bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of sex, pubertal stage, body mass index, oral contraceptive use, and C-reactive protein on vitamin D binding protein reference values
Authors: von Heimburg Philipp , Baber Ronny , Willenberg Anja , Wölfle Philip , Kratzsch Jürgen , Kiess Wieland , Vogel Mandy
Published: February 2025

Objective

Vitamin D binding protein (DBP) regulates the transport and availability of vitamin D. We aimed to establish age- and sex-specific reference ranges for serum concentrations of DBP in healthy infants, children, and adolescents. In addition, we investigated DBP’s associations with age, sex, puberty, body mass index (BMI), and oral contraceptive use.

Design and methods

2,503 serum samples from children and adolescents aged 3 months to 17 years from the LIFE Child cohort were analyzed to study DBP levels in this population (49.3% female subjects, 50.7% male subjects). Age- and sex-dependent reference percentiles were established using generalized additive models. We used linear mixed effects models to assess DBP’s associations with age, sex, pubertal status, the BMI standard deviation score (SDS), and oral contraceptives. To investigate associations between DBP and vitamin D metabolites, we applied univariate regression analysis. We used hierarchical regression models and linear mixed effects models to assess DBP’s associations with bone parameters, hormones, and inflammatory markers.

Results

Mean DBP values differed between males (347 mg/l) and females (366 mg/l) (p < 0.001). Age had no significant association with DBP levels. In both males and females, DBP levels remained relatively stable from infancy through late adolescence. Children and adolescents with obesity had lower mean DBP levels compared with normal-weight subjects (ß = -14.28, p < 0.001). The BMI-SDS was inversely associated with DBP levels in males (ß = -5.7, p < 0.001). Female subjects using oral contraceptives had higher levels of DBP (ß = 141.38, p < 0.001). DBP was positively associated with the vitamin D metabolites: 25(OH)D3 (females: ß = 0.8, p < 0.001; males: ß = 1.2, p < 0.001) and 1,25(OH)2-D3 (females: ß = 0.3, p < 0.001; males: ß = 0.4, p < 0.001). An inverse association between osteocalcin and DBP (females: ß = -0.1, p < 0.022; males: ß = -0.1, p = 0.027) was found. CRP levels were also positively associated with DBP levels (females: ß = 2.8, p = 0.001; males: ß = 5.1, p < 0.001).

Conclusion

We established age- and sex-specific reference ranges for the serum concentration of DBP. We suggest that BMI, pubertal stages, oral contraceptive use, and inflammation markers need to be considered when interpreting DBP as a stabilizer and regulator of vitamin D metabolism and vitamin D status in children and adolescents.

Clinical trial registration

ClinicalTrial.gov, identifier NCT02550236.
Ubiquitin-proteasome system: a potential participant and therapeutic target in antiphospholipid syndrome
Authors: Wang He , Tan Yuan , Liu Qi , Yang Shuo , Cui Liyan
Published: February 2025

APS (antiphospholipid syndrome) is an autoimmune disease characterized by thrombosis, pregnancy complications and persistent elevation of aPLs (antiphospholipid antibodies). Dysfunction of innate immune cells, ECs (endothelial cells), platelets and trophoblast cells are central to the development of APS. The UPS (ubiquitin-proteasome system) is a highly conserved post-translational modification in eukaryotes. Imbalance of the UPS potentially disrupts the protein homeostasis network and provokes prothrombotic and proinflammatory signaling during APS progression. In vivo, low-dose proteasome inhibitors are believed to effectively inhibit the production of proinflammatory factors and the clinical manifestations of APS. In this review, we would like to summarize the likely contribution of dysregulated UPS to the pathogenesis of APS. Given the significant progress made in understanding the molecular mechanisms of the UPS and how alterations in the UPS lead to the development of autoimmune diseases, targeting the UPS may represent a novel therapeutic strategy.
Association of composite dietary antioxidant index with high risk of prostate cancer in middle-aged and elderly men: insights from NHANES
Authors: Jin Xuefeng , Tong Wenhui , Sun Li , Lu Sujue , Sun Pan , Li Hangxu , Liu Yan
Published: February 2025

Objectives

In the US, the most common type of cancer and the second leading cause of cancer-related death in men is prostate cancer (PCa). Food and lifestyle factors may influence the risk of developing prostate cancer. Therefore, research on dietary components associated with prostate cancer is essential for its prevention. Data from the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2010 was used for this cross-sectional investigation involving 5,658 middle-aged and older American men.

Methods

Dietary antioxidant vitamins A, C, E, total carotenoids, zinc, and selenium were subtracted from the total mean, divided by the standard deviation, respectively, and then summed to become the CDAI. Participants were categorized as high risk for PCa if they had tPSA greater than 10 ng/mL or tPSA levels between 4 and 10 ng/mL with f/t PSA ratios of 25% or below; the remaining subjects were classified as being at low risk for PCa.

Results

The sample represented approximately 75,984,602 American men. After multivariate logistic regression, dose-effect analysis and stratified analysis, CDAI was significantly and linearly negatively associated with a high risk of prostate cancer (OR=0.95, P=0.002, P for linear=0.0021). Age moderation analysis showed a significant effect on the inverse relationship between CDAI and prostate cancer risk (B = -0.0097, SE = 0.0034, t = -2.85, P = 0.004). Among the independent effects of CDAI components, zinc and selenium were more strongly negatively associated with prostate cancer (zinc, OR = 0.80, P = 0.008; selenium, OR = 0.78, P< 0.001).

Conclusions

CDAI serves as a dietary indicator of prostate cancer risk in middle-aged and older men, and high dietary antioxidant intake has a significant protective effect on prostate cancer risk, especially in the older population of men.
Follow-up of humoral and cellular immune responses after the third SARS-CoV-2 vaccine dose in multiple myeloma patients
Authors: Raimondi Vincenzo , Storti Paola , Vescovini Rosanna , Franceschi Valentina , Toscani Denise , Notarfranchi Laura , Dalla Palma Anna Benedetta , Iannozzi Nicolas Thomas , Minesso Sergio , Scita Matteo , Lungu Oxana , Dessena Mattia , Donofrio Gaetano , Giuliani Nicola
Published: February 2025

The stability of immune responses to SARS-CoV-2 vaccines, especially concerning the cross-reactive recognition of the Omicron variant, remains incompletely characterized in multiple myeloma (MM) patients. This study evaluated humoral responses in 29 MM patients and cellular responses in a subset of 19 MM patients, specific to Wuhan and Omicron spike proteins, between 16 and 26 weeks following the third vaccine dose. After 26 weeks, we highlighted a significant reduction in the neutralizing antibodies to both spikes and the percentages of IFN-γ+CD107a+ spike-specific CD8+ T cells. On the other hand, patients who underwent an additional stimulation between the two time points, through either a fourth vaccine dose or breakthrough infection, showed a significant increase in neutralizing antibodies and stable levels of cytotoxic CD8+ T cells. Additionally, those with only three doses experienced a higher rate of breakthrough infections during the 32-week follow-up period. These findings underscore the waning of vaccine-induced immunity over time and may help benefit-risk evaluation in vaccination strategies in MM patients.
Combination of cadonilimab (PD-1/CTLA-4 bispecific antibody) and apatinib as salvage therapy achieves partial response in MSI-H advanced gastric cancer: a case report
Authors: Zhao Jiayu , Li Xiaoxiao , Sun Xiaoyuan , Xiao Ruoxi , Xue Juan , Sui Kexin , Liu Zimin
Published: February 2025

Microsatellite instability-high (MSI-H) gastric cancer (GC) is recognized as a unique subtype of gastric cancer. While patients with advanced MSI-H gastric cancer may respond favorably to a combination of immune checkpoint inhibitors and chemotherapy in first-line treatment, no definitive recommendations exist regarding the optimal regimen for subsequent therapy. Cadonilimab, a PD-1 and CTLA-4 bispecific antibody, has shown encouraging efficacy and safety in the first-line treatment of advanced gastric cancer. However, its utility in the MSI-H gastric cancer subtype following multiple lines of therapy remains uncertain. This case report describes a patient with advanced MSI-H gastric adenocarcinoma that progressed after multiple treatments and achieved notable efficacy with a combination of cadonilimab and apatinib. By examining the current therapeutic landscape for MSI-H gastric cancer, this study explores the potential of combining PD-1/CTLA-4 dual-immunity with anti-vascular therapy as salvage treatment for this gastric cancer subtype. The findings provide valuable reference points for future clinical trials, offering a promising perspective on backline therapeutic strategies for MSI-H gastric cancer and highlighting the potential of integrating bispecific antibodies with anti-vascular therapies.
Chaihushugan powder regulates the gut microbiota to alleviate mitochondrial oxidative stress in the gastric tissues of rats with functional dyspepsia
Authors: Liu Xuejiao , Yang Keming , Jia Yuebo , Yeertai Yeliya , Wu Chenheng , Wang Xiangxiang , Jia Qingling , Gu Zhijian , Cong Jun , Ling Jianghong
Published: February 2025

Introduction

Functional dyspepsia (FD) is a prevalent functional gastrointestinal disorder associated with oxidative stress (OS) and dysbiosis. Chaihushugan powder (CHSGP) demonstrates efficacy in treating FD; however, the underlying therapeutic mechanism is not yet elucidated. This study aims to investigate the effects of CHSGP on OS and gut microbiota (GM) in FD rats, with a particular emphasis on the role of GM as a potential target for the antioxidant properties of CHSGP.

Methods

The FD rat model was established with a modified tail-clamp stimulation and the administration of the CHSGP decoction at a dosage of 9.6 g/kg via gavage for a duration of 4 weeks. The GM was depleted by the administration of a cocktail of metronidazole (200 mg/kg), ampicillin (200 mg/kg), neomycin sulfate (200 mg/kg), and vancomycin (100 mg/kg). Fecal microbiota transplantation (FMT) was performed with CHSGP-treated fecal supernatant at a dosage of 10 mL/kg. The gastrointestinal motility was measured using the rates of gastric emptying and small intestine propulsion. Hematoxylin and eosin staining was employed to elucidate the pathological changes, while the transmission electron microscope was used to examine the microstructures of the interstitial cells of Cajal (ICC). Chemiluminescence, colorimetric assay, immunofluorescence co-staining, and western blot assay were employed to identify the OS-related markers (ROS, SOD, NOX4, PRDX1, and TRX2). Sequencing of fecal microbiota was performed utilizing 16S rDNA.

Results

The CHSGP decoction promoted gastrointestinal motility, protected the microstructure of ICC, and reduced OS in FD rats. The GM composition was also regulated by CHSGP. However, these effects disappeared after microbiota depletion. Fortunately, the FMT therapy reinstated them.

Conclusion

Chaihushugan powder decoction might regulate the GM to alleviate mitochondrial OS in the gastric tissues of FD rats.
Enhancing motion forecasting of ship sailing in irregular waves based on optimized LSTM model and principal component of wave-height
Authors: Gong Jiaye , Xu Jinya , Xu Lixin , Hong Zhichao
Published: February 2025

Irregular waves exhibit complex and erratic behavior, posing significant challenges for accurate short-term ship motion forecasting. Reliable ship navigation depends on precise motion predictions, necessitating effective feature extraction from wave data to enhance predictive models. This study proposes a hybrid model integrating a wavelet principal component analysis (WPCA) for dimensionality reduction with an optimized double circulation-long short-term memory (DC-LSTM) network. The WPCA method retains key variance components, reducing redundant data while preserving critical wave characteristics. The DC-LSTM model is optimized using both internal and external circulation mechanisms to enhance learning efficiency and stability. Numerical simulation data are used to train and validate the model. Compared with conventional LSTM and PCA-LSTM models, the proposed WPCA-DC-LSTM model improves R2 by 14% and reduces RMSE by 12% in validation datasets. The model demonstrates robust generalization, effectively capturing nonlinear and high-dimensional wave features. The results indicate that the hybrid model effectively mitigates the influence of redundant data, reduces prediction randomness, and improves stability in handling wave-induced ship movements. The study highlights the broad applicability of the WPCA-DC-LSTM model for complex maritime data analysis and ship motion forecasting.
Three-dimensional changes in temperature and circulation caused by northwestward-moving typhoons in a temperate semi-enclosed shelf sea in summer
Authors: Ma Yanping , Zhai Fangguo , Liu Xingchuan , Liu Cong , Liu Zizhou , Gu Yanzhen , Li Peiliang
Published: February 2025

Due to the complex coastline and topography, changes of temperature and circulation in global shelf seas caused by typhoons have significantly region-specific three-dimensional structures. As one temperate semi-enclosed shelf sea, the Yellow Sea is highly susceptible to typhoons in summer. In August 2012 Typhoon Damrey moving northwestward over the Yellow Sea was observed to cause significant bottom temperature warming in the southern coastal waters of the Shandong Peninsula, but its impacts on the three-dimensional changes of temperature and circulation in the whole Yellow Sea and the underlying dynamics are still unclear. Using observations and high-resolution numerical simulations, we showed that during Damrey’s passage the South Yellow Sea exhibited spatially coherent surface cooling, particularly forming a distinct surface cooling band on the right side of the typhoon track. With the mixed layer deepening, the subsurface layer deepened and experienced temperature warming, especially on the right side of the typhoon track. The surface cooling and subsurface warming were primarily caused by strong wind-enhanced vertical mixing. In the deep layer, temperature exhibited pronounced warming in the southern coastal waters of the Shandong Peninsula but cooling in a southeast-northwest band along the bottom slope just off the Subei Shoal. Bottom temperature warming in the southern coastal waters of the Shandong Peninsula was caused by coastal downwelling resulting from upper layer coastward Ekman transport. Conversely, vertically consistent temperature cooling just off the Subei Shoal was caused by coastward and upward advection of cold water across the temperature fronts and thermocline due to surface layer Ekman divergence. The intensity and spatial distributions of temperature cooling just off the Subei Shoal were related to the distance between the typhoon track and Subei Shoal. Closer proximity of the typhoon track to the Subei Shoal would lead to more pronounced bottom cooling. This study enriches our understanding of three-dimensional hydrodynamic changes induced by typhoons with different tracks in the Yellow Sea.
Ultrasonic phased array flexible coupling detection of defects in high-voltage cable terminal lead seals
Authors: Ziping Peng , Jishi Zheng , Zhiming Zhen , Yaosheng Huang , Xiaobin Li , Qiushen Cai
Published: February 2025

High-voltage cable terminal lead seals may develop defects such as holes, cracks, or delamination due to substandard installation quality or external forces during operation. Owing to the large curvature of the lead seal surface, using conventional ultrasonic probes for direct contact with the surface results in low efficiency in detecting lead seal defects and yields a low signal-to-noise ratio for defect echo signals. To address the ineffective detection of lead seal defects, a non-destructive detection method based on ultrasonic phased array flexible water bag coupling is proposed. This method employs an ultrasonic phased array probe and a flexible water bag coupling device to form a lead seal defect detection system. Firstly, a simulation model for lead seal defects is established using COMSOL finite element simulation software to design and optimize the detection parameters of the ultrasonic phased array probe. Detection experiments are then conducted on three typical artificially fabricated defect samples. The results indicate that different beam deflection angles and focal distances of the probe affect the detection outcomes. Through ultrasonic phased array probe sector scan (S-scan) images and ultrasonic pulse echo reflection (A-scan) images, both qualitative analysis and quantitative measurement of lead seal defects can be achieved. This method demonstrates that the ultrasonic phased array terminal lead seal defect detection technique, utilizing a flexible water bladder coupled probe, can quickly and intuitively identify lead seal defects, providing a new approach for defect detection in high-voltage cable terminal lead seals.
Hetrombopag treatment for immune thrombocytopenia in pregnancy refractory to corticosteroids and intravenous immunoglobulin: a case report
Authors: Pang Luyi , Yu Feng , Yang Xiaoyang
Published: February 2025

Pregnancy can lead to the recurrence or exacerbation of immune thrombocytopenia (ITP). Currently, first-line treatments of low-dose corticosteroids or intravenous immunoglobulin are considered safe and effective for both pregnant women and fetuses. However, there is no well-established treatment option for patients who are refractory to these medications. Herein, we report a case of a 31-year-old pregnant woman with recurrent and refractory ITP who was safely and effectively treated with hetrombopag, with no influence on the infant's platelet count. This case explores a new treatment option for the management of recurrent and refractory ITP in pregnancy.
The incidence of hyperkalemia in patients with secondary hyperparathyroidism after ultrasound-guided radiofrequency ablation vs. parathyroidectomy
Authors: Ren Mian , Liu Yueming , Lin Bo , Zou Wenli , Zhu Bin , Wu Juan
Published: February 2025

Introduction

The aim of our study was to compare the incidence of hyperkalemia in maintenance dialysis patients with secondary hyperparathyroidism(SHPT) after parathyroidectomy(PTX) or ultrasound-guided radiofrequency ablation(RFA), and to explore the risk factors and the best preoperative serum potassium threshold.

Methods

We defined hyperkalemia as serum potassium >5.30 mmol/L. Two operation methods were analyzed in subgroups, and the differences in demographic parameters, operation situation and perioperative laboratory indicators were compared between the two groups.

Results

A total of 154 maintenance dialysis patients were included, of which 91 patients received PTX and 63 patients received RFA. 53 patients (34.4%) developed postoperative hyperkalemia. Patients in hyperkalemia group had higher preoperative serum potassium, phosphorus, hemoglobin and 25-hydroxyvitamin D level (p < 0.05). It seemed that males were more prone to suffer hyperkalemia than females, but there was no statistically difference (40.9% vs. 25.8%, p = 0.05). The occurrence of hyperkalemia after the operation was obviously higher in hemodialysis patients. Logistic regression analysis showed that preoperative serum potassium level (OR = 3.269, 95%CI 1.638–6.534, p = 0.001) and PTX (OR = 18.119, 95%CI 5.716–57.438, p < 0.01) were independent risk factors for predicting postoperative hyperkalemia. According to ROC curve analysis, the optimal cutoff value for preoperative serum potassium was 4.66 mmol/L, with a sensitivity of 46.8% and a specificity of 86%.

Conclusion

Hyperkalemia after invasive treatment in patients with severe SHPT was common, and the incidence of hyperkalemia after PTX was significantly higher than that after RFA. Hemodialysis patients were more prone to hyperkalemia, which was related to the preoperative serum potassium level.
Rumen-protected guanidinoacetic acid improves growth performance in beef cattle under chronic heat stress by reshaping gut microbiota and modulating serum metabolism
Authors: Geng Qiang , Lin Wei , Yang Libin , Hu Xiaofei , Qiu Xinjun
Published: February 2025

This study aimed to investigate the effects of rumen-protected guanidinoacetic acid (RP-GAA) on growth performance, gut microbiota, and serum metabolism in beef cattle under chronic heat stress. A randomized block design was employed to allocate 14 F1 Simmental crossbred cattle (Simmental ♂ × Bos indicus ♀) with an average body weight of 312.5 ± 55.0 kg into two groups (n = 7): a control group was fed a basal diet without RP-GAA and a treatment group was fed the same basal diet supplemented with 10.0 g/day of RP-GAA. During feeding experiments, at 2 p.m., the average temperature increased to 31.5°C, with a relative humidity of 69.5% and a THI of 83.2. All animals are under chronic heat stress. The results indicated that RP-GAA supplementation significantly increased dry matter intake and feed conversion ratio in beef cattle under chronic heat stress (p < 0.05). RP-GAA supplementation tended to reduce respiratory rate or rectal temperature (p < 0.1). Compared to the control group, the treatment group exhibited significantly higher glucose, blood urea nitrogen, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels (p < 0.05). 16S rRNA gene sequencing revealed that RP-GAA supplementation significantly altered the ruminal microbiota composition, increasing the abundance of Firmicutes and Bacteroidota (p < 0.05), while reducing Proteobacteria (p < 0.01). Principal coordinate analysis (PCoA) and Adonis test (R2 = 0.190, p = 0.003) jointly revealed a distinct difference in fecal microbiota structures between the two groups. Metabolomic analysis identified significant changes in pathways related to creatine synthesis, energy metabolism, and nitrogen utilization, supported by the orthogonal partial least squares discriminant analysis model (R2Y = 0.983, Q2 = 0.836, p < 0.05). These findings suggest that RP-GAAenhances energy homeostasis, supports gut health, and mitigates the adverse effects of heat stress, providing a promising strategy to improve production efficiency and animal welfare in heat-stressed cattle.
Association between early coagulation disorders and the risk of severe acute kidney injury in traumatic brain injury patients: a retrospective cohort study using the MIMIC-IV database
Authors: Gao Yu , Li Yong , Zhou Hai , Wang Xin , Wang Guojun , Zhu Lin
Published: February 2025

Aim

Acute kidney injury (AKI) and coagulation disorders are two common complications of traumatic brain injury (TBI) that are associated with poor prognosis. However, the relationship between early coagulation disorders and the risk of severe AKI in TBI patients remains unclear. This study aimed to explore the association between early coagulation disorders and the risk of severe AKI in TBI patients admitted to the intensive care unit (ICU).

Methods

In this retrospective cohort study, adults diagnosed with TBI were selected from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The outcome was the risk of severe AKI within 7 days of ICU admission in TBI patients. Covariates including sociodemographic information, vital signs, scoring systems, and laboratory parameters were extracted from the database. Univariable and multivariable Cox proportional hazard regression models were used to assess the association between early coagulation disorders and the risk of severe AKI within 7 days of admission to the ICU in TBI patients. Subgroup analyses based on age and the Glasgow Coma Scale (GCS) score were further conducted to assess the association.

Results

A total of 846 patients were finally included, of whom 187 (22.10%) had severe AKI. After adjusting for all covariates, the TBI patients with early coagulation disorders had a higher risk of developing severe AKI within 7 days of ICU admission compared to the TBI patients without early coagulation disorders (hazard ratio (HR) = 1.40, 95% confidence interval (CI): 1.04–1.89), particularly among those aged ≥65 years (HR = 1.46, 95%CI: 1.01–2.04) and those with a GCS score ≤ 13 (HR = 1.91, 95%CI: 1.16–3.15).

Conclusion

TBI patients with early coagulation disorders had a higher risk of developing severe AKI within 7 days of ICU admission. This may serve as a promising biomarker and could be helpful for managing kidney health in TBI patients.
A comparative study of methods for dynamic survival analysis
Authors: de Swart Wieske K. , Loog Marco , Krijthe Jesse H.
Published: February 2025

Introduction

Dynamic survival analysis has become an effective approach for predicting time-to-event outcomes based on longitudinal data in neurology, cognitive health, and other health-related domains. With advancements in machine learning, several new methods have been introduced, often using a two-stage approach: first extracting features from longitudinal trajectories and then using these to predict survival probabilities.

Methods

This work compares several combinations of longitudinal and survival models, assessing their predictive performance across different training strategies. Using synthetic and real-world cognitive health data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we explore the strengths and limitations of each model.

Results

Among the considered survival models, the Random Survival Forest consistently delivered strong results across different datasets, longitudinal models, and training strategies. On the ADNI dataset the best performing method was Random Survival Forest with the last visit benchmark and super landmarking with an average tdAUC of 0.96 and brier score of 0.07. Several other methods, including Cox Proportional Hazards and the Recurrent Neural Network, achieve similar scores. While the tested longitudinal models often struggled to outperform simple benchmarks, neural network models showed some improvement in simulated scenarios with sufficiently informative longitudinal trajectories.

Discussion

Our findings underscore the importance of aligning model selection and training strategies with the specific characteristics of the data and the target application, providing valuable insights that can inform future developments in dynamic survival analysis.
Leber’s hereditary optic neuropathy and multiple sclerosis: overlap between mitochondrial disease and neuroinflammation
Authors: Rahimi Golbarg , Silverman Mackenzie , Lucas Maeve , Kazerooni Lilia , Yousuf Mariam M. , Jafarpour Saba , Santoro Jonathan D.
Published: February 2025

Although Multiple sclerosis (MS) and Leber hereditary optic neuropathy (LHON) have distinct pathophysiological mechanisms, they are both neurodegenerative conditions that involve mitochondrial dysfunction. MS is an autoimmune disease that is characterized by demyelination and neuroinflammation; and LHON is a mitochondrial disorder predominantly affecting the optic nerves, resulting in severe vision loss. Recent studies have highlighted the coexistence of these two conditions, particularly in females, suggesting that mitochondrial variants in LHON may predispose individuals to develop MS or affect its progression. Similar to MS, LHON-MS presents with visual impairment, neurological deficits, white matter lesions, and brain atrophy, which further supports a shared underlying pathophysiology. While MS is not inherently a mitochondrial disorder, its neuroinflammatory processes can lead to mitochondrial dysfunction. Reciprocally, mitochondrial impairment may be exacerbated in LHON-MS. Therefore, the role of mitochondrial dysfunction in these diseases is central, with impaired mitochondrial function contributing to cellular damage and neuroinflammation. This review explores the intersections of MS and LHON, emphasizing the need for further research to better understand mitochondrial dysfunction in these disorders.
Successful application of dietary ketogenic metabolic therapy in patients with glioblastoma: a clinical study
Authors: Kiryttopoulos Andreas , Evangeliou Athanasios E. , Katsanika Irene , Boukovinas Ioannis , Foroglou Nikolaos , Zountsas Basilios , Cheva Angeliki , Nikolopoulos Vaios , Zaramboukas Thomas , Duraj Tomas , Seyfried Thomas N. , Spilioti Martha
Published: February 2025

Introduction

Glioblastoma multiforme (GBM) ranks as one of the most aggressive primary malignant tumor affecting the brain. The persistent challenge of treatment failure and high relapse rates in GBM highlights the need for new treatment approaches. Recent research has pivoted toward exploring alternative therapeutic methods, such as the ketogenic diet, for GBM.

Methods

A total of 18 patients with GBM, 8 women and 10 men, aged between 34 and 75 years participated in a prospective study, examining the impact of ketogenic diet on tumor progression. The pool of patients originated from our hospital during the period from January 2016 until July 2021 and were followed until January 2024. As an assessment criterion, we set an optimistic target for adherence to the ketogenic diet beyond 6 months. We considered the therapeutic combination successful if the survival reached at least 3 years.

Results

Among the 18 patients participating in the study, 6 adhered to the ketogenic diet for more than 6 months. Of these patients, one patient passed away 43 months after diagnosis, achieving a survival of 3 years; another passed away at 36 months, narrowly missing the 3-year survival mark; and one is still alive at 33 months post-diagnosis but has yet to reach the 3-year milestone and is, therefore, not included in the final survival rate calculation. The remaining 3 are also still alive, completing 84,43 and 44 months of life, respectively. Consequently, the survival rate among these patients is 4 out of 6, or 66.7%. Of the 12 patients who did not adhere to the diet, only one reached 36 months of survival, while the rest have died in an average time of 15.7 ± 6.7 months, with a 3-year survival rate of 8.3%. Comparing the survival rates of the two groups, we see that the difference is 58.3% (66.7% versus 8.3%) and is statistically significant with p < 0.05 (0.0114) and X2 = 6.409.

Discussion

The outcomes observed in these patients offer promising insights into the potential benefits of the ketogenic diet on the progression of glioblastoma multiforme when compared to those who did not follow the diet consistently.
A prognostic model of lung adenocarcinoma constructed based on circadian rhythm genes and its potential clinical significance
Authors: Fu Cong , Sun Lin , Feng Cuncheng , Zhou Tong , Bi Yanzhi
Published: February 2025

Background

Lung adenocarcinoma (LUAD) is a common pathological category of lung cancer. Circadian rhythm (CR) disruption has been demonstrated to impact on lung tumorigenesis in mouse models. The aim of this study was to mine genes relevant to CR in LUAD and construct a corresponding risk model.

Methods

CRRGs from GSEA-MsigDB were filtered by overlapping DEGs in LUAD and NC specimens, two clusters with survival and clinical discrepancies, and CRRGs. Cox regression analysis (univariate and multivariate) was used to establish a CR-relevant risk model, which was validated in both the training and validation sets. Differences in immune infiltration, immunotherapy, and drug sensitivity between subgroups were explored. Prognostic gene expression was tested in clinical cancer and paracancer tissue samples using RT-qPCR.

Results

A grand total of two prognostic genes (CDK1 and HLA-DMA) related to CR were screened. The AUC values of a CR-relevant risk model in predicting 1/3/5-years survival in LUAD patients were greater than 0.6, indicating that the efficiency of the model was decent. Then, the results of CIBERSORT demonstrated noticeable differences in the tumor microenvironment between CR-relevant high- and low-risk subgroups. In addition, the CR-relevant risk score could be performed to estimate the effectiveness of immunotherapy in LUAD patients. The sensitivity of three common drugs (homoharringtonine, lapatinib, and palbociclib) in LUAD could be evaluated by the CR-relevant risk model. Ultimately, the experimental results confirmed that the expression trends of CDK1 and HLA-DMA in our collected clinical samples were in line with the expression trends in the TCGA-LUAD dataset.

Conclusion

In conclusion, a CR-relevant risk model based on CDK1 and HLA-DMA was constructed by using bioinformatics analysis, which might supply a new insight into the improved prognosis of LUAD.
Mechanism of PAVA-induced toxicity and inflammation in a cocultured skin cell model
Authors: Song Yunyang , Cheng Wenjie , Wang Zhen , Zhou Tianqi , Wu Fanghui , Yin Yifeng , Xu Dan , Liu Yanli
Published: February 2025

Background

Pelargonic acid vanillyl amide (PAVA), a stable synthetic analog of capsaicin, exhibits potential for therapeutic applications; however, it may present cytotoxic and pro-inflammatory risks. This study aims to investigate the injury effects of PAVA on a cocultured skin cell model in vitro.

Methods

Human keratinocytes and dermal fibroblasts were co-cultured and exposed to PAVA at concentrations ranging from 12.5 to 200 µM for durations of 5, 24, and 48 h. Cell proliferation was quantified using MTS assays. Morphological changes were observed through microscopy, reactive oxygen species (ROS) production was evaluated via fluorescence analysis, apoptosis was assessed using flow cytometry and Western blotting techniques, while inflammatory cytokines (IL-6, IL-8) were quantified by ELISA.

Results

The proliferation of cells was significantly inhibited by PAVA in a dose- and time-dependent manner, with concentrations of 100 µM and above inducing substantiazl cytotoxicity. Morphological analysis revealed an increase in cell dispersion, irregular morphology, and apoptosis, particularly after prolonged exposure. Treatment with PAVA led to elevated levels of ROS, indicating the presence of oxidative stress. Apoptosis was initiated through both extrinsic pathways (NF-κB, Caspase-8) at an early stage and intrinsic pathways (Caspase-3/9, Bax) at a later period. Furthermore, PAVA markedly increased the secretion of IL-6 and IL-8, suggesting a robust pro-inflammatory response.

Conclusion

100 μM PAVA elicits pronounced cytotoxic, oxidative, and pro-inflammatory effects on cocultured skin cell model, particularly at higher concentrations and prolonged exposure durations. These findings underscore the necessity of exercising caution when employing PAVA for therapeutic purposes and highlight the imperative for further research to mitigate its adverse consequences as a riot control agent.
Exploring the role of epigenetic regulation in cancer prognosis with epigenetic score
Authors: Zhang Ruiguang , Jin Shimin , Xu Qi , Dai Rongxiao
Published: February 2025

Background

The mechanisms of epigenetic regulation emerge as a fundamental determinant in the complex landscape of cancer initiation and advancement. However, the specific impact of epigenetic regulation on cancer progression remains unclear. To explore the relationship between epigenetic regulation and cancer progression, we utilized transcriptomic data from The Cancer Genome Atlas (TCGA) datasets to investigate the association.

Methods

We obtained transcriptomic data of epigenetic gene dataset from the TCGA database and calculated an epigenetic score using the Least Absolute Shrinkage and Selection Operator (LASSO) Cox model. Additionally, we created a nomogram that integrates the epigenetic score and clinical features, providing a more comprehensive tool for tumor patients prognosis assessment.

Results

We calculated the epigenetic score based on the expression levels of epigenetic-related genes. The nomogram we developed incorporates the epigenetic score and clinical characteristics. The epigenetic score was positively correlated with the expression of genes related to hallmarkers of cancer, including glycolysis, epithelial-mesenchymal transition (EMT), cell cycle, DNA repair, angiogenesis, and inflammatory response. Furthermore, we performed gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis to explore the signaling pathways and biological processes in high epigenetic score group.

Conclusion

The epigenetic scoring system developed in this investigation represents an innovative approach that demonstrates remarkable potential in forecasting survival trajectories across diverse cancer types. These groundbreaking insights not only illuminate the intricate interactions between epigenetic mechanisms and gene expression regulation in oncological contexts, but also indicate that the derived epigenetic metric could potentially emerge as a significant prognostic biomarker for cancer outcomes.
Marula [Sclerocarya birrea (A. Rich.) Hochst.] products as a food and medicine
Authors: Olas Beata
Published: February 2025

The fruit of Sclerocarya birrea (A. Rich.) Hochst., commonly known as the marula, is widely appreciated for its nutritious pulp and edible nuts. The pulp has a higher vitamin C than those of other fruits, including pineapple, guava, and oranges. In addition, fresh marula fruits are often used to produce delicious sweets, wine and flavorings: it is perhaps best known as the flavor of Amarula liqueur. In vitro and in vivo studies indicate that the various parts of marula have pro-health properties, such as antioxidant, antibacterial, antifungal, antidiabetic activities. This paper reviews the current state of knowledge regarding the marula fruit and its products, with a special emphasis on their chemical composition, biological activity and pro-health potential.
Comparison of gluteal muscle central activation in individuals with and without patellofemoral pain
Authors: Ho Kai-Yu , Carpio Michael , Donohue John , Kissman Jacob , Liang Jing Nong
Published: February 2025

Patellofemoral pain (PFP) is often linked to knee valgus during weight-bearing activities, commonly attributed to gluteal muscle weakness. However, recent research suggests that central nervous system adaptations may also influence muscle function and movement patterns in individuals with PFP. This study compared the central activation ratio (CAR) of the gluteus medius and gluteus maximus between individuals with and without PFP, and assessed the associations between gluteal CAR, frontal plane projection angle of the trunk and lower extremity, and knee function. Twelve individuals without PFP and 10 individuals with PFP participated. We tested CAR of the gluteal muscles with a superimposed burst protocol during a maximum voluntary isometric contraction and evaluated frontal plane kinematics of the trunk and lower extremities during five single leg tasks. Participants with PFP also completed the Anterior Knee Pain Scale (AKPS). Independent t-tests compared CAR between groups, and Pearson correlation coefficients evaluated the associations between CAR, frontal plane kinematics, and AKPS. Individuals with PFP tended to have lower gluteus maximus CAR, though the difference was not statistically significant (PFP: 90.8% ± 7.0%, Control: 94.4% ± 3.0%; p = 0.067). CAR of both the gluteus maximus (R = 0.790, p = 0.003) and gluteus medius (R = 0.584, p = 0.038) were significantly correlated with AKPS scores, and gluteus maximus CAR was associated with trunk lean angle during single leg landing (R = 0.533, p = 0.006). Our data suggest that higher gluteal CAR is associated with better function in individuals with PFP. Lower gluteus maximus CAR contributes to ipsilateral trunk lean during single leg landing, potentially to reduce external hip moments and muscle demand.
AoMYB114 transcription factor regulates anthocyanin biosynthesis in the epidermis of tender asparagus stems
Authors: Li Yanwen , Li Mengyao , Guo Zheng , Liu Junting , Chen Peiran , Lu Wei , Jiang Chengyao , Xiao Jiachang , Lei Fengyun , Zheng Yangxia
Published: February 2025

Introduction

Asparagus is a valuable vegetable, and its edible part is a tender stem. The color of the tender stem epidermis is an important trait. In particular, purple asparagus is rich in anthocyanins. However, the molecular mechanisms underlying anthocyanin accumulation in purple asparagus remains unclear.

Methods

The white variety ‘Jinguan’ (JG), the green variety ‘Fengdao 2’ (FD), and the purple variety ‘Jingzilu 2’ (JZ) were compared using physiological and transcriptomic analysis. High-performance liquid chromatography and real-time quantitative polymerase chain reaction were employed to detect anthocyanins and validate gene expression.

Results

Cyanidin 3-glucoside and cyanidin 3-rutinoside were detected as the main anthocyanins in JZ. Transcriptome data demonstrated that 4,694 and 9,427 differentially expressed genes (DEGs) were detected in the JZ versus FD and JZ versus JG control groups, respectively. These DEGs were significantly enriched in pathways associated with anthocyanin accumulation, including phenylalanine metabolism, phenylpropanoid biosynthesis, and flavonoid biosynthesis. A total of 29 structural genes related to anthocyanin biosynthesis were identified. The expression of these structural genes was higher in JZ than in FD and JG, thereby activating the anthocyanin biosynthesis pathway. Additionally, a candidate gene, AoMYB114, was identified based on transcriptomic data. The expression of AoMYB114 was associated with anthocyanin accumulation in different tissues. Further research found that overexpression of AoMYB114 activated the anthocyanin biosynthesis pathway. It promoted leaf pigment accumulation in transgenic Arabidopsis.

Discussion

These findings demonstrate that AoMYB114 positively regulated anthocyanin biosynthesis. This study elucidates the molecular mechanism underlying purple coloration in asparagus. It provides important insights for improving asparagus quality and for breeding high-anthocyanin varieties.
Difference in single-leaf and whole-plant photosynthetic response to light under steady and non-steady states in Arabidopsis thaliana
Authors: Sakoda Kazuma , Sakurai Atsushi , Imamura Sousuke
Published: February 2025

Although photosynthetic response to light has been extensively studied at the single-leaf level, little is known about the response at the whole-plant level. The present study aims to reveal the differences in the photosynthetic response to light under steady and non-steady states between the single leaf and whole plant in Arabidopsis thaliana and to investigate the mechanisms underlying these differences with respect to leaf aging. First, we developed an open system for gas exchange measurement of the whole plant of Arabidopsis. It enabled the photosynthetic response to dynamic environmental changes to be directly compared between the single leaf and whole plant. The photosynthetic response to the fluctuating light did not differ significantly between the single leaf and whole plant. This result is partly confirmed by the fact that the leaves at different ages showed no difference in the photosynthetic induction after a step change in light. On the other hand, light response analysis for steady-state photosynthesis showed a higher apparent quantum yield in the whole plant than in the single leaf. This difference might be attributed to the difference in the efficiency of light absorption and/or utilization of absorbed light among the leaves at different ages.
Adolescent campus bullying and non-suicide self-injury: chain mediating effect of negative affect and sleep quality
Authors: Anan Li , Yaoyao Li , Kunhang Xie , Yong Yuan , Xiaoyan Wang , Lina Li , Shaobo Lv
Published: February 2025

Aim

This study aimed to explore the chain mediating role of negative affect and sleep quality between campus bullying and non - suicidal self - injury (NSSI) among adolescents.

Methods

569 adolescents were selected through convenience sampling. Participants completed the Olweus Bully/Victim Questionnaire, Positive and Negative Affect Schedule, Pittsburgh Sleep Quality Index, and Adolescent Non - suicidal Self - injury Assessment Questionnaire.

Results

Our result showed significant positive correlations among campus bullying, negative affect, sleep quality and NSSI. Negative affect and sleep quality were identified as independent and sequential mediators in the relationship between campus bullying and NSSI.

Conclusion

These findings elucidate the mechanisms linking campus bullying to NSSI, providing a preliminary basis for exploring the causal relationships among these variables. this study offers theoretical support for future research and inform the development of targeted interventions to reduce NSSI and improve the overall mental health of adolescents in China.
Body mass index is associated with the antidepressant effects of intravenous ketamine in patients with depression
Authors: Tan Jian-Qiang , Gu Li-Mei , Zhou Yan-Ling , Wang Cheng-Yu , Lan Xiao-Feng , Zheng Wei , Ning Yu-Ping
Published: February 2025

Objectives

We aimed to explore the correlation between baseline body mass index (BMI) and the antidepressant properties of intravenous ketamine in patients with depression.

Methods

We divided 135 patients diagnosed with either major depressive disorder (n=103) or bipolar depression (n=32) into lower and higher BMI groups based on their baseline BMI. Patients with a lower BMI (BMI<24 kg/m²; n=92) were included in the lower BMI group, and those with a higher BMI (BMI≥24 kg/m²; n=43) were assigned to the higher BMI group. Each participant received six ketamine infusions. Antidepressant remission was determined using a Montgomery–Åsberg Depression Rating Scale (MADRS; total score of ≤10) within 24 hours after the sixth ketamine infusion on day 13. Antidepressant response was characterized by a ≥50% alleviation in the symptoms of depression at the same time point. Changes in symptoms of depression over time were assessed using a linear mixed model.

Results

The antidepressant response rate in the higher BMI group (67.4%, 95% confidence interval [CI]: 53.5%–81.4%) was higher than that in the lower BMI group (51.1%, 95% CI: 41.3%–60.9%). In addition, the remission rate was higher in the higher BMI group (39.5%, 95% CI: 25.6%–55.8%) than in the lower BMI group (31.5%, 95% CI: 21.7%–41.3%). However, these differences were not significant (all P>0.05). The linear mixed models with covariates indicated a significant group-by-time interaction in the MADRS scores (F13, 1729=3.0, P<0.001). A significant correlation was found between baseline BMI level and the change in depressive symptoms on days 13 and 26 (all P<0.05). However, these correlations were not significant after Bonferroni correction or controlling for baseline depressive symptoms (all P>0.05).

Conclusion

Our exploratory, post-hoc analysis of an open-label, single-arm study suggests that patients with depression and a higher baseline BMI may experience greater reductions in depressive symptoms compared with those with a lower baseline BMI after receiving six ketamine infusions.