diverse benthic habitats, including massive asphalt flows and surficial gas hydrates with gas seepage. Its associated benthic megafauna includes endemic cold-seep species and background species. This study describes the benthic habitat preferences, distribution patterns and diets of three crustacean species, the caridean shrimp Alvinocaris muricola and the galatheids Munidopsis geyeri and M. exuta. High-resolution imaging recorded eight habitats and helped depict their spatial distributions. A. muricola aggregates on Siboglinidae clusters and in gas seepage sites. M. geyeri and M. exuta are less selective and occur in almost all habitats. The carbon (δ13C) and nitrogen (δ15N) values of A. muricola show a nutritional preference of bacteria from mats and water column detritus retained among the Sibolindiae, whereas the two Munidopsis species have wider spectrum diets. Gut content analysis in all three species, validate the stable isotope values, food sources and confirm the secondary consumer’s trophic level. This study recognizes coexistence of A. muricola and the two Munidopsis species in the benthic habitats while using different resources. Compound specific isotope analyses of galatheid guts revealed females to have more 13C-depleted lipids (-35‰) compared to males (-28‰), calling for more detailed analyses to clarify this trophic segregation.
Mulberry leaf extract reduces damage by regulating the oxidative response, immune response and intestinal flora of largemouth bass (Micropterus salmoides) under chronic heat stress
Authors: Fu Bing , Zhou Donglai , Qiu Xiaotong , Zheng Jieqiu , Yang Qiong , Xiao Yang , Liao Sentai , Li Qingrong , Xing Dongxu
Published: February 2025

Chronic heat stress (HS) induces oxidative damage, low immunity, and intestinal flora disturbance of fish, posing great challenges to the aquaculture industry. As an important plant extract, mulberry leaf extract (MLE) has been shown to have antioxidant and immune-boosting properties. This study evaluated the protective effect of dietary MLE on HS-induced liver injury and intestinal flora disturbance in Largemouth bass (Micropterus salmoides) based on oxidative damage parameters, immune parameters, and intestinal flora composition. Fish were randomly assigned into three groups: CON group (ambient temperature, 26°C, basal diet), HS group (33°C, basal diet), and HS + MLE group (33°C, basal diet supplemented with 9 g/kg MLE). HS significantly decreased the final body weight, specific growth rate, intestinal villus length, muscular layer thickness, ACE and Chao1 indices, and lipase, trypsin, total superoxide dismutase (T-SOD), glutathione peroxidase (GPx), alkaline phosphatase (AKP), and lysozyme (LZM) activities, but significantly increased the feed conversion rate, aspartate aminotransferase (AST) activity, reactive oxygen species (ROS), malondialdehyde (MDA), complement 3 (C3) contents, and the relative abundances of Proteobacteria and Plesiomonas. Compared with the HS group, dietary MLE significantly improved lipase, trypsin, GPx, ACP, and LZM activities, and ACE and Chao1 indices in intestine, but significantly decreased the numbers of vacuoles and inflammatory cells, AST activity, and the GLU, MDA, and ROS contents. Dietary MLE also significantly up-regulated the mRNA expressions of gpx, tgf-β, il-10, jnk2, and bcl-2, but down-regulated the mRNA expressions of il-8, tnf-α, caspase-3, atf4, chop, ire1, traf2, jnk1, TRPV, MCU, and VDAC in liver. In conclusion, dietary supplementation with 9 g/kg MLE could improve the growth, immunity, and diversity of intestinal flora in heat-stressed largemouth bass, and alleviate hepatic injuries by regulating inflammation, oxidative stress, and apoptosis, providing a theoretical basis for the development of MLE as a treatment against HS.
ZIF-8/PLA porous composite microspheres: preparation, characterization, and effective removal of gaseous benzene
Authors: Li Jiali , Sun Peijian , Wang Yipeng , Sun Xuehui , Peng Bin , Xu Weili , Liu Mengmeng , Nie Cong
Published: February 2025

Benzene is a prevalent environmental contaminant, and its effective removal through adsorption is crucial to mitigate both environmental and health impacts. In this study, a series of zeolitic imidazolate framework-8/polylactic acid (ZIF-8/PLA) porous microspheres were prepared to adsorb/remove gaseous benzene. The ZIF-8/PLA microspheres were prepared via the double emulsion-solvent evaporation method with ammonium bicarbonate as the foaming agent, and the structures were well adjusted by varying the fabrication parameters of the microspheres. The adsorption of gaseous benzene by these microspheres was evaluated both in flowing benzene vapor and in cigarette smoke. These ZIF-8/PLA microspheres exhibited an interconnected porous network structure with a high surface area, which is beneficial for the fast gas diffusion and effective adsorption, particularly suitable for complex environments with high gas flow rates. The adsorption capacity of gaseous benzene on these ZIF-8/PLA microspheres is as high as 77–238 mg/g and 18%–44% of benzene can be removed from the cigarette smoke by using these ZIF-8/PLA microspheres as absorbents due to the interconnected hierarchical porous network enhancing the fast gas diffusion and the strong π-π stacking interactions of ZIF-8 towards aromatic hydrocarbons, showing the great potential of these ZIF-8/PLA microspheres as adsorbents for efficient removal of gaseous benzene.
A GA-BP neural network algorithm for fault detection of transmission tower bolts
Authors: Lu Ziqiang , He Pengjie , Liu Huiwei , Li Jie , Lu Ziying
Published: February 2025

Background

In the power system, the identification of the health status of the transmission tower is a daily task that must be performed. In addition, bolt loosening is a common damage mode affecting the main materials of transmission towers. When bolt loosening occurs, it weakens the bearing capacity of the transmission tower. If not detected and addressed in a timely manner, serious adverse events, such as tower collapse, may occur which will endanger the normal operation of the power system.

Methods

Based on this, in order to ensure the normal operation of the transmission tower and improve the identification effect of bolt loosening, the GP-BP neural network algorithm was applied to the detection process. The feasibility of this algorithm was evaluated through the quantitative analysis of different damage degrees.

Result

The results are as follows: 1) except for the average accuracy rate of substructure 7, which is 89.74%, the identification accuracy of other substructures is more than 90%, indicating that the GA-BP neural network algorithm is effective in identifying the single-damage degree of the tower bolt loosening in the main material; 2) the identification accuracy of double-damage substructure is also more than 90%, indicating that the GA-BP algorithm is effective in identifying the double-damage degree of the tower bolt loosening in the main material.

Conclusion

In summary, it can be concluded that both the single- and double-damage degree conditions exhibit a relatively considerable recognition accuracy. In addition, the recognition effect of the algorithm under the double-damage degree condition is better than that of the single-damage degree condition. Therefore, it can be applied in practical projects involving double-damage degree conditions to improve the recognition effect of bolt-loosening faults and provide reliable technical support for the safe operation of transmission equipment.
C-reactive protein to serum calcium ratio as a novel biomarker for predicting severity in acute pancreatitis: a retrospective cross-sectional study
Authors: Chen Xinqi , Huang Yisen , Xu Qiaoli , Zhang Bifeng , Wang Yubin , Huang Meixue
Published: February 2025

Background

Acute pancreatitis (AP) is a prevalent gastrointestinal emergency with a wide spectrum of clinical outcomes, varying from mild cases to severe forms. The early identification of high-risk patients is essential for improving prognosis. However, the predictive and prognostic potential of the C-reactive protein to serum calcium ratio (CCR) in AP has not been investigated. This study aims to explore the association between CCR and disease severity in patients with AP.

Methods

This retrospective cross-sectional study included 476 AP patients. The CCR was calculated from C-reactive protein and serum calcium levels within the first 24 h of admission. Multivariable logistic regression models were used to evaluate the relationship between CCR and AP severity, with restricted cubic spline analysis and receiver operating characteristic (ROC) analysis to assess dose–response and predictive performance, respectively.

Results

Of the 476 patients, 176 (37%) had mild acute pancreatitis (MAP) and 300 (63%) had moderate to severe AP. The CCR distribution had a median value of 17.5, with an interquartile range (IQR) of 3.0 to 60.2. Each unit increase in CCR was associated with a 7% increase in the risk of developing moderate to severe AP (OR: 1.07; 95% CI: 1.06–1.09). In fully adjusted models, this association remained statistically significant. The area under the curve (AUC) for CCR in predicting moderate to severe AP was 86.9%, with a sensitivity of 73.7% and specificity of 89.2%.

Conclusion

The CCR measured within the first 24 h of admission shows promise as a valuable biomarker for predicting the severity of AP. However, further multicenter prospective cohort studies are needed to confirm its clinical utility and investigate its role in improving treatment strategies and patient management.
Impact of climate change on the distribution of Isaria cicadaeMiquel in China: predictions based on the MaxEnt model
Authors: He Zhipeng , Ali Habib , Wu Junhao , Liu Zhiqian , Wei Xinju , Zhuo Zhihang
Published: February 2025

Introduction

Isaria cicadae, a historically valued edible and medicinal fungus in China, has been experiencing a critical decline in abundance due to ecological degradation and overexploitation. Understanding its potential distribution is essential for promoting sustainable harvesting practices.

Methods

This study utilizes the MaxEnt model, combined with known distribution records and 22 environmental variables, to predict the potential distribution of I. cicadae under three representative emission scenarios (CMIP6: SSP1-2.6, SSP2-4.5, and SSP5-8.5) for the 2050s and 2070s.

Results

The analysis identifies seven key environmental variables influencing the habitat suitability of I. cicadae: the mean temperature of the driest quarter (bio09), the mean temperature of the wettest quarter (bio08), precipitation in the wettest month (bio16), the mean diurnal range (bio02), isothermality (bio03), elevation, and slope. Currently, I. cicadae is mainly found in the provinces of Yunnan, Sichuan, Hunan, Hubei, Guizhou, Jiangxi, Guangxi, Fujian, Anhui, and Zhejiang, with Yunnan and Sichuan having the largest areas of high suitability at 25.79 × 104 km2 and 21.36 × 104 km2, respectively.

Discussion

Jiangxi, Hunan, Yunnan, Guizhou, Fujian, and the Guangxi Zhuang Autonomous Region are identified as primary regions of high suitability. This study aims to further elucidate the impact of the environment on the distribution of I. cicadae from a geographical perspective and provide theoretical insights for the future cultivation and conservation strategies of this species.
Dissemination of Staphylococcus epidermidis in Swedish bovine dairy herds: minimal overlap with human isolates
Authors: Persson Waller Karin , Myrenås Mattias , Kim Hyeyoung , Widerström Micael , Monsen Tor , Börjesson Stefan , Östlund Emma , Cha Wonhee
Published: February 2025

Knowledge of zoonotic links between bovine and human isolates of Staphylococcus epidermidis remains limited. The primary aim of this study was to assess the genetic relatedness of S. epidermidis isolates from bovine subclinical mastitis (SCM), bovine milk filters, healthy dairy farmers or farm personnel, and human hospital patients in Sweden, and to detect and compare genes encoding antimicrobial resistance (AMR) and virulence factors. A secondary aim was to explore the epidemiology of bovine S. epidermidis intramammary infections (IMI) by examining associations between genotypes and geographic location, persistence of IMI, severity of inflammatory response, and the persistence of S. epidermidis strains over time. A total of 283 S. epidermidis isolates were analyzed using whole genome sequencing (WGS): 128 SCM milk isolates, 55 milk filter isolates, 13 farmer/personnel isolates, and 87 human patient isolates. Sixty unique sequence types (STs) of S. epidermidis were identified. ST99, ST100, and ST570 were the most common among bovine isolates, collectively accounting for 49% (63/128) of the milk isolates and detected on multiple farms, while ST2 and ST215 were the most prevalent among human isolates. Only four STs (ST59, ST73, ST184, and ST218), representing a total of 13 isolates, were found in both bovine and human samples. Genes conferring AMR were more frequently identified in human patient isolates compared to bovine isolates. However, penicillin resistance, identified by presence of the blaZ gene, was detected in 42% of bovine S. epidermidis isolates. The average number of potential virulence factors (pVF) per isolate was 23.8 with 23.1 in milk isolates, 23.4 in milk filter isolates, 23.0 in farmer/personnel isolates, and 25.2 in human patient isolates. There was some variation in the total number of pVFs and the presence of specific pVFs or functional groups of pVFs between sample types and STs. In conclusion, the results indicate that the overlap of STs and AMR genes between human and bovine samples was minimal. However, the persistence of certain STs across multiple dairy farms suggests inter-farm transmission. This study provides new insights into the epidemiology of bovine S. epidermidis IMI, with implications for the control of these infections.
Distinct roles of Constitutive Photomorphogenesis Protein 1 homolog (COP1) in human hepatocyte models
Authors: Soubeyrand Sébastien , Lau Paulina , McPherson Ruth
Published: February 2025

Introduction

Constitutive Photomorphogenesis Protein 1 homolog (COP1) is a conserved E3 ligase with key roles in several biological systems. Prior work in hepatocyte-derived tumors categorized COP1 as an oncogene, but its role in untransformed hepatocytes remains largely unexplored. Here, we have investigated the role of COP1 in primary human hepatocytes and two transformed hepatocyte models, HepG2 and HuH-7 cells.

Methods

The role of COP1 was tested by silencing and transduction experiments in HepG2, HuH-7, and primary human hepatocytes. Transcription array data of COP1-suppressed cells were generated and analyzed using clustering analyses. Cellular impacts were examined by proliferation assays, qRT-PCR, western blotting, reporter assays, and APOB enzyme-linked immunosorbent assays.

Results and Discussion

COP1 suppression had no noticeable impact on HepG2 and HuH-7 proliferation and was associated with contrasting rather than congruent transcriptome changes. Transcriptomic changes were consistent with perturbed metabolism in primary hepatocytes and HepG2 cells and impaired cell cycle regulation in HuH-7 cells. In HepG2 and primary hepatocytes but not in HuH-7 cells, COP1 suppression reduced the expression of important hepatic regulators and markers. COP1 downregulation reduced hepatic nuclear factor-4 alpha (HNF4A) abundance and function, as assessed by a lower abundance of key HNF4A targets, reduced APOB secretion, and reporter assays. HNF4A function could be restored by introducing a siRNA-resistant COP1 transgene, whereas HNF4A restoration partially rescued COP1 silencing in HepG2 cells. Our results identify and detail a pivotal regulatory role of COP1 in hepatocytes, in part through HNF4A.
Serum glutathione peroxidase-3 concentration at diagnosis as a biomarker for assessing disease activity and damage of antineutrophil cytoplasmic antibody-associated vasculitis at diagnosis
Authors: Chung Jihye , Ha Jang Woo , Park Yong-Beom , Lee Sang-Won
Published: February 2025

Background

In this study, we investigated whether serum glutathione peroxidase-1 (GPX-3) concentration at diagnosis could be used to assess vasculitis activity and damage at diagnosis in immunosuppressive drug-naïve patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Methods

We included 71 immunosuppressive drug-naïve patients newly diagnosed with AAV. Medical records were retrospectively reviewed and serum GPX-3 concentration was measured using serum samples collected and stored at diagnosis. The degree of vascular activity and extent of damage were assessed using the Birmingham vasculitis activity score (BVAS) and vasculitis damage index (VDI), respectively. Poor outcomes including all-cause mortality, end-stage kidney disease, and cerebrovascular and cardiovascular diseases were also investigated.

Results

The median age of the study subjects was 63.0 years, 26 and 45 patients were males and females, respectively. The median GPX-3 concentration was measured as 82.8 ng/mL. Serum GPX-3 concentration at diagnosis was inversely correlated with BVAS (r = −0.280), VDI (r = −0.263), and C-reactive protein (r = −0.261) at diagnosis, whereas, it was positively correlated with haemoglobin (r = 0.255), and serum albumin (r = 0.240) at diagnosis, respectively. However, serum GPX-3 concentration at diagnosis was not significantly associated with poor outcomes during follow-up in patients with AAV.

Conclusion

In this study, we demonstrated for the first time that serum GPX-3 concentration at diagnosis correlates with vasculitis activity and damage at diagnosis in patients with AAV, suggesting a possible role of serum GPX-3 as a complementary biomarker for assessing AAV activity in real clinical practice.
Sensation seeking and risk adjustment: the role of reward sensitivity in dynamic risky decisions
Authors: Qianlan Yin , Shou Chen , Tianya Hou , Wei Dong , Liu Taosheng
Published: February 2025

Objective

The primary objective of our research is to delve into the relationships between sensation seeking (SS), reward sensitivity (RS), and risk adjustment (RA) within the context of dynamic risk-taking behaviors. By integrating the reinforcement learning model and neural measures obtained from dynamic risk-taking tasks, we aim to explore how these personality traits influence individual decision-making processes and engagement in risk-related activities. We aim to dissect the neural and cognitive mechanisms underlying this interplay, thereby shedding light on the stable brain-based characteristics contributing to the observed variability in risk-taking and decision-making behaviors. Understanding these links could significantly enhance our ability to predict individual differences in risk preferences and develop targeted interventions for managing risky behaviors across different contexts.

Method

We developed a task to measure RA through a structured yet uncertain environment modeled after the Balloon Analog Risk Task. We enlisted 80 young adults to perform this task, and of these, 40 were subjected to electroencephalography (EEG) to assess neural correlates of RS. Subsequently, we analyzed event-related potentials and spectral perturbations to discern neural distinctions related to RS. We compared these distinctions concerning RA among participants exhibiting different levels of SS.

Results

Individuals exhibiting higher levels of SS (HSS) in the study displayed a tendency to disregard past risks, potentially resulting in diminished behavioral adaptability. EEG results indicated that individuals with HSS exhibited reduced neural responses to feedback compared to those with low SS, potentially affecting their feedback processing and decision-making. Moreover, the comparison of effects underscores the significant impact of RS and SS on shaping RA during dynamic decision-making scenarios.

Conclusion

This study has advanced the understanding of how SS and RS influence RA, revealing that RS prompts RA, while individuals with HSS often exhibit blunted RS, leading to worse RA. Future research should focus on the specific aspects of HSS and their implications for decision-making across different risk contexts. Employing advanced neuroimaging and cognitive modeling techniques will be pivotal in unraveling the neural mechanisms driving these individual differences in risky behavior.
Diurnal variation in brain injury after cardiac arrest and cardiopulmonary resuscitation
Authors: Peng Fei , Wang Fei , Gao Bowen , Sun Ping
Published: February 2025

Background

Although the circadian rhythm is known to influence several neurological diseases and response to treatments, its potential impact on brain injury following cardiac arrest and cardiopulmonary resuscitation (CA/CPR) remains unclear.

Methods

We performed a retrospective observational study on out-of-hospital cardiac arrest (OHCA) cases that presented to the emergency department of our hospital between September 2022 and August 2024. Based on the CA/CPR onset time, all patients were divided into two cohorts: daytime and nighttime groups. The gray-to white-matter signal intensity ratio (GWR) was analyzed using brain computed tomography (CT) images. We used the Cerebral Performance Category (CPC) to estimate the neurological outcomes. C-reactive protein (CRP), white blood cell (WBC) count, and monocyte (MONO) count levels in the plasma were also analyzed.

Results

Our study included 138 patients, of whom 68 were subjected to CA/CPR during daytime (8:00 to 20:00) and the remaining 70 were subjected to CA/CPR during nighttime (20:00 to 8:00). The imaging data showed that GWR values were significantly lower among patients subjected to CA/CPR during nighttime compared to those who were subjected to CA/CPR during daytime. Consistently, lower survival rates were observed among nighttime CA/CPR survivors. The CPC results indicated that a greater number of patients who underwent CA/CPR during daytime were rated as class 1–2 on day 3, day 5, and day 7 after achieving return of spontaneous circulation (ROSC). In contrast, a larger proportion of CA/CPR survivors in the nighttime group were rated as class 5 at the same time points. Elevated levels of C-reactive protein, white blood cell count, and monocyte count were observed in the plasma of survivors who underwent nighttime CA/CPR.

Conclusion

We found that patients subjected to CA/CPR during nighttime (20:00–8:00) had worse neurological outcomes compared to those treated during daytime (8:00–20:00).
Clinical study on the treatment of acute epidural hematoma by embolization of middle meningeal artery through radial artery access combined with minimally invasive burr hole drainage
Authors: Zhang Cui , Wang Qingbo , Li Chenglong , Jing Zixuan , Zhao Xinyu , Chen Yang , Li Zefu
Published: February 2025

Objectives

This study aims to evaluate the clinical effectiveness of using coil embolization via radial artery access, combined with drilling and drainage, as a minimally invasive treatment for acute epidural hematoma compared to traditional craniotomy.

Materials and methods

A retrospective analysis was conducted on 134 patients with acute epidural hematoma treated at the Department of Neurosurgery, Binzhou Medical University Hospital, between January 2020 and April 2023. Among these patients, 37 underwent embolization of the middle meningeal artery through radial artery access combined with burr hole drainage, while 97 patients underwent craniotomy for hematoma removal. The 37 patients treated with embolization were designated as the experimental group, while the remaining 97 patients formed the control group. General patient characteristics, operation duration, intraoperative blood loss, postoperative complications, and Glasgow Coma Scale (GCS) scores upon admission and discharge were recorded and compared between the two groups.

Results

In comparison to the control group, the experimental group exhibited higher rates of postoperative hematoma residuals and longer average postoperative drainage times. Nevertheless, the experimental group demonstrated several advantages including shorter operation durations, reduced intraoperative bleeding, lower rates of postoperative rebleeding and complications, as well as decreased requirements for postoperative blood transfusions and transfusion volumes.

Conclusion

The surgical approach involving coil embolization via radial artery access combined with minimally invasive burr hole drainage yields favorable clinical outcomes. This technique presents as a viable treatment option for acute epidural hematoma resulting from middle meningeal artery hemorrhage.
Potential pharmacological effect of Quercetin Phytosome™ in the management of hyperuricemia: results from real-life clinical studies
Authors: Di Pierro Francesco , Rabbani Fazle , Tareen Meherullah , Nigar Roohi , Khan Amjad , Zerbinati Nicola , Tanda Maria L. , Cazzaniga Massimiliano , Bertuccioli Alexander , Falasca Paolo , Damiani Gabriele , Villanova Nicola
Published: February 2025

Background

Hyperuricemia is associated with several metabolic and cardiovascular disorders, and traditional treatments, such as xanthine oxidase (XO) inhibitors, often have limitations, such as severe hypersensitivity reactions or ineffectiveness in achieving target serum urate levels in some patients. Quercetin, a naturally occurring flavonoid, has shown potential as a hypouricemic agent through XO inhibition.

Objective

This study aims to evaluate the potential hypouricemic effect of Quercetin Phytosome™ (QP) supplementation across three cohort studies involving healthy adults with various metabolic health profiles, exploring its potential as a safe, effective intervention for hyperuricemia.

Methods

Clinical data collected in various clinics in Italy between September 2021 and April 2024 under real-life clinical settings from three distinct cohort studies, were analyzed. Cohort 1 consisted of 164 healthy participants (87 QP-treated, 77 probiotic Streptococcus salivarius (S. salivarius) K12-treated) who were monitored for 90 days. Cohort 2 included 22 mildly hyperuricemic adults with metabolic disorders receiving QP, while Cohort 3 comprised 64 obese adults with hypercholesterolemia, further divided into moderately hyperuricemic QP-treated group (n = 20), a moderately hyperuricemic Berberine Phytosome™ and monacolins (BM)-treated group (n = 22), and a normouricemic BM-treated group (n = 22). QP was administered at 400 mg of quercetin daily in all cohorts. Primary endpoints were reductions in serum uric acid levels, while secondary outcomes included effects on lipid profile, glycemia, liver enzymes, and treatment tolerability.

Results

In Cohort 1, QP significantly reduced uric acid levels by 15.2% in males and 13.8% in females, with no significant changes observed in the probiotic group. Cohort 2 showed a significant 13.1% reduction in uric acid (p < 0.01) and a concurrent 10.2% reduction in triglycerides (p < 0.05). In Cohort 3, QP led to a 13.7% decrease in uric acid and a 20.8% reduction in triglycerides (p < 0.01), with no significant uric acid changes in the BM-treated group. QP was well tolerated across all cohorts, with minimal, transient side effects.

Conclusion

QP supplementation demonstrates a significant hypouricemic effect. Additionally, triglyceride-lowering benefits were evident, particularly in metabolically compromised individuals (Cohorts 2 and 3), where these effects were statistically significant. With high tolerability, these findings highlight Quercetin Phytosome™'s potential as a safe adjunctive therapy for hyperuricemia management, meriting further investigation in larger, randomized trials to confirm its efficacy and safety.

Clinical Trial Registration

clinicaltrials.gov, identifier NCT06652035.
Review of the clinical status of cardiotoxicity of HER-2 positive breast cancer targeted therapeutic drugs
Authors: Zhang Xiang , Yin Yulian , Yu Qiuting , Chen Xinlin , Cheng Yiqin
Published: February 2025

Breast cancer is a major health challenge for women worldwide, and human epidermal growth factor receptor 2 (HER-2)-positive breast cancers have a relatively high incidence and are highly aggressive. Targeted therapeutic agents, represented by trastuzumab, have been effective in improving the survival rate of HER-2-positive breast cancer patients. However, in clinical applications, this type of targeted drugs exhibits varying degrees of cardiotoxicity, and the mechanism of their cardiotoxicity is currently unclear. In this paper, we classify them into three categories: monoclonal antibodies (mAbs), small-molecule tyrosine kinase inhibitors (TKIs), and antibody-drug conjugate (ADCs). We list the evidence of cardiotoxicity for various drugs based on current clinical trials and summarize their corresponding epidemiological profiles. We also discuss the regulation of cardiotoxicity from three perspectives: clinical biomarkers of cardiotoxicity, permissive cardiotoxicity, and the current status of cardiotoxicity regulation.
Organoid models: applications and research advances in colorectal cancer
Authors: Wu Yijie , Sha Yu , Guo Xingpo , Gao Ling , Huang Jian , Liu Song-Bai
Published: February 2025

This review summarizes the applications and research progress of organoid models in colorectal cancer research. First, the high incidence and mortality rates of colorectal cancer are introduced, emphasizing the importance of organoids as a research model. Second, this review provides a detailed introduction to the concept, biological properties, and applications of organoids, including their strengths in mimicking the structural and functional aspects of organs. This article further analyzes the applications of adult stem cell-derived and pluripotent stem cell-derived organoids in colorectal cancer research and discusses advancements in organoids for basic research, drug research and development, personalized treatment evaluation and prediction, and regenerative medicine. Finally, this review summarizes the prospects for applying organoid technology in colorectal cancer research, emphasizing its significant value in improving patient survival rates. In conclusion, this review systematically explains the applications of organoids in colorectal cancer research, highlighting their tremendous potential and promising prospects in basic research, drug research and development, personalized treatment evaluation and prediction, and regenerative medicine.
Dynamic monocyte changes as prognostic indicators in operable gastric cancer: a retrospective cohort analysis
Authors: Jiang Yiwei , Sun Xianwei , Yang Chen , Song Dandan , Zhou Chongjun , Chen Xinxin , Huang Chongquan , Wang Zhonglin , Li Jiante
Published: February 2025

Objective

This study aims to elucidate the relationship between postoperative monocyte count and gastric cancer prognosis. We introduce a standardized monocyte ratio (MMR) to predict postoperative survival rates in gastric cancer patients effectively.

Methods

A test cohort was created to develop and evaluate the pre- and postoperative MMR as a mortality predictor in gastric cancer patients. We used Kaplan-Meier survival analysis, complemented by univariate and multivariate analyses. The predictive utility of MMR was assessed via time-dependent ROC curves and decision-curve analysis.

Results

The sample distributions in both cohorts were similar. The MMR showed high predictive value and significant clinical benefits in 1, 3, and 5-year overall survival (OS) assessments. These findings enhance understanding of prognosis and aid in developing more precise treatment plans.

Conclusions

MMR is confirmed as an independent factor in predicting overall survival in gastric cancer patients, proving to be a reliable and cost-effective prognostic indicator.